Chemistry of Heterocyclic Compounds

vol.10

Hetarylation of organic compounds (review)

1-13
An investigation in the field of the stereochemistry of acetylenic oxides
14-16
Reaction of alkyl- and benzylglycidylmalonic esters with lactams
17-22
Stereoisomeric carboxamides of the bicyclo[2,2,1] heptene series in the epoxidation reaction
23-26
Investigations in the field of vinyl esters of the furan series
27-29
Reaction of and -methylpyrylium salts with orthoesters
30-33
Fluorosulfonyl-containing heterocyclic compounds
34-36
Fluorosulfonyl-containing heterocyclic compounds
37-40
Pyrylocyanines
41-44
Pyrylocyanines
45-49
Functional derivatives of thiophene
50-52
Investigation of some nitrogen compounds of 2,2-bithienyl
53-55
Reaction of perchlorates of condensed thiopyrylium derivatives with aromatic aldehydes
56-58
Photochromic and thermochromic spirans
59-66
Photochromic and thermochromic spirans
67-72
Synthesis and some properties of 1,3-diaryl-2,2-dibromoaziridines
73-74
The configuration of esters of -(indol-3- yl)--nitroacrylic acid
75-77
Indoles
78-79
Structure and reactivity of 3-hydroxypyridine N-oxide
80-83
Reaction of pentachloropyridine N-oxide with potassium hydrogen sulfide
84-87
Synthesis of 4-norpyridoxine (3-hydroxy-5-hydroxymethyl-2-methylpyridine)
88-91
Pyridinium salts
92-95
Pyridinium salts
96-98
Pyridinium salts
99-101
Pyridinium salts
102-104
A study of naphthyridines
105-107
Synthesis and properties of azoles and their derivatives
108-109
A smiles rearrangement in the pyridazine series
110-112
Mass spectra of methoxy-substituted 4-aminopyrimidines
113-116
Some derivatives of pyrimido [5,4-b]quinoline
117-119
Reaction of 2-amino-3-ethoxycarbonylthiophenes with 2,3-dibromopropyl isothiocyanate
120
Tri(ethoxycarbonyl)cyclopenta[b][1,4]benzothiazine A new ISO--electronic analog of azulene
121
Reaction of 2,4-diaryl-6-methylpyrylium salts with nitrite esters
122
Carbonyl derivatives of 2-arylthiophenes
123
2-Styrylperimidines
124
Benzo-1,2,3-thiaselenazolium salts
125
Reaction of 6-(cyanomethyl)phenanthridine with acylating agents
126
Conference on Coordination Chemistry
127-128
Polarography of heterocyclic compounds
129-141
PMR spectra of difuroyl peroxides
142
Research on polyfunctional oxides
143-146
Synthesis of derivatives of oleandomycin aminohydrin
147-150
Catalytic transformations of benzofuran
151-153
Synthesis of o- and p-hydroxyacetophenones and 2-methyl-4,6-diarylpyrylium and 2-aryl-4-methyl-benzopyrylium
salts by acetylation of some phenols
154-157
2-Benzopyrylium salts
158-160
2-Dichloromethylene-1,3-dioxolane in the diels-alder reaction with ,- unsaturated aldehydes
161-162
Synthesis of 1,3-dioxolane derivatives
163-165
Quantum-chemical investigation of some oligomeric heteroaromatic compounds
166-170
Synthesis of cyanoaminothiophenes with active fuctional groups
171-173
Synthesis of 2-benzamidothiazolines
174-176
Synthesis in the phenothiazine series
177-178
Indoles
179-181
Indole derivatives
182-185
Indole derivatives
186-188
Iodonium derivatives of heterocyclic compounds
189-192
Reaction of 5-hydroxyindole derivatives with o-nitrobenzenesulfenyl chloride
193-196
Research on the chemistry of pyrazolidine
197-199
Reaction of nitriles of enyne acids with hydrazines. synthesis of cyano derivatives of 2-pyrazolines
200-204
Dipyrazolodiazocines
205-206
Synthesis of substituted 1-isopropenyl- and 1-alkylbenzimidazolones
207-209
Reactivities of dianions of pyridyl phenyl ketones
210-213
Reactions of 1, 5-diketones
214-216
Investigation of naphthyridines
217-218
Cyanine dyes based on 2-phenyl-3,4-dimethyl-5,6-benzoquinoline
219-220
Comparative mass-spectrometric investigation of quinolizidine alkaloids and cytisine, sparteine, and matridine
derivatives
221-229
electron structure and reactivities of isomeric pyrrolo-sym-triazoles
230-234
Tetrazole derivatives
235-238
Nature and properties of tetracyanoquinodimethane complexes with azoles
239-142
Synthesis of a new heterocyclic system the thionaphtheno [2,3-c] pyrylium ion
240
Addition of hydrogen selenide to diacetylenic ketones
241
Synthesis of 1, 1, 3, 3-tetraethyl-5, 5-bis(trifluoromethylsulfonyl) imidatricarbocyanine
242
Anomers in the synthesis of imidazole nucleosides by the Shaw method
243-244
European conference on the chemistry of heterocyclic compounds
245-252
Mass spectrometry of indole compounds (review)
253-267
Research on unsaturated lactones
268-269
Isomerism of 5-arylfurfural oximes (according to PMR spectroscopic data)
270-275
Research on furan acetal compounds
276-279
-Electronic structure of the nitrofuran system
280-284
Dihydropyran derivatives
285-287
Dihydropyran derivatives
288-289
Some peculiarities of the cyclization of N-polynitroalkyl-N-nitrosoaminoacetic acids and their nitriles to sydnones and
sydnonimines
290-295
2-Benzopyrylium salts
296-298
Disintegration of 1-silalactones under the influence of electron impact
299-301
Research on the chemistry of phenoxazines
302-306
Synthesis of substituted 2-amino-5,6-dihydro-4h-1,3-oxazines and 2-iminotetrahydro-1,3-oxazines
307-309
Synthesis of substituted 2-amino-5,6-dihydro-4H-1,3-thiazines and 2-iminotetrahydro-1,3-thiazines
310-312
New method for the synthesis of cis-2,5-disubstituted sulfolane derivatives
313-317
Aminomethylation of some 4-thiazolidinones
318-319
Heterocyclic diazo compounds
320-323
Synthesis in the phenothiazine series
324-326
Chemistry of indole
327-330
Condensation of 2-(acetamido)cyclohexanone with malononitrile
331-333
Reaction of N-tritylamines with nitrogen-containing heterocyclic compounds
334-335
Lactam acetals
336-339
Structure, tautomerism, and transformations of -(3-nitro-2-pyridyl)- and -(3-nitro-4-pyridyl)pyruvic acid esters
340-344
Synthesis and stereoisomerism of N-oxides of the decahydroquinoline series
345-349
Research on 6- and 7-substituted 2-and 4-thioquinolones. Transmission of the electronic effects of substituents in the
benzene ring of thioquinolones to the reaction center
350-353
Research in pyrazolidine chemistry
354-357
Research on unsaturated azole derivatives
358-361
Research on unsaturated azole derivatives
362-365
Heterocyclic analogs of pleiadiene
366-368
Synthesis of azo compounds containing triazole and tetrazole residues
369-371
Cyclization of arylhydrazones of nitroformaldehyde and its derivatives
372-374
Catalytic synthesis of pyrrole from ethanolamines
375
Synthesis and properties of 4-chloroimidazo[4,5-d]-1,2,3-triazine
376
High-temperature synthesis of thioxanthene
377
Thermolysis of 1-methyl-2-acetamidobenzimidazole
378
Gala occasion for Soviet scientists
379-380
Photochemistry of quaternary salts of aromatic heterocycles and some of their mesoionic derivatives (Review)
381-392
Effect of structural factors on the disintegration of the molecular ions of nitrophenylisoxazoles during electron impact
393-396
Thermal isomerization of the isoxazole ring and rearrangement processes in the mass spectra of 3-aryl-5-
methylisoxazole-4-carboxylic acids
397-399
Synthesis and study of the luminescence properties of anhydrides and n-phenylimides of 4-(2-aryl-1,3,4-oxadiazol-5-
yl)naphthalic acids
400-402
Research on the chemistry of phenoxazines
403-405
Reaction of sulfolenes and their derivatives with some sulfur-containing nucleophiles
406-408
Fluorosulfonyl-containing heterocyclic compounds
409-412
Spectroscopic study of organosilicon derivatives of thiophene
413-417
Investigation of h complexes of 2-thienyl phenyl ketones by IR spectroscopy
418-420
Cyclization of some substituted 2-(n-acylthioureido)-3-carbethoxythiophenes
421-423
5,6-Trimethylenethiapyrylium and 5,6,7,8-tetrahydrothiochromylium salts
424-427
Benzazoles and naphthazoles
428-433
Cyclization of benzoylcyanothioacetic acid arylamides
434-436
Semicarbazones and thiosemicarbazones of the heterocyclic series
437-442
Reactions of N-acylated ethyleneimines with thioacetic acid and hydrogen sulfide
443-446
Indole derivatives
447-449
Electronic spectra of the ionic forms of,-unsaturated ketones Indole derivatives
450-454
Hydrogenation of vinylpyridines and styrene in the presence of the palladium chlorodimethylsulfoxide complex
455-456
4-Azaindane-1,3-dione derivatives i. study of the tautomeric and prototropic equilibria of some analogs of 4-
azaindane-1,3-diones
457-459
Investigation of lactams
460-462
Lactam acetals
463-465
Reactions of cyclammonium cations
466-470
Vibrational spectra of pyrazole in various aggregate states and their interpretation
471-476
Transformations of substituted tetrahydro-8h-indeno[1,2-d]imidazoles in concentrated sulfuric acid
477-479
5-Fluoro-4-alkyl(aryl)barbituric acids
480-481
Study of the nucleophilic substitution reactions of 2,4,10-trichloropyrimido[5,4-b]quinoline
482-484
Heterocyclic analogs of pleiadiene
485-488
Synthesis of triazolones and C-aminotriazoles by thermal condensation of carbamidoamidrazones
489-490
Condensation of protic salts of N-alkyl-substituted C-amino-sym-trlazoles with-diketones and-chlorovinyl ketones
491-494
Reactions of 2- and 4-(-ethoxyvinyl) pyrylium salts with nucleophiles
495
Debenzylation of N-benzylazoles
496
Cyclization of 4,4-dinitrobutenoic acid esters to 3-nitroisoxazoline N-oxides
497
Synthesis of 1,3-dihydro-5-alkyl-2H-1,4-benzodiazepin-2-ones
498-499
Indolylalkylamines from arylhydrazines and - or -halocarbonyl compounds (review)
501-510
Synthesis of coumarans from alkenylphenols
511-512
Research on polyfunctional oxides
513-515
Research in the isoxazole series
516-520
Research in the isoxazole series
521-522
Research on aromatic heterocycles
523-526
Synthesis and transformation of amides of 4H-3,1-benzoxazin-4-one-2-carboxylic acid
527-530
Atranes
531-534
Atranes
535-537
Exchange of the amino group in -amino derivatives of sulfolane
538-540
Reaction of sulfolanyl sulfonates with some nucleophilic reagents
541-545
Synthesis and structure of anils of 2-formyl-3-mercaptobenzo[b]thiophene and 2-formyl-3-mercaptobenzofuran
546-552
Synthesis and reactions of azides of heterocyclic compounds
553-555
Syntheses in the phenothiazine series
556-558
Indole derivatives
559-562
Azaindole derivatives
563-566
Vitamin b6 analogs
567-571
Mass spectrometry of negative ions of pyridine N-oxides
572-575
Hydrazones
576-578
Lactam acetals
579-582
Mechanism of the oxidative condensation of acridines with nucleophiles
583-586
6H-anthra[1,9,8-c,d,e,f]-2,7-naphthyridine derivatives
587-588
Synthesis and properties of 6-(p-tolyl)phenanthridines and 5,10-di(p-tolyl)diazapyrenes
589-591
N-phenyl-1-naphthylamine
592-595
Diazo compounds of the heterocyclic series
596-599
Research in the imidazole series
600-603
Mass spectra and structure of 4-aminouracils
604-608
Heterocyclic analogs of pleiadiene
609-612
Alkyl and 2-hydroxy derivatives of imidazo]4,5-b]pyrazine and their N-oxides
613-617
Condensation of dimethylidynehemicyanines with ketones
618-619
New method for the synthesis of thiophenethiols
620
Formation of substituted 1,3-dithiolanes in reactions of 3-amino-2-arylidene-1-thiones with diazomethane
621-622
Preparation of substituted thiiranes and ethylenes in the reaction of 3-piperidino-2-phenylidene-1-thione with mono-
and diphenyldiazomethanes
623
Symposium on the Chemistry and Technology of the Heterocyclic Compounds of Fossil Fuels
624-625
First All-Union Conference on the Chemistry of Heterocyclic Compounds
626-627
Interconversions of some nitrogen-containing heterocyclic systems (review)
629-639
Polarographic investigation of the tautomeric transformations of -formylacrylic acid and of the hydrolysis of its ethyl
pseudoester. I
640-644
Vinylpyrylation of aromatic compounds
645-646
Reactions of 1,5-diketones
647-649
Spiropyrans of the phenanthridine series
650-653
Charge migration in the molecular ions of isoxazole derivatives
654-657
2-Aryl-4H-3,1-benzoxazin-4-ones alcoholysis
658-661
Synthesis of substituted 2-amino-4H-1,3-oxazines
662-665
UV spectra of some derivatives of 5,10-dihydrophenarsazine and 5,10-dihydrophenoxarsine
666-667
Reactions of trichloromethyldialkylamines with 2-methylbenzothiazole, 2-methylbenzoxazole, and their salts
668-670
Research in the benzazole and naphthazole series
671-673
Mass spectra of derivatives of imidazo[2,1-b] thiazole and thiazolo[3,2-a]benzimidazole
674-678
Synthesis and properties of 1,2-dihydropyridazino[4,5-b]indole II
679-682
Synthesis of substituted indolizines from 1-phenacyl-5-methyl-4-phenyl-2-phenacylidene-1,2-dihydropyridine
683-686
Nucleophilic substitution in 2-nitro-3-halopyridines
687-690
Synthesis of methyl-substituted benzofuro-, benzothieno-, and benzoselenopheno[2,3-b] pyridines
691-692
Investigation of nitrogen- and sulfur-containing heterocycles
693-695
Optical and photochemical properties of N-benzalaminophenylpyridinium perchlorates
696-698
Nitro derivatives of 3-hydroxyquinoline
699-701
Hydroacridines and related compounds
702-704
-electron structure, reactivity, and absorption spectra of anthrapyridone
705-709
Proof of the structure of 1-tosyl-5-(2-nitrovinyl)imidazole
710-711
Synthesis and properties of azoles and their derivatives
712-714
Pyrimidines
715-719
Paramagnetic ring current in the diazepine ring of the 1H-benzo-1,5-diazepinium monocation
720-723
Synthesis of nitro-substituted 4-methyl-2,3-dihydro- and 2,3,4,5-tetrahydro-1H-1,5-benzo-2-diazepinones
724-727
1,4-Benzodiazepines and their cyclic homologs and analogs
728-731
New heterocyclic sym-triazolopyrimidinium systems Quinoline, pyridazine, and phthalazine derivatives
732-734
Reaction of 1-amino-, 2-amino-, and 1,2-diaminoimidazoles with -diketones
735-739
Acylation of some substituted 1,2,4-triazole-3-thiones
740-742
Synthesis of trimethylethylene sulfide
743
Direct replacement of a nitro group by a halogen in a number of imidazo[4,5-c]pyridine derivatives
744-745
Anthraquinoneisoimidazoles
746-747
Synthesis of isoflavones that have hypocholesterinemic activity
748
Synthesis of the 1-(5-tetrazolyl)-3,5-diphenylverdazyl radical
749
5-Fluorosulfonylcytosine
750
5-Polyfluoroalkyluracils
751
Elimination of bromine during the reaction of 2,8-dibromo-7-ethoxy-3-phenoxazinone with morpholine
752-753
Mechanism of the photochemical addition-substitution reactions of six-membered aza aromatic compounds in
hydrogen-containing solvents (review)
755-768
Reaction of 2-acyloxiranes with cyclic ketones
769-772
Research on unsaturated lactones
773-774
Reactions of 2- and 4-methylpyrylium salts with ethyl orthoformate
775-779
Reactions of -ethoxyvinylpyrylium salts with nucleophiles
780-783
Reaction of some aromatic nitrile oxides with dimedone
784-787
Synthesis of 2-R-fluorantheno[2,3-d]- and 2-R-fluorantheno[3,2-d]oxazoles
788-790
2-Aryl-4H-3,1-benzoxazin-4-ones nitration
791-792
Mass spectrometric study of 2- and 4-silalactones
793-795
Study of the formation of 2-substituted 3a,4,6,6a-tetrahydrothieno[3,4-d]oxazolines from cis- and trans-4-amino-3-
hydroxythiophans
796-800
Transmission of the electronic effects of substituents by the thiophene ring
801-805
Research on a number of substituted arylamides of dithiocarboxylic acids
806-809
Some cyclization reactions of -chloro--acylamidoacetophenones
810-812
Action of phosphorus pentasulfide on 5-acetamidothiohydantoins and 4-bromo-5-acetamidopyrazoles
813-815
Mass spectra of imidazo[2,1-b]thiazole and thiazolo[3,2-f]xanthene derivatives
816-820
Benzindoles
821-822
Synthesis and spectral characteristics of photochromic 6- and 8-phenyl- substituted indoline spirochromenes
823-825
3-Phenoxy-1,2,3,4-tetrahydrobenzo[h]-quinoline
826-831
Quantum-chemical investigation of the -electronic structure of 3-hydroxy-4-phenylazoquinoline and 4-hydroxy-3-
phenylazoisoquinoline
832-836
Investigation of the halogenation of 5-benyl-3-hydroxypyridine
837-838
Recyclization reactions of heterocycles
839-842
Investigation of 2,3-polymethylenequinolines
843-844
Investigation of naphthyridines
845-846
Application of mass spectrometry in structural and stereochemical investigations
847-852
Synthesis and properties of 1-methyl(aryl)-7-ethoxycarbonylindolizines
853-856
Synthesis of pyrazoline derivatives from halovinylacetylenes and haloallenes
857-858
Pyrimido [1,2-b]indazoles from 3-aminoindazoles and -diketones
859-860
PMR spectfa of alkyl-substituted 1-pyrazolines
861-863
Heterylimidazoles
864-866
Nucleophilic substitution of hydrogen (3-H) in quinoxalone by arylamines
867-870
-Oxides in reactions with N-H acids of the heterocyclic series
871-875
Reaction of aromatic aldehydes with 1-methylindole-2-carboxylic acid and its esters
876-877
Spiropyrans of the 3,4-dihydroisoquinoline series
878-879
Synthesis of heterocyclic compounds from cyclohexane-1,3-diones (review)
881-897
Synthesis of pyrylium salts by condensation of -chlorocinnamaldehydes with carbonyl compounds
898-901
Reaction of 2,4,6-substituted pyrylium salts with compounds containing a C = N bond
902-905
Synthesis of 3-(p-methoxyphenyl)-1, 3-dimethylspiro (indoline-2,2- [2H-1]-benzopyrans) and investigation of the
electronic absorption spectra of their merocyanine forms
906-908
Reaction of some amines with unsaturated N-acylbenzoxazolones
909-912
Synthesis and luminescence properties of anhydrides and N-phenylimides of substituted 4-(5-phenyl-2-oxazolyl)-
naphthalic acids
913-915
Synthesis of r-4-ethoxycarbonylamino-t-3-hydroxy-c-2-( -methoxycarbonylbutyl)-thiophan
916-918
Syntheses of di-and tetrahydropyrroles
919-922
Syntheses of di- and tetrahydropyrroles
923-926
Indole derivatives
927-929
Chemistry of indole
930-936
Nucleophilic addition of indole and its derivatives to -aroylacrylic acids
937-940
Indoles
941-942
Indoles
943-946
Lactam acetals
947-950
Nitration of 2- and 5-benzyl-3-hydroxypyridines and their N-oxides
951-952
Effect of annelation on the reactivities of benzoquinolines in hetarylation
953-960
Investigation of 2,3-polymethylenequinolines
961-964
Preparation of 6-styrylphenanthridines
965-969
Synthesis and structure of quaternary salts of acridinylhetarylmethanes and their anhydro bases
970-973
Oxidation of 4-styryl- 2- phenyl-5, 6-benzoquinoline with potassium permanganate
974-976
Reaction of 2-ethoxycarbonyl-3-oxoquinuclidine with nucleophilic reagents
977-980
Stereoisomeric 1,2,3,4,5,5a,6,10b-octahydroindeno [1,2-c]azepines
981-984
Bromination of alkaloids of carex parvae
985-988
Synthesis of 1-and 7-substituted 2,3-dihydro-1h-pyrrolo[1,2-a]benzimidazoles
989-991
Reaction of 2-aminopyrimidines with halocarboxylic acids and their esters
992-994
2,3,5,8(1)-Tetrahydroimidazo[1,2-a]pyrimidine-2,5-dione derivatives
995-997
Synthesis of 4, 6-diphenacylpyrimidines
998-999
Pyrimido [2,1-a]isoquinolinium salts
1000-1001
Thiopyrans (review)
1003-1015
Condensation of salicylnitrile with some -halo carbonyl compounds
1016-1018
Introduction of new substituents into some aromatic cations
1019-1022
Alkylation and some physicoc hemical characteristics of 6,7- and 7,8- dihydroxycoumarins
1023-1028
Competitive methylation of some phenolic compounds
1029-1031
Stereochemistry of heterocycles
1032-1037
Research in the chemistry of phenoxazines
1038-1041
Kinetics of the alkaline hydrolysis of 3-sulfolanol phenyl ethers
1042-1044
Functional thiophene derivatives
1045-1047
Protonation of imidazo[2,1-b]thiazole and thiazolo[2,3-f]purine
1048-1052
Lactam acetals
1053-1059
Lactam acetals
1060-1064
2-(3-dioxindolyl)-substituted steroids
1065-1067
Ir spectra and conformation of 2-acetylindoles
1068-1071
Indole derivatives
1072-1074
Indole derivatives
1075-1078
Study of the products of oxidative rearrangement in the indole series by mass spectrometry
1079-1082
Indole derivatives
1083-1084
2-Pyridones
1085-1086
Chlorosulfonation of 2-pyridones
1087-1089
Investigation of heterocyclic quinones
1090-1092
Synthesis of vinyl derivatives of acridine and phenanthridine
1093-1095
1,4-Benzodlazepines and their cyclic homologs and analogs
1096-1098
Reaction of ,-dimethyl--(1-phe nyl-3-methyl-4-pyrazolyl)-, -butenolide with primary amines and ammonia
1099-1101
Condensation of 1-acylpyrazolines
1102-1104
Investigation of quinones
1105-1108
Investigation of quinones
1109-1113
Investigation of nitrogen- and sulfur-containing heterocycles
1114-1116
Vibrational spectra and structure of 1,2,4-trlazole derivatives
1117-1120
Acid Base properties of 3(5)-azido-1,2,4-triazoles
1121-1123
Properties of tetracyanoethylene complexes with azoles
1124
New synthesis of 2 -aminobenzopyrylium salts
1125
Chemistry of pteridine N-oxides (review)
1127-1145
Morpholine derivatives
1146-1150
Reaction of 2-dialkyl-5-formylfurans, -thiophenes, and-selenophenes with aromatic diazonium salts
1151-1152
Nitration of 2-(2-quinolyl)thiophene and 5-(2-quinolyl)-2,2-dithiophene
1153-1155
Synthesis of 6-(-thienyl)azulene from 2-butoxy-4-(-thienyl)-5-dihydropyran
1156-1158
Reaction of 4-arylamino-2-sulfolenes with nucleophilic reagents
1159-1161
Thiazolopyridinium salts with an active methyl group and cyanine dyes based on them
1162-1165
Reaction of ethoxyvinyl derivatives of pyrylium and pyridinium salts with primary and secondary amines
1166-1171
N-Aminoarylpyridinium perchlorates and their behavior in diazotization
1172-1176
Properties of the amino group in N-(aminophenyl)pyridinium perchlorates
1177-1181
Some transformations in a number of (2-pyridyl)phosphonates
1182-1184
Spectroscopic study of hydrogen bonding in aminoanthrapyridones
1185-1191
Factors that affect the tautomeric equilibrium of hydroxyazopyridine derivatives
1192-1198
Indole derivatives
1199-1202
Indole derivatives
1203-1206
Preparation of 1-aryl-2-methyl-3-carbethoxy-4,5-dioxo-6-bromoindoles
1207-1209
Carbolines
1210-1214
Effect of hydrogen bonding on the frequency of the out-of-plane deformation vibrations of the NH bonds in pyrazole
and imidazole molecules
1215-1216
Synthesis and some properties of n,s-divinyl-2-mercaptobenzimidazole
1217-1220
Synthesis and spectral characteristics of bis- and tris(2-pyrazolinyl) benzenes
1221-1224
Research on benzimidazole derivatives
1225-1228
Benzimidazole derivatives
1229-1231
Synthesis and investigation of some bisbenzimidazoloquinazolines
1232-1236
Rearrangement of organometallic compounds of 1-benzylindazoles
1237-1240
Dehydrogenation of piperazine to pyrazine on oxide surfaces under chromatographic conditions
1241-1245
Reaction of succinonitrile with anhydrous hydrazine
1246-1247
Pyrimidines
1248-1250
Conversion of some substituted 1,2,4-triazole-3-thiones
1251-1253
Tetrazole derivatives
1254-1258
New synthesis of 2-amino-3-cyano-4,5-tetramethylenethiophene
1259-1260
Phosphorus-containing uracil analogs
1261
5-Benzyluracil and its derivatives
1262
Synthesis of sym-octahydroacridinium salts
1263-1264
1,3,4-selenadiazolo[3,2-a]pyrimidinium salts
1265-1266
Rearrangement of pyrimido[1,2-a]indoles to -carbolines
1267
Synthesis of substituted 4h-1,3-benzothiazines
1268
Heterocyclic compounds as organic luminophores (review)
1269-1284
Reaction of 2,4,6-trimethyl- and 2,4,6-triphenylpyrylium perchlorates with heterocyclic amines
1285-1290
Analysis of the PMR spectra of 3- and 5-substituted flavones with paramagnetic additives
1291-1293
Mass-spectral investigation of 4-aryloxazoles
1294-1297
Intramolecular cyclization of propargyl arylcarbamates
1298-1300
Structure and basicity of -substituted ethynyl 2-thienyl ketones
1301-1304
Formyl and formylvinyl derivatives of 2-methylenebenzo-1,3-dithiole
1305-1308
Biscyanines with unconjugated chromophores from 2,4-dimethylthiazole and lepidine derivatives
1309-1312
Indole derivatives C. Synthesis of -(3-indolyl)alkyl bromides
1313-1315
Indole derivatives CI. Synthesis and biological activity of some tryptamines
1316-1321
Indole derivatives CII. C-acylation of 3-indolylacetonitrile
1322-1324
Indole derivatives CIII. Esterification of -(3-indolyl)alkanoic acids in the presence of sulfonate cation-exchange
resins
1325-1326
Synthesis of 5-aminoindole derivatives from N-arylsulfonylquinone diimines
1327-1328
Diene synthesis with 2-pyrones and 2-pyridones XIV. 1,4-Cycloadducts of 1-alkyl-2-pyridones with N-
phenylmaleinimide and maleinimide
1329-1331
Fragmentation of substituted 4-hydroxy-2-quinolones under the influence of electron impact
1332-1336
IR and electronic absorption spectra and structures of 3-hydroxy-4-phenylazo-quinoline and 4-hydroxy-3-
phenylazoiso-quinoline derivatives
1337-1339
Structures of the products of reaction of 1,5-diketones with hydroxylamine
1340-1341
Unsaturated hydantoin derivatives XI. Synthesis and rearrangement of some ethyl esters of -substituted
hydantoest-5,-acetic acids
1342-1349
Heterylimidazoles IV. Homolytic dissociation of hexaaryldimidazolyls and their heterocyclic analogs
1350-1353
Research on benzimidazole derivatives XXXIV. Some transformations of N-alkenyl- and N-alkynyl-substituted
benzimidazoles
1354-1356
Research on unsaturated azole derivatives III. Electrophilic substitution reactions in the 2-ethynylbenzimidazole
series
1357-1359
Synthesis of fungitoxic derivatives of benzimidazole with a radioactive label
1360-1361
2,4-Dioxohexahydropyrimidine derivatives V. 5-Bromo-6-alkoxydihydroorotic acids, amides, and esters
1362-1365
Electronic spectra and structures of protonated pyrazine and quinoxaline N-oxides
1366-1370
Investigation of heterocyclic quinones XXV. Tautomeric and covalent hydration in the quinazolinequinone series
1371-1374
Heterocyclic nitro compounds XIX. Kinetics of the methylation of 3(5)-nitro-1,2,4-triazoles with dimethyl sulfate
1375-1378
Synthesis of bis(isoindolo-1,2-sym-triazol-5-on-2-yls) and 10,10-arylenebis[7H-benzo-[de]-sym-triazolo[5,1-
a]isoquinolin-7-ones]
1379-1381
Bromocyclization of some substituted 3-allyl-2-thiohydantoins
1382-1383
Direct nitrosation of 2-amino-1-alkyl-(aralkyl)benzimidazoles
1384
Selective alkylation of 5-aminouracil derivatives
1385
Formation of some isochromene derivatives by reaction of veratyl ketones and veratric acid with benzoin
1386
Synthesis of phenylsulfonyl-substituted phenoxazines
1387-1388
3-Ethynylimidazo[1,2-a]benzimidazoles
1389
Synthesis of imidazo[1,2 -a] perimidine derivatives
1390-1391
Hydrogenolysis of furylcyclopropane
1392
Fischer cyclization of N, N-diaryl- and N-aryl-N-hetarylhydrazines
1393-1394
Direct proof of the fischer synthesis of indoles via a scheme involving a sigmatropic [3,3]-shift
1395
Basic isotopic hydrogen exchange of heteroaromatic compounds (review)
1397-1417
Stereochemistry of bromoalkoxylation of 6-phenyl-2-dihydropyran and synthesis of 2-alkoxy-6-phenyl-3-
dihydropyrans
1418-1420
Synthesis of aza analogs of 2-aminocheomone
1421-1423
Mass spectra of some six-membered cyclic phosphites
1424-1426
2-Formyl-5-nitrothiophene as a reagent for phosphoranes
1427-1428
-Keto sulfone derivatives
1429-1431
Epimination of olefins by means of 3,3-pentamethyleneoxaziridine A one-step synthesis of aziridines
1432-1439
Saturated nitrogen-containing heterocycles
1440-1442
Synthesis of monosubstituted amides of 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid
1443-1445
Nucleophilic photosubstitution of halogen in the heterocyclic series
1446-1449
Research on perinone compounds
1450-1454
Spectrometric study of some N-substituted 3(5)-methylpyrazoles and their complexes with cupric chloride
1455-1458
Effect of bases on 1,3,4-thiadazolo[3,2-a] pyrimidinium salts
1459-1460
Analogs of pyrimidine nucleosides
1461-1463
Analogs of pyrimidine nucleosides
1464-1467
Analogs of pyrimidine mono- and polynucleotides
1468-1470
Analogs of purine nucleosides and purine mono- and polynucleotides
1471-1476
Analogs of purine nucleosides and purine mono- and polynucleotides
1477-1480
Analogs of purine nucleosides and purine mono- and polynucleotides
1481-1485
Dihydro-1,2-diazaphenazines
1486-1489
Synthesis of 7-methyl-9,10-dimethoxybenzimidazo -[3,2-b]isoquinolinium perchlorate
1490
Oxidative condensation of 2-ethylnylbenzimidazole
1491
Synthesis of condensed 1,2,4-triazine systems from 2(8)-methylmercaptoimidazoles
1492
Borodin hunsdiecker reaction in the isoxazole series
1493
Reaction of 2-diazocyclohexanone with azodicarboxylic acid esters
1494
Hydrogenolysis of -methylfuran over nickel on ionic supports
1495
Synthesis of N1-(3-furanidyl)thymine
1496
HETARYLATION oF ORGANIC COMPOUNDS (REVIEW)

A. K . S h e i n k m a n UDC 547.82.83 : 541.515

Reactions of the d i r e c t introduction of nitrogenous a r o m a t i c h e t e r o c y c l e s into nucleophflic

organic compounds with the u s e in situ of N-acyl salts of h e t e r o c y c l i c cations and also of
h e t e r o a r o m a t i c anion radicals a r e discussed.

The h e t a r y l a t i o n r e a c t i o n is the name which we give to the d i r e c t introduction of a r o m a t i c h e t e r o -

c y c l e s into organic compounds [1]. This r e v i e w c o n s i d e r s only those arylation r e a c t i o n s in which h e t e r o -
a r o m a t i c s y s t e m s a r e used d i r e c t l y without the p r e v i o u s production of hetarylating agents (such as q u a t e r -
n a r y salts, N-oxides and t h e i r q u a t e r n a r y salts, etc.) f r o m them. Such r e a c t i o n s include those of n i t r o -
genous a r o m a t i c h e t e r o c y c l e s with nucleophilic organic compounds in the p r e s e n c e of acylating agents or
in the p r e s e n c e of active metals. In the f i r s t case, h e t a r y l a t i o n is effected by the N-acyl salts of the h e t e r o -
c y c l e s f o r m e d as i n t e r m e d i a t e s in situ and is s i m i l a r in many r e s p e c t s to the widely-used and thoroughly
studied r e a c t i o n s of electrophilic substitution by tropylium, cyclopropenylium and arenediazoninm salts,
e t c . Naturally, the m e c h a n i s m s of h e t a r y l a t i o n with salts of other h e t e r o a r o m a t i c cations such as p y r y l i u m
salts (the s o - c a l l e d T r e i b s - - K r o h n k e r e a c t i o n [3, 4]) is s i m i l a r .
H e t a r y l a t i o n with nitrogenous h e t e r o c y c l e s in the p r e s e n c e of active m e t a l s is p e r f o r m e d by anion
radicals f o r m e d as i n t e r m e d i a t e s in the o n e - e l e c t r o n reduction of the nitrogenous h e t e r o a r o m a t i c
s y s t e m s [5].
Hetarylation of N-Acyl Salts of Aromatic Heter0cycles
The hetarylation r e a c t i o n with N - a c y l salts of pyridine in situ was f i r s t p e r f o r m e d , to t h e i r own s u r -
p r i s e , by Claisen and Haase [6] at the beginning of the p r e s e n t century. On acylatiug acetophenone with
benzoyl chloride in the p r e s e n c e of pyridine, in addition to the O-benzoyl derivative of the enolic f o r m of
acetophenone, they isolated a compound containing a pyridine nucleus the s t r u c t u r e of which was established
only in 1951 [7]. tn 1905, R e i s s e r t [8] d i s c o v e r e d that the r e a c t i o n of quinoline or isoquinoline with KCN
in the p r e s e n c e of benzoyl chloride f o r m e d N-benzoyl d e r i v a t i v e s of c~-cyano-l,2-dihydroquinoline o r
-isoquinoline. T h e s e compounds, subsequently called " R e i s s e r t ' s compounds," p r o v e d to be e x t r e m e l y
r e a c t i v e and have a s s u m e d an important place in p r e p a r a t i v e organic c h e m i s t r y (see the reviews [9, 10])
and the r e a c t i o n in which they a r e f o r m e d has e n t e r e d chemical h i s t o r y as R e i s s e r t ' s r e a c t i o n .
On considering f r o m the usual points of view r e a c t i o n s of nitrogenous h e t e r o a r o m a t i c compounds in
the p r e s e n c e of acylating agents, it b e c o m e s c l e a r that R e i s s e r t ' s r e a c t i o n is a special c a s e of the h e t a r y l a -
tion of an inorganic compound.
In a study of the acylation of dimethylaniline [11] and of some ketones [12-14] by acyl halides in the
p r e s e n c e of pyridine, it was found that in t h e s e c i r c u m s t a n c e s pyridine r e s i d u e s e n t e r e d the dimethylaniline
nucleus and the ketone m o l e c u l e s . It was possible to introduce a quinoline r e s i d u e s i m i l a r l y [15]. It was
c o n s i d e r e d [7, 11, 15] that N-acylpyridinium salts a r e f o r m e d in the c a s e s d e s c r i b e d . However, only in the
l a s t decade through the efforts of many w o r k e r s , including the author of the p r e s e n t review, have the syn-
thetic possibilities of this interesting r e a c t i o n been established and its m e c h a n i s m been studied. The
author hopes that the publication of the p r e s e n t r e v i e w and the unsolved questions connected with the
h e t a r y l a t i o n r e a c t i o n that r e m a i n will stimulate in the r e a d e r an i n t e r e s t in this field of the c h e m i s t r y of
h e t e r o a r o m a t i c compounds.

Donetsk State University. T r a n s l a t e d f r o m Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 3-18,

January, 1974. Original a r t i c l e submitted May 25, 1973.

9 1975Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy o f this article is available from the publisher for $15.00.
 Mechanism of the Reaction. The f i r s t stage of the r e a c t i o n of nitrogenous h e t e r o a r o m a t i c s y s t e m s
containing a "pyridine" nitrogen atom in the ring with organic compounds in the p r e s e n c e of acylating agents
is the formation of aromatic N-acyleyelammonium salts. Only in a few c a s e s have such hetarylating agents
been isolated [1, 16, 17], but their formation in solutions and t h e i r participation in reactions in situ has been
s t r i c t l y demonstrated [1. 22].

+ RCOX " " ~N

I X-
COR
i
T h e r e are grounds for believing, in spite of established opinion, that the simple equilibrium shown
above exists only in reactions of t e r t i a r y amines. In the r e a c t i o n of aeylating agents with nitrogenous
h e t e r o a r o m a t i c s y s t e m s not only are the N-acyl salts of type (I) then capable of decomposing into the initial
r e a c t a n t s but, as a r e s u l t of reaction with anions, they can also apparently be converted into other e l e c t r o -
neutral p a r t i c l e s [22]: for example:

+ X~

COR
. - - C x-
H X
- I
COR COR linch or
T_. iT "N~X N
- I J
COR COR
r~

In actual fact, the possibility of the e x i s t e n c e of the N-acyl salts {I) in the f o r m of c h a r g e - t r a n s f e r
complexes (CTes) (II) is not a m a t t e r of doubt in view of the i n c r e a s e d electrophilicity of the N-acyl h e t e r o -
a r o m a t i c cations as c o m p a r e d with the N-alkyl and N - a r y l * cations, where the existence of CTCs has been
demonstrated [25, 26]. The decomposition of the complexes (II) into f r e e radicals has been shown by means
of ESR and chemically [22]. In particular, in an investigation of m i x t u r e s of isoquir/51ine and of phenan-
thridine with benzoyl chloride (but not the fluoride) a signal was found by the ESR method corresponding to
an unpaired electron. The heating of m i x t u r e s of quinoline, isoqninoline, or benzoquinolines with acyl chlo-
rides led to the d i m e r s (VI). the formation of which can be explained only by the recombination of the N-acyl
h e t e r o a r o m a t i o r a d i c a l s (V) [22. 27].

{~ .--'~ ~ c C -, ~ + c L ' , . ~ +cL2

I i I l
CrtcOR COR ~ COR COR COR V-]

Compounds of type (VI) have also been obtained by the r e a c t i o n of quinoline or isoquinoline with acid
anhydrides in the p r e s e n c e of zinc dust [22, 28].
In general, the possibility of the formation of N-alkyl and N - a r y l h e t e r o a r o m a t i c radicals in the one-
e l e c t r o n reduction of the corresponding cations by s e v e r a l anions has been discussed repeatedly in the
l i t e r a t u r e [29-31] and is apparently inherent in all h e t e r o a r o m a t i c cations under c e r t a i n conditions which
depend on the electrophflieity of the cation, the nucleophflicity of the anion, and the ionizing capacity of the
solvent.
The r e a c t i o n of anions and h e t e r o a r o m a t i c cations with the f o r m a t i o n of a ~ b o n d between them (com-
pounds of type (IV). called "Kryptosalze" ["Crypto-salts" or pseudo-salts"] [32] or " p s e u d o - b a s e s " [33], or
" R e i s s e r t compounds" [9, 10] depending on the nature of the anion) is also well known and is d e t e r m i n e d by
the nature of the cation and of the anion. An analysis of much l i t e r a t u r e information (see. for example, the
reviews [26]) shows that anions of low nucleophilicity (C104-, BF4-, A1C14-, etc.) f o r m only ionic bonds with

* Concerning the influence of substituents attached to the h e t e r o a t o m on the electrophilicity of pyridinium

cations, see [23-25].
h e t e r o a r o m a t i c cations. S i m i l a r q u a t e r n a r y s a l t s a r e p r e s e n t in solution in the f o r m of ion p a i r s or of
s o l v a t e d f r e e ions and exhibit the g r e a t e s t r e a c t i v i t y with r e s p e c t to nucleophilic agents. M o r e highly
nucleophilic anions (r', OH-, CN-, etc.) r e a c t with cations to form, depending on the e l e c t r o p h i l i c i t y of the
cation, CTCs or new compounds with a r bond between the anion and a c a r b o n a t o m of a ring. The c o m -
pounds (IV) f o r m e d m a y also take p a r t in r e a c t i o n s with nucleophilie agents with the r e p l a c e m e n t of the X
g r o u p s by o t h e r r e s i d u e s , but the activation e n e r g y of such substitution r e a c t i o n s is a p p a r e n t l y higher than
the activation e n e r g i e s of r e a c t i o n s i n v o l v i n g the d i r e c t addition of nucleophiles to cations. Additional
p r o o f s of the c o n v e r s i o n of the N - a c y l s a l t s {I) initially f o r m e d into e l e c t r o n e u t r a l p r o d u c t s have been ob-
tained in a study of the e l e c t r i c a l conductivity of c r y s t a l l i n e 2 - ( N , N - d i p h e n y l c a r b a m o y l ) i s o q u i n o l i n i u m
chloride [22].
Thus, the f o r m a t i o n of the d i m e r s (VI) and a l s o a study of the e l e c t r i c a l conductivity and ESR s p e c t r a
of solutions of nitrogenous h e t e r o a r o m a t i c compounds and aeyl halides in neutral s o l v e n t s shows the s i m u l -
taneous p r e s e n c e of both N - a c y l h e t e r o a r o m a t i c cations (I) and N - a c y l h e t e r o a r o m a t i c r a d i c a l s (III) and (V).
Accordingly, the h e t a r y l a t i o n r e a c t i o n can t a k e p l a c e by two m e c h a n i s m s - - cationic and r a d i c a l m e -
c h a n i s m s [22] -- the r e a l i z a t i o n of one of which a p p a r e n t l y depends on m a n y f a c t o r s affecting the s t a b i l i z a -
tion of the cations (I) f o r m e d initially: the n a t u r e of the counter-ion, the p o s s i b i l i t y of the delocalization of
the p o s i t i v e c h a r g e in the cation, the ionizing c a p a c i t y of the solvent, etc. As a rule, N - a c y l a c r i d i n i u m salts
r e a c t in situ by the cationic m e c h a n i s m , N-acylquinolinium, -isoquinolinium, a n d - b e n z o q u i n o l i n i u m salts
by a r a d i c a l m e c h a n i s m , and p y r i d i n i u m s a l t s by both m e c h a n i s m s , but this can be changed by varying the
solvent or by using c a t a l y s t s and UV i r r a d i a t i o n . With the cationic r e a c t i o n m e c h a n i s m , fully a r o m a t i z e d
substituted h e t e r o c y c l e s a r e obtained as the r e s u l t of m i g r a t i o n of a hydride ion f r o m the N - a c y l dihydro
d e r i v a t i v e s f o r m e d as i n t e r m e d i a t e s to the N - a c y l h e t e r o a r o m a t i c cations (I). In the c a s e of h e t a r y l a t i o n
by the r a d i c a l s (V) such hydride m i g r a t i o n does not take p l a c e b e c a u s e of the r e d u c e d e l e c t r o p h i l i c i t y of the
N - a c y l h e t e r o a r o m a t i c r a d i c a l s and the r e a c t i o n stops at the stage of the f o r m a t i o n of the dihydro d e r i v a -
t i v e s [22]. F o r example, in the r e a c t i o n of acridine with dialkylanilines [34-37], indoles [38, 39], p y r r o l e s
[40], furan [41], and other nucleophflic a r o m a t i c h e t e r o c y c l e s and with aliphatic compounds [42-45], 9 - s u b -
stituted a c r i d i n e s and 1 0 - a c y l d i h y d r o a c r i d i n e s a r e f o r m e d :

-- ~ 4NR2-p ~R2-P+ ~-~

C6HsNR2 4-VII
--H-
I I I
I
CORq~ C~- COR CORI~~ , ~ CORx_
Vlll

~ Xt
R2- p

Apparently, the N - a c y l a c r i d i n i u m cation (VII), on attacking the activated a r o m a t i c nucleus of a dialkylaniline,

f o r m s a l 0 - a c y l - 9 - a r y l - 9 , 1 0 - d i h y d r o a c r i d i n e (VIII). Then, under the action of an e x c e s s of the compound
(VII), hydride m i g r a t i o n t a k e s p l a c e with the f o r m a t i o n of the N - a c y l d i h y d r o a c r i d a n e (X), which can be i s o -
lated in a l m o s t t h e o r e t i c a l yield [35], and the unstable N - a c y l salt (IX), which is r e a d i l y c o n v e r t e d in the
p r e s e n c e of an e x c e s s of a c r i d i n e into the final r e a c t i o n p r o d u c t (XI). Hydride m i g r a t i o n is p o s s i b l e in this
r e a c t i o n b e c a u s e of the g r e a t e r e l e c t r o p h i l i c i t y of the N - a c y l a c r i d i n i u m cation (VII) than of the cation (IX),
which has an e l e c t r o n - d o n a t i n g dialkylaminophenyl substituent.
To c o n f i r m the p r o p o s e d s c h e m e of cationic hetarylation, a m o d e l r e a c t i o n of hydride m i g r a t i o n arm-
logous to that d e s c r i b e d above has b e e n p e r f o r m e d [35]:

I I I- t z- I
CH~ C2H 5 CH 3 C2H s
>.:ii XHt XtV

3
 In this case, hydride t r a n s f e r also t a k e s p l a c e b e c a u s e of the g r e a t e r e l e c t r o p h i l i c i t y of the N - e t h y l -
a c r i d i n i u m cation {XII) than of the ion {XIII) in view of the p r e s e n c e of an electron-donating substituent in
the l a t t e r . The salt (XIII) f o r m e d in this p r o c e s s is stable and has been isolated t o g e t h e r with N-ethyldihy-
d r o a c r i d i n e [22. 35]. The hydride reduction of acridine methiodide to N - m e t h y l d i h y d r o a c r i d i n e by r e a c t i o n
with v a r i o u s N - m e t h y l d i h y d r o a e r i d i n e s having electron-donating substituents in position 9 t a k e s p l a c e
s i m i l a r l y [35].
H e t a r y l a t i o n by p y r i d i n e in.the p r e s e n c e of acylating agents m a y take p l a c e both by a r a d i c a l m e c h a -
n i s m with the f o r m a t i o n of 4--substituted 1 - a c y l - l . 4 - d i h y d r o p y r i d i n e s and by a cationic m e c h a n i s m with the
f o r m a t i o n of 4 - s u b s t i t u t e d p y r i d i n e s . In p a r t i c u l a r , when the r e a c t i o n of pyridine with indoles and acyl
ha]ides is p e r f o r m e d in absolute benzene. 1 - a e y l - 4 - ( i n d o l - 3 - y l ) - l . 4 - d i h y d r o p y r i d i n e s a r e f o r m e d [46]. In
m o r e highly p o l a r solvents, the r e a c t i o n t a k e s place with the f o r m a t i o n of 1 - a c y l - 3 - { p y r i d i n - 4 - y l ) i n d o l e s
[47]. The authors concerned do not d i s c u s s the r e a s o n s f o r the f o r m a t i o n of the 1,4-dihydropyridine (XV)
in s o m e c a s e s and the c o m p l e t e l y a r o m a t i c compound (XIX) in others. B e r g m a n [47] has given a r e a c t i o n
s c h e m e analogous to that shown above f o r the acridinylation of dialkylanilines [35] including the s t a g e of the
reduction of N - a c y l p y r i d i n i u m s a l t s to 1 - a c y l - l . 4 - d i h y d r o p y r i d i n e s ~XVII). for f o r m a t i o n of which was
d e m o n s t r a t e d [47]. However, instead of a s i m p l e h y d r i d e - t r a n s f e r scheme, B e r g m a n suggested the follow-
ing l e s s probable p r o c e s s :

--COR :o/. )(Vi'~

I
H COR
xv xv_.2 \

COF~ - - COR
XlX XVIII

It r e m a i n s u n c l e a r through what r e a g e n t s the t r a n s f e r of the acyl group is effected, while according to the
s c h e m e given above t r a n s a c y l a t i o n could take place a f t e r the l o s s b y compound (XV) of a hydride ion
through the r e s u l t i n g cation, since the acylating capacity of N - a c y l p y r i d i n i u m cations is e x t r e m e l y high [1].
In actual fact, under analogous conditions in the r e a c t i o n of pyridine with indole in the p r e s e n c e of t r i c h l o -
r o a c e t y l chloride, the a e y l a t i o n and not the pyridinylation of indole was o b s e r v e d [47].
The change in the m e c h a n i s m of the h e t a r y l a t i o n r e a c t i o n m a y a p p a r e n t l y be explained by the a s s u m p -
tion that in feebly ionizing solvents the N - a c y l p y r i d i n i n m s a l t s f o r m e d a r e in the s t a t e of a close ion p a i r .
which facilitates the t r a n s f e r of an e l e c t r o n of the anion to the lowest vacant ~ orbital of the cation with the
f o r m a t i o n of N - a c y l p y r i d i n i u m r a d i c a l s . In p o l a r solvents, however, nitrogenous h e t e r o a r o m a t i c cations
and anions in the d i s s o c i a t e d s a l t a r e solvated, the f o r m a t i o n of r a d i c a l s is m o r e difficult and. probably, in
this c a s e cationic h e t a r y l a t i o n t a k e s p l a c e with subsequent hydride m i g r a t i o n as was shown above.
To i n c r e a s e the activity of the N - a c y l p y r i d i n i u m s a l t s in cationic h e t a r y l a t i o n r e a c t i o n s it has been
p r o p o s e d to u s e Lewis acids as c a t a l y s t s [48-51]. In t h e s e c i r c u m s t a n c e s , the yields i n c r e a s e s h a r p l y and
it is p o s s i b l e to u s e various N - a e y l p y r i d i n i u m s a l t s in the r e a c t i o n and to d e t e r m i n e the influence of the
acyl r e s i d u e s on the r e a c t i v i t y of the salts. The action of the c a t a l y s t s is a p p a r e n t l y explained by a change
in the n a t u r e of the c o u n t e r - i o n and the r e s u l t i n g change of the cationic i n t e r a c t i o n in the N - a c y l p y r i d i n i u m
s a l t s . In the p r e s e n c e of A1C13 or other Lewis acids, the complex c o u n t e r - i o n s A1C14- o r o t h e r s with the
s a m e elevated nucleophilicity a r e f o r m e d , the r e a c t i o n of which with the p y r i d i n i u m cation is limited only
b y e l e c t r o s t a t i c f o r c e s . The following m e c h a n i s m of the h e t a r y l a t i o n of dimethylaniline can be imagined:

l& . N I A~CL3 ~ CBHsN(CHfl2 H

~O C--N/~LC6H4N (CH3)2- --

x-~ j
-- H H "1
+ XXI ~ . j
---= ~.-I-
CH3)2-p
I
COR
XXIII ~.~ J/ xx--9
 On r e a c t i o n with nucleophiHc a r o m a t i c [52-55], h e t e r o a r o m a t i c [41-43], and aliphatic [56] compounds,
N-acylquinolinium and N-acylisoquinolinium salts f o r m high yields of stable N-acyl derivatives of 1,2-di-
hydroquinoline and 1,2-dihydroisoquinoline. In t h e s e c a s e s , the r e a c t i o n s take place, even though slowly,
at r o o m t e m p e r a t u r e in the absence of catalysts. They can be a c c e l e r a t e d by heating or by irradiation with
UV light [57]. In c o n t r a s t to acylpyridinium salts, in r e a c t i o n s of acylquinolinium salts the yields a r e
p r a c t i c a l l y independent of the e l e c t r o n i c nature of the acyl residue (which again c o n f i r m s the radical m e -
chanism of the reactions). Also in h a r m o n y with a radical m e c h a n i s m of the r e a c t i o n s is the fact that the
yields a r e substantially affected by the n a t u r e of the anions of the 1-acylquinolinium salts. Thus, in the r e -
actions of quinoline and benzoyl fluoride, benzoyl chloride, benzoyl bromide, and benzoyl iodide with dimeth-
ylaniline under standard conditions the yields r i s e r e g u l a r l y with an i n c r e a s e in the nucleophilicity of the
anion, which p e r m i t s the assumption of the participation in the r e a c t i o n s not of the 1-acylquinolinium cation
but of a c h a r g e - t r a n s f e r complex which subsequently d e c o m p o s e s into a 1-acylquinolinium radical and halo-
gen [53, 57]. The p r e s e n c e of r a d i c a l s in the r e a c t i o n m i x t u r e has been confirmed by ESR spectroscopy.
A c h a r a c t e r i s t i c f e a t u r e of r a d i c a l hetarylation r e a c t i o n s is the formation of d i m e r s in the h e t a r y l a -
tion of compounds p o s s e s s i n g weak nucleophilicity (benzene. anisole, thiophene, cyclopentadiene, etc.):

COR COR ~ I
,.~OR
~ COR
N

R'
x.xvJ

[ ~ + (RCO)20
t I
COR COR
~q

Derivatives of types (XXVI) and (VI) a r e also f o r m e d in the definite r a d i c a l h e t a r y l a t i o n of nucleo-

philic organic compounds with N-acyl h e t e r o a r o m a t i c radicals under the conditions of the Dimroth r e a c t i o n
[58-62]. N-Substituted h e t e r o a r o m a t i c r a d i c a l s p o s s e s s electrophilic p r o p e r t i e s [22, 63] and t h e r e f o r e with
any hetarylation m e c h a n i s m t h e r e is an electrophilic r e a c t i o n . In all cases, the addition of the h e t e r o c y c l i c
r e s i d u e s to the position with the highest e l e c t r o n density is o b s e r v e d [1] although the ele'ctrophflieity of
h e t e r o a r o m a t i c r a d i c a l s has n e v e r t h e l e s s p r o v e d insufficient for the detachment of a hydride ion f r o m the
dihydro derivatives (XXVI). P a r t i a l l y hydrogenated compounds of type (XXVI) a r e c o n v e r t e d f a i r l y readily
into a r o m a t i c s y s t e m s e i t h e r by the detachment of a hydride ion or as the r e s u l t of the loss of earbanions,
p a r t i c u l a r l y in those c a s e s w h e r e the carbanions split off are stabilized by neighboring carbonyl groups
[64, 65]:

;(XVi
f
/ COR COR
/ -H-

COR COR
I
R=CH(CO2R) 2;cH(COCH3) 2 }CH(CN)CO2CzH5 ; R" =C6H4NR2 . D.

The e a s e of cleavage of a c a r b o n - c a r b o n bond in compounds of type (XXVI) with e l e c t r o n - a c c e p t i n g

substituents in the side chain is responsible f o r the possibility of the o c c u r r e n c e of t r a n s h e t a r y l a t i o n r e a c -
tions as a r e s u l t of which the h e t e r o c y c l i e r e s i d u e m i g r a t e s to other compounds with labile hydrogen atoms
[64, 65], as is the c a s e in cyclopentatriene compounds [66], f o r example [64]:

COC6H5 COC6H5
XXVll XXWL|

T h e r e a r e s i m i l a r examples of such e a s y cleavage of a C--C bond in the l i t e r a t u r e [66-68] and. as it ap-

p e a r s to us, the m e c h a n i s m of this p r o c e s s is s i m i l a r in many c a s e s to Grob fragmentation [69] and.
apparently, has a general nature. Thus, the reversibility of radical hetarylation reactions and the possibility
of the occurrence of transhetarylation reactions in some cases have been established [64, 65].
Hetarylating Agents. The following have been used successfully in situ as hetarylating agents in the
direct hetarylation of organic compounds: N-acylpyridinium salts [1, 6, 11, 14, 46-51], N-acylquinoliniu.m
salts [40-46. 52, 53. 70-751, N-acylisoquinolium salts [54. 56. 76-79L N-acylacridinium salts [34-39, 80-82J,
N-acylphenanthridinium and other N-acylbenzoquinolinium salts [22, 55, 78], and also N-acyl salts of some
azines [10. 22] and azoles [83, 84]. Thus, the hetarylation reaction apparently has a general nature and can
be extended to any heteroaromatic systems having a nitrogen atom of the pyridinium type in the ring. The
electronic effects of substituents in the benzene rings of benzopyridines have practically no influence on
the yields of hetarylation products [57. 70]. This has also proved to be valid, in particular, for 8-methyl.
quinoline [70], although it has been shown previously [72] that the Reissert reaction does not take place
with 8-substituted quinolines because (in the opinion of Poppet al. [72]) of the screening of the nitrogen
atom and the difficulty of formation of 1-acyI salts. The Reissert reaction could not be extended to many
substituted quinolines, to pyridine, and to acridine [9, 10], while the hetarylation of organic nucleophiles by
all these compounds takes place fairly readily. Exceptions are formed by 2- and 4-substituted pyridines
and quinolines. 1-Acyl salts of 2- and 4-methylquinolines do not take part in the hetarylation reaction but
are converted (with the capture of a hydride ion) into 1-acyl-l.2-dihydroquinoline derivatives [85]. 1-Acyl-
lepidinium and 1-acylquinaldinium salts behave differently. Depending on the conditions of performing the
reactions, acyllepidinium cations are converted either into 1-acyl-l,2-dihydroquinolines (XXIX) (at 50~
or into the "dimers" {XXX) (at 100~

+H- OH-

C,- [o]
COR
1-HCt
CH~-
XXIX COR
'
CH -COR CH HCOR
COR COR COR H
XXX

The reaction of acyl halides with quinaldine forms 1- acyl- 1,2,3, 4-tetrahydroquinaldines {XXXI), apparently
as the result of the disproportionation (with hydride transfer) of the intermediate 1-acyl-2-methyl-1,2-di-
hydroquinolines [85]:

2 H"~ 2 +

'co. ' L ao. "J co. co.

XXXl

Halides of aliphatic, aromatic, and heterocyclic carboxylic acids [1] and sulfonic acids [1, 9. 10, 46]
and chlorides of some acids of phosphorus [86-88] have proved suitable for the formation of N-acyl salts of
heteroaromatic cations and subsequent hetarylation with them. Hetarylation takes place in the presence of
some analogs and vinylogs of acyl halides such as cyanuryl chloride [74, 89. 90] and ~-chlorovinyl ketones
[91]. with the formation of compounds of types (XXXII) and (XXXIII).

.y. #
C~ xxxif!
XXXI[

Hetarylation of Activated Aromatic and Heteroaromatic Nuclei. A necessary condition for the sue-
cessful occurrence of the hetarylation reaction, as for the similar azo coupling reaction, is a sufficiently
high nucleophilicity of the compounds undergoing hetarylation. Such compounds include aromatic amines.
phenols, and other activated aromatic nuclei, and also It-excess heterocycles (pyrrole, indole, furan, etc.).
In the reaction of s i x - m e m b e r e d aromatic nitrogenous heterocyeles in the presence of aeyl halides with
such compounds, various heterocyelic derivatives of dialkylanilines and their analogs have been obtained:
N-phenylmorpholine, N-phenylpyrrolidine, and N,N,-diphenylpiperazine, and also 1- alkyl- 2, 3- dihydroindoles
and 1-alkyl-l,2,3.4-tetrahydroquinolines [6, 11, 15, 35, 48-55. 76, 92]. The most active hetarylating agents
have proved to be N-acylisoquinolinium salts [76] and acylacridinium salts [35-37]. Apart from the dialkyl-
anilines and their analogs, it has been possible to introduce an isoquinoline residue in this way only into the
nucleus of r e s o r c i n o l dimethyl ether and of 2, 6-di-tert-butylphenol, where the hydroxy group is screened
and is not aeylated: other activated aromatic compounds were either aeylated under the reaction conditions
(phenols, anilines) or were insufficiently nucleophilic (anisole).
The p y r r o l e ring hetarylates more readily. Attention was first drawn to the possibility of the hetar-
ylation of p y r r o l e by Fi s c he r and Ernst [93], who, by the reaction of pyridine and cyanogen bromide on 3-
ethoxycarbonyl-2,3-dimethylpyrrole,isolated a colorless substance containing a pyridine residue the struc-
ture of which they were unable to determine. L at er [94, 95] pyridinylpyrrole residues of undetermined
s t r u ctu r e were obtained in attempts at the acylation of pyrrol es with acyl chlorides in pyridine. In the re -
action of 2- ethoxy- 3,4- dimethylpyrrole with pyridine in the presence of ethyl chloroformate, 3,4- dimethyl-
2, 5-di(pyridin-4-yl)pyrrole was unexpectedly obtained [96]. As a result of a detailed study [97, 98] of the
conditions for the hetarylation of p y r r o l e it has been established that, contrary to other information in the
l i t e r a t u r e [99], it is possible with any N-acyl salts of nitrogenous heteroaromatic cations. The most active
proved to be N-acylisoquinolinium salts, the reaction of which with unsubstituted p y r r o l e at room t e m p e r a -
ture gave mono(2-acyl- 1,2-dihydroisoquinolin- 1-yl)pyrroles (XXXIV, XXXV) and bi s(2-acyl -l , 2-di hy d ro iso -
quinolin-l-yl)pyrroles (XXXVI). The ratio of the compounds formed depends to a considerable degree both
on the nueleophilicity of the p y r r o l e ring and on the electrephilicity of the N-aeylcyclammonium salts,
which is connected, under otherwise the s a m e conditions, with the nature of the acyl residue: with active
salts the bis derivative (XXXVI) is formed, in the main; with l ess active compounds a mixture of all three
compounds, and with the still less reactive N, N-diphenylcarbamoylisoquinolinium salt only the mono deri-
vative (XXXIV).

COR COR COR COR

)(XXI'V XXXV H XXXVl

It is possible to introduce only one heterocyclic residue into an a position of the p y r r o l e nucleus of
N-phenylpyrrole, the nucleophilicity of which is lowered because of the electron-accepting influence of the
phenyl substituent. The monohetaryl derivatives (XXXIV) may also take part in a hetarylation reaction with
the formation of {XXXVI) or of 2, 5-dihetarylpyrroles with various heteroeyclic residues or with the same
heterocycles but with different acyl substituents in them [98],
By a similar method, it has proved possible to obtain various heteroeyelic furan derivatives, as well,
in one stage [41, 100, 101]. In particular, the reaction of furan, sylvane, or 2,5-dimethylfuran with quino-
line, isoquinoline, or phenanthridine in the presence of acyl halides gave mono- and diheterocyclic deriva-
tives of furan:

COR COR

In this reaction, the formation of ~-hetarylfurans with a free a position as has been observed in the
hetarylation of p y r r o l e s was not found.
Under similar conditions, N-acyl salts of acridine react with the formation of N-acyldihydroacridines
and of 9-furylacridine.
Attempts have been made to extend the hetarylation reaction to thiophene, benzo[b]thiophene, 2-meth-
ylthiophene, selenophene, and 2-methylselenophene [22. 27]. It is known [102-105] that in electrophilie sub-
stitution reactions the relative reactivities of ~ - e x c e s s heterocyclic systems change in the following way*:

*The figures c h a r a c t e r i z e the reactivities of these heterocycles in electrophilic substitution reactions [102-105].
 1 1.5 150 300 3,5 .'I04 H105 "CH32.105
In a g r e e m e n t with this. all attempts to p e r f o r m the hetarylation of thiophene and of benzo[b]thiophene have
p r o v e d unsuccessful. In the reactions of N-acylpyridinium and N-acylacridinium cations, only the initial
r e a c t a n t s w e r e isolated, but the reaction of N-acylisoquinolinium salts with thiophene and benzo[b]thiophene
gave d i m e r s of the N - a c y l radicals f o r m e d as i n t e r m e d i a t e s .
It has been possible to extend the arylation reaction to the m o r e nucleophilic selenophene, 2-methyl-
selenophene, and 2-methylthiophene where, as in the case of the furans, mono- and dihetaryl derivatives
a r e f o r m e d [27].
In contrast to the hetarylation of p y r r o l e s and other f i v e - m e m b e r e d h e t e r o c y c l e s , in the indole s e r i e s
this reaction has r e c e n t l y attracted g r e a t attention [39, 46. 47, 58, 91]. The reactions of indoles with p y r i -
dine, quinoline, isoquinoline, and some benzoquinolines in the p r e s e n c e of chlorides of carboxylic and sul-
fonic acids and also of acids of phosphorus and B-halogenovinyl ketones f o r m the corresponding indole
derivatives [22]:

In the r e a c t i o n of acridine with indoles under s i m i l a r conditions, however. 9 - (indolin-3-yl)acridines

and N - a c y l d i h y d r o a c r i d i n e s w e r e obtained [39]. It must be mentioned that it has not p r e v i o u s l y been p o s s i -
ble to introduce an acridine residue into the indole molecule in this way. Acridinylindoles can also be ob-
tained by the r e a c t i o n of ~cridine h y d r o c h l o r i d e with indoles [39].

Hetarylation of Some CH-Acids

The most active N-acylisoquinolininm salts h e t a r y l a t e organic CH-acids with pK a values of about 20-
21 (for example, acetone, with pK a 20), while less active salts either a r e acylating agents under these con-
ditions, or f o r m d i m e r s , or h e t a r y l a t e the CH-acids. In particular, N-acylammonium salts a r e acylating
agents only when t e r t i a r y aliphatic amines a r e used, and in these c i r c u m s t a n c e s O-acylation and C-acyla-
tion of the carbonyl compounds take place to equal extents [6, 106, 107]. In the p r e s e n c e of pyridine, de-
pending on the n a t u r e of the carbonyl component, either O-acylation (in r e a c t i o n s with B-dicarbonyl com-
pounds) or pyridinylation (in reactions with ketones) takes place predominantly [12-15, 46]. As a rule,
N-acylquinolinium. N-acylisoquinolinium, and N-acylphenanthridinium salts h e t a r y l a t e both monocarbonyl
and ~ - d i c a r b o n y l compounds [7. 46, 78, 107]. Similarly, the r e a c t i o n of acridine with acetophenones in the
p r e s e n c e of acyl halides has led to 9-phenacylacridines and other ketones of the acridine s e r i e s [56], al-
though t h e r e is information in the l i t e r a t u r e that such reactions do not take place with acridine [46]. It has
also been possible to synthesize h e t e r o c y c l i c derivatives of oxosteroids in the same way [79, 108, 109].
Making use of the activation of the h e t e r o c y c l i c nucleus in the molecules of thiazolidinones and p y r -
azolinones, like ketones, it has been possible to extend the method of hetarylation by N-acyl salts to these
h e t e r o c y c l e s , as well [42. 43].

o R

COR COR
X=O,S,NCBH5, R=CH3; CBHs; N(CBH5)2 ; f u ~ l ; t~enyl ; Oc2H 5
Re=H ; C2H5; CsH5

The alkaline h y d r o l y s i s of the compounds synthesized f o r m s the corresponding thioglycolic acids of the
h e t e r o c y c l i c s e r i e s , and this can be r e g a r d e d as a convenient p r e p a r a t i v e method for obtaining them [42, 43].
It has also been possible to extend the hetarylation r e a c t i o n to such CH-acids as cyclopentadiene,
phenylacetylene, indene, azulene, and guaiazulene {pKa values 18, 15.5, 20, and 21, respectively) and others,
while fluorene (pKa 22.9) and f e r r o c e n e do not take p a r t in this r e a c t i o n [22, 110].
The Arbuzov Rearrangement under the Action
of N-Acyl Heteroaromatie Cations
Recently it has b e e n p r o p o s e d to s y n t h e s i z e phosphonic acids of the acridine s e r i e s b y the reaction of
a c r i d i n i u m salts with sodium diethyl phosphate [111].
O O O
II II II
H P--(OR). P--(OR)- P--(OH)_

Ncl PO (OR)2 ---.

j ? - N
I
E "
I
R R R R

Simultaneously [112], a general and m o r e convenient method for synthesizing h e t e r o c y c l i c phosphonic

acids on the b a s i s of the r e a c t i o n of h e t e r o a r o m a t i c cations with t r i a l k y l phosphites was developed. The
p e r f o r m a n c e of this reaction is p a r t i c u l a r l y convenient with protonic s a l t s of s i x - m e m b e r e d nitrogenous
h e t e r o c y c l e s or with t h e i r N - a c y l salts, since in t h e s e c i r c u m s t a n c e s the e n d - p r o d u c t s of the r e a c t i o n a r e
h e t e r o o c y c l i c phosphonic acids, and not t h e i r q u a t e r n a r y s a l t s [113-115].
It has p r o v e d p o s s i b l e to s i m p l i f y this method b y combining the s t a g e s of obtaining the acridine h y d r o -
chloride and the t r i a l k y l phosphites. F o r this purpose, the reaction of acridine with p h o s p h o r o c h l o r i d i t e s
is p e r f o r m e d in any alcohol, and the N - p h o s p h o r y l acridine s a l t s so f o r m e d r e a c t with the alcohol to f o r m
t r i a l k y l phosphites and acridine hydrochloride, which then takes p a r t in the Arbuzov r e a r r a n g e m e n t [116]:

(RO)IPO (RO)2PO (HO)2PO

AC~ H . O P( ,
_ H . I "oR"
~ R'OH
...... +c,o,oR,,- -- + o oR,,o.-
I ct- ~c, H
P(OR)2

In this way it has also been p o s s i b l e to obtain mixed e s t e r s of 9 . 1 0 - d i h y d r o a c r i d i n - 9 - y l p h o s p h o n i c

acid.

Hetarylation of Organic Compounds with Nitrogenous

Heteroaromatic Anion Radicals
It is not p o s s i b l e by using N - a c y l s a l t s to introduce h e t e r o c y c l i c r e s i d u e s into compounds containing
NH. OH, and SH groups, since in t h e s e c a s e s acylation, and not hetarylation, takes place. In view of this,
a m o r e u n i v e r s a l method f o r the d i r e c t h e t a r y l a t i o n of organic compounds used in h e t e r o a r o m a t i c anion
r a d i c a l s f o r m e d in the o n e - e l e c t r o n reduction of nitrogenous b a s e s with active m e t a l s has been developed
[117-119]. In p a r t i c u l a r , when a m i x t u r e of any s i x - m e m b e r e d nitrogenous h e t e r o c y c l e and indole is heated
with m e t a l s in an anhydrous a p r o t i c solvent in an a t m o s p h e r e of c a r e f u l l y dried nitrogen, a m i x t u r e of
h e t e r o c y c l i c d e r i v a t i v e s of indole and of b i h e t e r o c y c l e s is f o r m e d . The total yield of r e a c t i o n p r o d u c t s and
the r a t i o of the i s o m e r i c h e t a r y l i n d o l e s and b i h e t e r o c y c l e s f o r m e d is d e t e r m i n e d by the redox potential and
by the coordinating c a p a c i t y of the c a t a l y s t . Thus, in the r e a c t i o n of quinoline with indole, depending on the
catalyst, 2 , 2 ' - , 2 , 3 ' - , and 4,4'-biquinolinyls and 2- and 4- (indol-3-yl)qninolines, and also p a r t i a l l y h y d r o -
genated biquinolinyls, a r e obtained [117-119]:

H H
 Various hetarylindoles and also heterocyclic derivatives of other v - e x c e s s heterocyeles, phenols, and
aromatic amines have been obtained similarly. The hetarylation of ketones is possible in the same way
provided that the heterocycle used in the reaction is reduced more readily than the ketone [120]. Otherwise,
as the result of one-electron reduction of the ketones by the active metal, anion radicals are formed which
attack the heteroeyelic nucleus with the formation of t e r t i a r y alcohols or which dimerize with the formation
of pinacones (Emmert reaction [121, I22[). On comparing the reduction potentials of various N-heteracyeles
and ketones, it was found that almost all pyridines, with the exception of acridine, are reduced with greater
difficulty than acetophenone [123]. Because of this. on performing the Emmer~ reaction with pyridine,
quinoline, and isoquinoline the corresponding t e r t i a r y alcohols are formed, while with acridine in all cases
it was not carbinols but ketones of the acridine series that were obtained [120]:

In the absence of a nucleophilic organic compound, the reaction of six-membered nitrogenous hetero-
cycles with active metals gave bihetaryls as a result of the recombination of the heteroaromatic anion
radicals formed as intermediates, Preparative methods for obtaining pyridines, biacridinyls, biquinolinyls.
and other biheterocycles have been based on this [119, 124].

LITERATURE CITED
1. A. K. Sheinkman. S. I. Suminov. and A. N. Kost, Usp. Khim., 42, 1415 (1973).
2. M. Khamana. Khim. Gcterotsikl. Soedin.. 1155 (1973): Lectures in Heterocyclic Chemistry, 1 S-51
(1970).
3, A. Treibs and H. Bader, Bet., 9_00,789 {1957).
4. F, Krohnke and K. Dickor~, Bet.. 92, 46 (1959).
5. A. K. Sheinkman. V . A . Ivanov. and S. N. Baranov, Dopovidi AN URSR, 619 {1970).
6. J. Claisen and E. Haase. Ber.. 3..~6,3674 (1903).
7. W. Doering and W. McEwen. J. Amer. Chem. Sac., 7_22,2104 (1951).
8. A. Reissert, Bet., 38. 1603, 3415 (1905).
9. W. McEwen and R. Cobb, Chem. Rev.. 55. 511 (1955).
10. F. Popp, Adv. Heterocycl. Chem., 9, 1 (1968).
11. E. Koenigs and E. Ruppett, Ann. Chem., 509, 142 (1934).
12. E. Chigi, Ber.. 73, 677 (1940).
13. E. Chigi, Ber., 7_.55,764 (1942).
14. E. Chigi, Gazz. Cidm. It~L. 76. 352 (I946).
15. W. McEwen. R. Terss, and J. Elliot. J. Amer, Chem. Sot., 7__44,3605 (1952).
16. A. K. Sheinkman, Yu. N. Sheinker, S. L. Portuova. and A. N. Kost, Dokl. Akad. Nattk SSSR, 157, 14t6
(1964).
17, G. Olah and P. Szilagyi, J. Amer. Chem. Soc., 91, 2949 (1969).
18. R. Paul, D. Singh, and S. Sandhu. J. Chem. Soc., 315 {1959).
19. R. Paul. H. Khurana, S. Vasisht, and S. Chandra, J. Indian Chem. Sot., 4~6, 914 (1969).
BO. J, Hole6ec. Sbornik V6d. Praci. Vysok~ Skola Chem. Teehnol., Pardubiee. 6. 19 (1965).
21. S. V. Bogatkov. V. V. Korshak. T. L Mitafshvili. V. A. Vasnev, S. V. Vinogradova. gnd E. M. Cherka-
sova, DokI. Akad. Nauk SSSR, 19_~4,328 (1970).
22. A. K. Sheinkman, Doctoral Dissertation, Rostov State University, Rostov-on-Don (1972).
23. V. E. Kononenko, T. N. Kashtanova, A. K. Sheinkman, and S. N. Baranov. Reakts. Sposobnost' Organ.
Soedin., 8, 27 (1971).
24. A. Zoltewicz and L. Helmiek, J. Amer. Chem. Soc., 92, 7547 (1970).
ZS. A. K. Sheinkman. L. M. Kapkan, L. G. Gakh. E. V. Titov, S. N. Baranov, and A. N. Kost, Dokl. Akad.
Nauk SSSR. 193. 366 (1970).
26. E. M. Kosower. Progr. Phys. Org. Chem., _3, 81 (1965).
27. A. K. Sheirtkman. T. V. Stupnikova, and A. A. Deikalo, Khim. Geterotsikl. Soedin., 1147 (1973).
28. A. Nielsen, D. Moore, G. Muha, and K. Berry, J. Org. Chem., 2.9, 2175 (1964).
29. L. Winters, N. Smith. and M. Cohen, Chem. Comm., 642 (1970).
30. J. Happ and E. Janzen, J. Org. Chem., 3-5, 96 (1970).
31. E. Janzen, J. Pickett, J. Happ, and W. De Angelis, J. Org. Chem., 35, 88 (1970).

10
32. K. Wallenfels and H. Schiily, Ann. Chem., 621, 86, 106, 166, 198 (1959).
33. D. Beke. Advan. Heterocycl. Chem., I, 167 (1963).
34. A. K. Sheinkman, S. G. Potashnikova, and S. N. Baranov, Khim. Geterotsikl. Soedin.. 563 (1969).
35. A. K. Sheinkman, S. G. Potashnikova, and S. N. Baranov, Zh. Organ. Khim., 6, 614 (1970).
36. A. K. Shein]cman, S. G. Potashnikova, and S. N. Baranov, Methods of Obtaining Chemical Reagents and
Preparations [in Russian], IREA, Moscow, Vol. 23 (1971), p. 49.
37. S. G. Potashnikova. Candidate's Dissertation. Donetsk (1971).
38. A. K. Sheinkraan. S. G. Potashnikova, and S. N. Baranov, Khim. Geterotsikl. Soedin.. 1292 (1970).
39. A. K. Sheinkman, A. N. Kost, S. G. Potashnikova, A. O. Ginzburg. and S. N. Baranov. Khim. Getero-
tsiLl. Soedin.. 648 (1971).
40. A. K. Sheinkman and A. A. Deikalo, Khim. Geterotsikl. Soedin., 126 (1970).
41. A. K. Sheinkrnan, A. A. Deikalo, T. V. Stupnikova, N. A. Klyuev. and G. A. Mal'tseva. Khim. Getero-
tsikl. Soedin.. 1099 (1972).
42. A. A. Deikalo. A. K. Sheinkman, and S. N. Baranov, Khim. Geterotsikl. Soedin., 1359 (1972).
43. A. K. Sheinkman. A. A. Deikalo. T. V. Stupnikova, and S. N. Baranov. Khim. Geterotsikl. Soedin., 284
(1972).
44. A. K. Sheinkraan. G. V. Samoflenko. and S. N. Baranov. Zh. Obshch. Khirn., 6, 2339 (1970).
45. A. A. Deikalo. Candidate's Dissertation. Donetsk (1971).
46. H. yon Dobeneck and W. Goltsche, Ber.. 9_~5,1484 (1962).
47. J. Bergman, J. Heteroeyel. Chem.. 7, 1071 (1970).
48. A. K. Sheinkman. N. F. Kazarinova, and E. P. Babin. Zh. Vses. Khim. Obshchestva ira. D. I. Mende-
leeva. 7, 112 (1962).
49. A. K. Sheinkman, N. F. Kazarinova, and E. P. Babin. Author's Certificate No. 147, 187; Byul. Izobret..
No. I0 (1962).
50. A. K. Sheinkman, Candidate's Dissertation. Moscow (1964).
51. A. N. Kost, A. K. Sheinkman, and N. F. Kazarinova, Zh. Obshch. Khim., 3.._44.2044 (1964).
52. A. N. Kost, A. K. Sheinkman, and A. N. Prilepskaya, Khim. Geterotsikl. Soedin., Collection 1 [in
Russian] (1967), p. 248.
53. A. K. Sheinkrnan, A. N. Kost, A. N. Prflepskaya, and Zh. V. Shiyan, Zh. Organ. Khim., 4, 1286 (1968).
54. A. K. Sheinkman, A. K. Tokarev, and S. N. Baranov, Khim. Geterotsikl. Soedin., 82 (1971).
55. A. K. Sheinkman, A. P. Kucherenko, and S. N. Baranov, Khim. Geterotsikl. Soedin., 669 (1972).
56. A. K. Sheinkrnan, A. K. Tokarev, A. P. Kucherenko, S. G. Potashnikova, A. A. Deikalo. and S. N.
Baranov, Khim. Geterotsikl. Soedin., 643 (1971).
57. A. N. Prilepskaya, Candidate's Dissertation, Donetsk (1971).
58. A. K. Sheinkman and Yu. N. II'ina, Khim. Geterotsikl. Soedin., 568 (1971).
59 O. Dimroth and R. Heene, Ber., 5_~4,2934 (1921).
6O O. Dimroth and F. Fister, Ber., 5_~5,1223, 3693 (1922).
61 A. E. Arbuzov. Izv. Akad. Nauk SSSR, Ser. Khim., 451 (1945).
62 J. Wibaut, Rec. Tray. Chim., 60, 119 (1941).
63 M. K. Polievktov, A. K. Sheinkman, and L. N. Morozova, Khim. Geterotsikl. Soedin., 1067 (1973).
64 A. K. Sheinkman and A. K. Tokarev. Zh. Organ. Khim.. 7, 855 (1971).
65 A. K. Sheinkman, A. K. Tokarev, and A. N. Prilepskaya, Khim. Geterotsikl. Soedin., 529 (1972).
66. M. V. Vol'pin and I. S. Akhrem, DoLl. Akad. Nauk SSR, 161, 597 (1965).
67. K. Conrow, J. Amer. Chem. Soc., 8_.~i.5461 (1959).
68. F. KrShnke and J. Vogt, Ann. Chem., 600, 211 (1956).
69. K. A. Grob. in: Theoretical Organic Chemistry, Butterworth's Scientific Publications, London (1959).
70. A. K. Sheinlunan, A. N. Prilepskaya, and A. N. Kost, Khim. Geterotsikl. Soedin., 1515 (1970).
71. A. A. Deikalo, A. K. Sheinkman, and S. N. Baranov, Khim. Geterotsikl. Soedin.. 1359 (1972).
72. F. Popp, W. Blount, and P. Melvin, J. Org. Chem., 2_.66,4930 (1961).
73. A. K. Sheinlunan and A. N. Prilepskaya, Khim. Geterotsikl. Soedin., 1148 (1971).
74. A. K. Sheinkman and A. N. Prilepskaya, Khim. Geterotsikl. Soedin., 860 (1971).
75. A. K. Sheinkman, A. N. Prilepskaya, and R. D. Bondarchuk. USSR Authors' Certificate No. 188,496:
Byul. Izobret, No. 22 (1966).
76. A. K. Sheinkman and A. K. Tokarev, Khim. Geterotsikl. Soedin., 956 (1969).
77. A. K. Sheinlm~an, A. K. Tokarev, S. N. Baranov, and A. N. Kost, USSR Authors' Certificate No.
253,805; Byul. Izobret.. No. 37 (1969).
78. A. K. Sheinkman, A. P. Kucherenko, and S. N. Baranov, Khim. GeterotsiLl. Soedin., 1291 (1970).
79. A. K. Tokarev. L. N. Volovel'skii. A. K. Sheinkman, and S. N. Baranov, Zh. Obshch. Khim., 9__22,460
(1972).

ii
 80. A. K. Sheinkman. S. G. Potaslmikova, and S. N. Baranov, Author's Certificate No. 292,479: Byul. Izo-
bret., No. 29 (1971).
81, A . K . Sheinlmaan, S. G. Potaslmikova, and S. N. Baranovl Author's Certificate No. 327,197: Byul. Izo-
bret., No. 5 (1972).
82. A.K. Sheinkman and S. G. Potashnikova, Methods of Obtaining Chemical Reagents and Preparations
~in Russian], IREA, Vol. 23, Moscow (1971), pp. 49, 77, 137.
83. J. Bergman, Tetrahedron Lett., 4723 (1972).
84, T. V. Stupnikova, V. I. Sokolov, A. F. Pozharskii, and A. K. Sheinkman, Proceedings of the IInd Sym-
posium on the Chemistry and Technology of the Heterocyclic Compounds of Combustible Minerals
[in Russian], Donetsk (1973).
85. A . K . Sheinkman, A. N. Kost, A. N. Prilepskaya, and N. A. Klyuev, Khim. Geterotsikl. Soodin., 1105
(1972).
86. B. I. Stepanov and G. I. Migaehev, Zh. Obshch. Khim., 35. 2254 (1965).
87. B. L Stepanov and G. I. Migaehev. Zh. Obsheh. Khim., 36. 1447 (1966).
88. A. K. Sheinkman, G. V. Samoilenko, and S. N. Baranov, Proceedings of the 5th Conference on Organo-
phosphorus Compounds [in Russian], Moscow (1972).
89. B. I. Stepanov and G. I. Migaehev, Zh. Vses. Khim. Obshch. ira. D. I. Mendeleeva, 10, 712 (1965).
90. G. I. Migaehev and B. I. Stepanov, Zh. Obsheh. Khim., 38, 1368 (1968).
91. A.K. Sheinkman, A. N. Prilepskaya, O. A. Ginzburg, A. K. Tokarev, and A. A. Deikalo, Khim.
Geterotsikl. Soedin., 421 (1971).
92. A. N. Kost, A. K. Sheinkman, and N. F. Kazarinova, Khim. Geterotsikl. Soedin., 722 (1966).
93. H. Fischer and P. Ernst, Ber., 59, 138 (1926).
94. A. Treibs and A. Ohorodnik. Ann. Chem., 611, 149 (1958).
95. A. Treibs and A. Dietl, Ann. Chem., 619, 80 (1958).
96. H. Plieninger, U. Lereh, and J. Kurze, Angew. Chem., 75, 724 (1963).
97. A.K. Sheinkman, A. N. Kost. and R. D. Bondarehuk, Author's Certificate No. 202,143: Byul. Izobret.,
No. 19 (1967).
98. A. K. Sheinkmanand A. A. Deikalo, Khim. Geterotsikl. Soedin., 1654 (1971).
99. A. Treibs and M. Eligge. Ann. Chem., 652, 176 (1962).
100. A. K. Sheinkman, A. A. Deikalo, A. P. Kueherenko, and S. N. Baranov, Khim. Geterotsikl. Soedin.,
424 (1971).
101. A.K. Sheinkman and A. A. Deikalo, Methods of Obtaining Chemical Reagents and Preparations [in
Russian], IREA, Vol. 23, Moscow (1971), p. 24.
102. S. Clementi. F. Cenel. and G. Merino, Chem. Comm., 498 (1967).
103. A. G. Kamrad and A. I. Shatenshtein, Izv. Akad. Nauk LatvSSR, Ser. Khim.. 507 (1963).
104. A. I. Shatenshtein. A. G. Kamrad, I. O. Shapiro, Yu. I. Ranneva, and E. N. Zvyagintseva,Dokl. Akad.
Nauk SSSR, 168, 364 (1966).
105. A. I. Shatenshtein, N. N. Magdesieva, Yu. I. Ranneva, I. O. Shapiro, and A. I. Serebryanskaya, Teoret.
]~ksperim. Khim., 3, 343 (1967).
106. S. McElvain and D. Kundiger, J. Airier. Chem. Soc., 64, 254 (1942).
107. P. Wright and W. McEwen, J. Amer. Chem. Soe., 76, 4540 (1959).
108. L. N. Volovel'skii, A. Ya. Yakovleva, A. K. Sheinkman, and A. K. Tokarev, Zh. Obsheh. Khim., 43,
1414 (1973).
109. A. K. Sheinlm~an, A. K. Tokarev, and L. N. Volovel'skii, Author's Certificate No. 318,575: Byul. Izo-
bret., No. 32 (1972).
110. A. K. Sheinkman, G. V. Samoilenko, and S. N. Baranov, Zh. Obshch. Khim., 40, 2339 (1970).
I l L D. Redmore, J. Org. Chem., 34, 1420 (1969).
112. A. K. Sheinkraan, G. V. Samoilenko, and S. N. Baranov, Author's Certificate No. 281,468: Byul. Izo-
bret., No. 29 (1970).
113. G. V. Samoilenko and P. A. Gurevich, Proceedings of the 2nd Symposium on the Chemistry and Tech-
nology of the Heterocyclic Compounds of Combustible Minerals [in Russian], Donetsk (1973).
114. A. K. Sheinkman, G. V. Samoilenko, and S. N. Baranov, Zh. Obshch. Khim., 40. 700 (1970).
115, A.K. Sheinkman, G. V. Samoilenko, and S. N. Baranov, Dokl. Akad. Nauk SSSR, 196, 137 (1971).
116. A. K. Sheinkman, V. A. Ivanov, N. A. Klyuev, and G. A. Mal'tseva, Zh. Organ. Khim., 9, 2550 (1973).
117. A. K. Sheinkman, V. A. Ivanov, and S. N. Baranov, Author's Certificate No. 276,960. Byul. Izobret.,
No. 24 (1970).
118. A. K. Sheinkman, V. A. Ivanov, and S. N. Baranov, Author's Certificate No. 301,334: Byul. Izobret.,
No. 14 (1971).

12
119. A. K. Sheinkman, V. A. Ivanov, and S. N. Baranov, Author's Certificate No. 259,887- Byul. Izobret.,
No. 3 (1970).
120. A. K. Sheinkman. S. G. Potaslmikova, and S. N. Baranov, Zh. Organ. Khim., 7, 1550 (1971).
121. B. Emmert and E. Asendorf, Ber.. 72, 1188 (1939).
122. R. Abramovitch and A. Vinutha. J. Chem. Soc.. C, 2104 (1969).
123. A. P. Terent'ev and L. A. Yanovskaya, Reactions and Methods of Investigating Organic Compounds
[in Russian], Khimiya, Vol. 5. Moscow (1957). p. 256.
124. G. Badger and W. Sasse. Advan. Heterocyclic Chem., 2, 179 (1963}.

13
AN INVESTIGATION IN THE FIELD OF THE STEREOCHEMISTRY

OF ACETYLENIC ~ OXIDES

K. G. G o l o d o v a and S. I. Y a k i m o v i e h UDC 547.717 : 541.634 : 543.422.25

In the synthesis of 3 - m e t h y l - 2 , 3 - e p o x y p e n t - 4 - y n e b y the action of powdered caustic potash on

4 - c h l o r o - 3-methylpent- 1-yn- 3- ol, a m i x t u r e of e i s and trans-oxides is f o r m e d with p r e d o m i -
nance of the i s o m e r to which, on the basis of the PMR s p e c t r o s c o p y of saturated and acet-
ylenic a - o x i d e s , the cis configuration of the methyl groups has been ascribed.

Acetylenic a- oxides a r e usually obtained by the action of solid caustic potash and the corresponding
ehlorohydrins which, in t h e i r turn, a r e synthesized f r o m Iotsich reagents and a - c h l o r o carbonyl compounds.
The l a t t e r reaction is n o n s t e r e o s p e c i f i c and, in the general case, may lead to the formation of d i a s t e r e o -
r e e f s . The subsequent closure of the oxide ring should give a m i x t u r e of eis-and t r a n s - i s o m e r i c oxides.
The p r e s e n t p a p e r d e s c r i b e s the synthesis of 3 - m e t h y l - 2 , 3 - e p o x y p e n t - 4 - y n e (I) by the following route:

ClI-~CO~wI~I~IClI:II'IC--CM,gBr
- -
? Hs
HC~C--C.IlClEH 3
llC-.'C.~/Z~...~nHCL-.~...~.,,.CII
39
9 I C H ~ C H 3 + CH 3 / ~ - " ~ H
| OH
Ia Ib

The a oxide (I) is f o r m e d in quantitative yield mad, according to GLC and to PMR spectroscopy, it
f o r m s a mixture of cis and t r a n s i s o m e r s {Ia and Ib) in a ratio of 4: 1. The predominant i s o m e r was iso-
lated by fractionation through a column, and in its PMR s p e c t r u m (Table 1) the signal of the p r o t o n at-
tached to the oxide ring was in a weaker field and the signals of the protons of the methyl groups and of the
p r o t o n on the acetylenic bond w e r e in a s t r o n g e r field than the c o r r e s p o n d i n g signals in the s p e c t r u m of the
second i s o m e r .
F o r comparison, the PMR s p e c t r a of the oxides (II-VII) were taken (see Table 1). In the PMR spec-
t r a of the u n s y m m e t r i c a l disubstituted s a t u r a t e d oxides (II) and (HI), the protons attached to the oxide ring
give a single broad signal with 6 2.37 ppm. In the s p e c t r u m of the monosubstituted oxide (IV), the signals
of the protons at the ~ - e a r b o n atom have 6 2.28 and 2.54 ppm. Comparison with the s p e c t r a of the oxides
{II) and 0II) p e r m i t s an assignment of the signal at 2.54 ppm to the proton p r e s e n t in the trans position and
that at 2.37 ppm to the proton in the cis position r e l a t i v e to the alkyl group: Thus, the alkyl group s c r e e n s
the proton on the neighboring carbon atom of the oxide ring, which is in the cis position, in h a r m o n y with
l i t e r a t u r e information [1-3]. In the s p e c t r u m of the oxide (V), the signals of the protons on the B - c a r b o n
atom of the oxide ring have f a i r l y close chemical shifts, i.e., the acetylenic grouping exhibits s i m i l a r ef-
fects on the protons in the cis and t r a n s positions. In the s p e c t r a of the acetylenic oxides (VI) and (VII),
one of the protons gives a signal at the same values of 5 as the protons of the oxide (V). The signal of the
o t h e r p r o t o n is shifted upfield. By comparing the s p e c t r a of compounds (II-VII) it is possible to conclude
that in the acetylenic a oxides WI and (VII) ,the r e l a t i v e positiong~of the signals of the protons attached to
the oxide ring a r e d e t e r m i n e d mainly by the locations of these protons relative to the alkyl grouping on the
a - c a r b o n atom of the oxide ring, and t h e r e f o r e the signal of the proton in the Cis position is p r e s e n t in the
region of higher fields.
Thus, the predominating i s o m e r of the oxide (I), c h a r a c t e r i z e d by the appearance of the signal of the
p r o t o n attached to the oxide ring at lower field strengths, has the cis configuration (Ia). This is also

A. A. Zhdanov Leningrad State University. T r a n s l a t e d f r o m Khimiya Geterotsiklieheskikh Soedinenii.~

No. 1. pp. 19-21, January, 1974. Original a r t i c l e submitted June 14, 1971: r e s u b m i t t e d June 10, 1973.

9 19 75 Plenum Publishing Corporation, 22 7 West 17th Street, New York, iV. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher9 A copy o f this article is available from the publisher for $15.00.

14
 TABLE 1. PMR Spectra of the a. Oxides

CO1TI
pound
-
R* i 6, ppm R' 6, ppm R" I 6, ppm R"~ 6,ppm
Ia HC~C 2,15 CH3 1,36 1,20
Ib HC~C 2,25 CH3 . t,40 CHHs 1,30 2.77
II P -C3H7 t,41 CHa 1,17 2,37 H 2,37
Ilt
IV
P -C6H,3
P-CaH7
1,4I
1,42
CHs 1,17
2,73
HH 2,37
2,28
2,37
2,54
V CH3C--=C H 3,12 H 2,68 2,64

i
1,76
VI HC~C 2,15 CHs 1,46 2,83 H 2,56
VII CH3C-------C 1,74 CH3 1,39 H 2,73 2,52

*In the alkyl radicals, the values of 6 for the CH2 group c l o s e s t to
the oxide ring are given.

confirmed by the positions of the signals of the methyl groups. In the s p e c t r u m of the predominating i s o m e r
they a r e at higher field strengths. A s i m i l a r phenomenon has been observed in the s p e c t r a of the cis and
t r a n s b u t - 2 - e n e s , w h e r e the signals of the methyl groups of the cis i s o m e r a r e also p r e s e n t in the region
of higher fields [4].
A c o m p a r i s o n of the PMR s p e c t r a of the saturated (tI-IV) and the acetylenic 0c--VII) oxides shows
that the r e p l a c e m e n t of an alkyl group by an acetylenic group leads to a downfield shift of the signals of the
protons attached to the B - c a r b o n atom by 0.2-0.3 ppm and to the a - c a r b o n atom by 0.4 ppm.
The IR s p e c t r a of the oxides {In. V-VII) and of the mixture of the oxides (Ia and Ib) a r e e x t r e m e l y
s i m i l a r in the 1200-1300 c m - i and 800-900 cm -1 regions which a r e c h a r a c t e r i s t i c for the vibrations of an
oxide ring [5]. The s p e c t r a of the pure oxide (ia) and of the mixture of oxides (Ia) and (Ib) are v e r y s i m i l a r .
In this case. IPL s p e c t r o s c o p y does not provide the possibility of judging the p r e s e n c e of i s o m e r i c c o m -
pounds and is t h e r e f o r e unsuitable for d e t e r m i n i n g t h e i r configurations.

EXPERIMENTAL

The IR spectra were taken on a UR-20 spectrometer in the 700-3600 cm -i region (the pure substances
were used at a layer thickness of 18 #). The PMR spectra were taken on a Vartan HA-100-D/15 instrument
with HMDS as internal standard using 10?c solutions in c a r b o n t e t r a e h t o r i d e . G a s - c h r o m a t o g r a p h i c analysis
was p e r f o r m e d on a T s v e t - 1 c h r o m a t o g r a p h with a f l a m e - i o n i z a t i o n d e t e c t o r using a column 2m 0,4 cm. The
s t a t i o n a r y phase was dinonyl phthalate (10~) on Celite-545. The r a t e of flow of the c a r r i e r gas (H2) was
v a r i e d according to the s t r u c t u r e of the s u b s t a n c e s being investigated. F o r purification, the oxides were
redistilled through a column with glass packing (15 t h e o r e t i c a l plates).
3 - M e t h y l - 2 , 3 - e p o x y p e n t - 4 - y n e (I). The ethylmagnesium b r o m i d e obtained f r o m 24 g (1 g-atom) of
m a g n e s i u m and 109 g (I mole) of ethyl b r o m i d e in 500 m l of t e t r a h y d r o f u r a n was added in small portions
in a c u r r e n t of acetylene with cooling to a s a t u r a t e d solution of acetylene in t e t r a h y d r o f u r a n . After the end
of the addition, acetylene was p a s s e d through the reaction mixture for another 5 h and then. with cooling,
a solution of 95 g (0.88 mole) of 3 - e h l o r o b u t a n - 2 - o l in t e t r a h y d r o f u r a n was added. The resulting complex
was d e c o m p o s e d with 5~c h y d r o c h l o r i c acid, and the organic l a y e r was salted out and was d r i e d with m a g n e -
sium sulfate. Distillation yielded 106.9 g of 4 - c h l o r o - 3 - m e t h y l p e n t - l - y n - 3 - o l , bp 72.5-73.5~ (60 mm)~
157-158~ (760 ram): d42~ 1.0690: nD 2~ 1.4615. With stirring, 120 g (2.1 mole) of powdered KOH Was added
to an ethereal solution of 107 g (0.75 mole) of the chlorohydrin. The ethereal l a y e r was dried with m a g n e -
sium sulfate, and the ether was evaporated off. The r e s i d u e was evaporated, f i r s t at 100 ram, bp 58-59~
and then at a t m o s p h e r i c p r e s s u r e . This gave 74 g (96%) of 3 - m e t h y l - 2 , 3 - e p o x y p e n t - 4 - y n e (I), bp 108-110~
d420 0.8838: nD 2~ 1.4255. Found %: C 74.9: H 8.5. C6HsO. Calculated %: C 75.0: H 8.4.
The cis i s o m e r {In) was isolated by fractionation through a column, bp 109.5-110~ d42~ 0.8855: nD 2~
1.4273. Found %: C 74.9; H 8:4. C~H~O. Calculated %: C 75.0t H 8.4. IR spectrum, cm-1.9 760 s, 860 s.
920 w, 940 w, 985 s, 1040 m, 1080 s , 1120 m, 1150 s, 1235 s. 1310 m. 1390 s. 1420 m, 1450 m, 1460 s, 2125
w, 2890 w, 2940 s, 2980 s, 3010 s, 3300 s.
The oxides (II-VII) w e r e synthesized in a s i m i l a r m a n n e r to (I) [in the c a s e of compounds ffI-V and
VII) absolute e t h e r was used as the solvent]. The constants of the c h r o m a t o g r a p h i c a l l y pure saturated and
acetylenic oxides have been given p r e v i o u s l y [6].

15
 LITERATURE CITED
lo M. H. Gianni, E. L. Stogryn, and C. M. Orlando, J. Phys. Chem., 67, 1385 (1963).
2. G. Allen, D. J. Blears, and K. H. Webb, J. Chem. Soe,, 810 (1965).
3. A. T. Bottini andR. L. Van Etten, J. Org. Chem,. 30, 2994 {1965).
4. G. G. Lyle and L. K. Keefer, J. Org. Chem., 31, 3921 (1966).
5. L. Bellamy. Infrared Spectra of Complex Molecules, 2nd ed., Methuen, London {1958).
6. K. S. Mingaleva, K. G. Golodova, and A. A. Petrov, Zh. Organ. Khim., _1, 2078 (1965).

16
REACTION OF ALKYL- AND BENZYLGLYCIDYLMALONIC
ESTERS WITH a LACTAMS

~. G. Mesropyan. Yu. A. Bunyatyan, UDC 547.461.8 + 547.745

R. K. Aliev, and M. T . D a n g y a n

The r e a c t i o n of alkyl- and b e n z y l g l y c i d y l m a l o n i c e s t e r s with pyrrolidinone, piperidinone,

and c a p r o l a c t a m in the p r e s e n c e of catalytic amounts of w a t e r leads to compounds contain-
ing laetone and l a c t a m r i n g s and a l s o to 2 - a l k y l - and 2 - b e n z y l - 5 - h y d r o x y - y - v a l e r o l a c t o n e s .

It is known [1] that in the r e a c t i o n of compounds containing oxirane rings with l a c t a m s , the oxirane
r i n g s a r e c l e a v e d with the f o r m a t i o n of N - s u b s t i t u t e d l a e t a m s having a s e c o n d a r y alcohol group in an
open chain.
Continuing a study of the p r o p e r t i e s of alkylglycidylmalonic e s t e r s [2] in o r d e r to i n v e s t i g a t e c o m -
pounds containing a lactone and a l a c t a m ring, we have p e r f o r m e d the condensation of ~ l a c t a m s with alkyl-
and b e n z y l g l y c i d y l m a l o n i c e s t e r s .
The initial alkyl- and b e n z y l g l y c i d y l m a l o n i c e s t e r s (Table 1) w e r e s y n t h e s i z e d by a known method [2]
f r o m alkyl- and b e n z y l m a l o n i c e s t e r s mad epichlorohydrin:

COOCalls
I
RC~(COOqHp, + c~c~c~n,~a~~ eccH2c~---C.~
-- t \o/"
COOC.,Hs
I-IV
I R=CtH::: II R=C;,H]~,: III R=CIoH21; IV R=C~HsCH~

The IR s p e c t r a of (I-IV) (Table 1) have the bands of the s t r e t c h i n g v i b r a t i o n s of C--O. CH in the C H 2

of an epoxide group, and C = O bonds.
Under the action of l a c t a m s , the oxirane rings of the alkyl- and b e n z y l g l y c i d y l m a l o n i c e s t e r s a r e
r e a d i l y opened in a c c o r d a n c e with K r a s u s k i i ' s rule to f o r m i n t e r m e d i a t e compounds in which the l a c t a m
r i n g s a r e bound by the nitrogen a t o m with the y - c a r b o n atom of B - h y d r o x y a l k y l m a l o n i c e s t e r : t h e s e c o m -
pounds r e a d i l y c y c l i z e even u n d e r the conditions of the e x p e r i m e n t into yr l a c t o n e s with the splitting out of
an alcohol. Compounds (V-XVI) containing lactone and l a c t a m rings a r e obtained (Table 2).
The s t r u c t u r e of compounds (V-XVI) was c o n f i r m e d by the IR s p e c t r a (Table 2) which l a c k e d the ab-
s o r p t i o n bands of epoxy groups and showed f r e q u e n c i e s c h a r a c t e r i s t i c for lactone c a r b o n y l s and e s t e r and
laetam groups.
In the r e a c t i o n of (I-IV) with l a c t a m s , in addition to compounds (V-XVI) c e r t a i n amounts of the known
[3] 2 - a l k y l - and 2 - b e n z y l - 5 - h y d r o x y - y - v a l e r o l a e t o n e s (XVII-XX) (Table 3) w e r e i s o l a t e d f r o m the r e a c t i o n
mixtures.

COOC~Hs COOC=Hs ]
"~
I-IV,+ i" , ~
tlN(CIfa)DCO I R~CH~CH('OH)CH~N(CX2)aC
I I
r-'--'l O + IRCCH2CH(OH.)cHsOH /
L cooc,.5 ~ooc~.~ J

E r e v a n State University. T r a n s l a t e d f r o m K h i m i y a G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 1, pp. 22-28.

J a n u a r y , 1974. Original a r t i c l e s u b m i t t e d O c t o b e r 19, 1972.

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

17
 02 OD r eO

~~176 ~

!
! ke~
%&
<

.~

! !

GGGG ~~

9 1 6 9 1 6 9
ZXXZZZZZZZZZ

-~:~

if/ CD
0
r/1

~ o ~ a ~

(D
m I 0
0
lllllllll~ll

M P >

O0

18
 O~,O,,~CH2N(CH~)nCO + O~--~CH~OH

v-xvt xvu-xx

V R=CsHzT, n=3; Vt R=CgHIg, n=3; VII R=C,oH2. n=3; VIII R=C~"tsCH~, n=3;
IX R=CsHI~., n=4; X R=CgHzg, n=4; XI R=CloH.,I, n=4; Xll R=C6HsCH2, n=4;
XItl R=CsH~7, n=5; XIV R=CgHzg,n=5; XV R=CIoH2. n=5; XVI R=CsHsCH2, n=5;
XVI!.R=CaH1?;XVHI R=CgHL~;XIX R=CIoH~I;XX R=C6HsCH2.

In o r d e r to p r o v e the s t r u c t u r e of compounds (V-XVI). 2 - e t h o x y c a r b o n y l - 2 . n o n y l - 4 - ( 2 - o x o p y r r o l i d i n e -

m e t h y l ) - T - b u t y r o l a c t o n e (VI) was subjected to alkaline h y d r o l y s i s :

I.:~aOIl: --C2H~Otl
~
tl.,~C
'
9 .. F - - - 1 , ',
VI
2.1tCL -CO. O/f~.O/-% Ci1_~N( CII: )~CO
XXl

Compound (XXI) was also obtained by independent synthesis, in the following way [4]:

COOC,II
- ' I. NaOII,-2C.:II;OII +Br~
CH2 ~CHCI'I~--C~ Hi9 C|t2=CH CH2CIIC,,Ht~
2. HC1,-CO 2 C CI~, -HBr
COOC:~H; COOl!

4 I
It IgC~'~-""~ NaN(Cll2)3CO It 1 9 C ~ - - - ~ I---'-"
O~'~O/'~CH2Br O:" ~-0 / ~CttoN(CH~):~CO
XXI a

The 2-nonyl- 4- (2-oxopyrrolidinomethyl)- T - b u t y r o l a c t o n e s obtained by the different methods showed

no d e p r e s s i o n of the melting points. The IR s p e c t r a of compound {XXI) lacked the absorption band at 1732
em -1 that is c h a r a c t e r i s t i c f o r an e s t e r earbonyl and showed bands at 1770 and 1684 crn-1 which a r e c h a r -
a c t e r i s t i c for lactone and l a c t a m carbonyls, and in the s p e c t r a of compound (XXIa) t h e r e were analogous
bands at 1765 and 1680 cm -1.
To establish the s t r u c t u r e of compounds (XVII-XX), the alkaline h y d r o l y s i s of (I-IV) was p e r f o r m e d ,
as a r e s u l t of which the s a m e 2 - a l k y l - and 2 - b e n z y l - 5 - h y d r o x y - T - v a l e r o l a c t o n e s (XVIIa-XXd) (Table 4)
w e r e obtained; m i x t u r e s of them with the c o r r e s p o n d i n g compounds (XVIt-XX) gave no d e p r e s s i o n of the
melting points.

I.NaOH,-2C2HsOH :~___~
I-IV 2. XCI, -CO2 v v EH2Oll

XVII a-XX
I, XVIla R=EaHI7; II, XVIil b R=CgHtg:
III.XIXc R=CIoH21 ; IV, XX d R=C6HsCH 2

In the IR s p e c t r a of (XVII-XX) (Table 3) and of (XVIIa-XXd) (Table 4), the bands of C = O and OH stretching
vibrations were observed. A b r o a d band in the 3500-3100 cm -1 region with a c l e a r l y isolated doublet p r o b -
ably indicating different f o r m s of a s s o c i a t i o n c o r r e s p o n d s to the stretching vibration of the hydroxy groups
of these compounds [apart f r o m (XX) and (XXd), which a r e liquids]. Tables 3 and 4 give the m a x i m a of the
doublets.
The f o r m a t i o n of the 2 - a l k y l - and 2 - b e n z y l - 5 - h y d r o x y - 7 - v a l e r o l a c t o n e s {XVII-XX) as byproducts
takes place under the action of the l a c t a m s . When the epoxide is heated s e p a r a t e l y or with catalytic amounts
of water at 200-210~ in the absence of a lactam, the initial epoxide undergoes no changes.
Judging f r o m the experimental results, the l a c t a m acts both on the oxirane ring of the alkyl- and
benzylglycidylmalonic e s t e r and on one of the ethoxycarbonyl groups. Apparently, the l a c t a m converts the
ethoxycarbonyl group into an acid group which, under the experimental conditions, decarboxylates, and the
l a e t a m itself is converted into the N-ethyl derivative. A s i m i l a r effect on an e s t e r group has been r e p o r t e d
p r e v i o u s l y when ethyl e s t e r s of 2-substituted 7 - b u t y r o l a c t o n e - 4 - c a r b o x y l i c acids were t r e a t e d with p o t a s -
sium phthalimide. Under these conditions, phthalimide derivatives were obtained in low yields. The main

19
to
o

T A B L E 3. 2 - A l k y l . a n d 2- B e n z y l - 5 - h y d r o x y - T - v a l e r o l a c t o n e s

Com- mp, *C (solvent for crystal- bp, *C (pressure, Empirical _ Found. % Calculated, % IRspectra, Ymax, C ~ l ' l
pound
Yield. % (at
lization) ram) Iformula C H C H C-O OH n) *

XVII C8H17 72 172--174(I) C13H2403 68,5 10,8 68,4 10,5 i758 3332, 3236 37 (3)
44 (4) .
(petroleum ether)
2o (6)
XVIII CgHz9 76 176--177 CI4I~I26Os 70,0 ll,0 69,4 10,7 1754 3324, 3240 42 (3)
(petroleum ether) (1) 44 (4)
3o (s)
XIX CIoH~I 79 183--185 CI~H~8Os 70,7 I0,9 70,3 10,9 1756 3328, 3166 64 (3)
(acetic acid) (1) 25 (4}
18 (5)
XXT CsHsCH2 175--176 Cl2Hl4Os 70,I 6,7 69,9 6,8 1760 3416 48 (3)
(2) 41 (4)
21 (5)

* Y i e l d s c a l c u l a t e d a c c o r d i n g t o t h e a m o u n t s of s u b s t a n c e s o b t a i n e d in t h e r e a c t i o n of t h e e p o x i d e w i t h p y r r o l i d i n o n e r(n = 3),
p i p e r i d i n o n e (n = 4), a n d c a p r o l a c t a m (n = 5).
~d42~ 1.1870, riD2~ 1.5435. F o u n d : M R D 54.72. C12H1403. C a l c u l a t e d : MR D 54.99. In t h e s p e c t r a of (XX), a f r e q u e n c y o f 1605 c m - l ,
c h a r a c t e r i s t i c f o r t h e b e n z e n e r i n g . w a s found. T h e s p e c t r a w e r e t a k e n on a I K S - 1 4 i n s t r u m e n t in p a r a f f i n off.

T A B L E 4. 2 - A l k y l - a n d 2 - B e n z y l - 5 - h y d r o x y - T - v a l e r o l a c t o n e s
. . . . . '
Com- rap, ~ (solvent for crystal- [ bp,'*C (pres- Empirical "i Found"% 9Calculated, % ] IRspectra,/)max, cm-1
pound lization) I sure, mm) If~ ], ..'.C.:., .'I . H c I . /c-o,f ou . . . .
Yir .%
i

XVIIa C~H17 72 (petroleum ether) 68,4 I0i5 1756 [ 3328, 3166 67

XVIII b CgHIo 76 (petroleum ether) 176--177 (I) CNH~Os ' I0,7 69,4 10,7 1756 1 3320, 3240 89
XlXc, CtoH2t 79 (acetic acid) 204 (3) C15H,eOz 10,7 70,3 I0,9 " 1756 3324, 3150 83
XXd CsHsCH~ 175--176 (2) C'12Hi4Os 6,8 69,9 6,8 1760 : 3440 6.5

*d420 1.1872. nD 2~ 1.5441. F o u n d : MR D 54.78. C12H~403. C a l c u l a t e d : M R D 54.99. In t h e s p e c t r a of (XXd) a f r e q u e n c y of 1 6 0 5 e m -1

c h a r a c t e r i s t i c f o r t h e b e n z e n e r i n g w a s o b s e r v e d . T h e s p e c t r a w e r e t a k e n on a I K S - 1 4 i n s t r u m e n t in p a r a f f i n off.
p r o c e s s was the alkylation of the p o t a s s i u m phthalimide with the ethoxycarbonyl p a r t of the e s t e r - l a c t o n e .
However, in our c a s e it was i m p o s s i b l e to detect N - e t h y l d e r i v a t i v e s of the l a c t a m s in the m a s s of e x c e s s
l a c t a m distilled off.
The final s t a g e of the opening of the oxirane r i n g takes p l a c e by the action of two competing groups
-N(CH2)nCO and - O H , which also explains the f o r m a t i o n of the i n t e r m e d i a t e s y s t e m s :

~:OOC2Hs COOC2H s
p.icH2c.(ou)c.2 ~(CH2).~O I
and RCCH2CH(OH)CB2OH
COOC:~B,s COOC2H 5

A B

It might be expected that if no w a t e r w e r e used, the r e a c t i o n should take p l a c e only with the f o r m a t i o n of
the p r o d u c t of l a c t a m addition, but in this c a s e r e s i n i f i c a t i o n p r o d u c t s a r e f o r m e d in l a r g e amount.
The action of the l a c t a m on one of the ethoxycarbonyl groups in A o r B or in the p r o d u c t s of t h e i r
cyclization is not equiprobable, since only in the c y c l i z e d p r o d u c t f r o m B is t h e r e no ethoxycarbonyl group.

O:C~ H

o~CH 2- O and HOCH2-

The explanation of this c o n s i s t s in a c o n s i d e r a t i o n of s t e r i c f a c t o r s acting in the i n t e r m e d i a t e compounds

A and B or in the p r o d u c t s of t h e i r cyclization.
Compounds a r e obtained with two a s y m m e t r i c c e n t e r s , i.e., in application to the cyclic s t r u c t u r e s it is
p o s s i b l e f o r c i s - o r t r a n s - i s o m e r s to be f o r m e d . Judging f r o m the e x p e r i m e n t a l facts, it m a y be a s s u m e d
that only one i s o m e r is obtained in each case, i.e., c y c l i z a t i o n t a k e s p l a c e in s t e r e o d i r e c t e d fashion. Ap-
p a r e n t l y , in r e a c t i o n s involving cleavage of an epoxide r i n g with cyclization to a lactone, we have a p e c u l i a r
combination of s t e r i c and e n e r g y conditions which keep a definite ethoxycarbonyl group in contact with the
hydrogen a t o m of the hydroxy group in i n t e r m e d i a t e compound A or B, which we shall e x a m i n e with A as
e x a m p l e . On modeling this s t r u c t u r e , the following p o s s i b i l i t i e s of the a p p e a r a n c e of a gauche c o n f o r m a -
tion a r e found (only the hydrogen bonds between the groups - O H . . . . . . OCOC2H 5 a r e considered, since it is
I
the r e a c t i o n of just t h e s e groups that leads to the f o r m a t i o n of the T - l a c t o n e ring):

R R

It CHOH '

C2H~
OOCioi [ " COOC'|!5. C,HsOOC COOC2H5 C.: tl.j OOC"~ " x , ~ ?COOC21i
CHOtI II I ' H II I H II
I
a b c

With the p a r t i c i p a t i o n of a hydrogen bond in both c a s e s , the a p p e a r a n c e of s e v e n - m e m b e r e d cyclic t r a n s i -

tion s t a t e s is p o s s i b l e , but stabilization of the t r a n s i t i o n s t a t e s through the f o r m a t i o n of a T - l a c t o n e ring
with a p a r t i c i p a t i o n of e i t h e r of the ethoxycarbonyl g r o u p s is not equiprobable. The f o r m a t i o n of a ring
with ethoxy group I in c o n f o r m a t i o n b is e n e r g e t i c a l l y l e s s f a v o r a b l e since u n d e r t h e s e c i r c u m s t a n c e s the
bulky substituents R and R'. between which any i n t e r a c t i o n (apart f r o m van der Waals interaction) is ex-
cluded, occupy the t r a n s position with r e s p e c t to the plane of the ring, while cyclization through ethoxy-
c a r b o n y l groups I or II in c o n f o r m a t i o n a and through ethoxycarbonyl group II in c o n f o r m a t i o n c leads to a
r i n g in which the voluminous substituents a r e p r e s e n t in the cis position.

W COOC2Hs H

S i m i l a r c o n s i d e r a t i o n s a r e a l s o applicable to B taking into account only the f a c t that the CH2OH group
r e a c t s with the c a r b o n y l of the lactone ring.

21
 It has a l r e a d y b e c o m e c l e a r why t h e r e is no e s t e r group in compounds {XVII-XX) and why the reaction
of the l a e t a m is exclusively with the same group in compounds {V-XIV). The p r e s e n c e of an ethoxycarbonyl
group in some and its absence f r o m o t h e r compounds is evidence in favor of the t r a n s s t r u c t u r e of the p r o -
ducts obtained, since in compounds (V-XVI) the voluminous substituents --Ctt2--R' block the approach of the
l a c t a m to the ethoxyearbonyl group, while in (XVII-XX) the comparatively small hydroxymethyl group, con-
nected by interaction with the carbonyl laetone, does not p r e v e n t this interaction.

EXPERIMENTAL
Alkyl- and Benzylglycidylmalonic Esters (I-IV). These were obtained by the reaction of alkyl- and
benzylmalonic esters with epichlorohydrin by a known procedure [2] (Table I).
2-Alkyl- and 2-Benzyl- 2- ethoxycarbonyl- 4- (2-oxopyrrolidinomethyl)- 7-butyrolactones. 2-Alkyl- and
2- Benzyl- 2 - e t h o x y c a r b o n y l - 4- (2-oxopiperidinomethyl)- 7-butyrolactones. 2-Alkyl- and 2-Benzyl- 2- ethoxy-
earbonyl- 5- (2-oxoaz epin- 1-yl)- 7- valerolactones (V-XVI), and 2-Alkyl- and 2- Benzyl- 5-hydroxy- 7 - v a l e r o -
lactones (XVII-XX). A mixture of 1 mole of (I-IV), 4 moles of a laetam (pyrrolidinone. piperidinone, or
caprolaetam), and 3-4 drops of water was heated at 200-210~ for 10 h and was then distilled in vacuum:
the f i r s t fraction taken off was the excess of l a c t a m and the second fraction consisted of compounds {XVII-
XX) (they c r y s t a l l i z e d in the r e c e i v e r ) (Table 3), while the third fraction consisted of (V-XVI) (Table 2).
2-Nonyl-4-(2-oxopyrrolidinomethyl)-~/-butyrolactone (XXI). A m i x t u r e of 10.4 g (0.027 mole) of (VI)
and 3.27 g (0.081 mole) of a 50% aqueous solution of caustic soda was heated in the w a t e r bath for 6 h,
cooled, and worked up by known methods [5]. Distillation yielded 5.24 g (62%) of (XXI) with bp 228-230~
(1 ram), nD 2~ 1.4875. The substance c r y s t a l l i z e d in the c o u r s e of time, mp 63~ (from ethanol). Found %:
C 70.1: H 10.2: N 4.55. ClsH31NO3. Calculated %: C 69.9: H 10.03: N 4.53.
2 - N o n y l - 4 - ( 2 - o x o p y r r o l i d i n o m e t h y l ) - T - b u t y r o l a c t o n e (XXIa). A mixture of 1.18 g (0.011 mole) of the
sodium derivative of pyrrolidone, 14.6 ml of d r y N,N-dimethylformamide, and 3.5 g (0.01147 mole) of 5-
b r o m o - 2 - n o n y l - 7 - v a l e r o l a e t o n e was boiled for 5 h and was then cooled to r o o m t e m p e r a t u r e and filtered,
the d i m e t h y l f o r m a m i d e was driven off. the r e s i d u e was dissolved in d r y acetone, the solution was filtered,
the acetone was driven off. and the residue was distilled to give 1.3 g (37%) of {XXIa), bp 227-230~ (1 mm).
nD 2~ 1.4880. In the c o u r s e of time. the product crystallized: mp 63~ (from ethanol). Found %: C 69.1:
H 10.3: N 4.45. CIsH31NO3. Calculated %: C 69.9: H 10.3: N 4.45.
2-Alkyl- and 2 - B e n z y l - 5 - h y d r o x y - ' y - v a l e r o l a c t o n e s (XVIIa-XXd). A m i x t u r e of 1 mole of an alkyl-
or benzylglycidylmalonic e s t e r (I--IV) and 3 moles of 50% aqueous caustic soda was heated in the water bath
f o r 6 h, cooled, worked up by known methods [5]. and distilled to give (XVIIa-XXd), which c r y s t a l l i z e d in
the r e c e i v e r (Table 4).

LITERATURE CITED
1o M. F. Shostakovskii, F. P. Sidel'kovskaya, and M. G. Zelenskaya, Izv. Akad. Nauk SSSR, Otd. Khim.
Nauk._4, 738 (1959).
2. I~. G. Mesropyan, Z. T. Karapetyan, and M. T. Dangyan, Arm. Khim. Zh.. 22, 904 (1969): 24, 583
(1971).
3. S. V. Arakelyan and M. T. Dangyan, Nauehnye Trudy Erevansk. Gos. Un-ta, Khim. Nauk, 44, 35
(1954). 53, 3 (1956): 60, 17 (1957).
4. S. V. Arakelyan, Dissertation, Erevan State University (1961).
5. A. N. Kost, ed., Organieum: Practical Handbookof Organic Chemistry, Pergamon Press, Oxford
(1973).

22
STEREOISOMERIC CARBOXAMIDES OF THE BICYC LO[2,2,1] HEPTENE
SERIES IN THE EPOXIDATION REACTION

M. S. Malinovskii, L. I. Kas'yan, UDC 547.632 : 547.891

V. D. Ovsyanik, Yu. Yu. Samitov,
P. B. Terent'ev, and O. Zhuk

The epoxidation of i s o m e r i c c a r b o x a m i d e s of the bicyclo[2.2,1]heptene s e r i e s has been studied;

in the c a s e of e x o - c a r b o x a m i d e s it l e a d s to expoxides, and in the c a s e of e n d o - c a r b o x a m i d e s
to t r i c y c l i e l a c t o n e s .

The influence of the s p a t i a l f a c t o r on the d i r e c t i o n of the epoxidation r e a c t i o n in a n u m b e r of s t e r e o -

i s o m e r i c d e r i v a t i v e s of n o r b o r n e n e has been the subject of s e v e r a l investigations. With the exo a r r a n g e -
m e n t of the functional groups, the sole r e a c t i o n p r o d u c t was an epoxide [1, 2].
The endo configuration of c a r b o x y [1, 3], h y d r o x y m e t h y l [2, 4], and m e t h o x y c a r b o n y l [5] groups led
c o m p l e t e l y or p a r t i a l l y to the f o r m a t i o n of t r i c y c l i c s t r u c t u r e s containing h e t e r o a t o m s .
A s i m i l a r p a t t e r n was o b s e r v e d in the oxidation of endo a m i d e s of the n o r b o r n e n e s y s t e m with lead
t e t r a a c e t a t e and with thallium t r i a c e t a t e [6, 7].

Pb(OAcJ4 I. A~

The epoxidation of the endo a m i d e s of the bicycto[2,2,1]-

-"~o -c.,7 ~ / ~/~1~ heptene s e r i e s has not been d e s c r i b e d in the l i t e r a t u r e . Bi-
I ",.~~0 CH--CHO eyclo [2,2,1] hept- 5- ene- 2- c a r b o x a m i d e and 2 - m e t h y l b i c y c l o -
[2.2.1]hept- 5- ene- 2- c a r b o x a m i d e (the exo and endo s t e r e o -
'%.,A'CH--OH OH t qO, ",y'rn/e122
CH~-T-'-~ CH3 i s o m e r s of (I) and (II)) have been s y n t h e s i z e d f r o m the bicyclic
u n s a t u r a t e d acids through the acid c h l o r i d e s [8, 9].
+ CH~ C~C)3 ]
/~LH H'x~H..-- :OH M . \-CH OH
O~ ~H CH~" " -, Z t--CHO

O CH~ Cp5
'PPt
C'-"}' ~ m/e 81
l rn/e 140 CH~ @
H /-CH20H CH
~U~ CONH2
~ O N ~
la. ~ Ila. b Hz
CH~m/eSO CH3 m/e 109 rn/e 93
I, II a R=H, b R=CH~
Vo
C~H~"m/e 79 C6H9" rn/e 94
rn/e 81
The oxidation of the e x o - c a r b o x a m i d e s (Ia, b) containing
Fig. 1. F r a g m e n t a t i o n pathways f o r the a s t r a i n e d double bond takes place r e a d i l y with the f o r m a t i o n of
lactone of exo- 5- endo- 6- d i h y d r o x y - e x o : the c o r r e s p o n d i n g epoxides. The r e a c t i o n a p p a r e n t l y p r o c e e d s
2- m e t h y l b i c y c l o [2,2.1] heptane- end(>- 2- in s t e r e o c h e m i c a l l y homogeneous fashion with the f o r m a t i o n
c a r b o x y l i c acid. of an oxirane having the exo configuration of the oxirane ring.

D n e p r o p e t r o v s k State U n i v e r s i t y . T r a n s l a t e d f r o m K h i m i y a G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 1,

pp. 29-32, J a n u a r y , 1974. Original a r t i c l e s u b m i t t e d F e b r u a r y 16, 1972.

9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced, I
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.
I
23
 ? --CH3

67 1 ~ ' ~ ~ HelldO
0 -- C%0

H$ --OH H1
TMS

9 i i J I i i ~ ! ,

6 5 4 3 2 1 0 ~t ppm

Fig. 2. PMR s p e c t r u m of the lactone of e x o - 5 - e n d o - 6 - d i -

hydroxy- exo- 2- m e t h y l b i c y c l o [2, 2,11 heptane- 2- carboxylic
acid.

This is shown by the PMR s p e c t r u m of endo- 6 - m e t h y l - 3- o x a t r i c y c l o [3,2,1, @,41- octane- exo- 6- c a r b o x a m i d e

(IIIb) r e c o r d e d at a f r e q u e n c y of 100 MHz.
In f a v o r of the exo configuration of the oxirane ring is the c o n s i d e r a b l e nonequivalenee of the 8 - s y n
and 8-anti protons, which r e s o n a t e in the f o r m of an AB quadruplet with a g e m i n a l constant J = 11 Hz. The
a s s i g n m e n t of the r e s o n a n c e lines of the p r o t o n s was b a s e d on the m a g n e t i c anisotropie influence of the
oxirane r i n g and of the orbitals of the u n s h a r e d p a i r of e l e c t r o n s of the oxygen atom in it, which leads to a
shift in the r e s o n a n c e signal of the s y n - p r o t o n in the downfield d i r e c t i o n [10].

syn-~ H-anti

*~ ~CONH ~
~-endo
III a.b

The exo configuration of the amide grouping is shown b y the s m a l l (AS 0.06 ppm) nonequivalenee of the p r o -
tons attached to the oxirane ring and the c o n s i d e r a b l e nonequivalence of the p r o t o n s of the 7-CH2 group
(&6 1.5 ppm), which r e s o n a t e in the f o r m of a AB quadruplet each component of which is split into a doublet
u n d e r the action of the 1-H proton.

Iva, b vz, b

The epoxidatio n of the s t e r e o i s o m e r i c e n d o - c a r b o x a m i d e s (Ha, b) l e a d s to the f o r m a t i o n of lactones,

thanks to the nucleophilic attack of the c a r b o n a t o m of the carbonyl group in the d i r e c t i o n of the c a r b o n atom
b e a r i n g the p o s i t i v e c h a r g e in the i n t e r m e d i a t e c o m p l e x f o r m e d by the electrophilic attack of a p e r a c i d on
the double bond of the bicycloheptene.
The l a c t o n e s (IVa. b) give a p o s i t i v e t e s t for a vicinal diol with p e r i o d i c acid, which shows the ab-
s e n c e of a W a g n e r - M e e r w e i n r e a r r a n g e m e n t .
The s t r u c t u r e of the lactone (Wb) was c o n f i r m e d by its m a s s spectrtun. The p r i m a r y p r o c e s s of de-
c o m p o s i t i o n of the m o l e c u l a r ion, which is f a i r l y intensive, was the l o s s of the carbonyl group, c o n f i r m e d

24
b y a m e t a s t a b t e t r a n s i t i o n , tn addition to the typical lactone n a t u r e of the decomposition, the m o l e c u l a r ion
underwent the f r a g m e n t a t i o n c h a r a c t e r i s t i c for a l i c y c l i c alcohols, with the c l e a v a g e of the c~, ~ c a r b o n - c a r -
bon bond with r e s p e c t to the h y d r o x y group. The r e s u l t s of this investigation a r e given in Fig. 1.
A definitive p r o o f of the s t r u c t u r e of the lactone b e c a m e p o s s i b l e a f t e r an a n a l y s i s of the PMR s p e c -
t r u m r e c o r d e d at a f r e q u e n c y of 60 MHz at different t e m p e r a t u r e s and at a f r e q u e n c y of 100 MHz (Fig. 2).
The a s s i g n m e n t of the lines was m a d e on the b a s i s of l i t e r a t u r e i n f o r m a t i o n and the t e m p e r a t u r e dependence
of the s p e c t r u m . With a r i s e in the t e m p e r a t u r e of the s a m p l e , the b r o a d e n e d singlet line at 5 3.85 p p m
shifted upfield (at 50~ 5 3.40 ppm). which shows that it was due to a OH group p a r t i c i p a t i n g in an i n t r a -
m o l e c u l a r bond. The singlet line at 6 3.65 p p m m u s t be a s c r i b e d to the e n d o - 5 - H proton, in a g r e e m e n t with
l i t e r a t u r e i n f o r m a t i o n f o r a homolog of the lactone u n d e r c o n s i d e r a t i o n [11, 12]. The 1-H and 6-H protons
f o r m a AB spin s y s t e m with a constant JAB = 5 Hz. while 6 f o r 1-H is 2.75 ppm, and 6 f o r 6-H is 4.37 p p m .
The components of the AB quadruplet undergo s u c c e s s i v e s p i n - s p i n s p l i t t i n g w i t h a s m a l l constant b e c a u s e
of i n t e r a c t i o n with the e n d o - 5 - H and the 7-H. The doublet of the proton of the e n d o - 3 - H has a shift of ~ =
2.14 ppm, and the c o m p l e x m u l t i p l e t of the e x o - 3 - H is at the b o t t o m of the s h a r p singlet line of the CH 3
group. The m u l t i p l e t of the m e t h y l e n e group at 7-C has a shift of 6 = 1.59 p p m .
The acylation of the hydroxy lactones (IVa, b) led to the c o r r e s p o n d i n g a c e t a t e s (Va, b).

EXPERIMENTAL

To estimate the individuality of the substances obtained we used thin-layer chromatography on a non-
fixed layer of alumina of activity grade II [ether: ether-ethanol (50 : I); chromatograms revealed in iodine
vapor].
The m a s s s p e c t r a of the s u b s t a n c e s obtained w e r e t a k e n on a IKS-14 i n s t r u m e n t in p a r a f f i n oil.
The m a s s s p e c t r u m of the laetone of exo- 5- endo- 6 - d i h y d r o x y - e x o - 2-methylbieyelo[2,2,1]heptane- endo-
2 - e a r b o x y l i c acid (IVb) was t a k e n on a MKh-1303 i n s t r u m e n t with a modified s y s t e m f o r introduction into
the ion s o u r c e and o s c i l l o g r a p h i c r e c o r d i n g at an e n e r g y of the ionizing e l e c t r o n s of 20 eV, an e m i s s i o n
c u r r e n t of 150 mA, and an a c c e l e r a t i n g voltage of 2 kV.
The NMR s p e c t r a of the laetone {IVb) w e r e taken on J N M - C - 6 0 H L and J N M - 4 H - 1 0 0 i n s t r u m e n t s (of
the J a p a n e s e f i r m of JEOL).
3- Oxatricyclo [3,2,1,02. 4]octane- exe- 6- c a r b o x a m i d e gIIa) was obtained f r o m phthalic anhydride, con-
c e n t r a t e d H202. and b i c y c l o [ 2 . 2 , 1 ] h e p t - 5 - - e n e - e x o - 2 - c a r b o x a m i d e (In) [8] as d e s c r i b e d by Malinovskii et al.
[13]. Yield 55.5%, mp 164-165~C (benzene), R f 0.2 [ e t h e r - e t h a n o l (50-. 1)]. Found %: C 63.2: H 7.0: N 8.9.
CsHI1NO2, Calculated %: C 62.7: H 7.2: N 9.1. IR s p e c t r u m , era-l: 1656, 1626, 850.
ende- 6- M e t h y l - 3 - oxatricyclo[3,2.1,02" 4]octane- exe- 6 - c a r b o x a m i d e (IIIb) was obtained f r o m phthalic
anhydride, c o n c e n t r a t e d h y d r o g e n peroxide, and e n d o - 2 - m e t h y l b i c y c l o [ 2 , 2 , 1 ] h e p t - 5 - e n e - 2 - c a r b o x a m i d e (Ib)
[8] by the method f o r the s y n t h e s i s of substituted epoxy c a r b o x a m i d e s [13]. Yield 39%, mp 169-170~
(benzene). R f 0.2 [ e t h e r - e t h a n o l (50:1)]. Found %: C 64.5: H 8.0: N 8.1. C~H13NO2. Calculated %: C 64.6:
H 7.8: N 8.4. IR s p e c t r u m , em-~: 1632, 1598, 850.
Laetone of e x o - 5 - e n d o - 6 - D i h y d r o x y b i c y c l o [ 2 , 2 , 1 ] h e p t a n e - e n d o - 2 - c a r b o x y l i c Acid (l-Va). A m i x t u r e
of 5.92 g (0.04 mole) of phthalic anhydride. 1.6 g (0.04 mole, 1.2 ml) of 85% hydrogen peroxide, and 0.6 g
(0.01 mole) of u r e a in 10 m l of absolute e t h e r was s t i r r e d at 26-25~ for 5 h. and then 1.51 g (0.01 mole) of
b i c y c l o [ 2 , 2 , 1 ] h e p t - 5 - e n e - e n d o - 2 - c a r b o x a m i d e (Ha) [8] was added in portions at 20~ A f t e r the end of oxida-
t.ion (as shown b y TLC). the r e a c t i o n m i x t u r e was t r e a t e d with c h l o r o f o r m and with a s a t u r a t e d solution of
s o d i u m b i c a r b o n a t e , and the aqueous solution was e x t r a c t e d with c h l o r o f o r m . The c h l o r o f o r m solution was
d r i e d and the solvent was e v a p o r a t e d off. Yield 19.5%.mp 157-158~ (hexane-benzene) [2], R f 0.1 (ether).
Found %: C 62.4: H 6.7. C~H1003. Calculated %: C 62.3: H 6.5. IR s p e c t r u m , c m - l : 3300, 1760.
Lactone of e x o - 5 - e n d o - 6 - D i h y d r o x y - e x o - 2 - m e t h y l b i c y c l o [ 2 , 2 , 1 ] h e p t a n e - e n d o - 2 - c a r b o n i c Acid (IVb).
This was obtained f r o m e x o - 2 - m e t h y l b i c y c l o [ 2 . 2 , 1 ] h e p t - 5 - e n e - e n d o - 2 - c a r b o x a m i d e (IIb) in the s a m e way
as the p r e c e d i n g lactone. Yield 89%, mp 106-107~ ( h e x a n e - c h l o r o f o r m ) . R f 0.4 (ether). Found %: C 64.6:
H 7.2. C9H1203. Calculated ~c: C 64.3: H 7.1. IR s p e c t r u m , em-~: 3420, 1752.
Lactone of e x o - 5 - A c e t o x y - e n d o - 6-hydroxybicyclo[2, 2.1]heptane- endo- 2 - c a r b o x y l i c Acid (Va). A
m i x t u r e of 0.77 g (0.005 mole) of the lactone (iVa), 0.5 m l of acetic acid, and 0.6 m l of pyridine was boiled
in 10 ml of c h l o r o f o r m on the w a t e r bath f o r 2 h. A f t e r the usual working up, the yield was 74.7%, mp 96~
(hexane) [2], R f 0.5 (ether). Found %: C 60.3: H 6.2. C10H1204. Calculated %: C 61.22: H 6.2. IR s p e c -
t r u m , era-l: 1769. 1713.

25
 The lactone of ex-5-acetxy-end-6-hydrxy-ex-2-methybicy[22]heptane-end-2-carbxyic
acid (Vb) was obtained in the same way as the preceding lactone {Va). Yield 67.6%, mp 70-70.5~ (hexane).
Rf 0.8 (ether). Found %: C 63.2: H 6.6. CI1HI404. Calculated ~: C 62.8: H 6.7. IR spectrum, em -1:
1773, 1734.

LITERATURE CITED
1. G. Berti, F. Bottari, and B. Macchia, Gazz. Chim. Ital., 90, 1763 (1960~$~
2. H. Henbest and B. Niekolls, J. Chem. Soe., 221 (1959}.
3. I.N. Nazarov, V. F. Kucherov, and V. G. Bukharov, Izv. Akad. Nauk SSSR; Set. Khim., 192 (1958):
91 (1957).
4. M.S. Maiinovskii, L. I. Kas'yan, and D. S. Kramskaya, Zh. Organ. Khim.,5, 626 (1969).
5. M.S. Malinovskii, L. I. Kas'yan, V. D. Ovsyanik, and V. I. Avramenko. Zh. Organ. Khim., 6, 1173
(1970).
6. R. Moriarty and H. Gopal, Tetrahedron Lett., 347 (1972).
7. R. Moriarty, H. Walsh. and H. Gopal. Tetrahedron Left., 4363 (1966).
8. W. Boehme, E. Schipper, W. Scharpf, and J. Nichols, J. Amer. Chem. Soc.. 80. 5488 (1958).
9. W. Boehme, E. Siegmund, W. Scharpf, and E. Schipper. J. Med. Pharm. Chem., 5. 451 (1962).
10. K. Tori, A. Aono. V. Hata. R. Muneyuki, T. Tsuji, and H. Tanida, Tetrahedron Lett., 9 (1966).
11. E. Crundwell and W. Templeton, J. Chem. Soc., 1400 (1964).
12. K. Ramey, D. Lini, R. Moriarty, H. Gopal, and H. Walsh, J. Amer. Chem. Soe.. 89, 2401 (1967).
13. M.S. Malinovskii, L. I. Kas'yan, V. D. Ovsyanik. N. I. Stankevich. and V. I. Avramenko, Ukr. Khirn.
Zh., 38, 1040 (1972).

26
INVESTIGATIONS IN THE FIELD OF VINYL ESTERS

OF THE FURAN SERIES

XI.* INVESTIGATION OF THE KINETICS OF THE ALKALINE HYDROLYSIS

OF VINYL ESTERS OF ACIDS OF THE FURAN SERIES BY A POLAROGRAPHIC METHOD

G. G. Skvortsova, Yu. A. Mansurov, UDC 547.725.547.29.02'26:541.127

and N. M. Deriglazov

The k i n e t i c s of the alkaline h y d r o l y s i s of vinyl e s t e r s of f u r a n - 2 - c a r b o x y l i c , t r a n s - f l -

(2-furyl)acrylic, and t r a n s - c i n n a m i c acids and also the c o m p a r a t i v e e l e c t r o c h e m i c a l ac-
tivities of t h e s e compounds and of vinyl e s t e r s of 5 - b r o m o f u r a n - 2 - c a r b o x y l i c , 5 - n i t r o -
f u r a n - 2 - c a r b o x y l i c , and benzoic acids have been studied by a p o l a r o g r a p h i c method. A
s y m b a t i c i n c r e a s e in the r a t e of h y d r o l y s i s of the e s t e r s with a shift of the potential of
the h a l f - w a v e of reduction into the m o r e negative region has been established. Both the
p o l a r i t y and the p o l a r i z a b i l i t y of the m o l e c u l e s have a fundamental influence on the
p r o p e r t i e s of the e s t e r s .

At the p r e s e n t time, a l a r g e amount of m a t e r i a l has accumulated in the l i t e r a t u r e on the kinetics and

m e c h a n i s m of the alkaline h y d r o l y s i s of vinyl e s t e r s [2, 3]. In the p r e s e n t work, we have i n v e s t i g a t e d the
hydrolytic cleavage of vinyl e s t e r s of t r a n s - / 3 - ( 2 - f u r y l ) a c r y l i c (I), t r a n s - c i n n a m i c (II), f u r a n - 2 - c a r b o x y l i c
(III). benzoic (IV), 5 - b r o m o f u r a n - 2 - c a r b o x y l i c (V), and 5 - n i t r o f u r a n - 2 - c a r b o x y l i c (VI) acids in o r d e r to de-
t e r m i n e the influence of the furan ring with different substituents in position 5 on the r e a c t i v i t y of the e s t e r s
in alkaline h y d r o l y s i s . As follows f r o m the r e s u l t s obtained (Table 1), the r e p l a c e m e n t of a phenyl r a d i c a l
by a furyl r a d i c a l l e a d s to a d e c r e a s e in the r a t e of h y d r o l y s i s of {II) and (I). At the s a m e time, the g r e a t e s t
r e a c t i v i t y is p o s s e s s e d by the e s t e r (III). If one t a k e s into account the original slow addition of OH- ions to
the c a r b o n y l c a r b o n atom, the g r e a t e s t e l e c t r o n - d o n a t i n g c a p a c i t y is p o s s e s s e d by the furan ring.
The introduction of a double bond between the furan ring and the carbonyl group r e d u c e s the r a t e of
h y d r o l y s i s of the e s t e r (I). A c o m p a r i s o n of the r e a c t i v i t i e s of the e s t e r s (I) and (III) shows that the in-
fluence of the furan ring is not p u r e l y inductive but also includes a m e s o m e r i c effect.
The t h e r m o d y n a m i c p a r a m e t e r s of the h y d r o l y s i s r e a c t i o n of t h e s e compounds a r e in good a g r e e m e n t
with one another. The r e g u l a r changes in the f r e e e n e r g y AF, enthalpy AH, e n t r o p y AS, and the activation
e n e r g y E in a g r e e m e n t with the change in the h y d r o l y s i s r a t e constant p e r m i t s the conclusion that t h e r e is
a single m e c h a n i s m of the h y d r o l y s i s of the e s t e r s (I-III) f r o m the point of view both of the g e o m e t r y of the
t r a n s i t i o n s t a t e and of the e l e c t r o n i c influence of substituents.
It was i n t e r e s t i n g to c o m p a r e the h y d r o l y s i s r a t e constants with the p o l a r o g r a p h i c p r o p e r t i e s of t h e s e
compounds. T a b l e 2 g i v e s i n f o r m a t i o n c h a r a c t e r i z i n g the e l e c t r o c h e m i c a l activity of compounds (I-VI) on
e l e c t r o r e d u c t i o n at a dropping m e r c u r y e l e c t r o d e . This c o m p a r i s o n is b a s e d on the fact that t h e i r e l e c t r o -
philicity is a c o m m o n f a c t o r f o r the e s t e r s both in h y d r o l y s i s and in e l e c t r o r e d u c t i o n . At the s a m e time,
the c a p a c i t y f o r being r e d u c e d at an e l e c t r o d e is m o r e s e n s i t i v e to the dynamic p o l a r i z a t i o n of a molecule,
which explains the p r e s e n c e of two waves on the p o l a r o g r a m s of compounds (I) and (II) and of one wave on

* F o r C o m m u n i c a t i o n X, see [1].

I r k u t s k Institute of Organic C h e m i s t r y , Siberian Branch, A c a d e m y of Sciences of the USSR. T r a n s -

lated f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii. No. 1, pp. 33-36. January. 1974. Original a r t i c l e
s u b m i t t e d S e p t e m b e r 22, 1972.

9 1975Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

27
 TABLE 1. Kinetic C h a r a c t e r i s t i c s of the Hydrolysis of the Vinyl
E s t e r s RCOOH = CH2
Corn-./ t -~':"' ,o,, E. ,
pound I t~* l " m o l e " I - 1k c a l / m o l e a& 1 As. AH,
9 sec-t sec-t . kcal/molc ' cu kcal/mole
i
I C4HaOCH~CH ', 3.~ 10,8 ~ 20,8 --35,4 10,2
II C6HsCH=CH [ 4,12 11,6 20,7 --32,5 II.0
Ill Cr i 5.60 12,4 20,6 -29.4 11.8

* C41130- 2-furyl,

TABLE 2. P o l a r o g r a p h i e C h a r a c t e r i s t i c s for the

Vinyl E s t e r s R C O O C H = C H 2
Corn- R
pound -~,~, V n

I 2-(2-Furyl)vinyl 1,52 o,95

1,86 0,94
styryl 1,55 1,20
1,86 0,77
III 2-Furyl 1,85 2,11
IV Phenyl 1,83 t,71
V 5- Bromo-2- furyl 1,79 2,90
VI 5-Nitro-2-furyl 0,37
1,52

the p o l a r o g r a m s of compounds (III-V). This is connected with the p r e s e n c e of double bonds adjacent to the
e s t e r group, so that the m e c h a n i s m of the reduction of a s t r u c t u r e of type (III) is apparently limited by a
t w o - e l e c t r o n stage with the formation of the c o r r e s p o n d i n g s e m i a c e t a l [4]:

2e
R C O O C H = C H 2 "-~"- R,C H ( O H ) O C H ~ C H 2

The p r e s e n c e of an ethylenic bond in the a position to the earbonyl carbon atom extends to chain of
conjugation, modifying the m e c h a n i s m of e l e c t r o r e d u c t i o n in such a way that the l a t t e r takes place through
two o n e - e l e c t r o n stages [5] (I, II):

/OH le
Ile
RCH~CHCOOCH~CH 2 -'-''~
H RCH=CH--C.\O--cH=CH~ 1 H"~ RCH~CH2COOCH'~Cft'2

The c l o s e n e s s of the potentials of the second waves is due to the small difference in the delocalization
energies of the r a d i c a l s f o r m e d after the addition of the f i r s t electron in electroreduction. Of compounds
{I) and (II), the g r e a t e r tendency to delocalization is p o s s e s s e d by the s t y r y l radical. Because of the lower
d e g r e e of a r o m a t i z a t i o n of the furan ring as c o m p a r e d with the benzene ring, the polarizability of the mo-
lecule of the e s t e r (I) is g r e a t e r than that of {II), but the m e s o m e r i c effect of a furan ring is m o r e positive
than that of a benzene ring.
The reduction of the e s t e r s (V) and (VI) takes place in m o r e complex fashion, since the b r o m i n e atom
and the nitro group p r e s e n t in position 5 of the furan ring a r e t h e m s e l v e s reduced under our conditions.
However, in our opinion, the probability of the formation in the f i r s t stage of the reduction of the e s t e r (VI)
of an anion radical in a neutral aqueous alcoholic medium and, all the more, their subsequent reduction at
potentials of the o r d e r of - 1 . 5 V a p p e a r s unlikely. Consequently, the second wave of the e s t e r (VI) must be
assigned to a p r o c e s s of reducing the e s t e r group. Unfortunately, we have not been able to study the p o l a r o -
graphy of the e s t e r s c o n s i d e r e d over a wider range of changes of pH of the medium b e c a u s e of their ten-
dency to undergo both alkaline and acid h y d r o l y s i s . Nevertheless, in spite of the difference in the nature
of the e l e c t r o r e d u c t i o n of the e s t e r s discussed, it is possible to find a symbatie i n c r e a s e in the rate of hy-
d r o l y s i s of the e s t e r s (I-III) with a displacement of the half-wave reduction potential to a l e s s negative
region [for the e s t e r s (I) and (II), the potentials of the second waves]. This feature enables us to evaluate
the tendency to h y d r o l y s i s of those e s t e r s that could not be studied under our conditions, as well. On the
basis of the reduction potentials, the e s t e r s (I-VI) can be a r r a n g e d in the following sequence with r e s p e c t
to their r e s i s t a n c e to alkaline h y d r o l y s i s : (I) > (II) >" (III)> (IV) > (V) > (VI). One m u s t take into account the
fact that this sequence is due not only to the inductive p r o p e r t i e s of the substituents but also to the tendency
of the molecules to undergo dynamic polarization.

28
 EXPERIMENTAL
The kinetics of the alkaline h y d r o l y s i s of the vinyl e s t e r s l which w e r e obtained by known methods [1,
6-8], was studied by m e a n s of a L P - 7 p o l a r o g r a p h . The r e a c t i o n was p e r f o r m e d in the p o l a r o g r a p h i c cell.
During the c o u r s e of the reaction, a d e c r e a s e in the height of the wave of p o l a r o g r a p h i c reduction of the
c o r r e s p o n d i n g vinyl e s t e r with t i m e was o b s e r v e d at t e m p e r a t u r e s of 20, 25, 30, and 35~ (~0.1~ in 45%
aqueous ethanolic solutions. The c o n c e n t r a t i o n s of the vinyl e s t e r s amounted to 0.0025, 0.005, and 0.01 M.
The c o n c e n t r a t i o n s of the c a t a l y s t (LiOH) w e r e v a r i e d between 0.2 and 0.08 M. The support was a 0.1 N
solution of lithium chloride. The r e s u l t s of the m e a s u r e m e n t s w e r e u s e d to calculate the h y d r o l y s i s r a t e
c o n s t a n t s kii a c c o r d i n g to the equatiom
2.3 a
-T" log -~--Z-~
kIi= c ' (1)

w h e r e t is the time. sec~ a is the initial height of the wave c o r r e s p o n d i n g to the concentration of e s t e r at
t i m e t = 0; (a-x) is the height of the wave c o r r e s p o n d i n g to the concentration of e s t e r at t i m e t: and c is the
concentration of c a t a l y s t (M).
Calculation of the h y d r o l y s i s r a t e constant kii by the equation:

k~i 23 1 .log (cA,~176

.~ c,, O_c,~ o (c~'~~ ~, (2)

0
w h e r e c ~ l is the initial c o n c e n t r a t i o n of LiOH (IV[): CA2 is the initial c o n c e n t r a t i o n of vinyl e s t e r (M): ( c ~ l - x )
is the c o n c e n t r a t i o n of alkali at t i m e t~ and (g~2-x) is the concentration of vinyl e s t e r at t i m e t, showed the
c l o s e n e s s of the r e s u l t s of calculation to those obtained by m e a n s of Eq. (1), which is explained by the fact
that the o b s e r v a t i o n s w e r e m a d e only in the initial s t a g e of the r e a c t i o n and a l s o by the c o n s i d e r a b l e e x c e s s
of c a t a l y s t in r e l a t i o n to the initial e s t e r .
The p o l a r o g r a p h i e p a r a m e t e r s w e r e found with the aid of a L P - 6 0 p o l a r o g r a p h at 25~ on a support
of lithium a c e t a t e b u f f e r at pH 6.70 in 50% aqueous ethanol. The reduction potentials w e r e m e a s u r e d r e l a t i v e
to a s a t u r a t e d c a l o m e l e l e c t r o d e . The e r r o r in the m e a s u r e m e n t s of the potentials amounted to 5 inV.
The c h a r a c t e r i s t i c s of the c a p i l l a r y w e r e : m = 1.803 m g . sec -1, ~ = 4.24 sec -1. The diffusion coefficient D
w a s calculated by a modified S t o k e s - E i n s t e i n equation, and the n u m b e r of e l e c t r o n s n b y the Ilkovic equa-
tion [9]. The c o n c e n t r a t i o n of the e s t e r s was 0.001 M.

LITERATURE CITED
I. G.G. Skvortsova, V. V. An, Yu. A. Mansurov, V. K. Voronov, G. V. Ratovskii, and Yu. L. Frolov,
Khim. G e t e r o t s i k l . Soedin., 1443 (1972).
2. C . H . De Puy and L. R. Mahoney, J. A m e r . Chem. Soc., 86, 2652 (1964).
3. A . M . Shut and M. M. Filimonova, Zh. Obshch. Khim., .~7, 2603 (1967).
4. V . G . M a i r a n o v s k i i and G. I. Samokhvalov, A b s t r a c t s of Communications at the 5th Conference on the
E l e c t r o c h e m i s t r y of Organic Compounds [in Russian]. Nauka, Moscow (1967). p. 7.
5. G . J . Hoijting, R i c e r c a Sci., Suppl. (Contr. t e o r . s p e r . di p o l a r o g r a f i a ) , 5. 217 (1960).
6. M . F . Shostakovskii, L. I. K o m a r o v a . A. Kh. Fflippova. and G. V. Ratovskii, Izv. Akad. Nauk SSSR.
Set. Khim., 2526 (1967).
7. M . F . Shostakovskii, G. G. S k v o r t s o v a , Vo V. An, and Yu. A. Masurov, Khim. G e t e r o t s i k l . Soedin., 9
(1969).
8. R . L . Adelman, J. Org. Chem.. 14. 1057 (1949).
9. Ya. P. Stradyn', The P o l a r o g r a p h y of Organic Nitro Compounds [in Russian], I z d - v o Akad. Nauk
LatvSSR, R i g a (1961), p. 11.

29
REACTION OF a-AND ~/-METHYLPYRYLIUM SALTS
WITH ORTHOESTERS

G. N. D o r o f e e n k o , V. V. Mezheritskii, UDC 547.812.814

a n d A. L . V a s s e r m a n

The r e a c t i o n of o r t h o e s t e r s with a - and ~/-methylpyrylium salts gives 2- and 4-alkoxyvinyl-

p y r y l i u m salts the acid hydrolysis of which leads to 2- and 4-hydroxyvinylpyrylium salts
and the alkaline h y d r o l y s i s to pyranylideneaeetaldehydes.

Up to the p r e s e n t time, it has been c o n s i d e r e d that the reaction of c~- and -/-methylpyrylium salts
with o r t h o e s t e r s f o r m s only cyanine dyes [1, 2]. The synthesis of t h e s e compounds is p e r f o r m e d by boiling
the r e a c t a n t s in acetic acid in the p r e s e n c e of a basic catalyst. We have shown that when the r e a c t i o n is
p e r f o r m e d under m i l d e r c o n d i t i o n s - b y adding the o r t h o e s t e r to a hot (80-85~ solution of pyrylium salt
in glacial acetic acid without subsequent h e a t i n g - 2- and 4-alkoxyvinylpyrylium salts a r e f o r m e d with yields
close to quantitative. It was p r e v i o u s l y possible to effect such a t r a n s f o r m a t i o n only in the c a s e of special
examples among p y r y l i u m salts condensed with hydrogenated rings where the object of attack by the ortho-
e s t e r was a methylene link [3, 4]. The possibility of the u s e of a - and ~/-methylpyrylium salts c o n s i d e r a -
bly b r o a d e n s the range of applicability of this method, since it p e r m i t s e x t r e m e l y r e a c t i v e compounds to be
obtained the range of which is p r a c t i c a l l y unlimited, while the methods of p r e p a r a t i o n a r e simple.
Monoeyclic a - and ~/-methylpyrylium salts and related compounds with condensed a r o m a t i c n u c l e i -
the 1-benzopyrylium and 2 : b e n z o p y r y l i u m s a l t s - take p a r t in the r e a c t i o n with ethyl orthoformate. Ap-
p a r e n t l y the f i r s t stage of this p r o c e s s , as in the synthesis of cyanine dyes, must be the dissociation of the
p y r y l i u m salt into the methylene base (I) and a m i n e r a l acid. The latter, reacting with the o r t h o e s t e r (II)
gives the earboxonium salt (HI). the r e a c t i o n of which with the methylene b a s e and the subsequent splitting
off of a molecule of alcohol leads to the ethoxymethylene derivative {IV).

R~ R]

-.-.- + HCIO4 HCiO4 R~C(OR~)a ~ R ~C~'~R 4 + R~Oli

R 3 R~O*~H2
aoT II III

R' [ RJ Rt

l~ R2 R~
-R~OH I .

clo~" [ o07 CIO~"

IV.-j

It is probably the inductive, and not the m e s o m e r i c , effect of the substituent R 3 that has a decisive influence
on the r e a c t i v i t y of the cation (III). This conclusion is in s a t i s f a c t o r y h a r m o n y with the fact that, because
of the + I effect of the alkyl radical R 3, which lowers the positive c h a r g e on the carbonium carbon atom of
the ion (III), o r t h o e s t e r s of alkylearboxylic acids 0I, R ~ = CH3. C2H5)do not r e a c t under the conditions

Rostov State University. S c i e n t i f i c - R e s e a r c h Institute of Physical and Organic Chemistry. Rostov-on-

Don. T r a n s l a t e d f r o m Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 37-41, January, 1974. Original
a r t i c l e submitted D e c e m b e r 19, 1972.

9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15. 00.

30
 ~>

.,,J I ~/ ~ ~ 9
4

i',.,.,

oo
~
O O O ~ O O
a~eee~

T O~OoO~
o

, ~ ~ ~

I
I ~ ~ ~. ~ ~.

I-7
~ =~ ooooooo g g g

i r.r., rO

<+9,o
<~
i'O
ID
U
O

,. ~o o ~ T /--<\\ /2

Gc~cTu'~Z

~ ~ o o
9 ~
~ ~ - .,,

r O ~O

31
c o n s i d e r e d with p y r y l i u m salts, while methyl orthobenzoate (II, R 3 = C6H5, R 4 = CH3), in spite of the delocali-
zation of the p o s i t i v e c h a r g e on the phenyl substituent, r e a d i l y r e a c t with the s a m e salts.
In the IR s p e c t r a of the s a l t s 0Va-j) s y n t h e s i z e d t h e r e a r e strong bands in the 1640-1630 c m - t region
r e l a t i n g to the s t r e t c h i n g vibrations of the p y r y l i u m cation. In all the s p e c t r a , the b r o a d band of the C-----C
double bond of the ethoxyvinyl group o v e r l a p s the c h a r a c t e r i s t i c band of the p y r y l i u m cation.
The a b s o r p t i o n m a x i m a in the UV s p e c t r a of the initial m e t h y l p y r y l i u m s a l t s a r e located in the 250-
450 n m region. In the s p e c t r a of the s a l t s {IV), new a b s o r p t i o n a p p e a r s in ttm 500-800 n m region as a con-
sequence of the conjugation of the double C = C bond with the f r e e e l e c t r o n p a i r of the oxygen of the p y r y l i u m
ring. This a b s o r p t i o n p o s s e s s e s a low intensity, which m a k e s it p o s s i b l e to a s s i g n it to a n - - ~ * e l e c t r o n i c
transition.
Under conditions of acid h y d r o l y s i s , the ethoxyvinylpyrylium salts {IV) (R 3 = H: R 4 = C2H5) a r e con-
v e r t e d into the hydroxyvinyl d e r i v a t i v e s (Va-g).

R~ RI R+

+ ,,o __...o,
R~RI.=C.--OC~.~
00: clo; \o.

R~ RJ

oo: clot
Va-g v!

The p r e s e n c e in the IR s p e c t r a of the s a l t s (Va-g) of a strong band in the 1640-1630 c m -1 region, relating
to the absorption of the p y r y l i u m cation, and of a band at 3500-3300 c m -1, which is c h a r a c t e r i s t i c f o r an
enolic hydroxyl, show that the h y d r o l y s i s p r o d u c t s exist a l m o s t c o m p l e t e l y in the h y d r o x y m e t h y l e n e f o r m
{V) and not in the c a r b o n y l f o r m WI). This is also c o n f i r m e d by the UV s p e c t r a [the absorption m a x i m a of
the s a l t s (IV) and (V) coincide completely].
The alkaline h y d r o l y s i s of the s a l t s {iVa) and (Va) f o r m s the aldehyde {VII).

9 C6Hs
CgH~ NaHCO3 ~ HC|O4
C6H$ CH~CH--OC2H
s C6Hs~.Of~CH--CHONaHCOa CsHs.,"~.4b~,,~CH~W_Off
cto; no;"
IV 9 Vl| Va

The action of p e r c h l o r i c acid on (VII) r e - f o r m s the hydroxyvinylpyrylium salt (Va). In the IR s p e c t r u m of

(VII) t h e r e is a s t r o n g band in the 1680 c m -~ region c o r r e s p o n d i n g to the s t r e t c h i n g v i b r a t i o n s of a C = O
group conjugated with a C = C double bond.

EXPERIMENTAL

The IR spectra were taken on a UR-20 instrument in paraffin oil and the UV spectra on a Specord
UV-Vis spectrophotometer in acetic acid. The PMR spectra were recorded on a RYa-2305 spectrometer
(60 MHz) in t r i f l u o r o a c e t i c acid at r o o m t e m p e r a t u r e .
6 - E t h o x y - 2 , 4 - d i p h e n y l p y r y l i u m P e r c h l o r a t e {iVa). To a hot solution of 0.3 g (1 m m o l e ) of 6 - m e t h y l -
2 , 4 - d i p h e n y l p y r y l i n m p e r e h l o r a t e in glacial acetic acid was added 0.4 m l (2 m m o l e s ) of o r t h o f o r m i c e s t e r .
On cooling, g r e e n c r y s t a l s of {va) s e p a r a t e d out. PMR s p e c t r u m : quadruplet and t r i p l e t (3.98 and 1.75
ppm) of an ethyl group, two doublets (5.9 and 5.7 ppm) of vinyl protons, two multiplets (7.64 and 7.3 ppm) of
phenyl rings, and a singlet (8.1 ppm) of the protons of a p y r y l i u m ring.
The s a l t s (IVb-j) w e r e obtained s i m i l a r l y (see Table 1).
6 - H y d r o x y m e t h y l e n e - 2 , 4 - d i p h e n y l p y r y l i u m P e r c h l o r a t e (Va). A m i x t u r e of 0.4 g (1 mmole) of {iVa)
15 m l of 10% p e r c h l o r i c acid solution, and 2 m l of acetic acid was boiled for 10-15 rain, the hot solution
was filtered, and on cooling it deposited light yellow c r y s t a l s of {va).

32
 The h y d r o x y m e t h y l e n e p y r y l i u m salts (Vb-g) w e r e obtained s i m i l a r l y (see Table 2).
4, 6-Diphenylpyran-2-ylideneacetaldehyde (VII). a) An aqueous solution of sodium bicarbonate was
added to 0.4 g (1 mmole) of {IVa) in ether, and the m i x t u r e was left for a day. The e t h e r e a l e x t r a c t was
dried with anhydrous sodium sulfate, the ether was distilled off, and the substance was r e c r y s t a l l i z e d f r o m
p e t r o l e u m ether. Yield 0.25 g (92.7~c). mp 125~ According to the l i t e r a t u r e [5], rap 125-126~
b) A suspension of 0.17 g (0.5 mmole) of {Va) in ethanol was heated with sodium bicarbonate for 15
rain. Then it was filtered, the f i l t r a t e was cooled and diluted with w a t e r to turbidity, and left for a day.
The yield of product was 0.08 g (61.5%), mp 125~ A m i x t u r e with the substance obtained by method (a)
gave no d e p r e s s i o n of the melting point.

LITERATURE CITED

1, H. B r o c k m a n and H. Junge, Ber., 7._~7,529 (1944).

2. H. K i r n e r and R. Wizinger, Helv. Chim. Acta, 44, 1773 (1961).
3. H. K i r n e r and R. Wizinger, Helv. Chim. Acta. 44. 1766 (1961).
4. W. Stevens and R. Wizinger, Helv. Chim. Acta, 44, 1708 (1961).
5. G. A. Reynolds and I. A. Van Allan, J. Org. Chem.. 34, 2736 (1969).

33
F LUOROSU LFONYL- C ONTAINING HETEROCYCLIC COMPOUNDS
VI.* HEXAFLUOROTHIOACETONE DIOXIDE TRIMER

G. A. S o k o l ' s k i i , V. M. P a v l o v , UDC 547.718'412.74

V. M. G o l o v k i n , V. F . G o r e l o v ,
and I. L. Knunyants

The r e a c t i o n of bis (trifluoromethyl)ketene with bis(trifluoromethyl)methionic anhydride at

200~ has given hexafluorothioacetone dioxide t r t m e r : 2.2.3,3-tetrakis (trifluoromethyl)-
t h i i r a n e 1,1-dioxide is f o r m e d as a byproduct. The same t r i m e r is obtained by heating
hexafluoroisobutenylidene sulfate and by t r e a t i n g h e x a f l u o r e - a H - i s o b u t y r i c acid with sul-
fur trioxide.

It has been shown p r e v i o u s l y [1] that hexafluoroisobutenylidene sulfate (I) undergoes i n t r a m o l e c u l a r

sulfonation on being heated above its boiling point (-49~ with the liberation of bis (trifluoromethyl)ketene
(II): the internal anhydride of h e x a f l u o r o - a - p y r o s u l f o n y l i s o b u t y r i c acid (III) f o r m e d in this p r o c e s s d e c a r -
boxylates and is converted into his (trifluoromethyl)methionic anhydride (IV). On the basis of these facts,
it appeared that the anhydride (IV) could be obtained d i r e c t l y f r o m compound (i) by heating above 160~

2 {cv3hc=c/~ >s~176 /soo-o\ >ls0o /so:\

(crp.c - s o o ~ ( C e p o C o
~.~0 / -(CF3).,C~EO \.CO__O / - _ ~ " S02/

l II Ill IV

However, it p r o v e d impossible to isolate the anhydride (IV) and the ketene (iI) f r o m the products of the
p y r o l y s i s of the ketene sulfate (I). F u r t h e r m o r e , these compounds a r e incompatible in p y r o l y t i c p r o c e s s e s .
The f i r s t indications of the reaction of the anhydride (IV) with bis (trifluoromethyl)ketene (II) w e r e
observed at t e m p e r a t u r e s as low as 50-60~ (coloration of the r e a c t i o n mixture); at 120-130~ the r e a c t i o n
b e c a m e exothermie: when the mixture was heated above 180~ a vigorous evolution of carbon dioxide and of
sulfur dioxide took place. If the p r o c e s s was completed by heating the m i x t u r e to 200~ it was possible to
isolate the liquid 2,2.3,3-tetrakis(trifluoromethyl)thiirane 1,1-dioxide (V) (15%) and the c r y s t a l l i n e hexa-
fluorothioacetone dioxide t r i m e r (VI) {75%). The formation oftiaese compounds can be explained only by
the i n t e r m e d i a t e participation in the r e a c t i o n of the m o n o m e r i c hexafluorothioaeetone dioxide (VII).
Apparently, in the f i r s t stage the acylation of the ketene (iI) by the anhydride (IV) with the formation
(at 50-60~ of the ketene methionate (VIII), i n t r a m o l e c u l a r sulfonation in the l a t t e r (at 120~ and above),
and decarboxylation (at 180-200~ take place s u c c e s s i v e l y . The s y m m e t r i c a l cyclic disulfone (iX) f o r m e d
dissociates under the r e a c t i o n conditions into the m o n o m e r i c hexafluorothioacetone dioxide (VII): it is pos-
sible that this is an equilibrium p r o c e s s . The thioacetone dioxide (VII) is unstable and tends e i t h e r to
evolve sulfur dioxide with the f o r m a t i o n of the thiirane dioxide (V) or to undergo association to f o r m the
s i x - m e m b e r e d cyclic t r i m e r (VI).

* F o r Communication V, see [1].

Institute of Heteroorganic Compounds, Academy of Sciences of the USSR, Moscow. T r a n s l a t e d f r o m

Khimiya Geterotsiklicheskikh Soedinenii, No. 1. pp. 42-44, January, 1974. Original a r t i c l e submitted
November 1. 1972.

9 1975 PlenumPublishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy of this article is availablefrom the publisher for $15.00.

34
 s%
II + (CFa)2 ~ I I ~ (CFo)2C C(CF.).
O--SO2 OC~.o/S 180-2~176176~ ~'.S02/ ~ *

VIII ~ IX

/ S O2--Cx((CF~) 2
(CF3)2C SO 2 ~ (C F~)~C=S Oo ~ ( C F a ) l t C - - C (C Fa)~
XO0__~CFa)2 ~ " \SO/
VI VII V

The c o r r e c t n e s s of the c o n s i d e r a t i o n s put f o r w a r d follows f r o m the g e n e r a l laws of the c h e m i s t r y of the

thioketene dioxides [2] and f r o m the known c h a r a c t e r i s t i c s of t r a n s f o r m a t i o n s among hexafluorothioacetone
d e r i v a t i v e s [3. 4]. The t h e r m a l stability of the thioacetone dioxide t r i m e r O/I) f o r m e d at 200~ is not s u r -
p r i s i n g , since e x a m p l e s a r e known of stable cyclic compounds with an a l t e r n a t i n g a r r a n g e m e n t of p a i r s of
t r i f l u o r o m e t h y l substituents [3, 4].
The s t r u c t u r e of the t h i i r a n e dioxide O/) was c o n f i r m e d by the 19F NMR method and by the r e s u l t s of
alkaline h y d r o l y s i s , which took p l a c e in a c c o r d a n c e with the following equation:
V + 9OH-+CHa C (CF.~) _~SO2() + 2HCO3 + 6F + 2 H 2 0

The t r i m e r i c composition of compound O/I) was shown by a m o l e c u l a r - w e i g h t d e t e r m i n a t i o n (cryo-

s c o p y in F r e o n - l l 3 ) . The p r e s e n c e of t r i f l u o r o m e t h y l and sulfonyl groups was shown by IR s p e c t r o s c o p y .
The s h a r p values of the o b s e r v e d f r e q u e n c i e s of the s t r e t c h i n g v i b r a t i o n s show the m o n o t y p i c i t y of all six
CFa groups and of all t h r e e sulfonyl groups. This is evidence in f a v o r of the spatial s y m m e t r y of the
m o l e c u l e of the t r i s u l f o n e 0/I). Since the t r i s u l f o n e O/I) is a d e r i v a t i v e of 1.3,5-trithiane, on the b a s i s of
the g e n e r a l laws of c o n f o r m a t i o n a l analysis [5], the c h a i r - s h a p e d c o n f o r m a t i o n is the b e s t - j u s t i f i e d for it.
The 19F NMR s p e c t r u m of compound (VI) (melt, and a l s o solutions in dimethyl sulfate or in sulfuryl
chloride) contains only one singlet signal, which shows that u n d e r the conditions of the e x p e r i m e n t the
m o l e c u l e of O/I) e x i s t s in the f o r m of a single c o n f o r m a t i o n in which the sulfur a t o m s of the ring a r e p r e s -
ent on one side of the c h i r a l plane and the c a r b o n a t o m s of the ring on the other side. Probably, in the
m e l t (above 83~ o r in solution (at 34.5~ t h e r e is a rapid c o n f o r m a t i o n a l c o n v e r s i o n of the e h a i r s t r u t -
t u r e into its antipode, when all the axially a r r a n g e d t r i f l u o r o m e t h y l groups change into the equatorial p o s i -
tions, and c o n v e r s e l y .

CF3 CFa

The singlet n a t u r e of the signal in the 19F NMR s p e c t r u m r e f l e c t s s o m e a v e r a g i n g of the positions of the o
t r i f l u o r o m e t h y l groups (50~ a and 50~c e) and shows that the potential b a r r i e r to i n v e r s i o n is low. We have
o b s e r v e d s o m e d i f f e r e n c e s in the IR s p e c t r a of c r y s t a l l i n e and dissolved s a m p l e s (see [5]) which p e r m i t s
the a s s u m p t i o n that i n v e r s i o n t a k e s p l a c e through a s t a g e of a d i s t o r t e d " b o a t - s h a p e d " f o r m .
In spite of its e x t r e m e l y c o m p l e x composition, compound (VI) readily distills (bp 128-129~ and it
s u b l i m e s m o r e r e a d i l y than naphthalene and a d a m a n t a n e . Sublimation takes p l a c e even at a t m o s p h e r i c
p r e s s u r e (20-25~ and p r o c e e d s e x t r e m e l y r a p i d l y at a r e s i d u a l p r e s s u r e of 50-60 ram. If sublimation is
p e r f o r m e d in a closed s p a c e at a t e m p e r a t u r e drop of 20-30~ it is p o s s i b l e to grow a single c r y s t a l of the
t r i m e r (VI) r e s e m b l i n g m o t h e r of p e a r l and with a s i z e of 3-4 ram. the shape of the c r y s t a l is polyhedral
with the f o r m of a flattened crown having a t h i r d - o r d e r axis of s y m m e t r y .
The t r i m e r O/D can a l s o be obtained with a yield of 70% by the p y r o l y s i s of hexafluoroisobutenylidene
sulfate (I) o r d i r e c t l y (with the yield of 52%) by t r e a t i n g h e x a f t u o r o - ~ H - i s o b u t y r i c acid with sulfur trioxide.
3 (CFa)zCHCOOH + 6 S Q ~ V I ~--3i
--CO,,

EXPERIMENTAL
The 19F NMR spectra weretakenon a Hitachi-Perkin-Elmer model R-20 instrument (56.456 MHz).
The chemical shifts (6) were measured in parts per million of the field relative to trifluoroacefic acid
(external standard). The IR s p e c t r a w e r e obtained on a IKS-12 s p e c t r o g r a p h .

35
 Hexafluorothioaeetone Dioxide T r i m e r (VI). A. A mixture of 14.7 g (0.05 mole) of the anhydride (IV)
and 8.9 g (0.05 mole) of the ketene (II) was heated in a steel autoclave first at 120~ for 2 h and then at
200~ for 2 h. After cooling, the reaction mixture was filtered through a glass filter. The filtrate (4.2 g)
was washed with water, dried with magnesium sulfate, and fractionally distilled. This gave 2.7 g (15%) of
2,2,3.3-tetrakis(trifluoromethyl)thiirane 1,1-dioxide (V) in the form of a colorless liquid with bp 84~
d42~ 1.7330, nD2~ 1.3155. 19F NMR spectrum (20% solution in CC14): singlet with 6 -17.0 ppm. Found %:
C 19.4: F 62.0: S 9.0. C6F1202S. Calculated %: C 19.8: F 62.4: S 8.8. On alkaline hydrolysis (0.1 N KOH),
the consumption of alkali was 9.1 equivalents in the presence of phenolphtha~n and 6.9 equivalents in the
p r es en ce of Methyl Orange~ 5.94 equivalents of fluoride ion was found in the hydrolyzate.
The precipitate (17.1 g)was washed with water and was mixed with magnesium sulfate, and the mixture
was sublimed at 100-130 mm (in the water bath): this gave 16.0 g {75%) of the hexafluorothioacetone dioxide
t r i m e r (VI) in the form of colorless prismatic crystals with mp 83~ and bp 128-129~ 19F NMR spectrum
(melt at 85-90~ or 20% solutions in dimethyl sulfoxide or sulfuryl chloride at 34.5~ singtet with 6
- 1 8 . 3 ppm. IR spectrum: thin layer of a mull in paraffin oil-- 1130 and 1472 em -1 (sulfonyl group)~ 1270
em "i (trifluoromethyl group): in CC14--broad absorption bands at 1128-1135, 1265-1280~ and 1470-1478
cm -1. Found %- C 16.6: F 53.8: S 15.0; tool. wt. (cryoseopically in F r e o n - l l 3 ) 624. CsF1806S3. Calculated
%: C 16.8; F 53.5: S 15.0: tool. wt. 642. The substance is readily soluble in dimethyl sulfate and sulfuryl
chloride, fairly soluble (about 10%) in alcohols, ethers, and d i ~ a n e : sparingly soluble (about 5%) in benzene
and carbon tetrachloride: slightly soluble in carbon sulfide; and insoluble in water.
B. Under the conditions given above. 25.8 g of hexafluoroisobutenylidene sulfate yielded 1.8 g (10%)
of the thiirane dioxide (V) and 15.0 g (70%) of the t r i m e r (VI).
C. A mixture of 19.6 g (0.01 mole) of hexafluoro-aH-isobutyric acid and 16.0 g (0.02 mole) of freshly-
distilled sulfur trioxide was heated in a steel autoclave at 200~ for 8 h. The reaction mixture was filtered,
and the precipitate was washed with water and was mixed with magnesium sulfate. Sublimation yielded
11.0 g (52%) of hexafluorothioacetone dioxide t r i m e r .

LITERATURE CITED
1. V . M . Pavlov, V. N. Dergachev, G. A. Sokol'skii, and I. L. Knunyants. Khim. Geterotsikl. Soedin.,
1321 (1973).
2. G. Opitz, Angew. Chem.. 78, 1066 (1966).
3. W . J . Middleton, U.S. Patent No. 3.136.781 (1964): Chem. Abstr., 61. 5612 c (1964).
4. K . V . Martin, J. Chem. Soc., 2944 (1964).
5. E. Eliel. N. Allinger. S. Angyal, and G. Morrison, Conformational Analysis. Interscience (1965),
Chap. 2.
6. O. Hassel and H. Viervoll. Acta Chem. Scand., 1, 149 (1947).
7. M. Kimura and K. Aoki, J. Chem. Soc. Japan, 72. 169 (1951).
8. L . E . Sutton, Tables of Interatomie Distances and Configuration. Chemical Society Special Publica-
tion,No. 11. London (1958).
9. V.M. Pavlov. M. A. Belaventsev, V. F. Gorelov, G. A. Sokol'skii. and I, L. Kuunyants, Khim. Getero-
tsikl. Soedin., 13 (1973).

36
FLUOROSULFONYL-CONTAINING HETEROCYCLIC COMPOUNDS

VII.* E L E C T R O N - A C C E P T I N G P R O P E R T I E S OF HEXAFLUOROTHIOACETONE

DIOXIDE TRIMER

G. A. Sokol'skii, V. M. P a v l o v , UDC 547.876.221:543.422.25.6

V. V. E z h o v , and I. L. Knunyants

On the b a s i s of UV and NMR s p e c t r o s c o p y it has b e e n e s t a b l i s h e d that with e t h e r s and t e r t i a r y

a m i n e s the cyclic t r i m e r of hexafluorothioacetone dioxide f o r m s d o n o r - a c c e p t o r Complexes
in which t h e r e is t w o - c e n t e r coordination in the c a s e s of 1,4-dioxane, 1 - m e t h y l m o r p h o l i n e ,
and 1,4-diethylpiperazine, and t h r e e - c e n t e r coordination in the c a s e s of 1,3, 5 - t r i o x a n e and
h e x a m e t h y l e n e t e t r a m i n e . The r e a c t i o n of the t r i m e r with s e c o n d a r y a m i n e s has given a m i d e s
of hexafluor o- 2- H - p r o p a n e - 2- sulfonic acid.

The stable cyclic t r i s u l f o n e (I), which is the t r i m e r of the hypothetical hexafluorothioacetone dioxide,
h a s b e e n obtained b y v a r i o u s methods and is t h e r e f o r e p r e p a r a t i v e l y a c c e s s i b l e [1].

2 SOa + (CF~)2CHCOOH 1 CF3

/SO,~ CFa SO2--~CFa

(CFa)2C .0 + (CFa)2C~C=O CF3
9 \s OJ i

The c h e m i c a l p r o p e r t i e s of this t r i s u l f o n e (I) have not b e e n d i s c u s s e d p r e v i o u s l y - s o m e of t h e m a r e con-

s i d e r e d below.
The t r i s u l f o n e (I) is i n e r t to e l e c t r o p h i l i c r e a g e n t s : it does not r e a c t with bis (trifluoromethyl)ketene,
b r o m i n e , chlorine, sulfuryl chloride, and sulfur trioxide, even at 200~ At the s a m e t i m e it r e a c t s u n d e r
r e l a t i v e l y m i l d conditions with v a r i o u s e l e c t r o n - d o n a t i n g compounds. Thus. although solutions of the t r i -
sulfone (I) in m e t h y l e n e chloride, c h l o r o f o r m , c a r b o n t e t r a c h l o r i d e , and dichloroethane show no absorption
in the 250-380 nm region, its solutions in d i - n - b u t y l e t h e r p o s s e s s s o m e a b s o r p t i o n of light. The optical
density of such solutions r i s e s c o n s i d e r a b l y in the p r e s e n c e of e l e c t r o n - d o n a t i n g compounds containing co-
o r d i n a t i o n - u n s a t u r a t e d oxygen o r nitrogen a t o m s , which shows the p r e s e n c e of d o n o r - a c c e p t o r interactions
of t h e s e s u b s t a n c e s with the t r i s u l f o n e (I).
On c o m p a r i n g the UV s p e c t r a of the solutions investigated (Fig. 1), it can be s e e n that d i - n - b u t y l
e t h e r and 1 - m e t h y l p i p e r i d i n e r e a c t feebly with the t r i s u l f o n e (I): 1.4-dioxane. 1 - m e t h y l m o r p h o l i n e , and 1.4-
d i e t h y l p i p e r a z i n e r e a c t m o r e v i g o r o u s l y , and, finally. 1,3, 5 - t r i o x a n e and h e x a m e t h y l e n e t e t r a m i n e r e a c t
r e l a t i v e l y strongly. The d e c i s i v e c h a r a c t e r i s t i c of the e f f e c t i v e n e s s of such interactions is not the e l e c -
t r o n - d o n a t i n g c a p a c i t y of the reagent but s t e r i c f a c t o r s - the n u m b e r of e l e c t r o n - d o n a t i n g c e n t e r s in the
m o l e c u l e of the r e a g e n t and t h e i r spatial c o r r e s p o n d e n c e with the e l e c t r o n - a c c e p t i n g c e n t e r s of the m o -
lecule of the t r i s u l f o n e (I). which can be r e p r e s e n t e d by one, two, or even all t h r e e sulfonyl groups. The

* F o r C o m m u n i c a t i o n VI. see [1].

Institute of H e t e r o o r g a n i c Compounds, A c a d e m y of Sciences of the USSR, Moscow. T r a n s l a t e d f r o m

K h i m i y a G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 1, pp. 45-48, January, 1974. Original a r t i c l e submitted
F e b r u a r y 6, 1973.

@ 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, h r. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

37
 D p o s s i b i l i t y of the t w o - c e n t e r coordination of 1,4-dioxane and of the
t h r e e - c e n t e r coordination of h e x a m e t h y l e n e t e t r a m i n e with the molecule
of the trisulfone (I) is expl~tined by the following c o n s i d e r a t i o n s . The
6 9
O - O i n t e r a t o m i c distance in 1,4-dioxane ("chair" conformation) and
'~.o the N - N distance in h e x a m e t h y l e n e t e t r a m i n e {structure of the ada-
5 mantane type) are, respectively, 2.82 ~ [2] and 2.42 ~ [3]. Although
3 the g e o m e t r i c p a r a m e t e r s of the m o l e c u l e o f the t r i s u l f o n e (I) have
~.5
not b e e n d e t e r m i n e d , they can be e s t i m a t e d by c o m p a r i s o n with t h o s e
2
for 1, 3, 5-trithiane. Since the d e g r e e of oxidation of the sulfur a t o m
I does not fundamentally affect the C - S i n t e r a t o m i c distances (1.80 ~ in
dimethyl sulfoue and 1.82 ~ in dimethyl sulfide [4]}. it m a y be con-
~0 ~0 3~ 3~
s i d e r e d that the distance between the SO2 groups in the trisulfone (I)
differs little f r o m the S - S distance in 1.3, 5-trithiane, which is 2.90/~
Fig. 1. UV s p e c t r a of solutions [5]. The v e r y slight difference in the d i s t a n c e s between the e l e c t r o u -
of the trisulfone (I) in d i - n - b u t y l donating c e n t e r s in 1,4-dioxane or h e x a m e t h y l e n e t e t r a m i n e and the
e t h e r - 1) standard: 2) in the distance between the e l e c t r o n - a c c e p t i n g c e n t e r s in the t r i s u l f o n e I
p r e s e n c e of 1 - m e t h y l p i p e r i d i n e : p e r m i t the a s s u m p t i o n of the f o r m a t i o n of d o n o r - - a c c e p t o r c o m p l e x e s
3) in the p r e s e n c e of 1.4-dioxane. of the following types:
4) in the p r e s e n c e of 1 - m e t h y l -
morpholine- 5} in the p r e s e n c e of
1,4-diethylpiperazine: 6) in the
p r e s e n c e of 1,3.5-trioxane: 7) in
the p r e s e n c e of h e x a m e t h y l e n e -
tetramine.
i I I ' I
,I, I 11

In such complexes, i n v e r s i o n of the s i x - m e m b e r e d ring of the t r i s u l f o n e (I) is difficult o r is even i m -

p o s s i b l e ; consequently, in c a s e s of m u l t i c e n t e r coordination the " c h a i r " c o n f o r m a t i o n m u s t be i m m o b i l i z e d
and the t r i f l u o r o m e t h y l g r o u p s be fixed in the axial and equatorial 2 . 4 . 6 - p o s i t i o n s of the ring. It has been
p o s s i b l e to d e m o n s t r a t e the l a t t e r by the 19F NMR method. The s p e c t r u m of a 10~ solution of the t r i s u l f o n e
(I) in d i - n - b u t y l e t h e r contains only one singlet signal (6 ~ - 1 8 . 3 ppm). which r e f l e c t s s o m e a v e r a g i n g of the
positions of the t r i f l u o r o m e t h y l groups as the r e s u l t of ring i n v e r s i o n (see [1, 6]). At the s a m e t i m e . the
s p e c t r u m of a 10% solution of the t r i s n l f o n e (I) in dioxane contains two singlet signals of equal intensity (at
- 1 7 . 7 and - 1 8 . 7 ppm); on adding 1 , 4 - d i e t h y l p i p e r a z i n e (two equivalents) to this solution, the d i f f e r e n c e in
the values of this p a i r of c h e m i c a l shifts i n c r e a s e s slightly (-17.6 and - 1 8 . 8 ppm). Similarly, two signals
a r e found in the s p e c t r o m e t r y of a 10% solution of the trisulfone (I) in 1,3, 5-trioxane (-17.3 and - 1 8 . 9 ppm}
and likewise in the p r e s e n c e of h e x a m e t h y l e n e t e t r a m i n e Cat - 1 7 . 0 and - 1 9 . 1 ppm). T h e s e f e a t u r e s of the
NMR s p e c t r a show the p r e s e n c e of two t y p e s of spatially i s o m e r i c t r i f l u o r o m e t h y l substituents Ca") and
Ce") in the fixed "chair" c o n f o r m a t i o n of the t r i s u l f o n e (I} when it f o r m s a d o n o r - a c c e p t o r c o m p l e x t h r o u g h
m u l t i c e n t e r coordination with a p o l y e t h e r or a polyamine.
The o b s e r v e d d i f f e r e n c e s in the values of the c h e m i c a l shifts, just like the d i f f e r e n c e s in the intensi-
t i e s of a b s o r p t i o n in the UV region~ p r o b a b l y r e f l e c t different levels of c h a r g e t r a n s f e r in d o n o r - a c c e p t o r
coordination; it is natural that on p a s s i n g f r o m e t h e r s to a m i n e s the s t r e n g t h of the coordination bond r i s e s .
This explains the following phenomenon. The optical d e n s i t i e s of solutions of the trisulfone (I) in di-n-butyl
ether, 1.4-dioxane, and 1,3, 5 - t r i o x a n e r e m a i n constant for s e v e r a l weeks: under t h e s e c i r c u m s t a n c e s , the
t r i s u l f o n e (I) can be isolated quantitatively f r o m t h e s e solutions by f r a c t i o n a l distillation. If, however,
1 - m e t h y l p i p e r i d i n e , 1,4-diethylpiperazine, or h e x a m e t h y l e n e t e t r a m i n e was used as donor, the optical den-
s i t i e s of such solutions fell to one half a f t e r 2-3 h, and a f t e r a day the a b s o r p t i o n of light had fallen to zero;
it was i m p o s s i b l e to i s o l a t e the trisulfone (I) f r o m such solutions e i t h e r by f r a c t i o n a l distillation or even
b y t r e a t i n g the solution with m i n e r a l acids. Apparently. the a m i n e - t r i s u l f o n e d o n o r - a c c e p t o r complex
originally f o r m e d changes i r r e v e r s i b l y b y the t r a n s f e r of the r e a c t i o n c e n t e r into the anionic f r a g m e n t .
which leads to the decyclization of the t r i s u l f o n e (I) with the subsequent cleavage of s e v e r a l C - S bonds. It
has been p o s s i b l e to d e m o n s t r a t e this fact b y p r e p a r a t i v e e x p e r i m e n t s .

38
 TABLE 1. The Sulfonamides (CF3)2CHSO2NR 2
......... A!kalimetry . . . . . 19F NMR spectJ:a~
Corn- NR: i c o n .s.u. m
. . .p. t. i. o. .n. .o. f. K
. . O H , eqtsj f l u o r i d e chemical spin-spin
pound! i to p h e n o l - ito M e t h y l ! ion found, shift, p p m * coupling
: phthalein IOrange equivs constants, Hz

[la (CH;)C~H, ! 8,08 7.12 ,, 5,92 --16,6 8.1

l i b i ((;I-l~)s 8,04 i 7,05 ! 6,03 -I6,5 8,0
t i c i (CH2CH_-!,:O 7,96 ! 7,06 i 5.99 - 16,0 8.6

* The s p e c t r a of 20% solutions in ethanol w e r e r e c o r d e d : the signals

w e r e doublets.

It was found that diphenylamine, which is c h a r a c t e r i z e d by a low e l e c t r o n - d o n a t i n g capacity (because

of s t e r i c hindrance) does not r e a c t with the t r i s u l f o n e (I) even at 200~ The m o r e highly e l e c t r o n - d o n a t i n g
N-methylaniline, piperidine, and m o r p h o l i n e r e a c t with the t r i s u l f o n e (I) even at 0-10~ when 2-3 equi-
valents of t h e s e a m i n e s w e r e used, the c o r r e s p o n d i n g a m i d e s of h e x a f l u o r o - 2 H - p r o p a n e - 2 - s u l f o n i c acid (II)
w e r e isolated with yields of 86-90%.

S02---~(CF3)2
U~ + - . R2Xtt
(CF3) 2 -- SO2 R2Nlt ~ (CF3)2CSO2C(CF3)2SO2C(CF3)2SO2--NltR2 ....
I + R.NII ~ SO~'---/~
" (CFj):
- (C F3)~CHSO2NR~
II a-C

The s t r u c t u r e of the sulfonamides (II) was c o n f i r m e d by t h e i r 19F NMR s p e c t r a and by the r e s u l t s of

alkaline h y d r o l y s i s .
(CFa)2CHSO2NR2 + 70H ~ 6F + CO2 OOCCH2SO2NR2 + 3 H20

The b e h a v i o r of the t r i s u l f o n e (I) with r e s p e c t to eleetrophilic and nucleophilie r e a g e n t s that has b e e n

c o n s i d e r e d c h a r a c t e r i z e s it as an e l e c t r o n - a c c e p t i n g compound, which is due to the unique c o m p a c t a s s o c i a -
tion in its m o l e c u l e of t h r e e sulfonyl and six t r i f l u o r o m e t h y l groupings.

EXPERIMENTAL

The UV spectra were taken on a SF-4A spectrophotometer at 20~ using as standard a 0.01 M solution
of the trisulfone (I) in di-n-butyl ether, to which the substances under investigation were added in a concen-
tration of 0.05 M (Fig. 1). The 19F NMR spectra were taken on a Hitaehi-Perkin-Elmer model R-20 spec-
trometer at a field strength of 14,092 gauss, a frequency of 56.456 MHz, and a resolution of 3 9 10 -8 with tri-
fluoroacetie acid as internal standard at a temperature of 34.5~
N-Methylhexafluore-2H-propane-2-sulfonanilide (IIa). A solution of 3.2 g (0.03 mole) of N-methyl-
aniline in 50 ml of ether was added to a solution of 6.4 g (0.01 mole) of the trisulfone (I) in 150 ml of dry
ether. The solvent was distilled off and the residue was fractionally distilled under reduced pressure
giving 2.8 g i87%) of the sulfonanilide in the form of a colorless liquid with bp 136~ (5 ram), d4 z~ 1.6140-
nD 2~ 1.4586. Found %: C 37.6: H 3.0: F 35.2. N 4.6: S 9.6. CIoHgO2F6NS. Calculated %: C 37.4: H 2.8:
F 35.5. N 4.4. S I0.0.
Hexafluoro-2H-propane-2-sulfonpiperidide (fib). A solution of 2.1 g (0.025 mole) of piperidine in 50
m l of e t h e r was added to a solution of 6.4 g (0.01 mole) of the t r i s u l f o n e (f) in 150 ml of ether. The solvent
was distilled off and the r e s i d u e was t r e a t e d with boiling toluene (2 9 10 ml): on cooling, the e x t r a c t de-
p o s i t e d a p r e c i p i t a t e . R e c r y s t a l l i z a t i o n f r o m toluene gave 2.7 g (90%) of the sulfonpiperidide, white a c i e u l a r
c r y s t a l s with mp 58~ bp 120~ (2 m m ) . Found %: C 32.4z H 3.8: F 37.9: N 4.7: S 10.8. CsHIIO2F6NS.
Calculated %: C 32.1; H 3.7~ F 38.2: N 4.7: S 10.7.
H e x a f l u o r o - 2 H - p r o p a n e - 2 - s u l f o n m o r p h o l i d e (IIc). Similarly, 6.4 g (0.01 mole) of the t r i s u l f o n e (I)
and 1.7 g (0.02 mole) of m o r p h o l i n e gave 2.6 g (86%) of the sulfonmorpholide in the f o r m of white a c i c u l a r
c r y s t a l s with mp 86~ (from benzene). Found %: C 28.1$ H 3.1: F 37.6: N 4.7: S 10.4. CTH902F6NS. Calcu-
lated %, C 27.8: H 3.0; F 37.9,. N 4.7: S 10.6.
A l k a l i m e t r y . A weighed s a m p l e of the compound (0.02-0.03 g) was d i s s o l v e d in 10 m l of ethanol, and
20 m l of 0.1 N caustic p o t a s h solution was added to this solution. A f t e r 12-15 h, the e x c e s s of alkali was

39
back-titrated with 0.1 N hydrochloric acid to phenolphthalein, and then to Methyl Orange. In other experi-
ments the amount of fluoride ion in the alkaline hydrolyzate was determined by the thoriometric method.
The results of the analyses are given in Table 1.

LITERATURE CITED
1. G.A. Sokol'skii, V. M. Pavlov. V. NI. Golovkin. V. F. Gorelov, and I. L. Knunyants, Khim. Geterotmikl.
Soedin., 42 (1974).
2. L . E . Sutton and L. O. Brockway. J. Amer. Chem. Soc., 57, 473 (1935).
3. V. Sehomakem and P. A. Sehaffer J. Amer. Chem. Soe., 69, 1555 (1947):
4. P . W . Allen and L. E. Sutton, Acta Cryst., 3, 46 (1950).
5. O. Hassel and H. Viervoll, Aeta Chem. Seand., 1, 149 (1947).
6. E. Elie]. N. Allinger. S. Angyal, and G. Morriso~. Cord~rmational Analysis lnterscience {1965), Ch. 2.

40
PYRYLOCYANINES
IV.* SYMMETRICAL 2,6-DIPHENYLTHIO- AND 2,6-DIPHENYLSELENOPYRYLOCYANINES

A. I. Tolmaehev and M. A. K u d i n o v a UDC 547.818.1'818.9

F r o m 4 - m e t h y l - 2 . 6 - d i p h e n y l t h i o p y r y l i u m and 4 - m e t h y l - 2 , 6 - d i p h e n y l s e l e n o p y r y l i u m salts thio-

and selenopyrylocyanines with s y m m e t r i c a l s t r u c t u r e s have been synthesized. In the s e r i e s of
dyes synthesized, g r e a t e r values of the vinylidene shifts of the absorption m a x i m a a r e observed
than in the s e r i e s of t h e i r thio- and selenoflavylium analogs. The mono-, t r i - , and penta-
methinecyanines obtained are m o r e highly colored than the analogous thie- and selenoflavylo-
cyanines and, conversely, the 2, 6-diphenylselenopyrytoheptamethinecyanines are colored less
deeply than the s e l e n o f l a v y l o t r i c a r b o c y a n i n e s . The s t r u c t u r e of the product of the oxidation
of 4-methyl-2, 6-diphenylpyrylium p e r c h l o r a t e has been established.

We have r e c e n t l y d e s c r i b e d polymethine dyes containing no h e t e r o a t o m s other than s e l e n i u m - seleno-

flavylocyanines [1, 2] - which p r o v e d to be the most deeply colored among the known polymethine dyes with
the s a m e length of c h r o m o p h o r e . It appeared of i n t e r e s t to investigate the influence on the color of the r e -
p l a c e m e n t of the oxygen atom of a h e t e r o c y c l e by a sulfur or selenium atom in the pyrylocyanines, also.
F o r this purpose, in the p r e s e n t work we have obtained 2,6-diphenylthio- and 2.6-diphenylselenopyrylo--
cyanines. It is known that solutions of some p y r y l o c y a n i n e s can be used as Q switches for l a s e r s (QSLs).
[3]. Since thiopyrylium and selenopyrylfum salts a r e m o r e stable to h y d r o l y s i s than p y r y l i u m salts [4],
and, judging f r o m the b a s i e i t y of the p y r o n e s [5], than t h e i r benzo homologs, solutions of such dyes could
also be of i n t e r e s t for use in QSLs. Thiopyrylomone- and thiopyrylotrimethinecyanines have been syn-
thesized p r e v i o u s l y by the condensation of 2,6-diphenylthiopyrylium p e r c h l o r a t e with dibasic acids [6]. It
has not yet been possible to obtain pentamethinecyanines in the p u r e state in this way [6]. Setenopyrylo-
cyanines w e r e completely unknown.
We have synthesized t h i o p y r y l o t r i - , - p e n t a - , and -heptamethinecyanines (VII, IX, and XI) by the r e a c -
tion of 4 - m e t h y l - 2 , 6 - d i p h e n y l t h i o p y r y l i u m p e r c h i o r a t e (I) with o r t h o f o r m i c e s t e r (as in [7]) or with the hy-
d r o c h l o r i d e s of the dianils of malondialdehyde and glutacondialdehyde. The bis(2, 6-diphenylselenopyrylo-
4)-monomethinecyanine (V) was obtained by condensing 4-
methyl-2, 6-diphenylselenopyrylium p e r c h l o r a t e (II) [8] with
, Cott, ~__/C~Hs 2,6-diphenylselenopyrylium p e r c h l o r a t e (III) [8]. The seleno--
p y r y l o t r i - , - p e n t a - , a n d - h e p t a m e t h i n e c y a n i n e s (VIII, X, and
XII) w e r e synthesized by using the s e l e n o p y r y l i u m salt (II) in
clo: cto; the same way as t h e i r sulfur analogs. In addition to t r i e a r b o -
E-Ill Iu cyanines with open polymethine chains (XI, XII). the use of
C6Hs . . . . ~ IC~ //~C 6H~ the h y d r o c h l o r i d e of the dianil of B, 6 - t r i m e t h y l e n e g l u t a e o n d i -
aldehyde [9] also gave the thie- and selenopyrylium t r i c a r b o -
c n /--~ C~,H5 cyanines (XIII and XIV) containing a s i x - m e m b e r e d carbon
~6-s clo 4-
Xlil, xI? ring in the c h r o m o p h o r e .

I X=S; II III X=S~; 1,11 R=CH3; Ill R=H The thio- and s e l e n o p y r y l i u m salts (I and II) a r e dis-
tinguished by a high reactivity, thanks to which the synthesis

* F o r Communication III, see [1].

Institute of Organic Chemistry. Academy of Sciences of the Ukrainian SSR, Kiev. T r a n s l a t e d f r o m

Khimiya Geterotsiklieheskikh Soedinenii, No. 1, pp. 49-52, January. 1974. Original a r t i c l e submitted
S e p t e m b e r 25, 1972.

9 19 75 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy o f this article is available from the publisher for $15.00.

41
 TABLE 1. Absorption Maxima of the l>yrylo- of polymethine dyes f r o m t h e m is a c c o m p a n i e d by side
cyanines in N i t r o m e t h a n e r e a c t i o n s . One of the side r e a c t i o n s is the oxidation of
the 4 - m e t h y l e n e - 2 , 6 - d i p h e n y l - 4 H - p y r a n s f o r m e d f r o m
Compound n x ~-,,,=.nm* t h e s e s a l t s under the action of b a s e s . Thus. when a
suspension of the s a l t {I) in acetone was t r e a t e d with
IV 0 s 6276 (695) * alkali, a high yield of 1,2-bis (2,6-diphenylthiopyran-4-
V 0 Se 672 (744)
VI 1 O 676"]" (708) s ylidene)ethane (XV) was obtained. H e r e the r e a c t i o n
VII 1 S 755t (796) p r o b a b l y takes p l a c e in a s i m i l a r m a n n e r to the oxida-
VIII 1 Se 795 (835)
IX 2 S 879 (900) tion of 1 , 1 . 3 - t r i m e t h y l - 2 H - i n d o l e [12], except that it
X 2 Se 910 (935)
X! 3 S 1000 (1007) does not r e q u i r e a special oxidizing agent. The s t r u c -
Xtl 3 Se 1035 ( 1 0 3 0 ) t u r e of {XV) was c o n f i r m e d by PM_R s p e c t r o s c o p y . In
XIII S 1017 --
XIV I Se lO5O (1o35) solution in p h o s p h o r i c t r i s (dimethylamide), the s p e c t r u m
of (XV) contains t h r e e singlets, with c h e m i c a l shifts of
* The values of Xma x f o r the analogous thio- 8.53 p p m (2H}, 7.12 p p m (2H), and 6.72 p p m (2It) and a
flavylocyanines [10] and selenoflavylocyanines multiplet between 7.75 and 7.20 p p m (20 H}. The signal
a r e given in p a r e n t h e s e s . at 6.72 p p m we a s s i g n to the protons of the ethanediyli-
F i g u r e refined as c o m p a r e d with that given dene group, the multiplet at 7 . 7 5 - 7 . 2 0 p p m t o t h e protons
by Wizinger and Heldemaun [11]. of the phenyl groups, and the si_~glets at 8.53 and 7.12
p p m to the protons p r e s e n t in the 3.5- positiOns of the
t h i o p y r a n rings. T h e s e protons a r e nonequivalent b e c a u s e of the a b s e n c e of f r e e rotation of the h e t e r o c y c l i c
r e s i d u e s in the m o l e c u l e . In t r i f l u o r o a c e t i c acid solution, the b a s e (XV) adds two protons, f o r m i n g the c a t -
ion (XVI}, the PMR s p e c t r u m of which contains singlets at 8.80 p p m (4H. H e t - H ) and 3.90 p p m (4I-I, 2CH2)
and a multiplet at 8.05-7.53 p p m (20H, 4C6Hs).

%Hs')__~ ~/~ c6H~CF3COCtl C6HS"x__..` tC6Hs

(C/,'~-c~2c
k~, H'2-~~_.//+s
CfH~, / 2CF3CC, O - " ",CsHi '
9 CeHsY ~---\CsH s

XV XV1

In a g r e e m e n t with this is the fact that in the s p e c t r u m of the salt (I) the signal of the p r o t o n s attached t o
the 5 - c a r b o n a t o m s of the h e t e r o c y c l e is located at 8.78 ppm. that of the a r o m a t i c protons at 8.23-7.72 ppm,
and that of the methyl group at 3.20 p p m . It m u s t be mentioned that a compound analogous to (XV) is a l s o
f o r m e d by heating 4 - m e t h y l t h i o f l a v y l i m n p e r c h l o r a t e in d i m e t h y l f o r m a m i d e or pyridine with yields of 90
and 70%. r e s p e c t i v e l y . Consequently, in spite of the opinion of Van Allan and Reynolds [13, 14] it m u s t be
a s s u m e d f o r this case, also. that oxidation is brought about by a t m o s p h e r i c oxygen. A compound analogous
to (XV) with its a b s o r p t i o n m a x i m u m at 526 nm is also f o r m e d f r o m the s e l e n o p y r y l i u m s a l t (II).
Ethanolic solutions of the thio- and selenopyrylocyanines, like the thio- and selenoflavylocyanines, a r e
unstable: solutions of t h e s e dyes in nitromethane, c h l o r o f o r m , and glacial a c e t i c acid a r e r e l a t i v e l y stable.
The a b s o r p t i o n m a x i m a of the s e l e n o p y r y l o c y a n i n e s (V. VIII, X, and XII). like t h o s e of the s e l e n o -
flavylocyanines, a r e located in the l o n g e r - w a v e r e g i o n than the a b s o r p t i o n m a x i m a of t h e i r sulfur analogs
(IV, VII, IX. and XI), which, in t h e i r turn, a r e m o r e deeply colored than the dyes c o n s t r u c t e d f r o m oxygen
h e t e r o c y c l e s (Table 1). In the c a r b o c y a n i n e s (VI-VIII), the shifts of the l o n g - w a v e a b s o r p t i o n m a x i m u m on
p a s s i n g f r o m the p y r y l o - to the t h i o p y r y l o - and s e l e n o p y r y l o c y a n i n e s a r e 79 and 119 n_m, r e s p e c t i v e l y . F o r
the t r i m e t h i n e c y a n i n e s (VI-VIII) we a l s o calculated the values of 1W"~- the r a t i o of the z e r o m o m e n t s to the
f i r s t m o m e n t s , which d e t e r m i n e the a v e r a g e position of the absorption bands in the wavelengths s c a l e [2].
F o r the t r i m e t h i n e c y a n i n e s containing O. S. and Se, M"~ p r o v e d to be, r e s p e c t i v e l y , 657.8, 733.1, and 766.1
nm, i.e., the shifts of the m e a n position of the long-wave absorption band on p a s s i n g f r o m the dye (VI) to
the dyes (VII) and (VHI) a r e . r e s p e c t i v e l y , 75.3 and 108 urn. As can be s e e n f r o m the f i g u r e s given, the
vinylene shift of the l o n g - w a v e a b s o r p t i o n band in the 2, 6-diphenylthio- and 2, 6-diphenylselenopyrylocyanines
is a p p r o x i m a t e l y 120-125 nm. In the flavylium analogs of these dyes, however, it is only 100 nm. While
the absorption m a x i m a of the p y r y l o m o n o m e t h i n e c y a n i n e s (IV. V) a r e located 70 n m t o w a r d s the s h o r t e r -
wave region as c o m p a r e d with the a b s o r p t i o n m a x i m a of t h e i r flavylinm analogs, in the carbocyanines, in
view of the d i s s i m i l a r vinylene shifts, this d i f f e r e n c e (VII and VIII) falls to 40 n m and in the d i c a r b o c y a -
nines (IX and X) to 20-25 nm. C o n v e r s e l y , the 2 . 6 - d i p h e n y l s e l e n o p y r y l o c y a n i n e s (XII and XIII) a r e c o l o r e d
still m o r e deeply than t h e i r selenoflavylium analogs and, thus. a r e the m o s t deeply c o l o r e d of the known
p o l y m e t h i n e dyes with the s a m e length of e h r o m o p h o r e .

42
 EXPERIMENTAL

The PMR s p e c t r a w e r e t a k e n on a ZKR-60 s p e c t r o p h o t o m e t e r with a working f r e q u e n c y of 60 MHz at

a t e m p e r a t u r e of 29~ and a concentration of 0.12 M. The c h e m i c a l shifts a r e given r e l a t i v e to TMS (inter-
nal standard).
Bis ( 2 , 6 - d i p h e n y l s e l e n o p y r y l o - 4 ) m o n o m e t h i n e c y a n i n e P e r c h l o r a t e (V). A m i x t u r e of 0.204 g (0.5
m m o l e ) of 4 - m e t h y l - 2 , 6 - d i p h e n y l s e l e n o p y r y l i u m p e r c h l o r a t e (II), 0.196 g (0.5 m m o l e ) of 2,6-diphenylseleno-
p y r y l i u m p e r c h l o r a t e (Ill), and 0.04 g (0.5 m m o l e ) of anhydrous sodium a c e t a t e in 4 m l of glacial acetic acid
was heated at 100~ for 30 rain. The dye was f i l t e r e d off, r e p r e e i p i t a t e d f r o m solution in n i t r o m e t h a n e with
42% p e r c h l o r i c acid, and c r y s t a l l i z e d f r o m acetic anhydride. Yield 0.22 g (62%). G r e e n c r y s t a l s with m p
268~ Found %: Se 22.4. C35H25CIO4Se~ Calculated%: Se 22.5.
Bis ( 2 , 6 - d i p h e n y l s e l e n o p y r y l o - 4 ) t r i m e t h i n e c y a n i n e P e r c h l o r a t e (VIII). A m i x t u r e of 0.408 g (1 m m o l e )
of (II), 0.296 g (2 re_moles) of o r t h o f o r m i c e s t e r , and 0.082 g (1 m m o l e ) of anhydrous sodium a c e t a t e in 6 m l
of glacial acetic acid was heated at 120~ f o r 10 rain. Yield 0.36 g (98%). B r o n z e c r y s t a l s with decomp, pt.
291~ (from a c e t i c anhydride). Found ~c: Se 21.4. C37H27C104Se2. Calculated ~c. Se 21.7.
Bis (2,6-diphenylthiopyrylo-4)pentamethinecyanine P e r c h l o r a t e (IX). A solution of 0.129 g (0.5 m m o l e )
of the h y d r o c h l o r i d e of the dianil of malondialdehyde in 25 ml of acetic anhydride was added to a solution of
0.362 g (1 m m o l e ) of (I) and 0.082 g (1 m m o l e ) of anhydrous sodium a c e t a t e in 5 m l of acetic acid, and the
m i x t u r e was heated at l l 0 ~ for 30 rain. The dye was s e p a r a t e d off and was washed f r e e f r o m contaminating
m o n o m e t h i n e c y a n i n e with hot acetic acid. A f t e r c r y s t a l l i z a t i o n f r o m nitromethane, the product f o r m e d
l u s t r o u s g r e e n c r y s t a l s . Yield 24%. Found 7c: C1 5.1. C39H29C10~S2. Calculated ~c: C1 5.3.
Bis ( 2 , 6 - d i p h e n y l s e l e n o p y r y l o - 4 ) p e n t a m e t h i n e c y a n i n e p e r c h l o r a t e (X) was obtained s i m i l a r l y to (IX)
f r o m 0.204 g (0.5 m m o l e ) of (II) in 4 ml of a m i x t u r e of acetic anhydride and glacial acetic acid (1 : 1).
Yield 60~c. F o u n d % : Se 21.3. C39H29C104Se2. Calculated ffc: Se 20.9.
Bis (2,6-diphenylthiopyrylo-4)pentamethineeyanine P e r c h l o r a t e (XI). A solution of 0.56 g (2 rnmoles)
of the h y d r o c h l o r i d e of the dianil of glutacondialdehyde in 15 m l of acetic anhydride w a s added to a solution
of 0.362 g (1 m m o l e ) of (I) in 15 m l of the s a m e solvent at 20~ and the m i x t u r e was left in the dark. A f t e r
12 h, the dye was f i l t e r e d off and was washed with acetic anhydride, with d r y benzene, and with ether. Yield
0.04 g (12~c). Brown c r y s t a l s . Found %: C1 5.2. C41H31C104S2. Calculated~c: C1 5.2.
Bis ( 2 , 6 - d i p h e n y l s e l e n o p y r y l o - 4 ) h e p t a m e t h i n e c y a n i n e p e r c h l o r a t e (XII) was obtained in a s i m i l a r
m a n n e r to (X-I) f r o m 0.204 g (0.5 m m o l e ) of (II). Yield 50~c. Found ~: Se 20.2. CtiH31C104Se 2. Calculated
%: Se 20.2.
Bis (2,6- diphenylthiopyrylo- 4)- 9, l l - t r i m e t h y l e n e h e p t a m e t h i n e c y a n i n e P e r c h l o r a t e (XIII). A solution
of 0.064 g (0.2 m m o l e ) of the h y d r o c h l o r i d e of the dianil of 2 , 4 - t r i m e t h y l e n e g l u t a c o n d i a l d e h y d e in 3 ml of
acetic anhydride was added to a s u s p e n s i o n of 0.145 g (0.4 m m o l e ) of (I) and 0.032 g (0.4 m m o l e ) of anhy-
d r o u s sodium a c e t a t e in 3 m l of glacial acetic acid, and the m i x t u r e was heated at 90-100~ f o r 1 h. The
dye was f i l t e r e d off and was w a s h e d with acetic anhydride with benzene, and with ether, and was c r y s t a l l i z e d
f r o m n i t r o m e t h a n e . Yield 37%. Found %: S 8.9. C~4H35C104S2. Calculated %: S 8.8.
Bis (2,6-diphenylselenopyrylo-4)-9, l l - t r i m e t h y l e n e h e p t a m e t h i n e c y a n i n e p e r c h l o r a t e (XIV) was obtained
s i m i l a r l y to (XIII) f r o m (II) with 30 rain heating of the solution. Yield 50%. Found g0: Se 18o9o C4tH35CtO4Se2.
Calculated ~c: Se 19.2.
1,2-Bis (2, 6 - d i p h e n y l t h i o p y r a n - 4 - y l i d e n e ) e t h a n e (XV). A suspension of 0.724 g (2 m m o l e s ) of (I) and
0.4 g (10 m m o l e s ) of caustic soda in a m i x t u r e of 15 m I of acetone and 2 m I of w a t e r was shaken until the
solid m a t t e r had d i s s o l v e d c o m p l e t e l y . Then the organic l a y e r was s e p a r a t e d off, filtered, and diluted with
ice w a t e r . The p r o d u c t that then deposited was f i l t e r e d off and r e c r y s t a l l i z e d f r o m d i m e t h y l f o r m a m i d e .
Yield 0.877 g (84~c). L u s t r o u s d a r k r e d needles with decomp, pt. 258~ ~rnax 512 nm. Found ~c: C 82.8:
H 5.0: S 12.1. C36H26S2. Calculated %: C 82.8: H 5.0; S 12.3.

LITERATURE CITED

1o A. I. T o l m a e h e v and M. A. Kudinova, Khim. G e t e r o t s i k l . Soedin., 1177 (1971).

2. A. I. T o l m a c h e v and M. A. Kudinova, Khim. G e t e r o t s i k l . Soedin., 924 (1971).
3. J. W i l l i a m s and G. Reynolds, J. Appl. Phys., 3_~9, 5327 (1968).
4. J. Degani, R. Fochi, and C. Vincenzi, Boll. Sci. Fac. Chim. Ind. Bologna, 2__3_3,21 (1965): Chem. Abstr.,
6__33, 8137 (1965).

43
 5. A . I . Tolmachev, L. M. Shulezhko, and A. A. Kisilenko, Zh. Obshch. Khim., 38, 118 (1968).
6. R. Wizinger and H. Angliker, Helv. Chim. Acta, 4_.99,2046 (1966).
7. R. Wizinger and P. Ulrich, Helv. Chim. Acta, 3._9.9,217 (1956).
8. M.A. Kudinova, S. V. Krivun, and A. L Tolmaehev, Khim. Geterotsikl. Soedin., 857 {1973).
9. Yu. L~ Slominskii, M. A. Kudinova, and A. I. Tolmachev, USSR Authors' Certificate No. 299,503 {1969).
Byul~ Izobret., No. 12, 90 (1971).
10. A . I . Tolmachev and M. A~ Kudinova, Khim. Geterotsikl. Soedin., 804 {1969).
11. R. Wizinger and W. Heldemann, Ber., 9._33,1533 {1960).
12. S. Hiinig and F. Linhart, Tetrahedron Lett., 1275 (1971).
13. J, Van Allan and G. Reynolds, Tetrahedron Lett., 2047 (1969).
14. G. Reynolds and J. Van Allan, J. Heterocycl. Chem., 5, 623 (1969).

44
PYRYLOCYANINES
V.* UNSYMMETRICAL 2, 6- PHENYL-SUBSTITUTED PYRYLO-,
THIOPYRYLO-, AND SELENOPYRYLOCYANINES

A. I. T o l m a c h e v , M. A. K u d i n o v a . UDC 547.812.5.818.1.818.9
a n d N. A. D e r e v y a n k o

U n s y m m e t r i c a l 2, 6-diphenyl-substituted p y r y l o - , thiopyrylo-, and s e l e n o p y r y l o t r i m e t h i n e -

cyanines containing 1,3, 3-trimethylindolinium or 3-methylbenzothiazolium nuclei have been
synthesized. F r o m the values of the deviations calculated f r o m the long-wave absorption
m a x i m a and by the method of "bond m o m e n t s , " it follows that in the polymethine dyes the
b a s i c i t i e s of the h e t e r o c y c l e s r i s e in the sequence, selenopyrylium < thiopyrylium < p y r y -
lium. In view of the high e l e c t r o n i c a s y m m e t r y of the dyes synthesized, in the long-wave
bands of the absorption s p e c t r u m the s t r o n g e s t are the maxima corresponding to the f i r s t
vibrational sublevel.

In a p r e c e d i n g communication s y m m e t r i c a l 2, 6-diphenylthio- and 2, 6-diphenylselenopyrylocyanines

have been d e s c r i b e d [1]. F o r a m o r e detailed investigation of the influence of the r e p l a c e m e n t of an oxygen
atom by a sulfur or selenium atom in the p y r y l o c y a n i n e series, in the p r e s e n t work we have obtained a num-
b e r of u n s y m m e t r i c a l p y r y l o - , thiopyrylo-, and selenopyrylocyanines. The initial compounds for the syn-
t h e s i s w e r e 4- methyl- 2.6- diphenyl- substituted p y r y l i u m and thio- and selenopyrylium salts (!-tII), and also
4- (a- anilinovinyl)- 2,6- diphenylthiopyrylium p e r c h l o r a t e (IV) and its selenium analog (V).

R CH=CHC6H4N(CH3)2-P

C6Hs~C6H,~ %Hs,~C6H 5
CIO~- CiO~-
I--Y VI -VHI

l - H I R=CH3; IV,V R=CH=CHNII%HS; [,V[ X=O; II,IV,VII X=S; III,V,VIII' X-Se

Compounds (IV) and (g) w e r e synthesized by the r e a c t i o n of the salts (II) and (III) with e t h y l i s o f o r m -
anflide. The p - d i m e t h y l a m i n o s t y r y l s (VI-VIII) were synthesized by the usual m e t h o d - by the condensation
of the salts (I-III) with p-dimethylaminobenzaldehyde [2]. 4 - ( p - D i m e t h y l a m i n o s t y r y l ) - 2 , 6 - d i p h e n y l s e l e n e -
p y r y l i u m p e r c h l o r a t e (VIII, kma x 705 nm)~ p r o v e d to be colored considerably m o r e deeply than its sulfur
analog (VII, Xma x 675 nm) and its oxygen analog (VI, ~ m a x 635 nm).
The u n s y m m e t r i c a l carbocyanines (IX), (X), and (XII) (Table 1) w e r e obtained by the r e a c t i o n of the
p y r y l i u m salt (I) with, r e s p e c t i v e l y , 4-(a'-anilinovinyl) derivatives of 2,6-diphenylthio- and 2, 6-diphenyl-
s e l e n o p y r y l i u m p e r c h l o r a t e s (IV, V) and flavyliuxn p e r c h l o r a t e . The trimethinecyanines (XI) and (XIII) w e r e
obtained by an analogous r e a c t i o n s t a r t i n g f r o m the selenopyrylium salt (III) and the hemicyanine (IV) o r
4- (~'- anilinovinyl)selenoflavylium p e r c h l o r a t e . Compounds (XIV-XVI) were synthesized by condensing the

* F o r Communication IV, see [1].

H e r e and below, the values of k m a x are given for solutions in nitromethane.

Institute of Organic Chemistry, Academy of Sciences of the Ukrainian SSR. Kiev. T r a n s l a t e d f r o m

Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 53-57, January, 1974. Original a r t i c l e submitted
October 25, 1972.

9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

45
 TABLE 1
C6H S ~ , k
~
C6H5
CH=CHCH~Z
cio~-
Conl- Xmax, M-St DM ,
X Z log D, n m
pound nm nm nrfl

IX S 2,6- Diphenylpyran- 4- ylidene 715 5.19 684.1 0.5 m

X Se 2,6- Diphenylpyr an- 4- ylidene 734 5.31 706.5 0.5 w

XI Se 2,6- Diphenylthiopyran- 4- ylidene 775 5.23 750.6 0

XII O 2- Phenylbenzopyr an- 4- ylidene 683 5.16 9
XIII Se 2- Phenylbenzos elenopyr an- 4- ylidene 8OO 5.0 15
XIV 0 1,3,3- Trimethylindolin- 2-ylidene 585 4.91 582.3 14.5 8.6
625 4.96
XV S 1,3.3- T r i m e t h y l i n d o l i n - 2-ylidene 615 4.90 613.0 10 15.5
660 4.90
XVI Se 1.3, 3- T r i m e t h y l i n d o l i n - 2-ylidene 630 4.89 618.3 -5 26.7
675 4.81
XVII O 3- Ethylbenz othiaz olin- 2-ylidene 575 4.86 570.6 -3 27.9
620 4.87
XVIII S 3- Methylbenzothlazolin- 2- ylidene 6O5 4.76 589.9 7.5 46.1
648* 4.65
XIX Se 3~ Methylbenzothiazolin- 2- ylidene 610 4.81 592.1 15,5 60.3
660* 4.63
* Shoulder.

s a l t s (I- III) with 2- f o r m y l m e t h y l e n e - 1,3,3-trimethylindoline. The u n s y m m e t r i c a l t h i a c a r b o c y a n i n e s (XVII)

w e r e obtained by condensing p y r y l i u m salt {I) with 2 - ( ~ - a c e t a n i l i d o v i n y l ) - 3 - e t h y l b e n z o t h i a z o l i u m iodide,
and (XVIII) and ( X I X ) f r o m the h e m i c y a n i n e s (IV and V ) a n d 2,3-dimethylbenzothiazolium toluenesulfonate.
In o r d e r to d e t e r m i n e the r e l a t i v e b a s i e i t i e s of the r e s i d u e s of the oxygen-, sulfur, and s e l e n i u m - c o n -
taining s i x - m e m b e r e d h e t e r o c y c l e s we have studied the deviations [3] of the c a r b o c y a n i n e s obtained. In the
c a s e of the t r i m e t h i n e c y a n i n e s (IX-XI) {Table 1), constructed solely f r o m p y r y l i n m , thiopyrylium, and
s e l e n o p y r y l i n m r e s i d u e s , t h e r e is no deviation (D), which indicates the c o m p a r a t i v e l y c l o s e b a s i c i t i e s of
the h e t e r o c y c l i c s y s t e m s considered. The e x i s t e n c e of deviations for the dyes (XII) and (XIII) is due to the
fact that the fusion of a benzene ring to s i x - m e m b e r e d oxygen- or s e l e n i u m - c o n t a i n i n g h e t e r o c y e l e s is a c -
companied by a d e c r e a s e in t h e i r basicity. F o r the u n s y m m e t r i c a l indo- and t h i a c a r b o c y a n i n e s (XIV-XIX),
in addition to the calculation of the deviations with r e s p e c t to the long-wave a b s o r p t i o n m a x i m a (D), as
e l s e w h e r e in the l i t e r a t u r e [4, 5], we m a d e u s e of the d e t e r m i n a t i o n of the deviations f r o m the m e a n p o s i -
tions of the a b s o r p t i o n bands M- l d e t e r m i n e d by the r a t i o of the z e r o and f i r s t m o m e n t s of t h e s e bands (DM)
[6]. In the calculation of D and D M, the values of ) ' m a x and of M-~ for the s y m m e t r i c a l pyrylc~-, t h i o p y r y l o - ,
and s e l e n o p y r y l o c y a n i n e s w e r e taken f r o m [1], those f o r the s y m m e t r i c a l flavylo- and selenoflavylocyanines
f r o m [7]. and those for the s y m m e t r i c a l t h i a - * and indoearbocyanines f r o m [5]. The values of D for the
dyes (XIV-XVI) and (KVII-XIX) calculated f r o m the l o n g - w a v e a b s o r p t i o n m a x i m a cannot be u s e d to judge
the c o m p a r a t i v e b a s i c i t y of the O-. S-, and Se-containing h e t e r o c y c l e s considered. F o r the c a r b o c y a n i n e s
(XVI. XVII), t h e s e magnitudes even have negative values. Conversely. the deviations D M calculated by the
method of band m o m e n t s h e r e give the c o r r e c t c h a r a c t e r i s t i c s . Depending on the n a t u r e of the h e t e r o c y c l e ,
both for the i n d o c a r b o c y a n i n e s and for the t h i a c a r b o c y a n i n e s they i n c r e a s e on p a s s i n g f r o m oxygen to sul-
fur and s e l e n i u m in the s a m e way as in the analogous dyes containing flavylium, thloflavylium, and s e l e n o -
flavylium r e s i d u e s [5]. Consequently, judging f r o m the values of D M, in the polymethine dyes the seleno-
p y r y l i n m nucleus is l e s s b a s i c than the t h i o p y r y l i u m nucleus which, in its turn, b e h a v e s as l e s s b a s i c than
the p y r y l i u m nucleus.
The method of deviations in its g e n e r a l f o r m p r o v e d inapplicable to the p r e s e n t c a s e b e c a u s e of the
m a r k e d difference in the shapes of the a b s o r p t i o n c u r v e s of the dyes (XIV-XIX) and the s y m m e t r i c a l c a r b o -
cyanines e o n s t r u e t e d f r o m the s a m e h e t e r o c y e l i c r e s i d u e s . As can be s e e n f r o m Fig. 1. the a b s o r p t i o n

* M-1 f o r 3 , 3 - d i m e t h y l t h i a c a r b o c y a n i n e is 538.7 nm.

46
 c u r v e of the s y m m e t r i c a l bis-[2,6--dlphenylseleno--
log e / ~ p y r y l o - 4 ] - t r i m e t h i n e c y a n i n e (XX) has the shape
typical for p o l y m e t h i n e dyes [8-10] with a s h o r t -
5,0 ~-~,~'~,2 wave " s e c o n d a r y " m a x i m u m located at a distance
/ / of 1250 c m - i f r o m the m a i n m a x i m u m . A s i m i l a r
/,d s h a p e of the c u r v e s is o b s e r v e d f o r the oxygen and
sulfur analogs of the dye (XX) and of the u n s y m -
m e t r i c a l c a r b o c y a n i n e s (IX-XIII) c o n s t r u c t e d f r o m
h e t e r o c y c l e s of c o m p a r a t i v e l y s i m i l a r b a s i c i t i e s :
,,oL /,::/ X Solutions in a e e t o n i t r i l e of the s e l e n o p y r y l o -
cyanine (XX), its oxygen and sulfur analogs, and
the c a r b o c y a n i n e s (IX-XI) p o s s e s s intense l u m i n e -
s c e n c e (}'max of the l u m i n e s c e n c e of dye (XX) is
~40 500 600 700 800 )~ nm 840 nm). In all c a s e s , the l u m i n e s c e n c e s p e c t r a
Fig. i. Electronic absorption spectra of solutions showed a second m a x i m u m which is m i r r o r - s y m -
in nitromethane: I)"bis- [2,6-diphenylselenopyrylo]- m e t r i c a l with r e s p e c t to the a b s o r p t i o n s p e c t r a .
trimethinecyanine (XX). 2) [2,6-diphenylpyrylo]- This shows that the second m a x i m u m belongs to a
[indo]-trimethinecyanine 0flV): 3) [2,6-diphenylthio- v i b r a t i o n a l sublevel of the s a m e e l e c t r o n i c transition.
pyrylo]- [indo]-trimethinecyanine (XV)- 4) [2,6-di- The a b s o r p t i o n c u r v e of the u n s y m m e t r i c a l
phenyls elenopyrylo]- [indo]-trimethinecyanine (XVI). i n d o c a r b o c y a n i n e s (XIV-XVI) each have two well-
defined m a x i m a (see Fig. 1 and Table 1). Attention
is a t t r a c t e d by the facts that in the p y r y l o i n d o t r i m e t h i n e c y a n i n e (XIV) the l o n g e r - w a v e m a x i m u m is still
s o m e w h a t s t r o n g e r than the s h o r t - w a v e m a x i m u m : in its sulfur analogs (XV) the two m a x i m a have a l m o s t
equal i n t e n s i t i e s : and in the l e a s t s y m m e t r i c a l i n d o s e l e n o p y r y l o t r i m e t h i n e c y a n i n e (XVI) the l o n g e r - w a v e
m a x i m u m is now c o n s i d e r a b l y w e a k e r than the s h o r t e r - w a v e m a x i m u m . A complex shape of the c u r v e s is
a l s o o b s e r v e d for the u n s y m m e t r i c a l t h i a c a r b o c y a n i n e s (VII-XIX). The r a t i o of the intensities of the in-
dividual m a x i m a in the solutions of t h e s e dyes does not depend on the concentration, which excludes an ex-
planation of one of the bands by the s t a t e of a g g r e g a t i o n of the dye. Under o r d i n a r y conditions, solutions of
compounds (XIV-XIX) do not f l u o r e s c e . However, on the b a s i s of the fact that, as for the s y m m e t r i c a l cy-
anines [11], the d i f f e r e n c e in the f r e q u e n c i e s between the two m a x i m a in the s p e c t r a of t h e s e dyes does not
depend on the n a t u r e of the solvent (it is the s a m e - a p p r o x i m a t e l y 1250 c m - 1 - in nitromethane, c h l o r o f o r m ,
and nitrobenzene), it m u s t be c o n s i d e r e d that in the dyes (XIV-XIX), as well, the two l o n g - w a v e m a x i m a b e -
long to the s a m e e l e c t r o n i c t r a n s i t i o n . We have o b s e r v e d a s i m i l a r s h a p e of the a b s o r p t i o n c u r v e s for un-
s y m m e t r i c a l thin- and i n d o c a r b o c y a n i n e s containing flavylium and thio- and s e l e n o f l a v y l i u m r e s i d u e s [5].
However, in the l a t t e r the intensity of the l o n g e r - w a v e m a x i m u m was still s m a l l e r , which m u s t be connected
with the g r e a t e r e l e c t r o n i c a s y m m e t r y of t h e s e dyes. Solutions of the carotenoids have a b s o r p t i o n c u r v e s
of s i m i l a r shape [12]. Apparently, it is c h a r a c t e r i s t i c for solutions of all dyes in the m o l e c u l e s of which
the c a r b o n - c a r b o n bonds of the c h r o m o p h o r e differ s t r o n g l y in t h e i r o r d e r . F o r example, the fact that in
s o m e t e t r a - and h e x a m e t h i n e m e r o c y a n i n e s a change in the p o l a r i t y of the solvent causes, in addition to a
shift in the a b s o r p t i o n band itself, a change in the r a t i o of the intensities of the "main" and " a u x i l i a r y "
m a x i m a is undoubtedly connected with a change in the equivalence of the bonds of the c h r o m o p h o r e [13].

EXPERIMENTAL
4-(o:-Anilinovinyl)-2,6-diphenylthiopyrylium P e r c h l o r a t e (IV). A m i x t u r e of 0.725 g (2 m m o l e s ) of
(II) and 4 m l of ethylisoforrnanilide was heated at 70~ for 1 h. The p r e c i p i t a t e was f i l t e r e d off and was
p u r i f i e d by c h r o m a t o g r a p h y f r o m c h l o r o f o r m on a l u m i n a with subsequent p r e c i p i t a t i o n f r o m ethanolic solu-
tion with 20~c p e r c h l o r i e acid and c r y s t a l l i z a t i o n f r o m glacial acetic acid. Yield 0.225 g (24~c). D a r k r e d
needles with decomp,pt. 219-220~ ~'max 512 nm. Found ~: S 6.9. C25H20CINOr Calculated %: S 6.9.
4 - ( ~ - A n i l i n o v i n y l ) - 2 , 6 - d i p h e n y l s e l e n o p y r y l i u m p e r c h l o r a t e (V) was obtained f r o m (III) in a s i m i l a r
m a n n e r to (IV), but with heating at 50-55~ Yield 62%. D a r k r e d c r y s t a l s with decomp, pt. 205-207~ (from
glacial acetic acid), ~'max 532 nm. Found %: Se 15.4. C25H20C1NO4Se. Calculated %: Se 15.4.
4 - ( p - D i m e t h y l a m i n o s t y r y l ) - 2 , 6 - d i p h e n y l s e l e n o p y r y l i u m P e r c h l o r a t e (VIII). A m i x t u r e of 0.205 g
(0.5 m m o l e ) of (III) and 0.074 g (0.5 m m o l e ) of p - d i m e t h y l a m i n o b e n z a l d e h y d e in 2 m l of acetic anhydride
was heated at 100-110~ f o r 30 rain. Yield 0.230 g (85~c). G r e e n c r y s t a l s with decomp, pt. 260~ Found
%: Se 14.4. C27H24C1NO4Se. Calculated %: Se 14.6.

47
 [2,6-Diphenylpyrylo-4]- [2,6-diphenylthiopyrylo--4]-trimethinecyanine iDerchlorate (IX). A m i x t u r e of
0.230 g (0.6 mmole) of (I), 0.310 g (0.6 mmole) of (IV), and 0.054 g (0.6 mmole) of anhydrous sodium acetate
in 4 ml of a 1 : 1 m i x t u r e of acetic anhydride and glacial acetic acid was heated at 13"0~ for 30 rain. The
dye was filtered off, Teprecipitated f r o m solution in nitromethane with 20% p e r c h l o r i c acid, and c r y s t a l l i z e d
f r o m acetic anhydride. Yield 3.60 g (87%). Lustrous g r e e n c r y s t a l s with mp 288~ Found %: S 5.1.
C37H27C105S. Calculated%: S 5.2.
[2,6-Diphenylpyrylo-4]- [2,6-diphenylselenopyrylo-4]-trimethinecyanine p e r c M o r a t e (X) was obtained
s i m i l a r l y to (IX). but heating was p e r f o r m e d for 15 rain. Yield 80%. Green needles with d e c o m p . p t . 262~
(from a 1 : 1 m i x t u r e of acetic anhydride and acetic acid). Found %: Se 11.7. C37H27C1OsSe. Calculated %:
Se 11.9.
[2,6-Diphenylselenopyrylo-4]- [2.6-diphenylthiopyrylo-4]-trimethinecyanine p e r c h l o r a t e {XI) was ob-
tained s i m i l a r l y to (IX) f r o m the salts {III) and (IV) by heating for 1 h. Yield 72%. Golden needles with de-
c o m p . p t . 296~ (from acetic anhydride). Found%: Se 11.7. C37H27C104Se. C a l c u l a t e d ~ : Se 11.6.
[2,6-- Diphenylpyrylo- 4]- [flavylo- 4]-trimethinecyanine p e r c h l o r a t e {XII) was obtained s i m i l a r l y to (IX)
f r o m {I) and 4- (a'-anilinovinyl)flavylium p e r c h l o r a t e [14] with a yield of 70%. Dark g r e e n c r y s t a l s with
decomp, pt. 298~ (from a 1 : 1 m i x t u r e of acetic anhydride and acetic acid). Found %: C1 6.1. C3~H25C10c.
Calculated %: C1 6.1.
[2,6-Diphenylselenopyrylo-4]- [selenoflavylo-4]-trimethinecyanine p e r c h l o r a t e (XIII) was obtained si-
m i l a r I y to (IX) f r o m (III) and 4- (w-anilinovinyl)setenoflavylinm p e r c h l o r a t e [5] with a yieId of 74%. Bronze
c r y s t a l s with decomp, pt. 271~ (from a 1 9 1 m i x t u r e of acetic anhydride and acetic acid). Found %: Se
22.2. C35H25C104Se2. Calculated%: Se 22.5.
[2,6- Diphenylpyrylo- 4]- [1,3.3-trimethylindo-- 2]-trimethinecyanine P e r c h l o r a t e (XIV). A m i x t u r e of
0.173 g (0.5 mmole) of (I), 0.1 g (0.5 mmole) of 2 . f o r m y l m e t h y l e n e - l , 3 , 3 - t r i m e t h y l i n d o l i n e , and 0.04 g (0.5
mmole) of anhydrous sodium acetate was heated in 2 ml of a 1 : 1 m i x t u r e of acetic anhydride and acetic
acid at 130~ for 15 man. The dye was f i l t e r e d off. r e p r e c i p i t a t e d f r o m acetic acid solution with 42% p e r -
chloric acid, and c r y s t a l l i z e d f r o m the s a m e solvent. Yield 0.160 g (60%). Green c r y s t a l s with decomp, pt.
231~ Found%: C1 6.5. C3~H28C1NO5. Calculated%: C1 6.7.
[2,6-Diphenylthiopyrylo-4]- [1,3,3-trimethylindo- 2]-trimethinecyanine p e r c h l o r a t e {XV) was obtained
s i m i l a r l y to (XIV) f r o m {iI). Yield 90~c. Lustrous g r e e n needles with decomp, pt. 231~ (from glacial acetic
acid). Found %: S 5.9. C31H28C1NO4S. Calculated%- S 5.9.
[2, 6- Diphenyls elenopyrylo- 4]- [1.3,3- trimethylindo- 2]-trimethinecyanine p e r c h l o r a t e (XVI) was ob-
tained s i m i l a r l y to (XIV) f r o m {iII). Yield 80~c. Lustrous green needles with decomp, pt. 236~ (from a
m i x t u r e of nitromethane and ethanol). Found%: Se 13.2. C3tH28C1NO4Se. Calculated ~c: Se 13.3.
[2,6-Diphenylpyrylo-4]- [3-ethylthia-2]-trimethinecyanine P e r c h l o r a t e (XVII). A m i x t u r e of 0.190 g
(0.54 mmole) of {i), 0.240 g (0.54 m m o l e ) o f 2-(cc-acetanilinovinyl)-3-ethylbenzothiazolium iodide, and 0.2
ml (0.14 g, 1 mmole) of t r i e t h y l a m i n e in 6 ml of absolute ethanol was boiled f o r 5 rain. The dye was filtered
off and was c r y s t a l l i z e d f r o m glacial acetic acid. Yield 0.092 g (36%). Dark blue needles with decomp, pt.
232~ Found%: C1 6.45. C29H24C1NOsS. Calculated%: C1 6.65.
[2.6-Diphenylthiopyrylo-4]-[3-methylthia-2]-trimethinecyanine P e r c h l o r a t e {XVIII). A m i x t u r e of
0.232 g (0.5 mmole) of the hemicyanine (IV), 0.184 g (0.54 mmole) of 2,3-dimethylbenzothiazolium toluene-
sulfonate, and 0.04 g (0.5 mmole) of anhydrous sodium acetate in 7 ml of a 1 : 1 mixture of acetic anhydride
and acetic acid was heated at 100~ for 5 rain. The dye was f i l t e r e d off and was chromatographed f r o m a
1 : 1 m i x t u r e of c h l o r o f o r m and nitromethane on alumina, was r e p r e c i p i t a t e d f r o m solution in a 1 : 1 m i x t u r e
of ethanol and nitromethane with 20% p e r c h l o r i c acid. and was c r y s t a l l i z e d f r o m a 1 : 3 m i x t u r e of acetic
anhydride and acetic acid. The yield was 0.180 g (60%). Dark blue c r y s t a l s with decomp, pt. 283~ Found
%: S 11.8. C28H22C1NO4S2. Calculated %: S 11.9.
[2.6-Diphenylselenopyrylo-4]- [3-methylthia-2]-trimethinecyanine p e r c h l o r a t e (XIX) was obtained
s i m i l a r l y to (XVIII)from the hemicyanine (V) and 2.3-dimethylbenzothiazolium toluenesulfonate, except that
the m i x t u r e was heated for 15 rain. Yield 86%. G r e e n needles with decomp.pt.249~ (from a 1 : 1 m i x t u r e
of nitromethane and ethanol). Found %: Se 13.4. C28H22C104SSe. Calculated %: Se 13.6.

LITERATURE CITED
I. A. I. Tolmachev and M. A. Kudinova, Khim. Geterotsikl. Soedin.. 49 (1974).
2. R. Wizinger and P. Ulrich. Helv. Chim. Acta, 399, 207 (1956).

48
 3. A . I . Kiprianov, Introduction to the Electronic Theory of Organic Compounds [in Russian], Naukova
Dumka, Kiev (1965)o p. 156.
4. E.D. Sych, Zh. N. Belaya, and G. G. Dyadyusha, Ukr. Khim. Zh.. 30, 1065 (1964).
5. A. L Tolmachev and M. A. Kudinova, Khim. Geterotsikl. Soedin., 1177 (1971).
6. B . I . Stepanov and V. L. Gribkovskii, Introduction to the Theory of Luminescence [in Russian], Minsk
(1963), p. 156.
7. A . I . Tolmachev and M. A. Kudinova, Khim. Geterotsikl. Soedin., 924 (1971).
8. S. L Vavflov, Sobr. Soch., Izd. Kad. Nauk SSSR, 1, 105 (1952).
9. A . I . Terenin. The Photonics of Dye Molecules [in Russian], Nauka, Leningrad (1967). p. 177.
10. J. Pouradier, J. Chem. Phys., 61, 1107 (1964).
11. W. West and A. Geddes. J. Phys. Chem., 68, 837 (1964).
12. O. Isler, R. Ruegg; and P. Schudel, Chimia, 15, 208 (1961).
13. F . A . Gershtein, Z. P. Sytnik, I. I. Levkoev, E. B. Lifshits, L. O. Leont'eva, and Yu. S. Rozum, in.
Collection of Scientific Papers on the Synthesis, Treatment, and Investigation of Special Organic
Compounds for the Photographic Chemicals Industry [in Russian]. Moscow, No. 7 (1972), p. 4.
14. R. Wizinger and W. Heldemann, Chem. Ber., 93, 7 (1960).

49
FUNCTIONAL DERIVATIVES OF THIOPHENE
VIII.* SYNTHESIS OF FORMYL DERIVATIVES OF ACYLAMINOTHIOPHENES,
THIE NO[2,3-b] PYRIDINES, THIENO [2.3- d] PYRIMIDINES.
AND THIENO[3', 2': 5, 6] PYRIDO[2,3-d] PYRIMIDINES

V. I. Shvedov. I. A. Kharizomenova. UDC 547.736.07

and A. N. Grinev

A method is p r o p o s e d f o r the s y n t h e s i s of 5- a c y l a m i n o - 2.3- dimethylthiophene- 4- carbaldehydes

and 5 - a c y l a m i n o - 2 . 3 - t e t r a m e t h y l e n e t h i o p h e n e - 4 - c a r b a l d e h y d e s by the f o r m y l a t i o n of the c o r -
responding thiophenes using the V i l s m e i e r r e a c t i o n . F r o m the f o r m y l d e r i v a t i v e s obtained,
p r e v i o u s l y u n a c c e s s i b l e d e r i v a t i v e s of thieno[2, 3-b]pyridine, thieno[2,3-d]pyrimidine, and
thieno[3'. 2': 5.6]pyrido[2,3-d]-pyrimidine have been synthesized.

The f o r m y l a t i o n by the V i l s m e i e r method of the 5 - a c y l a m i n e - 2 . 3 - d i m e t h y l - and 5 - a e y l a m i n o - 2 , 3 -

t e t r a m e t h y l e n e t h i o p h e n e s (Ia-e) that have now b e c o m e widely available [2] has enabled a s e r i e s of p r e v i o u s -
ly unknown f o r m y l d e r i v a t i v e s (Ha-e) to be obtained in high yield. The IR s p e c t r a of (Ha-e), as c o m p a r e d
with those of (ta-e), have an additional a b s o r p t i o n band in the region of the f r e q u e n c i e s of the v i b r a t i o n s of
the e a r b o n y l group at 1600-1690 e m - I . In the PMR s p e c t r u m , a singlet in the region of a r o m a t i c protons
that is o b s e r v e d f o r 4 . H in compounds (ia-e) has d i s a p p e a r e d .
To c h a r a c t e r i z e the compounds obtained, d e r i v a t i v e s of t h e m w e r e synthesized, the phenylhydrazone
(III), the is onicotinoylhydraz one (IV), the t h i o s e m i e a r b a z o n e (V), and the anil (VI). The reduction of (VI)
with sodium t e t r a h y d r o b o r a t e gave 4 - a n i l i n o m e t h y l - 5 - b e n z o y l a m i n o - 2 , 3 - t e t r a m e t h y l e n e t h i o p h e n e (VII).
In the a c y l a m i n o t h i o p h e n e c a r b a l d e h y d e s (Ha-e), the functional groups a r e located in the ortho position
with r e s p e c t to one another, and t h e r e f o r e they a r e of i n t e r e s t as the s t a r t i n g compounds f o r the synthesis
of various condensed h e t e r o c y c l e s .
The action of cyanoacetie e s t e r in the p r e s e n c e of piperidine on (IIa, b, d) gave high yields of 6 - a m i n o -
5-ethoxycarbonylthieno[2,3-b]pyridines (VIII. IX). The r e a c t i o n of (Ha, d) with m a l o n o n i t r i l e and benzo-
n i t r i l e took p l a c e s i m i l a r l y and also led to d e r i v a t i v e s of 6-aminothieno[2,3-b]pyridine (X, XI, XII). The
acyl r e s i d u e substituted in the amino group of (Ha, b, or d) was eliminated by the p i p e r i d i n e in the r e a c t i o n
p r o c e s s . On r e a c t i o n with cyanoacetic e s t e r , (fib) and (IId), differing by t h e i r acyl substituents, both gave
(IX). The IR s p e c t r a of (VIII) and (IX) each had a band at 1690 e m -1 which is c h a r a c t e r i s t i c f o r the C ~ O
of an ethoxycarbonyl group, and the s p e c t r a of (X) and (XI) each had a band at 2230 c m -1 c h a r a c t e r i z i n g a
CN group. In all the d e r i v a t i v e s (VIII-XII) obtained, the a b s o r p t i o n bands of the NH2 group w e r e found in
the 3400-3490 c m -1 region.
The r e a c t i o n of (IX) and (3:) with an e x c e s s of f o r m a m i d e gave the t h i e n o p y r i d o p y r i m i d i n e s (XIII)
and (XIV). In the IR s p e c t r u m of (XIII), the carbonyl group is c h a r a c t e r i z e d by a band at 1670 c m -1, which
shows the p r e s e n c e of a l a e t a m s t r u c t u r e in (XIII).

* F o r C o m m u n i c a t i o n VII. see [1].

S. Ordzhonikidze All-Union S c i e n t i f i c - R e s e a r c h Institute of P h a r m a c e u t i c a l C h e m i s t r y . Moscow.

T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i e h e s k i k h Soedinenii, No. 1. pp. 58-60, January. 1974. Original
a r t i c l e submitted F e b r u a r y 8, 1973.

9 19 75 Plenum Publishing Corporation, 22 7 West 1 7th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

50
 ~--~CH2NHC6Hs__ ~ C M = N % ~ 5 R2 ~__~M=NN.C6, s
NFICOC~sH~, ~ " ~ S ' J ~ N H C O C o H 5 R"~'~S'/\NFI.CDR 3 V ~S ./ ~NHCOCsfl5

u VI . I a-e / I11

Rt/~Sf~N-~F'~N H2 RI~$~NHCOR3 ~,,,~S~,N HCO C6tt5

XIII-XIV XV-XIX V

Ia, I I a , X V Rz= R~ = R4 = CH3; Ib, I I b , R1 + R2 = (CH2)4, R4-- CH3; I c , I I c , X V I I Rt = R2 =

CH 3, R4= C8H5; Id, IId, XVTII R~ +R2:(CH2)4, R4=C6H~; Ie,IZe X I R1 +R 2 =(CH2)4, R4=
CHzC6Hs; V I I I R~=R ~ : CH~, R~ = COOC~H~; IX Rz ~P.~ =(CH3)~, R~ = COOC~H~; X R ~= P~ =
CH 3, R~ = C N : X I Rz +P.~ = (CH~)~, R~ -~ CN; X I I R~ +R ~ = (CH~)~, R~ = C O t e r i e ; R5 = OH,
X I V P.~ = N[-] z.

The r e a c t i o n of (IIa-d) with ammonium acetate was p e r f o r m e d with heating in acetic acid, i.e.. under
conditions differing f r o m those for the synthesis of the quinazolinones [3]. As a result, we obtained high
yields of the thienopyrimidine derivatives (XV-XIX) with position 4 f r e e f r o m substituents. In the PMR
s p e c t r u m for (XV), singlets of the protons of the CH 3 groups are o b s e r v e d at 2.78, 2.28, and 2.45 ppm, and
the singlet of a proton at 8.77ppm, c o r r e s p o n d i n g to the 4-H atom.

EXPERIMENTAL

The PMR spectra were taken on a JEOL-4H-100 instrument using HMDS as internal standard. The
IR spectra were taken on a UR-10 instrument with the liquid substances in the form of thin films and the
solids in paraffin oil.
5-Acetylaminothiephene-4-earbaldehydes (IIa-e). In drops. 0.3 mole of freshly-distilled phosphorus
oxyehloride was added to 0.3 mole of dimethylformamide cooled to ~ 0~ The mixture was kept at room
temperature for 15 rain and was then cooled again, and 30 ml of dry diehloroethane and a solution of 0.195
mole of a compound (la-e) in 900 ml of dry diehloroethane was added. The mixture was boiled for 15 rain
and was then cooled, 0.9 mole of sodium acetate in 600 ml of water was added to it, and the new mixture
was boiled for 20 rain. After cooling, the organic layer was separated off, and the aqueous layer was ex-
tracted several times with dichloroethane. The combined extracts were washed with potassium carbonate
solution and then with water until the wash-waters were neutral. The dichloroethane was distilled off to
dryness and the residue was recrystallized from ethanol. Information on compounds (IIa-e) is given in
Table I.
The phenylhydrazone of 5-benzoylamino- 2,3-tetramethylenethiophene- 4-earbaldehyde (Ill), the iso-
nicotinoylhydrazone of 5-benzoylamino- 2,3- tetramethylenethiophene- 4- carbaldehyde (IV), and the thios emi-
carbazone of 5-benz oylarnino- 2.3-tetramethylenethiophenyl- 4- carbaldehyde (V) were obtained by the usual
methods. Information on compounds (III-V) is given in Table I.
5- Benzoylamino- 2.3-tetramethylene- 4-thenylidenaniline (VI). To a solution of 2.8 5 g (0.01 mole) of
(lid) in I00 rnl of absolute ethanol was added 1 ml (0.01 mole) of aniline. The reaction mixture was boiled
for 3 h 30 rain and was then cooled, and the precipitate that deposited was filtered off and was recrystal-
lized from dioxane. Yield 1.4 g (39%) of (VI)with mp 196-197~ (from dioxane). Found %: C 73.3. H 5.6:
N 7.8. S 9.0. C22H20N2OS. Calculated %. C 73.3: H 5.6: N 7.7: S 8.9.
4-Anflinomethyl- 5-benzoylamino- 2,3-tetramethylenethiophene (VII). With stirring, 0.6 g (I 60 rnmoles)
of sodium tetrahydroborate was added in small portions to a solution of I.I g (2.8 mmoles) of (VI) in a mix-
ture of 40 rnl of dioxane and 20 ml of methanol. After the addition of the whole of the sodium tetrahydro-
borate, the mixture was stirred for 30 rain and was then poured onto ice. The precipitate that deposited
was filtered off and was reerystallized from methanol. Yield 0.8 g (75%) of (VII) with mp 134-135~ (from
methanol). Found %: C 73.0; H 6.1: N 7.8. S 9.0. C22H22N2OS. Calculated %: C 72.9- H 6.1. N 7.7: S 8.8.
6 - A m i n o - 5 - e t h o x y e a r b o n y l - 2 . 3 - d i m e t h y l t h i e n o [ 2 , 3 - b ] p y r i d i n e (VIII) and 6 - A m i n o - 5 - e t h o x y c a r b o n y l -
2,3-tetramethylenethieno[2,3-b]pyridine (IX). The r e a c t i o n m i x t u r e obtained f r o m 0.02 mole of (IIa, b, or
d). 0.037 mole of cyanoacetie e s t e r , 40 ml of ethanol, and 0.5 ml of piperidine was boiled f o r 1 h 30 rain

51
 T A B L E 1. C h a r a c t e r i s t i c s of the Compounds Obtained

Com- Empirical Found. % Calculated, % i ~-

Mp, ~ ~
pound formula
C H Ni S C 4 H N S .~

{
IIa 134,5--135,5 CIgH,tN02S 54 8 5,7 7,0 16,41~4,8i 5,6! 7,1,6,2 73
IIb 123--124 CuH,3NO2S i 59,51 5,9 6,3 14,6i59 2 5,9 j 6,3!14,41 78
Ilc 156--157 C,4H,3NO2S 6521 5,0 5,3112,4 64;8! 5 0 5,4[,2,41 80
IId 134--135 C16H~NO2S 67,2 5,2 49 112i67,~ 5,3i :4,9;11,2 80
lie I05,5--I06,5 C,THITNO2S 68,0] 5,6 4'8 t0'7, 68'2[ 5,7 I 4,7!10,71 84
III 214--215 C~H21NsOS --
.,1 8,7i-
]
111,2i 8,6j 88
-

IV 280.5--281.5 { C2eH~N40~S [3,8 8,0!65,415,0 13;9i 7,9! 99

V 245--248(decomp.) C,~H,sN40~-q 57,3 5,2 [5,5, 17.8570 5,1 t 15,6 17,9 89
VIII 193,5--194,5 CI2H,('N20~S 57,61 5,6 [0,9," :57,6 5,6jI1,2':-- !90
IX 199,5--200,5 C~,H~sN~O,S 61,0 5,7 [0,1ill,6 60;815,8!10,1i116:88
X 249,5--250,5 C~oH~N~S 59,oi 4,4 20,7~ 15,7L59,1]4,5 20,7i 15,8 93
XI 218,5--219,5 CI~H.N~S 62,71 4,8 18,0', 139'6281 4,8 18,3 14,0:97
XII[ >330 (decomp.) C,~H,INaOS 60,6! 4,6 *16,3,1 - - : 6 0 , 7 4.3 16,3-- ! 86
XIV >350 C,aH,~N(S i 61,3! 4,6 121 8~ : 60.9, 4,7 21,8 -- ' 70
XV 163--164/9T88_.89mm Cg[tIoN.-S 16o.4! 5,4 if8.0' - 60.6 5,6 18,o. -- 194
] ; ) . ! i
XVI 184--186/7Tmm57_58 C.FImN2S ~64,9' 5,9 I -- : 15,5 64,7! 5,9 !--115,6 95
XVII 164--165 i C,4H,~N2S 7001 50 i' 11,8;' ,3.3: 7o.oii 5,o 11,6' 13,3 98
XVIII 120,5--121,5 C16HI4N2S 72'2', 513 if0,3 12,O72 1 5,3 10,5112,0:98
XIX 87"88 { C17H,6N2S 172,9 5,7 ig,,t i,,2!7_o,8:5 8 10,0 tL4 95
* T h e s u b s t a n c e s w e r e p u r i f i e d b y r e c r y s t a l l i z a t i o n : (IIa-e) f r o m
ethanol: (V, VII, VIII, X. XIV) f r o m dioxane: (VI) f r o m dioxane--di-
m e t h y l f o r m a m i d e (4 : 1): (IX, XVIt, and XVIII) f r o m a c e t o n e : (XI)
f r o m m e t h a n o l : (XIII) f r o m d i m e t h y l f o r m a m i d e : {XIX) f r o m aqueous
methanol.
tBp.

and w a s t h e n cooled, and the p r e c i p i t a t e that d e p o s i t e d was f i l t e r e d off. I n f o r m a t i o n on c o m p o u n d s (VIII)

and (IX) is given in T a b l e 1.
6 - A m i n o - 5 - c y a n o - 2 , 3 - d i m e t h y l t h i e n o [ 2 , 3 - b ] p y r i d i n e (X) and 6 - A m i n o - 5 - e y a n o - 2 , 3 - t e t r a m e t h y l e n e -
t h i e n o [ 2 , 3 - b ] p y r i d i n e CKI). The e x p e r i m e n t w a s p e r f o r m e d with 12.7 m m o l e s of (IIa o r d), 21 m m o l e s of
m a l o n o d i n i t r i l e , 40 m l of ethanol, and 0.5 m l of p i p e r i d i n e . The r e a c t i o n and t h e i s o l a t i o n of the s u b s t a n c e s
w e r e p e r f o r m e d u n d e r the conditions of the s y n t h e s i s of (VIII) and (IX). I n f o r m a t i o n on c o m p o u n d s (X) and
{XI) is g i v e n in T a b l e 1.
6- A m i n o - 5 - b e n z o y l - 2 . 3 - t e t r a m e t h y l e n e t h i e n o [ 2 , 3 - b ] p y r i d i n e (XII). The e x p e r i m e n t was p e r f o r m e d
with 5.6 g (19.5 m m o l e s ) of {IId), 2.91 g (20 m m o l e s ) of b e n z o y l a c e t o n i t r i l e , 100 m l Of ethanol, and 3 m l of
p i p e r i d i n e . The r e a c t i o n and the i s o l a t i o n of the s u b s t a n c e w e r e p e r f o r m e d u n d e r the conditions f o r the
s y n t h e s i s of (VIII) and (IX). Yield 5.6 g (98.2%) of {XII) with m p 199-200~ (from acetone). Found %: C 7 0 . 1 :
H 5.3: N 9.0: S 10.5. CIsH15N2OS. C a l c u l a t e d %: C 70.1: H 5.2: N 9.1: S 10.4.
3,4- D i h y d r o - 6,7- t e t r a m e t h y l e n e t h i e n o [ 2 , 3 - b ] p y r i d o [ 2 , 3 - d ] p y r i m i d i n - 4- one (XIII) and 4 - A m i n o - 6 , 7 -
t e t r a m e t h y l e n e t h i e n o [ 2 , 3 - b ] p y r i d o [ 2 , 3 - d ] p y r i m i d i n e (XIV). A solution of 0.01 m o l e o f ( I X ) o r (XI) in 5 m l of
f o r m a m i d e w a s b o i l e d f o r 1 h 30 rain. The r e a c t i o n m i x t u r e w a s cooled, and the p r e c i p i t a t e was f i l t e r e d
off and w a s h e d with m e t h a n o l . I n f o r m a t i o n on c o m p o u n d s (XIII) and {XIV) is given in T a b l e 1.
The T h i e n o p y r i m i d i n e D e r i v a t i v e s (XV-XIX). A m i x t u r e of 21 m m o l e s of a c o m p o u n d (IIa-e), 5.6 g
of a m m o n i u m a c e t a t e , and 35 m l of a c e t i c a c i d w a s boiled f o r 1 h. P a r t of the a c e t i c a c i d was distilled off
u n d e r r e d u c e d p r e s s u r e , and the r e s i d u e w a s p o u r e d into 200 m l of w a t e r and e x t r a c t e d with e t h e r (or, if
the d e s i r e d p r o d u c t s e p a r a t e d out in the f o r m of c r y s t a l s , t h e s e w e r e f i l t e r e d off). The c o m b i n e d e x t r a c t s
w e r e w a s h e d with s o d i u m c a r b o n a t e s o l u t i o n and with w a t e r , and w e r e d r i e d with m a g n e s i u m sulfate, and
t h e e t h e r w a s distilled off. I n f o r m a t i o n on c o m p o u n d s (XV-XIX) is given in T a b l e 1.

LITERATURE CITED

I. V. I. Shvedov, V. K. V a s i l ' e v a , Yu. I. T r o f i m k i n , and A. N. Grinev, Khim. G e t e r o t s i k l . Soedin., 1628

(1973).
2. V. I. Shvedov. I. A. Kharizomenova. and A. N. Grinev. Khim. Geterotsikl. Soedin., 1624 (1973).
3. A. Bisbler and IV[. Lang. Bet.. 28. 279 (1895).

52
INVESTIGATION OF SOME NITROGEN COMPOUNDS
OF 2,2'-BITHIENYL
VI.* FORMYLATION OF 5- (QUINOLIN-2-YL)-2,2'-BITHIENYL

P. L. Trakhtenberg and A. E. Lipkin UDC 547.734.831.542.951

The formylation of 5- (quinolin-2-yl)-2,2'-bithienyl leads to the 5 ' - f o r m y l derivative, and

f r o m this a n u m b e r of azomethines has been obtained.

Developing investigations on the electrophilic substitution of derivatives of 2,2'-bithienyl that have

been d e s c r i b e d previously, the V i l s m e i e r formylation of 5- (quinolin-2-yl)-2,2'-bithienyl (I) has been p e r -
f o r m e d . The position of the aldehyde group in the f o r m y l derivative (II) has been established f r o m the
identity of (H) with a model compound obtained by the V i l s m e i e r formylation of 5- (4-carboxyquinolin-2-yl)-
2,2'-bithienyl followed by the decarboxylation of the resulting 5'- (4- carboxyquinolin- 2-yl)- 2,2'-bithienyl- 5-
carbaldehyde (HI). The position of the aldehyde group in {III) was established, in its turn. f r o m the identity
of the product of the e s t e r i f i c a t i o n of (HI) and the 5'-(4-methox-ycarbonylquinolin-2-yl)-2,2'-bithienyl-5-
carbaldehyde (IV), which we have d e s c r i b e d p r e v i o u s l y [1].
The condensation of the aldehyde group of the bithienylcarbaldehyde with aniline, naphthylamines.
other a r o m a t i c amines, some h e t e r o c y c l i c amines, and malonic and hippuric acids has been p e r f o r m e d
(see Table 1).

R R COOH

| R:H II II!

In the c a s e where R = H, the condensation of (II) with amines containing electron-donating substituents
takes place c o m p a r a t i v e l y r e a d i l y with the f o r m a t i o n of azomethines (V-XIV), while when R = COOC2H 5 or
C O O C H 3 , the aldehyde group is p a s s i v a t e d even with r e s p e c t to amines having a high basicity. The con-
densation of (IV) and (II) with malonic and hippuric acids in the p r e s e n c e of catalysts takes place satis-
f a c t o r i l y with yields of about 83%.

EXPERIMENTAL
The IR s p e c t r a w e r e taken on a IKS-14 s p e c t r o p h o t o m e t e r In K B r tablets.
5- (Quinolin-2-yl)-2,2'-bithienyl (I) was obtained by the decarboxylation of 5- (4-carboxyquinolin-2-yl)-
2,2'-hithienyl [3] as d e s c r i b e d by the F i e s e r s [2], mp 142~ (from a m i x t u r e of ethanol and acetone): ac-
cording to the l i t e r a t u r e [3], mp 142-143~
5 ' - ( Q u i n o l i n - 2 - y i ) - 2 . 2 ' - b i t h i e n y l - 5 - c a r b a l d e h y d e (II) was obtained by the formylation of (I) as de-
s c r i b e d p r e v i o u s l y [1]. Yield 60%, mp 152-153~ (from ethanol), tR s p e c t r u m : 1662 cm -I (CHO). Found
%: C 66.8; H 3.5: N 3.8. C18HllNOS 2, Calculated %: C 67.3: H 3.5: N 4.3. Semicarbazone (XX). mp 284~

* F o r Communication V, see [1].

V. V. Kuibyshev Polytechnic Institute, Kuibyshev. T r a n s l a t e d f r o m Khimiya Geterotsiklicheskikh

Soedinenii. No. 1. pp. 61-63, January. 1974. Original a r t i c l e submitted October 16, 1972.

9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

53
 (from ethanol). Found %: C 59.9: H 3.4: N 14.6.
ClsHI4NOS2. Calculated %: C 60.3: H 3.7: N 14.8.
T h i o s e m i c a r b a z o n e (XXI), mp 257~ (from a m i x t u r e
of ethanol and acetone). Oxime (XXII), mp 190~
(from ethanol). Hydrazone (XXIII), mp 278-280~
(from ethanol).
5'- (4- C arboxyquinolin- 2- yl)- 2, 2 ' - b i t h i e n y l - 5-
earbaldehyde 0II) was obtained by the f o r m y l a t i o n of
5- ( 4 - c a r b o x y q u i n o l i n - 2 - y l ) - 2 , 2 ' - b i t h i e n y l [1]. Yield
50.2%, mp 302-304~ (from aqueous dioxane). IR
s p e c t r u m . 1703 c m - t (COOH), 1657 c m - I (CHO).
Found %: C 62.3: H 3.0: N 3.9. C19HllNOaS 2. Calcu-
lated %: C 62.5: H 3.0: N 3.8.
Deearboxylation of (IlI). A m i x t u r e of i g of
(III) and 1 g of c o p p e r in 2 m l of quinoline was s t i r r e d
and heated to the boil, and heating was continued until
the evolution of c a r b o n dioxide c e a s e d (45 rain), a f t e r
which the quinoline was distilled off with s t e a m . The
~ 6 ~ 6 6 ~ 4 6 6 ~ 4 4 ~ p r e c i p i t a t e was f i l t e r e d off and was r e c r y s t a l l i z e d
f r o m a m i x t u r e of ethanol and acetone. Nip 152~
Yield 60%.
5 ' - (4- Methoxycarbonylquinolin- 2- yl)- 2 , 2 ' - b i -
t h i e n y l - 5 - c a r b a l d e h y d e (IV) was obtained as d e s c r i b e d
o
p r e v i o u s l y [1]. Oxime (XXIV) m p 230~ (from e t h a n o l -
~0000~000000
ZZZZZZZZZZZZ~ZZ .~ acetone). Found %: C 60.8: H 3.9: N 6.9. C20HI4N203S2.
Calculated %: C 60.9: H 3.8: N 7.1. Hydrazone (XXV),
m m p 330~ (decomp., f r o m e t h a n o l - a c e t o n e ) .

%,
The a z o m e t h i n e s (V-XIX) (see T a b l e 1) w e r e
obtained by the usual method in ethanolic solution.
~-'~~ ..... I I I^. I 1
4- [5'- (4- Methoxycarbonylquinolin- 2- yl)- 2, 2 ' -
z a bithienyl- 5--ylmethyl ene] - 2-phenyloxazolin- 5- one
II
(XXVI) [4]. A m i x t u r e of 0.32 g (0.84 m m o l e ) of (IV),
~2
N
0.187 g (1.04 g) of hippuric acid, 0.165 g (2.01 m m o l e s )
oN o:~,~ ~ : oN o
.~ of fused sodium acetate, and 7 m l of acetic anhydride
= was boiled f o r 2-3 rain. and then the homogeneous
o ~' o,-! ~ ~ ~ ~ boo m i x t u r e was heated in the w a t e r bath f o r another 30
o rain and was left overnight. The b r i g h t r e d c r y s t a l s
that had deposited w e r e f i l t e r e d off and w e r e washed
N with w a t e r and ethanol. Mp 244~ (subl.). Found %:
C 65.3: H 3.4: N 5.0. C29H18N204S2. Calculated %:
C 66.7: H 3.5: N 5.4.
2- Phenyl- 4- [ 5'- (quinolin- 2-yl)- 2 , 2 ' - b i t h i e n y l -
5 - y l m e t h y l e n e ] o x a z o l i n - 5 - o n e (XXVII) was obtained
f r o m (II) by a method analogous to the p r e c e d i n g ex-
p e r i m e n t . Bright orange needles with m p 208~ (from
m acetic anhydride). Found %: C 69.3: H 3.5: N 5.8.
U~UUUU
C27Hl~N202S2. Calculated %: C 69.8: H 3.5: N 6.0.
O
oooooo
oooooo
o fl- [ 5'- (4- Methoxycarb onylquinolin- 2-yl)- 2,2 ' -
b i t h i e n y l - 5 - y l ] a c r y l i c Acid (XXVIII) [4]. A m i x t u r e
of 0.3 g (0.79 m m o l e ) of (IV) and 0.154 g (1.48 m m o l e )
of malonic acid in 5 m l of d r y p y r i d i n e containing five
m d r o p s of p i p e r i d i n e was heated at 8 5~ f o r 1 h and was
8 * then boiled for 2 h, cooled, and acidified with dilute
h y d r o c h l o r i c acid to Congo Red. The p r e c i p i t a t e was
f i l t e r e d off. washed with water, and dried. Yield 80%.

54
Dark cherry-red plates with mp 269~ (from glacial acetic acid). Found %: C 62.5: H 3.6: N 3.7. C22H15"
NO4S2. Calculated %: C 62.7: H 3.6: N 3.3.
~-[5'-(Quinolin-2-yl)-2,2'-bithienyl-5-yl]acrylic acid (XXIX) was obtained from (II) by a method ana-
logous to the preceding experiment. Yield 83%. Dark yellow crystals with mp 230-231~ (from glacial
acetic acid). Found %: C 66.3: H 4.1: N 3.3. C20H13NO2S2. Calculated ~c: C 66.1: H 3.6: N 3.8.

LITERATURE CITED

1. P. L. Trakhtenberg, A. E. Lipkin, and Z. I. Nuzhdina, Khim. Geterotsikl. Soedin., 773 (1972).

2. L. F i e s e r and M. Fieser, Reagents for Organic Synthesis, Wiley (1967-1972).
3. W. Steinkopf and H. Petersdorff, Ann. Chem., 543, 127 (1940).
4. M. A. Kazanbieva. B. A. Tertov, and F. T. Pozharskii, Khim. Geterotsikl. Soedin., 394 (1965).

55
REACTION OF PERCHLORATES OF C O N D E N S E D
THIOPYRYLIUM DERIVATIVES WITH AROMATIC ALDEHYDES

V. G. K h a r c h e n k o , T . I. K r u p i n a , UDC 547.815.8.222 + 543.422

S. K. K l i m e n k o . N. M. Y a r t s e v a .
M. N. B e r e z h n a y a , V. I. M i l o v a n o v a ,
a n d N. I. K o z h e v n i k o v a

The synthesis of new monomethinecyanines from 2.3-trimethylene- and 2-phenyl-5, 6,7,8-

tetrahydrothiochromylium. 2-phenyl-5.6-trimethylenethiopyrylinm, sym-octahydrothioxan-
thylium and sym-octahydroxanthylium perchlorates and aromatic aldehydes is described.

Monomethinecyanines ar e of interest as potential photosensitizers and dyes [1, 2]. In the present
communication we describe the synthesis of the new monomethinecyanines (VI-XXII) (Table 1) from sym-
octahydrothioxanthylium {I), sym-octahydroxanthylium (lI), 2, 3-trimethylene- 5, 6. 7, 8-tetrahydrothiochrom-
ylium (III), 2-phenyl-5.6,7.8-tetrahydrothiochromylium (IV), and 2-phenyl-5,6-trimethylenethiapyrylium (V)
perchlorates and aromatic aldehydes:

+ Rs ClIO ' ~ (

~ ' ~ . ~ " ~CIO~"

R' R S~-~' / ~ CH
~'' - CIO-

R~,9 "-R3

I-V VI-XXII

VI X=S, n=3, RI--R2-(CH2)4, R3=R4=I{, RS=N(CHa)~; VII X=S, n - 3 , RI--R 2~

--I[:H2)~, R3=OH. R~=RS=H; VIII X='S, n=3, RI--I~2=(CH~)4, R~=R4='rI, R~=OCll~;
iX X=S. n=3, R 1 R~-=(CH2)4, R3=H, R4=Rs=OCHa; X X - O , n=3, R1--R-~-(CH2)4,
R'~=R4=H, RS=N(CH3)2; Xl X=O, n=3, R1=R~= (CH~)4, R3-OH, R4=RS=H; Xtl X - O ,
n - 3 . RT--R~-(CH_~)4, R3=R4=H, Rs=OCHz; XIII X=O, n=3, RI--R~=(CH2)4, R3=H,
R4-Rs=OCH3; XIV X=O, n=3, R1--R2=(CH2)4, Ra=R4=H, Rs=NO~; XV X = S , n-2,
R1--R2=(CH2)4, R~=R4-H, RS=N(CH3)2; XVI X=S, n=2, RI~R~-(CH2)4, R~=OH,
R~=RS=H; XVII X=S n=2, R~--R2-(CH~)4, R~=R~=H, Rs-OCH~; XVIII X=S, n=2,
R 1 R~=(CH~)~, R~=H. R~--R~=OCH3; XIX X=S, n=3, R~=CsH~, R-~=R~=R~=H, R~=
=N(CHa):; XX X=S, n=3, R'-C~H~, R:='R~-H, R4=R~=OCHz; XXI X=S, n=2, R ' =
=CsH~, RZ=RZ-R~=H, Rs=N(CH3)~; XXII X=S, n - 2 , RI=C~H~, R~=RZ=H, R~-R~=
:=OCH~

The reactivity of sym-octahydrothioxanthylium perchlorate (I) is lower than that of the oxygen analog
{II). Thus. the condensation of the perchlorate (iI) with aromatic aldehydes takes place in 30 rain at ~ 100~
and the yield of the end-products is 60-88%, while in the case of the sulfur analog, (I), the reaction mixture
must be boiled (~130~ for an hour. and the yield of products does not exceed 39% [with the exception of
(VI)] (Table 1). 2,3- Trimethylene- 5, 6,7.8-tetrahydrothiochromylium perchlorate (III), obtained for the first
time, is less stable than its analog (I). which explains the lower.yields of condensation products (XV-XVIII)
(Table 1). Of the aromatic aldehydes, p-dimethylaminobenzaldehyde reacts most readily. In all cases,
condensation takes place at the a-methylene group and does not affect the heterocyclic ring, as is shown
by the IR spectra of (VI-XXII) (Table 2).
F o r comparison, Table 2 also gives characteristic frequencies of the thiopyrylium cation in the initial
perchlorates. The possible overlapping of the absorption bands of the thiopyrylinm cation and of the

N. G. Chernyshevskii Saratov State University. Saratov Polytechnic Institute. Translated from

Khimiya Geterotsiklicheskikh Soedinenii. No. 1. pp. 64--66, January, 1974. Original article submitted
November 17, 1972.

9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

56
 T A B L E 1. The M o n o m e t h i n e c y a n i n e s {VI-XXII)

Meth-[ Found, % Calculated, %

inecy-[ Mp, *C Empirical
anine formula H Cl S C H Cl S .: .9~

VI 164--167 C2~H~CINO4S 60,8] 5,9 ! 60,E 7,4 71

Vll 213--215 C2oH21CIO5S 58,9 5,4 58,~ 7,8 28
VIII 180--181 C~IH23CIO5S 59,5 5,7 59,6 7,6 33
IX 183--185 C~,H~sCIOaS 58,3 5,4 58,3 7,1 39
X 181--183 C~H~CINOs 62,9 6,4 62,9 -- 71
XI 147--149 C2oH2tCIO6 60,71 52 61,~ -- 87
XII I64--166 C2tH2aCI06 61,9 1 5,7 61,7 -- 88
XIII 169--171 C22H~sC1Oz 60,7 5,7 60,5 -- 6t
XIV 251--253 C2oH~oCINOz 57,21 4,7 56,s -- 37
XV 280(decomp, C21H24C1NO~S 60,l 5,7 59,8 7,6 48
XVI 210--212 CtgHIgC1OsS 57,61 5,0 57,~ 8,1 20
XVII 200--201 C2oH21CIO5S 59,01 5,0 58,~ 7,8 21
XVIII202(decomp C2,H23CIO6S 57,81 5,4 57,~ 7,3 23
XIX 202--204 C24H~4CIN04S 7,0 84
XX 161--162 C24H.~CIO6S 6,8 44
XXI 206--208 E'~H~CINO~S
XXII 189--191 C.~H~CIO~S
:! 7,2 91
6,9 43
!

T A B L E 2. A b s o r p t i o n S p e c t r a of the I n i t i a l P e r c h l o r a t e s {I, IV, and V)

and of the M o n o m e t h i n e c y a n i n e Dyes WI-IX and XV-XXII)
Characteristic frequencies of the
Corn- stretching vibrations of the thiapy- kmax , am (log a)
pound rviium cation; v, cm "~
! 1402m, 1488m, 1550w, 1608w 275(3,44), 327(3,98)
VI 1390s, 1503m, 1588m, 1600m 260(4.10), 289(4,08), 391(4,11),
680(4,53)
VII 1392s, 1500s, 1551m, 1596m 260(3,72), 322(3,71), 490(3,81)
, VIII 1390s, 1513m, 1555m, 1597m 278(4,06), 322(4,11), 515(4,28)
IX 1385--1398s. 159C--1505m, i[55m, 258(4.31), 327(4,13), 525(4,30)
1590m
XV 1380s, 1497m, 1565m, 1592m
XVI 1390s, 1500m. 1565m, 1596m
XVII 1390s, 1500--1507w, 1560m, 1590m 279(4,13), 335(4,16), 545(4,54)
XVIII I393s. 1502m, 1568m, 1598m 253(4,20), 326(4,11), 558(4,50)
IV 1410m. 1493--1497w, 1569m, 1597w 251 (4,27), 382(4,29)
XIX 1398s, 1502m, 1568--1572m, 1602m 271 (4,54), 415(4,54), 700(4,99)
XX 1390s, 1500--1505m, 1568m, 1590-- 265 (4,44), 371 (4,26), 560 (4,23)
1595w
V 1402m, 1495w, 1562m, 1592w 248(4.41), 382(4,38)
XXI 13988, 1505m, 1568m, 1590rn 274(4,39), 420(4,18), 730(4,87)
XXII 14008, 1500--1505m, 1565m, 1598m 270(4,59), 375(4,44), 590(4,62)

* T h e b a n d at 1590-1680 c m -1 o v e r l a p s the b a n d s of t h e s t r e t c h i n g v i -
b r a t i o n s of the a r o m a t i c r i n g .

a r o m a t i c r i n g c o m p l i c a t e the i n t e r p r e t a t i o n of the s p e c t r a of c o m p o u n d s (VI-IX and XV-XXII), but t h e i n -

t e n s e a b s o r p t i o n at 1380-1410 c m - , t o g e t h e r with t h e a b s o r p t i o n at 1560-1570 c m - i , c a n b e u s e d to i d e n t i f y
t h e t h i a p y r y l i u m c a t i o n i n t h e s e c o m p o u n d s [3].
It is k n o w n t h a t w i t h a n i n c r e a s e i n t h e s t r a i n of the r i n g t h e f r e q u e n c y of a n e x o c y e l i c C = C d o u b l e
bond r i s e s [4]. In t h e s p e c t r a of c o m p o u n d s (XXI) a n d (XXII), u n l i k e t h o s e of {X'IX) a n d (XX). a b s o r p t i o n
a p p e a r s at 1610 c m -1, which m u s t a p p a r e n t l y b e a s c r i b e d t o t h e s t r e t c h i n g v i b r a t i o n s of a d o u b l e b o n d at a
f i v e - m e m b e r e d r i n g . S i n c e i n the r e a c t i o n of the p e r c h l o r a t e {III) with a r o m a t i c a l d e h y d e s the f o r m a t i o n
of i s o m e r s is p o s s i b l e t h r o u g h the m e t h y l e n e g r o u p s of the two d i f f e r e n t a l i c y c l i c s y s t e m s , we c o m p a r e d
t h e s p e c t r a of the m e t h i n e c y a n i n e s (XV, XVI, and XVIII) a n d t h e i r a n a l o g s (VI, VII, and IX). In a g r e e m e n t
with the a b s o r p t i o n at 1610 c m -1 i n t h e s p e c t r a of c o m p o u n d s (XV, XVI, and XVIII) m e n t i o n e d above, t h i s
p e r m i t s us to c o n s i d e r t h a t c o n d e n s a t i o n t a k e s p l a c e t h r o u g h the m e t h y l e n e g r o u p of the f i v e - m e m b e r e d
r i n g . In t h e c a s e of c o m p o u n d s (V-I-IX. XIX, a n d XX) the b a n d at 1610 c m -1 is a b s e n t .
I n the IR s p e c t r a of s y m - o c t a h y d r o x a n t h y l i u m p e r c h l o r a t e {II) and t h e p r o d u c t s of i t s c o n d e n s a t i o n
(X-XIV) a b s o r p t i o n b a n d s of the p y r y l i u m c a t i o n [5] a r e o b s e r v e d at 1405-1415, 1480-1500, 1580-1590. and
1 6 0 5 - 1 6 1 5 c m -1. A l l t h e c o m p o u n d s i n v e s t i g a t e d a r e c h a r a c t e r i z e d b y s t r o n g a b s o r p t i o n at 620-625 and
1085-1110 c m - I (CIO4-).

57
 EXPERIMENTAL

The IR s p e c t r a w e r e taken on a UR-20 s p e c t r o m e t e r in paraffin oil and hexachlorobutadiene. The

e l e c t r o n i c s p e c t r a w e r e t a k e n on a SF-4A s p e c t r o m e t e r in methylene chloride at a concentration of 10.3 M.
The p e r e h l o r a t e s (I. II, IV. and V) w e r e obtained as d e s c r i b e d p r e v i o u s l y [6-81.
2,3- T r i m e t h y l e n e - 5, 6, 7 , 8 - t e t r a h y d r o t h i o e h r o m y l i u m p e r e h l o r a t e (iII) was obtained b y a lmown method
[6] f r o m 7.8 g (0.04 mole) of 2-[(2-oxocyclopentyl)methyl]cyclohexanone, hydrogen sulfide, and 70~ p e r -
chloric acid. Yield 6.8 g (58%). Mp 78-81~ (after r e p r e c i p i t a t i o n f r o m c h l o r o f o r m with a 6 : 1 m i x t u r e of
e t h e r and benzene). It was identified through its t e t r a c h l o r o f e r r a t e , into which it was c o n v e r t e d by the ac-
tion of a h y d r o c h l o r i c acid solution of f e r r i c chloride [9]: mp 82-84~ f r o m acetic acid. Found %: C1 36.4:
S 8.2. C12H15C1FeS. Calculated %: C1 36.4: S 8.2.
The m o n o m e t h i u e c y a n i n e s (Table 1) w e r e obtained by condensing e q u i m o l a r amounts of the p e r c h l o -
r a t e s ( I - V ) w i t h a r o m a t i c aldehydes with heating to 100~ or boiling in glacial acetic acid f o r 30 m i n - 2 h.

LITERATURE CITED
1. L. Roosens and R. Wizinger, Bull. Soe. Chim. Belges, 66, 109 (1957).
2. G. A, Reynolds and J. A. Van Allan, U.S. Patent No. 3,4t7,083 (1969).
3. V. G. Kharchenko. M. E. Stankevich. A. R. Y a k o r e v a A. A. Rassudova, and N. M. Yartseva, Khim.
Geterotsikl. So.din.. 916 (1972).
4o L. Bellamy, Advances in I n f r a r e d Group F r e q u e n c i e s , Methuen, London (1968).
5. A. T. Balaban. B. D. Matteescu, and M. Elian, T e t r a h e d r o n Lett., 1083 (1962).
6. V. G. Kharchenko. M. E. Stankevich, N. M. Kupranets, A. R. Yakoreva. and S. K. Klimenko, Zh.
O r g a n . K h i m . . 8, 193 (1972).
7p V. G. Kharchenko, S. K. Klimenko, and T. I. Krupina. Zh. Organ. Khim., 3, 1709 (1967).
8. V. G. Kharchenko, S. K. Klimenko. and T. I, Krupina. Khim. Geterotsikl. Soedin., Collection 3 (1971),
p. 76.
9. V. O. Kharchenko. Z. A. Rassudova. T. I. Krupina. S. K. Klimenko, and T. P. Chepurnenkova, Khim.
G e t e r o t s i k I . Soedin.. 338 (1970).

58
PHOTOCHROMIC AND THERMOCHROMIC SPIRANS
IV.* A T H E O R E T I C A L STUDY OF THE ELECTRONIC STRUCTURE
AND SPECTRA OF THE VALENCE ISOMERS OF 2H-CHROMENES,
THIOCHROMENES, AND 1.2-DIHYDROQUINOLINES

V. I. M i n k i n , B. Ya. Simkirt, UDC 541.651'67 : 547.814.816'831.3

L. E. Nivorozhkin, a n d B . S. Luk'yanov

By m e a n s of the SCF MO LCAO method in the ~r-electronic (PPP) and a l l - v a l e n c e (CNDO)

a p p r o x i m a t i o n s the e l e c t r o n i c s t r u c t u r e s and s p e c t r a l c h a r a c t e r i s t i c s of the valence i s o -
m e r s of 2 H - c h r o m e n e s , t h i o c h r o m e n e s , and 1,2-dihydroquinolines have been calculated.
On the b a s i s of a c o n s i d e r a t i o n of the e l e c t r o n i c configuration of v a r i o u s excited states, an
explanation has been given of the m e c h a n i s m of the p h o t o c h r o m i s m of the c h r o m e n e s and
t h e i r analogs. A hypothesis has been put f o r w a r d concerning the p o s s i b i l i t y of t h e r m o -
c h r o m i s m in 1,2-dihydronaphthalene. It has b e e n shown that the d i f f u s e n e s s of the long-
wave a b s o r p t i o n band of the open f o r m s of the compounds investigated is not connected with
the existence of s e v e r a l s t e r e o i s o m e r s . The influence of the h e t e r o a t o m and of b e n z o - f u s i o n
on the l o n g - w a v e a b s o r p t i o n h a s b e e n analyzed. The nature of the e l e c t r o n i c t r a n s i t i o n r e -
sponsible f o r the l o n g - w a v e a b s o r p t i o n of the p h o t o - c o l o r e d f o r m s has been explained.

Compounds of type A - the c h r o m e n e s (X = O) [2, 3], t h i o c h r o m e n e s (X = S) [4], the s e l e n o c h r o m e n e s

(X = Se) [1], the dihydroquinolines (X = NR) [5, 6], and the dihydronaphthalenes (X = CH2) [7, 8] - undergo
v a l e n c e i s o m e r i z a t i o n on i r r a d i a t i o n .

4 8

The r e a c t i o n explains the n a t u r e of the t h e r m o c h r o m i s m and p h o t o c h r o m i s m of compounds of the

s p i r o p y r a n s e r i e s (R', R" t o g e t h e r r e p r e s e n t a h e t e r e n e r e s i d u e ) [9. 10]. It also a t t r a c t s attention sinee
it p o s s i b l y d e t e r m i n e s the c a p a c i t y of g r e e n plants containing c h r o m e n e alkaloids for accumulating s o l a r
e n e r g y [2]. To u n d e r s t a n d the m e c h a n i s m of the p h o t o c h e m i c a l c l e a v a g e of a ~ bond on i r r a d i a t i o n and to
d e s c r i b e and p r e d i c t p h o t o r e a e t i o n routes, i n f o r m a t i o n is n e c e s s a r y on the e l e c t r o n i c s t r u c t u r e of the
ground and excited s t a t e s and the n a t u r e of the low-lying e l e c t r o n i c t r a n s i t i o n s . With t h e s e a i m s , we have
p e r f o r m e d a calculation of the e l e c t r o n i c s t r u c e a r e , e n e r g y states, and s p e c t r a of the valence i s o m e r s of
a n u m b e r of 2 H - c h r o m e n e s , t M o e h r o m e n e s , .and 1,2-dihydroquinolines, and of 1,2-dihydronaphthalene g-XI)
in the ~r-electronic and a l l - v a l e n c e a p p r o x i m a t i o n s of the 8CF M e method.
The calculations of the e l e c t r o n i c s t r u c t u r e and the s p e c t r a of the cyclic (A) and open (B-E) i s o m e r s
of the compounds i n v e s t i g a t e d w e r e p e r f o r m e d by m e a n s of the P a r i s e r - P a r r - P o p l e (-PPP) method and a
method taking into account all the v a l e n c e o r b i t a l s in the a p p r o x i m a t i o n of c o m p l e t e neglect of differential
o v e r l a p (CNDO) [11]. T h e r e is no i n f o r m a t i o n in the l i t e r a t u r e on the m o l e c u l a r g e o m e t r y of the c h r o m e n e s

* F o r C o m m u n i c a t i o n III, s e e [1].

R o s t o v State University. R o s t o v - o n - D o n . T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii.

No. 1, pp. 67-75, J a n u a r y , 1974. Original a r t i c l e s u b m i t t e d N o v e m b e r 30, 1972.

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

59
and t h e i r analogs. Consequently, we u s e d the standard values of the valence angles and bond lengths taking
into account the hybrid s t a t e s of the a t o m s [11]. The calculations b y the P P P method w e r e p e r f o r m e d in the
" v a r i a b l e ~" a p p r o x i m a t i o n [12], and for the C - S bonds we used the constants that we obtained p r e v i o u s l y
[13]. The t w o - e l e c t r o n Coulomb r e p u l s i o n i n t e g r a l s w e r e calculated by m e a n s of the M a t a g a - N i s h i m o t o
f o r m u l a . In the c o n s t r u c t i o n of the m a t r i x of the configurational interaction, 20 singly excited configurations
w e r e taken into account. To calculate the e n e r g y of the t r i p l e t l e v e l s the p a r a m e t r i z a t i o n introduced s p e c i a l -
ly for t h e s e p u r p o s e s was used [14]. The o s c i l l a t o r f o r c e was calculated by a well-known f o r m u l a [21] with
the subsequent introduction of the coefficient 0.5 in a g r e e m e n t with Bailey [22]. More details of the c a l -
culations by the P P P method a r e given e l s e w h e r e [13].

I
It
I~U HI. IV V, Vi

VII, VII! IX, X Xl

I,IIl, V, X R = H ; i l R=C6Es; IV, IX R=OCH3; VI R=COR'; VII. IX X = O ; V I I I , | X=S

The CNDO method was applied in the p a r a m e t r i z a t t o n p r o p o s e d for the calculation of s p e c t r a l c h a r -

a c t e r i s t i c s [15]. F o r t y s i n g l y - e x c i t e d configurations w e r e taken into account. The calculations by the CNDO
method w e r e p e r f o r m e d a c c o r d i n g to a p r o g r a m written and modified by I. I. Z a k h a r o v f o r a B~.SM- 6 c o m -
p u t e r . The r e s u l t s of the calculations a r e given in T a b l e s t - 5 .

O;OO~ --09002
H H

o oo too o o~

H
o~oo4 I A ~S o

O~OO5 - 0~,OO3
H H

O~O03 I__O~O23 107016 OpO1g

H
o~oa4 ~ - I 51

60
 0;004 --0~O04
H N

o,oo, l_o,oo Loo, oo

~

H - 0t112
o, oo2 IA ~

The Closed F o r m s (A). T a b l e 1 gives the s p e c t r a l c h a r a c t e r i s t i c s of the closed f o r m s of the c o m -

pounds investigated c a l c u l a t e d by the P P P and CNDO m e t h o d s . The calculated and e x p e r i m e n t a l values
a g r e e s a t i s f a c t o r i l y . The calculation c o r r e c t l y r e p r o d u c e s the o b s e r v e d b a t h o c h r o m i e shift of the long-
wave band on p a s s i n g f r o m 2 H - c h r o m e n e (I) to 2 H - t h i o c h r o m e n e {III) and 1,2-dihydroquinoline (V). A s i -
m i l a r change in the s p e c t r u m is o b s e r v e d on p a s s i n g f r o m the c h r o m e n e (I) and the t h i o c h r o m e n e (III). r e -
spectively, to the b e n z o c h r o m e n e s (VII. IX) and b e u z o t h i o c h r o m e n e s (VIII. X). Calculations by the CNDO
method show that v~* t r a n s i t i o n s a r e r e s p o n s i b l e f o r the f i r s t t h r e e excited s t a t e s of 2 H - c h r o m e n e (I). of
1,2-dihydroquinoline (V), and of 1, 2-dihydronaphthalene (XI).
The m o l e c u l a r d i a g r a m s give the total (r + ~) c h a r g e s on the a t o m s and the bond indices of 2H-
c h r o m e n e (I) c a l c u l a t e d a c c o r d i n g to Wiberg [16] in the ground (So) and in the f i r s t excited singlet (S1) and
t r i p l e t (T1) s t a t e s . In the $1 and T1 states, the C2-O bond is the m o s t loosened, as can be s e e n f r o m the
value of the bond index. In addition, on excitation t h e r e is a c o n s i d e r a b l e equalization of the C3-Cr and the
C4-C4a bonds in the p y r a n ring, which a r e s t r o n g l y l o c a l i z e d in the ground state. Thus, on p a s s i n g to the
f i r s t excited s t a t e s (S1 and T 0 the p e r t u r b a t i o n of the e l e c t r o n i c s t r u c t u r e of the p y r a n ring s t r o n g l y f a v o r s
the e l e c t r o c y c l i c r i n g - o p e n i n g r e a c t i o n . We obtained the s a m e r e s u l t for 1,2-dihydroquinoline (V) and so
has Tinland [23] f o r 1,2-dihydronaphthalene (XI).
F i g u r e 1 shows g r a p h i c a l l y the highest occupied m o l e c u l a r orbitals (HOMO) of the ground (So) and
f i r s t t r i p l e t (T 1) excited s t a t e s of the closed and open f o r m s (A and B) of 2 H - c h r o m e n e (I) and of 1.2-dihydro-
naphthalene (XI) obtained by the CNDO method. All t h e s e o r b i t a l s a r e of the ~ type. it is e a s y to s e e that
the HOMOs of the ground s t a t e s of the c l o s e d and open f o r m s of the c h r o m e n e s do not c o r r e l a t e . Because
of this, the e l e c t r o c y c l i c r e a c t i o n of the opening of the p y r a n ring does not take p l a c e in the ground s t a t e
even on heating. At the s a m e t i m e , the HOMOs of the t r i p l e t s t a t e s of the A and B f o r m s p r a c t i c a l l y coin-
cide, and as a r e s u l t the opening of the p y r a n ring b e c o m e s a p e r m i t t e d p r o c e s s . Thus, the t r a n s i t i o n f r o m
the open f o r m (A) into the closed f o r m 03) of c h r o m e n e m u s t take p l a c e through excited s t a t e s with the
p a r t i c i p a t i o n of t r i p l e t l e v e l s of both the closed and the open f o r m s .
In the c a s e of 1.2-dihydronaphthalene. the HOMOs of the closed (A) and open (B) f o r m s c o r r e l a t e
both in the ground s t a t e (So) and in the f i r s t t r i p l e t s t a t e (T1) (Fig. 1). On this b a s i s , it m a y be concluded
that the cleavage of the C1--C 2 bond is p e r m i t t e d in the ground and in the excited states, i.e., i , 2 - d i h y d r o -
naphthalene should p o s s e s s p h o t o c h r o m i c and t h e r m o c h r o m i c p r o p e r t i e s . Unlike its p h o t o c h r o m i s m [7, 8],
the t h e r m o c h r o m i s m of 1,2-dihydronaphthalene h a s n e v e r been investigated.
The Open F o r m s (B-E). The p r e s e n c e of a b r o a d s t r u c t u r a l a b s o r p t i o n band in the 400-500 nm r e -
gion for the open f o r m s of the c h r o m e n e s , t h i o c h r o m e n e s , and dihydroquinolines is connected [5, 10] with
the e x i s t e n c e of s e v e r a l s t e r e o i s o m e r s the e q u i l i b r i u m between which depends on the t e m p e r a t u r e and the
solvent.

IB(cis-s-cis) Ic(cis-s-trans) ,D (trans-s-trans) IE(trans-s-as)

We h a v e p e r f o r m e d a calculation of the s p e c t r a of all four allylidenecyclohexadienone i s o m e r s of

c h r o m e n e (IB-IE) b y the P P P method. The c a l c u l a t e d e n e r g i e s of the l o n g - w a v e s p e c t r a l t r a n s i t i o n a r e

61
 T A B L E 1. S l n g l e t : - S l n g l e t E l e c t r o n i c T r a n s i t i o n s of t h e C l o s e d F o r m s
(A) of 2 H - C i a r o m e n e s , T h i o c h r o m e n e s , a n d 1 , 2 - D i h y d r o q u i n o ! i n e s

Calculation Experiment
Cornpoundl
hE, eV f AE, e V f solvent
1 4,17 0,07 4,00 0,02 a Isopentane [2! .
4.90 0,11 4,68 0,03
5,85 0,16
ib 4,38 0,09 4.00 0.02" Isopentane [2]
4,52 0,02 4,68 0,03
5,36 0.02
-11 4,12 0,07
4~63 0~00
4,73 9,09
111 3,92 0.O2 3,82 - 0,02 tsopentane, ptopan-
4.54 0.01 4.35 o,01 2-ol [4]
5,11 o,00
IV 3~78 0,04
4,42 O.Ol
5,00 0,03
V 3.85 0,08 3;58 0,10c Dioxane [5]
4,75 0,04
5,59 O,O5
4,21 0.10 3,58 0.t0 c Dioxane [5]
4.45 0,01
4,78 0,01
V1 4.t5 0,06 -4.05 0,04 Dioxane d
4,57 0,09
5,44 0,46
Vll 3.74 O,13 3,57 0,08 Ethanol [24]
4.16 0,08 3,95 0,04
4.98 0.04-
VIII 3,,~ O,OS 3,40 0.Ol Ethanol [1]
4,10 0,07 3,93 0.Ol
4.32 0,18 4.39 O.O6
IX 3,61 0.68 3.47 0.O7 3-Methyl-
4,O6 0,06 pentane [3]
4,79 0,46 4.50 0,21
X 3,51 0,04
3.98 0,01
4,5O 0,03
Xlb 3,91 0.12 4;20 0,09 3-Methyl-
4.26 0,01 pen~ane [17]
4.68 0,02

a T h e a b s o r p t i o n and i n t e n s i t i e s of t h e b a n d s a r e t a k e n f r o m i n f o r m a -
t i o n on t h e s p e c t r u m of 2 , 2 - d i e t h y l c h r o m e n e . b C a l c u l a t e d b y t h e CNDO
m e t h o d : f o r (I) and (V) a l l t r a n s i t i o n s of t h e ~rv* t y p e . T h e o t h e r c a l c u -
l a t i o n s b y t h e P P P m e t h o d . CThe a b s o r p t i o n a n d i n t e n s i t i e s of t h e b a n d s
w e r e t a k e n f r o m i n f o r m a t i o n on t h e s p e c t r u m of 2 . 2 , 4 - t r i m e t h y l - l . 2 - d i -
h y d r o q u i n o l i n e , d T h e a b s o r p t i o n a n d i n t e n s i t i e s of t h e b a n d s w e r e t a k e n
f r o m the s p e c t r u m of N - a c e t y l - 2 , 2 , 4 - t r i m e t h y l - 1 . 2 - d i h y d r o q u i n o l i n e .

TABLE 2

Isomer 1B 1 IC 1E
'~ t
~ , eV
j, 2,77 3,05 3,08 3,04
0.10 0,22 0,28 0,23

g i v e n i n T a b l e 2. T h e r e s u l t s of t h e c a l c u l a t i o n s show t h a t t h e i s o m e r s I C - I E a r e i n d i s t i n g u i s h a b l e in t h e
r e g i o n of t h e l o n g - w a v e a b s o r p t i o n , a n d t h e i s o m e r IB m u s t u n d e r g o r a p i d s - e i s - t r a n s i s o m e r i z a t i o n b e -
c a u s e of i t s s t e r i c h i n d r a n c e . In v i e w of t h i s . t h e d i f f u s e n e s s of t h e l o n g - w a v e a b s o r p t i o n b a n d of t h e p h o t o
f o r m s of t h e c h r o m e n e s m u s t b e c o n n e c t e d e i t h e r w i t h f e a t u r e s of t h e a p p e a r a n c e of a v i b r a t i o n a l s t r u c t u r e
o r w i t h i n t e r m o l e c u l a r e f f e c t s . T h e c a l c u l a t e d s p e c t r a l c h a r a c t e r i s t i c s (the e n e r g i e s of t h e t r a n s i t i o n s a n d
t h e i r i n t e n s i t i e s ) of t h e i s o m e r s B a n d C a r e g i v e n i n T a b l e 3, t o g e t h e r w i t h t h e a v a i l a b l e e x p e r i m e n t a l r e -
s u l t s . T h e a g r e e m e n t b e t w e e n t h e v a l u e s c a l c u l a t e d b y b o t h t h e m e t h o d s u s e d and t h e e x p e r i m e n t a l v a l u e s
i s f a i r l y g o o d . T h e f i r s t two s i n g l e t s of t h e open f o r m of e h r o m e n e (I) a n d of 1 . 2 - d i h y d r o q u i n o l i n e (V)

62
TABLE 3. S i n g l e t - S i n g l e t E l e c t r o n i c T r a n s i t i o n s of th e Open F o r m s
(13 and C) of the 2 H - C h r o m e n e s , T h i o c h r o m e n e s , and 1,2-Dihydro-
quinolines
I Calculation Experi ment
Com- i isomer B . I._ isomer C ._
pound!--~E,
eV ----f---- AE, eV f AE, e V solvent
I 2,77 1 0,10 3,05 0,22 2,68a Isopentane [2]
3,82 0,06 4,00 0,16 3,52
4,82 O,I0 5,04 0,18
.i b 2,68 0,06r 3,00 0,20c 2,68a Isopemane [2]
3,49 0,0tc 4,01 0,22r 3,52
3,89 0,04c 4,88 0,0Od
H ,60 0 19 2,61 0,37
3,79 0,17 3,86 0,12 1
4,24 0,13 4,13 0,0t I
III 1,85 0,05 2,36 0,19 2,18 Isopent ane, propan-
3,t I 0,04 3,38 0,06 3,10 2-ol [41
3,64 0'03 3,52 0,03 3,44
IV 1,85 0,06 2,27 O,16
2,85 0,04 2,99 0,05
3,39 0,02 3,45 0,08
V 2,71 0,09 3,02 0,24 3,02; 3,26e Dloxane [5]
3,83
4.61
0,03
0,08
4,O6
4,25
0.08
0,15
&72

v b 2;90 0,21c 3,02; 3,26e Dioxane [5]

4,07 0,16c 3,72
4,55 0'00 d
Vl 2.44 ~ 0,I0 2.69 0;22 2,84; 2,95f Dioxarm
3,62 { 0'06 3,81 0,16
I 4,27 10'02 4,~5 0,O2
Vtl 3,12: I 0,06 3,35 0,22 3,16 3-Methylpentane [3]
: 3,57 | 0,03 3,71 0,II
4,36 I 0,20 4,40 0,30
VIII 2,05 i 026 2,53 0;20
2,95 { O,O8 3,12 0,14
3,64 t 0,18 3,63 0 10
IX 2,68 10,i4 2,91 0,32 2,91 3-Methylpentane [3]
3,83 ] 0,01 4,05 0,02 3,88
4,1t ! 012 4,31 0,t9
X 1,76 0,06 9 2,23 0,24
3,13 { 0,01 3,46 0,08
3,25 0'04 3,52 0,09
XI b 2,20 0,00~ 2,29 0,00g Isopentane [7]
2 74 0,09( 2,86 0,3~ 3,02
3,59 t 0'01( 3,77 0,01c i

a T h e a b s o r p t i o n a n d t h e i n t e n s i t i e s of t h e b a n d s w e r e t a k e n f r o m i n f o r -
m a t i o n o n t h e s p e c t r u m of 2 , 2 - d i e t h y l c h r o m e n e . bCalculation by the
C N D O m e t h o d , t h e o t h e r c a l c u l a t i o n s b e i n g b y t h e P P P m e t h o d . Crr~*
transition, d~r(r* t r a n s i t i o n , eThe absorption and intensities of the
b a n d s w e r e t a k e n f r o m i n f o r m a t i o n on t h e s p e c t r u m of 2 , 2 , 4 - t r i m e t h y l -
1, 2 - d i h y d r o q u i n o l i n e . f T h e a b s o r p t i o n a n d i n t e n s i t i e s of t h e b a n d s w e r e
t a k e n f r o m i n f o r m a t i o n on t h e s p e c t r u m o f N - a c e t y l - 2 , 2 , 4 - t r i m e t h y l - l , 2 ,
dihydroquinoline, g(r~ transition.

T A B L E 4. r r - E l e c t r o n i c C h a r g e s o f t h e G r o u n d (So) a n d F i r s t S i n g l e t
E x c i t e d (Si) S t a t e s o f t h e O p e n F o r m s of C h r o m e n e , 1 , 2 - D i h y d r o q u i n o -
line, and Thioehromene Obtained by the PPP Method

Struc- IB VB IIIB
ture No. So Sj So Sl So $1

1 -0,428 --0,418 - 0,274 -- 0,259 --0,415 -- 0,084

2 0,232 0,153 0,142 0,076 0,131 0,055
3 - 0,022 --0,015 -0,014 -- 0,006 --0,011 --0,018
4 0,01 l 0,083 0,008 0,054 0,019 0,016
5 -0,011 0,104 -0,006 0,069 --0,003 0,014
6 0,040 --0,00l 0,028 0,000 0,044 0,017
7 . --0'011 0,122 -0'007 0,081 0,007 0,049
8 0,119 --0,072 0,078 --0,O48 0,130 -- 0,055
9 0,018 0'039 0,010 0,026 0,020 0,025
10 0,052 0,005 0,036 0,008 0,077 --0,020

63
 i',~, T, i~% ,T, RTA,v, ~ B,T,

IIA, So ..lIB ,SO ~A,S o X-IB,So

Fig. 1. The highest occupied m o l e c u l a r o r b i t a l s of the ground

(So) and f i r s t t r i p l e t (T1) excited s t a t e s of the closed and open
f o r m s of 2 H - e h r o m e n e (IA and IB) and of 1,2-dihydronaph-
thalene (XIA and XIB). The open c i r c l e s c o r r e s p o n d to p o s i -
tive and the filled-in c i r c l e s to negative values of the coef-
ficients f o r the a t o m i c o r b i t a l s . The a r e a of each c i r c l e is
p r o p o r t i o n a l to the value of the coefficient.

TABLE 5. S i n g l e t - T r i p l e t (S0" T1) E l e c t r o n i c T r a n s i t i o n s of C h r o -

m e n e s , T h i o c h r o m e n e s , 1,2- Dihydroquinolines, and 1,2- Dihydro-
naphthalene
Charac- AE,eV Charac- AE, eV
teristics Formula A formula C teristics formula A formula

1 2,43 1,01 VI 2,56 0,92

3,33 2,39 3,48 2,38
3,51 3,24 3,81 3,36
Ia 2,82b 1,49b VII 2,08 1,52
3,80b 2,44b 3,11 2,45
3,96b 3,30c 3,58 3,48
II 2,34 0,94 VIII 2,19 0,51
3,29 2,36 3,18 2,04
3,47 !
3,2t B,63 3,71
Ill 2,56 0,22 IX 1,95 1,43
3,60 2,21 2,58 2,56
3,89 2,87 3,24 3,19
IV 2,50 0,24 X 2,04 0,41
3,48 I 2,18 2,82 2,00
3,76 2,81 3,41 3,36
u 2,42 0,89 XI 2,57 0,69
3,32 I 2,44 8,63 2,49
3,57 3,40 3,98 3,01
Va 2,64b 1,24b XIa 2,36b 0,38b
3 76.b 2,47b 3,55 b 2,29b
3;92b 3,31c 3,81 b 2,93 D

a c a l c u l a t i o n by the CNDO method: other calculations by the P P P

method, b~r~r* transition, c ~ * t r a n s i t i o n , d a ~ . t r a n s i t i o n .

r e l a t e ~r* t r a n s i t i o n s , which follows f r o m the calculations by the CNDO method. In the c a s e of 1,2-dihy-
dronaphthalene (XI), a forbidden o~r* t r a n s i t i o n is r e s p o n s i b l e for the f i r s t singlet state. The second and
t h i r d singlets r e l a t e to ~ * s t a t e s . In all the i s o m e r s of type C, the calculated a b s o r p t i o n band m a x i m u m
is shifted h y p s o c h r o m i e a t l y b y 0.3-0.4 eV r e l a t i v e to the i s o m e r B.
When in the open f o r m s of type B oxygen is r e p l a c e d by sulfur and selenium, the l o n g - w a v e m a x i m u m
shifts b a t h o c h r o m i c a l l y b y 100-120 nm [1, 4]. Calculation c o r r e c t l y p r e d i c t s t h e s e f e a t u r e s of the a b s o r p -
tion s p e c t r a . The r e s u l t s of the calculations a l s o p e r m i t an explanation of the unexpected h y p s o e h r o m i e
shift in the s p e c t r u m of 5, 6 - b e n z o - 2 H - c h r o m e n e and 5, 6 - b e n z o - 2 H - t h i o c h r o m e n e (VII, VIII) as c o m p a r e d
with (I, III). At the s a m e time, the fusion of a benzene nucleus in the 7,8 position (compounds (IX) and {X))
l e a d s to a b a t h o e h r o m i c shift of the l o n g - w a v e m a x i m u m .
The n a t u r e of t h e ! o n g - w a v e a b s o r p t i o n of the open f o r m s is of s p e c i a l i n t e r e s t , since it is just this
a b s o r p t i o n that d e t e r m i n e s the p r o p e r t i e s of the p h o t o c h r o m i c s y s t e m . The m o l e c u l a r d i a g r a m s show the
((T+v)-eleetronic c h a r g e s and the bond indices of the ground (S0) and the f i r s t singlet excited (S~) s t a t e s of
the i s o m e r C of the open f o r m of the e h r o m e n e (I) calculated by the CNDO method. O n S 0 - S 1 excitation, a

64
t r a n s f e r of e l e c t r o n density (about 0.25 of an e l e c t r o n ) f r o m the benzene ring to the c~-carbon a t o m of the
side chain takes place. The dipole m o m e n t v a r i e s insignificantly on excitation, which l e a d s t o t h e absence
of s o l v a t o c h r o m i s m .

0 - 0,005 - O.013
H H H

-0,07~ T_otlg 3 .-~" ~ r _ o , 1 4 ~ H

io_ $ I | " o, o o 2

Ac'O.o. M
H ~ ~.o o I,, o
O,0~I
O~OO, Yo,44; "?___
- 0,263
t ~ )Jg:3,35D
0H~0~1 I C., So

o - o.oo~ - 0.o13
H H

0,003 10,060 LO.O~5 . I0.03,

o,osgl " - T-O,~ " -r-o,~o6 H

A:-,__,o H
O,2O7
I ' ~e : 4,45 O
H
o,o- IC , S,

The influence of the h e t e r o a t o m X on the f i r s t e l e c t r o n i c t r a n s i t i o n can be d e t e r m i n e d by making use

of the figures of Table 4, which gives the v - e l e c t r o n i c c h a r g e s of the ground and f i r s t singlet excited s t a t e s
of 2 H - c h r o m e n e , 2 H - t h i o c h r o m e n e . and 1.2-dihydroquinoline. On S0-S 1 excitation, the c h a r g e on the oxygen
a t o m {for c h r o m e n e ) and the nitrogen a t o m (for 1,2-dihydroquinoline) s c a r c e l y changes. At the s a m e time,
on excitation, the sulfur a t o m (in the c a s e of t h i o c h r o m e n e ) l o s e s 0.35 unit of e l e c t r o n density actively
p a r t i c i p a t i n g in conjugation, which leads to a b a t h o c h r o m i c shift of the l o n g - w a v e m a x i m u m of 2H-thio-
e h r o m e n e r e l a t i v e to 2 H - e h r o m e n e and 1.2-dihydroquinoline.
The e n e r g i e s of the s i n g l e t - - t r i p l e t t r a n s i t i o n s of the open and closed f o r m s of the compounds i n v e s t i -
gated as calculated by the CNDO and P P P methods a r e given in Table 5. A knowledge of the absorption and
the n a t u r e of the t r i p l e t s t a t e s is p a r t i c u l a r l y i m p o r t a n t since, a c c o r d i n g to the point of view accepted at
the present time. valence isomerism of the A ~ B type takes place by a ]A0-~IA,-+3A,-+~B0: mechanism, i.e.,
through an intereombinational conversion from the triplet state of the cyclic form A [18. 19]. In the case
of the ehromenes, apart from those containing a nitro group in the nucleus [20]. fluorescence is absent.
Therefore the experimental possibilities of determining the positions of the triplet levels are limited.
As can be seen from Table 5, the energy of the S0-T ~transitions calculated by the CNDO method are
0.3-0.4 eV higher than those obtained in the v-electron approximation. The first two triplets of all the
compounds investigated with the exception of 1,2-dihydronaphthalene (XI) belong to the ~ * type. The second
triplet state of 1,2-dihydronaphthalene is a cnr* transition.
The first triplet state of the closed form of the thiochromene (III) lies 0.15 eV above that for the
chromene (1). This result is extremely important in the analysis of the photochromic behavior of the spiro-
pyranothiopyrans considered in the following paper [25].

65
 LITERATURE CITED

1. B. S. Lukyar~ov, M. I. Knyazhanskii, Yu. V. Revinskii, L. E. Nivorozhkin. and V. I. Minkin, Tetrahedron

Lett., 2007 (]973).
R. S. Becket and J. Michl, J. Amer. Chem. Soc., 8.88, 5931 (1966).
3. J. Kolc and R. S. Seeker. Photoehem. PhotobioL. 12. 383 (i970).
4. R. S. Beaker and J. Kolc, J. Phys. Chem., 7_.~2,997 (1968).
5. J. Kole and R. S. Becket. J. Amer. Chem. Soc., 9_~1.6514 (1969).
6. J. Kole and R. S. Seeker, J. Amer. Soc.. B__,17 (1972).
7. H. Kleinhuis R. L. C. Wijting, and E. Havinga, Tetrahedron Lett., 255 (1971).
8. K. Salisbury, Tetrahedron Lett., 737 (1971).
9. R. Exeiby and R. Grinter, Chem. Rev., 6._55,247 (1965).
10 J. Koszar. Light-Sensitive gysterns. Wiley, New York (1965).
11 J. A. Pople and D. L. Beveridge. Agproximate Molecular Orbital Theory. McGraw Hill (I970).
12 K. Nichimoto and L. S. Forster, Theor. Chim. Acta, 4. 155 (1966).
13 V. I. Minkin, B. Ja. Sirnkin, and L. P. Oleehnovich, Int. J. Sulf. Chem., 3A.A,No. 3 (1973).
14 R. Zahradnik, L Tesarova, and J. Pancir, Collection Czech. Chem. Commun., 3._66,2867 (1971).
15 J. Del Bene and H. H. Jaffe, J. Chem. Phys., 4.~8, 1807 (1968): 49, 1221 (1968).
16 K. B. Wiberg, Tetrahedron, 2_~4,1083 (1968).
17. R. S. B e c k e t E. Dolan, and D. E. Balke, J. Chem. Phys., 5_O.0,239 (1969).
18. T. Bercavici and E. Fischer. J. Arner. Chem. Soc.. 8.~6. 5687 (1964).
19. G. L Lashkov and A. V. ShapIya, Opt. i Spektroskopiya. 2_~1,546 (1966).
20. N. W. Tyer and R. S. Becket, J. Amer. Chem. Soc., 9_22, 1295 (1970).
21. R. S. Mulliken and C. A. Rieke, Rep. Prog. Phys., _8231 (1941).
22. M. L. Bailey, Theor. Chin. Acta, 2__66,87 (1972).
23. B. Tinland and C. Decoret, Tetrahedron Leg., 3019 {1971).
24. J. Iwai and J. Ide, Chem. Pharm. Bull. Japan, 1_.00,926 (1962).
~5. B. Ya. Sirnkin, V. I. Minkin, and L. E. Nivorozhkin, Khim. Geterotsikl. Soedin., 76 (1974).

66
PHOTOCHROMIC AND THERMOCHROMIC SPIRANS

V.* A THEORETICAL STUDY OF THE ELECTRONIC STRUCTURE

AND SPECTRAL PROPERTIES OF THE PHOTO-COLORED FORMS

OF INDOLINE SP]IIOPYRANS, SPIRODIPYRANS, AND SPIROTHIOPYRANOPYRANS

B. Ya. Simkin, V. I. Minkin, UDC 541.651'67:547.751'816.818

and L. E. Nivorozhkin

By m e a n s of the SCF MO LCAO method in the ~ - e l e c t r o n i c a p p r o x i m a t i o n (PPP). the e l e c -

tronic s t r u c t u r e s and s p e c t r a l c h a r a c t e r i s t i c s of indoline s p i r o p y r a n s , s p i r o d i p y r a n s , and
s p i r o t h i o p y r a n o p y r a n s have been calculated. The calculated s p e c t r a l c h a r a c t e r i s t i c s of the
p h o t o - c o l o r e d f o r m s of the s p i r o p y r a n s a g r e e b e s t with the e x p e r i m e n t a l r e s u l t s when a
g e o m e t r i c configuration c o r r e s p o n d i n g to a b i p o l a r s t r u c t u r e is taken. The diffuseness of
the l o n g - w a v e a b s o r p t i o n band is not connected with a difference in the s p e c t r a l c h a r a c -
t e r i s t i c s of the s t e r e o i s o m e r s . It has b e e n shown that the l o n g - w a v e e l e c t r o n i c t r a n s i t i o n
is localized in the allylidenecyclohexadienone f r a g m e n t of the m o l e c u l e . An explanation of
the m e c h a n i s m of the opening up of the s p i r o t h i o p y r a n o p y r a n s at the C - O bond is given.
The e x i s t e n c e of s p i r o t h i o p y r a n o p y r a n s in which the thiopyran f r a g m e n t m u s t be opened is
predicted.

Compounds of the s p i r o p y r a n s e r i e s f o r m one of the m o s t i m p o r t a n t c l a s s e s of organic p h o t o e h r o m e s

[2-4]. The nature of the p h o t o c h r o m i c p r o p e r t i e s of the s p i r o p y r a n s is d e t e r m i n e d by valence i s o m e r i z a -
tion initiated by i r r a d i a t i o n in the a b s o r p t i o n band of the s p i r a n f o r m A.

A BI B2
z - heterene residue, R- substkuents, arene nuclei

A l a r g e n u m b e r of publications have been devoted to e x p e r i m e n t a l investigations of the s p e e t r a l p r o p e r -

t i e s and p h o t o e h r o m i s m of the s p i r a n s (see the r e v i e w s [2-6]), but a t t e m p t s to study the e l e c t r o n i e s t r u e -
t a r e s and s p e c t r a of compounds A and B with the aid of the methods of quantum c h e m i s t r y have not b e e n
m a d e . N e v e r t h e l e s s . c o n s i d e r i n g the c o n s i d e r a b l e difficulties that a r e not infrequently encountered in the
study of the s p e c t r a l p r o p e r t i e s of the unstable p h o t o - c o l o r e d f o r m s B. the frequent n e c e s s i t y for an ex-
t r e m e l y complex s y n t h e s i s p r e c e d i n g the investigation of the p r o p e r t i e s mentioned, the value of which does
not always justify the e f f o r t s involved, and a l s o c o n s i d e r i n g the f a i r l y high a c c u r a c y achieved in the m o s t
i m p r o v e d s e m i - e m p i r i c a l methods of calculating s p e c t r a l p r o p e r t i e s , the p r o b l e m of a t h e o r e t i c a l d e s c r i p -
tion and p r e d i c t i o n of e l e c t r o n i c s t r u c t u r e s and s p e c t r a of the p y r a n s m u s t be c o n s i d e r e d as v e r y urgent.
In the p r e s e n t p a p e r , with the aid of the SCF MO method in the P a r i s e r - P a r r - P o p l e (PPP) method,
we i n v e s t i g a t e the e l e c t r o n i c s t r u c t u r e s of the ground and the singlet and t r i p l e t excited states, and also
the s p e c t r a of the open f o r m s (I-V) of a s e r i e s of p y r a n s .

* F o r C o m m u n i c a t i o n IV. see [1].

R o s t o v State University. R o s t o v - o n - D o n . T r a n s l a t e d f r o m K h i m i y a G e t e r o t s i k l i c h e s k i k h Soedinenfi.

No. 1. pp. 76-83. J a n u a r y . 1974. Original a r t i c l e submitted N o v e m b e r 30. 1972.

9 19 75 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy o f this article is available from the publisher for $15.00.

67
 I
II III

X
IV Y
X,Y=O,S

The calculations w e r e p e r f o r m e d by the Plop method taking configurational i n t e r a c t i o n (CI) into ac-
count. In the construction of the CI m a t r i x , the 20 s i n g l y - e x c i t e d configurations c l o s e s t to the ground state
w e r e considered. An i n c r e a s e in the n u m b e r of configurations c o n s i d e r e d has p r a c t i c a l l y no effect on the
e n e r g i e s of the s p e c t r a l t r a n s i t i o n s and t h e i r i n t e n s i t i e s . T w o - e l e c t r o n i c Coulomb i n t e g r a l s w e r e calcu-
l a t e d by the method of Mataga and NisMmoto [7]. The r e s o n a n c e i n t e g r a l s #pv w e r e calculated as functions
of the i n t e r a t o m i c distance r ~v .., f r o m the f o r m u l a s of Allinger and Miller [8]. The e n e r g i e s of t r a n s i t i o n
into t r i p l e t s t a t e s w e r e calculated with the u s e of the special p a r a m e t r i z a t i o n p r o p o s e d by Zahradnik et al.
[9]. The o s c i l l a t o r f o r c e calculated by a well-known f o r m u l a [10] was then halved, following B a i l e y ' s p r e -
s c r i p t i o n s [11]. The technique of the calculations has been given in m o r e detail e l s e w h e r e [12, 13].
The calculations of the s p e c t r a l c h a r a c t e r i s t i c s of a, ~ - substituted polyenes has shown that they de-
pend substantially on the sequence of a l t e r n a t i o n of o r d i n a r y and double bonds, and also on the alternation
value [14]. In the c a s e of the s p i r o p y r a n s , a s i m i l a r p r o b l e m a r i s e s . Qualitatively, the s t r u c t u r e of the
open f o r m of a s p i r o p y r a n can be given by two s t r u c t u r e s : a quinoid (B1) and a b i p o l a r (B2) form, in which
different polyenic configurations (different m o l e c u l a r g e o m e t r i e s ) exist: for example, f o r (IIt):

II! Bt 111B~ ii1 C

In addition, the c o m p l e t e equivalence of the lengths of the bonds of the four--carbon chain connecting the two
nuclei (structure IIIC) m a y be a s s u m e d .
We p e r f o r m e d the calculations with a c o n s i d e r a t i o n of the g e o m e t r i e s or all the p o s s i b l e s t r u c t u r e s
(B1, B2, and C) of compounds {I) (X = O) and (III) (X = Y ~ O). The r e s u l t s of calculations f o r (III) a r e given
in Table 1 t o g e t h e r with the e x p e r i m e n t a l values. The length of an o r d i n a r y bond was taken as 1.43 ~ and
that of a double bond as 1.37 .~. In calculating the s t r u c t u r e of (IIIC), the lengths of the bonds of the f o u r -
c a r b o n chain w e r e t a k e n as 1.40/~. The other g e o m e t r i c p a r a m e t e r s w e r e s i m i l a r to those u s e d in p r e -
vious w o r k [12. 13].
T h e f i g u r e s of T a b l e 1 show that the s p e c t r a l c h a r a c t e r i s t i c s of the b i p o l a r s t r u c t u r e (IIIB2) p r a c t i -
c a l l y coincide with the e x p e r i m e n t a l f i g u r e s . The r e s u l t s of calculations for compound (I) (X = O) a r e si-
m i l a r to those given. This r e s u l t c o n f i r m s the conclusion [15] of the p r e d o m i n a n t contribution of the b i p o l a r
s t r u c t u r e in the open f o r m s of the s p i r o p y r a n s .
The Indoline S p i r o p y r a n s (I and II). The complex s t r u c t u r e of the l o n g - w a v e absorption band of the
colored f o r m s of the indoline s p i r o p y r a n s is g e n e r a l l y connected with the existence of four s t e r e o i s o m e r s
the equilibrium between which depends on the t e m p e r a t u r e and the solvent [15-17]. All t h e s e i s o m e r s
(Ia-Id) p o s s e s s the t r a n s configuration r e l a t i v e to the c e n t r a l bond. Steric f a c t o r s for t h e m a r e a p p r o x i -
m a t e l y the s a m e , and t h e r e f o r e the stabilities of the i s o m e r s a r e connected with the distances between the
N and O a t o m s [18-20]. The stable i s o m e r (Ic) m u s t have the s h o r t e s t - w a v e a b s o r p t i o n [15, 21].

O.+N/~ O-

I I
Ja Ib .Ic |d

68
 TABLE 1. S p e c t r a l C h a r a c t e r i s t i c s of Various S t r u c t u r e s of C o m -
pound (III) (X = Y = O)

Struc-
ture ] Hm, I[[B= ] IIIC

AE, eV* 2,83 [ 3,76 =j 4,21 1,93 2,78l 3,32!2,33 i 3,21 3,82
f i . 0,64 ]i 0,051 , 0,04 0,71 ~ 0,18 'b 0,06 0,76 i 0,04 0,04

* The calculated f i g u r e s a r e given. The e x p e r i m e n t a l f i g u r e s a r e :

1.93 and 2.85 eV in isopentane--isopropanol (7 : 2).

TABLE 2. Spectral C h a r a c t e r i s t i c s of Compounds (I-V)

Charac- la lb ] Ic Id i ]e I (X--S)
teristics

( calc, ev 0,42
2,18 3,22 3,82 12,22 3,25 3.85 i2,24 3,23 3,87 221324 3,83 "233374462 1,742,813,18
i '07,0' 19 0 '02 0,24 0,02 0,36
0,20 0,02 0,51 0,2l 0,04 0,50 0,20 0,03 01440120 0,04 10 t ' b'
Eexp, eV ,2 11 3,10 a [2,26 :1,66 2,80 c
I (X=O) 9 II (X=S) ',Ill (X=Y=O) I iii (x=o, i IH (Y=o, i zv (x=Y=O)
l
I Y=S) ] X=S) ]2,10
~a!~ , ev2,413,08 3,59 1,952,67 3,02 11,982,78 3,32 ]2 02 2 70 3,00 !1,632,723,13 2,84 3,34
0,560,080,16 0,32 0,01 0,36 0,71 0,180,06 ,0,76 0,10 0,08 i0,46 0,15 0.40 i2,17f0'70,06
5 0,10
Eexp, eV 2,22 3,10 3,49g 1,93 2,85e
IV(Y=S,x.o) i IV (Y=O. : V (X=Y=O) V (Y=S, X=O) V (Y=O, X=S) i
- X=S)
~ calc, eV 2,13 2,76 3,25 } 1,74 2,69 3,08 ! 1,88 2,68 3,03 ~,1,922,57 2,98 1,53 2,67 3,01 I}
0,80 0 05 0 03 0,46 0,07 0 I0 0,74 0,18 0,09 0,83 0,08 0,02 0,48 0,17 0,14 1
F-exp, ev 2,18g t I L

aIn a m i x t u r e of m e t h y l c y c l o h e x a n e and 2 - m e t h y l p e n t a n e (2 : 1) [23].

bin benzene [15]. cin 3 - m e t h y l p e n t a n e [28]. din m i x t u r e of ethanol
and toluene (1 : 1) [24]. ein a m i x t u r e of isopentane and p r o p a n - 2 - o -
(7 : 2). fin a m i x t u r e of ethanol and methanol [25]. gin isopeniane.

It is a s s u m e d [15, 18] that when the C - O bond is

5, (3,74 eV) cleaved the colored molecule is c o n v e r t e d into an unstable
S~(3,-~8 e V ) f o r m which is m o s t p r o b a b l y the nonplanar cis i s o m e r (Ie)
with a n u c l e a r configuration close to the s p i r a n s t r u c t u r e .

f
i\ 1
~(2~ 9 e V ) ~ , 0 8 e S~ (2~04 eV)
The a b s o r p t i o n of the i s o m e r {Ie) m u s t be at s h o r t e r w a v e -
lengths than that of (Ia-Id).
To c o n f i r m this hypothesis, we have m a d e calculations
of the i s o m e r s (Ia-Ie) (Table 2). The calculated s p e c t r a l
c h a r a c t e r i s t i c s of the i s o m e r s (Ia-Id) s c a r c e l y differed f r o m
another and a g r e e d well with the e x p e r i m e n t a l figures. Of
So So So the four i s o m e r s . (Ic) actually has the s h o r t e s t - w a v e a b s o r p -
A~ Aa B tion, but the difference, of 0.04 eV, is not significant. The
p r e s e n c e of a b r o a d absorption band f o r the open f o r m s of
Fig. I. D i a g r a m of the e n e r g y l e v e l s of the
the s p i r o p y r a n s is p o s s i b l y connected with f e a t u r e s of the
s p i r o t h i o p y r a n o p y r a n (V-I): A t and A2 . the
a p p e a r a n c e of a v i b r a t i o n a l s t r u c t u r e or with i n t e r m o l e c u l a r
2 H - t h i o p y r a n and 2 H - p y r a n m o i e t i e s of the
i n t e r a c t i o n s . The long-wave m a x i m u m of the nonplanar cis
m o l e c u l e of (VI), r e s p e c t i v e l y : B - the
i s o m e r (Ie), retaining the g e o m e t r y of the spiran, is shifted
opened p y r a n f r a g m e n t of the m o l e c u l e .
h y p s o c h r o m i c a l l y r e l a t i v e to the t r a n s i s o m e r s , which is in
h a r m o n y with the r e s u l t s of e x p e r i m e n t [15].
In a p r e c e d i n g c o m m u n i c a t i o n [1], we showed that the fusion of a benzene nucleus at positions 5, 6, of
c h r o m e n e o r t h i o c h r o m e n e l e a d s to a h y p s o c h r o m i c shift of the l o n g - w a v e a b s o r p t i o n band of the open f o r m s .
This r e s u l t a l s o p r o v e s to be c o r r e c t f o r the s p i r o p y r a n s , as can be e s t a b l i s h e d by c o m p a r i n g the long-wave
m a x i m a of compounds {I) and (II) (Table 2). The s a m e change in the s p e c t r u m is o b s e r v e d e x p e r i m e n t a l l y [22].
Spirodipyrans and S p i r o t h i o p y r a n o p y r a n s . F o r the open f o r m s of the s p i r o d i p y r a n s and spirothio-
p y r a n o p y r a n s , just as for the indoline s p i r o p y r a n s , four t r a n s i s o m e r s a r e p o s s i b l e . The calculated e n e r -
gies of the l o n g - w a v e t r a n s i t i o n s of all the t r a n s i s o m e r s p r a c t i c a l l y coincide (difference of not m o r e than
0.05 eV), and t h e r e f o r e we give the calculation of only one of them. The e n e r g i e s of the s i n g l e t - s i n g l e t
t r a n s i t i o n s a r e in s a t i s f a c t o r y a g r e e m e n t with e x p e r i m e n t , as can be s e e n f r o m Table 2. The r e p l a c e m e n t

69
TABLE 3. Calculated Energies of Singlet-.Triplet of oxygen by sulfur in the benzo- and naphthopyran
T r a n s i t i o n s (S0-T 0 of Compounds {I-V) nucleus has p r a c t i c a l l y no effect on the s p e c t r a l c h a r -
a c t e r i s t i c s of the open f o r m s . At the same time, an
Compound aE, eV Compound AE, e.V
analogous substitution in the allylidenecyclohexa-
I 0,40 III 0,35
dienone p a r t strongly shifts the long-wave m a x i m u m
X= 0 2,34 Y~O, X = S 2,12 bathochromically, by approximately 120-130 nm (0.35
3,17 2,35
eV). Benzo-fusion in position 3,4 of the allylidene-
I 0,21 III 0,97
X=S 2,13 Y=S, X = O 2,05 cyclohexadienone nucleus (compound (IV) leads to a
2,79 3,00 h y p s o c h r o m i c shift of the long-wave maximum, while
II 0,54 IV 1,21 benzo-fusion in position 5,6 of the 2 H - c h r o m e n e (thio-
X=O 2,40 X=Y=O 2,00
3,07 2,76 chromene) nucleus [compound (V)] shifts the long-wave
III 1,08 V 0,99 t r a n s i t i o n b a t h o c h r o m i c a I l y . T h e s e facts can be used
X=Y=O 1,93 X=Y=O 1,98
2,84 2,89 to establish the method of opening up of u n s y m m e t r i c a l
spirodipyrans and spirothiopyranopyrans.
In the spirothiopyrans that we have studied [26], on photoexcitation only the p y r a n and not the thio-
p y r a n ring opens. This r e s u l t can be explained by making use of the diagram of m o l e c u l a r levels that we
calculated on the basis of the m e c h a n i s m p r o p o s e d by B e r c o v i c and others [22, 23. 27]. The diagram of
l e v e l s (Fig. 1) was constructed on the basis of the figures of Tables 2 and 5 of the preceding p a p e r [1]. In
view of the absence of appreciable spiroconjugation effects between the spiro-linked nuclei [29], the dia-
g r a m of levels of the s p i r o t h i a p y r a n o p y r a n WI) can be constructed additively f r o m r e s u l t s for the energy
level of 2 H - c h r o m e n e and 2H-thiochromene (VII, X = O, S).

VI VII X = O,S

The f i r s t t r i p l e t state of the closed f o r m of thiochromene is 0.15 eV higher than the t r i p l e t state of
c h r o m e n e (see Table 5 of the p r e c e d i n g p a p e r [1]). In view of this. the rapid internal conversion into the
t r i p l e t state of e h r o m e n e will be p r e v e n t e d by the population of the triplet level of the thiochromene. Con-
sequently, only the triplet level of the c h r o m e n e is populated, which leads to the opening of the s p i r o p y r a n
at the C - O bond. F o r the spirothiopyranopyran to open at the C - S bond, the f i r s t t r i p l e t state of the thio-
p y r a n m o i e t y of the molecule must be lower than the t r i p l e t state of the p y r a n moiety. Making use of the
figures of Table 5 of the preceding p a p e r [1] it is possible to p r e d i c t some spirothiopyranopyrans (VIII. IX)
in which the thiopyran fragment should open.

Vdl R H CH lg

Nature of the Long-Wave Absorption. The ~ - e l e c t r o n i c charges and bond o r d e r s of the f o u r - c a r b o n

chain in the ground (So) and f i r s t excited singlet (S~) states of the indoline s p i r o p y r a n (I, X = 0), the s p i r o -
dipyran {iII. X = Y = 0). and the spirothiopyranopyran (IIt, X = 0, Y = S) a r e shown in the m o l e c u l a r
diagrams.

OtO'~ - 0,0o~ .Or054

0,02o ~ ' ~ -0,009 0,,18
o,o,r[ J-o,~, o,,32 o ~ ~ 1 7 6 ? ~176
-"0)073 0,d77 _ 0t033
-o,oo= o,3~ /
0
o,s~ yg : 10,53 O
So

70
 I -0~007 0)064
0t015 - 0~047
0~0o7~ - o , o2o ~o,o2~ )-o,o13
- o ~ ~ ' o.,172~./
,/ o,o,o

-0~014 0~317 0 e~
-o,~35 P : o,gg O

51
0T047 -0f012
0~01~-0,124 0~012 -0~036
_o,oo,/ \-'--L/~176176 ,31 /CA
)2~ -0~036 " ~'~'7 --0,023
0
-o,466 .~g : 6 , 8 6 O
SO

. O~OZ5 OrOO8
-- 0~016 ~ - - 0 t 0 ~3 1 "
'~..~0,004 0 024 --0,025 0,036

o,oo, (\ ~-~-_0
/0,035 -%1
~,- o,57,~ /{0,043
" - k ) -0t015
~_._J " 0,258 -%044 X /
0f022 0p054 . Op1~-"-~ 0,003

0 .~ : 4?63
--%408
Sl
%026 -0,008
0~006 ~ - 0 t 0 2 2

o,5,o~176176176176176
OfO09 OtO01 0,207 0g023

0
50 - 0,33~
,~g : 3~34 D
%008 0,023
0~,006 / F ' ~ - O , O 15 Or030
0,006 /-"~,ulu ~ - 0,009 0,021
( _kC=.2 %\ O,582 / " - - k
:o,o,o <o,o0,>_o,oo
0,,021 0~001 0),186
~ 0 0,003

0
51 -%334 .,Ue = 4~18 O

F r o m a c o m p a r i s o n of the c h a r g e s and a consideration of the f o r m of the m o s t i m p o r t a n t MOs of the

ground and excited states, it m a y be concluded that the e l e c t r o n i c t r a n s i t i o n is localized in the allylidene-
cyclohexadienone component of the m o l e c u l e of the s p i r o p y r a n . It b e c o m e s understandable why the r e p l a c e -
m e n t of oxygen by sulfur in the benzo- and naphthopyran nuclei has p r a c t i c a l l y no effect on the s p e c t r a l
p r o p e r t i e s of the open f o r m s of the s p i r o p y r a n s [26]. The s i m i l a r r e a c t i o n to the b e n z o - f u s i o n of the long-
wave a b s o r p t i o n band of the s p i r o p y r a n and of the c h r o m e n e c o r r e s p o n d i n g to it is also understandable. It
follows f r o m the r e s u l t s p r e s e n t e d that s t r u c t u r a l modifications having the a i m of substantially changing
the s p e c t r a l p r o p e r t i e s of the s p i r o p y r a n s m u s t affect the allylideneeyclohexadienone p a r t of the molecule.
A c o n s i d e r a t i o n of the o r d e r s of the ~ bonds of the f o u r - c a r b o n chain shows a b i p o l a r s t r u c t u r e (B2)
of the ground s t a t e of the s p i r o p y r a n s , while the c h a r g e distribution does not c o r r e s p o n d to complete

71
polarization. For the indoline spiropyran in the first excited state, the dipole moment decreases by almost
10 D, which leads to a hypsoehromie shift of the corresponding absorption band on passing to polar solvents
[15]. The dipole moments of the spiropyran and of the spirothiopyranopyran scarcely change on passing to
the excited state. This explains the absence of solvatoehromy that is actually observed.
The energies o f t h e s i n g l e t - t r i p l e t transitions of some. spiropyrarm are given in Table 3. The first
triplet state of the open forms of the spiropyrans (I. X = O S, and III, X = S, Y = O) is located very close to
the ground state, which must hinder its observation. The absence of experimental results on the position
of the triplet levels of the open forms of the spiropyrans does not yet enable the correctness of the calcu-
lations to be checked.

LITERATURE CITED
I. V. L MiD_kin. B. Ya. Simkin, L. E. Nivorozhkin. and B. S. Luk'yanov, Kbim. Geterotsikl. Soedin.. 67
(1974).
2. J. Koszar, Light Sensitive Systems, Wiley, (1965)o
3. R. Exelby and R. Grinter, Chem. Roy., 6__55.247 (1965).
4. M.V. Savost'yanova, Trudy GOI. 3_66,No. 165, 70 (1969).
5. J. Calvert and J. l>itts, Photochemistry. Wiley (1966).
6. A.N. Terenin. The Photonies of Dye Molecules [in Russian], Nauka, Leningrad (1967).
7. N. Mataga and K. Nishimoto, Z. Phys. Chem., I__33,140 (1957).
8. N . L . Allinger and M. A. Miller. J. Amer. Chem. Soc.. 8_~6.Z811 (~964).
9. R. Zahradnik, L Tesarova, and J. Pancir, Collection Czech. Chem. Commun., 3__66,2867 (1971).
10. R . S . Mulliken and C. A. Rieke, Rep. Prog. Phys., 8, 231 (1941).
11. M . L . Bailey, Theor. Chim. Acta, 2_66, 87 (1972).
12. V . I . Minkin. L. P. Olekhnovich, and B. Ya. Simkin, Zh. Organ. Khim., 8, 2364 (1971).
13. V . I . Minkin, B. Ya. (Ja.) Simkin, and L. P. Olekhnovich (Olechnovich), Int. J . Sulf. Chem., 3A_A,No.
3 (1973)o
14. L . A . Yanovskaya (Janovskaya), Vo Io Kucherov. B. Ya~ Simkin, V. L Minkin, e t a l . , Tetrahedron, 29,
2O53 (1973).
15. J . B . Flannery, J. Amer. Chem. Soc., 9._00,5660 (1968).
16. G . I . Lashkov and A. V. Shablya, Opt. i Spektroskopiya, 1_99,821 (1965).
17. Y. Hirshberg and E. Fischer, J. Chem. Soc., 297, 3129 (1954).
18. R. Heiligman-Rim, Y. Hirschberg, and E. Fischer, J. Phys. Chem., 66, 2465, 2470 (1962).
19. G.I. Lashkov, M. V. Savost'yanova, A. V. Shablya, and T. A. Shakhverdov, in: Molecular Photonics
[in Russian]. Nauka, Leningrad (1970).
20. O. Shaude. Cahiers de Physique. 8. NN50-52 (1954).
21. T . A . Shakhverdov, Izv. Akad. Nauk SSSR, Ser. Fiz., 32. 1564 (1968).
22. T. Bereovici, R. Heiligman-Rim, and E. Fischer. Mol. Photochem., 1, 23 (1969).
23. T. Bercovici and E. Fischer, J. Amer. Chem. Soc., 86. 5687 (1964).
24. Y. Hirshberg, J. Amer. Chem, Soc.. 7_88,2304 (1956).
25. R. Heiligman-Rim, Y. Hirshberg, and E. Fischer, J. Chem. Soc., 156 (1961).
Z6. V. L Minkin. N. E. Shelepin, L. E. Nivorozhkin, and N. S. Voloshin, Int. J. Sulf. Chem. (1973)~
ZT. G . I . Lashkov, V. A. Ermolaev. and A. V. Shablya, Opt. i Spektroskopiya. 2_~1,546 (1966).
28. R.S. Becker and J. Kole, J. Phys. Chem., 7__22.997 (1968).
29. N . W . Tyer and R. S. Becket, J. Amer. Chem. Soe., 92, 1289 (1970).

72
SYNTHESIS AND SOME PROPERTIES
OF 1,3- DIARYL- 2.2- DIBROMOAZ IRIDINES

N. S. K o z l o v , V. D. Pak, UDC 547.717.07 : 542.938

a n d V. V . M a s h e v s k i i

1 , 3 - A r y l - 2 , 2 - d i b r o m o a z i r i d i n e s have been s y n t h e s i z e d and their hydrolytic c l e a v a g e in an

aqueous m e d i u m has been p e r f o r m e d .

The r e a c t i o n of a z o m e t h i n e s with d i c h l o r o c a r b e n e is well known [1. 2], but the reaction of d i b r o m o -

c a r b e n e with Schiff's b a s e s has not been studied. We have established that the main direction of the r e a c -
tion of a r o m a t i c Schiff's b a s e s (I) with b r o m o f o r m in the p r e s e n c e of p o t a s s i u m tert-butoxide is the f o r m a -
tion of 1 , 3 - d i a r y l - 2 , 2 - d i b r o m o a z i r i d i n e s (II):

C H Bra, t'C~,HgOK RC6H4--~/)N--C~H4R' H20

I~CrH4CH=NC6H~,R" Br~, Br RCoHICHBrCONHC6H4R'

Apparently, the d i b r o m o c a r b e n e f o r m e d by the reaction of the b r o m o f o r m with the p o t a s s i u m t e r t -

butoxide, as an electrophilic reagent, adds to the a z o m e t h i n e bond of compound (I) with the f o r m a t i o n of the
substituted a z i r i d i n e s ffl) (Table 1). Schiff's b a s e s with a high b a s i c i t y r e a c t c o n s i d e r a b l y m o r e rapidly
with d i b r o m o c a r b e n e than a z o m e t h i n e s with a l o w e r basicity. Thus, while the r e a c t i o n of p - m e t h o x y b e n z -
ylideneaniline (pK a 11.16) with d i b r o m o c a r b e n e takes p l a c e in f r o m 2 h 30 rain to 3 h, the r e a c t i o n of b e n z -
y l i d e n e - m - n i t r o a n i l i n e (pKa 7.88) with d i b r o m o c a r b e n e is c o m p l e t e only after 8 h. B e n z y l i d e n e - p - n i t r o -
aniline (pK a 7.47) and p - n i t r o b e n z y l i d e n e - p - n i t r o a n i l i n e (pK a 6.08) are c o m p l e t e l y inert. H a l o g e n - s u b s t i -
tuted Schiff's b a s e s , such as p - c h i o r o b e n z y l i d e n e a n i l i n e (pK a 9.10) and b e n z y l i d e n e - p - b r o m o a n f l i n e (pK a
9.00) [3], the b a s i c i t y of which is fairly high, a l s o f o r m the a z i r i d i n e s (II) v e r y readily.
The structure of compounds (1I) w e r e c o n f i r m e d by their c o n v e r s i o n into a - a r y l - a - b r o m o a c e t a n i l i d e s
(III) (Table 2).

TABLE 1. 1 , 3 - D i a r y l - 2,2- d i b r o m o a z i r i d i n e s (II)

Empirical N, %
rap, *c formula found calcu-
lated %
H p-Cl 89--91 CL,HIoBrzCIN 3,7; 3,8 3,6 55
H o-CI 111--112 Ct4HIoBrzCIN 3,6; 3,7 3,6 74
p.-F H 75--77 C~4HIoBr2FN 3,7; 3,7 3;8 63
p-F p-Ci 88--90 CI4HgBr~C1FN 3,5; 3,6 3,4 66
p-F p-CHa 74--75 CIsHtzBr2FN 3,7; 3,8 3,6 73
o-F m-Br 90 C14HgBraFN 2,9; 3,0 3,1 56
o-F p-[ 109--110 Cl4HgBr2FIN 2,9; 3,0 2~8 54
p-Br m -C 1 98--100 C14HgBr=CIN 2,8; 2,9 3,0 63
p-Cl o-Ct 102--104 C ~4HgBrzCIzN 3,4; 3,4 3,3 69
p-I o-Br 120--!P2 CI4H~Br~IN 2,4; 2,5 2,5 52
p-I o-Ci 110--111 C14HgBr2CIIN 2,8; 2,9 2,7 71
p-I m-Br 12i--123 CI4HgBraIN 2.3; 2,4 2,5 60
pC1 H 96--98 CI4Hl~Br2CIN 3,5; 3,6 3,6 75
H m-NO~ 117--119 C~4H:0BreN20,_, 6.8; 6,9 7,0 67
p-OCHa H 97--98 CisHIaBr2NO 3,5; 3,6 3,6 61

D. N. P r y a n i s h n i k o v P e r m Agricultural Institute. Translated f r o m Khimiya G e t e r o t s i k l i c h e s k i k h

Soedinenii, No. 1, pp. 84-85, January, 1974. Original article submitted July 12, 1972.

9 19 75 Plenum Publishing Corporation, 22 7 West 1 7th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of th.e publisher. A copy o f this article is available from the publisher for $15.00.

73
 T A B L E 2. a , Aryl-a-bromoaeetanilides (III)

Empirical N,% Yield,

R' Mp, ~ formula calcu-
found lated ~0
H p-Cl 154--156 c,4HHBrC1NO 4,4; 4,5 4,3
p-F H 137--139 9Ct~H,tBrF~O 4,6; 4,6 4,5 79
p-F p-Cl 145--147 C,4H,oBrC1ENO 4,1; 4,2 4,1 67
p-F p-CH8 162--163 CtsH,sBrFNO 4,2; 4,3 4,3 71
o-F p-I 130--131 CI4HIoBrFINO 3,2; 3,3 3,2 73
H m-NO~ 154--156 C14HnBrN,Oz 8,3; 8,4 8,4 66
, p-Br m-Cl " 151--153 Ct4HIoBr2CINO 3,4; 3~5 3,5 80
p-I o-Cl t41--142 CI4HaoBrCIINO 3,2; 3,3 3,1 78
p-I o-Br 152--154 CI~H~eBrflNO 2,9; 3,0 2,8 82
p-I ,n-Br 170--172 C14H,oBr21NO 2,8; 2;9 2,8 76

The P M R s p e c t r a of (II) h a v e s i g n a l s at 3 . 5 - 3 . 6 p p m (proton of a t h r e e - m e m b e r e d ring), and s i g n a l s

at 7 . 1 - 7 . 2 p p m (protons of b e n z e n e rings), w h i c h is in good a g r e e m e n t with i n f o r m a t i o n f o r substituted
aziridines [4]. The IR s p e c t r a of the a m i d e s (III) have the bands of C = O s t r e t c h i n g v i b r a t i o n s (1650-1648
c m -1) and the b a n d of NH s t r e t c h i n g v i b r a t i o n s (3260 c m -1) [5, 6].

EXPERIMENTAL

T h e P M R s p e c t r a w e r e t a k e n on a Y a M R - 5 5 3 5 (40 MHz) s p e c t r o m e t e r in CC14 with HMDS as i n t e r n a l

s t a n d a r d . The IR s p e c t r a w e r e taken in p a r a f f i n oil.
1 , 3 - D i a r y l - 2 , 2 - d i b r o m o a z i r i d i n e s (II) (Table 1). With s t i r r i n g and c o o l i n g in an a t m o s p h e r e of n i t r o -
gen, 0.4 m o l e of b r o m o f o r m w a s added d r o p w i s e o v e r 1 h 30 rain t o a m i x t u r e of 0.01 m o l e of an a z o m e t h i n e
{I), 0.04 m o l e of p o t a s s i u m t e r t - b u t o x i d e , and 40 m l of h e x a n e . The m i x t u r e w a s s t i r r e d at 16-18~ f o r
a n o t h e r 4-7 h. The h e x a n e l a y e r w a s f i l t e r e d off and the s o l v e n t w a s p a r t i a l l y distilled off. The p r e c i p i t a t e
t h a t d e p o s i t e d w a s f i l t e r e d off and was c r y s t a l l i z e d f r o m hexane. The d i b r o m o a z i r i d i n e s f o r m c o l o r l e s s
c r y s t a l l i n e s u b s t a n c e s r e a d i l y soluble in ethanol, e t h e r , and dioxane. T h e y a r e u n s t a b l e at r o o m t e m p e r a -
t u r e : thus, 2 . 2 - d i b r o m o - 3 - ( p - m e t h o x y p h e n y l ) - l - p h e n y l a z i r i d i n e r e s i n i f i e s a f t e r 2 0 - 3 0 rain, while 2 , 2 - d i -
b r o m o - 1 - ( m - n i t r o p h e n y l ) - 3 - p h e n y l a z i r i d i n e is s t a b l e f o r t h r e e d a y s . T h e d i b r o m o a z i r i d i n e s can be s t o r e d
f o r s e v e r a l w e e k s in v a c u u m at 0~
a-Aryl-a-bromoacetanilides (III) (Table 2). An a z i r i d i n e (II) (0.005 mole) was boiled in 20 ml of
w a t e r until the oil f o r m e d had b e e n c o n v e r t e d into a c r y s t a l l i n e m a s s . The r e a c t i o n p r o d u c t was c r y s t a l -
l i z e d f r o m ethanol.

LITERATURE CITED
1, E. Fields and J. Sandri, Chem. Ind., 1216, London (1959).
2. N. S. Kozlov, V. D. Pak, and V. V. Mashevskii. Khim. Geterotsikl. Soedin., 180 (1972).
3. V. I. Minkin and V. A. Bren'. Reakts. Sposobonost' Organ. Soedin.. 4, 115 (1967).
4. J. A. Deyrup and R. B. Greenwald. J. Amer. Chem. Soc.. 87, 4543 (1965).
5. L. Beilamy. Infrared Spectra of Complex Molecules, 2nd ed.. Methuen. London.
6. L. Bellamy. Advances in Infrared Group Frequencies. Methuen. London (1968).

74
THE CONFIGURATION OF ESTERS

OF fl-(INDOL-3-YL)-a-NITROACRYLIC ACID

N. P . K o s t y u c h e n k o , O. D. S h a l y g i n a , UDC 5 4 1 . 6 3 4 : 5 4 7 . 7 5 7
L. Kh. V i n o g r a d , a n d Y u . N. S h e i n k e r

It has been shown by PMR s p e c t r o s c o p y that for the methyl and benzyl e s t e r s of ~- (indol-3-
y l ) - a - n i t r o a e r y l i c acid and their N - a c e t y l a t e d derivatives the i s o m e r s with the cis a r r a n g e -
ment of the n i t r o group and the indole nucleus a r e the m o r e stable.

E s t e r s of fl- (indol-3-yl)- ~ - n i t r o a c r y l i c acid (I and II), the synthesis of wlzich has been described
p r e v i o u s l y [1] can exist in the f o r m of cis and t r a n s i s o m e r s .

~ ,,cn;.=ccooR" I ~ P,=H. R'=CH3;

IF~T---T[ " " b R=COCH3, R'=CH~
Ik ;s U NO~
~'~-/'~N/ II a R=H, R'=Ctl2C61%:
I
R b R=COCII:~, R'= CH~C6H~

It has been found that in the PMR s p e c t r a of compounds (Ia) and (IIa) t h e r e is a double set of signals
c o r r e s p o n d i n g to the two g e o m e t r i c i s o m e r s in r e l a t i v e p r o p o r t i o n s of 3 : 2. In the a r o m a t i c region, in ad-
dition to the complex multiplets due to the p r o t o n s of the benzene ring, t h e r e a r e two singlets f r o m the
/3-H and 2-H protons, one of which is c o n s i d e r a b l y broadened. A f t e r the addition of CD3OD, this signal be-
c o m e s c o n s i d e r a b l y n a r r o w e r . On this basis, the broadened signal was a s c r i b e d to the proton at C2, i n t e r -
acting with N~H, and the other one to the p r o t o n at CB. However. even after the elimination of the influence
of NH, the signal of the 2-H p r o t o n p r o v e d t o b e wider than that of the f l - H . This broadening is apparently
due to i n t e r a c t i o n with the p r o t o n s of the benzene ring or to the influence of quadrupole relaxation of the N
atom. In the s p e c t r u m it is p o s s i b l e to o b s e r v e the l o n g - r a n g e SSCC of the 2-H and B-H protons (J=0.6Hz).
The i s o m e r s (Ia) and (IIa) could not be s e p a r a t e d by c r y s t a l l i z a t i o n or by c h r o m a t o g r a p h y on various
adsorbents. When a benzene solution of the mixture (Ia) or (IIa)with a ratio of the i s o m e r s of 3 -. 2 was i r -
radiated with a quartz - m e r c u r y lamp for 1 h. the partial c o n v e r s i o n of t h e m o r e stable i s o m e r into the
other one took place, and the relative p r o p o r t i o n of the i s o m e r s b e c a m e 1 : 1.
When a solution of compound (In) was heated to 65~ [solvent (CD3)2CO], a fusion of the analogous
signals of the two i s o m e r i c f o r m s was observed. Such a low t e m p e r a t u r e of c o a l e s c e n c e indicates a low
b a r r i e r to rotation around the C ~ C double bond.
F o r compounds (Ib) and (IIb), acetylated at the nitrogen atom, it was possible to isolate one of the
i s o m e r s in the pure f o r m in each case. The second i s o m e r s of {Ib) and {IIb) were isolated by p r e p a r a t i v e
c h r o m a t o g r a p h y on plates coated with s i l i c a gel (Ib, R f 0.69. 0.61": IIb, R f 0.57, 0.46): however, they v e r y
rapidly i s o m e r i z e d and in the PMR s p e c t r a they a l r e a d y appeared in the fbrm of a m i x t u r e of i s o m e r s .
When the s p e c t r a of (Ib) and (nl0) in (CD3)2CO were r e c o r d e d at 60~ it was possible to o b s e r v e the partial
t r a n s f o r m a t i o n of the m o r e stable into the l e s s stable i s o m e r s . Equilibrium was achieved after about 20
rain. In the r e g i o n of a r o m a t i c signals, in addition to the multiplets f r o m the protons of the benzene ring,
two singlets w e r e o b s e r v e d due to the 2-H and 13-H protons (J = 0.6-0.8 Hz), while for both the i s o m e r s

* F o r (Ib) the eluent was b e n z e n e - e t h e r (4 : 1), and for (IIb) it was benzene.

S. Ordzhonikidze All-Union S c i e n t i f i c - R e s e a r c h Institute of P h a r m a c e u t i c a l Chemistry, Moscow.

T r a n s l a t e d f r o m Khimiya Geterotsiklicheskikh Soedinenii. No. 1, pp. 86-89. January, 1974. Original article
submitted J a n u a r y 2, 1973.

9 19 75 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

75
 TABLE 1. C a l c u l a t e d and E x p e r i m e n t a l Values of the C h e m i c a l
Shifts of the a - H and fi-H P r o t o n s in (Ill) {ppm)

Calculation Experiment* aS=Scalc--8exp

HI3 NO~ &z-H 7,73. A~a_H --0,12
N / Ilia
C=C 6p-H 8,27 AfS-H--0,17
I I
Ar H~
6~-H 7,61 8~-H 7,74 hSa H--0,13
IIIb
~-H 8,10 6~-H 8,15 AS~.H--0,05

S o l v e n t - CDC13.

one of the s i n g l e t s was s o m e w h a t b r o a d e n e d . As in the c a s e of the N - u n s u b s t i t u t e d d e r i v a t i v e s , the b r o a d e n e d

s i n g l e t was a s c r i b e d to the p r o t o n at C2.
A t t e n t i o n is a t t r a c t e d by the c o n s i d e r a b l e d i f f e r e n c e in the v a l u e s of the c h e m i c a l shifts of the fl-H
p r o t o n s f o r each p a i r of i s o m e r s : 0.55 p p m ([a), 0.45 p p m (lb), 0.51 p p m (IIa), and 0.45 p p m {lib). the B-H
s i g n a l s in the s t a b l e i s o m e r s b e i n g l o c a t e d in the s t r o n g e r field. T h i s can be u s e d to d e t e r m i n e the c o n -
f i g u r a t i o n of compounds of t h i s s e r i e s .
P a s c u a l et al: [2, 3] have p r o p o s e d a s c h e m e of c a l c u l a t i n g c h e m i c a l s h i f t s of p r o t o n s of s u b s t i t u t e d
o l e f i n s which a d d i t i v e l y t a k e s into account the influence of the s u b s t i t u e n t s p r e s e n t in the gem. cis. and
t r a n s p o s i t i o n s r e l a t i v e to the p r o t o n being d e t e r m i n e d .

cis
H~C = CX 6C=C =5"25+'~Zi"
/
Rgem ~ trans \H

w h e r e Zi r e p r e s e n t s the i n c r e m e n t s of the s u b s t i t u e n t s f o r the gem. c i s . and t r a n s p o s i t i o n s .

We have m a d e u s e of this s c h e m e to e v a l u a t e the c h e m i c a l shifts of the fl-H p r o t o n s in the two i s o -
m e r i c f o r m s , and on t h i s b a s i s have m a d e an a s s i g n m e n t of t h e c o n f i g u r a t i o n in compounds (I) and (ID. The
v a l u e s of t h e i n c r e m e n t s of the NO2 * and COOR g r o u p s w e r e t a k e n f r o m the l i t e r a t u r e [3, 4]. Since in
finding the v a l u e s of t h e i n c r e m e n t s t h e h e t e r o a r o m a t i c s y s t e m s w e r e not c o n s i d e r e d , in o u r c a l c u l a t i o n s
t h e i n c r e m e n t s f o r the indole r i n g w e r e taken as equal to the i n c r e m e n t s of the a r o m a t i c s y s t e m s [3].
To e v a l u a t e the j u s t i f i c a t i o n for such a change, a c a l c u l a t i o n was p e r f o r m e d on the c h e m i c a l s h i f t s of
t h e a and fl p r o t o n s in compounds (III) (a, b) the t r a n s c o n f i g u r a t i o n of which had b e e n e s t a b l i s h e d f r o m
the v a l u e s of the SSCCs of a - H and B-H (J = 13.6 Hz (IIIa) and 13.8 Hz (IIIb)).

Ha HI a R=H;
R b R~Ac

The c a l c u l a t e d and e x p e r i m e n t a l v a l u e s of the c h e m i c a l shifts of the a - H and B-H p r o t o n s in (HI) a r e

given in T a b l e 1. It follows f r o m T a b l e 1 that t h e s e values f o r (IIIa and b) a r e in good a g r e e m e n t and & 6
d o e s not e x c e e d 0.17 p p m [3]. Thus. to t a k e into account the influence of the N - u n s u b s t i t u t e d and N - a c e t -
y l a t e d i n d o l e r i n g s it is p o s s i b l e to u s e the i n c r e m e n t s f o r the a r o m a t i c ring. The c i s i s o m e r was not
a v a i l a b l e to us, but c a l c u l a t i o n f o r it g a v e v a l u e s of the c h e m i c a l s h i f t s of 7.18 p p m f o r the a - H and 7.09
p p m f o r the fl-H. The d i f f e r e n c e s in the v a l u e s of the c a l c u l a t e d c h e m i c a l s h i f t s f o r a - H and B-H f o r the
t r a n s a n d c i s i s o m e r s a r e f a i r l y l a r g e (&6a_ H = 0.43. &6B_ H = 1.01 ppm). Hence, when two i s o m e r i c
f o r m s a r e p r e s e n t , the p o s s i b i l i t y a r i s e s of d e t e r m i n i n g the c o n f i g u r a t i o n of each i s o m e r f r o m the d i f f e r -
ence in the c h e m i c a l s h i f t s of the a - H and, in p a r t i c u l a r , the B-H p r o t o n s .
This m e t h o d of c a l c u l a t i o n was u s e d f o r compounds (I) and (II). F r o m a c o m p a r i s o n of the c a l c u l a t e d
v a l u e s of t h e c h e m i c a l s h i f t s of fl-H f o r the c i s and t r a n s i s o m e r s (Table 2) it can be s e e n that. as was the

* In the p a p e r of D e s c o t e s et al., a p r i n t i n g e r r o r has b e e n found f o r the value of Zci s of the NO2 group:
Z c i s = 1.47 p p m (and not 1.67 ppm).

76
 TABLE 2. Calculated and Experimental Values of the Chemical
Shifts of the /3-H Protons in (1) and (II) (ppm)

Com- trans* Con, cis Con-

pound A 6 trans-cis
figuration figuration

5 calc 8,55 8,10 0,45

la 6 exp 8,52T 7,97 0,55
A5 calc-exp 0,03 O,13
6 exp 8,46 7,95 0,5~
IIa
A 6 calc-exp 0,09 ! 0,15
5exp 8,19 ~ 7,74 0,45
Ib
A 5 calc-exp 0,36 ', 0,36
6 exp 8,20 7,75 0,45
lib
/% eaic-exp 0,35 0.35

* The t r a n s i s o m e r is c o n s i d e r e d to be that in which the indole ring

and the NO2 group a r e in the t r a n s position with r e s p e c t to one an-
other. In this case, the universal configurational symbols E and Z
are l e s s c l e a r .
t S o l v e n t - C DCla.

case for the disubstituted derivatives, the t r a n s i s o m e r has the f~-H signal in a weaker field than the cis
i s o m e r , although the difference A6trans_ci s f o r the fi-H (0.45 ppm) is somewhat s m a l l e r than in the case
c o n s i d e r e d (1.01 ppm). Starting f r o m this, as the signals of the t r a n s i s o m e r s in the s p e c t r a we took the
signals p r e s e n t in the w e a k e r field and under t h e s e c i r c u m s t a n c e s the difference AStrans_eis, as noted
above, was in the range f r o m 0.45 to 0.55 ppm for all the p a i r s of i s o m e r s , i.e., e x t r e m e l y close to the
calculated figure. The assignment of the i s o m e r s of compounds {Ia, 11), IIa, and IIb) to the cis and t r a n s
f o r m s was made on this b a s i s , tt follows f r o m this that the m o s t stable i s o m e r s p r o v e d to be those with
the cis a r r a n g e m e n t of the nitro groups and the indole rings. It can be seen f r o m Table 2 that the a g r e e -
ment of the calculated and experimental values of the chemical shifts of the of the fi-H protons for (Ia) and
{IIa) is good. For the N - a c e t y l a t e d d e r i v a t i v e s (Ib and IIb) the deviation of the calculated and experimental
values is g r e a t e r than can be accepted. Apparently, the p r e s e n c e of the N-acetyl groups in the indole ring
leads to c o n s i d e r a b l e d i p o l e - d i p o l e i n t e r a c t i o n s with the voluminous NO2 and COOR a c c e p t o r groups, which,
in its turn. disturbs the additivity of the influence of the substituents. The c a u s e s of such deviations in
compounds of types (I) and {II) are being made the subject of f u r t h e r investigation.

EXPERIMENTAL
The PMR s p e c t r a were taken on a JNM 4H-100 s p e c t r o m e t e r with a working frequency of 100 MHz
and a C - 6 0 - H L s p e c t r o m e t e r with a working frequency of 60 MHz. The internal standard was t e t r a m e t h -
ylsflane.
Compounds (Ia and IIa) were obtained by the method of Babievskii et al. [5], and compounds (1t)) and
(IIb) by the method of Vinograd et al. [6].

LITERATURE CITED

I. L. Kh. Vinograd, O. D. Shalygina, N. P. Kostyuchenko, and N. N. Suvorov, A b s t r a c t s of L e c t u r e s at

the XIIth Scientific Session on the C h e m i s t r y and Technology of Organosulfur Compounds and the Or-
ganic Compounds of Sulfur-Containing Oils [in Russian], Zinatne, Riga (1971), p. 62.
2. C. Pascual, I. Meier, and W. Simon, Helv. Chim. Acta, 49, 164 (1966).
3. U. E. Matter, C. Pascual, E. P r e t s c h , A. P r o s s . A. Simon, and S. Sternhell, Tetrahedron, 25, 691
(1969).
4. G. Descotes, J. Bahurel, M. Bourillot. G. Pingeon, and R. Rostaing, Bull. Soc. Chim. France, 282
(1970).
5. K. K. Babievskii, V. M. Belikov, and N. A. Tikhonova, Khim. Geterotsikl. Soedin., Collection 1 (1967),
p. 46.
6. L. Kh. Vinograd and N. N. Suvorov, Khim. Geterotsikl. Soedin., 1505 (1970).

77
INDOLES
XL.* SYNTHESIS OF TRYPTOPHOLS AND HOMOTRYPTOPHOLS

FROM CYCLIC SEMIACETALS AND ARYLHYDRAZINES

I. I. Grandberg and T. 1~ Moskvina UDC 547.754.07 : 542.953.4

The reaction of arylhydrazines and cyclic semiacetals (a-hydroxytetrahydropyran and a - h y -

droxytetrahydrofuran) on heating leads, with the evolution of water and ammonia, respective-
ly, to homotryptophols and tryptophols.

In the synthesis of homotryptophols and tryptophols, we have previously investigated cyclic vinyl
ethers of the type of A2-dihydropyran and A2-dihydrofuran [2]. The latter, by adding arylhydrazine salts
at the activated double bond, undergo opening of the oxygen-containing ring and are converted into hydra-
zinomethylene derivatives of aliphatic alcohols, which, in the manner of the Fi scher reaction, form
3- {hydr oxyalkyl)indoles.
We have found that cyclic semiacetals (a-hydroxytetrahydropyran and a-hydroxytetrahydrofuran) on
being heated with free arylhydrazines first lose a molecule of water (at 80-100~ and, at a higher tempera-
ture (about 200~ also split off a molecule of ammonia, giving, respectively, homotryptophols and
tr~t~h~s.

I~' r' r'

11 n = 1,2 Ill IV

s CH2OH CH2OH (~H,pH

I R /
R\.~.~
(-':. -.-\ F/\

I I I
R' R' R'
V VI VII VIII

In the first stage of the reaction, apparently, the formation of the a-hydrazino ether (III) takes place,
and on further heating at a higher temperature, through ~ elimination, the opening of the tetrahydropyran
ring takes place with the formation of the hydrazinomethylene (IV). This hydrazinomethylene, as the result
of a sigmatropic (3,3) shift [3], is converted into the 1,5-dienic structure (V), which is stabilized by aroma-
tization into the substituted aniline (VI). The latter undergoes intramolecular addition at the C = N bond,
giving the aminoindoline (VII), which aromatizes by the ejection of ammonia to form the tryptophol system
(VffI). In confirmation of some stages of the proposed scheme, we have succeeded in isolating an inter-
mediate compound of type (1TI).

* For Communication XXXIX, see [1].

K. A. Timiryazev Moscow Agricultural Academy. Translated from Khimiya Geterotsiklicheskikh

Soedinenii, No. 1, pp. 90-91, January, 1974. Original article submitted December 30. 1972.

9 19 75Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

78
The IR s p e c t r u m of substance {IlI) has no absorption band c h a r a c t e r i s t i c for the s t r e t c h i n g vibrations of a
hydroxy group or f o r a double C ~ N bond in the 1620-1640 cm -~ region that would be observed in the ease
of hydrazone. In the UV s p e c t r u m the absorption m a x i m a in the 275 um region and two inflections in the
245 and 300 nrn regions likewise do not c o r r e s p o n d to a hydrazone s t r u c t u r e .

EXPERIMENTAL
Chromatography was performed on AI~O3 (activity grade V) in the benzene-isopropanol (9 : I) system.
The UV spectra were taken on a Hitachi EPS-3T instrument in ethanol and the IR spectra on a Jasco IRS
instrument with a NaCI prism in chloroform solution or as liquid films.
a-Methyl-fl-(tetrahydropyran-2-yl)phenylhydrazine. This was obtained by heating c~-rnethylphenyl-
hydrazine and ~-hydroxytetrahydrofuran in benzene with the removal of water by distillation, followed by
vacuum distillation. Yield 80%: bp 160-165~ at 1 mrn. Found %: C 69.7- H 8.6. C~IHI6N20. Calculated %-
C 69.9; H 8.7. Rf 0.67. UV spectrum: krnax 245. 275. 300 rim; log ~ 3.76, 4.23, 3.00. IR spectrum, ern-i:
3400 (NH), 1590, 1500 (stretching vibrations of the phenyl nucleus).
Hornotryptophol. A solution of 5.4 g (0.05 mole) of phenylhydrazine and 5.05g (0.05 mole) of a-hy-
droxytetrahydropyran in 50 rnl of benzene was boiled on the water bath in a flask with a Dean- Stark trap
until the calculated amount of water had been evolved (0.8 ml). The benzene was evaporated off and the
residue was slowly heated under a reduced pressure of 130 rnrn in a current of nitrogen to 230~ for 1 h,
and was then distilled at a lower pressure. This gave 6 g of a substance in the form of an off with bp 197-
200~ (2 rnrn), yield 68%. Rf 0.62. UV spectrum: kma x 224, 280 nm; log e 4.46, 3.77. IR spectrum, cm -I,
3600, 3480 (OH, NH), 1615, 1600. 1500 (stretching vibrations of the nucleus) [2]. Found %- C 75.2: H 7.5.
CIiHI3NO. Calculated %- C 75.4. H 7.5.
7-Methylhornotryptophol. This was obtained similarly from o-tolylhydrazine. Yield 38~c. bp 200-
203~ (2 rnm). Found%: C 76.4-H 7.9. CI2HI5NO. Calculated%- C 76.2. H 8.0. Rf 0.59. UV spectrum:
kma x 222, 280. 290 nm: log a 4.39. 4.10. 4.01. IR spectrum, crn-i: 3580. 3280 (OH. NH)~ 1620. 1590. 1485
(stretching vibrations of the nucleus) [2].
5-Methylhornotryptophol. This was obtained similarly from p-tolylhydrazine. Yield 48.5%, bp 205-
215~ (2 rnrn), Rf 0.63. UV spectrum: krnax 227, 287, 297 nrn; log e 4.21, 3.63, 3.56. IR spectrum, em -I-
3480, 3360 (OH, NH). 1590, 1515, 1480 (stretching vibrations of the nueleus) [2]. Found %. C 76.4. H 8.0.
C12HI~NO. Calculated %: C 76.2- H 8.0.
N-Methylhornotryptophol. This was obtained similarly from N-methylphenylhydrazine. Yield 60%,
bp 175-178~ (I rnnrn), Rf 0.65. UV spectrum: krnax 226, 290 nrn: log e 4.46. 3.69. IR spectrum, ern-1:
3620 (OH), 1615, 1550, 1470 (stretching vibrations of the nucleus) [2]. Found %- C 15.7; H 8.1. CI2HIsNO.
Calculated %- C 76.2; H 8.0.
Tryptophol: This was obtained from a-hydroxytetrahydrofuran and phenylhydrazine. Yield 37%. bp
170-172~ (I rnrn): rnp 59~ [from benzene-petroleum ether (I : i)]. Rf 0.61. UV spectrum: kma x 224,
264, 280 nm: log ~ 3.71, 3.33, 3.24. IR spectrum, ern -i: 3585, 3385 (OH, NH), 1600, 1570. 1510. 1465
(stretching vibrations of the nucleus) [4]. Found %. C 74.9. H 6.9. Ci0HiINO. Calculated %. C 74.6: H 6.8.

LITERATURE CITED

1. R. A. Khrnel'nitskii, N. A. Klyuev, A. F. Dolgikh. T. P. Moskvina, and I. I. Grandberg, Izv. TSKhA,

No. 3, 192 (1973).
2. I. I. G r a n d b e r g and T. P. Moskvina. Khim. Geterotsikl. Soedin., 942 (1970).
3. I. I. Grandberg, Izv. TSKhA, No. 5, 188 (1972).
4. I. I. G r a n d b e r g and T. P. Moskvina, Khirn. Geterotsild. Soedin., 1366 (1972).

79
STRUCTURE AND REACTIVITY OF 3-HYDROXYPYRIDINE N-OXIDE

V. T. Grachev, B. E. Zaitsev, UDC 547.831.7 : 547.67

K. M. D y u m a e v , and L. D. Smirnov

It has b e e n e s t a b l i s h e d b y UV s p e c t r o s c o p y that 3 - h y d r o x y p y r i d i n e N-oxide in aqueous and

acid solutions exists in the f o r m of the conjugate acid, and in an alkaline m e d i u m in the
anionic f o r m : no b i p o l a r f o r m has b e e n detected in aqueous solution. Using H u c k e l ' s MO
LCAO method the indices of the ~r-electronic s t r u c t u r e have been calculated for v a r i o u s
+
f o r m s of 3 - h y d r o x y p y r i d i n e N-oxide. The values of the localization e n e r g i e s L r obtained
a g r e e with the e x p e r i m e n t a l l y o b s e r v e d sequence of electrophilic substitution in 3 - h y d r o x y -
p y r i d i n e N-oxide in acid and alkaline media.

It has been e s t a b l i s h e d by UV s p e c t r o s c o p y that 3 - h y d r o x y p y r i d i n e N-oxide (I) exists in ethanol [1] in

the f o r m of the f r e e b a s e (In)' and in an acid m e d i u m [2, 3] in the f o r m of the conjugate acid (Ic).
It has been shown by IR s p e c t r o s c o p y [4] that compound (I) in the c r y s t a l s t a t e exists in the f o r m of
the ion p a i r s (In ~ Ib).

la lb Ic Id

Electrophilic substitution in compound (I) t a k e s p l a c e in position 2 in an acid m e d i u m [5] and in p o s i -

tions 2 and 6 in an alkaline m e d i u m [6]. It has been e s t a b l i s h e d by PMR [7] that in the a c i d - c a t a l y z e d ex-
change of hydrogen in position 2, compound (I) r e a c t s as the f r e e base, but it is not known whether in f o r m
f~a) o r fib).
In the p r e s e n t work we have m e a s u r e d the UV s p e c t r a of compound {I) and its d e r i v a t i v e s in v a r i o u s
m e d i a (Table 1) and have calculated the indices of the ~r-electronic s t r u c t u r e by H u c k e l ' s MO LCAO
method [8].
In aqueous solution, 3 - h y d r o x y p y r i d i n e e x i s t s in the neutral and b i p o l a r f o r m s [9], which a r e c h a r -
a c t e r i z e d by l o n g - w a v e rr~rr* a b s o r p t i o n bands at 277 and 313 nm, r e s p e c t i v e l y . The rr ~ band, which
c h a r a c t e r i z e s the b i p o l a r form. is at a longer wavelength than the band c h a r a c t e r i s t i c for the anionic f o r m
(298 nm) in an alkaline m e d i u m . The UV s p e c t r a of compounds of type {I) (Table 1) in aqueous and acid
solutions a r e s i m i l a r to one another. This indicates the p r e s e n c e in aqueous solution of only the cationic
f o r m fic). In ethanolic and alkaline solutions b a t h o c h r o m i c shifts of the l o n g - w a v e ~r~ r * band a r e observed,
a v e r a g i n g 9 and 16 nm, r e s p e c t i v e l y . This can be explained by the loss of one. and then of another, proton
b y the conjugate acid {Ic). Thus, compound (I) and its d e r i v a t i v e s exist in t h r e e f o r m s in ethanolic, aque-
ous, and alkaline media: (Ia). (Ic), and (Id), r e s p e c t i v e l y . It follows f r o m the calculated values of the de-
l o c a l i z a t i o n e n e r g i e s f o r one rr electron, equal to 0.228, 0.216, and 0.234 B for f o r m s (Ia), (Ic), and {Id),
r e s p e c t i v e l y , t h a t t h e stabilities of the t h r e e f o r m s of compounds (I) a r e s i m i l a r . This is in h a r m o n y with
the c a s e of t r a n s i t i o n of compound ([) f r o m one f o r m to another. The lowest e m p t y and highest occupied
MOs calculated f r o m e n e r g y differences, of 1.68, 1.77. and 1.62 B and the values of Xmax for the l o n g - w a v e
rr ~ ~r* band at /3 = - 2 . 4 4 5 eV [10] for the f o r m s (Ia), (Ic), and (Id) a g r e e well with the e x p e r i m e n t a l values

S c i e n t i f i c - R e s e a r c h Institute of Organic I n t e r m e d i a t e s and Dyes. Institute of Chemical Physics.

A c a d e m y of Sciences of the USSR, Moscow. T r a n s l a t e d f r o m Khimiya G e t e r o t s i l d i e h e s k i k h Soedinenii.
No. 1, pp. 92-95, January. 1974. Original a r t i c l e submitted May 26, 1972.

9 19 75 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy o f this article is available from the publisher for $15.00.

80
 T A B L E 1. U V S p e c t r a of 3 - H y d r o x y p y r i d i n e N-Oxides

Com- ~. Medium ~-msx. nm

pound

Ethanol 224 244 262 302 3,56 3,75 3.97 2,98

Water 220 253 295 4,16 3,94 3.29
H' E 1 N fiC1 220 255 289
1 N KOH 234 3 I4
Ethanol 222 262 300 4,22 3,92 3'32
Water 220 254 295 4,23 3,87 3,40
CH3 H 1 N HCI 220 255 29t 3,92 3.42 3.66
I N KOH 235 316 4,34 3,75
Ethanol 222 257 307 4.19 3"90 3.38
Water 220 250 301 4,22 3,95 3,59
Ill H C: I /V HCI 220 252 295 4,05 3,57 3,63
1 N KOH 232 320 4,41 3'64
Ethanol 222 257 305 4,32 3"90- 3,38
Water: 220 251 300 4,32 3,92 3,56
IV CH~ CH~ 1 g HCI 220 251 297 3,93 3,27 3,74
I N KOH 232 320 4,43 3.75
Ethanol 244 265 310: 4,22 3.80 3,50
Water 222 255 302 4,26r 3,38 3,56
V t CsH~ I N HCI 220 302 4.20 4.00
1 N KOH 240 324 4,32 4.00
Ethanol 230 246 310 4.26" 4,31 3,75
Water 222 305 4.23 3.70
VI p-CHaCsH4 H 1 N HC1 222 305 4.28 3,83
1 /7 KOH 236 323 4,85 3,86
Ethanol 230 255 316 3,49 3A8 3,06
Water 222 248 306 4,29 4.07 3,72
VII p-CH~OC6H4 H I N HCI 222 305 4.27 3,83
l N KOH 235 329 4.26 3,78
Ethanol 245 312 4,34 3.69
Water 222 238 303 4.28 4A6 3,68
I!IA p-CICsH~ H I N HCI 222 238 302 4,16 4,00 3,68
1 ,V }(OH 237 323 4,36 3.85
Ethanol 230 242 312 4,20 4.31 3,74
Water 222 238 304
IX o-(CH3)2CHCsIL H" I N HCt 222 238 305
1 N KOH 236 323 4,36 3,86
Ethanol 220 265 305
Water 220 258 300
p-NO~C~H, H ' Y HCl 9 220 258 302
,v KOtl 237 258 315 3,96 3.73 3,4]
Ethanol 220 282 3.62 3"6b
Water 220 249 290 316 3,62 3,51 3,47 3,60
XI 3-Hydroxy-2-meth- 1 hr HCI 224 288 3.44 3,80
ylpyridine :V t(OII 220 245 306 3;42 3,90 3,72
Ethanol 300 4,15
3-Hydroxy-2-phen- Water 295 345 3,77 3,62
XII ylpyridine N HCI 245 317 4,02 4.36
; N KOH 252 322 3,91 4,06

o f X m a x . T h e v a l u e s o f t h e i o n i z a t i o n p o t e n t i a l s f o u n d f r o m t h e e n e r g i e s of t h e h i g h e s t o c c u p i e d M O s o f
0.738 a n d 0.887 /3 f o r f o r m s (Ia) a n d (Ic) a r e 8 . 6 0 a n d 9 . 0 0 eV. r e s p e c t i v e l y , a n d a r e c l o s e t o t h e i o n i z a t i o n
p o t e n t i a l o f p h e n o l (8.50 e V ) .
T h e l e n g t h of t h e C - - - C a n d C - - : N b o n d s c a l c u l a t e d f r o m t h e b o n d o r d e r s b y m e a n s o f t h e f o r m u l a s
o f D e w a r a n d M o r i t a a n d t h o s e o f t h e N - O b o n d f r o m G i i n t e r ' s f o r m u l a [12] a g r e e w i t h t h e k n o w n e x p e r i -
m e n t a l r e s u l t s f o r p y r i d i n e , p h e n o l , a n d t h e c o n j u g a t e a c i d of p y r i d i n e N o x i d e [13].
T h e c a l c u l a t e d v a l u e s o f t h e l o c a l i z a t i o n e n e r g i e s (L +) f o r c o m p o u n d (I) i n t h e f o r m s {Ia, e, a n d d)
g i v e a s e q u e n c e of e l e c t r o p h i l i c s u b s t i t u t i o n o f 2 > 6 > 4 > 5, w h i c h a g r e e s c o m p l e t e l y w i t h t h e k n o w n e x -
p e r i m e n t a l f a c t s f o r a c i d a n d a l k a l i n e m e d i a ( T a b l e 3). A t t h e s a m e t i m e , i t c a n b e s e e n f r o m T a b l e 3 t h a t
t h e c a l c u l a t e d ~r- e l e c t r o n i c c h a r g e s Q r a n d t h e l i m i t i n g e l e c t r o n d e n s i t i e s f r + d o n o t g i v e t h e e x p e r i m e n t a l -
l y o b s e r v e d s e q u e n c e o f e l e c t r o p h i l i c s u b s t i t u t i o n o f c o m p o u n d fi). T h i s l e a d s t o t h e c o n c l u s i o n t h a t t h e
e l e c t r o p h i l i c s u b s t i t u t i o n of c o m p o u n d {I) t a k e s p l a c e t h r o u g h t h e f o r m a t i o n o f a n i n t e r m e d i a t e ~ c o m p l e x ,
a n d n o t a v c o m p l e x . I t m u s t b e n o t e d t h a t t h e v a l u e s o f L + a n d Q r f o r t h e f o r m s (ia), (Ic), a n d (Id) s h o w

81
 T A B L E 2. 9 - E l e c t r o n i c C h a r g e s , Bond O r d e r s and L e n g t h s of t h e
F o r m s {Ia, c, and d) of 3 - H y d r o x y p y r i d i n e N - O x i d e
~o I. ~r-Electronic charge Bond Bond order (bond- length, ~)
~I la I Ic Id , Ia Ic Id
1 +0,123]' +0,168 +0,123 1--2 0,636 (1,334)- 0,647 (1,332) 0,639 (1,334)
3
2 -0,011i+0,026 -0,0261
+0029 +0,027 +0,033]
~_-~ 0,659
0,649
(1,397)
(I,399)
0,656 (1,397)
0,651 (1,398)
0,647 (1,399)
0,637 (1,401)
4 1-0022[ +0,006 -0,0361 4--5 0,665 (1,396) 0,667 (1,396) 0,668 (1,395)
5 -0,001 i - 0 0021 -0,00l ] 5--6 0,671 (1,395) 0,669 (1,395) 0,669 {1,395)
6 I -0,003 +0,037] -0,0161 1--6 0,633 (1,335) 0,644 (1,333) 0,631 (l,336}
7 i +0,039j +0,039[ +0,076i l--8 0,282 (1,368) 0,182 (1,406) 0,282 (1,368)
8 i +0,093I +0,041 I +,0,69313--7 0,197 (1,36l) 0,197 (I,361) 0,275 (I,350)

TABLE 3

Form l
No. of I O. t ~v + f,- f,~ .F, L; L,- II L,~
I atoms I
.

2 - 0,01l 0,045 0,170 0,I07 0,440 2,358 2,486 2,422

- 0,022 0,202 0,295 0,248 0,42l 2,394 2,522 2,458
-0,001 9,011 0,123 0,062 0,399 2,544 2,544 2,544
6 -0,003 0,137 0,044 0,090 O,431 2,374 2,504
L
2,439
2 -0,026 0,150 0,170 0,I10 0,432 2,482 2,544 I 2,513
Ic 4 +0,006 0,077 0,o00 0,188 0,417 2,516 2,5~0 ! 2,548
5 --0,002 0,080 0,088 0,084 0,399 2,542 2,542 i 2,542
6 +0,033 I 0,280 0,083 0,182 0,422 2,500 2,562 ~ 2,531
2 -0,026 0,010 0,I93 0,101 0,449 2,278 2,496 ] 2287
id 4~ --0,036 0,194 0,282 0,238 0,430 2,314 2,532 [ 2,424
--O,O01 0,022 0,i40 0,131 0,398 2,546 2,546 2,546
--0,016 0,220 0,031 0,130 0,435 2,310 2,530 2,420

t h e g r e a t e r r e a c t i v i t y of c o m p o u n d (I) in an alkaline m e d i u m than in an acid m e d i u m , which is a l s o in a g r e e -

m e n t with e x p e r i m e n t . T h e r e is no i n f o r m a t i o n in the l i t e r a t u r e on nucleophflic and r a d i c a l s u b s t i t u t i o n
r e a c t i o n s in c o m p o u n d (I). The r e a c t i v i t y i n d i c e s f o r n u c l e o p h i l i c substitution (Lr, Qr, a n d f r ) a n d f o r
r a d i c a l substitution (Lr~ a n d f r ~ and the f r e e - v a l e n c e index (Fr) f o r the r e a c t i o n c e n t e r s of f o r m s (Ia), {Ic),
and (Id) have b e e n c a l c u l a t e d and a r e given in T a b l e 3.

EXPERIMENTAL

C o m p o u n d s (V-X) w e r e obtained b y oxidizing the c o r r e s p o n d i n g b a s e s [14]. The UV s p e c t r a w e r e r e -

c o r d e d on a S F - 8 s p e c t r o p h o t o m e t e r . In the c a l c u l a t i o n we u s e d the C o u l o m b and r e s o n a n c e p a r a m e t e r s
w h i c h we found f o r 3 - h y d r o x y - 2 - p h e n y l p y r i d i n e [10] and an a u x i l i a r y inductive p a r a m e t e r f o r the n i t r o g e n
+
a t o m of hi = hs/10. The r e s o n a n c e p a r a m e t e r s R ~ _ O = 0.76 and R N _ O H = 0.68 w e r e found f r o m the v a l u e s
of k m a x f o r the l o n g - w a v e v--~r* a b s o r p t i o n band in the UV s p e c t r a of c o m p o u n d (I) in n e u t r a l and a c i d
m e d i a [10].

LITERATURE CITED

1. E. Shaw, J. A m e r . C h e m . Soc., 71, 67 (1949).

2. H . H . Jaffe, J. A m e r . C h e m . Soc., 7_.~7,4451 (1955).
3. J . N . G a r d n e r and E. Snell, J. Chem. Soc., 4375 (1957).
4. K . M . Dyumaev, G . N. Rodionova, and R. E. Lokhov, Khim. G e t e r o t s i k l . Soedin. (1974).
5. K. L e w i c k a and E. P l a z e k , R e c . T r a v . China., 7.88, 644 (1959).
6. K. L e w i c k a and E. P l a z e k , R o c z n . Chem., 40, 405 (1966).
7. G . P . Bean, P. J. B r i g n e l l , C. D. J o h n s o n , A. R. K a t r i t z k y , B. I. Ridgewell, H. O. T a r h a n , and A. M.
White, J. Chem. Soc., B, 1222 (1967).
8. E. S t r e i t w i e s e r , M o l e c u l a r O r b i t a l T h e o r y f o r O r g a n i c C h e m i s t s . W i l e y (1961).
9. D . E . M e t z l e r and E. Snell, J. A m e r . Chem. Soc., 77, 2431 (1955).
10. V . T . G r a c h e v , V. N. Kostylev, B. E. Zaitsev, V. I. K u z ' m i n , K. M. Dyumaev, and L. D. Smirnov,
T e o r e t . l~ksperim. Khim., 8, 224 (1972).
11. M . J . S . D e w a r and T. Morita, J. A m e r . Chem. Soc., 9-7, 796 (1969).
12. H. Giinter, B e r . , 103, 3370 (1970).

82
13. L . E . Sutton, Tables of Interatomic Distances and Configuration in Molecules and Ions, The Chemical
Society, London (1958).
14. L . D . Smirnov. V. I. Kuz'min, A. E. Zbarskii, V. P. Lezina. and K. M. Dyumaev, Izv. Akad. Nauk
SSSR, Set. Khim. (1974).

83
REACTION OF PENTACHLOROPYRIDINE N-OXIDE
WITH POTASSIUM HYDROGEN SULFIDE

S. D. Moshehitskii, G. A. Zalesskii, UDC 547.822.5'825.07

and A. F. Pavlenko

Depending on the conditions, the r e a c t i o n of pentachloropyridine N-oxide with potassium h y d r o -

gen sulfide leads to the N-oxide of the potassium salt of 3,4, 5 , 6 - t e t r a c h l o r o p y r i d i n - 2 - t h i o l o r
the dipotassium salt of 3,4.5-trichloropyridine-2,6-dithiol, which a r e converted by the action
of dimethyl sulfate into the corresponding methylthio derivatives. Oxidation of the l a t t e r has
given sulfones. It has been shown that for these sulfones,reactions with nucleophilic reagents
take place at the methylsulfonyl group and not at the chlorine atoms.

Continuing a study of sulfur-containing derivatives of polychloropyridines [1], we have investigated

the r e a c t i o n of pentachloropyridine N-oxide ([) with potassium hydrogen sulfide. In c o n t r a s t to pentachloro-
pyridine itself, which r e a c t s in ethanolic solution with potassium hydrogen sulfide at 50~ exclusively at
position 4 of the pyridine nucleus with the formation of 2 , 3 . 5 . 6 - t e t r a c h l o r o - 4 - m e r c a p t o p y r i d i n e [2], com-
pound (I) r e a c t s with p o t a s s i u m hydrogen sulfide to give two produc~s, depending on the t e m p e r a t u r e condi-
tions: at 0~ the N-oxide of the potassium salt of 3 , 4 , 5 , 6 - t e t r a c h l o r o p y r i d i n - 2 - t h i o l (II) is obtained, and
at 80~ the N-oxide of the dipotassium salt of 3,4, 5 - t r i c h l o r o p y r i d i n e - 2 . 6 - d i t h i o l (III). On acidification,
substances (II) and (III) give unstable products in which the N-oxide group is r e a d i l y reduced on r e c r y s t a l l i -
zation, giving, in the case of (II) di (3,4, 5, 6 - t e t r a c h l o r o p y r i d i n - 2-yl) disulfide mono- S- oxide (IV). The s t r u c -
t u r e of (IV) was shown by a m o l e c u l a r weight determination and by IR spectroscopy. Its It~ s p e c t r a lack an
absorption band at 1150 c m -1 c h a r a c t e r i s t i c for a sulfoxide group [3]. By the action of dimethyl sulfate,
(I!) and (III) w e r e c o n v e r t e d into 3,4, 5, 6 - t e t r a c h l o r o - 2 - ( m e t h y l t h i o ) p y r i d i n e N-oxide (V) and 3,4, 5 - t r i c h l o r o -
2,6-di(methylthio)pyridine N-oxide (VI). The oxidation of (V) with nitric acid or hydrogen p e r o x i d e in acetic
acid gave the N-oxide of methyl 3 , 4 , 5 , 6 - t e t r a c h l o r o p y r i d i n - 2 - y l sulfoxide (VII). Under the action of PC13,
the l a t t e r lost the two oxygen atoms attached to the nitrogen and sulfur atoms and gave 3,4, 5 , 6 - t e t r a e h l o r o -
2-methylthiopyridine (VIII): the r e a c t i o n of (V) with PC13 took place similarly. The action of phosphorus
t r i c h l o r i d e on (VI) yielded 3,4, 5-trichloro-2,6-di(methylthio)pyridine {IX). The oxidation of (V) and (VI)
with hydrogen peroxide in t r i f i u o r o a c e t i c acid gave the corresponding sulfones (X and XI), which lost the
N-oxide group u n d e r the action of PC13 with considerably g r e a t e r difficulty than (V) and (VI). The p r o -
longed heating of (X) with phosphorus t r i c h l o r i d e gave 3.4.5, 6 - t e t r a c h l o r o - 2 - m e t h y l s u l f o n y l p y r i d i n e (XII).
Attempts to" r e m o v e the oxygen atom of the N-oxide group in (XI) under the same conditions were
unsuccessful. [See s t r u c t u r e on top of next page.]
The p r e s e n c e of strong e l e c t r o n - a c c e p t i n g substituents and the N-oxide group in the pyridine nucleus
must strongly activate the 3-C1 and 5-C1 atoms with r e s p e c t to nucleophilic reagents, as o c c u r s in the c a s e
of the N-oxides of 3 - h a l o - 4 - n i t r o p y r i d i n e s , in which the halogen atoms a r e activated considerably m o r e
strongly than in the analogous compounds having no N-oxide group [4. 5]. However. we have established
that the action of nucleophilic reagents on (X) and ~ I ) leads to the r e p l a c e m e n t of the methylsulfonyl groups
and not of the chlorine atoms of the pyridine nucleus. Thus. the action of methylamine o r of an aqueous
solution of caustic soda on (X) gave the c o r r e s p o n d i n g N-oxides of 3,4, 5, 0 - t e t r a c h l o r o - 2 - ( m e t h y l a m i n o ) -
pyridine and of 3,4, 5.6--tetrachloro-2-hydroxypyridine (XIIt, XIV), and (XI) gave the N-oxides of 3,4, 5 - t r i -
chloro-2.6-di(methylamino)pyridine and of 3 . 4 . 5 - t r i c h l o r o - 2 . 6 - d i h y d r o x y p y r i d i n e (XV, XVI). When {XIV)
and (XVI) w e r e heated with phosphorus t r i c h l o r i d e , the corresponding known 3, 4, 5 . 6 - t e t r a c h l o r o - 2-hydroxy-

Institute of Organic Chemistry, Academy of Sciences of the Ukrainian SSR, Kiev. T r a n s l a t e d f r o m

Khimiya Geterotsiklicheskikh Soedinenii. No. 1, pp. 96--99, January, 1974. Original a r t i c l e submitted July 2. 1972.

9 19 75 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N.Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy of this article is available from the publisher for $15.00.

84
 CI El CI El

0 II ~-\ IV // VIII
I \\ \\~ //
Cl c1 9 \ o \ ~ o t // Cl l

0 0 0 0

IIX Vl III Y VlI

\ "\
cl ~ o Cl "x Cl

o 5 o 8
XV X1 XIII X
/
/ ./
s CI Ct GI "~ CI

o ,

.O-~N2"-OH .02%N2"-0. C~N-~-O. CI~O. CI~.N2"-SO.C.~

0 0
XVII| XVI XYll XIV XII

pyridine {XVII) [6] and 3,4, 5 - t r i c h l o r o - 2 , 6 - d i h y d r o x y p y r i d i n e (XVIII) [7] w e r e obtained: t h e i r f o r m a t i o n

shows the p o s i t i o n of the substitution of the chlorine a t o m s in the p y r i d i n e ring by m e r c a p t o groups in the
r e a c t i o n of (I) with p o t a s s i u m hydrogen sulfide.

EXPERIMENTAL
N-Oxide of the P o t a s s i u m Salt of 3, 4. 5, 6- T e t r a c h l o r o p y r i d i n - 2-thiol (II). A solution of 6.2 g (0.11
mole) of caustic p o t a s h in 500 m l of ethanol was s a t u r a t e d with hydrogen sulfide at 0~ for 2 h, and then,
with s t i r r i n g , 13.25 g (0.05 mole) of p e n t a c h l o r o p y r i d i n e N-oxide was added and the m i x t u r e was again
s a t u r a t e d with hydrogen sulfide at 0~ f o r 2 h. The t e m p e r a t u r e of the m i x t u r e was r a i s e d to 20~ and the
p r e c i p i t a t e was f i l t e r e d off and d i s s o l v e d in 750 m l of w a t e r at 60~ the f i l t r a t e was e v a p o r a t e d to d r y n e s s
in vacuum. Yield 10.5 g (70~c). Found ~c: S 10.2. CsC14NOSK. Calculated ~c: S 10.5.
N-Oxide of the D i p o t a s s i u m Salt of 3 , 4 . 5 - T r i c h l o r o p y r i d i n e - 2 , 6 - d i t h i o l (iII). A solution of 5.6 g (0.1
mole) of caustic p o t a s h in 250 m l of ethanol was s a t u r a t e d with hydrogen sulfide at 0~ for 2 h and then,
with s t i r r i n g , 2.7 g (0.01 mole) of p e n t a c h l o r o p y r i d i n e N-oxide was added. The r e a c t i o n m i x t u r e was
boiled f o r 1 h with the s i m u l t a n e o u s p a s s a g e of hydrogen sulfide through the m i x t u r e . The isolation of
compound (III) was s i m i l a r to that of (IT). Yield 2.9 g (85~c). Found %: S 18.7. CsC13NOS2K2. Calculated
~ : S 18.9.
D i ( 3 , 4 . 5 , 6 - t e t r a c h l o r o p y r i d i n - 2 - y l ) Disulfide Mono-S-oxide (IV). A solution of 2.6 g (0.01 mole) of
3,4, 5, 6 - t e t r a c b l o r o p y r i d i n e - 2 - t h i o l N-oxide in dioxane (or ethanol o r acetone) was boiled f o r 5 rain. The
p r e c i p i t a t e that had deposited was f i l t e r e d off, giving 2.3 g (92%) of (IV) with mp 225-227~ (from dioxane).
IR s p e c t r u m : 1080 c m -1 (SO). Found %: C1 55.5: S 12.7; tool. wt. 475. C10ClsN2OS 2. Calculated %: C1 55.5;
S 12.5: tool. wt. 512.
3,4, 5, 6 - T e t r a c h l o r o - 2 - ( m e t h y l t h i o ) p y r i d i n e N-Oxide (V). With s t i r r i n g at 20~ 7.6 g (0.06 mole) of
dimethyl sulfate was added d r o p w i s e to a solution of 9 g (0.03 mole) of (tI) in 500 m l of water, the m i x t u r e
being kept alkaline by the addition of 50% aqueous c a u s t i c soda. Then the r e a c t i o n m i x t u r e was s t i r r e d at
20~ for 2 h, and the p r o d u c t that had p r e c i p i t a t e d was f i l t e r e d off. Yield 8 g (95%), mp 138-139~ (from
ethanol). IR s p e c t r u m : 1165 c m - t (N--O). Found ~c: C1 50.9: S 11.8. C6H3C14NOS. C a l c u l a t e d % : C1 50.9:
S 11.5.
3,4, 5 - T r i c h l o r o - 2 , 6 - d i ( m e t h y l t h i o ) p y r i d i n e N-Oxide {VI). To a solution of 3.4 g (0.01 mole) of (HI)
in 50 m l of water, 5 g (0.04 m o l e ) of dimethyl sulfate was added dropwise. Isolation of the p r o d u c t in the
s a m e way as in the c a s e of compound (V) gave 2.8 g (96%) of (VI), m p 212-214~ (from dioxane). ~t s p e c -
t r u m : 1050 e m -1 (N-O). Found %: C1 36.5: S 22.2. CTHGC13NOS2. Calculated ~c: C1 36.7: S 22.0.

85
 3,4, 5, 6- T e t r a c b t o r o - 2 - (methylsutfinyl)pyridine N-Oxide (VII). A. A solution of 1.4 g (5 mrnotes) of
(V) in 2 - 5 m - l o - { ~ a - ~ ~42~ 1 - ~ w - ~ s k--~ ~ ' 2 ~ f-~, and was---~hen heated at 60~ for 15 rain. The
n i t r i c acid was eliminated by evaporation to d r y n e s s in vacuum, and the residue was t r e a t e d with water.
Yield 1.3 g (90%), mp 188-189~ (from aqueous dioxane). IR spectrum: 1150 (N-O), 1080 crn-~ (SO). Found
%: C1 48.1: S 10.7. CGH3C14NO2S. Calculated %: C1 48.1: S 10.9.
B. In drops. 5 m l of a 30% aqueous solution of hydrogen p e r o x i d e was added to a solution of 1.4 g
(5 mmoles) of (V) in 50 m l of glacial acetic acid and the m i x t u r e was kept at 20~ for 16 h. Then it was
diluted with w a t e r and the product was f i l t e r e d off. Yield 1.3 g (90%).
3 , 4 , 5 , 6 - T e t r a c h l o r o - 2 - ( m e t h y l t h i o ) p y r i d i n e (VIII). A. A solution of 0.6 g (2 mmoles) of (VII) in 50 ml
of absolute benzene was t r e a t e d with 1 m l of PC13, and the m i x t u r e was boiled for 30 rain. Then it was eva-
p o r a t e d in vacuum to dryness, and the r e s i d u e was t r e a t e d with water. Yield 0.5 g (96%). mp 100-101~
(from ethanol). Found %: C1 54.2: S 12.4. C6H3C14NS. Calculated 7c: C1 54.0: S 12.2.
B. Compound (VIII) was obtained f r o m (V) in a s i m i l a r m a n n e r to method A. Yield 87%.
3,4. 5 - T r i c h l o r o - 2 , 6-di (methylthio)pyridine (IX): This was obtained in a s i m i l a r m a n n e r to (VIII) by
method A. Yield 73%, mp 148-149~ (from heptane). Found%: C1 38.7: S 23.6. CTH6C13NS2. Calculated %:
C1 38.8,~ S 23.4.
3,4, 5, 6 - T e t r a c h l o r o - 2 - ( m e t h y l s u l f o n y l ) p y r i d i n e N-Oxide (X). With cooling, 5 ml (0.045 mole) of a
30% aqueous solution of hydrogen p e r o x i d e was added to a solution of 2.8 g (0.01 mole) of (V) in 50 m l of
t r i i l u o r o a c e t i c acid, and the m i x t u r e was kept at 20~ for 72 h. Then the bulk of the solvent was distilled
off in vacuum, and the r e s i d u e was diluted with water. Yield 2.9 g (93%), mp 182-183~ (from ethanol).
IR spectrum, cm-~: 1330 and 1145 (SO2), 1160 (N-O). Found 7c: C1 45.8: S 10.2. C6H3C14NO3S. Calculated
%: C1 45.7: S 10.3.
3,4, 5 - T r i e h l o r o - 2 , 6 - d i ( m e t h y l s u l f o n y l ) p y r i d i n e N-Oxide (XI). With cooling, 10 ml (0.09 mole) of 30%
aqueous hydrogen p e r o x i d e was added to a solution of 2.9 g (0.01 mole) of (VI) in 25 m l of t r i f l u o r o a c e t i e
acid, and the m i x t u r e was kept at 20~ for 48 h. Then the product was isolated in the same way as of).
Yield 3.4 g (96%), mp 212-213~ (from ethanol). IR spectrum, c m - I : 1330, 1150 (SO2). Found %: C1 29.7:
S 18.2. CTII6C13NOsS2. Calculated %: C1 30.0: S 18.1.
3 . 4 , 5 , 6 - T e t r a c h l o r o - 2 - ( m e t h y l s u l f o n y l ) p y r i d i n e ofII). A solution of 0.62 g (2 mmoles) of of) in 25 ml
of absolute benzene was t r e a t e d in l ml of PC13 and the m i x t u r e was boiled for 3 h. Then the solution was
e v a p o r a t e d i n v a c u u m , a n d t h e residue was t r e a t e d with w a t e r . Yield 0.5 g (85%), mp 165-167~ (from
heptane). Found %: C1 47.8t S 10.7. CsH3C14NO2S. Calculated %: C1 48.1: S 10.8.
3 , 4 , 5 , 6 - T e t r a c h l o r e - 2 - ( m e t h y l a m i n o ) p y r i d i n e N-Oxide ofIII). A solution of 0.3 g (1 mmole) of (X) in
25 ml of absolute dioxane was saturated with methylamine at 20~ for 15 rain. Then the solvent was dis-
tilled off in vacuum and the residue was t r e a t e d with water. Yield 0.25 g (95%), mp 166-167~ (from aque-
ous ethanol). Found %: C1 54.1: N 11.0. CGH4C14N20. Calculated %: C1 54.2: N 10.7.
3 . 4 . 5 . 6 - T e t r a c h l o r c - 2 - h y d r o x y p y r i d i n e N-Oxide (XtV). A m i x , are of 0.3 g (1 mmole) of Of) and 25
ml of a 2% aqueous solution of caustic soda was boiled for 15 rain and was then p a r t i a l l y evaporated under
r e d u c e d p r e s s u r e and acidified, and the p r e c i p i t a t e that deposited was filtered off. Yield 0.2 g (80%), mp
176-178 ~ (from heptane). According to the l i t e r a t u r e [8], mp 180~
3 . 4 . 5 - T r i c h l o r o - 2 , 6-di (methylamino)pyridine N-Oxide OfV). This was obtained f r o m (XI) in a s i m i l a r
m a n n e r to the p r e p a r a t i o n of (XIII). Yield 75%, mp 156-157~ (from aqueous ethanol). Found ~: C1 41.2:
N 16.1. CvHsCI~N30. Calculated %: C1 41.5: N 16.4.
3,4, 5 - T r i e h l o r o - 2 , 6-dihydroxypyridine N-Oxide OfVI).. This was obtained f r o m of I) in a s i m i l a r
m a n n e r to the p r e p a r a t i o n of (XIV). Yield 75%, mp 177-178~ (from heptane). Found %: C1 46.1: N 6.0.
CsH2C13NO~. Calculated %: C1 46.2: N 6.1.
3]4, 5 . 6 - T e t r a c h l o r e - 2 - h y d r o x y p y r i d i n e (XVII). This was obtained f r o m OfIV) in the same way as
(VIII) by method A. Yield 75%. mp 220-222~ (from ethanol). According to the l i t e r a t u r e [6], mp 224-225~
3.4, 5 - T r i c h l o r o - 2 . 6 - d i h y d r o x y p y r i d i n e (XVIII). This was obtained f r o m OfVI) in the s a m e way as
(VIII) by method A. Yield 78%. mp 190-191~ (from aqueous ethanol). According to l i t e r a t u r e [7], mp
193-195~

86
 LITERATURE CITED

1. S. D. Moshchitskii, G. A. Zalesskii, Ya. N. Ivashchenko, and L. M. Yagupol'skii, Khim. Geterotsikl.

Soedin.. 1094 (1972).
2. Netherlands Patent Application No. 6,516,409 (1966)i Chem. Abstr., 6_~5.18,564,
3. L. Bellamy, Infrared Spectra of Complex Molecules, 2nd ed., Methuen, London (1958).
4. T. Talik, Roczn. Chem., 3.~6, 1563 (1962).
5. T. Ta!ik and Z. Tatik, Roezn. Chem.. 4_.0.0,1675 (1966).
6. A. Roedig and K. Grohe. Bet.. 98. 923 (1965).
7. A. Roedig and G. M~rkl, Ann. Chem., 636, 1 (1960).
8. F, Binns and H. Suschitzky. J: Chem. Soe.. C. 1223 (1973).

87
SYNTHESIS OF 4-NORPYRIDOXINE
(3- HYDROXY- 5-HYDR OXYMETHYL- 2- ME THYLPYRIDINE)

V. P . C h e k h u n , E . N. Z v o n k o v a , UDC 547.823.824/722.3 o07:

M. I . S t r u c h k o v a , T. P. Belova, 543.422.25.6 : 542.942.4
and R. P. Evstigneeva

3 - H y d r o x y - 5 - h y d r o x y r n e t h y l - 2 - m e t h y l p y r i d i n e (4-norpyridoxine) has been synthesized by the

heterodiene condensation of 4 - m e t h y l - 5-propoxyoxazole and 5- ethoxy- 2 . 5 - d i h y d r o f u r a n - 2 - o n e
through the stage of 3 - h y d r o x y - 2 - methylpyridine- 5- carbaldehyde with reduction of the l a t t e r
by NaBH 4. One of the i s o m e r i c adducts has been isolated, and its s t e r e o c h e m i s t r y has been
established by PMR s p e c t r o s c o p y .

Recently, i n t e r e s t has i n c r e a s e d in 3 - h y d r o x y - 2 - m e t h y l p y r i d i n e s with various substituents in posi-

tions 4 and 5, which are vitamins B 6 and t h e i r s t r u c t u r a l analogs. Great possibilities for the building up of
such s t r u c t u r e s a r e opened up by the heterodiene condensation r e a c t i o n of 5-alkoxy-4-rnethyloxazoles with
various dienophiles [1].

NII~....~_../u " ~ / CH,P"~N/ r

(~C2He
t II Ill / IV
/ -
l

VI V
O
O%H7
9 LO%H ? ., I~ n~
C H ~ ltc e-3-.fq- ~.~_~o
// I
"~ .3.--T~o~:o.~
n~ He ~ -
1! C
lila

O ~\ 9c3n7
/UOC:,H7
C H ~ Hc C I I ~

N H
H!LIr
C~HsO'~HQ
Ill d
mb

M. V. Lomonosov Moscow Institute of Fine Chemical Technology. T r a n s l a t e d f r o m Khimiya

Geterotsiklicheskikh Soedinenii, No. 1, pp. 100-103, January, 1974. Original a r t i c l e submitted July 14, 1972.

9 19 75 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy o f this article is available from the publisher for $15.00.

88
 a

H HO ~ HiS

b { II
,~ 3 z , 3'. p p m

Hc
b I HI

3 ~ = e.5 H z
~= , HZ

5,75 5,00 3,75 ~,5o 3.2~ ~', p p m

Fig. 1. PMR s p e c t r u m of the adduct (IIIa): a) usual f o r m :

b) 1/5.

~,10-3' We have i n v e s t i g a t e d the heterodiene condensation of 4-

Z~
m e t h y l - 5 - p r o p o x y o x a z o l e (i) and 5 - e t h o x y - 2 , 5 - d i h y d r o f u r a n - 2 - o n e
21 ,/-~" (II), which is r e a d i l y f o r m e d by the p h o t o c h e m i c a l oxidation of
f u r f u r a l [2] and is an active dienophile. Thus, under mild condi-
tions a m i x t u r e of e q u i m o l e c u l a r amounts of (I) and (II) r e a c t s
with the f o r m a t i o n of the adduct (II[).
A f t e r p u r i f i c a t i o n and c r y s t a l l i z a t i o n , we isolated with a
yield of 32.4~c an adduet to which, on the b a s i s of its PMR s p e c -
t r u m (Fig. 1) s t r u c t u r e (iIIa) m a y be a s s i g n e d [3]. The endo con-
220 260 300 3/.0 380 k~ [tiT] f i g u r a t i o n of the adduct (IIIa) is c o n f i r m e d by the p r e s e n c e in the
Fig. 2. UV s p e c t r u m of 3 - h y d r o x y - 2 - s p e c t r u m of the signal of the p r o t o n H A in the f o r m of a doublet
m e t h y l p y r i d i n e - 5 - c a r b a l d e h y d e (IV): at 5.67 p p m (JAB = 4 Hz). The adducts (IIIa) amounted to m o r e
1) pH 12: 2} pH 8; 3) pH 6. 4) pH 2. than 60% of the m i x t u r e t a k e n for c r y s t a l l i z a t i o n . The n o n e r y s -
tallizing oil a p p a r e n t l y contained a g e o m e t r i c i s o m e r with a dif-
f e r e n t spatial a r r a n g e m e n t of H D (IIIb) and the two exo adducts
(lIIc and d), which a r e f o r m e d in s m a l l e r amount.
The a r o m a t i z a t i o n of the m i x t u r e of adduets t a k e s p l a c e in the p r e s e n c e of an acid without heating
and is a c c o m p a n i e d by the c l e a v a g e of the laetone ring and by d e c a r b o x y l a t i o n with the f o r m a t i o n of 3-hy-
d r o x y - 2 - m e t h y l p y r i d i n e - 5 - c a r b a l d e h y d e (IV). It is known that the adducts of the h e t e r o d i e n e condensation
of oxazoles with m a l e i c anhydride [4] and with diethyl f u m a r a t e [5] behave s i m i l a r l y , decarboxylation taking
p l a c e in position 4 of the p y r i d i n e nucleus. The 3 - h y d r o x y - 2 - m e t h y l p y r i d i n e - 5 - c a r b a l d e h y d e (IV) was c h a r -
a c t e r i z e d in the f o r m of the f r e e b a s e and in the f o r m of the Schiff's b a s e with p-phenetidine (VI). The IR
s p e c t r u m of the b a s e (IV) has an a b s o r p t i o n band at 1690 c m -~ due to the c a r b o n y l of the f o r m y l group [6].
A study of the e l e c t r o n i c s p e c t r a of compound (IV) enabled the mutual t r a n s i t i o n s of the ionic f o r m s with a
change in the pH of the solution to be e s t a b l i s h e d (Fig. 2) [7]. To d e t e r m i n e the n u m b e r of ionic f o r m s and
to e s t i m a t e pK a, we p e r f o r m e d s p e c t r o p h o t o m e t r i c t i t r a t i o n at t h r e e wavelengths (292, 312, and 354 nm}
(Fig. 3). As can b e s e e n f r o m the r e s u l t s given, in the pH r a n g e f r o m t to 12 t h e r e a r e two o n e - p r o t o n
t r a n s i t i o n s with pK a 4.5 and 8.0, which c o r r e s p o n d s to the e x i s t e n c e of t h r e e ionic f o r m s :

89
 D'
I -O~f~CHO"
,.4 ~Ka 4.G HO~j/CHO

'4
0,9 J . '~ .... Apparently, at pH 5-7, an equilibrium of the b i p o l a r ion
C,S~ with the uncharged f o r m exists, which p e r m i t s compound (IV)
to be isolated by e x t r a c t i o n at these pH values.
By reduction with sodium t e t r a h y d r o b o r a t e , the pyridine
0,5i
OA'4 (IV) was c o n v e r t e d into the 5-hydroxymethyl d e r i v a t i v e (V), the
0,3i s y n t h e s i s of which has been effected p r e v i o u s l y by different
0.21 ~,%,oo methods [5, 8]. The compound (V) obtained can be c o n s i d e r e d
0,I4 3 I : an analog of pyridoxine lacking the hydroxymethyl group in p o s i -
Oi 1 2 3 ~ 5 6 7 9 TO 11 12 13 14 p H tion 4 of the pyridine n u c l e u s - 4 - n o r p y r i d o x i n e - which is p h o s -
Fig. 3. Curves of the spectrophoto- p h o r y l a t e d by pyridoxal phosphokinase in the s a m e way as p y r i -
m e t r i c t i t r a t i o n of 3 - h y d r o x y - 2 - m e t h - doxal [9].
y l p y r i d i n e - 5 - c a r b a l d e h y d e (IV): 1) at
292 nm: 2) at 312 rim: 3) at 354 nm. EXPERIMENTAL

The UV s p e c t r a w e r e taken on a Hitachi E P S - 3 T i n s t r u -

m e n t at a concentration of 5" 10 -5 M. The s p e c t r o p h o t o m e t r i c
t i t r a t i o n in the pH r a n g e f r o m 1 to 12 was p e r f o r m e d at a concentration of (IV) of 2.2" 10 -4 M in 0.1 N HC104
with 4.0 N NaOH using a p H - m e t e r {glass electrode) on a SF-4A s p e c t r o p h o t o m e t e r . The PMR s p e c t r u m
was m e a s u r e d on a J N M - 4 H - 1 0 0 i n s t r u m e n t in CC14 solution with t e t r a m e t h y l s i l a n e as internal standard,
and the c h e m i c a l shifts a r e given in the 6 scale. The IR s p e c t r a w e r e taken on a P e r k i n - E l m e r 2 5 7 i n s t r u -
m e n t (in p a r a f f i n oil). T h i n - l a y e r c h r o m a t o g r a p h y was p e r f o r m e d on Silufol UV-254 in the ethyl a c e t a t e -
a c e t o n e - 2 5 % a m m o n i a (10 : 5 : 0.75) s y s t e m .
Adduct of 4--Methyl-5-propoxyoxazole with 5 - E t h o x y - 2 , 5 - d i h y d r o f u r a n - 2 - o n e (III). A m i x t u r e of 4.78 g
{0.034 mole) of 4 - m e t h y l - 5 - p r o p o x y o x a z o l e (I), 4.34 g {0.034 mole) of 5-ethoxy-2, 5 - d i h y d r o f u r a n - 2 - o n e (II),
and 50 ml of hydroquinone was kept at 18-20~ for 12 h. Then it was dissolved in 10 m l of d r y benzene and
was deposited on a column filled with 180 g of alumina of activity g r a d e IV. The s u b s t a n c e was eluted with
d r y benzene. After elimination of the solvent, 4.88 g {53.6~) of an oily s u b s t a n c e which c r y s t a l l i z e d on
standing was obtained. The yield of the adduct (IIIa) was 2.95 g (32.4~c). mp 69-70~ {from hexane). Found
%: C 58.1: H 6.9: N 4.9. CI3HI9NO5. Calculated %- C 58.0: H 7.1; N 5.2. IR s p e c t r u m , c m - l : 1780 (C=O):
1630 {C = N ) .
3 - H y d r o x y - 2 - m e t h y l p y r i d i n e - 5 - c a r b a l d e h y d e (IV). A m i x t u r e of 1.6 g (12.3 m m o l e s ) of (I), 1.45 g
(12.3 m m o l e s ) of (II), and 50 mg of hydroquinone was kept at 18-20~ for 12 h. Then it was dissolved in
30 m l of ether, and the solution was cooled to 0~ and was e x t r a c t e d with 150 m l of 5% h y d r o c h l o r i c acid.
The aqueous solution was t r e a t e d with sodium a c e t a t e to pH 6 and e x t r a c t e d with ether. The e t h e r and the
acetic acid w e r e driven off and the r e s i d u e was dried. Yield 0.55 g (35~c), m p 245-249~ (from ethanol).
R f 0.5. Found %-. C 61.2: H 5.1: N 10.3. CTHTNO2. Calculated %: C 61.3: H 5.1: N 10.2. Sehiff's b a s e
with p--phenetidine (VI): mp 226-230~ (from ethanol). Found %: C 70.0: H 6.3: N 10.9. C15Ht6N202. Calcu-
lated %: C 70.3: H 6.1: N 10.9. UV s p e c t r u m in ethanol, k m a x, nm (e 9 10-3): 228 {22.6), 341 {18.0). IR
s p e c t r u m , c m - l : 1625 (C=N): 1610, 1580, 1510 ( C = C , nucleus).
3 - H y d r o x y - 5 - h y d r o x y m e t h y t - 2 - m e t h y l p y r i d i n e Hydrochloride (V). With s t i r r i n g . 0.25 g 06.6 m m o t e s )
of sodium t e t r a h y d r o b o r a t e in 3 ml of w a t e r was added to a solution of 0.5 g (3.6 m m o l e s ) of (IV) in 25 ml
of methanol. The r e a c t i o n m i x t u r e was s t i r r e d f o r 30 rain and was evaporated, the r e s i d u e was t r e a t e d
with 12 m l of methanol, the solution was filtered, and the f i l t r a t e was evaporated. The r e s i d u e was d i s -
solved i n e t h e r , and the solution was s a t u r a t e d with hydrogen chloride. The p r e c i p i t a t e was s e p a r a t e d off.
The yield of the h y d r o e h l o r i d e (V) was 0.51 g (78%). mp3 169-170~ {from a m i x t u r e of ethanol and ether) [7].
R r 0.21. UV s p e c t r u m in 0.1 N HC1, k m a x, mn (~. 10- ).- 226 (3.5), 291 (9.9): in 0.1 N NaOH, k m a x, nm
(~. 10-3): 243 (7.35). 304 (6.0) [10]. IR s p e c t r u m , era-l: 3340-3330 (OH). 1630, 1530-1520.

90
 LITERATURE CITED
I. M. Ya. Karpeiskii and V. L. Florent'ev, Usp. Khim.i 3_~8,1244 (1969).
2. G.O. Sehenek, Ann., 64, 12 (1952).
3. T. Naito. K. Ueno. M. Sano. Y. Omura, I. Itoh, and F. Ishikawa, Tetrahedron Lett.. 5767 (1968).
4. R.A. Firestone, E. E. Harris, and W. Reutor, Tetrahedron. 23, 943 (1967).
5. T. Yoshikawa. F. Ishikawa, Y. Omura, and T. Naito. Chem. Pharm. Bull., 13, 873 (1965).
6. N.A. Drobinskaya. L. V. Ionova, M. Ya. Karpeiskii, and V. L. Florent'ev, Khim. Geterotsikl. Soedin..
356 (1971).
7. V.L. Florent'ev. N. A. Drobinskaya. L. V. Ionova, and M. Ya. Karpeiskii, Khim. Geterotsikl. Soedin.,
1028 (1969).
8. L.A. Perez-Medina. R. P. Mariella, and S. M. MeElvain, J. Amer. Chem. Soe., 69, 2574 (1947).
9. D.B. McComiek and E. E. Snell, J. Biol. Chem., 236, 2085 (1961).
10. R.W. Burd, V. W. Rodwell. and E. E. Snell, J. Biol. Chem.. 235, 1164 (1960).

91
PYRIDINIUM SALTS
I. REDUCTION OF 4-(BENZAZOL-2-YL)PYRIDINIUM SALTS
IN A NEUTRAL MEDIUM

P. P. Z arin', 1~. S. L a v r i n o v i c h , UDC 547.821.3:547.822.1

a n d A. K . A r e n

New 4-(benzazol-2-yl)pyridinium salts have been synthesized. T h e i r reduction in a neutral

medium with sodium t e t r a h y d r o b o r a t e has given 2- (1,2,5, 6 - t e t r a h y d r o p y r i d i n - 4-yl)benza-
zoles. The catalytic hydrogenation of the l a t t e r leads to piperidine derivatives which have
also been synthesized by an independent route.

Pyridinium salts are of i n t e r e s t as physiologically active substances, and they also provide the p o s s i -
bility of synthesizing p a r t i a l l y and completely hydrogenated piperidine derivatives which a r e inaccessible
by other routes. The reduction of pyridinium salts containing h e t e r o c y c l i c substituents has been studied
only for the c a s e of indolylpyridinium salts [1, 2]. In view of the physiological activity of a z o l - 4 - y l p y r i d i -
nium salts [3] and of hydrogenated pyridylindoles [4, 5]. it appeared of i n t e r e s t to obtain a s e r i e s of benza-
zolylpyridinium salts and to study t h e i r reduction.
The initial pyridinium salts (I-III) w e r e obtained by methods proposed in the l i t e r a t u r e [6, 7]. In
t h e i r UV spectra, the long-wave absorption band of the benzazolylpyridinium salts has undergone a bathe-
c h r o m i c displacement of 50-60 nm relative to the absorption band of the initial pyridinylbenzazoles. In
10 -3 M solutions of the iodides in chloroform, a weak CTC band [8] is found at 450 nm. In the PMR s p e c t r a ,
the signals of the a and B protons of the pyridine ring a r e shifted downfield by ~ 1 ppm in c o m p a r i s o n with
the initial b a s e s (in D20. ~ 9.5-8.45 ppm).
The reduction of the salts (I-HI) with sodium t e t r a h y d r o b o r a t e in a neutral medium (ethanol, water)
led in all c a s e s to 2 - ( 1 - R - 1 , 2 , 5 , 6 - t e t r a h y d r o p y r i d i n - 4 - y l ) b e n z a z o l e s (IV-VI. Table 2). The homogeneity of
the r e a c t i o n products was confirmed by t h i n - l a y e r chromatography. The p r e s e n c e of a conjugated double
bond in each of compounds ~IV-VI) is manifested in a bathochromic shift of the long-wave absorption m a x i m a
with r e s p e c t to the c o r r e s p o n d i n g benzazoles (~max 290-298 urn).

, ~

I-Ill IV-VI VII-IX

~,IV, Vll Z=O; II, V, Vtll Z=S; Ill,Vl, IX Z=Nii; X . - I , Br, CI; I - I g R-ME. CHIG~tt5.
CH2CH2C6H5, CH2CH~CHCoHs

In the PMR s p e c t r u m of compound {IVa) in CDC13 a doublet of the a ' protons is observed at 3.13 ppm
(J = 3.3 Hz), a multiplet of the a and B protons at 2.8-2.4 ppm, a b r o a d triplet for the B' p r o t o n at 6.76 ppm.
a multiplet of the a r o m a t i c protons of the benzoxazole s y s t e m at 7.7-7.0 ppm, and a N - C H 3 singlet at 2.26
ppm. Compounds (Va) (in CC14) and (Via) (in CD3OD) give s i m i l a r s p e c t r a .

Institute of Organic Synthesis. Academy of Sciences of the Latvian SSR. Riga. T r a n s l a t e d f r o m

Khimiya Geterotsiklicheskikh SoedineniL No. 1, pp. 104-107, January, 1974. Original a r t i c l e submitted
November 22. 1972.

9 19 75Plenum Publishing Corporation, 227 West 17th Street, New York, N.Y. 10011. No part of this publication may be reproduced,
stored in a relrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy of this article is availablefrom the publisher for $15.00.

92
 T A B L E 1. 4 - ( B e n z a z o l - 2 - y l ) p y r i d i n i u m Salts (I-III)
=- --'~] I Empirical Found, % ]Calculate< % ~
o'~ Z
Oc~ R 5~4 Mp,
X ~=~l Mn_
-r, "C
"C
- ] formula . . . . . "=
I ~ c . N x c H N x ~

q 7 cH3 - 3os-3o7,o,c
Ia* O ICHa !Br A i334--335 [C,,I-InBrN=O~ ~ , 7 1 9,3[~7,1 21
Ibt O IC2Hs ii A t265--268 ,C,4HIalN=O ~ , 4 t 8,9135,796
Ibt O IC=H5 !Br A ,247--248 iC,~H~zBrN=O~ " 5513'4~7~K5126~320
Ict 0 tCaH7 iBr a 249--250 IC,sH,sBrN20 ~ ~ {7125,2 45
Id I O i-c,ttv Br B [256--257 C sH 5BrN=O ~ ~ , 6 : 8 ' , 4 ; 9 1 811124~824
Ie] 0 IC,H9 l [B !240--243 IC,6HivlN20 ~ 4 , 4 1 7,4133,0 70
Iet O iC4H9 ~Br B 244--246 !C 8H rBrN~O ~ , ~ T A ~ k l 8,2124,027
Ifl 0 It-C~Ho Clt~ '3oo (de,c.)iC ~H ~C'lX~O ~ : 0 i 1 0 3 _ 1 _ . ~ 4I
IgI O iCsH,t !Br ~ ;235--236 !C~vH~gBrN20~ 5 1 , 5 ~ t4~9] 6[7t32,a46
]hi O C6HsCH2 ,I [ A 255--256 'CI.HI,IN20 ~ 6~. ' 4, ! ~3 ,' .\6~ ,~, , 5 ,,] , , ~ . ~a~
lhlO !C~HsCH2 Br A i256--258 ~C~,H]~BrN2032.114,117,6!21,7162,814,2t7.8121,5]94
thj O ~C6H~CH= CI i B i233--235 !C .d-t ~CLN=O70,7 4.71 8,7111,0',69,714,6 B,5 10,5178
Ill O ICgHI9 iBr ! B 200--201 C2~H2~BrN~O52,5~16,7 6,9!19,ff62,T~6,717,0120,2i41
Ij] O [CsH~CH~CH~ Bri A 303--304 C~oH7BrN~O530 45 7321(3633142 74 20552
Iki O !C~HsCH=CHCH.. C B 2!8--220 [C.lH 7C N20 72'3 49 8[0 10'2}72'1i4'417'91 915149
IIa S CHa " I A 256--257u C~aI-II~IN~S 44~131 7935',844',23'3 7',535,3i76
IIbl S C~HS I A 228--229 !C~4H~alN2S ]45,7i316':71634,545,21313!7,4134,0146
IIc! S ]CaHr i,Br A ',225--226 :C,sH,sBrNIS153,7!4,5:8,4:23;8'53,4]4,4!8,2123,548
IIdl S C4H, ~I ~ 1228--229 CI6H7IN~S 48514,3 7.1!32;0~8,3 4,0! 7,0 32;4 46
IIg I S: CsH I i ~ '235--236 CTH,slN=S 499!44 68 310'499143i 68306'63
ilh S !C6HsCH= ]CI iB 204--205 C,.H sCIN~S 6731415[8',31'J0:567',0',4218211010154
Ilia S ]C6H~CH~ iBv]A i229--300 Ci;H,sBrN2S 59,513,9~ 7.3[20,859,4 38 70'20,5166
IIj! S ICoHsCH=CHe ]Br A 1268--269 C=oH~TBrN~S60,5!4.3" 7,0 20 1590!4 11 6520,4160
IIIalNHCHa I IA;269--270 C~HzlNa 46.3:36'1251376!461135i124'37280
tlbNHC~Hs I IAI237--238 !Ct~H~4INa 47940d20] ' 147'8!3'8'11'61 ' i70
IIItZ NH]C.~H~ iBr i A i227--228 C~sH~6BrNz i5616!5'II13',2',25Ii56'3 5'3 12'91 69
IIte~NH]C4H9 Br B 150--151 C,6H~sBrN.~ 1578;5'5d2624'657'515'3i12'4~24059
IIIh NH CsHsCH2 'I A '247--248 C]g}'II6INz 15512'3191011i30',7'54',g'~3',810'.331',0'94
ItIhiNHIC6HsCH~ 'Br A 240m241 Ca,I-I~6BrNa 162.3141411,5 21,8~51~14.3 11,221,5 66
IIIhlNHCsH~CH~ CIlB 947--248 CgH~6CIN~ 70950130110705 49127113 59
jBr [C i 82-43 Cz H~sBrNa ,627i70 104 199825,7,0i10 I[19574
9 ," ' - ' : " : , , , , 9 , , ,

[lit NH C9H19
[IIjNHIC~HsCH=CH2 iBr A 1149---150 'C=oHsBrNa 1630 5011021052951~I10200194
II1k NH C~HsCH=CHCH. "C ! B :240--242 C= ttlsCiNa 72'5 5'2~12'010'279"0!5'0112'2! 9'8 a~
j - I ! ! '!' i 'i 'l"i'i 'I 'I ~

The c h a r a c t e r i s t i c t r i p l e t of the / 3 ' - p r o t o n s at 6 . 8 - 6 . 5 p p m is o b s e r v e d in all the P M R s p e c t r a of the

2- ( l - R - 1,2,5, 6-t err a h y d r o p y r i d i n - 4 - y l ) b e n z a z oles (IV- VI).
The c a t a l y t i c h y d r o g e n a t i o n of c o m p o u n d s (IVa-VIa) o v e r A d a m s c a t a l y s t gave the 2- ( 1 - m e t h y l p i p e r i -
d i n - 4 - y l ) b e n z a z o l e s (VII-IX). w h i c h w e r e a l s o obtained by the m e t h y l a t i o n of the 2 - ( p i p e r i d i n - 4 - y l ) b e n z a -
z o l e s {X-XII). The d i r e c t h y d r o g e n a t i o n of the p y r i d i n i u m s a l t s {I-III) t a k e s p l a c e with e x t r e m e difficulty.
w h i c h is e x p l a i n e d by the p o i s o n i n g of the c a t a l y s t . The r e p l a c e m e n t of the anion 1- b y C1- does not a c c e l e -
r a t e h y d r o g e n a t i o n . In the P M R s p e c t r a (X) (in CC14) , m u l t i p l e t s of the fi and /3' p r o t o n s at 2 . 4 - 1 . 5 ppm. of
the e, a ' . and T p r o t o n s at 3 . 3 - 2 . 4 ppm, and of the a r o m a t i c p r o t o n s at 7 . 7 - 7 . 0 p p m a r e o b s e r v e d . The
i n t r o d u c t i o n of a N - m e t h y l g r o u p (VII) is shown b y the a p p e a r a n c e of a signal at 2.2 p p m (CC14) without ap-
p r e c i a b l e c h a n g e s of the c h e m i c a l shifts of the s i g n a l s of the o t h e r p r o t o n s . The P M R s p e c t r a of c o m p o u n d s
(VIII-XlI) a r e analogous.
T h e t r e a t m e n t of c o m p o u n d (Ia) with p y r i d i n e - b o r a n e [9] and with l i t h i u m t e t r a h y d r o a l u m i n a t e led to
u n s t a b l e r e s i n s , while with s o d i u m t e t r a h y d r o b o r a t e in p y r i d i n e solution s t a b l e c o m p l e x e s of (IVa) and BH 3
w e r e f o r m e d . In the P M R s p e c t r u m (CDCla +CDaOD) a single signal of the N - C H a p r o t o n s (singlet at 2.15
ppm) is o b s e r v e d , w h i c h s h o w s the f o r m a t i o n of a s i n g l e i s o m e r , o b v i o u s l y the p r e f e r e n t i a l N - a x i a l c o m p l e x
of BH 3 [11]. R e d u c t i o n with s o d i u m t e t r a h y d r o b o r a t e in an alkaline m e d i u m led to the f o r m a t i o n of c o m p l e x
p r o d u c t s w h i c h will be d e s c r i b e d in a s e p a r a t e c o m m u n i c a t i o n .

EXPERIMENTAL

The P M R s p e c t r a w e r e t a k e n on a P e r k i n - E l m e r R - 1 2 A (60 MHz) i n s t r u m e n t . C h r o m a t o g r a p h y was

p e r f o r m e d -with a l u m i n a of a c t i v i t y g r a d e II a c c o r d i n g t o B r o e k m a n n .
4- ( B e n z a z o l - 2 - y l ) p y r i d i n i u m Salts (I-III, T a b l e 1). A. An e q u i m o l a r m i x t u r e of a 2- ( p y r i d i n - 4 - y l ) -
b e n z a z o l e and the a p p r o p r i a t e alkyl halide in a c e t o n e was h e a t e d in the w a t e r b a t h f o r 30 min. A f t e r cooling,
t h e p r e c i p i t a t e was s e p a r a t e d off and r e c r y s t a l l i z e d f r o m w a t e r .
B__a A n e q u i m o l a r m i x t u r e of a 2 - ( p y r i d i n - 4 - y l ) b e n z a z o l e and the a p p r o p r i a t e alkyl halide in d i m e t h y l -
f o r m a m i d e solution w a s h e a t e d ill a s e a l e d g l a s s tube at 95-100~ f o r 30 h. The s o l v e n t w a s e v a p o r a t e d off, :
and the r e s i d u e was w a s h e d with a c e t o n e and w a s r e c r y s t a l l i z e d f r o m w a t e r .

93
 T A B L E 2. 2- (1,2, 5, 6 - T e t r a h y d r o p y r i d i n - 4 - y l ) b e n z a z o l e s (IV-VI)

Calculated,
Empirical Found, %
Mp,2G* formula O
C I H N C H
V,
}
lVa O CHs 83--84 0,57 C,~H,4N2O" i 72.9[ 13,1172,4 6,5 12,7 72
IVb C~Hs 53--54 C.HIsN20 73,71 12,3173,6/ 7,0 11,9 71
IVc CsH7 83--85 0,63 CIsHI~N20 74,41 11,6174,11 7,1 11,2 88
lYd 0 i-CzHv 63--65 C15HlsN~O 74,41 II.,6174,11 7,1 11,2 75
IVe 0 C~H9 50--5l 0,82 C,~H~oN20 75,0/ 10,9' 74,71 8,0 t0,8 72
IVg C~Hti 48--49 CITH2~N20 75,5/ 10,4:75,51 8,2 1fl,4 75
IVi 0 CgH~ 75--76 C~,H~oN20 77,2| 8,6 77,1] 9,2 8,3 80
IVh O C6H~CH~ 135--136 0,71 C19HIaN~O 78,6] 9,6 78,81 6,2 9,7 69
C6H~CH2CH~]I21--122 0,79 C2oH~N~O 78,91 9,2 78,9/ 6,9 9,0 92
CHs 96--97 0,62 !C sH 4N25 67,81 12,2 67,9] 6,1 12,3 8t
Vb C~Hs 67--68 i 0,71 [C,4H~sN2S 68,8] 11,5 6921 63 1 t,6 91
Vc S C~H7 80--8! 0,75 [ C,~H,sN2S 69,71 10,8 70,11 7,2 I1,0 86
Ve S C~H9 52--53 0,78 Ct~H2oN~S 70,51 10,3 7051 7,5 10,5 76
Vg S C~H, 56--58 0,81 CtTH:~N2S 7t~51 9,8 7114 7,8 10,3 93
VIa C~H~CH~ 114--115 0,84 C19H2cN2S 74,51 9,1 74,5! 5,8 9,2 86
vj s C~HsCH~CH~ ll0--111 C2oH~oN2S 75,0j 8,7 74,7i 6,1 8,5 88
Via CH~ 222--223 0,46 CIsH,6N~ 73,6 19,8 73,41 6,5 19,5 95
VIb NH C~H~ 221"222 CI4H,7N3 74,0 18,5 73,5{ 7,4 18,2 91
VIe NH C~H7 200--201 0,60 CIsHIgN3 74,6 17,4 74.01 8,1 17,4 96
VIe NH C4H9 192--193 0,66 C16H21Ns 75,2 16,4 75,01 8,4 16,2 98
Vii NH C~HI~ I t51--152 0 C21HzINz 77,5 12,9 77,11 9,2 12,5 99
vIh NH C~H~CH~ 201--202 0,73 CIgHIgN3 78,8 14,5 78,7 6,6 14,5 80
VIj NH C~H~CH~CI-I~ 207--208 0,71 C2oH~INs t79,2 13,9 79,1 7,3 13,9 99

* C o m p o u n d s (IV, V, and VI) w e r e c r y s t a l l i z e d f r o m 50% a q u e o u s

methanol.
On a l u m i n a i n c h l o r o f o r m f o r c o m p o u n d s (IV) and (V) and in t h e
e t h a n o l - c h l o r o f o r m (3 : 97) s y s t e m f o r c o m p o u n d s {VI).

C__~. A n e q u i m o l a r m i x t u r e of a 2 - ( p y r i d i n - 4 - y l ) b e n z a z o l e and n o n y l b r o m i d e w a s h e a t e d in a s e a l e d
g l a s s t u b e at 95-100~ f o r 30 h. T h e r e a c t i o n p r o d u c t w a s w a s h e d w i t h a c e t o n e and r e c r y s t a l l i z e d f r o m
b e n z e n e . X m a x i n c h l o r o f o r m f o r c o m p o u n d (I) w a s 355 n m , f o r c o m p o u n d (11) 357 ran, a n d f o r c o m p o u n d
(III) 375 n m .
2-(1,2,5,6-Tetrahydropyridin-4-yl)benzazoles (IV-VI, T a b l e 2). In p o r t i o n s , 0.76 g (0.02 m o l e ) of
s o d i u m t e t r a h y d r o b o r a t e w a s a d d e d to a s o l u t i o n of 0.01 m o l e of a p y r i d i n i u m s a l t {i-III) in ~ 100 m l of
ethanol. The originally yellow-orange solution gradually became decolorized. The reaction mixture was
l e f t o v e r n i g h t and w a s t h e n f i l t e r e d a n d e v a p o r a t e d . C o m p o u n d s (IV) and (V) w e r e d i s s o l v e d in b e n z e n e
a n d t h e s o l u t i o n w a s - f i l t e r e d t h r o u g h a I - c m - t h i c k l a y e r of a l u m i n a and w a s e v a p o r a t e d . T h e r e a c t i o n p r o -
d u c t s c r y s t a l l i z e d on s t a n d i n g in t h e r e f r i g e r a t o r .
C o m p l e x of 2 - ( 1 , 2 , 5 , 6 - T e t r a h y d r o p y r i d i n - 4 - y l ) b e n z o x a z o l e w i t h BH 3, A s o l u t i o n of 3.37 g (0.01 m o l e )
of t h e s a l t (Ia) in 100 m l of p y r i d i n e w a s t r e a t e d w i t h 0.76 g (0.02 m o l e ) of s o d i u m t e t r a h y d r o b o r a t e . T h e
r e a c t i o n m i x t u r e w a s l e f t o v e r n i g h t , f i l t e r e d , a n d e v a p o r a t e d . T h e w h i t e c r y s t a l l i n e r e s i d u e of t h e c o m p l e x
w a s r e c r y s t a l l i z e d f r o m m e t h a n o l . Y i e l d 1.37 g (60%), m p 209-210~ F o u n d %: C 68.3: H 7.5: N 12.4.
C13H14N20. BH 3. C a l c u l a t e d %-. C 68.5: H 7.5: N 12.3.
2- ( P i p e r i d i n - 4 - y l ) b e n z o x a z o l e (X). A m i x t u r e of 68.0 g (0.5 m o l e ) of i s o n i p e c o t i n i c a c i d , 54.5 g (0.5
m o l e ) of o - a m i n o p h e n o l , a n d 200 m l o f p o l y p h o s p h o r i c a c i d w a s h e a t e d at 240-250~ f o r 30 rain. c o o l e d to
120~ and p o u r e d i n t o 1 l i t e r o f c o l d w a t e r , a n d t h e m i x t u r e w a s m a d e a l k a l i n e to pH 8. A n o i l s e p a r a t e d
out w h i c h r a p i d l y c r y s t a l l i z e d . T h e c r y s t a l s w e r e s e p a r a t e d off and d i s s o l v e d in c h l o r o f o r m , and t h e s o l u -
tion was filtered through a 1-cm layer of alumina. The chloroform was evaporated and the residue crys-
t a l l i z e d in t h e f o r m of s i l v e r - w h i t e c r y s t a l s . T h e y i e l d of (X) w a s 40.4 g (40%), m p 118-119~ F o u n d %:
C 71.0: H 6.8: N 13.5. CI2HI4N20. Calculated %: C 71.2: H 7.0: N 13.8.
2- (Piperidin-4-yl)benzo~hiazole(XI)was obtained similarly to (X) with a yield of 63%. Mp 100-102~
(from hexane). Found %: C 65.8: H 6.2: N 12.8. CI2HI4N2S. Calculated %: C 66.0. H 6.2: N 12.8.
2- (Piperidin-4-yl)benzimidazole (XII) was obtained similarly to (X) with a yield of 63%. Mp 262-264~
(from water). Found %: C 71.3: H 7.5: N 20.6. CI2HIsN3. Calculated %: C 71.6: H 7.5: N 20.9.
2- (1-Alkylpiperidin-4-yl)benzazoles (VII-IX). A. Compounds (IV-VI) were hydrogenated in ethanol
at room temperature and at atmospheric pressure with Adams catalyst. 2- (1-Methylpiperidin-4-yl)benzox-
azole (VIIa). mp 48-49~ (fromhexane). Found %: C 71.7: H 7.7: N 12.7. CI3HI6N20. Calculated %: C 72.2:
H 7.5: N 13.0. 2-(1-Benzylpiperidin-4-yl)benzoxazole (VIIh), m p 97-99~ (from h e x a n e ) . F o u n d %: C 78.1:

94
H 6.71 N 9.4. CIgH20N20. Calculated %: C 78.01 H 6.9~ N 9.6. 2- (1-Methylpiperidin-4-yl)benzimidazole
(IXa), mp 210~ (from hexane). Found %: 72.4: H 7.2: N 19.3. C13H17N3. Calculated %: C 72.8: H 7.5: N
19.6. 2- (1-Benzylpiperidin-4-yl)benzimidazole (IXh), mp 202-203~ (from benzene). Found %: C 78.2:
H 7.1: N 14.1. CIgHzlN3. Calculated %: C 78.3: H 7.3: N 14.4. 2-(1-Methylpiperidin-4-yl)benzothiazole
{V]/Ia). mp 73-74~ (from hexane). Found %: C 67.3: H 6.6: N 13.6. C~3HlsN2S. Calculated %: C 67.2:
H 6.9: N 13.8.
B.._~. Compounds (X-XII) were heated in dimethylformamide with equimolar amounts of methyl iodide
in the p r e s e n c e of a twofold excess of K2CO3 at 95-100~ for 30 h. The solutions were filtered and evapo-
rated. This gave compounds (VII-IX), identical with those obtained by method A. The yields of (VII-IX)
were 95%.

LITERATURE CITED
1. D. Bek and K. Schenker, Helv. Chim. Aeta, 5.~1, 260 (1968).
2. R. N. Schut, F. E. Ward, and O. J. Lorenzetti, J. Med. Chem., 13, 395 (1970).
3. G. E. Wiegand, V. J. Bauer, and S. R. Safir, J, Med. Chem., 12, 943 (1969).
4. V. J. Bauer, W. J, Fanshave, H. P. Dalalian, and S. R. Safir, J. Med. Chem., 1~1, 984 (1968).
5. Miles Lab., Inc., GFR Patent 1,901,637 (1969): Chem. Abstr., 7-2. 66,828 (1970).
6. K. Hideg and O. H. Hankovszky0 Acta Chim. Acad. Sci. Hung., 4-3, 263 (1963).
7. V. M. Zubarovskii and A. L Voronina, Zh. Obshch. Khim., 2.3, 1561 (1953).
8. J. W. Verhoeven, I. P. Dirx, and T. J. Deboer, Tetrahedron, 25, 4037 (1969).
9. R. P. Barnes, J. H. Graham. and M. D. Taylor, J. Org. Chem., 2-3, 1561 (1958).
10. M. Ferles, Coll., 24, 2221 (1959).
11. R. E. Lyle, E. W, Southwick, and J. J. Kaminsky, J. Amer. Chem. Soc., 9-4, 1413 (1972).

95
PYRIDINIUM SALTS
II.* REDUCTION OF 3-(BENZAZOL-2-YL)PYRIDINIUM SALTS

P. P. Zarin', E . S. L a v r i n o v i c h , UDC 547.821.3 : 547.822.1

and A. K. Aren

The catalytic hydrogenation and the reduction with p y r i d i n e - borane of N-alkyl-3- (benzazol-
2-yl)pyridinium salts gives piperidine derivatives; other reducing agents a r e unsuitable.

Continuing an investigation of benzazolylpyridinium salts, we have synthesized 3- (benzazol- 2- yl)pyri-

dinium salts (I-III. Table 1) by methods d e s c r i b e d p r e v i o u s l y [1]. In the UV s p e c t r a of (I-III), the long-wave
absorption band was o b s e r v e d in the 322-332 n m region. The bathochromic shift of the maximum of the
long-wave absorption of the salts {I-III) r e l a t i v e to the f r e e b a s e s amounted to ~ 20 nm. In the case of the
4-substituted pyridinium salts, a g r e a t e r shift was found b e c a u s e of the conjugation of the pyridinium ring
with the benzazole a r o m a t i c s y s t e m [1]. As in the case of 4- (benzazol-2-yl)pyridinium salts, in c h l o r o f o r m
solutions (10-3 M) of the iodides (Ia-IIIa) a weak CTC absorption band is found at about 450 nm [2].
With sodium t e t r a h y d r o b o r a t e , the 3- 0oenzazol-2-yl)pyridinium salts (I-III) cause an intense red
coloration of the reaction mixture. B r i g h t l y - c o l o r e d resinous products a r e f o r m e d which cannot be c r y s -
tallized. It m a y be assumed that the reduction takes place through 1,4-dihYdropyridine derivatives, which
a r e unstable [3] and are rapidly oxidized. In the c a s e of (Ia), n e v e r t h e l e s s , it was possible to obtain a
c r y s t a l l i n e derivative of 1.2.5,6-tetrahydropyridine (IVa). The s t r u c t u r e of (IVa) was c o n f i r m e d by the
p r e s e n c e of a c h a r a c t e r i s t i c signal of a vinyl p r o t o n 5 6.98 ppm in the PMR s p e c t r u m . Attempts to r e d u c e
compounds (I-HI) by F e r l e s ' method with lithium t e t r a h y d r o a l u m i n a t e led to unstable r e s i n s .
P y r i d i n e - b 0 r a n e has b e e n u s e d successfully in the reduction of carbonyl compounds [5]. The t r e a t -
ment of (Ia,f, g-IIIa, f, g) with p y r i d i n e - b o r a n e g a v e a m i x t u r e of two products in each case. The PMR
s p e c t r a of the reduction products showed the predominance in each m i x t u r e of the piperidine derivative
~-~).

* F o r Communication I, s e e [1].

F-Ill ~.~ vii a,f,g -IX a,f,g Iv a,f,g -vl a,f,g

N ~ ~-NH2 ".,.,N~J

X~XI H Xll

i-ll R-AII~ CH2CsHl, CH2Clt2C6H$, CHs--CmC, CH2:CHCH2; I. IV, VII, X Z~O;

II,V, VIII, XI Z : S ; IIl,Vl, I I Z-NH, X : I , Br, CI

Institute of Organic Synthesis of the Academy of Sciences of the Latvian SSR, Riga. T r a n s l a t e d f r o m
Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 108-111, January, 1974. Original a r t i c l e submitted
November 22, 1972.

9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

96
 T A B L E 1. 3- ( B e n z a z o l - 2 - y l ) p y r i d i n i u m Salts (I-II1)

| ,~ x Mp,~ ] Empirical Found, % Calculated, % ~'~

g
formula

ht~ CHa I295-- CIaHnlN20

_296~:s
8I
~bl o
]r 0 CaH~
c/., ~t
[,
254--255 i,C:4HlalN~O
175--I77 C~HIsiN~O
87
42
Ic] O C~H~ ] Br 194--195 ClsHlsBrN20 75
9 Id 1 0 C~H~ [I 157--159 Ct6HITIN20 79
I.c| 0 CsHn !I 160~162 CITHIgIN20 63
~fl o C~H~EH~ IBr 235--238 CtgHIsBrN20 94
C~H~CH~CH~ Br 230 CmHIzBrN20 59
s~ 215-- CIaHnlN~S 88
--2i67'8
Ilbt S C~Hs ]I t 228 --229C.HIaIN2S 92
IIe~ S Call7 i Br [ 199--281 CIsHjsBrN2S 74
Id S C,H~ i I 1 188--t89 CIaHldN2S 83
lie I S CsH,, I I ] 179--180 iClqt alN2S 69
Hfl s C~H~CH~ ] Br / 213--214 C '~HsBrN2S 95
IIg/ S C~HsCH~CH~] Br 281--232 'C2oH~7BrN,S 48
nhl s C~HI2 B r 145--146 IC21H2TBrN2S 70
74
IIil S CHaCH---~C CI 131--132 IG15H12CIN28
Ilj] S C~H,z I 122--123C~aH211N~S 29
l'Ik/ S CH==CHCH~ I 198~199 ICIsHxaIN2S 87
IIla[ ~H CHa I 246--247 CIaH~INa 96
lllb ~HIC~Hs I ~53--~54 C~H~INa 77
IIlcl ~HICaH~ Br 256--~57 C~aFI~BrN~ 56
}C~H~ l 2'20--221 C~6H~sIN~ 64
IIIdl ~HIC~H~ Br 287--288IC~H~sBrNa 50
IIleiNH CsH. I 213--214 :C~?H~INa 94
i i ~fINH CsHsCH~ Br 225--227 C~gHIsBrNa 83
IIIg]NH C~HsCH~CHa Br 254--256 iCaoH~BrNa 72
IIIhlNH C~H~s Br 170--172 iC~IH~sBrN~ 62

F o r example, in the PMR s p e c t r u m of the p r o d u c t of the r e d u c t i o n of c o m p o u n d (IIa) all the s i g n a l s

c h a r a c t e r i s t i c f o r {VIIIa) o b t a i n e d b y independent s y n t h e s i s w e r e o b s e r v e d , and a l s o a weak s i g n a l of a
vinyl p r o t o n at 6.98 p p m , which shows the p r e s e n c e of O r a l The a m o u n t s of t e t r a h y d r o p y r i d i n e s in the
m i x t u r e s v a r i e d b e t w e e n 5 and 10%.
T h e b e n z o t h i a z o l e d e r i v a t i v e s (II) could not be c a t a l y t i c a l l y r e d u c e d , while c o m p o u n d s (Ia, g and IIIa, e)
on c a t a l y t i c r e d u c t i o n (Pt) g a v e the p i p e r i d i n e d e r i v a t i v e s WIIa, g: IXa, f).
To c o n f i r m t h e s t r u c t u r e s of the r e d u c t i o n p r o d u c t s , c o m p o u n d s (VIIa. VIIIa, f) w e r e a l s o obtained b y
the alkylation of the c o r r e s p o n d i n g 2- ( p i p e r i d i n - 3 - y l ) b e n z a z o l e s 0:, XI) as d e s c r i b e d p r e v i o u s l y [1]. The
r e a c t i o n b e t w e e n n i p e c o t i n i c a c i d and o - p h e n y l e n e d i a m i n e led to the f o r m a t i o n of the a m i d e (XII). On sub-
s e q u e n t h e a t i n g with p o l y p h o s p h o r i e acid, no c l o s u r e of the r i n g took p l a c e . Thus, only r e d u c t i o n with
p y r i d i n e - b o r a n e followed by c a t a l y t i c h y d r o g e n a t i o n gives an u n a m b i g u o u s p a s s a g e f r o m p y r i d i n i u m salts
to p i p e r i d i n e d e r i v a t i v e s .

EXPERIMENTAL

The P M R s p e c t r a of s o l u t i o n s in CC14 w e r e r e c o r d e d on a P e r k i n - E l m e r R - 1 2 A (60 MHz) i n s t r u m e n t

u s i n g t e t r a m e t h y l s i l a n e as i n t e r n a l s t a n d a r d .
T h e 3- ( b e n z a z o l - 2 - y l ) p y r i d i n i u m s a l t s (Table 1) w e r e obtained as d e s c r i b e d p r e v i o u s l y [1] and w e r e
recrystallized from water.
2 - ( t . 2 . 5 . 6 - T e t r a h y d r o p y r i d i n - 3 - y l ) b e n z o x a z o l e (IVa); A s o l u t i o n of 3.37 g (0.01 m o l e ) of the salt (Ia)
in 30 m l of ethanol and 30 ml of w a t e r was t r e a t e d with 0.76 g (0.02 mole) of s o d i u m t e t r a h y d r o b o r a t e . A
v i g o r o u s r e a c t i o n b e g a n and the r e a c t i o n m i x t u r e a c q u i r e d a r e d - o r a n g e c o l o r . It was left o v e r n i g h t and
the s o l v e n t w a s e v a p o r a t e d off. The r e s i n o u s r e s i d u e was t r e a t e d with a 30% s o l u t i o n of h y d r o c h l o r i c acid.
The solution w a s f i l t e r e d t h r o u g h a l a y e r of a c t i v e c a r b o n , and 30% alkali w a s added to pH ~ 9 . The oil that
s e p a r a t e d out solidified on standing. C o l o r l e s s c r y s t a l s with mp 64~ (from 507c ethanol). Yield 0.43 g
(20%). Found % : C 72.5: H 6.5. N 12.7. Ct3Ht4N20. C a l c u l a t e d %: C 72.4: H 6.5: N 12.7.
2- ( 1 - R - l > i p e r i d i n - 3 - y l ) b e n z a z o l e s (IVa, f, g - V i a , f, g: Table 2). A. To a solution of 0.01 m o l e of a
p y r i d i n i u m salt (Ia, f, g-IIIa, f, g) in a m i x t u r e of 30 m l of methanol and 30 m l of glacial acetic acid was
added 7.44 g (0.08 m o l e ) of p y r i d i n e - b o r a n e [6] andthe m i x t u r e was heated at 95-100~ for 24 h and was
then evaporated, and the r e s i d u e w a s d i s s o l v e d in h y d r o c h l o r i c acid (1 : 1). The solution w a s t r e a t e d with
carbon, n e u t r a l i z e d with alkali, and e x t r a c t e d with ether. The extract was dried with s o d i u m sulfate and

97
 TABLE 2. Hydrochlorides of 2- (1-R-l>iperidin-3-yl)benzazoles
(VII-IX)
Empirical h Fouad~% [ Calc., % ]Yield. % .
Corn-I z rap. :c_t formula t B['. _
pound*l _ l
Vlta 1 0 CH3 280--283 C~HI6N20.HCI 61916,6/111,3 61,8 6,8 ll,1
(300*) 611716,5111,4161,8 6,8 I1,11 175[89
V11f/ O CsHsCH2
VIIg 228--232 C,0HIsN~O.HCI 69,516,3/ 8,51 69,416,4l 8,5121] |
C6H,CH2CH~221--225 C20H22N~O9HCI 70,316,6] 8,1170,tl6,8 8,2251 t
(255--257*) 70,216,6] 8,2 zo,116,81 8,21 17019o
VIIIa S CH8 238.--241 :13HtTN~S'
HCI 58,315,4 10,4 58,1~6,4|10,4165[ |
(204*) 58,ff6,21102158,1t 6,4] 10,41 I 173
VIIIf! S C6HsCH2 233--236 C19H20N2S'HCI 66,2 5,9 8,0 66,2)6,1/ 8,1144
(207*) 65,g 6,1[ 8,o166,2[6,11 8,11 t 169
VIIIg S CsHsCH2CHa 235--238 C2oHz~N2S'HCI 67,0 6,1 7,8!66,916,5 7,8148] t
IXalNHCHs 270--273 C13HIdqs.2HC1 54,4 6,2 14,6: 5~ 2! 6 61 14,61211 /
(283--285*) 54,3 6,7114,4i ~4,2i 6,5114,61 ~821
IXf NH C6HsCH2 210--213 C19HstNz-2HC1 62,5 6,0111,6162,6 i 6,4111,5 19!
(220--223*) 62,5 6,3 11,51626E6,4111,5[ 79t
IX g NHC6HsCH2CH2 260--262 C~H2aN3-2HCI 63,2 6,4 ll,O 63,516,7! 11,li211 1

*According to the PMR spectra, samples of the hydroehlorides ob-

tained by method A) contained about 5% of the hydroehlorides of the
corresponding 2- (l-R-1,2, 5, 6 - t e t r a h y d r o p y r i d i n - 3 - y l ) benzazoles.
The melting points of t h e s e samples a r e shown in p a r e n t h e s e s .
The 2 - ( 1 - R - p i p e r i d i n - 3 - y l ) b e n z a z o l e hydroehlorides w e r e r e c r y s -
tallized f r o m isopropanol.

was saturated with HC1. The p r e c i p i t a t e of a m i x t u r e of hydrochlorides of (VII-IX) and {IV-VI) was f i l t e r e d
off and was r e c r y s t a l l i z e d f r o m isopropanol.
B. A pyridinium salt (Ia, g: IIIa, f) (5 mmoles) in 40 ml of 25% aqueous methanol was hydrogenated at
r o o m te---mperature and atmospheric p r e s s u r e with Adams catalyst.
C. The alkylation of (X) and (XI) by a method we have d e s c r i b e d p r e v i o u s l y [1] gave (VIIa- HC1) and
the h y d r o c h l o r i d e s of (VIIg) and of (VIIIa, f), identical with those d e s c r i b e d above.
Hydrochloride of 2- (Piperidin-3-yl)benzoxazole (X. HC1). The condensation of o-aminophenol with
nipecotinic acid was p e r f o r m e d as d e s c r i b e d f o r isonipecotinic acid [1]. The base was extracted with ben-
zene, the solution was f i l t e r e d through alumina (1 cm), and HC1 was p a s s e d in. The yield of h y d r o c h l o r i d e
was 60%. mp 267-268~ Found %: C 60.3: H 6.9: N 11.9. C12Hi4N20.HC1. Calculated %: C 60.4: H 6.3;
N 11.7.
The hydrochloride of 2- (piperidin-3-yl)benzothiazole (XI 9HCI) was obtained in a similar manner to
(X.HCI). Yield 30%. mp 226~ Found%: C 56.4. H 6.0-N10.6. C12HI4N2S'HCI. Calculated %: C 56.6:
H 5.9: N 11.0.
o-Aminoanilide of Nipecotinic Acid (XII). A mixture of 32.5 g (0.25 mole) of nipeeotinic acid, 27.0 g
(0.25 mole) of o-phenylenediamine, and 100 ml of polyphosphoric acid was heated at 240-250~ for 30 mill.
After cooling to 120~ the mixture was poured into 500 ml of cold water and the mixture was made alkaline
with concentrated caustic soda to pH 8. An oil separated out which rapidly solidified. This gave 27.0 g
(54%) of (XII), mp 242-243~ (from water). Found %: C 65.4: H 7.6: N 18.9. CI2HITN30. Calculated %:
C 65.7. H 7.8. N 19.2.

LITERATURE CITED

1. P. P. Zarin'0 ]~. S. Lavrinovieh, and A. K. Aren, Khim. Geterotsikl. Soedin., 104 {1974).
2. J. W. Verhoeven, I. P. Dirk, and T. J. Deboer, Tetrahedron, 25. 4037 {1969).
3. K. Wallenfels. M. Gellrich, and M. Dubowitz, Ann. Chem.. 621. 137 {1959).
4. M. F e r l e s , Coll., 24, 2221 (1959).
5. R. P. Barnes, J. H. Graham, and M. D. Taylor, J. Org. Chem.. 23, 1561 {1958).
6. M. D. Taylor, L. R. Grant, and C. A. Sands, J. A m e r . Chem. Soc., 77, 1506 {1955).
7. K. Hideg and Q. H. Hankovszky, Acta Claim. Acad. Sci. Hung., 43, 263 {1963).
8. V. M. Zubarovskii and A. I. Voronina. Zh. Obsheh. Khim.. 23, 140 {1953).

98
PYRIDINIUM SALTS

III.* ALKYLATION OF 2- (PYRIDIN-2-:YL)BENZAZOLES

P. P. Z arin', I~. S. Lavrinovich. UDC 547.821.3 : 547.822.1

and A. K. Aren

The r e a c t i o n of 2 - ( p y r i d i n - 2 - y l ) b e n z o x a z o l e and 2 - ( p y r i d i n - 2 - y l ) b e n z o t h i a z o l e with m e t h y l

iodide f o r m s the c o r r e s p o n d i n g p y r i d i n i u m s a l t s . In the c a s e of 2 - ( p y r i d i n - 2 - y l ) b e n z i m i d -
azole, the i m i d a z o l e ring is q u a t e r n i z e d f i r s t , and only then the pyridine ring. The catalytic
hydrogenation of 2 - { b e n z o x a z o l - 2 - y l ) - l - m e t h y l p y r i d i n i u m s a l t s gives 2 - ( 1 - m e t h y l p i p e r i d i n -
2-yl)benzoxazole.

It has b e e n c o n s i d e r e d [2] that 2- ( p y r i d i n - 2 - y l ) b e n z a z o l e s a r e not capable of f o r m i n g q u a t e r n a r y p y -

r i d i n i u m salts, since they p o s s e s s a low b a s i c i t y . However, by the prolonged heating of 2 - { p y r i d i n - 2 - y l ) -
b e n z o x a z o l e (Ia) and of 2 - ( p y r i d i n - 2 - y l ) b e n z o t h i a z o l e (ib) with methyl iodide in d i m e t h y l f o r m a m i d e we have
s u c c e e d e d in obtaining 2- 0oenzothiazol-2-yl)-l-methylpyridiniu_m s a l t s (IIa, b). The PMR s p e c t r u m of (IIa)
in CD3OD+D20 showed the singlet of t h e N - C H 3 protons at 4.84 ppm, a doublet of doublets at 5 9.16 p p m
f o r the a proton, and multiplet of the /~ p r o t o n with its c e n t e r at 824 p p m ( J a B = 6.4 Hz), a multiplet of the
and fl' p r o t o n s at 8.8 ppm, and a multiplet of the benzoxazole p r o t o n s at 8.05-7.25 ppm. In the PMR
s p e c t r u m of (lib) a singlet of the N - C H 3 protons was o b s e r v e d at 4.54 ppm, a doublet of doublets with ~ 9.14
p p m of the a proton, a multiplet of the B p r o t o n with its c e n t e r at 8.6 ppm, and a multiplet of the benzo-
thiazole p r o t o n s at 8.2-7.5 p p m .

, Z 9

CHa CH.~
I a-C Ila, b Ya-c
[CH,I K2COs[CH3I

HI ~ CHa 7. [8~]~ ~

VJ VII IV b, C
1,11, V a Z=O; I, II, IV, Vb Z=S; I, IV, Vc Z=NH

In c o n t r a s t to compounds (Ia and b), 2- ( p y r i d i n - 2 - y l ) b e n z i m i d a z o l e (Ie) g i v e s a m i x t u r e of the s a l t s

(III) and (IV) with m e t h y l iodide even at an e q u i m o l e c u l a r r a t i o (1 : 1) of the r e a c t a n t s . Since the alkylation
of (Ic) obviously begins with the i m i d a z o l e ring, it is i m p o s s i b l e to obtain compound (IIc) by the atkylation
of (ic).
The PMR s p e c t r u m of (VI) in CD3OD showed a singlet of the N - C H 3 protons of the i m i d a z o l e ring at
3.99 ppm, a doublet of doublets of the a proton with ~ 8.91 ppm. a multiplet of the /~/~'~ protons with its

* F o r C o m m u n i c a t i o n II, see [1].

Institute of Organic Synthesis, A c a d e m y of Sciences of the Latvian SSR, Riga. T r a n s l a t e d f r o m

K h i m i y a G e t e r o t s i k l i c h e s k i k h Soedinenii. No. 1. pp. 112-114, January. 1974. Original a r t i c l e submitted
O c t o b e r 22, 1972.

9 19 75 Plenum Publishing Corporation, 22 7 West 1 7th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy of this article is available from the publisher for $15.00.

99
c e n t e r at 8.15 ppm (JaR = 4.5 Hz) and a multiplet of the benzimidazole protons at 7.85 ppm (6H). The
signals of the protons of the benzimidazole and pyridine rings a r e shifted by 1 ppm downfield as c o m p a r e d
with the pyridinylbenzimidazole {Ia), since, obviously, the positive charge is delocalized over the whole
molecule.
In the PM_R s p e c t r u m of the b i s q u a t e r n a r y salt (VII) in CD3OD +D20, a singlet of the N - C H 3 group of
the imidazole ring was o b s e r v e d at 4.12 ppm. a singlet of the N - C H 3 group of the pyridine ring at 4.39 ppm
(3H), a doublet of doublets of the a p r o t o n at 8 9.56 ppm, a multiplet of t h e ~ ' T ~ p r o t o n s at 9.19-8.38 ppm
(Jail = 5.4 Hz), and multiplets of the benzimidazole protons at 8.04 ppm. The signals of the protons of the
benzimidazole and pyridine rings of compound (VII) a r e still f u r t h e r shifted in the downfield direction than
in (VI).
In t h e i r UV s p e c t r a (CHC13), the salts (IIa and b) have t h e i r long-wave absorption m a x i m a at 332 and
350 nm, respectively, b a t h o c h r o m i c a l l y shifted (~ 30 nm) with r e s p e c t to {Ia) and (Ib). Compound (VI) has
its absorption m a x i m u m at 286 nm and (VII) at 272 and 286 nm.
The quaternization of compounds (Ia and b) with higher alkyl halides did not take place, apparently
because of s t e r i c factors, since it can be seen on S t u a r t - B r i e g l e b models that in the salts (Ha and b) even
the CH 3 group is accomodated with difficulty.
The pyridinium salts (IIa and b) could not be reduced e i t h e r With sodium t e t r a h y d r o b o r a t e , with
p y r i d i n e - b o r a n e b y F e r l e s ' method [3]. o r with lithium t e t r a h y d r o a l u m i n a t e [4]. Unstable r e s i n s were ob-
tained. Catalytic reduction p r o v e d to be successful only in the c a s e of the benzoxazolylpyridinium salt (IIa).
The salt (IIb) was not reduced, which can be explained by the poisoning of the catalyst, while the reduction
of (VI) and (VII) gave complex m i x t u r e s f r o m which it was impossible to isolate individual substances.
Co~lpounds (Vb and c) w e r e obtained only by the methylation of the 2-(piperidin-4-yl)benzazoles (IVb, c),
whmh, in t h e i r turn, w e r e synthesized by condensing nipecotinic acid with o-aminophenol and o - p h e n y i e n e -
diamine.

EXPERIMENTAL
The PMR s p e c t r a w e r e taken on a P e r k i n - E l m e r R-12A i n s t r u m e n t (60 MHz).
2 - ( B e n z o x a z o l y l ) - l - m e t h y l p y r i d i n i u m Iodide (IIa). A m i x t u r e of 0.01 mole of (Ia) and 0.01 mole of
methyl iodide in dimethylformamide was heated in a sealed tube at t00~ for 36 h. The solvent was evapo-
r a t e d off and the unchanged (Ia) was washed out with acetone. Yield 50%. Mp 217-218~ (from water).
Found %: C 45.9: H 3.4. I 37.2- N 8.0. CI3HIIIN20. Calculated %: C 46.2. H 3.3: I 37.5: N 8.3.
2-(Benzothiazol-2-yl)-l-methylpyridinium iodide (llb) was obtained similarly with a yield of 50%.
Mp 232-233~ (fromwater). Found ~: C 44.2. H 2.9: I 35.4. N 7.8. C13HIII~N2S. Calculated %: C 44.1.
H 3.1. I 35.8. N 7.9.
113-Dimethyl-2- (pyridin-2-yl)benzimidazolinm Iodide (V-I)and 103-Dimethyl-2- (1-methylpyridinio-2-
yl)benzimidazolium Diiodide (VII). The mixture of (VI) and (VII) obtained in the same way as (IIa) was
crystallized from 50% ethanol. On cooling the solution to room temperature, crystals of (VI) separated out,
and these were recrystallized several times. Yield 45% (withrespect to the CH3I). Mp 251-252~ Found
%. C 47.5. H 3.8: N 11.6. C14HI41N3. Calculated %: C 47.9: H 4.0. N 12.0. Evaporationof the mother solu-
tions gave (VII). Yield 30% (on the CH31). Mp 253-255~ Found %: C 36.4. H 3.2- N 8.2. C15HITI2N3.
Calculated %: C 36.6. H 3.5: N 8.5.
The 2- (Piperidin-2-yl)benzazoles (IVb, e). These were obtained in a similar manner to the 2- (piperi-
din-3-yl)benzazoles [I]. 2- (Piperidin-2-yl)benzothiazole (IVb), yield 60%, 89-90~ (from.heptane). Found
%. C 65.7. H 6,3: N 12.8. CI2HI4N2S. Calculated %: C 66.0: H 6.5: N 12.8. PMR spectrum, 6, ppm (CC14):
aH 3.4-2.5 m, ~Hfl'HTH 2.4-1.4 m, a'H 4.2-3.9 m, benzothiazole protons (7.95-7.1 m).
2-(Piperidin-2-yl)benzimidazole (IVc), yield 27%, mp 248-249~ (fromdioxane). Found %: C 71.4:
H 7.4. N 20.8. CI2HIsN3. Calculated %: C 71.6: H 7.5: N 20.9. PMR spectrum (CD3OD): ~H 3.1-2.6 m,
flHfl'HTH 2.2-1.4 m, a'H 3.94 m, benzimidazole protons 7.64-7.0 m.
2-(1-Methylpiperidin-2-yl)benzothiazole (Vb) was obtained by a method that we have described pre-
viously [1] with a yield of 89%. mp 60-61~ (from hexane). Found%- C 67.3: H 6.8: N 11.6. CI3HI6N2S.
Calculated %: C 67.2: H 6.9: N 12.1.

i00
 2- (1-Methylpiperidin-2-yl)be.nzimidazole (Vc! was obtained in a similar manner to compound (Vb) with
a yield of 90%. It was crystallized from 50% propan-2-ol: it sublimed above 230~ Found %: C 72.3: H 8.0:"
N 19.6. C~H1TN3. Calculated %: C 72.5: H 8.0: N 19.5.
2- (1-Methylpiperidin-2-yl)benzoxazole (Va) was obtained with a yield of 30% by the hydrogenation of
the salt (Ha) with Adams catalyst in ethanol at room temperature and at atmospheric p r e s s u r e , and was iso-
lated in the form of the hydrochloride Wa" HC1), mp 172~ (from hexane). Found %: C 61.6: H 6.7: N 11.3.
CI3H~N20- HC1. Calculated %: C 61.8: tt 6.8: N 11.1.

LITERATURE CITED
1. P . P . Zarin, E. S. Lavrinovich, and A. K. Area, Khim. Geterotsikl. Soedin., 108 (1974).
2. V.M. Zubarovskii and A. L Voronina. Zh. Obsheh. Khim.. 23, 140 (1953).
3. M. Ferles, Coll. Czech. Chem. Commun.. 24, 2221 (1959).
4. V . M . Mi~ovi~ and M. L. Mihailovi~,J. Org. Chem.. 18. 1190 (1953).

101
PYRIDINIUM SALTS
IV.* REDUCTION OF 4-(BENZAZOL-2-YL)PYRIDINIUM SALTS WITH SODIUM
TETRAHYDROBORATE IN AN ALKALINE MEDIUM

P. P. Zarin'0 E. E. Liepin', UDC 547.821,3:547.822.1

~. S. L a v r i n o v i c h , a n d A. K. A r e a

The reduction of 4-(benzoxazol-2-yl)- and 4 - ( b e n z o t h i a z o l - 2 - y l ) - l - m e t h y l p y r i d i n i u m iodides

with sodium t e t r a h y d r o b o r a t e ia an alkaline m e d i u m f o r m s p r o d u c t s of the d i m e r i z a t i o n of
the c o r r e s p o n d i n g 1,2-dihydropyridine d e r i v a t i v e s . Under s i m i l a r conditions, 4 - ( b e n z i m i d -
a z o l - 2 - y l ) - l - m e t h y l p y r i d i n i u m iodide gives a 1,2,5,6-tetrahydropyridine d e r i v a t i v e .

We have found p r e v i o u s l y [1] that the reduction of the 4-(benzazol-2-yl)pyridinium s a l t s (In-c) with
sodium t e t r a h y d r o b o r a t e in a neutral m e d i u m leads to 2 - ( 1 - m e t h y l - l , 2 , 5 , 6 - t e t r a h y d r o p y r i d i n - 4 - y l ) b e n z a z o l e s
(IIIa-c). Continuing this work, we have p e r f o r m e d the reduction of the s a m e s a l t s (In-c) with sodium t e t r a -
h y d r o b o r a t e in an alkaline m e d i u m . Generally, the reduction of p y r i d i n i u m s a l t s under these conditions
gives 1 , 2 : d i h y d r o p y r i d i n e s [2]. The t r e a t m e n t of the benzoxazole and benzothiazole d e r i v a t i v e s (Ia, b) with
sodium t e t r a h y d r o b o r a t e in aqueous ethanolic s u s p e n s i o n at pH ~14 gives compounds (IVa, b), the e l e m e n -
t a r y a n a l y s i s of which c o r r e s p o n d e d to the substituted 1 , 2 - d i h y d r o p y r i d i n e s (IIa, b). However, the m o l e c u -
l a r weights of compounds (IVa, b) p r o v e d to be double those calculated for (IIa, b).

Z Z Z

NoSD4 . . . . . . . .~ ,m,

NaOD qH.;OH
CD3OD
CH3 CH 3 CH3 CH 3
Vl/a
CH~ D I/
z CHo Z CH 3 ~Z
14 ~ H.,,....~r

z 1 z I z I.
CH 3 CH 3 C~'~,
V-]la~b

Ia-tla : Z = benzoxazol-2-yl
Ib-VIb : Z = benzothiazot-2-yl
Ic-IIIc : Z= benzimldazol-2-yl

It has r e c e n t l y b e e n e s t a b l i s h e d [3] that the r e d u c t i o n of 4 - c y a n o - l - m e t h y l p y r i d i n i u m iodide under

conditions s i m i l a r to ours g i v e s a Diels - A l d e r adduct: 7,11- dicya no-e ado- 4 - endo-9- dimethyl--4,9-diazatri-
cyclo[6,2,2,02,7]dodeca-5,11-diene. To d e t e r m i n e the s t r u c t u r e s of the d i m e r s that we had obtained, we
studied the PMR s p e c t r u m of compound (IVa) (Fig. 1). In the 2.2 p p m region t h e r e a r e two singlets of N-
m e t h y l groups, which c o n f i r m s the d i m e r i c nature of the compound.
* F o r Communication III, see [t]. . . . . . . . . . .
Institute of Organic Synthesis, Academy of Sciences of the Latvian SSR, Riga. T r a n s l a t e d f r o m Khin~-
iya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 1, pp. 115-118, J a n u a r y , 1974. Original a r t i c l e submitted Novem-
b e r 11, 1972.

9 1975 Plenum Publishing Corporation, 227West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy of this article is available from the publisher for $15.00.

102
 At 5.69 and 4.53 ppm the absorption of the HX
and Hp protons is o b s e r v e d in the f o r m of two dou-
,, blets forming an AX s y s t e m (J = 7.6 Hz)~ The values
of their chemical shifts c o r r e s p o n d to the usual ones for
the a and fl protons at an enamine double bond [4].
P a r t of another AX s y s t e m is o b s e r v e d at 4~ ppm (HM).
6 $~ ppm The second p a r t of this s y s t e m is hidden, as was
shown by a d o u b l e - r e s o n a n c e e x p e r i m e n t (Fig. 1), by
Fig. 1. PMR s p e c t r u m o f 7,11-di(benzoxazol-2-
the multiplet of a r o m a t i c protons and is located at
yl)- e n d o - 4 - endo-9- dimethyl- 4 , 9 - d i a z a t r i c y c l o -
7.3 ppm. This weak-field signal (6 7.3 ppm) can be
[6,2,2,02,7]dodeca-5,11-diene in CD3C1.
assigned to the H y proton on the double bond adjacent
to a benzoxazole residue, In the 2-(1,2 ,5 , 6 - t e t r a h y -
d r o p y r i d i n - 4 - y l ) b e n z o x a z o l e s , the signal of the vicinal proton has been found at 6.76 ppm [1].

The p r e s e n c e of an enamine s y s t e m and of a vinyl proton in the d i m e r (IVa) shows the formation,
as the r e s u l t of a Diels--Alder reaction, of the adduct of two m o l e c u l e s of the 1,2-dihydropyridine (Ha). The
existence of (IVa) in the m o r e p r e f e r r e d endo conformation is shown by the observed long-range s p i n - s p i n
coupling (SSC) of the P and D p r o t o n s (J = 0.5 Hz) and the absence of such coupling between the D and the E
p r o t o n s . The a s s i g n m e n t of the other signals was made on the basis of the r e s u l t s of experiments with
double r e s o n a n c e (Fig. 1). The doublet at 2.97 ppm with a relative i n t e n s i t y of 2H can be a s c r i b e d to the A
and B p r o t o n s r e a c t i n g identically (J = 3.2 Hz) with the D proton, which approximately c o r r e s p o n d s to the
s p i n - s p i n coupling constant usually o b s e r v e d [5] for a hindered conformation with dihedral angles of 60 ~ be-
tween the A, B, and D p r o t o n s . The doublet of doublets (1H) at 1.90 ppm (J = 8.72 and 1.77 Hz) m u s t be as-
signed to the E proton. The multiplet at 3.6-3.2 ppm (3H) is f o r m e d by the absorption signals f r o m the N,
C, and D p r o t o n s . Tile o b s e r v e d geminal s p i n - s p i n coupling constant (JEN = 8.7 Hz) is in good a g r e e m e n t
with the established SSCC constant between the p r o t o n s of a methylene group adjacent to nitrogen in six-
m e m b e r e d rings with the eclipsed c o n f o r m a t i o n of the p r o t o n and the unshared e l e c t r o n p a i r of the nitrogen
[6]. This is p o s s i b l e when there is no i n v e r s i o n of the N9 nitrogen atom. A confirmation of the fixed posi-
tion of the unshared e l e c t r o n p a i r of the N9 atom is also the large difference in the chemical shifts of the
geminal N and E p r o t o n s (~1.5 ppm) [6, 7]. As is well known [3, 6], the cis-diaxial position of the H N p r o -
ton and the unshared e l e c t r o n p a i r of the nitrogen causes a downfield shift of the absorption signal, and the
t r a n s e q u a t o r i a l position of the E p r o t o n and of the unshared p a i r of electrons causes an opposite shift. It
m u s t be mentioned that inversion of the N9 atom m u s t also be prevented by the voluminous benzoxazole
residue at N7, as is shown by a m o l e c u l a r model. The p r o p o s e d s t r u c t u r e p e r m i t s an explanation of the
shift of the 4-CH 3 signal in the upfield direction (6 2.28 ppm) by the influence of the ring c u r r e n t s in the
benzoxazole s y s t e m located at Cll.
A f u r t h e r p r o o f of the c o r r e c t n e s s of the a s s i g n m e n t of the signals was obtained by the p e r f o r m a n c e
of a r e a c t i o n of the salt (Ia) with NaBD 4. According to c u r r e n t ideas on the m e c h a n i s m of the reduction of
p y r i d i n i u m salts with sodium t e t r a h y d r o b o r a t e [8], the p r i m a r y r e a c t i o n p r o d u c t m u s t be 2-(1-methyl-2-
d e u t e r o - l , 2 - d i h y d r o p y r i d i n - 4 - y l ) b e n z o x a z o l e . Its d i m e r of s t r u c t u r e (VIIa) m u s t contain two deuterium
atoms in positions 3 and 10. In the PMR s p e c t r u m observed for (VIIa), the intensity of the signal at 1.90
ppm had d e c r e a s e d to 0.5 relative units. The signal at 2.97 ppm c o r r e s p o n d e d to 1 H, and the intensity of
the multiplet at 3.6-3.2 ppm to 2.5 H. The change in the intensities and the c o r r e s p o n d i n g simplification of
the s p e c t r u m show an equiprobable substitution of the A and B p r o t o n s and also of the N and E p r o t o n s .
Thus, the s t r u c t u r e of compound (IVa) that we obtained is analogous to the d i m e r of 4 - c y a n o - l - m e t h y l - l , 2 -
d i h y d r o p y r i d i a e d e s c r i b e d p r e v i o u s l y [3]. But the conformational angles in (IVa) apparently differ s o m e -
what f r o m the angles of the latter, judging from the isochronicity of the A and B p r o t o n s , and also their
s i m i l a r constants of SSC with the D proton. The action of DC1 on the d i m e r s (IVa and b) led to rapid r e -
p l a c e m e n t of the P and U p r o t o n s by deuterium (Via and b), as in the case of the d i m e r d e s c r i b e d by L i b e r a -
tore et al. [3]. It appeared that a s i m i l a r exchange also takes place under the action of D20 and even in an
alkaline solution (NaOD in D20). Consequently, the crude compound (VIIa) gives a PMR s p e c t r u m in which
a ~25% r e p l a c e m e n t of the P and Y p r o t o n s by deuterium is observed. The washing of the crude (VIIa) with
w a t e r and with ethanol leads to deuteration at C 6 and C12.
The catalytic hydrogenation of the d i m e r s (IVa and b) takes place e x t r e m e l y slowly. Their reduction
with p y r i d i n e - b o r a n e gives s a t u r a t e d compounds (Va and b) which a r e distinguished by t h e r m a l stability and
gives the expected m o l e c u l a r ions with m/e 432 (Va) and 460 (Vb) in their m a s s s p e c t r a . It m u s t be men-
tioned that on m a s s s p e c t r o s c o p y , (IVa) and (IVb) gives m o l e c u l a r ions with m / e 216 and 230 c o r r e s p o n d i n g

103
to t e t r a h y d r o p y r i d i n e d e r i v a t i v e s (IIIa and b). The l a t t e r a r e obviously f o r m e d by the t h e r m a l r e t r o d i e n e
r e a c t i o n and the d i s p r o p o r t i o n a t i o n of the 1 , 2 - d i h y d r o p y r i d i a e f o r m e d under the e x p e r i m e n t a l conditions.
Decomposition of the d i m e r s (IVa and b) is o b s e r v e d when they a r e heated b r i e f l y in solution to 40-50~
and also on s t o r a g e . Attempts to t r a p 1,2-dihydropyridine (IIa) on heating (IVa) with m a l e i c anhydride or
m a l e i c acid w e r e unsuccessful.
The d i m e r i c s t r u c t u r e of the benzothiazole d e r i v a t i v e (IVb), just like that of compound (IVa),is con-
f i r m e d by the p r e s e n c e in the PMR s p e c t r u m of the c h a r a c t e r i s t i c signals f r o m t w o N - C H 3 g r o u p s a t 2.32
p p m , and a l s o by an enamine AX q u a r t e t at 5.80 and 4.53 p p m and the signal of a vinyl p r o t o n (6.99 p p m )
adjacent to the multiplet of the benzothiazole r e s i d u e s (8.0-7.1 p p m ) . The d e u t e r i u m d e r i v a t i v e (VIIb) was
also obtained, its p r o p e r t i e s being analogous to those of compound (VIIa).
The reduction of the b e n z i m i d a z o l y l p y r i d i n i u m s a l t (Ic) with sodium t e t r a h y d r o b o r a t e even in a
s t r o n g l y alkaline m e d i u m led to the f o r m a t i o n of the m o n o m e r i c compound (IIIc) e x c l u s i v e l y . To explain
the o b s e r v e d phenomenon r e q u i r e s additional investigations.

EXPERIMENTAL
The PMR spectra of 10% solutions in CDCI 3 were obtained on aPerkin-ElmerR-12A(60 MHz) instru-
ment at 36~ The chemical shifts 5 were measured relative to TMS as internal standard with an accuracy
of 0.5% of the depth of scanning.
7,1 l-Di (be nz oxaz ol-2-yl)-endo- 4- e ado-9- dimethyl- 4,9- diazatri cycio[6,2,2,02,7] dodeca-5,1 I- die ne (IVa).
To a mixture of 3.37 g (0.01 mole} of (In) and 0.4 g (0.01 mole} of NaOH in 20 ml of water and 30 ml of
ethanol was added 0.76 g (0.01 mole) of sodium tetrahydroborate in portions. A vigorous reaction began.
The precipitate was filtered off, washed with hot water (~30~ and dissolved in chloroform, and the solu-
tion w a s p a s s e d through a l a y e r of ahmlina of activity g r a d e II a c c o r d i n g to Brockmanno Distillation of the
solvent left l i g h t - y e l l o w c r y s t a l s . Yield 51%. Mp 169-170~ Found: C 73.1; H 5.4; N 13.2%. M 423 (cryo-
scopy in benzene). C26H24N40 2. Calculated: C 73.6; H 5.7; N 13.2%. Mol~ ~ t . 424.
7,11-Di (be nzothiazol-2-yl)- e n d o - 4 - endo-9- dimethyl-- 4,9- diazatricyclo[6,2,2,02,7] dodeca-5,11- diene
(IVb). This was obtained in a s i m i l a r m a n n e r to (IVa). L i g h t - y e l l o w c r y s t a l s . Yield 30%. Mp 138-140~
Found: C 68.0; H 5.3; N 12.0%. lVi 455 (eryoscopy in benzene). C26H24N4S2. Calculated: C 68.6; H 5.3; N
12.3%. Mol. wt. 454.
7,11-Di (be nz oxaz ol-2-yl)- e ndo - 4 - e ndo -9- dime thyl- 4,9-dtazatr i cycl o[ 6,2,2,02,7] dode ca-5,11- die ne-3,10-
D 2 (VIIa). In p o r t i o n s , 0.42 g (0.1 mole) of NaBD 4 was added to a m i x t u r e of 1.68 g (0.005 mole) of (In), and
0.61 g (0.01 mole) of NaOD 9 D20 in 10 m l of D20 and 15 ml of CD3OD. The m i x t u r e was left overnight. Then
the p r e c i p i t a t e was f i l t e r e d off and was washed with D20, H20, and C2H~OH. This g a v e 1.33 g (34%) of white
c r y s t a l s with mp 172-173~C. Found: C 73.0; H 6.0; N 13.3%. C26H22D2N40 2. Calculated: C 73.2; H 6.1; N
13.1%.
7 ,ll-Di (benzoxaz ol-2-yl)- endo- 4 - endo -9- dimethyl- 4,9- diazatricyclo[6,2,2,02,7] dodecane (Va). To a
suspension of 0.57 g (0.0025 mole} of (IVa) in 20 ml of ethanol was added 0.93 g (0.01 mole) of pyridine-
borane, and the mixture was heated on the water bath for 20 min. During the reaction, the (IVa) dissolved
completely. The solvent was evaporated,and the residue was washed with water, giving 0.97 g (90%) of a
product with mp 227-228~ (from propan-2-ol). Found: C 72.7; H 6.5; N 13.1%. Mol. wt. 428 (mass spec-
trometry). C26H28N402. Calculated: C 72.9, H 6.6; N 12.1%. Mol. wt. 428.
7,11 -Di (benzothiazol-2 -yl)-endo-4-endo-9-dimethyl-4,9-diazatricyclo [6,2,2,02,7 ]dodecane (Vb). Ob-
tained in the same way as (Va). Colorless crystals. Yield 85%. Mp219-220~ Found: C 67.7; H 6ol;
N 12.2%. Moi. wt. 460 (mass spectrometry). C2sH28N4S 2. Calculated: C 67.8; H 6.1; N 12.2%. Molo wt. 460.

LITERATURE CITED
1. P. P. Z a r i n ' , ]~. S. Lavrinovich, and A. K. Aren, Khim. G e t e r o t s i k l . Soedin., 112 (1974).
2. J. Kuthan and U. E i s n e r , Chem. Rev., 72__, 1 (1972).
3. F. L i b e r a t o r e , A. Casini, and V. Carelli, T e t r a h e d r o n Lett., 2381 (1971}.
4. NMR S p e c t r a catalog, Varian A s s o c i a t e s , 2, No. 542 (1963).
5. V. F. B y s t r o v , Usp. Khim., 41__, 512 (1972}.
6. P. J. Chivers and T. A. Crabb, T e t r a h e d r o n , 26., 3389 (1970}.
7. J . B. L a m b e r t W. L. Oliver, and B. S. P a c k a r d , J~ A m e r . Chem. Sot., 93.___,933 (1971).
8. P. S. A n d e r s o n and R. E. Lyle, T e t r a h e d r o n Lett., 153 (1964}.

104
A STUDY OF NAPHTHYRIDINES
III.* SYNTHESIS O F 4,4-DIARYL-1,4-DIHYDRO-2,3-BENZO-1,8-NAPHTHYRIDtNES

M. E. Konshin and V. P. Chesnokov UDC547.823'834.2.07:541.132

4 , 4 - D i a r y l - l , 4 - d i h y d r o - 2 , 3 - b e n z o - l , 8 - n a p h t h y r i d i n e s have been synthesized by the c y c l i z a -

tion of diaryl 2 - a r y l a m i a o p y r i d i n - 3 - y l c a r b i n o l s . The l a t t e r w e r e obtained by the r e a c t i o n of
m e t h y l 2 - a r y l a m i n o n i c o t i n a t e s with a r y l m a g n e s i u m halides. With acid c h l o r i d e s , the 4 , 4 -
d i a r y l - l , 4 - d i h y d r o - 2 , 3 - b e n z o - l , 8 - n a p h t h y r i d i n e s f o r m 1-acyl d e r i v a t i v e s . The pK a values of
the 4,4 - d i a r y l - l , 4 - dihydro-2,3-benzo-l,8-naphthyridines in nitrobe azene have been d e t e r m i n e d ,
and a c o r r e l a t i o n has b e e n found of the pK a values with the (r* constants of the substituents
(r = 0.955, p* = - 1 . 5 3 , P K a c a l c 2.51, s = 0.0i)

4 , 4 - D i a r y l - l , 4 - d i h y d r o - 2 , 3 - b e n z o - l , 8 - n a p h t h y r i d i n e s have not been studied. The c l o s e s t s t r u c t u r a l

analogs of these compounds a r e the 9 , 9 - d i a r y l d i h y d r o a c r i d i n e s , which a r e obtained by the i n t r a m o l e c u l a r
c y c t i z a t i o n of d i a r y l 2 - a r y l a m l n o a m y l c a r b i n o l s [2, 3]. It a p p e a r e d of i n t e r e s t to p e r f o r m the s y n t h e s i s of
diaryl 2 - a r y l a m i n o p y r i d i n - 3 - y l c a r b i n o l s and to study the p o s s i b i l i t y of converting them into 4 , 4 - d i a r y l - l , 4 -
d i h y d r o - 2 , 3 - b e n z o - l , 8 - n a p h t h y r i d i n e s , since the l a t t e r a r e p r o m i s i n g for the s y n t h e s i s of potentially p h y s i o -
logically active compounds.

RC~Ha\/C6H4 R
" ~,~OH ~

. . . . ~.co..r,-p ~N,Y"-N"~'--
H
~
I-VI
F'RCsH4~.I./c'H4R 7

I H tl I tt [
L. -I COr~

ViI-XII XIII-XVIII

The d i a r y l 2 - a r y l a m i n o p y r i d i n - 3 - y l c a r b i n o l s (I-VI, Table 1) w e r e obtained with good yields by the r e -

action of a r y l m a g n e s i u m ha]ides with m e t h y l 2 - a r y l a m i n o n i c o t i n a t e s . They a r e c o l o r l e s s c r y s t a l l i n e s u b -
s t a n c e s r e a d i l y soluble in organic s o l v e n t s . With c o n c e n t r a t e d sulfuric acid they give a rapidly d i s a p p e a r -
ing coloration, the a p p e a r a n c e of which is a p p a r e n t l y due to the f o r m a t i o n of a doubly-charged p y r i d i u m -
c a r b o n i u m ion. The IR s p e c t r a of compounds (I-VI), in which only the bands of f r e e hydroxy and amino
groups a r e o b s e r v e d , shows the a b s e n c e of i n t r a m o l e c u l a r hydrogen bonds in these compounds. The r e a s o n
for this is the low b a s i c i t y of the amino groups in the c a r b i n o l s (I-VI).
When acetic acid solutions of the c a r b i n o t s w e r e heated with catalytic amounts of concentrated sul-
furic acid, i n t r a m o l e c u l a r c y c l i z a t i o n took p l a c e with the f o r m a t i o n of the 4 , 4 - d i a r y l - l , 4 - d i h y d r o - 2 , 3 - b e n -
z o - l , 8 - n a p h t h y r i d i n e s (VII-XII, Table 2) with good y i e l d s . Since with c o n c e n t r a t e d sulfuric acid the carbinols

* F o r C o m m u n i c a t i o n II, see [1].

P e r m P h a r m a c e u t i c a l Institute. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 1, pp.

119-121, J a n u a r y , 1974. Original a r t i c l e submitted J a n u a r y 30, 1973.

9 19 75 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N.Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy o f this article is available from the publisher for $15.00.

105
 T A B L E 1. Diaryl~2-Arylaminopyridin-3-yl C a r b i n o l s (I-VI)

Com- Empirical ~ :~"~ cm

pound R R" Mp,, "C formula f~nd~lcalc.~ - - - - 7

I 168--170 C~4H~N~O 7.9 7,9 3600 3407 56

I1 CHa 170--172 CmH~NzO 7.6 7,6 3600 3407 49
Iit H ]CHsO 150--151 C~sH~N~OI . 7,3 7,3 3603 3411 40
IV t77--179 C~HIsCIN~D 7,2 7,2 3603 3400 31
V H Br 182--183 C~Ht~BrN~O 6,5 6,5 3603 3396 32
VI p-CH~ CH,O 180---182 C~rH~N~O~ 62 6,8 3603 3407 45

T A B L E 2. 4 , 4 - D i a r y l - l , 4 - d i h y d r o - 2 , 3 - b e n z o - l , 8 - n a p h t h y r i d i nes
(VII-XtI)

1 Empirical
i "' ~ ,~ pI<a in lit-
.............. 91 I trobenzene
R R, IMp, *-C formula
found Iealc. ~ o I

VII H H 282--284 C24H~sN~ 8.5 8,4 !3424] 2.52 t5,98 180

VIII CHa 255--257 C2~H2oN.~ 7,9 8,0 3428! 2,76-~0,06 15,74 84
IX ~CHzO 232--234 C25H2oN20 7,7 7,7 3432. 2,66 15~,-4 69
X Ce~HtrCIN2 %5 7,6 3428 2,1,9~:0.05 |6~40 74
XI
XII p-CHz
Br
:Lo
270--272 C24HI~BrNz
222--224 C.oTH24N20
6,8
73
6,8 3428 2,11
7,2 ,3426] --
16.3918o
[ - - 55

*pK a f o r diplmnylgttanidine in n i t r o b e n z e n e 8.5 + 0.02.

T A B L E 3. 1 - A c y l - 4 , 4 - d i a r y l - l , 4 - d i h y d r o - 2 , 3 - b e n z o - l , 8 - n a p h t h y r i -
d i n e s (XIII-XVIII)
N,% "h~
Com- Empirical
Rt R: Mp, *C formula
pound found 'talc~ ' ~
.N

t
XIll H CH3 241--243 C26Hu0N20 7,5 ] 7.4 85
XIV ~p3C C6Hs 271--273 CziH22NzO 6'4 ~l 6.4 34
xv ~ CHa 196--198 C27H~2N20~ 6,8 6'9 37
xvI C6H~ 211--213 CaH21CIN20 6,0 5,9 72
XVIl H Br CHa 240--242 C26H19BrN20 6.3 6.2 59
XVllt p-CHa CH30 C6Hs 200--202 C34H28N20~ 5.7 5,6 42

g i v e h a l o c h r o m i c s a l t s , the h y p o t h e s i s m a y b e put f o r w a r d t h a t t h e m e c h a n i s m of the c y c l i z a t i o n of t h e s e

c o m p o u n d s into t h e n a p h t h y r i d i n e s (VII-XII) in an a c i d m e d i u m c o n s i s t s in the f o r m a t i o n of a c a r b o n i u m ion
which p l a y s the r o l e of an e l e c t r o p h i l i c a g e n t , a t t a c k i n g t h e n e i g h b o r i n g b e n z e n e r i n g . The high a c t i v i t y of
the c a r b o n i u m ion, and a l s o the s p a t i a l p r o p i n q u i t y of the p h e n y l r a d i c a l , w h i c h i s the n u c l e o p h i l i c r e a c t i o n
c e n t e r , l e a d to a h i g h r a t e of c y c l i z a t i o n w h i c h it i s i m p o s s i b l e to c o n t r o l u n d e r the u s u a l c o n d i t i o n s . An
a t t e m p t to s t u d y t h e UV s p e c t r a of the d o u b l y - - c h a r g e d c a t i o n (I) o r (III) w a s u n s u c c e s s f u l , s i n c e i m m e d i a t e l y
a f t e r the p r e p a r a t i o n of s o l u t i o n s of (I) and of (III) in c o n c e n t r a t e d s u l f u r i c a c i d t h e y g i v e the s p e c t r a of the
c a t i o n s (VII) a n d (IX), and not t h o s e of the h a l o c h r o m i c c a t i o n s . The n a p h t h y r i d i n e s (VII-XII) a r e c o l o r l e s s
c r y s t a l l i n e s u b s t a n c e s s p a r i n g l y s o l u b l e i n t h e u s u a l o r g a n i c s o l v e n t s . The s t r u c t u r e s of t h e s e c o m p o u n d s
w e r e c o n f i r m e d by t h e i r IR s p e c t r a , w h i c h c o n t a i n e d a VNH b a n d a t 3 4 2 4 - 3 4 3 4 e m -1 and, u n l i k e the s p e c t r a
o f ( I - V I ) , l a e k e d t h e b a n d of a h y d r o x y g r o u p . T h e i r i o n i z a t i o n c o n s t a n t s in n i t r o b e n z e n e w e r e s t u d i e d , and
the v a l u e s of A p K a r e l a t i v e to t h e p K a v a l u e of d i p h e n y l g u a n i d i n e in the s a m e s o l v e n t w e r e c a l c u l a t e d ( T a b l e
2). T h e p K a v a l u e s of (VII-XI) d e p e n d on the s u b s t i t u e n t s in the b e n z e n e r i n g of the h e t e r o c y c l i c s y s t e m a n d
f a l l i n the s e q u e n c e of c o m p o u n d s w i t h the f o l l o w i n g s u b s t i t u e n t s : CH 3 > CH30 > H > B r > C1. Since the
s u b s t i t u e n t s in (VII-XI) a r e s e p a r a t e d f r o m the p y r i d i n e r i n g b y a n o - p h e n y l e n e g r o u p , and a l s o s e v e r a l cr
b o n d s , t h e h y p o t h e s i s c a n be p u t f o r w a r d t h a t the p K a v a l u e s of t h e s e c o m p o u n d s w i l l c o r r e l a t e with T a f t ' s
or* c o n s t a n t s of t h e s u b s t i t u e n t s [4]. An a n a l y s i s of the P K a - c r * r e l a t i o n s h i p s h o w e d t h a t a g o o d c o r r e l a -
t i o n i s o b s e r v e d with the f o l l o w i n g c o r r e l a t i o n p a r a m e t e r s : r = 0.995; p* = - 1 . 5 3 ; P K a c a l c = 2.51; s = 0 , 0 1 .
C o m p o u n d s (VII-XII) a r e a c y l a t e d b y a c i d c h l o r i d e s in a b e n z e n e m e d i u m i n the p r e s e n c e of t r i e t h y l a m i n e
w i t h the f o r m a t i o n of 1 - a c y l - 4 , 4 - d i a r y l = l , 4 - d i h y d r o - 2 , 3 - b e n z o - l , 8 - n a p h t h y r i d i n e s (XIII-XVIII, T a b l e 3} with
y i e l d s of 3 4 - 8 5 % .

106
 EXPERIMENTAL
The IR s p e c t r a w e r e t a k e n on a IKS-14 i n s t r u m e n t using 0.005 M solutions in c a r b o n t e t r a c h l o r i d e
(LiF p r i s m ) . The ionization constants of the 4 , 4 - d i a r y l - l , 4 - d i h y d r o - 2 , 3 - b e n z o - l , 8 - n a p h t h y r i d i n e s w e r e de-
t e r m i n e d by the p o t e n t i o m e t r i c t i t r a t i o n with a 0.1 N dioxane solution of p e r c h l o r i c acid of 0.005 M solu-
tions of (VII-XI) in nitrobenzene, using a LPM-60M p o t e n t i o m e t e r with g l a s s and s i l v e r chloride e l e c t r o d e s .
The calculation was p e r f o r m e d by the usual method [5] f r o m eight points c o r r e s p o n d i n g to 10-90% neutrali-
zation.
Diaryl 2-Arylaminopyridin-3-yl Carbinols (I-VI). A solution of 0.I mole of a methyl 2-arylaminonico-
tinate [6] in 50 ml of anhydrous ether was added to the Grignard reagent obtained in the usual way from 0.03
mole of an aryl bromide at 0.03 g-atom of magnesium. The mixture was heated for I h 30 min to 2 h and
was then decomposed with a saturated solution of ammonium chloride. The ethereal solution was separated
off and was treated with steam. The residue was crystallized from ethanol.
4,4-Diaryl-l,4-dihydro-2,3-benzo-l,S-naphthyridines (VII-XII). A drop of concentrated sulfuric acid
was added to a solution of 1 g of diaryl 2-arylaminopyridin-3-yl carbinol in I0 ml of glacial acetic acid, and
the mixture was heated on the water bath for 30 min and was cooled and poured into I00 ml of water, and
the precipitate that deposited was filtered off, treated with 10% sodium carbonate solution, washed with
water, and crystallized from dioxane.
l-Acyl-4,4-diaryl-l,4-dihydro-2,3-benzo-l,8-aaphthyridines (XIII-XVIII). A solution of 1 g of a 4,4-
diaryl-l,4-dihydro-2,3-benzo-l,8-naphthyridine in 50 ml of anhydrous benzene was treated with 1 ml of tri-
ethylamine, and then 0.I mole of an acyl chloride was added dropwise, after which the mixture was left at
room temperature for 1 h and was poured into 10-16 ml of ice water and treated with steam. The residue
was crystallized from acetone.

LITERATURE CITED
1o M. E. Konshin and V. A. Khaldeeva, Khim. G e t e r o t s i k l . Soedin., 1393 (1973).
2. A. B a e y e r and V. Villiger, Ber., 37__._,3191 (1904).
3. I~. E. Konshin and P. A. Petyunin, Zh. Obshch. Khim., 34__, 3429 (1964).
4. R. W. Taft, in: Steric Effects in Organic C h e m i s t r y , e d i t e d by M. S. Newman, Wiley (1956).
5. A. Albert and E. Serjeant, Ionization Constants of Acids and B a s e s , 1st ed., Methuen, London (1962).
6. V. P. Chesnokov and M. E. Konshin, Izv. Vysshykh Uchebn. Zaved., Ser. Khim. (1974)(in p r e s s ) .

107
SYNTHESIS AND PROPERTIES OF AZOLES AND THEIR DERIVATIVES
XVIII. * P R E P A R A T I O N OF 1-SUBSTITUTED 2-(BENZIMID.AZOL-2-YL}IMIDAZOLINES

G. A . S h v e k h g e i m e r and V. I . K e l a r e v UDC547.785.5'781.3

The condensation of 2 - t r i c h l o r o m e t h y l b e n z i m i d a z o l e with v a r i o u s N-monosubstituted ethyl-

e n e d i a m i n e s h a s given 1-substitued 2-(benzimidazol-2-yl)imidazolines.

Substituted 2-imidazotines find wide use as biologically active compounds [2, 3]. The p r e s e n t work
was devoted to the p r e p a r a t i o n of N-substituted i m i d a z o l i n e s containing a b e n z i m i d a z o l e r e s i d u e in position
2. This type of compound cannot be obtained by the usual methods for the s y n t h e s i s of 2-imidazolines [4],
since the initial b e n z i m i d a z o l e - 2 - c a r b o x y l i c acid and its d e r i v a t i v e s a r e difficultly a c c e s s i b l e compounds or
a r e unreactive (for e x a m p l e , the nitrile). Consequently, for the s y n t h e s i s of 1-substituted 2-(benzimidazol-
2-yl)imidazolines we m a d e use of the capacity of 2 - t r i c h l o r o m e t h y l b e n z i m i d a z o l e (I) for taking p a r t in
nucleophilic exchange r e a c t i o n s under the influence of a m i n e s without undergoing the h a l o f o r m d e c o m p o s i -
tion [5]. The use in this r e a c t i o n of N-monosubstituted e t h y t e n e d i a m i n e s (II-VII) enabled the 2-(benzimida-
zol-2-yl)imidazolines (VIII-XIII) to be obtained.

i-i H I
R
| II-Vll Vlll-Xnl

]L VIII R=CsHsCH2;ltI, 1X R=HOCH2CH~; iV, X R=NCCH,CH=; V, Xt R= furfuryl

Vl, XII R= 1-benzotriaz01ylmethyl VII, XIII R= l c~-thienylmethyl

In the IR s p e c t r a of compounds (VHI-XHI) t h e r e a r e intense a b s o r p t i o n bands in the 1610-1595 cm -~

r e g i o n r e l a t i n g to the v i b r a t i o n s of t h e C = N bond [6], and t h e r e a r e also bands in the 1430-1420 cm -l r e -
gion which r e l a t e to the d e f o r m a t i o n v i b r a t i o n s of a C - H bond or to the " s c i s s o r s " v i b r a t i o n s of the CH 2
g r o u p s in an imidazoline ring [7]. In addition, t h e r e a r e a b s o r p t i o n bands c h a r a c t e r i s t i c for b e a z i m i d a z o l e s
and for the groupings p r e s e n t in position 1 of the imidazoline ring.

EXPERIME NTAL
T h i n - l a y e r c h r o m a t o g r a p h y was c a r r i e d out on A120 s of activity g r a d e II in the h e p t a n e - i s o p r o p a n o l
(5 : 1) s y s t e m .
Compounds (I) [5], (II) [8], (IH) [9], (IV) [10], and (V) [11] w e r e p r e p a r e d by known m e t h o d s .
N-(~-Thienylmethyl)ethylenediamine (VI): At 15-20~ with s t i r r i n g , 11.7 g (0.088 mole) of a-chloro--
methylthiophene was added to 26.5 g (0.44 mole) of 100% ethylenediamine in 30 m l of absolute methanol, the
m i x t u r e was s t i r r e d at 40~ for 4 h and at 60~ for 30 m i n and was then cooled to 0~ and a solution of
2.02 g (0.088 mole) of sodium in 15 m l of absolute methanol was added and the r e s u l t i n g m i x t u r e was s t i r r e d
at 0~ f o r 1 h. The p r e c i p i t a t e that deposited was f i l t e r e d off, the f i l t r a t e was e v a p o r a t e d under r e d u c e d

* F o r Communication XVII, see [1].

I. M Gubkin Moscow Institute 'of the P e t r o c h e m i c a l and Gas Industry. T r a n s l a t e d f r o m Khimiya

G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 1, pp. 122-123, J a n u a r y , 1974. Original a r t i c l e submitted J a n u a r y 15,
1973.

9 19 75 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

108
 TABLE 1. 1-Substituted 2-(Benzimidazol-2-yl)imidazolines

Empirical Found, % Calculated, %

oml 9
ponudt Mp. ~ Rr formula
C H N C H N

VIII 193--194 0,79 CiTH!16N4 75,1 5,8 20,5 75,0 5,8 20,3 90
IX 183--184"I" 0,62 74
X 170 0,54 / CI3HI~N~ 5S 29,7 65,2 2 ,3 93
XI 209--210 0,72 !CI~H14N40 67,5 5,7 21,1 67,3 5,6 20,9 90
XtI 188--188.5 0,84 CIsHI4N~S 63,6 5,1 20,1 63,8 4,9 19,8 88
XHI 205--206 0,75 C17HI~N7 63,9 4,6 30,6 64,3 4,7 31,0 75
* Compounds (VIII, X, and XII) w e r e c r y s t a l l i z e d f r o m a c e t o a i t r i l e ,
(IX) and (XI) f r o m ethyl a c e t a t e , and (XIII) f r o m n i t r o m e t h a n e .
According to the l i t e r a t u r e [5], mp 180~

p r e s s u r e , and hhe r e s i d u a l oil was distilled in vacuum giving 10o3 g (75%) of (VI) with bp 115-116~ (7 m m ) ,
nD2~ 1.5512; d42~ 1.1024. Found.* C 53.8; B 7.7; N 18.1%. CTH12N2. Calculated: C 53.7; H 7.6; N 17.9%.
Dipicrate of (VI). Mp, 113-114~ (50% acetone).
N - ( B e a z o t r i a z o l - l - y l m e t h y l ) e t h y l e n e d i a m i n e (VII). This was obtained in a s i m i l a r m a n n e r to (VI) f r o m
15.0 g (0.25 mole) of 100% e t h y l e n e d i a m i n e and 8.4 g (0.05 mole) of 1 - c h l o r o m e t h y l b e n z o t r i a z o l e [12]. Yield
of (VII) 7.7 g (81%); v i s c o u s undistillable oil. Dipicrate of (VII). Mp,219-220~ (50% ethanol). Found: C
38.7; H 2.9; N 24.2%. CgH!3N 5.2C6H3N307. Calculated-" C 38.8; H 2.9; N 23.7%.
2 - ( B e a z i m i d a z o l - 2 - y l ) - l - b e n z y l i m i d a z o l i n e (VIII). In p o r t i o n s , 1.0 g (0.0042 mole) of (I) was added
with s t i r r i n g at 10~ to 2.5 g (0.017 mole) of (II) in 15 ml of w a t e r . The r e a c t i o n m i x t u r e was s t i r r e d at
20~ for 1 h and was p o u r e d into 30 m l of cold w a t e r , and the p r e c i p i t a t e was collected, washed with 10%
KOH, and dried.
The other 1-substituted 2-(benzimidazol-2-yl)imidazolines (IX-XIII) w e r e obtained s i m i l a r l y (Table 1).

LITERATURE CITED
1. G . A . S h v e k h g e i m e r and V. I. K e l a r c v , Khim. G e t e r o t s i k l . Soedin., 1674 (1973).
2. G. Holan, U.S. Patent No, 3,377,239 (1966); Chem. Abstr., 69__ 59,237k (1968).
3. M. M o u s s e r o n , J. Kamenka, and A. Stenger, J. Med. Chem., 11__ 889 (1968).
4. R . J . F e r m and J. L. R i e b s o m e r , Chem. Rev., 54__ 593 (1954).
5. B . C . Ennis, G. Holan, and E. Samuel, J. Chem. Soc., C, 33 (1967).
6. L. Bellamy, I n f r a r e d S p e c t r a of Complex Molecules, 2nd ed., Methuen, London (1958).
7. A . R . K a t r i t z k y , P h y s i c a l Methods in the C h e m i s t r y of H e t e r o c y c l i c Compounds, A c a d e m i c P r e s s
(1963).
8. R . P . L a s t o v s k i i and N. D. Kolpakova, Methods of Obtaining Chemical Reagents and P r e p a r a t i o n s
[in Russian], Vol. 12 {1965), p. 31.
9. F. Bailes and C. Paquot, Ol@agineux, 21__ No. 7, 449 (1966).
10. A . P . T e r e n t ' e v and A. N. Kost, Zh. Obshch. Khimo, 20__ 2069 (1950).
11. A . A . P o n o m a r e v and I. M. Skvortsov, Zh. Obshch. Khim., 32__ 97 (1962).
12. T. B u r k h a l t e r , V. Stephens, and L. Hall, J. A m e r . Chem. Sot., 74__ 3868 (1952).

109
A SMILES REARRANGEMENT IN THE PYRIDAZINE SERIES

V. G. E r m o l a e v a , M. N. S h c h u k i n a , * UDC 547.852
a n d N. F . K o r o l e n o k

In the h y d r a z i n o l y s i s of 6-chloro-3-(fl-phthalimidoethoxy)-pyridazine a r e a r r a n g e m e n t takes

p l a c e with the f o r m a t i o n of 6-chloro-3-(/3-hydroxyethylamino)pyridazine. The action of thi-
onyl chloride on the l a t t e r has given 6-chloro--2,3-dihydroimidazo[1,2-b]pyridazinium c h l o -
r i d e . The r e a c t i o n of fl-hydroxyethylguanidine with 3 , 6 - d i c h l o r o p y r i d a z i n e leads to 6 - c h l o -
r o-3-(#-hydr oxyethylguanidino)pyridazine.

In r e c e n t y e a r s , the s e a r c h for new drugs has been c a r r i e d on intensively among guanidine d e r i v a t i v e s

(see, for e x a m p l e , [1]).
In this connection, we p r o p o s e d to s y n t h e s i z e 3-(fl-aminoethoxy)-6-chloropyridazine, which would be
the key compound for a s e r i e s of d e r i v a t i v e s having biological i n t e r e s t by the r e a c t i o n of 3 , 6 - d i c h l o r o p y r i d -
azine with the sodium d e r i v a t i v e of 2-aminoethanolo However, instead of the expected 3-(fl-aminoethoxy)-6-
c h l o r o p y r i d a z i n e we obtained 6-chloro-3-(B-hydroxyethylamiao)pyridazine (I).

cl x..--.~.N
NH CNHCH.~CH~OH
~
CI/~.N -N
NHCH2CH2OH

CI-
VII !
V V!
[
CI.,~/'Ct
CV'%N.N
II

IV

The condensation of 3 , 6 - d i c h l o r o p y r i d a z i n e with N-(fl-hydroxyethyl)phthalimide in the p r e s e n c e of

p o t a s s i u m c a r b o n a t e yielded 6-chloro--3-(B-phthalimidoethoxy)pyridazine (II), the saponification of which with
dilute h y d r o c h l o r i c acid led to 3 - c h l o r o p y r i d a z i a - 6 - o n e (III) and with dilute acetic acid to 6-hydroxy-3-(3-
phthalimidoethoxy)pyridazine (IV). When compound (II) was heated with an ethanolic solution of h y d r a z i n e
h y d r a t e the saponification of the phthalimide p r o t e c t i o n was a c c o m p a n i e d by a Smiles r e a r r a n g e m e n t with
the f o r m a t i o n of 6-chloro-3-(B-hydroxyethylamino)pyridazine (I). As is well known, the Smiles r e a r r a n g e -
m e a t , which is an i n t r a m o l e c u l a r anionoid c l e a v a g e , takes p l a c e under the influence of b a s e s . Apparently,
a s i m i l a r r e a r r a n g e m e n t takes p l a c e in the r e a c t i o n of 3 , 6 - d i c h l o r o p y r i d a z i n e with the sodium d e r i v a t i v e
of 2-aminoethanol.

~Deceased.

S. Ordzhonikidze All-Union Scientific--Research Institute of P h a r m a c e u t i c a l C h e m i s t r y , Moscow.

T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 1, pp. 124-126, J a n u a r y , 1974. Original a r t i -
cle submitted May 11, 1972.

9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, N.Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy o f this article is available from the publisher for $15.00.

ii0
 When compound (I) was treated with thionyl chloride, 6-chloro-2,3-dihydroimidazo[1,2-b]pyridazinium
chloride (V) and 6-chloro-2,3-dihydroimidazo[1,2-b]pyridazine (VI)were isolated.
The r e a c t i o n of 2-guanidinoethanol [2] with 3 , 6 - d i c h l o r o p y r i d a z i n e in the p r e s e n c e of a sodium alkox-
ide f o r m e d 6'chloro-3-(B-hydroxyethylguanidino)pyridazine (VII). The latter showed no hypotensive activity.

EXPERIMENTAL
6-Chloro-3-(B-hydroxyethylamino)pyridazine (I). A. With s t i r r i n g , 5.96 g (0.04 mole) of 3 , 6 - d i c h l o r o -
p y r i d a z i n e was s c a t t e r e d onto a solution of the sodium alkoxide obtained from 0.96 g (0.041 g-atom) of
sodium and 20 ml of 2-aminoethanol. On the following day the sodium chloride was filtered off, the a m i n o -
ethanol was distilled off in vacuum, the r e s i d u e was t r i t u r a t e d with 10 ml of absolute ethanol, and 4.76 g of
compound (I) was filtered off; yield 69%, mp 131-133~ (from ethanol). According to the l i t e r a t u r e [3], mp
135~
B. A m i x t u r e of 8.32 g (0.027 mole) of compound (II), 1.4 ml of hydrazine hydrate, and 100 ml of ab-
solute ethanol was boiled for 2 h. The p r e c i p i t a t e of phthalhydrazide (5.66 g) was filtered off~ The filtrate
was evaporated to d r y n e s s and the r e s i d u e was r e c r y s t a l l i z e d from a small amount of absolute ethanol, giv-
ing 2.82 g (59%) of the amino alcohol (I), mp 132-133~ (it gave no d e p r e s s i o n of the melting point with the
sample obtained previously).
3-(~-Acetoxydthylamino)-6-chloropyridazine. A mixture of 1 g of the amino alcohol (I) and 20 ml of
acetic anhydride was heated to 40~ and left overnight. The acetic anhydride was distilled off in vacuum to
d r y n e s s , 2 m! of w a t e r was added to the residue, and 1 g of 3-(fi-acetoxyethylamino)-6-chloropyridazine was
filtered off; it f o r m e d c o l o r l e s s c r y s t a l s with mp 151-153~ {from ethanol). Found.~ C 44.6; H 4.8; C1 16.1;
N 19.3%. CsH10C1N302. Calculated: C 44.6; H 4.7; C1 16o4; N 19.5%.
6-Chloro-3-(N-hydroxyethyl-N-nitrosoamino)pyridazine. A saturated solution of sodium nitrite was
added to a solution of 1 g of the amino alcohol (I) in 45 ml of 0.5 N h y d r o c h l o r i c acid until a r e a c t i o n was
given with s t a r c h - i o d i d e paper, The p r e c i p i t a t e was filtered off and washed with water. C o l o r l e s s c r y s t a l s
with mp 104-105.5~ (from ethanol). Found: C 35.8; H 3.6; C1 17.0; N 27.6%. CGHTC1N402. Calculated:
C 35.6; H 3.5; C1 17.5; N 27.7%.
3-(N-Acetoxyethyl-N-nitrosoamino)-6-chloropyridazine. This was obtained in a s i m i l a r m a n n e r to the
p r e c e d i n g compound from 3-(fl-acetoxyethylamino)-6-chloropyridazine. Colorless c r y s t a l s with mp 73.5-
74.5~ (from absolute ethanol). Found: C 39.2; H 3.8; C1 14.1; N 22.9%. CsH~C1Nr 3. Calculated: C 39.3;
H 3.7; C1 14.5; N 22.9%.
6-Chloro-3-(~-phthalimidoethoxy)pyridazine (II). A mixture of 12.3 g (0.083 mole) of diehloropyrid-
azine, 16.51 g (0~ mole) of ~-hydroxyethylphthalimide [4], and 11.5 g of calcined p o t a s s i u m carbonate
was heated at 140~ for 2 h. After cooling, the r e a c t i o n mixture was c r y s t a l l i z e d f r o m absolute ethanol.
This gave 9.86 g {39%) of (II) in the f o r m of c o l o r l e s s c r y s t a l s with mp 168.5-170~ Found: C 55.4; H 3.4;
C1 11.4; N 13.8%. C14H10C1N303. Calculated: C 55.4; H 3.2; C1 11.7; N 13.8%.
6-Chloro-2,3-dihydropyridazin-3-one (III). A mixture of 1 g of compound (II) and 30 ml of dilute (1:1)
h y d r o c h l o r i c acid was boiled for 3 h and cooled, and 0.38 g of phthalic acid was filtered off. The aqueous
l a y e r was evaporated to d r y n e s s in vacuum, a small amount of water was added, the phthalic acid that had
deposited was filtered off, and the filtrate was t r e a t e d with aqueous a m m o n i a to pH 7.5-8. The (III) that
s e p a r a t e d out was filtered off. C o l o r l e s s needles with mp 146-148~ {from absolute ethanol). Found: C
36.4; H 2.2; N 22.0%. C4H3C1N20. Calculated: C 36.8; H 2.7; N 21.5%.
3-Hydroxy-6-(fl-phthalimidoethoxy)pyridazine (IV). A m i x t u r e of 1 g of compound (II) and 30 ml of 50%
acetic acid was boiled for 10 h. Then the solution was evaporated to d r y n e s s , the r e s i d u e was neutralized
with ammonia, and 0.58 g of {IV) was filtered off. Colorless c r y s t a l s with mp 239-241~ (from absolute
ethanol). Found: C 58.9; H 3.8; N 14.9%. C14HliN304. Calculated: C 58.9; H 3.9; N 14.7%.
6-Ch!ore-2,3-dihydroimidazo[1,2-b]pyridazinium Chloride (V). Thionyl chloride (2.8 ml) was grad-
ually added to a solution of 2.84 g (0.02 mole) of (I) in 240 ml of d r y dichloroethane. The r e a c t i o n m i x t u r e
was evaporated to d r y n e s s . The r e s i d u e was t r e a t e d with 20 ml o f w a t e r , a n d , with cooling, the mixture was
made alkaline with aqueous ammonia. The p r e c i p i t a t e was filtered off and washed with water, to give 2.2 g
(58%) of the chloride (V). C o l o r l e s s c r y s t a l s with mp 235-236~ (decomp., f r o m absolute ethanol). Found:
C 37.5; H 3.8; C1 36.7; C1- 18.2; N 21.2%. C6H?C12N3. Calculated: C 37.5; H 3.7; C1 36.9; C1- 18.2; N 21.9%.

111
 The aqueous solution was e x t r a c t e d with e t h e r , the e x t r a c t was d r i e d with calcined m a g n e s i u m sul-
fate, and the e t h e r was distilled off, giving 0.5 g of the i m i d a z o p y r i d i n e (IV) in the f o r m of yellow p l a t e s
with mp 116-117~ According to the l i t e r a t u r e [5], mp 113-115~
Hydrochloride of 6-Chloro-3-(~-hydroxyethylguanidino)pyridazine (VII). To a solution of the sodium
ethoxide obtained f r o m 0.2 g of sodium and 7 m l of absolute ethanol was added 1.33 g of B-hydroxyethyl-
guanidiae h e m i s u l f a t e , the m i x t u r e was t r i t u r a t e d , and a f t e r 30 m i n it was filtered. The f i l t r a t e was t r e a t e d
with 1.3 g of dichloropyridazine; the r e s u l t i n g p r e c i p i t a t e was f i l t e r e d off. The addition of absolute e t h e r
to the solution yielded a g r a d u a l l y c r y s t a l l i z i n g p r e c i p i t a t e of (VII); weight 1 g, c o l o r l e s s c r y s t a l s with mp
186-187~ Found: C 33.5; H 4.3; N 27.8%. CTHi0C1NsO2-HC1. Calculated: C 33.4; H 4.4; N 27.7%.

LITERATURE CITED
1. J. B. Brown, C. W. P i c a r d , T. G. White, and H. L a v e n e r , J. Med. Chem., 1051 (1970).
2. B. J. Ludwig, D. B. R e i s n e r , M. Meyer, L. S. PoweI1, L, Simet, and F. Y. Steifel, J. Med. Chem., 60
(1970).
3. M. Kunogai, Nippon Kagaku Zasshi, 82__227 (1961); Chem. Abstr., 56___,10140 (1961).
4. H. D. Drew, Ber., 54___,3158 (1921).
5. S. Ostrover~nik, B. S. Stanovaik, and M, T i l l e r , C r o a t i c a Chem. Acta, 41__ 135 (1965).

112
MASS SPECTRA OF METHOXY-SUBSTITUTED
4-AMINOPYRIMIDINES

R. A. Khmel'nit'skii, N. A. K l y u e v , UDC 543.51:547.853.7 '854

E. A. Kunina, a n d A. A. K r o p a c h e v a

In a study of the m a s s s p e c t r a of methoxy-substituted 4 - a m i n o p y r i m i d i n e s it has been

shown that in the m o l e c u l a r ion the positive charge is predominantly concentrated on the
oxygen atom of the methoxy group, which explains the appearance of the f r a g m e n t a r y ions
(M--H) + and (M-CH2O) +. In c o n t r a s t to the halopyrimidines, the m o l e c u l a r ion does not exist
in the imine f o r m , which is c h a r a c t e r i s t i c only for the f r a g m e n t a r y i o n s (M-CH20) +.

An investigation that we have p e r f o r m e d of simple p y r i m i d i n e s y s t e m s under the action of e l e c t r o n

impact [1, 2] r e v e a l e d the influence of halogens and of various functional groups on the i s o m e r i z a t i o n of the
m o l e c u l a r ion and its behavior in the f i r s t stages of decomposition.
In the p r e s e n t p a p e r , we consider the m a s s s p e c t r a of the following methoxy-substituted 4 - a m i a o p y -
r i m i d i u e s : 4 - a m i n o - 2 - m e t h o x y - 6 - m e t h y l p y r i m i d i n e , 4-amino-6-methoxy-2-methylpyrimidine (II), 4 - a m i n o -
2-methoxy-5-methylpyrimidine (HI), 4-amino--2,6-dimethoxypyrimidine (IV), and 4-amino-6-chloro-2-meth-
oxypyrimidine (V) (Table 1).

The m a s s s p e c t r a were obtained on a Varian MAT-CH-6 instrument with the d i r e c t introduction of the
substance into the ion s o u r c e at a t e m p e r a t u r e of the ionization chamber of 180~ and ionizing voltages of
70 and 20 V.

Table 2 gives the values of the stabilities of the molecules to e l e c t r o n impact (WM) as the r a t i o s of
the intensities of the polyisotopic peak of the m o l e c u l a r ion to the total c u r r e n t in p e r c e n t a g e s , and the
values of the selectivity of d e c o m p o s i t i o n ($1/2), consisting of the number of the m o s t intense peaks in the
m a s s s p e c t r u m amounting to half the total ion c u r r e n t , and the intensities of some c h a r a c t e r i s t i c peaks of
the ions.

The values of WM for the compounds investigated a r e far lower, not only than for the c o r r e s p o n d i n g
4 - a m i n o ( m e t h y l ) p y r i m i d i n e s but also than for the analogous 4-amino0aalo)pyrimidines [2], which, together
with the absence f r o m the m a s s s p e c t r a of compounds (I-V) of peaks of the ions (M-HCN) + and (M-CHzCN) +
shows* the p r e d o m i n a n t localization of the c h a r g e in the m o l e c u l a r ion on the oxygen atom and the fact that
the methoxy group d e t e r m i n e s the m e c h a n i s m of decomposition of these compounds.
It follows from a c o n s i d e r a t i o n of the m a s s s p e c t r a that the imine f o r m of the m o l e c u l a r ion, which is
p r e d o m i n a n t in the case of halogen-substituted 4 - a m i n o p y r i m i d i n e s [2] is not formed in the dissociative
ionization of methoxy-substituted a m i n o p y r i m i d i n e s if they do not contain halogen as a second substituent.
It is known that in the decomposition of methoxy-substituted a r o m a t i c compounds under e l e c t r o n im-
p a c t [3], ions a r i s i n g through the cleavage of one of the two A r - O - C H 3 bonds are f o r m e d with high probabil-
ity. However, in the m a s s s p e c t r a of compounds if-V), the peak of the ion (M-CH3) + is p r a c t i c a l l y absent.
In the f i r s t stage, two p r o c e s s e s are p r e d o m i n a n t : the splitting off of a hydrogen atom and the elimination

*Here and below, M is the m a s s of the m o l e c u l a r ion.

K. A. T i m i r y a z e v Moscow Agricultural Academy. T r a n s l a t e d f r o m Khimiya Geterotsiklicheskikh

Soedinenii, No. 1, pp. 127-130, J a n u a r y , 1974. Original a r t i c l e submitted October 24, 1972.

9 19 75 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

113
 TABLE 1. Mass Spectra of the Compounds Investigated (I-V) (the
peaks with intensities g r e a t e r than 370 of the m a x i m u m peak are
given)
!~ 4"A mino-2- methoxy -6 -methvipyrimidine_ "
26 (3.3). 27 (7.6), 29 (3.6), 30 (4,2), 38 (4,8). 39 (I0.6), 40 (25,8). 41 (45,5). 42 (47,0)..
43 (9,1), 52 (3.6), 53 (4,8), 54 (9,1), 55 (9,1), 56 (9,1), 58 (4,2), 66 (12,1), 67 (5,2). 68
(100,0), 69 (10,6), 70 (3,9), 82 (6,1), 103 (5,5), 1O9 (16,7), 110 (12,1), 116 (5,8). 138 (81,8),
139 (62,1), 140 (6,0)
4"A mino -6- methoxy - 2-methylpyrimidine
27 (6,9), 29 (4,6), 30 (3,2), 40 (5,5), 41 (19,6), 42 (49,4), 43 (37,4), 45 (4,2), 54 (3,5),
55 (6,1), 56 (8,6), 57 (80), 66 (7,5), 67 (210) 68 (I00,0), 69 (14,4), 70 (3,9), 82 (61),
109 (18,2), ll0 (12,4), 138 (15.2). 139 (75,8), 140 (6,6)
4"A mino -2-methoxy - 5-methylpyrimidine
26 (4.4), 27 (8,7). 29 (6.3), 38 (6,5), 39 (22,0), 40 (15.7), 41 (27.5), 42 (26,4), 43 (23,1),
52 (9,4), 53 (6,6}, 54 (18,2), 55 (t3,7), 56 (4,6). 58 (12.8), 65 (4,6), 66 (20,9), 67 (35,2},
68 (12,9), 69 (48,4), 70 (3,7). 81 (5,8), 82 (54,9), 83 (7,8), 92 (5,7), 93 (5,8), 94 (13,0),
97 (3,8), 108 (t3,6), 109 (100,0), ll0 (18,8). ll6 (4,9), 138 (44,0), 139 (96.7), 140 (7,9)
4-Amino-2,6-dimethoxypyrimidine
26 (13,2), 27 (45,9), 29 (41,0), 30 (20,6), 31 (25,9), 38 (13,2), 39 (19,0), 40 (41,0), 41 (55,7),
42 (36,1), 43 (44,3), 45 (3,7), 50 (5,3), 51 (4,8), 52 (4,8), 53 (10,6), 54 (11,1). 55 (23,8),
56 (t3,2), 57 (24,3), 58 (24,3), 66 (29,6), 67 (15,9), 68 (45,9), 69 (24,9), 70 (16,9), 71 (7,9),
80 (3,7), 81 (15,8), 82 (14,9), 83 (10,6), 84 (13,2), 85 (7,4), 93 (7,4), 94 (6,9), 95 (14,3),
96 (9,5). 97 (ll,6), 98 (6,9), I09 (12,7), 110 (45,9). III (12,7). ll2 (4,8), 125 (49,2), 126
(20,6), 127 (5,3), 153 (ll.6), 154 (96,7), 155 (100,0), 156 (8.9)
4-A mino-6-chloro-2-methoxypyrimidine
27 (12,8), 29 (I1,5), 30 (15,7), 31 (5,1), 38 (8,1), 39 (17,9), 40 (12,8), 41 (11,1), 42 (18,3),
43 (76,5), 47 (4,3), 51 (8,1), 52 (14,0), 53 (11,9), 54 (6,8), 55 (9.4), 56 (5,5), 57 (22,5),
58 (4,7), 60 (4,3), 62 (6,8), 84 (4,3), 65 (7,7), 66 (14,0), 67 (45,1), 68 (13,2), 69 (8,5).
74 (8,4), 76 (7,2), 82 (23,8), 86 (5,1), 87 (12,3), 88 (5,5), 89 (6,8), 92 (11,9), 93 (5,1).
94 (29,8),95 (3,4), 102 (9,4), 104 (5,1), 118 (6,8), 123 (5,1), 124 (21,7), 125 (4,3), 128 (6,8),
129 (36,6), 130 (32,7), 131 (17,4), 132 (ll.1), 142 (3,8), t43 (4,3), 154 (42), 155 (4,7),
158 (65,5), 159 (100,0), 160 (29,3), 161 (31,5)

of a neutral f r a g m e n t with the s t r u c t u r e of formaldehyde~ The probability of the l a t t e r p r o c e s s r i s e s by a

f a c t o r of ~ 2 w i t h a r e d u c t i o n i n t h e e n e r g y of t h e i o n i z i n g e l e c t r o n s to 20 e V .

T h e e l i m i n a t i o n of h y d r o g e n i n t h e r e a c t i o n of i o n i z i n g e l e c t r o n s w i t h c o m p o u n d s (I-III) c a n t a k e p l a c e
b o t h f r o m t h e m e t h y l g r o u p a n d f r o m t h e m e t h o x y g r o u p . I n f a v o r of t h e f i r s t d i r e c t i o n i s t h e c o n s i d e r a b l e
m o b i l i t y of t h e h y d r o g e n a t o m s of m e t h y l g r o u p s i n p o s i t i o n s 2, 4, a n d 6 of the p y r i m i d i n e r i n g , a n d a l s o the
g e n e r a l t e n d e n c y f o r t h e d e t a c h m e n t of a h y d r o g e n a t o m f r o m the fl p o s i t i o n w i t h r e s p e c t to a n a r o m a t i c
n u c l e u s o n e l e c t r o n i m p a c t . H o w e v e r , t h e h i g h i n t e n s i t y of the i o n ( M - H ) + i n t h e m a s s s p e c t r a of c o m -
p o u n d s (IV) a n d (V) c o n t a i n i n g no m e t h y l s u b s t i t u e n t s s h o w s t h a t , at l e a s t , the b u l k of the i o n s ( M - H ) + i s
f o r m e d b y the d e t a c h m e n t of a h y d r o g e n a t o m f r o m t h e m e t h o x y g r o u p .

N"~"~ICI13-CHoO N~'~ , ~ CH~3+" N / ~ " f CH3

Structure A
.~.13~(12.2) iog,z.o) / \-c,~c-c,~

N=CH--NH--C~-NII
./~.~c.~ "-:.q.. ~-~-I +" 0~16.,)
c. 2=;J~N' lfl"N"2 81 "
(0,8)
H
3 / HCN ~H.~.m
~ 82 16,9) 9
42 (3,3) N=C=N--Cm-NH
"~38 (5,6) J 1-H2CN 67 14,41
58O,7) 84 (~,3)

T h e e j e c t i o n of a f o r m a l d e h y d e p a r t i c l e i s c o n n e c t e d w i t h t h e f o r m a t i o n of a s t a b l e p s e u d o m o l e c u l a r
i o n ( M - C I I 2 0 ) + of m a s s 109, w h i c h h a s t h e s t r u c t u r e of a 4 - a m i n o ( m e t h y l ) p y r i m i d i n e ( s t r u c t u r e A). T h i s
i o n p r o b a b l y e x i s t s p r e d o m i n a n t l y i n t h e i m i n e f o r m [2]. T h e e l i m i n a t i o n of a n e u t r a l f r a g m e n t H C N f r o m
t h e i o n ( M - C I I 2 0 ) + l e a d s to t h e f o r m a t i o n of a n o t h e r p s e u d o m o l e e u l a r i o n w i t h m a s s 82 a n d the s t r u c t u r e
of a m e t h y l i m i d a z o l e .
A c h a r a c t e r i s t i c f e a t u r e f o r c o m p o u n d (III) i s the o p e n i n g of t h e p y r i m i d i n e r i n g o n t h e e l i m i n a t i o n of
a m o l e c u l e of m e t h y l a c e t y l e n e f r o m t h e i o n w i t h s t r u c t u r e A. I n t h e c a s e of c o m p o u n d (II) the e j e c t i o n of a

114
 T A B L E 2. S t a b i l i t y of t h e M o l e c u l e s to E l e c t r o n I m p a c t (WM), S e -
l e c t i v i t y of D e c o m p o s i t i o n (S~/2), and I n t e n s i t i e s of t h e C h a r a c t e r i s -
t i c Ions in the M a s s S p e c t r a of M e t h o x y - S u b s t i t u t e d P y r i m i d i n e s
( i n t e n s i t i e s of the p e a k s g i v e n in % of the t o t a l i o n c u r r e n t )
Compounds
Ions
I l] III IV V
i
10,0 14,7 12,2 8,9 12.6
31[~ 6,0 6,0 9,0 11,0 7,0
(M--H) 13,2 3,1 5,6 8,6 10,2
M--CH20) t 2.7 3,5 12,6 4,4 4.9
I
structure A)
(A--HCN) + 1,0 1,2 6,9 1,2
(A--CH3C'rH) 1,7 1,5 6,1
(A--CHsCN) 16,2 19,5 1,6
(A--CH3)+ 4,1
(A.- Clf,Ot 7. 1,3
(M - H C N ) 1.8
(M--CI) + 2,4
(M--H) +/(M--CH20) ~ .O,9 2,0 2.0

m o l e c u l e of a c e t o n i t r i l e f r o m the s a m e ion t a k e s p l a c e with high p r o b a b i l i t y , w h i c h l e a d s to the a p p e a r a n c e

of a n i o n w i t h m a s s 68 c o r r e s p o n d i n g to the m a x i m u m p e a k in the s p e c t r u m of t h i s c o m p o u n d .
The d i s s o c i a t i v e i o n i z a t i o n of c o m p o u n d (IV), w h i c h h a s two m e t h o x y g r o u p s i n the p y r i m i d i n e n u c l e u s ,
d i f f e r s l i t t l e in p r i n c i p l e f r o m t h e d e c o m p o s i t i o n of c o m p o u n d s (I-III). O b v i o u s l y , in t h i s c a s e one m u s t
c o n s i d e r the e q u i p r o b a b i l i t y of t h e l o c a l i z a t i o n of t h e c h a r g e on the two o x y g e n a t o m s .
L i k e the d e c o m p o s i t i o n of the m o l e c u l e of m - d i m e t h o x y b e n z e n e [3], f o r c o m p o u n d (IV) the s u c c e s s i v e
s p l i t t i n g off f r o m the m o l e c u l a r ion of two f o r m a l d e h y d e m o l e c u l e s i s c h a r a c t e r i s t i c . A s a r e s u l t of t h i s
p r o c e s s , f r a g m e n t a r y i o n s a r i s e with m a s s e s of 125 and 95 w h i c h h a v e t h e s t r u c t u r e s of a 4 - a m i n o ( m e t h -
o x y ) p y r i m i d i n e and of u n s u b s t i t u t e d 4 - a m i n o p y r i m i d i n e , r e s p e c t i v e l y . The a p p e a r a n c e of a p s e u d o m o l e e u -
l a r ion with m a s s 125 i s a c c o m p a n i e d b y the f o r m a t i o n of a n a d d i t i o n a l d e c o m p o s i t i o n p a t h w a y c o n n e c t e d
with c l e a v a g e of the C - O b o n d t h a t is c h a r a c t e r i s t i c f o r m e t h o x y c o m p o u n d s . The c l e a v a g e of t h i s bond
l e a d s to the d e t a c h m e n t of a m e t h y l g r o u p f r o m t h e m e t h o x y s u b s t i t u e n t with t h e f o r m a t i o n of an ion h a v i n g
m a s s 110. The s u b s e q u e n t e l i m i n a t i o n o f . c a r b o n m o n o x i d e l e a d s to the f o r m a t i o n of a s t a b l e fragmentary
ion with m a s s 82.

+.
OCH~ OCH3

~}CH 3 0

I-O5 (4,4] II0 (4,1)

J -CH20 X~ 42 (3,2)

95 (I,3) 68 14,1) 41 (5.01

T h e i n t r o d u c t i o n of a c h l o r i n e a t o m into t h e n u c l e u s of the m o l e c u l e of (V) i s r e s p o n s i b l e f o r the a p -

p e a r a n c e of a new f i e l d of l o c a l i z a t i o n of t h e c h a r g e in the m o l e c u l a r ion, w h i c h l e a d s to t h e f o r m a t i o n of
the i o n s (M-C1) +. In a d d i t i o n , y e t a n o t h e r c o m p e t i n g d i r e c t i o n a r i s e s w h i c h i s c o n n e c t e d with the l o c a l i z a -
t i o n of t h e c h a r g e on the n i t r o g e n a t o m of the a m i n o g r o u p , a s i s c o n f i r m e d b y t h e p r e s e n c e in the s p e c t r u m
of c o m p o u n d (V) of t h e p e a k of t h e f r a g m e n t a r y ion ( M - H C N ) +.

115
 The i n t e n s i t i e s of the c h a r a c t e r i s t i c p e a k s of the ions given in Table 2 p e r m i t each of the compounds
under c o n s i d e r a t i o n to be c l e a r l y identified. Thus, in the case of the i s o m e r i c compounds (I-III) the s t r u c -
t u r e of each compound is e a s i l y e s t a b l i s h e d f r o m the r a t i o of the p e a k s of the ions (M-H) + and (M-CH20) +.
The ejection of a p a r t i c l e of a e e t o n i t r i l e f r o m the ion with s t r u c t u r e A is c h a r a c t e r i s t i c only for compounds
(I) and (ID, while the elimination of a p a r t i c l e of m e t h y l a c e t y l e n e takes p l a c e with g r e a t e r p r o b a b i l i t y in the
c a s e of compounds (III).

~H
(M_CO+-C! ~ " (M-H) +
124(2,4) CHsO NH2 158 (10,2)
M, 159 (12,6)

N N - - ' ~ , Cl"~ "

Nn2 c.~o~
129 (4,9) ~-HCN 132(1,3)
"'N .C,-~.+ ~:o
%J H
-CI 67 (5,3)

102 (I,21

Compounds (IV) and (V) differ s h a r p l y both f r o m the analogs (I)-(III) and f r o m one another with r e s p e c t
to the p e a k s of the ions (M-HCN) + and (M-C1) +.

LITERATURE CITED
I, R~ A. K h m e l ' n i t s k i i , E. A. Kunina, A. B. Belikov, and Yu. P. Shvachkin, Izv. TSKhA, No. 2, 231 (1971).
2. R. A. K h m e l ' n i t s k i i , N. A. Klyuev, E. A. Kunina, and A. A. Kropaeheva, Khim. Geterotsikl. Soedin.,
1689 (1973).
3. C. S. Baxnes and I. L. Occolowitz, Austral. J. Chem., 16__219 (1963).

116
SOME DERIVATIVES OF PYRIMIDO[5,4-b]QUINOLINE

N. E . B r i t i k o v a , L. A. Belova, UDC 547.831'854.07

O. Y u . M a g i d s o n , * a n d A. S. E l i n a

10-Chloro-2,4 - dioxo d e r i v a t i v e s of pyrimido[ 5,4 -b] quinoli ae have been s y n t h e s i z e d , and nu-
cleophilic substitution r e a c t i o n s in these compounds have been studied.

Investigations in the field of little-studied [1, 2] d e r i v a t i v e s of pyrimido[5,4-b]quinoline a r e of i n t e r -

est, since pyrimido[5,4-b]quinoline is a d e a z a analog of benzopteridine, and s u b s t a n c e s of natural origin
a r e found in the benzopteridine s e r i e s .
We have d e s c r i b e d the s y n t h e s i s of pyrimido[5,4-b]quinolines f r o m d e r i v a t i v e s of orotic acid substi-
tuted in p o s i t i o n 5 by aniline or p - m e t h o x y - or p - c h l o r o a n i l i n e r e s i d u e s (Ia-d) synthesized p r e v i o u s l y [3].
Ring c l o s u r e with the f o r m a t i o n of 1,2,3,4,5,10-hexahydropyrimido[5,4 -b] quinoline-2,4,10-triones was p e r -
f o r m e d by boiling compounds (Ia-d) with an e x c e s s of phosphorus oxychloride. At a higher t e m p e r -
a t u r e , in addition to ring c l o s u r e the r e p l a c e m e n t of one of the hydroxy groups by chlorine took place.
The m o n o c h l o r o d e r i v a t i v e f o r m e d f r o m the acid (Id) can have only s t r u c t u r e (IIId), while in the m o n o c h l o r o
d e r i v a t i v e s obtained f r o m the acids (In-c) the chlorine m a y be p r e s e n t in one of t h r e e p o s s i b l e positions:
2, 4, or 10.

0 H 0 0
R , ,~.~N..y/_._._._._._~,~
N O I /N ~ ~ R" ..11. N - C 6 H a R ~' -p

0 R"' l~oiling O~-..~.~tCOOH boiling ~ - . N ~ , , , ,

R R' R' CI

~1 a-b ! a-d 111 a-d

a R'=R'=H, R'=OCHa; b R'=R'=R"=H; CR'=R'=H, R"=CI; d R'=R'=CH 3, R"=OCIta

To p r o v e the s t r u c t u r e s of s u b s t a n c e s (IIIa-c), the halogen in (IIIb) was r e p l a c e d by a piperidine r e s i -

due, and the r e s u l t i n g compound (IV) was cleaved with aqueous alkali. This gave 3 - a m i n o - 4 - p i p e r i d i n o q u i n -
oline-2-carboxylic acid (V), which was c o n f i r m e d by its c o n v e r s i o n into butyl 3 - b u t y l a m i n o - 4 - p i p e r i d i n o q u i n -
oline-2-carboxulate (VI).
Under f a i r l y s e v e r e conditions, the chlorine in compounds (IIIa-d) r e a c t s with a m i n e s . Thus, c o m -
pound (IV) was obtained by heating s u b s t a n c e (IIIb) with p i p e r i d i n e in d i m e t h y l f o r m a m i d e at a high t e m p e r a -
t u r e . S i m i l a r l y , the a m i n e s (VII) and (VIII) w e r e obtained f r o m (IIIb). In the 8,10-dichloro d e r i v a t i v e (IIIc),
the mobility of the chlorine in position 10 was reduced, and to obtain compound (IX) it was n e c e s s a r y to heat
the chloride (IIIc) with m o r p h o l i n e for a longer p e r i o d . The r e a c t i v i t y of the chlorine in the d e r i v a t i v e (IIIa)
and (IIId) containing a methoxy group in position 8, is lowered to a p a r t i c u l a r l y a p p r e c i a b l e d e g r e e . Under
the conditions mentioned above, these compounds did not take p a r t in the r e a c t i o n with a m i n e s . An a t t e m p t
to r e p l a c e the chlorine in (IHd) by p i p e r i d i n e by heating the r e a c t a n t s in phenol [4] led to the f o r m a t i o n of
the 10-phenoxy d e r i v a t i v e (X). The reduction in the mobility of chlorine on the introduction of an e l e c t r o n -

*Deceased.
S. Ordzhonikidze All-Union S c i e n t i f i c - R e s e a r c h Institute of P h a r m a c e u t i c a l C h e m i s t r y , Moscow.
T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 1, pp. 131-133, J a n u a r y , 1974. Original a r t i -
cle submitted F e b r u a r y 20, 1972.

9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy of this article is available from the publisher for $15.00.

117
 T A B L E 1. Pyrimido[5,4-b]quinolines

Com-] Mp,: ~ ' Found, % Calculated, %

Empirical i
pound[ (decomp.) formula C H CI N C H Cl N
I

Ilia, i >350* CI2HsCIN3Os52,2 3,0 12,4 [ 14,9 51,9 2,9 12,8 1 15,1 40,0
Illc >340* CItHsCbN30246,5 1,7 24,9 I 14,6 46,8 1,8 25.2 [ 14,9 33,6
III& 258* 55,3
C t4HI2C1N~O~ 4,0 ll,3 13,6 55,0 3,9 11,6 13,7 62,0
VII 334* ~ CtsHIoN40~ 60,5 4,8 - - 19,1 60,4 4,7 18,8 55,5
- -

VlIl 278 ~ / CIsHI4N402 68,0 4,7 - - 18,0 67,9 4,4 17,6 66,1
IX 340"[" i Ct~HI~CIIN403 54,5 3,7 ll,0 17,0 54,1 3,9 10,7 ! 16,8 64;2

* From dimethylformamide.
From aqueous dimethylformamide.

d o n a t i n g s u b s t i t u e n t i n t o p o s i t i o n 8 w a s a l s o s h o w n i n the d i f f e r e n t s t a b i l i t i e s of c o m p o u n d s (Ilia and b) to

the a c t i o n of a c i d s . T h u s , on b e i n g h e a t e d w i t h d i l u t e h y d r o c h l o r i c a c i d c o m p o u n d (IIib) w a s c o n v e r t e d
c o m p a r a t i v e l y r e a d i l y i n t o t h e c o r r e s p o n d i n g 1 0 - 0 x o d e r i v a t i v e (IIb), w h i l e s u b s t a n c e (IIIa) r e m a i n e d un-
c h a n g e d u n d e r the s a m e c o n d i t i o n s .

0 Rt

H t
R' V
~'g4 HgOH
'IH2SO4
R'
IV R'ffiN(CH2)~,O, R"ffiH;
VII R'=NHCH2EsHs, R'ffiH;

vm r,=n(cRiho r,,=cl VI
V, VI R'=N(CH2)4 O, W'=H

EXPERIME NTAL
8-Methoxy-l,2,3,4,5,10-hexahydropyrimido[5,4-b]quinoline-2,4,10-trioae (IIa). A mixture of 3.5 mmoles
of compound (In) and I0 ml of POCI 3 was heated at 80~ for 1 h and cooled, the precipitate was filtered off,
it was treated with glacial acetic acid and again filtered off, and was then washed with dimethylformamide
and with water. This gave 0.6 g (67%) of substance (IIa). It did not melt below 350~ Found" C 55.0; H
3.4; N 16.6%. CI2H2N304. Calculated" C 55.6; H 3~ N 16.6%. IR spectra, cm-1: 3240, 3140, 3080, 3000
(NH); 1730, 1690, 1640 (amide C = O).
10-Chloro-l,2,3,4-tetrahydropyrimido[5,4-b]quinoline-2,4-dione (IIIb). A mixture of 3.8 mmoles of
compound (Ib) and 15 ml of POCI 3 was boiled for 3 h and cooled, the precipitate was filtered off and was
treated with ice water and again filtered off; the filtrate was distilled in vacuum and the residue was worked
up as is described above and was p~ified by crystallization from dimethylformamide and was then added
to the main reaction product. This gave 0.52 g (56%) of compound (IIIb). Mp 320~ (decomp., from dimethyl-
formamide). Found- C 53.6; H 2.4; C1 14.0; N 16.9%. CIIH~CIN302. Calculated. C 53.3; H 2.4; C1 14.3; N
17.0%. IR spectrum, cm -I- 3320, 3220, 3080 (NH); 1730, 1710, 1690 (amide C =O).
Compounds (Ilia), (IIIc), and (IIId) were obtained similarly (see Table I). In the preparation of sub-
stance (IIId), the reaction time was 50 rain.
3-Amino-4-piperidinoquinoline-2-carboxylic Acid (V). A mixture of 4 g (13.5 mmoles) of substances
(IV) and 90 ml of 15% aqueous NaOH was heated in an autoclave at 160~ for 5 h. The precipitate was fil-
tered off, treated with dilute hydrochloric acid to pH 3.4, again filtered off, and repreeipitated from aqueous
alkaline solution with hydrochloric acid. This gave 2.7 g (74%) of substance (V). Mp 168~ (decomp., from
water). Found" C 66.9; H 6.4; N 15.4%. CIsHITN302. Calculated; C 66.7; H 6.3; N 15.5%. IR spectrum,
em-~: 3400, 3240 (NH2); 1660 (amino acid C = O with the possible saperpositioa of 6 NH2). PMR spectrum
(DMSO), ppm: 1.70 (B, T-CH2 of the piperidiae substituent), 3.23 (~-CH 2 of the piperidine substituent), 7.44,
7.80 ( m u l t i p l e t s of the b e n z e n e r i n g ) .

118
 Bu~yt 3 - B u t y l a m i n o - 4 - p i p e r i d i u o q u i a o l i n e - 2 - c a r b o x y l a t e (VI). A m i x t u r e of 0.3 g of substance (V),
10 ml of n-butanol, and 0.5 ml of concentrated sulfuric acid was boiled for 5 h. Then the solution was e v a p -
orated in vacuum and the r e s i d u e was t r e a t e d with aqueous NaHCO 3 to pH 7 and was extracted with c h l o r o -
f o r m . This gave 0.2 g (48%) of (VI). Mp 78~ (decomp., from aqueous ethanol). Found: C 72.2; H 8.6; N
11,0%. C23H33N302. Calculated: C 72.1; H 8.6; N 11.0%. IR spectrum, cm-~: 3440, 3330 (NH); 1690 (ester
C = O).
1 0 - P i p e r i d i n e - l , 2 , 3 , 4 - t e t r a h y d r o p y r i m i d o [ 5 , 4 - b ] q u i a o t i ~ e - 2 , 4 - d i o n e (IV). A mixture of 2 g (8.1
m m o l e s ) of (IIIb), 3.4 g (40 mmoles) of piperidine and 30 ml of d i m e t h y l f o r m a m i d e was boiled for 3 h and
was then cooled, and the p r e c i p i t a t e was filtered off and washed with water. This gave 1.3 g (54%) of the
amine (IV). Mp 340~ (decomp., f r o m dimethytformamide). Found: C 64.5; H 5.4; N 19.2%. C16H16N402.
Calculated: C 64.9; H 5.4; N 18.9%. IR s p e c t r u m , cm-l: 3260, 3190, 3070 (NH); 1730, 1700 (amide C~---O).
Compounds (VII), (VIII), and (IX) were obtained s i m i l a r l y (see Table 1). In the p r e p a r a t i o n of (VIII), the
d i m e t h y l f o r m a m i d e was distilled off in vacuum and the r e s i d u e was t r e a t e d with aqueous d i m e ~ y l f o r m -
amide. In the p r e p a r a t i o n of {IX), the r e a c t i o n time was 8 h.
8-Methxy-3-dimethy--phenoxy-1234-tetrahydrpyrimid[54-b]quioine-24-dione (X). A mix-
ture of 0.5 g (1.6 mmole) of the chloride (IIId), 2 g of phenol, and 0.6 g (7 mmoles) of piperidine was heated
at 140~ for 2 h and was cooled and t r e a t e d with 5% aqueous NaOH, and the precipitate was filtered off and
washed with water. This gave 0.33 g (55%) of compound (X) with mp 296~ (decomp., from d i m e t h y l f o r m -
amide). Found: C 66.5; H 4.9; N 11.6. C20H~TN304. Calculated: C 66.1; H 4.7; N 11.6%.
1,2,3,4,5,10-Hexahydropyrimido[5,4-b]quinoline-2,4,10-trione (lib). A m i x t u r e of 0.5 g of the chloride
(IIIb) and 10 ml of dilute h y d r o c h l o r i c acid (1 : 1) was boiled for 3 h and was cooled, and the p r e c i p i t a t e was
filtered off and washed with water. This gave 0.4 g (87%) of the derivative (IIb). It did not melt below
350~ Found: C 57.3;'H 2.9; N 18.3%. CllHTN303. Calculated: C 57.6; H 3.0; N 18.3%.

LITERATURE CITED
1. D. M. Besly and A. A. Goldberg, J. Chem. Soc., 4997 (1957).
2. E. M. Lerine and T. I. Bardos, J. Heteroeycl. Chem., 9, 91 (1972).
3. N. E. Britikova, L. A. Belova, K. A. Chkhikvadze, and O. Yu. Magidson, Khim; Geterotsikl. Soedin.,
273 (1973).
4. O. Yu. Magidson, A. M. Grigorovskli, et al., P r o m . Org. Khim., 1, No. 10, 586 (1936}.

119
L E T T E R S T O TIIE E D I T O R

REACTION OF 2-AMINO-3-ETHOXYCARBONYLTHIOPHEN]'=S
WITH 2,3-DIBROMOPROPYL ISOTHIOCYANATE

A. A. D o b o s h , I . V. S m o l a n k a , UDC547.732.733'854:542.944.1
a n d S. M. K h r i p a k

In the bromination of 4,5-dialkyl-2-(N-~llylthioureido)-3-ethoxycarboaylthiophenes, a m i x t u r e difficult

to s e p a r a t e is obtained. In the r e a c t i o n of 4,5-dialkyl-2-amino-3-ethoxycarbonylthiophenes (I) with 2,3-
dibi:omopropyl isothiocyanate, however, the closure not only of a thiazoliae but also of a p y r i m i d i n e ring
takes p l a c e , leading to a thieno[2,3-d]thiazolo[3,2-a]pyrimidine (ID.

O
R,~._~OO C2Hs H2_ H--CH 2 K N
"R~S/'XNH2[I
II + Br fir NCS R CH2Br

I a,b !1 a,b
R--R=(CH2)4; b R=CH 3

2-Bromomethyl-2,3,4,5,6,7,8,9- octahydrobe nz o[ 4,5] thieno[2,3-d] thiazolo[3,2-a]pyrimidin-5- one (IIa).

A m i x t u r e of 4.5 g (0.02 mole) of 2-amino-3-ethoxycarbonyl-4,5,6,7-tetrahydrobenzo[b]thiophene (in) and 5.2
g (0.02 mole) of 2,3-dibromopropyl isothiocyanate in carbon t e t r a c h l o r i d e was heated on the boiling water
bath for 4 h. The p r e c i p i t a t e was s e p a r a t e d off and washed with e t h e r . Yield 5.6 g (78%), mp 150-151~
(from methanol). UV s p e c t r u m (in ethanol, c 10-~ M), ?~max, nm (log ~): 275 (3.09), 320 (3.27). Found: N
7.9; 7.7%. Ci3Hi3BrNzOSz. Calculated: N 7.8%~
2-Bromomethyl-6,7- dimethyl-2,3,4,5-tetrahydrothie no[2,3- d] thiazolo[3,2-a]pyrimidin--5- one (IIb) was
obtained s i m i l a r l y from 2-amino-3-ethoxycarbonyl-4,5-dimethylthiophene (Ib). Yield 71%, mp 159-160~
(from methanol). UV s p e c t r u m (in ethanol, c 10-5 M), ~max, nm (log e): 275(3o93), 325 (4.15). IR s p e c t r u m
(molding with KBr): 1670 (C =O), 1310-1200 (CHa), 660-540 (C-Br)o Found: N8.6; 8.5%. CtlHllBrN2OS z.
Calculated: N 8.5%.
The same bases (II) w e r e obtained by decomposing the corresponding h y d r o b r o m i d e s synthesized by
an independent route [1].
LITERATURE CITED
1. I . V . Smolanka, A. A. Dobosh, and S. M. Khripak, Khim. Geterotsikl. Soedin., 1289 (1973).

Uzhgorod State University. T r a n s l a t e d from Khimiya Geterotsiklieheskikh Soedinenii, No. 1, p. 134,

January, 1974. Original a r t i c l e submitted May 3, 1973.

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, iV_Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without w~tten permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

120
TRI(ETHOXYCARBONYL)CYCLOPENTA[b][I,4]BENZOTHIAZINE -

A NEW ISO-zr-ELECTRONIC A.NALOG OF AZULENE

N. V. S u m l i v e n k o and G. F . Dvorko UDC 547.869.2:542.953

The condensation of t r i ( e t h o x y c a r b o n y l ) , 1 , 2 - h y d r o x y e y c l o p e n t a d i e n o n e with o-aminothiopheno ! (I) gives

compounds (II) and (III), depending on the conditions. The imine (II) is f o r m e d in ~ 50% yield in m e t h a n o l
(60~ 10 min) with a twofold e x c e s s of (I). After c r y s t a l l i z a t i o n f r o m a m i x t u r e of benzene and hexane
(1 : 1) it f o r m e d a yellow c r y s t a l l i n e s u b s t a n c e (mp 142~ Xmax 420 nm, log a 3.9 in C2HsOH). Found: C
57.6; H 5.1; N 3.4; S 7.9%. C20H21NOTS. Calculated: C 57.3; H 5.1; N 3.3; S 7.6%.

CO2C2H5

~NH~ t C02C:~H5 J ""~/ "S H HO'~C.~_C. H

L~..J j.,.s l| 0~'~C02C2H5 II C02C2S
+ llO~~ "
CO2C2Hs~"x N ~ C02c2H
5
I ~S CO2C~H5
C02C2H5
III

A new i s o - r r - e l e c t r o n i c analog of a z u l e n e - 1,2,3-tri(ethoxycarbonyl)cyclopenta[b][1,4]benzothiazine

(III) was obtained in ~35% yield in p y r i d i n e (100~ 10 min) with e q u i m o l a r concentrations of the r e a c t a n t s
( d a r k - v i o l e t c r y s t a l s with mp 126~ Xmax 558 nm, log c 3.4 in C2H5OH). Found: C 59.4; H 4.6; N 3.6; S
7.8%. C2sHI906NS. Calculated: C 59.8; H 4.8; N 3.5; S 8~ Compound (II) is r e a d i l y converted into (III)
by heating it in a c e t i c anhydride.
The IR s p e c t r u m of (II) shows a band at 3350 cm -1 (OH), which is absent in (III); and the PMR s p e c -
t r u m of (II) (CHC13), unlike that of (III), shows the signal of the p r o t o n of a SH group at 3.55 p p m . The ethyl
p r o t o n s of (II) give six g r o u p s of lines at 1.29, 1.32, a n d 1.38 p p m (CH3, triplet) and 4.23, 4.29, 4.41 p p m
(CH 2, quadruplet). In (III), the ethyl p r o t o n s in p o s i t i o n s 1 and 3 give two groups of lines at 1.37 p p m (CH 3)
and 4.50 p p m (CH2),while the lines of the ethyl p r o t o n s in position 2 a r e d i s p l a c e d with r e s p e c t to them -
1.48 p p m (CH 3) and 4.61 p p m (CH2). The equivalence of the ethyl p r o t o n s of the t e r m i n a l e s t e r groups of
(III) is due to the s i m i l a r values of the c h a r g e in these positions (MOH method).

All-Union S c i e n t i f i c ' R e s e a r c h and Design and Construction Institute of the P e t r o l e u m - P r o c e s s i n g and

P e t r o c h e m i c a l Industry, Kiev. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i e h e s k i k h Soedinenii, No. 1, pp. 134-
135, J a n u a r y , 1974. Original a r t i c l e submitted May 3, 1973.

9 1975Plenum Publishing Corporation, 227 Nest 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy of this article is availablefrom the publisher for $15.00.

121
REACTION OF 2,4-DIARYL-6-METHYLPYRYLIUM SALTS
WITH NITRITE ESTERS

Yu. P. Aadreichikov, G. E . T r u k h a n , UDC 547.812:542.958

N. V. K h o l o d o v a , and G . N. D o r o f e e a k o

We have found that with isoamyl nitrite 2 , 4 - d i a r y l - 6 - m e t h y l p y r y l i u m p e r c h l o r a t e s f o r m the nitroso

compounds (I).

R R R

GlO~" 2 ClO~-
I II

The r e a c t i v i t y of the nitroso groups in compounds (I) probably depends on the electron-donating p r o p -
e r t i e s of the substituents in the p y r y l i u m nucleus. Thus, where R = C6H5, the main product of this r e a c t i o n
is the nitroso compound (I). But where R = 4-CHsOC6H 4 or 3,4-(CHsO)2C6H 3, the nitroso compound formed
immediately condenses with the initial p y r y l i a m salt to f o r m the azomethines (II).
With an e x c e s s of isoamyl nitrite and b r i e f heating in acetic anhydride, 2-methyl-4,6-diphenylpyryl-
ium p e r c h l o r a t e f o r m s 2-nitrosomethyl-4,6-diphenylpyrylium p e r c h l o r a t e (I), yield 93%, g r e e n p r i s m s with
mp 197-198~ (from acetonitrile). IR s p e c t r u m (paraffin oil), cm-l: 1650, 1530, 1100, 940. UV s p e c t r u m
(in CH2C12, ~max, am (log e)~" 270 (0.3), 380 (4.34), 400 (4.33).
We have been unable to observe the i s o m e r i z a t i o n of (I} into an oxime (absorption band of the = N -
OH group absent from the s p e c t r a .
With the initial p y r y l i u m salt in acetic anhydride, (D f o r m s (4,6-diphenylpyrylio-2-ylmethyl)(4,6-
diphenylpyrylio--2-yl-methylene)amine d i p e r c h l o r a t e (II), yield 50%, d a r k - g r e e n p r i s m s with mp 224-225~
(from glacial a c e t i c acid). UV s p e c t r u m , ~max, um (log e): 260 (4.36), 350 (4.65), 380 (4.80).
With isoamyl nitrite in acetic anhydride in the p r e s e n c e of sodium acetate, 2,4-di(p-methoxyphenyl)-
and 2,4--bis(3,4-dimethoxyphenyl)-6-methylpyrylinm p e r c h l o r a t e s f o r m the azomethiaes (ID: [4,6-di(p-
methxyphenypyryi-2-ymethy][46-di(p-methxyphey)pyryi--2-ymethyee]amine d i p e r c h l o r a t e , yield
55%, d a r k - g r e e n p r i s r n s with mp 202-203~ (from glacial acetic acid); UV s p e c t r u m , Xmax, um (log e): 270
(4.60), 380 (4.87), 450 (5.24); and [4,6--bis(3,4-dimethoxyphenyl)pyrylio-2-ylmethyl][4,6-bis(3,4-dimethoxy-
phenyl)pyrylio-2-ylmethyle ne] amine diperchlorate, yield 75%, d a r k - g r e e n p r i s m s with mp 241-242 ~ (from
glacial acetic acid). UV spectrum, ~max, am (log e)g 270 (4.38), 300 (4.39), 350 (4.39), 420 (4.58), 480 (4.98).
T h e r e s u l t s of e l e m e n t a r y analysis for all the compounds obtained c o r r e s p o n d e d to the calculated figures.

Rostov State University. Scientific-Research Institute of Physical and Organic Chemistry, Rostov-
on-Don. T r a n s l a t e d f r o m Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 135-136, January, 1974. Orig-
inal a r t i c l e submitted May 10, 1973.

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher, A copy o f this article is available from the publisher for $15.00.

122
CARBONYL DERIVATIVES OF 2-ARYLTHIOPHENES

V. K. Polyakov, Z. P. Zaplyuisveehka, UDC 547.733.734:543.422

and S. V. Tsukerman

The r e a c t i o n of 4 - R - b e n z e n e d i a z o n i u m chlorides (R = H, CH a, CHaO, C1, Br) with thiophene (Gomberg

reaction) has given 2-arylthiophenes, which have been converted by V i l s m e i e r f o r m y l a t i o n into 5 - a r y l t h i o -
p h e n e - 2 - c a r b a l d e h y d e s (Table 1), as d e s c r i b e d by D e m e r s e m a n et al. [1]. The l a t t e r , on condensation
(methanolic solution of caustic soda, 45-55~ with acetophenone has given chalcone analogs (Table 2):

|-V ','~--X

P r e v i o u s l y , 3 - ( 5 - p h e n y l - 2 - t h i e n y l ) - l - p h e a y l p r o p - 2 - e n - l - o n e (VI) has been d e s c r i b e d [2] with a yield of 51%

and mp 110-112~ The s t r u c t u r e of the compounds obtained has been c o n f i r m e d by UV and IR s p e c t r o -
scopy. The e l e c t r o n i c s p e c t r a showed that the thiophene ring is a b e t t e r t r a n s m i t t e r of e l e c t r o n i c influences
than a 1,4-phenylene s y s t e m .

TABLE I. 5-Arvlthiophe ne-2-carbaldehyde s (I-V)

S. % i
C OITI- ] Empirical Yield, Xmax, nm (log s)
eai-
pound R formula found culat- % (in ethanol)
,ed
I
I H' 90 CuHsOS 87 231 (3,96) ~ 332 (4,33)
II CHa 93 Cl2HioOS 15,8 83 235 (4,00) ] 335 (4,37)
III 116 C~2HtoO2S 14,9 15,0 14,7 85 24, (4,00) 350 (4,30)
IV 87 C12HmC1OS 14,1 14.2 14,4 81 235 (4,01) 331 (4,34)
V Br 114 Ct2HloBrOS 11,8 12,1 12,0 80 237 (4,00) 331 (4,38)

TABLE 2. 3-(5-Aryl-2-thienyl)-l-phenylprop-2-ea-1- ones (VI-X)

s, %
Com - .~p, Empirical Yield, kmax, nm (log ~)
pound R fou nd eulat- % (in ethanol)
formula ed

VI H 122 CzgH,4OS 98 270 (4,12) 378 (4,48)

VII CHs 132 C2oHI,OS 97 273 (4,14) 387 (4,47)
v,IIix H3o 149
153
C2oH1602S
CIoHIzCIOS
10,2
10,0
10,3
10,1
10,0
9,9
98
99
282 (4,16)
272 (4,13)
397 (4,43)
382 (4,50)
X Br 166 CIgHIsBrOS 8,7 8,8 8,7 98 268 (4,52) 381 (4.65)

LITERATURE CITED
I. P. Demerseman, Ng. Buu-Ho~', and R. Royer, J. Chem. Soc., 4193 (1954).
2. A. E. Lipkin, N. I. Putokhin, and S. I. Borisov, Khim. Geterotsikl. Soedin., 1021 (1967).

A. M. Gor'kii Khar'kov State University. Translated from Khimiya Geterotsiklicheskikh Soedinenii,

No. 1, p p . 1 3 6 - 1 3 7 , J a n u a r y , 1 9 7 4 . O r i g i n a l a r t i c l e s u b m i t t e d M a y 2 9 , 1 9 7 3 .

9 19 75 Plenum Publishing Corporation, 227 West 1 7th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

123
2-STYRYLPERIMIDINES

V. A . Anisimova and A. F. Pozharskii UDC 547.856.7

We have e s t a b l i s h e d that 2 - m e t h y l p e r i m i d i n e s r e a d i l y r e a c t with a r o m a t i c a l d e h y d e s at 100-190~ in

the a b s e n c e of a s o l v e n t o r c a t a l y s t , f o r m i n g deeply c o l o r e d 2 - s t y r y l p e r i m i d i n e s (III) with y i e l d s of about
95%.

#-A. 0,,
N ArCHO . ~kr_.CH__CIi~& r

1 a,b I! a, b Ill a - d

Ia R=H, Ila Ar=--C~H4NO2-p. IIIa R=H. Ar=C6H~;

Ib R=CH3; lib Ar=5-nitrofuryl b R=CH3, Ar=C6Hs;
e R=CH3, Ar=-C~H4NO2-p'
dR=CH3. Ar= 5-mtrofuryl'

In the c a s e of a l d e h y d e s with e l e c t r o n - a c c e p t i n g s u b s t i t u e n t s (p-nitrobenzaldehyde, 5 - n i t r o f u r f u r a l ) ,

at a l o w e r t e m p e r a t u r e it is p o s s i b l e to i s o l a t e the c a r b i n o l s (II) f o r m e d a s i n t e r m e d i a t e s , and on being
h e a t e d to a h i g h e r t e m p e r a t u r e t h e s e d e c o m p o s e with the f o r m a t i o n of the 2 - s t y r y l p e r i m i d i n e s .
The s t r u c t u r e of the c o m p o u n d s obtained (Table 1) was shown by e l e m e n t a r y a n a l y s e s , IR s p e c t r a ,
and the independent s y n t h e s i s of s u b s t a n c e s (IIIa) and (IIIb) s t a r t i n g f r o m the c o r r e s p o n d i n g naphthalene-
d i a m i n e and c i n n a m o y l c h l o r i d e .

T A B L E 1' C h a r a c t e r i s t i c s of the Compounds Obtained

Corn- Mp, ~ .. Solvent for crys- I Color Yield, Conditions of

pound i tallization I fusion
IIa 193 j:DMFA IDark yellow i o5 120~ 5 min.
IIb 100 (decomp,) (* . Brown 9 ~ 6o 60~ 5 m)n
Ilia 136 " | Petromum ether Claret ~ 70 150~ 2 h
IIIb 124--125 Petroleu m ether Claret 150o, 5 h
file 195 Benzene-petrO-leum
ether Dark claret !90--t95 ~ 30rain
IIld 202--203 ! Benzene Dark violet 50 75 100~ lOmin T

9 It w a s i m p o s s i b l e to s e l e c t a solvent.
t The r e a c t i o n t a k e s p l a c e b e t t e r in a c e t i c a n h y d r i d e .

" R o s t o v State U n i v e r s i t y . S c i e n t i f i c - R e s e a r c h Institute of P h y s i c a l and O r g a n i c C h e m i s t r y , R o s t o v -

on--Don. T r a n s l a t e d f r o m K h i m i y a G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 1, pp. 137-138, J a n u a r y , 1974.
O r i g i n a l a r t i c l e s u b m i t t e d June 18, 1973.

9 19 75 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N.Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

124
BENZO-1,2,3-THIASE LENAZ OLIUM SALTS

Yu. I. Akulin, B. Kh. Strelets, UDC 547.789.8:543.422.25

and L. S.t2fros

We have found that the action of seleaous acid in acetic or f o r m i c acid on o-aminothiophenols r e a d i l y
f o r m s b e n z o - l , 2 , 3 - t h i a s e l e n a z o l i u m salts (I) {yields 28-54%). These new h e t e r o c y c l i c cations, which a r e
the 2-selena analogs of the Hertz salts, c r y s t a l l i z e well in the f o r m of double salts with zinc chloride and

+ e ZnCl 2-
R S
In, b

I a R=CI; b R=CH~0

in the form of p e r c h l o r a t e s . Their s t r u c t u r e is shown unambiguously by their PMR s p e c t r a in which multi-

plets of a r o m a t i c p r o t o n s of the ABX type a r e seen. The downfield shift of the signals of the protons, and
also the deeper coloration of the compounds as c o m p a r e d with the Hertz s a l t s , shows the g r e a t e r t r a n s f e r
of charge into the benzene nucleus. UV s p e c t r u m , ~max, nm flog ~): (In) 445 (3.59); (Ib) 475 (3.92).

Leningrad Branch of the All-Union Scientific-Research Institute of Synthetic Fiber. Translated from
Khimiya Geterotsiklicheskikh Soedinenii, No. 1, p. 138, January, 1974. Original article submitted June 18,
1973.

9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy of this article is available from the publisher for $15.00.

125
REACTION OF 6-(CYANOMETHYL)PHENANTHRIDINE
WITH ACYLATING AGENTS

E. V. G r i s h i n a , ]~. R. Z a k h s , UDC 547.836.3:542.951

and V. P. M a r t y n o v a

We have e s t a b l i s h e d that on b e i n g heated in acetic anhydride 6-(cyanomethyl)phenanthridine (I) f o r m s

a neutral compound (II) differing s h a r p l y f r o m phenanthridine d e r i v a t i v e s by the intense splitting of the ab-
sorption band at about 400 am. On the b a s i s of a d e t e r m i n a t i o n of its composition and m o l e c u l a r weight,
and a l s o f r o m its IR and PMR s p e c t r a , compound (II) m u s t be a s s i g n e d the s t r u c t u r e of 5 - a c e t y l - 6 - c y a n o -
methyl dihydrophenanthridine. The acid h y d r o l y s i s of compound (II) gives a high yield of 6-methylphenan-
thridine, compound (I) being detected c h r o m a t o g r a p h i c a l l y as an i n t e r m e d i a t e compound. Compound (II) is
a p p a r e n t l y f o r m e d by the splitting off of a p r o t o n f r o m the cyanomethyl group of the phenanthridinium s a l t
f o r m e d initially.

| I|

Compound (II) is r e l a t i v e l y inert: it does not change at r o o m t e m p e r a t u r e under the action of 2 N

alkali, does not add hydrogen under n o r m a l conditions in the p r e s e n c e of Raney nickel, and does not r e a c t
on being heated with benzaldehyde and its d e r i v a t i v e s . However, on being heated with p - d i m e t h y l a m i n o b e n z -
aldehyde in acetic acid it is converted into 6 - ( ~ - c y a n o - p - d i m e t h y l a m i n o s t y r y l ) p h e n a n t h r i d i n e [t]. A com-
pound analogous to (II) is f o r m e d by the r e a c t i o n of compound (I) with benzoyl chloride.
5-Acetyl-6--cyanomethylene--5,6-dihydrophenanthridine (II). A m i x t u r e of 0.2 g of compound (I) and 6
m l of a c e t i c anhydride was boiled for 4 h, and a f t e r cooling 0.15 g of (II) was filtered off and was c r y s t a l -
lized f r o m benzene (1:40). Yellow needles with mp 214-215~ In CDC13, 5 2.55 p p m (COCH3, singlet). IR
s p e c t r u m (KBr), c m - l * : 2180, 1630, 1600, 1585, 1530, 1500, 1480, 1405, 1360, 1280, 1225, 1170, 1140, 985,
950, 935,765, 7 5 0 , 7 1 0 . In ethanol ~max, am (log e): 241 (4.54), 255 (4.32, shoulder), 272 (4.18), 293 (3.95),
320 (3.70), 335 (3.70), 387 (4.29), 408 (4.32). Found: C 78.7; H 4.9; N 11.1%; m o l . wt. 273 ( r e v e r s e e b u l l i o -
scopy in c h l o r o f o r m ) . CITH12N2O. Calculated: C 78.5; H 4.6; N 10.8%; mol. wt. 260. F o r h y d r o l y s i s , 0.1 g
of compound (II) was heated in 6 ml of 30% H2SO4 at 140~ for 8 h, and the m i x t u r e was neutralized and ex-
t r a c t e d with benzene to give 0.06 g (84%) of 6-methylphenanthridine, identical with an authentic s a m p l e .
5-Benzoyl-6-cyanomethyl-5,6-dihydrophenanthridine. & m i x t u r e of 0.25 g of compound (I) and 5 m l of
benzoyl chloride was heated at 140~ for 2 h and was then e v a p o r a t e d in vacuum to 2 ml, poured into water,
and n e u t r a l i z e d with sodium carbonate. This gave 0.26 g of yellow c r y s t a l s with mp 254~ (from ethanol).
In ethanol, 7hnax, am (log a): 248 (4.65), 272 (4.25), 295 (4.18), 325 (3.84), 340 (3.82), 395 (4.44), 415 (4.52}.
IR s p e c t r u m (KBr), cm-l: 2184, 1630, 1600, 1565, 1535, 1500, 1480, 1440, 1410, 1360, 1340, 1315, 1260,
1230, 1170, 1000, 925,755, 740, 718, 698. Found: N 8.8%; m o t . wt. 316. C22HI4N20. Calculated: N 8.7%;
m o l . wt. 322.

*The s t r o n g e s t a b s o r p t i o n bands a r e underlined.

L e n s o v e t Leningrad Technological Institute. T r a n s l a t e d f r o m Khimiya Geterotsiklicheskikh Soedi-
nenii, No. 1, pp. 138-139, J a n u a r y , 1974. Original a r t i c l e submitted July 13, 1973.

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy o f this article is available from the publisher for $15.00.

126
CHRONICLES

CONFERENCE ON C O O R D I N A T I O N CHEMISTRY

M. G. V o r o n k o v

The 15th International Conference on Coordination C h e m i s t r y , organized by the Academy of Sciences

of the USSR and by Moscow State University, was held in Moscow on June 25-30, 1973. More than 1300 s c i -
entists f r o m v a r i o u s c o u n t r i e s took p a r t in it. Ten p l e n a r y l e c t u r e s and 386 sectional c o m m u n i c a t i o n s
w e r e d e l i v e r e d . The c o n f e r e n c e was opened in the K r e m l i n P a l a c e of C o n f e r e n c e s by a s p e c i a l s e s s i o n de-
voted to the c e n t e n a r y of the b i r t h of L. A. Chugaev. The sectional c o n f e r e n c e s w e r e grouped a c c o r d i n g to
the p r o b l e m s of coordination c h e m i s t r y : s p e c t r o s c o p y , s t r u c t u r e and the c h e m i c a l bond, the s y n t h e s i s of
new types of coordination compounds, c a t a l y s i s , kinetics and r e a c t i o n m e c h a n i s m s , t h e r m o d y n a m i c s , and
complex f o r m a t i o n in nonaqueous and g a s e o u s m e d i a . In ~tctual fact, in these sectional s e s s i o n s , as in the
p l e n a r y l e c t u r e s , a c o n s i d e r a b l y w i d e r r a n g e of questions was c o n s i d e r e d - b e g i n n i n g f r o m the r o l e of c o m -
p l e x f o r m a t i o n in the activity of e n z y m e s and ending with the study of the p r o d u c t s of the t h e r m o l y s i s , p h o -
t o l y s i s , and r a d i o l y s i s of coordination s t r u c t u r e s (lecture of A c a d e m i c i a n V. I. Spitsyn). Some of the l e c -
t u r e s w e r e e s s e n t i a l l y devoted to the l a t e s t p r o b l e m s of organic c h e m i s t r y , such as: the s t r u c t u r e and r e -
actions of r c o m p l e x e s , the r e a c t i o n s of olefins with the p a r t i c i p a t i o n of Z i e g l e r c a t a l y s t s , and the d e t e r -
mination of the c o n f o r m a t i o n s of organic s u b s t a n c e s f r o m t h e i r PMR s p e c t r a with the aid of shift agents of
the type of e u r o p i u m d i p i v a l o y l m e t h a n a t e . F u r t h e r m o r e , a p p r o x i m a t e l y half the l e c t u r e s dealt with subjects
and p r o b l e m s lying at the boundary between o r g a n i c and inorganic c h e m i s t r y . They naturally r e q u i r e d the
wide use of m e t h o d s of both b r a n c h e s of c h e m i c a l s c i e n c e . Consequently, it is not s u r p r i s i n g that in a num-
b e r of the investigations r e p o r t e d wide use was m a d e of the methods of m o d e r n organic c h e m i s t r y (NMR
s p e c t r a in d i v e r s e v a r i a n t s , including the O v e r h a u s e r effect, m a s s s p e c t r a , ESR s p e c t r a , and optical r o t a -
t o r y d i s p e r s i o n and c i r c u l a r d i c h r o i s m ) . The specific nature of coordination c h e m i s t r y , enabling ions of
v a r i o u s m e t a l s to be included in the c o m p o s i t i o n of organic m o l e c u l e s , has opened up the p o s s i b i l i t y of
using the M S s s b a u e r effect, ESR s p e c t r o s c o p y , and other m e t h o d s . A w h o l e s e r i e s of c o m m u n i c a t i o n s was
devoted to d e t e r m i n i n g the s t r u c t u r e s of c o m p l e x e s by m e a n s of the F a r a d a y effect, and also by x - r a y s t r u c -
tural analysis.
The l e c t u r e s devoted to complex h e t e r o c y c l i c compounds (we do not include in this c o n c e p t m e t a l l o -
cycles of coordination s t r u c t u r e and chain s t r u c t u r e s ) , r e l a t e d p r e d o m i n a n t l y to c l a s s i c a l coordination de-
r i v a t i v e s of p y r i d i n e . A n u m b e r of Soviet, Slovak, A m e r i c a n , and Hungarian s c i e n t i s t s have i n v e s t i g a t e d the
optical and m a g n e t i c p r o p e r t i e s of c o m p l e x e s (including those with m i x e d ligands) including a m o l e c u l e of
p y r i d i n e or a substituted d e r i v a t i v e of it. Some c o m m u n i c a t i o n s r e l a t e d to c o m p l e x e s of the b i p y r i d y l s . A
c o m m u n i c a t i o n of the B r a z i l i a n s c i e n t i s t M. I. D. Holand m u s t be mentioned; he has shown that 2 - ( a m i n o -
m e t h y l ) p y r i d i n e is capable in the p r e s e n c e of F e 2+ s a l t s of converting oxo acids into the c o r r e s p o n d i n g
amino acids, and, consequently, it can be used as a convenient model for studying t r a n s a m i n a t i o n . The p r o b -
lem of the r o l e of complex f o r m a t i o n in t h e m e c h a n i s m of the action of biologically active s u b s t a n c e s w a s
widely c o n s i d e r e d in the p l e n a r y l e c t u r e by the Polish p r o f e s s o r B. J ~ z o w s k a - T r z e b i a t o w s k a . H e r own
investigations, r e p o r t e d at the c o n f e r e n c e , r e l a t e d to c o m p l e x e s b a s e d on m a c r o m o l e c u l a r ligands (in p a r -
ticular, 1 4 - m e m b e r e d r i n g s with four nitrogen a t o m s , which m o d e l the inner ring of the p o r p h y r i n s ) . Au-
t h o r s f r o m v a r i o u s countries gave a n u m b e r of p a p e r s devoted to p o r p h y r i n s t r u c t u r e s , including the kinet-
ics of c o m p l e x - f o r m a t i o n .
Rostov c h e m i s t s (0. A. Osipov, A. D. Garnovskii, and V. I. Minkin arid t h e i r c o - w o r k e r s ) p r e s e n t e d a
s e r i e s of c o m m u n i c a t i o n s on c o m p l e x e s b a s e d on azoles and t h e i r Schiff's b a s e s or acyl d e r i v a t i v e s (diel-
c o m e t r i c a n d e l e c t r o c h e m i c a l investigations, c o r r e l a t i o n a n a l y s i s , and q u a n t u m - c h e m i c a l calculations).

T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 1, pp, 140-141, J a n u a r y , 1974.

9 19 75 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

127
 Of t h e investigations devoted to complexes based on nitrogenous heteroaromatic compounds, those
relating to complexes of imidazole, histidine, and histamine must be mentioned. They are connected with
the elucidation of the r o l e of complex formation in the biological action of such substances. The American
J. Vill gave a lecture on complex compounds of some purines and pyrimidiaes. Of interest were the review
lectures of V. A. Kabanov on the modeling of enzyme systems by means of copper complexes of polyvinyl-
pyridine, of V. M. Dziomko on the synthesis of extractants belonging to the pyrazole, imidazolylimidazole,
and iadoloquinoxaline s e r i e s , and of N. D. Rus'yanova on the separation of pyridine and quinoline bases of
coal via their halostibates. A s er i e s of papers of a traditional analytical direction related to the use of
various heterocyclic compounds as analytical reagents (8-hydroxy- and 8-mercaptoquinolines and some
dithiocarbamates). Connected with these were some communications, for example, on complexes of o-hy-
droxythiopyrone or triazinetrithione having as their aim the search for antidotes.
Lectures by A. N. Nesmeyanov and his colleagues were devoted to the fine synthesis of organic com-
pounds of gold and of complexes of iron carbonyls with pyrazoles. The propert i es of the latter resemble
those of the analogous complexes of cyclopentadiene, but they are very unstable. Consequently, they have
been studied mainly by PMR methods~ Nitrosyl complexes of iron with suitable ligands, including azoles,
figured in a number of papers.
On the whole, the conference presented much that was new and interesting not only for inorganic,
physical, analytical, and organic chemistry, but also for the chemistry of heterocyclic compounds.

128
POLAROGRAPHY OF HETEROCYCLIC COMPOUNDS
II.* H E T E R O E T H Y L E N E AND H E T E R O P A R A F F I N COMPOUNDS.
E F F E C T OF SUBSTITUENTS IN THE RIDE CHAIN ON PARAMETERS
FOR THE E L E C T R O R E D U C T I O N OF HETEROCYCLIC COMPOUNDS (REVIEW)

Ya. P. Stradyn', V. P. Kadysh, UDC 543.253:547.7.8

and S. A. Giller

The l i t e r a t u r e data on the p r i n c i p l e s of the e l e c t r o c h e m i c a l reduction of h e t e r o e t h y l e n e and

h e t o r o p a r a f f i n compounds (pyrazoline, diazepine, diaziridine, p y r a n , p y r i d a z o n e , aziridine,
o x a z i r i d i n e , and other d e r i v a t i v e s ) , cyclic anhydrides, i m i d e s , and h y d r a z i d e s of acids on a
d r o p p i n g m e r c u r y e l e c t r o d e a r e c o r r e l a t e d . In addition, the effect of substituents attached
to the h e t e r o c y c l i c ring on the p o l a r o g r a p h i c b e h a v i o r of h e t e r o c y c l e s is analyzed.

Heteroethylene Systems
C o n s i d e r a b l y l e s s study has been devoted to h e t e r o e t h y l e n e s y s t e m s than to h e t e r o a r o m a t i c compounds
in a p o l a r o g r a p h i c r e s p e c t . E l e c t r o c h e m i c a l reduction c o n s i s t s e i t h e r in s a t u r a t i o n of a double b o n d -
usually the C -----Nb o n d - or in the r e d u c t i o n of an e l e c t r i c a l l y active group, which m a y also be conjugated
with the ring double bond, attached to the h e t e r o r i n g . The p r e s e n c e of a sufficient n u m b e r of conjugated
bonds o r high p o l a r i z a b i l i t y of the m o l e c u l e is n e c e s s a r y to confer e l e c t r o c h e m i c a l activity on the h e r e t o -
ring. We r e f e r to A 2 - p y r a z o l i n e d e r i v a t i v e s as an e x a m p l e of p o l a r o g r a p h i c a l l y active hetoroethylene c o m -
pounds.
P y r a z o l i n e s that a r e unsubstituted in the 3 position o r substituted with a methyl group do not have
p o l a r o g r a p h i c activity. The introduction of a phenyl g r o u p o r of h e t e r o a r o m a t i c groups into the 3 position
leads to the a p p e a r a n c e of a wave for the reduction of the azomethine bond at - 2 . 0 V with the c o n s u m p t i o n
of two e l e c t r o n s [2-4]. ..

, . . . . l_~Ar +2e + /Ar

Ar Ar

Like 1 , 3 , 5 - t r i p h e n y l - A 2 - p y r a z o l i n e , all of its h e t e r o c y c l i c analogs have p o l a r o g r a p h i c activity. The

investigated h e t e r o a r o m a t i c r e s i d u e s a r e e l e c t r o n a c c e p t e r s with r e s p e c t to the p y r a z o l i n e ring, and t h e i r
e l e c t r o n - a c c e p t e r p r o p e r t i e s i n c r e a s e in the o r d e r ce-furyl, ~ - t h i e n y l , c~-selenienyl; this is m a n i f e s t e d in
a d e c r e a s e in the reduction potential of the c o r r e s p o n d i n g p y r a z o l i n e d e r i v a t i v e s (-2.14, - 2 . 0 7 , and - 2 . 0 3 V).
B e c a u s e of its r e m o t e n e s s f r o m the r e a c t i o n c e n t e r , a s u b s t i t u e n t in the 5 position has a weak effect on the
reduction of the C = N group, and only its inductive effect is the deciding f a c t o r in this c a s e [3].
The p o l a r o g r a p h i c reduction of 1 , 4 - b e n z o d i a z e p i n e s also a p p a r e n t l y c o n s i s t s in s a t u r a t i o n of the C = N
bond [5]. The reduction p r o c e e d s with the addition of two e l e c t r o n s and two p r o t o n s , for e x a m p l e :
CH3 ~H3

C6Ns C6Hs

* See [1] for p a r t I of this r e v i e w .

Institute of Organic Synthesis, Academyof Sciences of the Latvian SSR, Riga. Translated from Khimiya
Geterotsiklicheskikh Soedinenii, No, 2, pp. 147-162, February, 1974. Original article submitted October 10,
1973.
9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced, I~
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.
1
129
 The reduction of 7 - c h l o r o - 3 - h y d r o x y - 5 - p h e n y l - l , 3 - d i h y d r o - 2 H - 1 , 4 - b e n z o d i a z e p i n - 2 - o n e ("oxazepam")
has been studied m o r e thoroughly [6]. The half-wave potential (El/2) lies in the interval -1.0 to -1.2 V. In
acidic media, oxazepam is reduced with the addition of four electrons to 7 - c h l o r o - 5 - p h e n y l - l , 3 , 4 , 5 - t e t r a -
h y d r o - l , 4 - b e n z o d i a z e p i n - 2 - o n e . In alkaline media, it undergoes 2e reduction to the 4,5-dihydro derivative:

~" .~.,,~/NH: 0 H +"+. ,5 ,/ ~. -,, , ( N H - ~ O +

C6H5 C6H5
~H20 //~4e +3H +
I ::.:._(o:
C l / ~ -':"-~---N H
C6H5 C6H ~

One 2e wave (El/2 -1.45 V), which is ascribable to reduction of the C = N bond, is o b s e r v e d in the r e -
duction of 7 - c h l o r o - 2 - m e t h y l a m i n o - 5 - p h e n y l - 4 , 5 - d i h y d r o - 3 H - 1 , 4 - b o n z o d i a z e p i n e [7]. As a r e s u l t of this
reduction, the ring undergoes contraction to give 6 - c h l o r o - 2 - m e t h y l - 4 - p h e n y l - 3 , 4 - d i h y d r o q u i n a z o l i n e :

El / ~ "[~-NI!
C6H5 C6H5
.I-CH3NH2

CI'2~'~ '~NII CI'~-"~N II

C6H~ C6H.~

Cleavage of the N - N bond of the h e t e r o r i n g is respons ible for the e l e c t r o c h e m i c a l activity of 3,6-
diphenyl-2,3,4,5-tetrahydropyridazine [8, 9] in acidic media:

C6flS"~N'N, H +4e +4 H+ NHo

i ~ NH~
I "
L ~ L v xC6H~ C6HsCHCH2CH2CHC6h~

The e l e c t r o r e d u c t i o n of 3,3-pentamethylenediazirine in alkaline media at - 1 . 5 V consists in 2e s a t u r a -

tion of the N = N bond to give the corresponding diaziridine [10].
However, in acid media (at -1.3 V) this compound undergoes 4e reduction. Cyclohexanone and a m -
monia were isolated in the hydrolysis of the products of the e l e c t r o c h e m i c a l reaction:

+,,2., ,,+2., I
.~ ~-J ,n. I \ ~ ,n.~/
1247 1

C i" H
+ 2 OH
- C =0

Of the heteroethylene derivatives, those in which the double bonds of the h e t e r o r i n g a r e conjugated
with the carbonyl group s e e m of g r e a t e s t i n t e r e s t .
y - P y r o n e [11] and chromone [12] are reduced i r r e v e r s i b l y with the consumption of two e l e c t r o n s , and
the corresponding alcohol is apparently formed:
0 OH HO H

Benzopyrones, p a r t i c u l a r l y flavones, give, at - 0 . 9 to -1.3 V, a r e v e r s i b l e l e wave with subsequent d i m e r i z a -

tion of the resulting f r e e radical; a second reduction wave is also o b s e r v e d at higher pH values, and both
waves s o m e t i m e s m e r g e into an overall 2e wave [13-15].

130
 Flavanones give a 2e wave at s o m e w h a t g r e a t e r negative potentials than flavones, and this wave is
also due to reduction to the alcohol. Isoflavones a r e r e d u c e d i r r e v e r s i b l y with the consumption of two e l e c -
t r o n s . The m o r e negative (than in the c a s e of flavones) reduction potentials (from - 1 . 1 to - 1 . 5 V) and the
distinctly e x p r e s s e d c o m p e t i t i o n between the e l e c t r o r e d u c t i o n waves of the protonated and unprotonated
c a r b o n y l groups in the m e d i u m pH r a n g e m a k e it p o s s i b l e to p o l a r o g r a p h i c a l l y distinguish isoflavones
f r o m flavones [14]. A p o l a r o g r a p h i c method was u s e d to follow the is o m e r i z a t i o n of o - h y d r o x y c h a l c o n e to
c h o r o m a n o n e (i.e., into flavanone and its h e t e r o c y c l i c analogs containing furan, thiophene, p y r r o l e , and
pyridine r e s i d u e s ) , s i n c e the E~/2 values of the s t a r t i n g compounds and final i s o m e r i z a t i o n products differ
s u b s t a n t i a l l y f r o m one another [15]:

11
0
Ar -- phenyl -0,69V - 1,08V
a-thienyl -0,61V - 1,07V
a-furyl -0,67 V - I,IOV

Since s u b s t i t u t e d flavones and isoflavones a r e e n c o u n t e r e d in the plant world in the f o r m of glucos ides
and have high physiological activity, p o l a r o g r a p h i c methods for the d e t e r m i n a t i o n of compounds of this
s e r i e s have been developed (for e x a m p l e , s e e [16]).

, ~ +e+"~+ ~ / ~ --dimer

C o u m a r i n is r e d u c e d [12, 17-21] a~ El/2 - 1 . 5 3 V with the consumption of one e l e c t r o n and subsequent

d i m e r i z a t i o n . C o n t r o l l e d - p o t e n t i a l e l e c t r o l y s is gives two h i g h - m e l t i n g lactones, which a r e p r o b a b l y the
m e s o - and dl - d i m e r s [18]. f l - H y d r o x y c o u m a r i n is p o l a r o g r a p h i c a l l y inactive, while f l - m e t h o x y c o u m a r i n
gives a 2e wave with s a t u r a t i o n of the C = C bond (probably b e c a u s e of s t e r i c h i n d r a n c e to the d i m e r i z a t i o n
r e a c t i o n [12]). Xanthone is r e d u c e d in a l e r e v e r s i b l e p r o c e s s at El/2 -0.91 V with s u b s e q u e n t d i m e r i z a -
tion of the r a d i c a l [22].

+e +H + ~ _ ~ . ~
= " ~ dimer
O OH

The thio and thia analogs of ~(-pyrones also have p o l a r o g r a p h i c activity. However, no l i n e a r c o r r e l a -
tion between the c o r r e s p o n d i n g Et/2 values and the energies of the lower vacant MO was detected [22]; this
indicates different reduction m e c h a n i s m s and different a d s o r p t i o n c h a r a c t e r i s t i c s of the individual r e p r e -
s e n t a t i v e s of the s e r i e s .
0 0 S $

P y r i m i d o n e s and t h i o p y r i m i d o n e s in aqueous methanol m e d i a give a wave in the i n t e r v a l - 1 . 0 to - 1 . 7

V, depending on the pH, with t r a n s f e r of one e l e c t r o n , a f t e r which t h e r e is rapid d i m e r i z a t i o n of the r e s u l t -
ing r a d i c a l s [23, 24]. In a n u m b e r of c a s e s , anomalous waves a s s o c i a t e d with a d s o r p t i o n on the dropping
m e r c u r y e l e c t r o d e (DME) of the d i m e r i c e l e c t r o r e d u c t i o n products a p p e a r . The introduction of e l e c t r o n -
donor groups into the 4 position in p r i n c i p l e hinders e l e c t r o r e d u c t i o n , but, b e c a u s e of the p o s s i b i l i t y of
s u r f a c e protonation, 6 - a m i n o - 2 - p y r i m i d o n e (cytosine) and the c o r r e s p o n d i n g nucleotides and nucleosides
a r e reduced on the DMg s u r f a c e [24-27] (see p a r t I of this r e v i e w ) . On the other hand, u r a c i l does not give
a reduction wave. 6 - A z a u r a c i l and 6 - a z a u r i d i n e a r e r e d u c e d in the protonated f o r m at - 1 . 3 to - 1 . 4 V, and
the wave d e c r e a s e s and g r a d u a l l y b e c o m e s a kinetic wave as the pH i n c r e a s e s [28, 29]. The possibilities
of p o l a r o g r a p h y in the s t u d y of h e t e r o c y c l i c b a s e s of nucleic acids w e r e examined in a p a p e r by Berg and
c o - a u t h o r s [30].

R R

X=O, 5; R = H , CH 3

131
 in acidic media, 6 - m e t h y l - 3 - p y r i d a z o n e is reduced in two 2e stages (at - 0 . 7 and - 0 . 9 V, r e s p e c t i v e l y ) ,
which in the medium pH range m e r g e into one 4e wave; in alkaline media, the compound gives only one 2e
wave [31]. The f i r s t 2e step leads to 6 - m e t h y l - 4 , 5 - d i h y d r o - 3 - p y r i d a z o n e , while the second wave, in the
opinion of Pflegel and Wagner [31], is due to ring opening (cleavage of the N - N bond). However, the p r o b -
l e m of the c l e a v a g e of the N - N bond in the pyridazone ring is still an open question, at l e a s t for 6-
pyridazones that do not have an e l e c t r o n - a c c e p t e r substttuent in the 4 and 5 positions of the ring, if they
a r e investigated on a s h o r t - p e r i o d DME. The following s c h e m e f o r the e l e c t r o r e d u c t i o n of substituted 6-
pyridazones was substantiated in [32]. This s o r t of m e c h a n i s m is o b s e r v e d in both protogenic and aprotic
s o l v e n t s . The p o l a r o g r a p h i c method can be u s e d for the analytical d e t e r m i n a t i o n of the h e r b i c i d e phen-
azone (pyramine, chlorazone) [33, 34].

.... , J.
R R/N II
O 0 0

--2e + s /d \
e+2H + t
not reduced

II
0 , R = H, C6H5

l(2H)-phtl~laT.inones and the potential p r i m a r y products of their elec~oreducUon- 3 A - d i h y d r o -

l(2H)-phthalazinones - which are reduced in acidic media to phfhalimidines with the formation of two 2e
waves, have been more thoroughly studied. 2-phenyl-substiteted derivatives give only the f i r s t stage of r e -
duction [35].
R R R

O O O

R = H , CH3CI; R' = H, GH 3

5 - P h e n y l p y r i d a z i n o n e s a r e reduced with ring opening [9]:

L~o ~ CsHsCHC|I2CH2CONttI~'

The s a m e thing is also o b s e r v e d in the c a s e of 6-alkylpyridazinones, only h e r e the azomethine

d e r i v a t i v e f o r m e d in the f i r s t s t e p undergoes h y d r o l y s i s [9]:

+2 H.O
Ctl~Ctt~cu:CONtl 2 ~ - - CHsCOCtt~C"2COOtt
' L,,,./~, ~
Nil

Saturated Heterocycles (Heteroparaffin Compounds)

Of the s a t u r a t e d h e t e r o c y c l e s , only single r e p r e s e n t a t i v e s , for example, ethyleneimine (aziridine)
d e r i v a t i v e s , have p o l a r o g r a p h i c activity. In the opinion of Mantsavinos and C h r i s t i a n [36], the e l e c t r o r e -
duction waves o b s e r v e d in the i n t e r v a l - 1 . 1 to - 1 . 2 V a r e due to 2e reductive c l e a v a g e of the aziridine ring
to give a t r i a l k y l a m i n e :

/x,
R R'

However, one cannot exclude the p o s s i b i l i t y that the waves a r e due to catalytic evolution of hydrogen via
the following s c h e m e . [371:

+ I//2H2

R H

132
 It has been shown in [38] that N , N - d i e t h y l a z i r i d i n i u m p e r c h l o r a t e is r e d u c e d in aqueous solution in
one 2e s t e p at about - 1 , 5 V. O n e - e l e c t r o n c l e a v a g e of the a z i r i d i n e ring to give a f r e e radical, which is
then r e d u c e d to a c a r b a n i o n , a p p a r e n t l y o c c u r s initially. The r e s u l t i n g c a r b a n i o n can e i t h e r r e a c t with
w a t e r (or with unreduced a z i r i d i n i u m ion) or d e c o m p o s e to give a diethylamine anion and ethylene:

C~Hs\/C2H5

/ ~H.O -OH
...- t

~C2Hs)2N- + C H 2 ~ C H 2 (C21t5)3N (/'~41) N--( H ~ C H 2

P o l a r o g r a p h y was used to study the cyclization of / 3 - c h l o r o d i e t h y l a m i n e s , which is r e s p o n s i b l e for

the d e v e l o p m e n t of the c3rtostatic activity of this s e r i e s of compounds [39]:

F'x.,~/r
RN(CH2CH2CI)2 - - L / ' ~'CH. CH.C|I

Cytostatic agents containing a quinone group along with an a z i r i d i n e ring give the reduction wave of
the quinone ring and, in addition - at g r e a t e r cathode potentials - a wave for the reduction of the aziridine
ring, which has kinetic c h a r a c t e r , d e t e r m i n e d by the r a t e of protonation of the a z i r i d i n e ring [40-44]. Under
c e r t a i n conditions, the second wave is due to catalytic evolution of h y d r o g e n .
0 OH 044 Oh

11 I ! i
O OH OH OH

D i a z i r i d i n e s a r e r e d u c e d on a D M g in two 2e steps (at - 0 . 4 to - 1 . 0 V and at - 1 . 3 to - 1 . 5 V, r e s p e c -

tively) [45].

r'- "n, ~ r'" "~:.., ~ r,/"\n.% a, ~"

The dication f o r m e d as a r e s u l t of c l e a v a g e of the N - N bond is e x t r e m e l y unstable and d e c o m p o s e s

rapidly to give an imine, which is r e d u c e d in the second s t e p to an a m i n e . The i s o h y d r a z o n e s of c y c l o h e x -
anone and methyl ethyl ketone [45] a r e r e d u c e d s p e c i f i c a l l y via this s c h e m e [45].
It follows f r o m a c o m p a r i s o n of the El/2 values of diaziridines with the El/2 values of s o m e s u b s t i t u t e d
h y d r a z i n e s and h y d r a z o n e s that the e l e c t r o c h e m i c a l c l e a v a g e of the N - N bond in a t h r e e - m e m b e r e d ring
o c c u r s c o n s i d e r a b l y m o r e r e a d i l y (by 200 mV) than in a noncyclic s t r u c t u r e . The c o r r e s p o n d i n g waves a r e
m a r k e d l y c o m p l i c a t e d by a d s o r p t i o n of the components of the e l e c t r o c h e m i c a l r e a c t i o n .
Oxaziridines a r e r e a d i l y r e d u c e d on a DME [46], and t h e i r p o l a r o g r a p h i c waves a r e begun by the
wave for the dissolving of m e r c u r y . 2 - t e r t - B u t y l - 3 - p h e n y l o x a z i r i d i n e gives t h r e e w a v e s . The f i r s t wave
(about - 0 . 3 V) c o r r e s p o n d s to reduction to the g e m - a m i n o alcohol, which is d e h y d r a t e d at low pH values to
give a Schiff base, but is d e a m i n a t e d at higher pH values to give a c a r b o n y l compound. Both products can
be r e d u c e d f u r t h e r .
CrH.--v-~--N--C, ff. +2e + 3H + + pH>4
. ~/ . . . . . . C6HsCHNH2C~Hg. . . . C6H~CHO

O +2e+2H + _H2OI~:!+ l+2e+2H+

C6H5CH~I2C4H o C~HsCH=NHC4H
9 gHsCH~OlI

In a study of pyridoxine d e r i v a t i v e s [47, 48] it was shown that the product of condensation of pyridoxal
with c y s t e i n e - 2 - ( 2 - m e t h y l - 3 - h y d r o x y - 5 - h y d r o x y m e t h y l - 4 - p y r i d y l ) t h i a z o l i d i n e - 4 - c a r b o x y l i c a c i d - is r e -
duced in two 2e steps at - 0 . 5 to - 0 . 7 V and - 1 . 1 to - 1 . 4 V, r e s p e c t i v e l y , as a r e s u l t of which the thiazolidine
ring is opened.

.~---y~ ~, +2~ .2, Cl"2-c"i r, .~+2 ,+ ~:.~-~:.r,

133
 The distinct l e polarographic waves at sufficiently positive potentials {about -0.3 V) give stable
iminoxyl f r e e radicals, which are i r r e v e r s i b l y reduced on a DME to the corresponding hydroxylamine
derivatives [49].
o

Cyclic Anhydrides, Imides, and Hydrazides of A.cids

F o r m a l l y speaking, cyclic anhydrides, imides, and hydrazides of dibasic acids can also be classified
as h e t e r o c y c l i c compounds. The e l e c t r o r e d u c t i o n of maleic, phthalic, and pyromellitic anhydrides, etc.,
in aprotic media leads to anion radicals with t r a n s f e r of one e l e c t r o n [15]. The C : C bond is s a t u r a t e d in
aqueous media [51].
In acidic media, phthalimides are reduced with the consumption of two e l e c t r o n s , while in alkaline
media the 2e wave is split into two l e waves [52, 53]. It is assumed that the r e s u l t of the p r o c e s s is r e d u c -
tion to hydroxyphthalimidine , although the possibility of saturation of the C ~ C bond of the phthaloyl ring
has also been discussed [52]. The polarographic activity of phthalimides was used for the study of the
kinetics of hydrolytic cleavage of the phthalimide ring in numerous derivatives of this type [54-56].
9Cyclic maleic hydrazide (pyridazinedione) is reduced to succinic acid hydrazides with the formation
of s e v e r a l waves at - 0 . 8 to - 1 . 8 V, depending on the pH. The absence of an anode oxidation peak indicates
that t h e r e is no diazahydroquinone in solution and that it cannot be f o r m e d [57, 58].
0 O

NH +2e +2H + NH
fl it
U
O O

The corresponding cyclic phthalylhydrazides, according to the data in [59], are polarographically in-
active, since conjugation with the phenylene ring stabilizes them. However, Lurid has found that they are
reduced in a 6e p r o c e s s to phthalimidine in acidic media at E~/2 = -1.0 V [60].

OH O

0 0 O

-%-.....
dimer p~s ~"~"fi~'~/N
3 0 [ I~C H pN 0-2 ~ \ C N ~

Heteroaromatic Compounds with an Electroactive

Functional Group in the Side Chain
Heterocyclic compounds, in the c o u r s e of the polarographic reduction of which an e l e c t r i c a l l y active
substituent added to the h e t e m r i n g r a t h e r than the h e t e r o r i n g itself is involved, undoubtedly constitute the
most important group of compounds of the g r e a t e s t d i v e r s i t y . This classification includes d i v e r s e h e r e t o -
aromatic aldehydes, ketones, amides, hydrazides, aldimines, ketimines, halo derivatives, nitro compounds,
azo compounds, disulfides, etc., and derivatives of not only ~ - d e f i c i e n t (electroactive) h e t e r o a r o m a t i c s y s -
tems (such as pyridine, quinoline, pyrimidine, purine, eto.) but also derivatives of lr-surplus (inactive in a
polarographic r e s p e c t ) h e t e r o a r o m a t i c systems (such as p y r r o l e , furan, thiophene, thiazole, imidazole, etc.).
In general, the assumption noted in the review in [1] that polarographically active groups attached to a
h e t e r o a r o m a t i c ring behave like polarographically active groups attached to aromatic (benzene) rings, i.e.,
they a r e reduced approximately in the s a m e ranges of electrode potentials and via the same chemical m e c h -
anism, is generally justified, but one cannot overlook a number of specific complicating f a c t o r s .

134
 F i r s t of all, the change in the nature of the h e t e r o a r o m a t i c r i n g owing to p u r e l y e l e c t r o n i c effects
s o m e w h a t shifts the e l e c t r o c h e m i c a l r e d u c t i o n potential of this group to one o r another side as c o m p a r e d
with the potential of the s a m e group attached to an a r o m a t i c ring. Although this change in the El/2 value
usually does not exceed 0.1-0.2 V, n e v e r t h e l e s s it s o m e t i m e s m a y t r a n s f e r the e l e c t r o r e d u c t i o n p r o c e s s to
a different r e g i o n of the e l e c t r o c a p i l l a r y c u r v e , w h e r e a d s o r p t i o n of the d e p o l a r i z e r m o l e c u l e s and the e f -
fect of the e l e c t r i c a l double l a y e r a r e m a n i f e s t e d differently, and a r e s u l t of this m a y be a change in the
m e c h a n i s m of the e l e c t r o c h e m i c a l p r o c e s s .
Second, h e t e r o a r o m a t i c compounds, p a r t i c u l a r l y n i t r o g e n - and s u l f u r - c o n t a i n i n g h e t e r o c y c l e s , a r e
a d s o r b e d on the e l e c t r o d e s u r f a c e c o n s i d e r a b l y m o r e s t r o n g l y than the c o r r e s p o n d i n g benzene d e r i v a t i v e s ,
t h e r e b y intensifying the effect of a d s o r p t i o n f a c t o r s on the c o u r s e of the e l e c t r o c h e m i c a l p r o c e s s . In the
c a s e of h e t e r o a r o m a t i c compounds, a d s o r p t i o n f o r e w a v e s , s u r f a c e kinetic points (drops on the p o l a r o g r a m s )
etc., often a p p e a r .

CN CH~NH2 CN

H H

Third, owing to the s p e c i f i c effect of the h e t e r o r i n g , those substituents which, b e c a u s e they a r e added
to the a r o m a t i c ring, a r e incapable of e l e c t r o r e d u c t i o n , acquire p o l a r o g r a p h i c activity. Thus, in c o n t r a s t
to inactive benzoic acids, all of the i s o m e r i c p y r i d i n e c a r b o x y l i c acids a r e r e d u c e d on a DME in t h e a c c e s -
s i b l e r a n g e of p o t e n t i a l s . In c o n t r a s t to the p o l a r o g r a p h i c a l l y inactive benzonitrile, 4 - c y a n o p y r i d i n e and
2 - c y a n o p y r i d i n e a r e r e d u c e d on a DME, and in this e a s e a 4e p r o c e s s o c c u r s in acidic m e d i a , while 2e
c l e a v a g e of the C - C N bond o c c u r s in b a s i c m e d i a [61, 62]. Of c o u r s e , the opinion that we a r e dealing h e r e
with e l e c t r o r e d u c t i o n of the pyridine ring [63] v i a the following s c h e m e has been e x p r e s s e d :

+2e +2 H +

IT

In c o n t r a s t to N - p h e n y l h y d r o x y l a m i n e , which is p o l a r o g r a p h i c a l l y inactive in the unprotonated f o r m ,

waves c o r r e s p o n d i n g to reduction of the unprotonated h y d r o x y l a m i n o group [64] a p p e a r on the p o l a r o g r a m s
of 2 - n i t r o f u r a n d e r i v a t i v e s with e l e e t r o n - a c c e p t o r s u b s t i t u e n t s .
P r o t o n a t i o n of the h e t e r o a t o m has a p e c u l i a r effect on the El/2 value of a side group in the c a s e of
d e r i v a t i v e s of n i t r o g e n - c o n t a i n i n g h e t e r o c y c l e s (pyridine, p y r r o l e , thiazole, etc.). Depending on the pH of
the solution, the h e t e r o r i n g in the compound is in the protonated (salt) o r unprotonated (base) f o r m , each of
which is r e d u c e d at definite potentials; this is r e s p o n s i b l e for the c o m p e t i t i v e e l e c t r o r e d u e t i o n of the two
different f o r m s , the f o r m a t i o n of kinetic w a v e s , etc., which is not o b s e r v e d in the c a s e of the c o r r e s p o n d i n g
d e r i v a t i v e s of benzene o r of h e t e r o c y c l e s that do not have basic p r o p e r t i e s (furan, thiophene, etc.) (this
should not b e confused with the kinetic c u r r e n t s that a r i s e b e c a u s e of the p r e s e n c e of a s u b s t i t u e n t in two
different f o r m s , f o r e x a m p l e , a protonated and unprotonated c a r b o n y l group, an acid and its anion, etc.).
The p o l a r o g r a p h i c c l e a v a g e of the C - H a l bond in v a r i o u s monohalopyridines m a y s e r v e as an e x a m p l e [65].
In addition, h y d r a t i o n of the c a r b o n y l group is typical for a n u m b e r of h e t e r o a r o m a t i c aldehydes ; this
distinguishes t h e m f r o m the c o r r e s p o n d i n g benzaldehydes and naphthaldehydes. The e q u i l i b r i u m between
the e l e c t r o a c t i v e unhydrated f o r m of a h e t e r o a r o m a t i c aldehyde and its inactive h y d r a t e d f o r m is mobile,
and the height of the waves is l i m i t e d by the r a t e of dehydration of the aldehyde group, which is an a c i d -
b a s e c a t a l y z e d p r o c e s s , and, consequently, depends on the pH. This m e c h a n i s m for dehydration, which p r e -
cedes e l e c t r o r e d u c t i o n , is c h a r a c t e r i s t i c for i s o m e r i c f o r m y l p y r i d i n e s [66-69], f o r m y l i m i d a z o l e s [70], 5-
n i t r o f u r f u r a l s [64, 71], 2 - f o r m y l t h i a z o l e s [68], etc., in aqueous media; the c o m p l e x dependence of the wave
height on the pH is r e s p o n s i b l e f o r it. F o r n i t r o g e n - c o n t a i n i n g h e t e r o c y c l e s , this m e c h a n i s m is additionally
c o m p l i c a t e d by a c i d - b a s e e q u i l i b r i u m between the b a s e and protonated f o r m of the h e t e r o r i n g , which a r e
distinguished with r e s p e c t to t h e i r d e g r e e of hydration: the cation, owing to its positive c h a r g e , is usually
h y d r a t e d m o r e s t r o n g l y than the f r e e b a s e . A c o m p l e x s e t of equations a r i s e s b e c a u s e of all that was s t a t e d
above, lOrotonation m a y show up in at l e a s t t h r e e different ways: its effect on the ring h e t e r o a t o m , on the
r a t e of dehydration, and on the s u r f a c e protonation of the aldehyde g r o u p in the c o u r s e of its e l e c t r o r e d u c -
tion, f o r e x a m p l e [72]:

135
 ~ H
CtI(OH)~_H20 ~ , C H O

However, the g e n e r a l principles of polarographic reduction of a r o m a t i c c a r b o c y c l i c compounds a r e

applicable on the whole to the polarographic b e h a v i o r of h e t e r o a r o m a t i c compounds that have an e l e c t r o -
active functional group in the side chain. M o r e o v e r , these principles take on p a r t i c u l a r significance for the
solution of the p r o b l e m s of the c h e m i s t r y of h e t e r o a r o m a t i c compounds, since the t a s k in the i n t e r p r e t a t i o n
of the s t r u c t u r e s of natural and synthetic biologically active substances with e x t r e m e l y d i v e r s e possibilities
of s t r u c t u r a l i s o m e r i s m , t a u t o m e r i c f o r m s , etc., v e r y often is e s t a b l i s h m e n t of the p r e s e n c e and c h a r a c t e r -
ization of the fine e l e c t r o n i c s t r u c t u r e of one or another functional group. In this r e s p e c t , p o l a r o g r a p h y ,
together with m o r e m o d e r n physical methods, can give valuable information. The d e t e r m i n a t i o n of the c o n -
c r e t e El/2 v a l u e s in the c h e m i s t r y of h e t e r o c y c l i c compounds also takes on m o r e significance for the r e l a -
tive evaluation of the r e a c t i v i t i e s of one or another position in the h e t e r o r i n g , etc., which is not always e a s y
to do with other methods, and also for modeling of the b i o c h e m i c a l redox s y s t e m s in which r e d o x c o e n z y m e s
of h e t e r o a r o m a t i c s t r u c t u r e , t h e i r model analogs, inhibitors, etc., often p a r t i c i p a t e .
Insofar as the effect of the nature of the h e t e r o r i n g on the El/2 Value of reduction of the h e t e r o a r o m a t i c
s y s t e m bonded to it is concerned, one can p a r t i c u l a r l y a p p r o x i m a t e l y use the rule that groups attached to
h e t e r o a r o m a t i c s y s t e m s with a deficit of ~ electrons in the ring a r e reduced at m o r e positive potentials, and
groups bonded to ~ - s u r p l u s h e t e r o a r o m a t i c s y s t e m s a r e r e d u c e d at m o r e negative potentials. In the f i r s t
c a s e , the e l e c t r o n density on the p o l a r o g r a p h i c a U y active group d e c r e a s e s , and this facilitates e l e c t r o r e -
duction, while the r e v e r s e o c c u r s in the second c a s e . The r e l a t i v e e a s e of reduction of a group depends
also on its position with r e s p e c t t o t h e h e t e r o a t c m . F o r example, if the ring nitrogen h e t e r o a t o m in the
pyridine molecule is c o n s i d e r e d to be a substituent with a s t r o n g negative m e s o m e r i c effect, e l e c t r o a c t i v e
groups in the 4 and 2 positions should be r e d u c e d c o n s i d e r a b l y m o r e r e a d i l y than a substituent in the 3 p o s i -
tion; this is e x p e r i m e n t a l l y o b s e r v e d [66, 73, 74]. E l e c t r o a c t i v e groups in the 2 position in furan, thiophene,
and selenophene d e r i v a t i v e s a r e reduced c o n s i d e r a b l y m o r e r e a d i l y than the group in the 3 position; this
was used, for example, for the analysis of the i s o m e r i c composition of the products of nitration of thiophene
[75].
Imoto [76], Z u m a n [77, 78], Tirouflet [79], and o t h e r authors c o m p a r e d the r e l a t i v e e a s e of e l e c t r o -
reduction with the s o - c a l l e d h e t e r o r i n g constants ~ F - , which c h a r a c t e r i z e the e l e c t r o n i c effect (including
the m e s o m e r i c effect) of a h e t e r o a r o m a t i c ring (with r e s p e c t to the phenyl ring). The investigated s y s t e m s
can be a r r a n g e d in the following o r d e r with r e s p e c t to the i n c r e a s e in the negative potentials of e l e c t r o -
c h e m i c a l reduction:

4-pyridyl ~2-thiazolyl. ,~ 2-pyridyl ~3~.pyrs ~2-thienyl ~2-furyl

oF- + 1,86 + 1,64 + 1,5 +0.72 +0,24 +0,18
<L phenyl < 3-thienyl < 2-pyridyl < 3-pyridyl
aF- 0 -- 0.09 - 0,70 -- 1.68
Depending on the r e p r o d u c i b i l i t y of a given e l e c t r o a c t i v e functional group to the effect of substituents,
the c o r r e s p o n d i n g i n c r e a s e or d e c r e a s e in the h a l f - w a v e potentials on passing f r o m one h e t e r o a r o m a t i c
s y s t e m to another m a y b e c o n s i d e r a b l e or l e s s pronounced. Thus, on p a s s i n g f r o m the 4 - p y r i d y l f r a m e -
w o r k to the phenyl f r a m e w o r k the 1~1/~ values for e l e c t r o r e d u c t i o n of b r o m o d e r i v a t i v e s a r e shifted to the
cathode side by about - 1 . 1 V, c o m p a r e d with shifts of - 0 . 5 V for aldehydes and ketones and -0.25 V for
aldoximes and nitro compounds [78]. However, these data a r e only a p p r o x i m a t e in nature, s i n c e the values
of the ~ F - constants m a y v a r y o v e r v e r y wide limits, depending on the m e s o m e r i c i n t e r a c t i o n of the h e t e r o -
a r o m a t i c ring with the e l e c t r o a c t i v e group, while the e l e c t r o c h e m i c a l p r o c e s s depends also on the p o s s i -
bility of protonation of the h e t e r o r i n g , its a d s o r b a b i l i t y , etc. In the c a s e of s m a l l e l e c t r o n i c effects of the
h e t e r o r i n g , the El/2 values m a y also change to the positive side - thus 5 - n i t r o f u r a n is reduced m o r e r e a d i l y
by 40-50 mV than 5-nitrothiophene, while the l a t t e r , just as 5-nitroselenophene, has a p p r o x i m a t e l y the
s a m e potential as nitrobenzene [71]. In addition, t h e r e is a l m o s t no r e s e a r c h in which one author has
studied, under identical (strictly compared) conditions, the p o l a r o g r a p h i c b e h a v i o r of the s a m e e l e c t r o -
active group in various h e t e r o a r o m a t i c s y s t e m s .

136
 0 N---X O N--X

o 0

An investigation of angular h e t e r o c y c l i c derivatives of anthraquinone of the a n t h r a q u i n o n e - l , 2 , 5 - X -

diazole type and r e l a t e d compounds gave interesting results [79-81]. Since the rings of 1,2,5-X-diazoles
a r e strong e l e c t r o n a c c e p t o r s , t h e i r introduction into a molecule i n c r e a s e s the e l e c t r o n affinity of the
quinone, which can be c h a r a c t e r i z e d by the E~/2 value of the f i r s t wave for e l e c t r o r e d u c t i o n of the quinone
grouping in an aprotic solvent to a semiquinone anion r a d i c a l . The c o r r e s p o n d i n g N1/2 values c o r r e l a t e
l i n e a r l y with the r e s u l t s of kinetic m e a s u r e m e n t s [82] (Table 1).
The effect of an extraneous substituent (X) that is incapable of e l e c t r o r e d u c t i o n on the E~/2 value for
polarographic reduction of an e l e c t r o a c t i v e functional group (R) was studied quite thoroughly in a number
of derivatives of furan, thiophene, and selenophene [78]:

It was shown that, in general, the s a m e principles as in the effect of substituent X on the e l e c t r o r e -
duction of group R in e l e c t r o c h e m i c a l reactions of the benzene s e r i e s a r e o b s e r v e d h e r e , and the gl/2
values c o r r e l a t e l i n e a r l y with the H a m m e t t constants; the 2,5-position in these h e t e r o r i n g s is approximately
equivalent to the p a r e position in the benzene ring, while the 2,4-position is a p p r o x i m a t e l y equivalent to the
m e t a position [71, 83-85]. The PTr constants in a number of derivatives of these h e t e r o a r o m a t i c rings differ
somewhat f r o m the c o r r e s p o n d i n g values in the benzene s e r i e s [78]. The d e c r e a s e in t r a n s m i s s i o n of the
e l e c t r o n i c effect of substituent X is also caused by interposition of the - C H 2 - , - C H ~---CH-, etc., bridge
groups [84-86]. It is interesting that a d e c r e a s e in the A E 1 / J A p H coefficients of various derivatives of the
s e r i e s [85] in the l i n e a r dependence on the Hammett substituent constants is o b s e r v e d in a number of 2-
substituted derivatives of 5 - n i t r o f u r a n on o r d i n a r y c a p i l l a r i e s , and that this d e c r e a s e is o b s e r v e d only on
s h o r t - p e r i o d c a p i l l a r i e s in a n u m b e r of nitrobenzene derivatives [87].
T h e r e are numerous data on the polarographic reduction of e l e c t r o a c t i v e groups bonded to a h e t e r o -
a r o m a t i c ring, The functional derivatives of pyridine [88-92], p y r r o l e [93, 94], furan [95, 96], thiophene
[97, 98], imidazole [70, 99], thiazole [100], etc., p a r t i c u l a r l y the c o r r e s p o n d i n g carbonyl, nitro, and halo
derivatives, and derivatives of p y r i d i n e c a r b o x y l i c acids (cyanides, h y d r a z i d e s , amides, etc.) have been
studied thoroughly. Many of these compounds - derivatives of nicotinic and is onicotinic acids, 2-nitrofuran,
c~-nitropyrrole, e t c . - h a v e high chemotherapeutic activity, and the possibility of t h e i r polarographic de-
t e r m i n a t i o n s e e m s of substantial analytical i n t e r e s t .
N-Oxides occupy a special place among substituted derivatives of nitrogen-containing h e t e r o c y c l e s ;
the polarographic behavior of N-oxides has been studied e x t r e m e l y intensely in view of t h e i r low p o l a r o -
graphic r e d u c t i o n potentials, which are convenient for analytical work, and also because of the g r e a t i m -
portance that they have for the p r e p a r a t i v e c h e m i s t r y of h e t e r o c y c l e s . The N-oxides of pyridine, quinoline,
piperidine, and a number of alkaloids give an i r r e v e r s i b l e 2e wave in acidic media at potentials f r o m - 0 . 7

TABLE 1. El/2 Values (in Dimethylformamide) of 9,10-Anthraquinone

and A n t h r a q u i n o n e - l , 2 , 5 - X - d i a z o l e s

Annelamd heteroring s V Annelated heteroring E~h , V

9,10-Anthraquinone -0,82 -0.43

N~N
--0,57

-- 0,43 -0,42

~ .--.-C~H5
--0,57 N---'-O
N
"0,27

137
 9169 ".'."
,o 9
O OH

to - 1 . 0 V, the El/2 value of which depends on the pH [101-110]. The height of the wave d e c r e a s e s with in-
c r e a s i n g pH, g r a d u a l l y takes on kinetic c h a r a c t e r , and finally d i s a p p e a r s . This is a s s o c i a t e d with the fact
that pyridine N-oxide itself is p o l a r o g r a p h i c a l l y inactive but in the protonated f o r m acquires the+ c a p a c i t y
for e l e c t r o r e d u c t i o n , as shown above. The height of the wave c o r r e s p o n d i n g to c l e a v a g e of the N - O bond
is limited by the protonation kinetics, which have volume c h a r a c t e r in the c a s e of N - m e t h y l p i p e r i d i n e and
p a r t i a l l y s u r f a c e c h a r a c t e r with the participation of a d s o r b e d N-oxide molecules in the c a s e of pyridine
[1031.
In acidic media, 7 - c h l o r o - 2 - m e t h y l a m i n o - 5 - p h e n y l - 3 H - 1 , 4 - b e n z o d i a z e p i n e 4-oxide (chlordiazepoxide}
gives t h r e e reduction w a v e s . The f i r s t wave (g~/2 -0.38 V) c o r r e s p o n d s to 2e reduction of the N-~ O group,
the second wave (E~/2 -0.72 V) c o r r e s p o n d s to 2e reduction of the C = N double bond in the 4,5 position, and
the third wave (El/2 - 1 . 2 V) c o r r e s p o n d s to 2e reduction of the N = C double bond in the 1,2 position [109-
112].
i ~ ' ~ ~N_...--~NHCH 3 N HCH3 N [i~.H~ N H CH3

C6H5 CsH5 C6H~

The effect of substituents on the El/2 values for reduction of N-oxides and the reduction of other e l e c -
t r o a c t i v e groups contained in N-oxide molecules was examinedin [102,104-106, 108, 109].
I s a t o g e n s , which a r e reduced like 1,4-quinones on a DME and consequently have quinoid c h a r a c t e r
[113], a r e c l o s e to N-oxides:

R - 2-pyridyl, phenyl,
4-nltropheny1 .
0 4-memoxypnenyl

The m e c h a n i s m of e l e c t r o r e d u c t i o n of the N-oxides of 1,2,5-oxadiazoles (furoxans) is fundamentally

different [114]. Depending on the pH, two or t h r e e waves a r e o b s e r v e d on the p o l a r o g r a m s of 1,2-naphtho-
f u r o x a n - 4 - s u l f o n i c acid. The f i r s t wave at - 0 . 1 to - 0 . 2 V c o r r e s p o n d s to 2e reduction to 1,2-quinodioxime-
4-sulfonic acid. The next waves p e r t a i n to the reduction of the protonated and unprotonated f o r m s of the
dioxime. Eight e l e c t r o n s a r e c o n s u m e d in the c o m p l e t e reduction to give the final p r o d u c t - 1 , 2 - d i a m i n o -
naphthalene-4-sulfonic acid. Thus c l e a v a g e of the ring bonds o c c u r s m o r e r e a d i l y in the c a s e of furoxan
than splitting out of an exocyclic oxygen a t o m .
N--OH

SO811 gO3N

T w o - e l e c t r o n and s i x - e l e c t r o n waves a r e o b s e r v e d s e p a r a t e l y in the reduction of naphthofuroxan in

anhydrous d i m e t h y l f o r m a m i d e . The absence of a l e s t e p m a y be a s s o c i a t e d with weakening of the a r o m a t i c
c h a r a c t e r of the molecule on passing f r o m furazans to furoxans.
The S-oxides and S-dioxides of phenothiazine [115] and b e n z o - and dibenzophenothiazines a r e reduced
on a DME in an alcohol solution of t e t r a m e t h y l a m m o n i u m chloride at - I .7 to 2.3 V (relative to the m e r c u r y
bottom). In acidic m e d i a (in h y d r o c h l o r i c , acetic, and nitric acids) the S-oxides undergo l e reduction at
- 0 . 8 to - 1 . 0 V. The m e c h a n i s m of the e l e c t r o r e d u c t i o n has not been adequately studied, but it is a s s u m e d
that in this c a s e the resulting phenothiazonium salts, which, by adding one electron, give s t a b l e s e m i q u i n -
ones that a r e not r e d u c e d up to the point of d i s c h a r g e of the b a s e e l e c t r o l y t e a r e r e d u c e d .
Benzothiophene 1,1-dioxide in b e n z e n e - m e t h a n o l solution gives two reduction waves with E~/2 - 0 . 9 7
and -1.93 V, r e s p e c t i v e l y [116]. On the b a s i s of data in [116, 117], Lund p r o p o s e s c l e a v a g e of the thiophene
ring to give/3-phenylethanesulfinic acid [118]:

138
 *2e+2H+ ~ +2e+2H+~CH2CH:~SO2H

Cleavage of the C - S bond is the p r i m a r y electrode reaction in the reduction of saccharin; chemical
reaction follows after p r i m a r y electrochemical cleavage [118]:

~ . % H* ++2e
:2H___._+..C,H~CONH~
~ * SO~
0#~"~0

Thus, abundant - and frequently the most diverse - variations of mechanisms of electrochemical r e -
duction, which are far from being completely discovered, are manifested among the extremely diverse
heterocyclic compounds. Not all of the literature data have been obtained under comparable conditions and
cannot be c o r r e l a t e d from a single position. However, the electrochemical material already available
makes it possible to both expose the peculiarities of the reactivities of individual heterorings and to use
the polarographic method for the quantitative analysis and evaluation of the reactivities of numerous h e re to -
rings.

LITERATURE CITED
1o Ya. P. Stradyn', V, P. Kadysh, and S. A. Giller, Khim. Geterotsikl. Soedin., 1587 (1973).
2. N. P. Shimanskaya, N. A. Lodygin, and V. D. Bezuglyi, Zh. Obshch. Khim., 3__88,929 (1968).
3. N. P. Shimanskaya, E. G. Buryakovskaya, V. D. Bezuglyi, and S. V. Tsukerman, Zh. Obshch. Khim.,
38, 1676 (1968).
4. N. P. Shimanskaya, V. D' Bezuglyi, and V. E. Bondarenko, Zh. Obshch. Khim., 39, 2171 (1969).
5. H. Oelschl~ger, J . Volke, and H. Hoffman, Coll. Czech. Chem. Commun., 3_11,1264 (1966).
6. H. Oelschl~iger, J. Volke, G. T. Lim, and U. Brem er, Arch. Farm., 30__33,364 (1970).
7. H. Oelschl~ger and H. Hoffman, Arch. Farm . , 300, 817 (1967).
8. H. Lund, O s t er r ei ch Chem. Z., 6_88,43 (1967).
9. H. Lurid, Disc. Faraday Soc., 4_5, 193 (1968).
10 H. Lurid, Coll. Czech. Chem. Commun., 3__11,4175 (1966).
11 C. Parkanyi and R. Zahradnik, Coll. Czech. Chem. Commun., 217, 1355 (1962).
12 E. Knobloch, in: Advances in Polarography, Vol. 3, Pergamon P r e s s (1960), p. 875.
13 T. A. Geissman and S. L. F r i e s s , J. Am. Chem. Soc., 71, 3893 (1949).
14 J. Volke and V. Szabo, Coll. Czech. Chem. Commun., 2__33,221 (1958).
15 J . Tirouflet, Abh. Deutsch. Akad. Wiss., Berlin, K1. Chem., Geol., Biol., No. 1, 58 (1964).
16 M. B~ezina and P. Zuman, Die Polarographie in der Medizin, Biochemie und Pharmazie, Akadem.
Verlagsgesellschaft Leipzig, 270 (1956).
17 O. ~apka, Coll. Czech. Chem. Commun., 1__55,965 (1950).
18 A. J . Harle and L. E. Lyons, J. Chem. Soc., 1575 (1950).
19 R. Patzak and L. Neugebauer, Monatsh., 82, 662 (1951).
20 R. Patzak and L. Neugebauer, Monatsh., 8-8, 776 (1952).
21 A. Foffani, Atti Accad. Naz. Lincei, 1_44,418 (1953).
22 W. E . Whitman and L. A. Wiles, J . Chem. Soc., 3016 (1956).
23 G. K. Budnikov, Zh. Obshch. Khim., 3-8, 2431 (1968).
24 B. Czochralska and D. Shugar, Biological Aspects of E l e c t r o c h e m i s t r y (Experientia Supplementum),
1-8, 251 (1971).
25. D. L. Smith and P. J . Elving, J . Am. Chem. Soc., 8__44,2741 (1962).
26. B. Janik and E. Pale~ek, Arch. Biochem. Biophys., 10.5, 225 (1964).
27. E. Pale~ek and B. Janik, Arch. Biochem. Biophys., 9-8, 527 (1962).
28. J . KrupicVka and J . Gut, Coll. Czech. Chem. Commun., 2__55,592 (1960).
.v
29. J . Kruplcka and J . Gut, Coll. Czech. Chem. Commun., 27, 546 (1962).
30. H. Berg, J. Flemming, g . Pale~ek, and V. Vetterl, Stud-~a Biophysica, 3__33,81 (1972).
31. P. Pflegel and G. Wagner, Z. Chem., 6, 263 (1966).
32. Ya. P. Stradyn', I. K. Tutane, V. T. Glezer, L. Ya. Avota, and S. A. Giller, Zh. Obshch. Khim., 4__33,
1150 (1973).
33. M. Gruca, Z. Janko, J. Kanty, and A. Kotarski, Chem. Anal., 12, 1331 (1967).
34. K. Dulak, J. Koran, and P. Rapos, J. Chromat., 31, 354 (1967)-7
35. H. Lund, Coll. Czech. Chem. Commun., 30, 4237 (1965).

139
36. R.Mantsavinos andJ. E. Christian, Anal. Chem., 3_00,1071 (1958).
37. J . K . Pauncz, Polarography 1964, Vol. 2, London-Melbourne, Macmillan (1966), p. 913.
38. D . A . Tussee and M. M. Baizer, J. Electrochem. Soc., 118, 1420 (1971).
39. R. Mantsavinos and J. E. Christian, J. Amer. Pharm. Ass., 4_77,570 (1958}.
40. H. Berg and K. H. KSnig, Anal. Chim. Acta, 18, 140 (1958).
41. H. Wagner and H. Berg, J. Electroanal. Chem., 1, 61 (1959/60).
42. H. Wagner and H. Berg, J . Electroanal. Chem., 2, 452 (1961).
43. A. Anhalt and H. Berg, J. Electroanal. Chem., 4, 218 (1962}.
44. G. Horn, Abh. Deutsch. Akad. Wiss., Berlin, K1. Chem., Geol., Biol., No. 1, 37 (1964).
45. Yu. P. Kitaev and G. K. Budnikov, Coll. Czech. Chem. Commun., 30, 4178 (1965}.
46. H. Lund, Acta Chem. Scand., 2__33,563 (1969).
47. O. Manou~ek and P. Zuman, Coll. Czech. Chem. Commun., 29, 1432 (1964).
48. O. Manou~ek and P. Zuman, Coll. Czech. Chem. Commun., 29, 1719 (1964).
49. M . B . Neiman, S. G. Mairanovskii, B. M. Kovarskaya, ]~. G. Rozantsev, and E. G. Gintsberg, Izv.
Akad. Nauk SSSR, Ser. Khim., 1518 (1964}.
50. M . E . Peover, Trans. Faraday Soc., 588, 2370 (1962).
51. M. Maturov~, A. N~me~kov~, and F. Santav~, Coll. Czech. Chem, Commun., 27., 1021 (1962).
52. J. Tirouflet, R. Robin, and M. Guyard, Bull. Soc. Chim. France, 571 (1956).
53. J. Tirouflet and E. Le Trouit, Compt. Rend., 241, 1053 (1955).
54. J. Tirouflet and E. Laviron, Bull. Soc. Chim. France, 534 (1957}.
55. J. Tirouflet, R. Dabard, and E. Laviron, Bull. Soc. Chim. France, 570 (1957).
56. R. Dabard and J. Tirouflet, Bull. Soc. Chim. France, 565 (1957).
57. D. Miller, Can. J. Chem., 3_.33,1806 (1955}.
58. D. Miller, Can. J . Chem., 3__44,1760 (1956}.
59. E, T. See and T. Kuwana, J. Electroanal. Chem., 6, 417 (1963).
60. H. Lund, Coll. Czech. Chem. Commun., 30, 4237 (1965).
61. E. Laviron, Compt. Rend., 250, 3671 (1960).
62. J. Volke and J. Holubek, Coll. Czech. Chem. Commun., 2__8_,8 1597 (1963}.
63. V . A . Serazetdinova, B. V. Suvorov, and O. A. Songina, Izv. Akad. Nauk KazSSR, Set. Khim., No. 3,
64 (1968).
64. G . O . Reikhman and Ya. P. Stradyn', Izv. Akad. Nauk LatvSSR, Ser. Khim., 23 (1967).
65. J. Holubek and J. Volke, Coll. Czech. Chem. Commun., 27, 680 (1962).
66. J. Volke, Coll. Czech. Chem. Commun., 23, 1486 {1958).
67. J. Tirouflet, P. Fournari, and J. P. Chan~, Compt. Rend., 242, 1799 (1956).
68. J. Tirouflet, E. Laviron, J. Metzger, and J. Boichard, Coll. Czech. Chem. Commun., 25, 3277 (1960).
69. E. Laviron, Bull. See. Chim. France, 2325, 2350 (1961).
70. P . E . Iversen and H. Lurid, Acta Chem. Scand., 2_!1, 279 (1967).
71. Ya. Stradyn!, S. Giller, and Yu. Yur'ev, Dokl. Akad. Nauk SSSR, 129, 816 (1959).
72. J. Volke and P. Valenta, Coil. Czech. Chem. Commun., 25, 1580 (1960).
73. J. Holubek and J. Volke, Coll. Czech. Chem. Commun., 2_55,3286 (1960).
74. J. Volke, Coll. Czech. Chem. Commun., 25, 3397 (1960).
75. J. Tirouflet and P. Fournari, Compt. Rend., 246, 2003 (1958).
76. E. Imoto, R. Motoyama, and H. Kakiuchi, Bull. Naniwa Univ., Ser. A., 3, 203 (1955).
77. P. Zuman, in: Advances in Polarography, Vol. 3, Pergamon (1960), p. 812.
78. F. Zuman, Substituent Effects in Organic Polarography, Plenum, New York (1967).
79. J. Tirouflet and M. Person, Ricerca Sci., 30, Suppl. A, 269 (1960).
80. E . S . Levin, M. V. Gorelik, O. S. Zhdamarov, and Z. V. Todres, Zh. Obshch. Khim., 40, 1577 (1970).
81. M . V . Gorelik, O. S. Zhdamarov, t~. S. Levin, B. E. Zaitsev, and L. A. Chetkina, Zh. Fiz. Khim., 7,
1044 (1971).
82. ]~. S. Levin, O. S. Zhdamarov, and M. V. Gorelik, t~lektrokhimiya, 7, 1799 (1971).
83. J . Tirouflet and J. P. Chan~, Compt. Rend., 2.43, 500 (1956).
84. J. Strodyn' (Stradins) and S. Giller (Hillers), Tetrahedron, 20, Suppl. 1 (Nitrocompounds), 409 (1964}.
85. Ya. P. Stradyn' and G. O. Reikhman, l~lektrokhimiya, 3, 178 (1967).
86. Ya. P. Stradyn', I. Ya. Kravis, G. O. Reikhman, and S. A. Giller, Khim. Geterotsikl. Soedin., 1309
(1972).
87. Ya. P. Stradyn' and I. Ya. Kravis, in: Electrochemical Processes with the Participation of Organic
Substances [in Russian], Nauka, Moscow (1970), p. 110.
88. J. Volke and M. M. Amer, Coll. Czech. Chem. Commun., 2_99,2134 (1964).

140
 89. J. Volke, Coll. Czech. Chem. Commun., 2_~7,483 (1962).
90. E . S. Gazda, Anal. Chem., 41, 212 (1969).
91. N. G. L o r d i and E. M. Cohen, Anal. Chim. Acta, 25, 281 (1961).
92. P . Tomasik, Roczn. Chem., 4__44,1211 (1970).
93. M. P e r s o n , Compt. Rend., 25__~5,301 (1962).
94. P. F o u r n a r i and J . Tirouflet, Bull. Soc. Chim. F r a n c e , 484 (1963).
95. R. A. Day, J . A m e r . C h e m . Soc., 7__66,280 (1954).
96. R. A. Gavar, V. K. Grin', G. O. Reikhman, and Ya. P. Stradyn', T e o r . i l~ksperim. Khim., 6, 685
(1970).
97. S. G, Mairanovskii, N. V. Kondratova,I. B. Karmanova, and Yu. B. Vol'kenshtein, Izv. Akad. Nauk
SSSR, Set. Khim., 2429 (1971).
98. F. M. Stoyanovich, S. G. Mairanovskii, Ya. L. Gol'clfarb, and I. A. D'yachenko, Izv. Akad. Nauk SSSR,
Ser. Khim., 1439 (1971).
9 v v

99. M. Slamnik, F. Kajfez, and V. Sunjic, J. Polarogr. Soc., 1__33,83 (1967).

100. Ya. Stradyn', I. Tutane, M. Alberta, and S. Giller, Izv. Akad. Nauk LatvSSR, Ser. Khim., 371 (1963).
101. A. Foffaniand E. Fornasari, Gazz. Chim. Ital., 8_~3,1051 (1953).
102. G. Horn, Acta Chim. Acad. Sci. Hung., 27, 123 (1961).
103. S. G. Mairanovskii, N. V. Barashkova, and F. D. Alashev, Zh. Fiz. Khim., 3_66, 562 (1962).
104. Yu. S. Rozum, S. B. Serebryanyi,E. F. Karaban, V. P. Chernetskii, and M. I. Dronkina, Zh. Obshch.
Khim., 3_~4,2599 (1964).
105. T. Kubotaand H. Miyazaki, Bull. Chem. Soc. Japan, 3__55,1549 (1962).
106. T. Kubota and H. Miyazaki, Bull. Chem. Soc. Japan, 3__99,2057 (1966).
107. T. R. Emerson and C. W. Rees, J. Chem. Soc., 1923 (1962).
108 E. G. Novikov and A. G. Pozdeeva, Zh. Prikl. Khim., 4_0, 217 (1967).
109 A. G. Pozdeeva and E. G. Novikov, Zh. Prikl. Khim., 422, 2626 (1969).
110 C. R. Warner and P. J. E1ving, Coll. Czech. Chem. Commun., 3__00,4210 (1965).
111 B. Z. Senkowski, M. S. Levin, J. R. Urbigkit, and E. G. Wollish, Anal. Chem., 36, 1991 (1964).
112 H. Oelschl~iger, J. Volke, H. Hoffman,and E. Kurek, Arch. Farm., 300, 250 (1967).
113 J. E. Bunneyand M. Hooper, J. Chem. Soc. B, 1239 (1970).
114 E. S. Levin, Z. I. Fodiman, and Z. V. Todres, I~lektrokhimiya,2, 175 (1966).
115 N. A. Kudryavtseva,Z. V. Pushkareva, and V. F. Gryazev, Zh. Obshch. Khim., 3__55,14 (1965).
116 H. V. Drushel and J. F. Miller, Anal. Chem., 30, 1271 (1958).
117. O. Manou~ek, O. Exner, and P. Zuman, Coil. ~zech. Chem. Commun., 3__33,4000 (1968).
118. H. Lund, in: Organic Electrochemistry, M. Baizer and Marcel Dekker (eds.), New York (1973),
p. 564.

141
PMR SPECTRA OF DIFUROYL PEROXIDES

O. P. Yablonskii and N. N . B o r i s o v a UDC 543.422.25:547.725.727

The PMR s p e c t r a of difuroyl peroxides w e r e r e c o r d e d . It is shown that the introduction of

a peroxide grouping in place of an anhydride grouping does not lead to changes in the s p e c -
trum.

We have p r e v i o u s l y [1] d e s c r i b e d the synthesis and s o m e p r o p e r t i e s of s y m m e t r i c a l furoyl p e r o x i d e s .

The p r e s e n t p a p e r is devoted to a study of their PMR s p e c t r a . The s p e c t r u m of furoyl peroxide (X = H ) is
an AMX s y s t e m with f i r s t - o r d e r coupling (v05 >>J). The ratio ( 1 : 1 : 1 ) of the integral intensities of the s i g -
nals and the c h e m i c a l shifts (7.49, 6.73, and 7.94 ppm) w e r e d e t e r m i n e d proceeding f r o m the a s s u m p t i o n
that the t r u e position of the r e s o n a n c e absorption for each ring coincides with the c e n t e r of s y m m e t r y of
the multiplet; the coupling constants w e r e JAX = 1 Hz, JMX = 1.6 Hz, and JAM = 4 Hz. The r e l a t i v e signs
of these constants a r e identical, as follows f r o m e x p e r i m e n t s with double r e s o n a n c e for a s i m i l a r s y s t e m -
f u r a n - 2 - c a r b o x y l i c acid [2]~

x-~-~-c-o- o-c-~--~-x
~ 11 "0 ~
0 0

The s p e c t r u m of 5 , 5 ' - d i b r o m o f u r o y l peroxide (X = Br) contains two doublets; the distances between
the components of each doublet a r e 4 Hz. The c h e m i c a l shifts a r e 6.65 and 7.35 ppm. The s p e c t r u m of
5 , 5 ' - d i n i t r o f u r o y l peroxide (X=NO2) is affiliated with the AB type ( J / v o 6 ~ 1). The r a t i o of the intensities
of the inner and outer lines calculated on the basis of these values is 0.334, c o m p a r e d with the e x p e r i m e n t a l
value 0.360. The c h e m i c a l shifts a r e 7.70 and 7.82 ppm.
No effect of the peroxide group on the electronic e n v i r o n m e n t of the protons of the furan ring is ob-
s e r v e d . The PMR s p e c t r u m of the arthydride of f u r a n - 2 - c a r b o x y l i c acid, as in the c a s e of furoyl peroxide,
is an AMX s y s t e m with the s a m e c h e m i c a l shift and s p i n , s p i n c o u p l i n g constants (A53, 4 0.76 ppm). Identical
c h a r a c t e r of the PMR s p e c t r a is also o b s e r v e d for benzoyl peroxide and benzoic anhydride.

EXPERIMENTAL
The s p e c t r a of acetone and dioxane solutions w e r e r e c o r d e d with a J N M - 3 H - 6 0 s p e c t r o m e t e r with
hexamethyldisiloxane (HMDS) as the i n t e r n a l s t a n d a r d . The m e a n - s q u a r e e r r o r in the m e a s u r e m e n t s was
0.02 p p m .

LITERATURE CITED
1. V . G . Kul'nevich and N. N. B o r i s o v a , Khim. G e t e r o t s i k l . Soedin., No. 2, 48 (1970).
2. J . E m s l e y , J . Finet, and L. Suteliff, High-Resolution Nuclear Magnetic Resonance Spectroscopy,
Vol. 1, P e r g a m o n .

Y a r o s l a v S c i e n t i f i c - R e s e a r c h Institute of M o n o m e r s for Synthetic Rubber. K r a s n o d a r s k P o l y t e c h -

nical Institute. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 2, p. 163, F e b r u a r y , 1974.
Original a r t i c l e s u b m i t t e d June 5, 1972.

9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, N.Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy of this article is available from the publisher for $15.00.

142
RESEARCH ON POLYFUNCTIONAL OXIDES
VII.* STUDY OF THE REACTION OF SOME ESTERS OF
4 , 5 - E P O X Y - 2 - H E X E N O I C ACID WITH ALCOHOLS

M. S. Malinovskii, L. P, Glushko,. UDC 547.717

and N. I. Pokhodenko

E s t e r s of 5 ( 4 ) - h y d r o x y - 4 ( 5 ) - a l k o x y - 2 - h e x e n o i c acid w e r e obtained by r e a c t i o n of e s t e r s of
4 , 5 - e p o x y - 2 - h e x e n o i c acid with alcohols in the p r e s e n c e of acid c a t a l y s t s . It was e s t a b -
lished that the r e a c t i o n p r o c e e d s s e l e c t i v e l y in the p r e s e n c e of s m a l l amounts of BF 3 with
p r e d o m i n a n t opening of the oxide ring on the side of the e s t e r group.

We h a v e p r e v i o u s l y studied the r e a c t i o n of s o m e e s t e r s of 4 , 5 - e p o x y - 2 - h e x e n o i c acid with ketenes [2]

In the p r e s e n t c o m m u n i c a t i o n we have studied the direction of opening of the epoxide ring in e s t e r s under
the influence of alcohols in the p r e s e n c e of acid c a t a l y s t s (H2SO4,KU-2, and BF3). As in the c a s e of o t h e r
epoxides [3, 4], the r e a c t i o n of the above oxides with alcohols m a y p r o c e e d with the f o r m a t i o n of i s o m e r i c
alkoxy alcohols with the following s t r u c t u r e s :
CH3--CH-- CH-- CH~CHCOOC2H5
I
CH3-~CH-CH-CH~GHCOOC2H5 CH30H OIt OCH31
%/ c.~:.--c.-c.=c.coog,,
OCH3 OH
|1

The r e a c t i o n of the oxides with alcohols in the p r e s e n c e of BF 3 gives p r i m a r i l y i s o m e r I (Table 1), and
i s o m e r II is f o r m e d in 1.5-2% amounts, a c c o r d i n g to the r e s u l t s of g a s - l i q u i d c h r o m a t o g r a p h y (GLC). In a
detailed investigation of this r e a c t i o n in the p r e s e n c e of other c a t a l y s t s (H2SO4 and KU-2), it was shown that
the r e a c t i o n conditions have a g r e a t effect on the s e l e c t i v i t y of the addition of the alcohols ; depending on the
r e a c t i o n conditions, a second i s o m e r is f o r m e d along with product I. The r a t i o of the i s o m e r i c e s t e r s was
d e t e r m i n e d by GLC (Table 2).
The s t r u c t u r e of the alkoxy alcohols obtained was proved on the basis of IR and m a s s s p e c t r o s c o p y .
The IR s p e c t r a of the alkoxy alcohols contained a b s o r p t i o n bands c h a r a c t e r i s t i c for the C -----Ogroup of
e s t e r s (1723 c m - t ) , C----C groups (1650 cm-1), and OH groups (3450 c m -1) linked by an i n t e r m o l e c u l a r
hydrogen bond. We e s t a b l i s h e d the type of hydrogen bond by IR s p e c t r o s c o p y . The p r e s e n c e of a hydroxyl
group was also c o n f i r m e d by acylation of e s t e r IV with acetyl c h l o r i d e in c h l o r o f o r m in the p r e s e n c e of
pyridine.
The m a s s s p e c t r u m of ethyl 4 - e t h o x y - 5 - h y d r o x y - 2 - h e x e n o a t e (IV) contained intense peaks with m / e

45 (CH3CH=(~H), 85 [ C~I C=O ] and 159(H2C 2 +=CH-CH2COOC2Hs). The absence of ion peaks with
/
m / e 73 (CHaCH =+C2H~) inthe m a s s s p e c t r u m c o n f i r m s that the hydroxyl g r o u p is attached to the c a r b o n
a t o m in t h e 5 position and that the ethoxy group is attached to C 4.

* See [1] for c o m m u n i c a t i o n VI.

D n e p r o p e t r o v s k State U n i v e r s i t y . T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 2,
pp. 164-167, F e b r u a r y , 1974. o r i g i n a l a r t i c l e s u b m i t t e d J a n u a r y 30, 1973.

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, iV. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is avMlable from the publisher for $15.00.

143
i...i

TABLE 1. Esters of 5-Hydroxy-4-alkoxy-2-hexanoic Acid C,37~H--~n--cn=cncooR

OH OR

ng~o E mpixical Found Calc.

R R" bp, deg "C (ram!? I d42o MRD Yield, %
pound J formula C.%. H, % MR D C, % H,%
i
I C2Hs C2H6 120---121 (3) 1,0276 1,4575 " CloHls04 59,8 9,1 52,90 59,4 8.9 52,8 - 50
II C2Hs CH3 96--97 (2) 9 1,4590 C9H1804 57,2 8,7 49,10 57,4 8,5 48,9 51
' Ill ! n-C3Hr CH3 102--103 (4) 1,6423 1,4595 C1oHla04 ,,69,6 8,8 53,01 59,4 8,9 52,8 , 53
.IV : i-CaH7 CHa I04--105 (1) 1,0244 I ;4560 C loll 1804 59,5 8,9 52,83 59,4 8,9 53,6 43
V CH, C~H5 96--97 (3) 1,0249 1,4545 C9H1604 57,2 8,7 49,55 57,4 8,5 48,9 44
VI 'C2H~ C3H7 107--109 (4) 1,0135 !,4535 C 11H~o04 61,4 9,4 57,48 61,1 9,2 57,5 35
"VII . C2H~ C (CHa) s 112--113 (8) 1,0186 1,4590 C |2H2204 62,4 9,3 61,73 62,6 9,6 63,9 35

TABLE 2. Products of the Reaction of Ethyl 4,5-Epoxy-2-hexenoate

with Methanol
Exptl. conditions ' , --- bp, : c .
Ratio of
a ~ o u n t "reaction isomers I
reaction !,(mm) d4 ~o n D2o
and II, %
catalyst of ox. temEy time, h
[ide, molel ~ ~"i

KU-2 (lg) 0,015 5020._~ 20 114--116 (2) 1,0485 1,4585 59:41

20
H~so, (O,lma) o,o36 5o~6o 5 106 (3) ] 1,0688 I 1,4600[ 64 : 36
H2SO4 (0,1 ml) 0,02 5 119--122 (6) ! 1,0723 I 1,46001 67 :.33
BF8 (0,1 ml) 0,07 60 15 115--116 (6) 1,0468 1,4590 98 :2
BFa (0,2 ml) 0,2 25 20 110--112 (5) 1,0544 1,4580 95:5
 The c o r r e c t n e s s of the p r o p o s e d s t r u c t u r e was also p r o v e d by a c h e m i c a l method - by c o n v e r s i o n of
e s t e r IIi to the known 4-ethoxyhexanoic acid [5].

CH3CH_ CH_ CH=CHCOOC2H " H~(Ni) CH3CH_CH_(CH2)2COOC2H~

I 1 5 I I ,

c.~,~.-~:.-(c.~cooc~.~ CH3CH-H
I
C-,(CH2)2COOC
I 2
Hs

Br OC2VH5N=:I~ CH3OC 0 O%H 5

VIII

CH.~CH2CH--(CH2)2COOC2H5 ~ CH3CH2--~H(CH2)~COOH
OC2H5 OC2H5"
V.' VII

Thus, openingup the epoxide ring in e s t e r s of 4 , 5 - e p o x y - 2 - h e x a n o i c acid with alcohols in the p r e s e n c e

of BF 3 o c c u r s on the side of the e s t e r group; this is in a g r e e m e n t with the influence of the inductive effect
of the methyl group.

EXPERIMENTAL
The IR s p e c t r a of films of the s u b s t a n c e s w e r e r e c o r d e d with an IKS-14 s p e c t r o m e t e r (NaC1 and L i F
p r i s m s ) at 700-3700 c m -1. The m a s s s p e c t r a w e r e r e c o r d e d with an MKh-1303 s p e c t r o m e t e r at 100 ~ with
an ionizing voltage of 30 eV. C h r o m a t o g r a p h y was c a r r i e d out with a UKh-1 c h r o m a t o g r a p h with a 3 - m -
long column with SE-301 on NaCl; the c a r r i e r gas was hydrogen, and the flow r a t e was 50 m l / m i n at 150 ~
The e s t e r s of 4 , 5 - e p o x y - 2 - h e x e n o i c acid w e r e obtained by the method in [6].
Ethyl 5 - H y d r o x y - 4 - e t h o x y - 2 - h e x e n o a t e (III). The r e a c t i o n of 9 g (0.059 mole) of ethyl 4 , 5 - e p o x y - 2 -
hexenoate and 28 ml of ethanol in the p r e s e n c e of 0,2 ml of BF 3 e t h e r a t e at 50-60 ~ gave 4.6 g (50%) of a s u b -
s t a n c e with bp 120-122 ~ (2 m m ) , n~ 1.4575, d~~ 1.0276, and R f 0.28 [in e t h e r - h e x a n e (1:1)]. Found, %: C
59.8; H 8.9. C10H1804. Calculated, %: C 59.4; H 8.9. Compounds II-VII (Table 1) w e r e s i m i l a r l y obtained.
Ethyl 5 - H y d r o x y - 4 - e t h o x y h e x a n o a t e (IV). A 4.04 g (0.02 mole) Sample of ethyl 5 - h y d r o x y - 4 - e t h o x y -
2 - h e x e n o a t e was h y d r o g e n a t e d with hydrogen o v e r Raney nickel. The t h e o r e t i c a l l y c a l c u l a t e d amount of
hydrogen (450 ml) was a b s o r b e d . Distillation of the r e a c t i o n m i x t u r e gave 3.6 g (8.8%) of an e s t e r with bp
105-107 ~ (4 ram), n~ 1.4370 and d~~ 1.01!0. Found, %z C 58.9; H 10.01. C10H2004. Calculated, %: C 58.8;
H 9.8.
Ethyl 5 - B r o m o - 4 - e t h o x y h e x a n o a t e (V). A solution of 5.6 g of P B r 5 in 20 ml of CHC13 was added d r o p -
wise to a solution of 5.5 g (0.027 mole) of IV in 10 ml of c h l o r o f o r m , and the m i x t u r e was heated for 12 h
and poured into w a t e r . Workup gave 3.2 g (45%) of a s u b s t a n c e with bp 118-119 ~ (5 mm), n~ 1.4630, d~~
1.2051, and R f 0.68 [ h e x a n e - e t h e r (1 : 1)]. Found, %: C 44.8; H 7.2. C10H19BrO 3. Calculated, %: C 44.9;
H 7.1.
Ethyl 4-Ethoxyhexanoate (VI). A 2 g s a m p l e of zinc dust was added to a solution of 2.1 g (0.008 mole)
of 5 - b r o m o - 4 - e t h o x y h e x a n o i c acid in 10 m l of glacial acetic acid. Neutralization of the r e a c t i o n m i x t u r e
with EaCH gave 0.5 g (35%) of a s u b s t a n c e with bp 97 ~ (3 mm) and n~ 1.4470. Found, %: C 63.8; H 10.1.
Ci0H2003. Calculated, %: C 63.5; H 10.0.
4-Ethoxyhexanoic Acid (VII). Ethyl 4-ethoxyhexanoate (VI) was heated with 10 ml of 0.5% alcoholic
KOH, and the m i x t u r e was worked up to give VIII with bp 115 ~ (2 ram) and n~ 1.4525. The physical constants
of the product w e r e in a g r e e m e n t with the l i t e r a t u r e data [5].
Ethyl 5 - A c e t o x y - 4 - e t h o x y h e x a n o a t e (VIII). Acylation of 1.1 g (0.005 mole) of IV was c a r r i e d out with
18 ml of CH3COOC1 in 15 m l of c h l o r o f o r m in the p r e s e n c e of 8 ml of pyridine. The m i x t u r e was worked up
to give 1 g of VIII with bp 110 ~ (3 m m ) , r ~ 1.4360 and d 2~ 1.0061. Found, %: C 58.2; H 8.8; MR D 63.69.
C12H2205. Calculated, %: C 58.5; H 8.9; MR D 62.34.

LITERATURE CITED
1. L. P. Glushko, M. M. K r e m l e v , Yu. Yu. Samitov, and T. M. Malinovskaya, U k r . Khim. Zh., 3_99, 801
(1973).

145
 2. Yu. Yu. Samituv, L. P. Glushko, M. S. Malinovskii, and N. I. Pokhodenko, Khim. Geterotsikl. Soedin.,
447 (1971).
3. N. N Lebedev, Trudy MKhTI im. D. I. Mendeleeva, 64, 85 (1970).
4. A.A. Petrov, Zh. Obshch. Khim., I_~4,1038 (1944).
5. Albert B. Boese, US Patent No. 2,484,067 (1949); Chem. Abstr., 44, 1529 (1950).
6. M.S. Malinovskii, L. P. Glushko, N. I. Pokhodenko, L. I. Kopeiko, and V. I. Avramenko, in: Chemical
Structure, Properties, and Reactivities of Organic Compounds [in Russian], Kiev (1969), p. 721.

146
SYNTHESIS OF DERIVATIVES OF OLEANDOMYCiN AMINOHYDRIN

Ya. A. Kastron, V. V. Novikova, UDC 615.33:542.958:543.422.4.6

t~. I~. L i e p i n ' , and S. A. Giller

Reaction of oleandomycin with s e c o n d a r y amines p r o c e e d s at the epoxy group of the anti-

biotic in c o n f o r m i t y with the K r a s u s k i i rule to give biologically active d e r i v a t i v e s of
oleandomycin a m i n o h y d r i n .

The constantly developing r e s i s t a n c e of m i c r o o r g a n i s m s r e q u i r e s constant renovation as well as i m -

p r o v e m e n t in the a n t i b a c t e r i a l , p h a r m a c o l o g i c a l , and p h y s i c o c h e m i c a l p r o p e r t i e s of the existing anti-
b i o t i c s . This can be achieved by c h e m i c a l t r a n s f o r m a t i o n of the l a t t e r .
The p r e s e n t p a p e r iis devoted to a study of the reaction of oleandomycin (I) with s o m e aliphatic and
h e t e r e c y c l i c s e c o n d a r y a m i n e s . Nucleophilic addition at the epoxy group of the antibiotic p r o c e e d s u n d e r
r e l a t i v e l y mild conditions (30-40~ in 15-30 h). P r a c t i c a l l y individual addition products II-VIII (Table 1)
w e r e obtained when the r e a c t i o n was c a r r i e d out in ether; other products of unestablished s t r u c t u r e a r e
f o r m e d in s m a l l amounts along with II-VIII when the r e a c t i o n is c a r r i e d out in alcohol. In c o n f o r m i t y
with the K r a s u s k i i r u l e , one m i g h t have expected r e a c t i o n to f a v o r the f o r m a t i o n of d e r i v a t i v e s of oleando-
m y c i n a m i n o h y d r i n * containing a hydroxyl group attached to the less hydrogenated c a r b o n a t o m .

N(CHD. OCff3

CH~ CHa Ctl~ Ctt~

I I1 - V I I I
II NR~=N(CH~)2i III NR2=N(C2Hs)2; IV NR2=pyrrolidino y Nl~=pipericlino
VI ~R2~ morpnolino VII NR2= emymniminovIII NR2= nexamemyLemmino

The IR s p e c t r a of II-VIII show that the lactone ring (1080, 1710-1730 c m -1) and the c a r b o n y l group
of the oleandolide ring (1690 c m -1) a r e r e t a i n e d in t h e m and that they contain hydroxyl g r o u p s . In addi-
tion, the a b s o r p t i o n at 3075 c m -1 for VII is evidence for the p r e s e n c e of an ethyleneimine function.
The UV s p e c t r a of II-VIII, which, like the oleandomycin b a s e s , contain a low-intensity or concealed
m a x i m u m at 280-295 nm, indicate that they cannot be the anhydro f o r m s : in the opposite c a s e , we would
have o b s e r v e d a b a t h o c h r o m i c shift of the m a x i m u m to 310 nm and the a p p e a r a n c e of a new intense m a x i -
m u m at about 240 nm, as o c c u r s in the c a s e of anhydrooleandomycin.
The protons of the epoxy group in the PMR s p e c t r u m of b a s e I g i v e a singlet at 8.23 r . This singlet
d i s a p p e a r s in the s p e c t r u m of the product of r e a c t i o n of oleandomycin with d i m e t h y l a m i n e , while a new
singlet at 7.93 9 and the c h a r a c t e r i s t i c AB q u a r t e t of the anisochronic protor~, of the N - C H 2 group at 7.3-
7.8 9 (J = 14.5 Hz) a p p e a r , and the r e m a i n i n g s p e c t r a l r a n g e s a r e unchanged. These data a r e in c o n f o r m -
ity with s t r u c t u r e II.
9 In analogy with the n a m e s "oleandomycin c h l o r o h y d r i n and glycol" [1-3].
Institute of Organic Synthesis, A c a d e m y of Sciences of the Latvian SSR, Riga. T r a n s l a t e d f r o m
Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 2, pp. 168-171, F e b r u a r y , 1974. Original a r t i c l e s u b m i t t e d
F e b r u a r y 27, 1973.

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No txzrt of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is a~ailablefrom the publisher for $15.00.

147
 T A B L E 1. N,N-Disubstituted Derivatives of Oleandomycin Amino-
hydrin
,, ,,,
/CSIT ~1 Dihyd , bXo de I F #

Com= inp: *C
pound

II
'
I Empirical~ ,ound.
formula

98----102] CsrHn~q~)l,
c IH1N

I1
Ca*r

' 1/1
9.6,3.6 .3,9.3 3.8 -78.9"
tt-J (c .t
c I_ H ] N t .a.n.o.l.) . . . . ~aterj_,!

-61. o t 97
Iit 93---96 ] CsH:,~N2OI2 61,519,713,9161,619,513,71 -87,5 1r -62,0 197
IV 98----101/ CzHr0N2Ot~ 61,6[9,61 3,6161,719,313,71 -74,2 126--130 -44.4 186
V 151--153"[C40HT~NzOI~ 61,9 9,613,7 6~,119,413'6] -81,6 133--137 -37,8 180
VI 206~206 ] CsgHroN~O~ 60,4 9,3[3.6 60A[9,113,6] -80,2 128--130 -67.8 [75
VII 118--121] CzTH6~N2Ow 60,5]9,1~3,7160.8~9,1] 3'8] -73,6 -- ]92
VIII 152--154[ C41H74N2OI2 82.419,413'616~610,613'5/ - 8 5 , 2 14o--142 -67,7 8o,

T A B L E 2. I o n i z a t i o n C o n s t a n t s of N , N - D i s u b s t i t u t e d O l e a n d o m y c i n
A m i n o h y d r i n s (in aqueous ethanol at 20~

Com- Computational method Noycs method

pound pKa I PKa: PKa, "e PK a~ T PKv i P K a~

II 8,74-+0,10 7,34-+0,03 ] 8,72-+0,09 7,19-+0,06 8,74--+0,06 7,51__0,03

III 9,10+0,09 7,82+0,05 9 10-+0,06 7,68 8,95-+0,06 7,93_+Q,04
IV 9,45-+0,07 7,93-+0,08 9,43-+0,02 7,79-+-0,(}6 9.28-----0,05 8,14_+0,06
V 9,49-+0,06 7,85-+~,0fi 9~ 7,74-+0,05 9,38-+0.06 7.98_+0,03
VIII 9,48-+0,10 7,89-+0,06 9 9~45-+0,10 7,7'5-+0,06 9,26-+0,06 8,t 4 _+0,03
VI 8,57-+0,02 4,61-+0.02 8,54-+0,09 4,48~ 0,(12 '8.50" 4,60"
VII &52-+0,05 5~09-+r0.06 8,50-+0,04 4,97-+0,04 8,60* 6,25*
I 8.47-+0,02 '8,50"

* G r a p h i c a l m e t h o d (the pH at the h a l f - n e u t r a l i z a t i o n point).

The i o n i z a t i o n c o n s t a n t s of e a c h a m i n o g r o u p w e r e d e t e r m i n e d for the o l e a n d o m y c i n d e r i v a t i v e s o b -

tained (II-VIID (Table 2). The t h e r m o d y n a m i c ionization c o n s t a n t s ( p K ; ) [4] w e r e also c a l c u l a t e d . The
b a s i c i t y of the d i m e t h y l a m i n o g r o u p of the d e s o s a m i n e function of the a m i n o h y d r i n s is c h a r a c t e r i z e d by
p I ~ l, the value of which depends on the s t r u c t u r e of the N , N - d i s u b s t i t u t e d r e s i d u e of the a m i n o h y d r i n . The
pKa2 v a l u e r e f l e c t s p r o t o n a t i o n of the l a t t e r . In this c a s e , c o r r e l a t i o n between the pKa values of the
s e c o n d a r y a m i n e s [5-7] * u s e d in the p r e p a r a t i o n of I I - V I I I and the p K a i a n d PKa2 v a l u e s is o b s e r v e d f o r
I I - V and VIII. The h i g h e r the b a s i c i t y of the s e c o n d a r y a m i n e s , the h i g h e r the pKal and PKa2 values of the
substituted aminohydrins.
In the c a s e of VI, we d e m o n s t r a t e d t h a t N , N - d i s u b s t i t u t e d a m i n o h y d r i n s of o l e a n d o m y c i n f o r m N -
oxides at both a m i n o g r o u p s in a dilute m e t h a n o l s o l u t i o n of h y d r o g e n p e r o x i d e . N-Oxide IX was i s o l a t e d
as a s t a b l e s o l v a t e with c h l o r o f o r m . This is a l s o indicated by the PlVIR s p e c t r u m of IX (in h e x a d e u t e r o -
acetone): a singlet, which c a n be a s s i g n e d to the p r o t o n of s o l v a t e d c h l o r o f o r m , is o b s e r v e d at 2.1 r . The
f o r m a t i o n of s o l v a t e s with c h l o r o f o r m and o t h e r c h l o r i n a t e d h y d r o c a r b o n s is a c h a r a c t e r i s t i c p r o p e r t y of
o l e a n d o m y c i n [2].
A c c o r d i n g to p r e l i m i n a r y data, I I - V I I I d i s p l a y a c t i v i t y with r e s p e c t to G r a m - p o s i t i v e m i c r o o r g a n i s m s .
P r i o r to tiffs, only o n e b i o l o g i c a l l y a c t i v e d e r i v a t i v e of o l e a n d o m y c i n with an open epoxide r i n g - o l e a n d o -
m y c i n c h l o r o h y d r i n [8] - was known.

EXPERIMENTAL
The homogeneity of the oleandomycin aminohydrin derivatives was monitored by thin-layer chrom-
ategraphy (TLC) on Silufol in butanol-water-acetone-ammonia (200:150:25:25) and butanol-acetic-
acid-water (3 :I :I) systems; the chromatograms wore developed with "aldehyde sulfuric acid.,, The P M R
spectra of I and II (20% solutions in C6D6) , N-oxide IX [in (CD3)aCO], and amine VI (in CDCI3) were recorded
with aPerkin-Eimerl~12A spectrometer. The internal standard was tetramethylsilane. The basicity of
the amines wore measured with a Seibold D V N potentiometer with glass and silver chloride electrodes. A
0.5 m m o l e sample of II-V and VIII was dissolved in 10 ml of ethanol, and 75 ml of water was added (VI and
VII were dissolved in 5 ml of methanol, and 80 ml of water was added); the solutions were titratedunder
nitrogen with 0.I N hydrochloric acid at 20 * 1~ . The pK a values were determined both by a graphical
method from the titrationcurves [9] and by the usually employed computational method [4].

* W e d e t e r m i n e d the b a s i c i t y of h e x a m e t h y l e n e i m i n e (pK a 11,20) by p o t e n t i o m e t r y at 20 ~

148
 Oleandomycin N , N - D i m e t h y l a m i n o h y d r i n (II, Table 1). A. A m i x t u r e of 6.87 g (0.01 mole) of oleando-
m y c i n in 100 m l of absolute e t h e r and 51 ml of 1.97 N d i m e t h y l a m i n e in ether was held at 30 ~ in a s e a l e d
ampule for ,20 h. F i l t r a t i o n of the m i x t u r e , r e m o v a l of the s o l v e n t b y distillation, and drying of the r e s i d u e
g a v e 7.13 g (977e) of c h r o m a t o g r a p h i c a l l y homogeneous II, which was quite soluble in e t h e r , benzene, m e t h -
anol, and c h l o r o f o r m but only slightly soluble in w a t e r . IR s p e c t r n m (in Nujol): 3480 (OH), 1730 (lactone
C = O ) , 1690 {shoulder, C = O of the keto g r o u p of the oleandolide ring), 1080 c m -1 (lactone ring). UV s p e c -
t r u m in 3% aqueous ethanol: inflection at 280-295 n m , s ~ 80-115. The dihydrochloride was p r e p a r e d as
follows. A total of 4,38 ml of a 0.915 N e t h e r solution of hydrogen chloride was added to a solution .of 1.446
g {0.002 mole) of amino alcohol II in 250 m l of absolute ether, and the m i x t u r e was allowed to stand o ~ e r -
night in a r e f r i g e r a t o r . The gelatinous p r e c i p i t a t e was r e m o v e d by filtration, washed with ether, aild dried
o v e r phosphorus pentoxide to give 1.38 g of the dihydrochloride as a h y g r o s c o p i c powder with mp 120-123 ~
and [a]~ = - 6 1 . 5 ~ (c 2, w a t e r ) . Found,%: C 55.0; H 8.8; N 3.3; C1 9.1. CsTH68N~O12 9 2HC1. Calculated, %:
C 55.1; H 8.8; N 3.5; C1 8.8. The diphosphate was p r e p a r e d as follows. -A 0.244 g {0.002 mole) s a m p l e of
88% phosphoric acid in 150 ml of absolute e t h e r was added to a solution of 0.72 g {0.001 mole) of amino a l -
cohol II in 1 0 0 ' m l of absolute e t h e r . The solution was s t o r e d in a r e f r i g e r a t o r f o r 24 h. The gelatinous
p r e c i p i t a t e was s e p a r a t e d and dried in vacuo to give 0.71 g (76%) of the diphosphate as a powder with mp
142-146 ~ and [a]~ = -58.1 ~ (c 2, w a t e r ) Found, %: C 47.7; H 7.9; N 3.0; P 6.9. Cs~HssN2012 9 2HsPO 4. The
methiodide was p r e p a r e d as follows. A 0.5 m l s a m p l e of methyl iodide was added to a solution of 0.50 g of
amino alcohol II in 50 ml of absolute ether, and the m i x t u r e was allowed to stand in the d a r k for 24 h. The
light-yellow p r e c i p i t a t e was r e m o v e d by filtration, washed with ether, and d r i e d to give 0.30 g of the m e t h -
iodide with mp 170-175 ~ {dec.). R e p r e c i p i t a t i o n f r o m alcohol solution by the addition of e t h e r gave a p r o d -
uct with mp 175-177 ~ (dec.). Found, %: C 51.9; H 8.1; N 3.2. C38H71N2OI2. Calculated, ~c: C 52.2; H 8.2;
N 3.2.
B__: P e r f o r m a n c e of the r e a c t i o n in ethanol gave 7.27 g of c h r o m a t o g r a p h i c a l l y nonhomogeneous p r o d -
uct, containing two c o m p o n e n t s , with mp 78-83 ~. T r e a t m e n t with e t h e r gave 1.19 g of e t h e r - i n s o l u b l e
m a t e r i a l with mp 179-181 ~. Compound II, with mp 98-102 ~ was isolated by passing the e t h e r e x t r a c t through
finely g r a i n e d powdered KSK s i l i c a gel.
Oleandomycin N , N - D i e t h y l a m i n o h y d r i n (III, Table 1). A. A total of 14.66 g (97~0) of analytically p u r e
powdered III with mp 88-94 ~ was obtained f r o m 13.74 g {0.02 mole) of epoxide I and 21.-5 ml (0.21 mole) of
diethylamine in 200 ml of absolute e t h e r (at 30 ~ for 23 h). C h r o m a t o g r a p h i c a l l y p u r e amino alcohol III, with
mp 93-96 ~ was obtained a f t e r t r e a t m e n t with KSK s i l i c a gel.
B. A t w o - c o m p o n e n t m i x t u r e was obtained when the r e a c t i o n was c a r r i e d out in ethanol. T r e a t m e n t
of the m i x t u r e with e t h e r g a v e 13.80 g of amino alcohol III. The r e s i d u e contained 0.66 g of a product of un-
e s t a b l i s h e d s t r u c t u r e with mp 186-188 ~ (from 50% ethanol) and [~]~ = - 5 2 . 6 ~ (c 2, methanol).
Aminohydrins IV-VI (Table 1). The r e a c t i o n of epoxides I with p y r r o l i d i n e , piperidine, and m o r p h -
oline was c a r r i e d out in ethanol at 40 ~ for 13-16 h. Reaction products IV-VI w e r e isolated and purified as
in the p r e p a r a t i o n of amino alcohol III. Compound VI was r e c r y s t a l l i z e d f r o m e t h e r to give fine needles.
Oleandomycin E t h y l e n e i m i n o h y d r i n {VII). A 14 ml {0.27 mole) s a m p l e of f r e s h l y distilled ethylene-
imine was added to a solution of 6.87 g (0.01 mole) of oleandomycin in 150 ml of absolute ether, and the
m i x t u r e was held at 30 ~ for 34 h. The s o l v e n t was r e m o v e d by distillation, and the r e s i d u e was dried
thoroughly in vacuo o v e r KOH and P~O 5. It was then dissolved in 200 m l of d r y ether, and the solution was
f i l t e r e d through a dense f i l t e r . C r y s t a l l i z a t i o n c o m m e n c e d when the solution was c a r e f u l l y e v a p o r a t e d with
a r o t a r y e v a p o r a t o r . The solid m a t e r i a l was r e m o v e d by filtration, w a s h e d with d r y ether, and d r i e d to
give 6.69 g (92%) of c h r o m a t o g r a p h i c a l l y p u r e amino alcohol VII with mp 118-121 ~ Quantitative d e t e r m i n a -
tion of the ethyleneimine ring by means of p o t a s s i u m thiocyanate [10] in acidic m e d i a showed that its p e r -
c e n t a g e was 95%. IR s p e c t r a (in Nujol): 3520, 3075 ( a s y m m e t r i c a l vibrations of the a z i r i d i n e ring), 1720,
1680, 1080 c m -i . UV s p e c t r u m {in 3% aqueous ethanol): k m a x 288 nm, s 59. In ethanol, this r e a c t i o n
g a v e a m i x t u r e of two products of unestablished s t r u c t u r e : one, with mp 58-60 ~ was soluble in ether, and
the other (rap 139-140 ~ was insoluble in e t h e r . Both products gave a qualitative r e a c t i o n for a p r i m a r y
amino group with dibepine [11].
Oleandomycin N , N - B e x a m e t h y l e n e a m i n o h y d r i n {VIII). This compound was obtained by the method
u s e d to p r e p a r e VII by heating the r e a c t i o n m ~ h ~ e f o r 10 h. The product was purified by r e c r y s t a l l i z a t i o n
from ether.

149
 N,N-Dioxide of Amine VI (IX). Water (8 ml} and 1.30 ml (12.8 mmole) of 30% hydrogen peroxide w e r e
added to a solution of 0.5 g (0.64 mmole) of amine VI in 18 ml of methanol, and the mixture was allowed to
stand for 24 h. The methanol was then r e m o v e d by vacuum distillation, and the residue was extracted
s e v e r a l times with c h l o r o f o r m to give 0 2 9 g of a white, powdery, chromatographically homogeneous solvate
of N-oxide IX with c h l o r o f o r m , with mp 111-115 ~ (dec.). IR s p e c t r u m (in NujoD: 950 c m -1 iN ~ O). A p r o -
nounced shift to weak field of the singlet of the dimethylamino group as c o m p a r e d with the starting amine
(7,72 T i n V I and 6.80 ~" in IX) was o b s e r v e d in the PMR s p e c t r u m . Found, %: C 51.6; H 7.8; N 3.1.
C39BToN2Oi5 9 CHC13. Calculated, %: C 51.9; H 7.7; N 3.0.

LITERATURE CITED
1, ]~. I. Rodionovskaya, G. S. Rozenfel'd, V. M. Baikina, and D. M. Trakhtenberg, Antibiotiki, 705 (1966).
2. H. Els, W. D. C e l m e r , and K. Mural, J . A m e r . Chem. Soc., 8_00,3777 (1958).
3. D . M . Trakhtenberg, G. S. Rozenfel'd, and A. I. Reznik, Antibiotiki, 874 (1968).
4. A. A l b e r t and E . Serjeant, Ionization Constants of Acids and Bases, Methuen (1962).
5. A . G . Evans and S. D. Hamann, T r a n s . F a r a d a y Soc., 4_!, 34 (1951).
6. S. Searles, M. T a m r e s , F. Block, and L. A. Quarterman, J. A m e r . Chem. Soc., 7_88,4917 (1956).
7. R . J . Bruehlman and F. H. Verhoek, J . A m e r . Chem. Soc., 7__00,1401 (1948).
8. D . M . Trakhtenberg and t~. I. Rodionovskaya, Antibiotiki, 52 (1959).
9. R. Linstead, J . Elvidge, M. Valli, and G. Wilkinson, Modern Methods of Investigation in Organic
C h e m i s t r y [Russian t r a n s l a t i o n ] , IL, Moscow (1959), p. 192.
10. N. Ya. Ozolin' and V. ]~. Egert, Izv. Akad. Nauk LatvSSR, Ser. Khim., 554 {1968).
11. G. Ya. Dubur and G. Ya. Vanag, Izv. Akad. Nauk LatvSSR, Ser. Khim., 25 (1962).

150
CATALYTIC TRANSFORMATIONS OF BENZOFURAN
IV.* VAPOR-PHASE ALKYLATION OF BENZOFURAN WITH

t e r t - B U T Y L CHLORIDE

l~. A . K a r a k h a n o v , G. V. Drovyannikova, UDC 547.728.1.542.971.3

and E. A. Viktorova

When benzofuran is alkylated with t e r t - b u t y l chloride in the v a p o r phase (190-260~ in a flow

s y s t e m , the r a t i o of the 2 - and 3 - t e r t - b u t y l b e n z o f u r a n s f o r m e d v a r i e s f r o m 2 : 1 to 20 : 1, d e -
pending, on the acidity of the c a t a l y s t used (ZnCl~/A1203) , b e c a u s e of c o n v e r s i o n of the 3-
i s o m e r to the 2 - i s o m e r .

We studied the alkylafion of benzofuran with t e r t - b u t y l chloride at 190-260~ in a flow-type apparatus

on s a m p l e s of A1203 and ZnC12/A120 ~ of different acidity (Table 1). The chief r e a c t i o n products were 2- (I)
and 3 - t e r t - b u t y l b e n z o f u r a n s (II), the ratio of which v a r i e d f r o m 2 : 1 to 20 : 1, r e s p e c t i v e l y , while i s o m e r II
always predominated in experiments at lower t e m p e r a t u r e s (60-100 ~ in the c a t a l y z a t e s in a static s y s t e m [2].
The p r e d o m i n a n t f o r m a t i o n of i s o m e r I in experiments in the v a p o r phase is a s s o c i a t e d with i s o m e r i -
zation of II to I, which o c c u r s under the influence of catalysts with an acidic function (Table 2); r e v e r s e
t r a n s f o r m a t i o n was not o b s e r v e d under the investigated conditions. This s o r t of i s o m e r i z a t i o n of alkyl-
benzofurans in the p r e s e n c e of a heterogeneous c a t a l y s t with a r e l a t i v e l y low acidity has not been p r e v i o u s l y
noted. It follows f r o m Table 2 that the i s o m e r i z a t i o n of II to I is accompanied by the formation of b e n z o -
furan and isobutylene, the amount of which i n c r e a s e s as the t e m p e r a t u r e r i s e s and the acidity of the c a t a l y s t
i n c r e a s e s ; this apparently is evidence for i n t e r m o l e c u l a r i s o m e r i z a t i o n [3].

* S e e [1] f o r c o m m u n i c a t i o n III.
TABLE 1. Alkylation of Benzofuran with t e r t - B u t y l Chloride (space
velocity 0.15 h -1, r e a g e n t r a t i o 1 : 1 )
Yield based on converted
Cataly~ Temp., benzofuran, %
Catal~t acidity* aC ,.
I I~ Iphenols
186 25 10 1
200 28 12 2
Al~Os 0,2 230 28 13 2
260 30 15 5
185 28 11 2I
200 38 I0 20
5% ZnC'I~/AI20~ 1,0 230 36 20
260 38 2 35
185 36 4 20
200 42 4 25
10% ZnCldAl2Os 1,5 230
260 g 2
27
43
185 21 1 " 33
'2O0 20 I 42
90% ZnCI2/AI~Os 3,0 230 15 -- 60
260 7

* The n u m b e r of millieNuivalents of n-butylamine consumed in the

titration of 1 g of c a t a l y s t is p r e s e n t e d .
M. V. Lomonosov Moscow State U n i v e r s i t y . T r a n s l a t e d f r o m Khimiya Geterotsiklicheskikh Soedinenii,
No. 2, pp. 172-175, F e b r u a r y , 1974. Original a r t i c l e submitted November 26, 1972.

9 19 75 Plenum Publishing Corporation, 227 West 1 7th Street, New York, N. X 10011. No part of this publication may be reproduced, ]
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming, [
recordingorotherwise, without written permission of the publisher. A copyofthisartiele.isavazTablefromthepublisherfor$15100.

151
 I Degree of conversion of ~gy, I
/ be~zofuran, mole % 1,3-
II

I,I

0,9

20 . / / 0,7

~ Catalyst wt, r I "103

r
i r i i I
9 0,4 0,8 1,2 1,6 2,0 l:g 2;0 ~;~ 2,2 2;3"
Fig. 1. Dependence of the degree of c o n v e r - Fig. 2. Dependence of the amount of alkyla-
sion of benzofuran on the amount of A1203 tion products formed on the temperature:
(space velocity 0.8 h -I at 230~ I) 2 - t e r t - b u t y l b e n z o f u r a n ; II) 3 - t e r t - b u t y l -
ber~ofuran.

TABLE 2. I s o m e r i z a t i o n of 3 - t e r t - B u t y l b e n z o f u r a n (I1) (space velocity

1.15 h -i)
' ] Comp~ition of the liquid catalyzate, %
Catalyst remperamreJ " -
"~C" - -~enzofttran i Ii ]phenols

A120~ 260 m
99 --
5% ZnCI2/AI2Os 260 2 94
200 -- 90 3
220 ,I 84 3 83 2
240 9 8 77 4
10% ZnCldAlaOs 2~0 13 ~ 5
280 23 3
300 20 4 73 3
320 19 1 77 3
20% ZnCI2/AI2Os 260 20 19 56 5

TABLE 3. Dependence of the D e g r e e of C o n v e r s i o n o f

Benzofuran on the T e m p e r a t u r e (space velocity 0.8 h -1,
~/-A1203 catalyst)
"r~ - IYield, i Amount of benzo-
"~mpes_a__mre,' %mole Converted benzo- furanr~am~s~
furan, mole % on me c~ ly ,
9 .c i ~ mole %

44
200 17 37
208 i 14 30
24
230 20
240 4 17

We studied s o m e kinetic principles of the alkylation of benzofuran in a flow s y s t e m under conditions

that exclude i s o m e r i z a t i o n . The experiments w e r e c a r r i e d out on y-A120~ (0.25"O~5-mm fraction).
The experimental conditions also excluded o c c u r r e n c e of the r e a c t i o n both in the external and internal
diffusion r e g i o n s . The dependence of the degree of c o n v e r s i o n df benzofuran on the amount of c a t a l y s t is
p r e s e n t e d in Fig. 1; s e g m e n t ab on the c u r v e c h a r a c t e r i z e s the kinetic region of the o c c u r r e n c e of the r e a c -
tion.
The amount of converted benzofuran (in the p r e s e n c e of a tenfold excess of t e r t - b u t y l chloride) is in-
dependent of its concentration; a s i m i l a r pattern is also o b s e r v e d for t e r t - b u t y l chloride, which means ap-
p a r e n t z e r o - o r d e r of the r e a c t i o n with r e s p e c t to both benzofuran and t e r t - b u t y l chloride. The i n d e p e n d e n c e
of the degree of c o n v e r s i o n of benzofuran on the space velocity also confirms a z e r o - o r d e r r e a c t i o n . This
makes it possible to suppose that the slow step in the alkylation is c o n v e r s i o n of the adsorbed complex on
the c a t a l y s t .
The f o r m a t i o n of i s o m e r s I and II is c h a r a c t e r i z e d by identical t e m p e r a t u r e coefficients (Fig. 2), and
the step involving the f o r m a t i o n of cr complexes A and B is apparently the r a t e - l i m i t i n g step.

152
 (CH3)~CO + K*~:. . . " .

c(CH3hCl- | -HCl I
J ads C(CHB)3
A I

It follows f r o m Table 3 that the d e g r e e of c o n v e r s i o n of benzofuran in the p r e s e n c e of a tenfold excess

of t e r t - b u t y l c h l o r i d e d e c r e a s e s as the t e m p e r a t u r e r i s e s .
A s i m i l a r p a t t e r n was also o b s e r v e d with 1 : 1, 1 : 2, and 2 : 1 r a t i o s of r e a c t i n g s u b s t a n c e s . The r e g u -
l a r i t i e s obtained a r e a s s o c i a t e d with s u p p r e s s i o n of alkylation due to poisoning of the active c e n t e r s of the
c a t a l y s t s by the condensation products and inhibition by the r e a c t i o n p r o d u c t s .

EXPERIMENTAL
The i s o m e r i z a t i o n was c a r r i e d out in a flow s y s t e m with a 1.5 ml detachable r e a c t o r in a s t r e a m of
d r y nitrogen. The v o l u m e of the c a t a l y s t (0.25-0.5 m m fraction) was 1 ml. The yield of c a t a l y z a t e was 98-
99%.
A detachable quartz r e a c t o r i S 0 - m m long and 10 m m in d i a m e t e r ) was u s e d to d e t e r m i n e the kinetic
p a r a m e t e r s . The c a t a l y s t was an industrial s a m p l e of AI20 ~ (0 .5-0~ fraction) with a s u r f a c e a r e a of
206 m 2 / g , d e t e r m i n e d by the gas s o r p t i o n method (with nitrogen). The aluminum oxide was calcined at
500 ~ for 4 h and t r e a t e d with 60% w a t e r (based on the weight of AI203) p r i o r to the e x p e r i m e n t s . The c a t a l y s t
was d r i e d at 300 ~ for 4 h. All of the e x p e r i m e n t s w e r e c a r r i e d out in a s t r e a m of nitrogen on a f r e s h p o r -
tion of c a t a l y s t (from 0.4 to 2 g). Samples w e r e s e l e c t e d a f t e r 10 min.

LITERATURE CITED
1. ]~. A. Karakhanov, G . V . Drovyannikova, L. A. Kiseleva, and E. A. Viktorova, Khim. G e t e r o t s i k l .
Soedin., 1020 (1971).
2. t~. A. Karakhanov, G. V. Drovyannikova, and E. A. Viktorova, Khim. G e t e r o t s i k l . Soedin., 156 (1971).
3. A . N . Kost, V. A. Budylin, E. D. Matveeva, and D. O. Sterligov, Zh. Organ. Khim., 6, 1503 (1970).

153
S Y N T H E S I S OF o- AND p - H Y D R O X Y A C E T O P H E N O N E S AND
2-METHYL-4,6-DIARYLPYRYLIUM AND 2 - A R Y L - 4 - M E T H Y L -
BENZOPYRYLIUM S A L T S BY A C E T Y L A T I O N OF SOME P H E N O L S

G. N. D o r o f e e n k o and V. V. T k a c h e n k o UDC 547.577.814.5

Acylation of phenols with acetic anhydride in the presence of 70% perchloric acid results in
the synthesis of hydroxyaryl methyl ketones and substituted benzopyrylium s alte.

It is known that acylation of aromatic hydrocarbons and ethers of phenols with acid anhydrides in the
presence of 70% perchloric acid leads to 2-alkyl-4,6-diarylpyrylium salts [1,2].
It was not possible to synthesize pyrylium salts from phenols by this method [3], since phenol acetates
are obtained by the action of acetic anhydride under mild conditions [4], while reaction with aliphatic acids
in the presence of perchloric acid gives o-hydroxyaryl alkyl ketches [5].
In the present research we investigated the acetylation of phenols (phenol, m- and p-cresols, p-thymol,
o-xylenol, and resorcinol) with acetic anhydride in the presence of perchloric acid. It was found that the
formation of 2-aryl-4-methylbenzopyrylium or 2-methyl-4,6-diarylpyrylium salts was observed along with
the formation of o- and p-hydroxyacetophenones when the reaction mixture was heated (100-135~
The direction of this reaction depends substantially on the structure of the phenol and the phenol-
acetic anhydride-perchloric acid ratio. In the presence of equimolecular amounts of perchloric acid (re-
agent ratio 1 : 3 : 1 ) , 4-methylflavylium salts (IVa-e, Table 2) are isolated in good yields, and o-hydroxy-
acetophenones are formed (30-80o/0 yields):

CH3
R.~ -/~2O = R , ~ R~COCH~ CH3 /~R HCIO,.. R
Oil HCIO4 OCOCH3 ~'011 . HGI04 ~'~../ " 0 II OH - H20 R

OH
I II IH IV

The phenol acetates (I) formed in the first step undergo Fries rearrangement to give o-hydroxyaceto-
phenones (II, Table 1), which, under the reaction conditions, are condensed to chalcones (III), which are
further cyclized to 4-methylflavylium salts (IV).
Salts IV are formed readily in the acylation of p-substituted phenols (p-cresol and p-thymol) and are
also obtained from those phenolic compounds (m-cres el and o-xylenol) which are converted primarily to o-
hydroxyaeetophenones during the Fries rearrangement.
Under similar conditions, phenol also gives a low yield (4%) of 4-methyl-2-(2-hydroxyphenyl)benzo-
pyrylium salt (IVe). When 70% HC104 is introduced into the reaction of o-hydroxyacetophenone with acetic
anhydride, the yield of IVe, as expected, increases and reaches 41.6%.
In the case of resorcinol, one observes the formation (in high yield) of resacetophenone or resodi-
acetophenone, depending on t h e r e a g e n t ratio. 4-Methyl- 7-acetoxy-2-(2,4-diacetoxyphenyl)benzopyrylium
perchlorate (IVf) is formed from resorcinol in 12.4% yield only when the reagent ratio is 1 : 6 : 0.5.

Rostov State University. Scientific-Research Institute of Physical and Organic Chemistry, Rostev-on-
Don. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 176-180, February, 1974.
Original article submitted January 2, 1973.

9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy of this article is availablefrom the publisher for $15.00.

154
 TABLE 1. o-Hydroxy Ketones COCH a

u a-f

I Phenol- ace-I
tic anhy- l Reaction;I Reaction! mp, ~ ~-
Com- dride-per- mixture i time, ]
pound R R~ Rz ehlorie acid temp., bp "~"
molecular i min I (ram) * "~
ratio *C

I1a ff CHa H 1:3:1 125--135i 20--30 21 i 30

IIb H tt Clla 1:3 : 1 125--135 20--30 50(7)i~ 30.
Ile H CIta i- (CHa)2-CH 1:3:1 125--135 30--40 110--1 32
I
Ild CHa CHa II 1:3 : 1 125--135 40--50 105--1: 35,
, ~ (7) $
1I e H OH H I :3: 1 90--95 40--50 146 70
I1 f H Oit COC1t3 1 : 3 : 0,5 125--135 15--20 182 42

* The melting points and boiling peints were in agreement with the
d a t a i n [10].
r C 79.8;H 6.9. C12H150 2. C a l c u l a t e d , % : C 79.6; H 6.7.
S Found,%: C 73.3; H 7.4. CIoHI?O 2. C a l c u l a t e d , % : C 73.2; H 7.3.

TABLE 2. 2-Aryl-4-methylbenzopyrylium Perchlorates (IVa-f) CH a

R ' ~ /R a

R' CIO 4 R / " R I'

Gem- I mp,* Found, go Calc., % ,

R R' R= R~ R" R" I R" Empirical for- _1
pound t IR s p e c t r u m , cm
, i '1 mula c H C!

IVa OH H CHa H H CHa H 245--247 C~8HI7ClO6 I" 59,0 4,7 9,4 59,4 4.7 9,7 3250--3200, 1620, 55
1590,1520,1110
IVb OH H H CHa H [H Ct:I3 i 256--258 C18H17CIO6 59,3 4,8 9,4 59,4 4,7 9,7 3300--3220,1620, 44
1595,1540,1110
IVe OH H CHa [ i-(CHa)2CH H [CHa ]i-(Ctta)~CiI [! 273--274 C24H~gCIOs 64,6 6,3 7,6 64,2 6,5 7,9 1,520, 1590, 154~, 26,
I 1370, 1120
IVd 1. rc, r26 -202 60,8 8,4 61,2 5,3 9,0 3360, 3300, 1620, 24
1600,1535,1105
IVe OH H H I H ti H H 230--231 CI6HIaCIO6 57,1 3,9 10,0 57,l 3,9 10,5 3520, 324,0, 16'20, 4
1605, 1530, 1120
IVf OCOCHa H OCOCHa}H H OCOCH3 H 181--182 C22H~gCIOn"~ 53,7 4,0 6,7 53,4 3,8 7,16 1755, 1625, 1545, 12,,~
1090

*All of the perchloratas were purified by recrystallization from nitromethane or glacial acetic acid in the presence of a few drops of
g~ perchleric acid and melted with decomposition.
O1 t The perchlorates were obtained by alternative synthesis from the corresponding o-hydroxyaryl alkyl ketones.
 A c o n f i r m a t i o n of the p r o p o s e d s c h e m e for the production of s a l t s IV is the fact that o - h y d r o x y a c e t e -
phenones, as a r e s u l t of s e l f - c o n d e n s a t i o n in acidic media, f o r m the s a m e s a l t s as the c o r r e s p o n d i n g phenols.
The p r o p o s e d method for the production of 4 - m e t h y l b e n z o p y r y l i u m s a l t s differs f a v o r a b l y f r o m the
r e c e n t l y developed method for the s y n t h e s i s of t h e s e compounds by condensation of o-hydroxyacetophenones
with a l i p h a t i c - a r o m a t i c ketones [6] with r e s p e c t to the convenience in the method and the a c c e s s i b i l i t y of
the s t a r t i n g phenols.
When p - h y d r o x y a c e t o p h e n o n e s a r e f o r m e d in the F r i e s r e a r r a n g e m e n t and when t h e r e is a f r e e
acylium cation in the r e a c t i o n m i x t u r e (1 : 3 : 0.5), the r e a c t i o n can p r o c e e d via a different route to f o r m 2-
m e t h y l - 4 , 6 - d i a r y l p y r y l i u m s a l t s (V), which a r e obtained in low yield (5-8%) v i a the p r e v i o u s l y studied
m e c h a n i s m of acylation of a r o m a t i c compounds and methyl ketones [2].
ca'

COCH3 ~"~R
R~ A~2o. HCIO4 CH3 --OR I
OH Cm~-~/----
Va-~
V .aR=CH,~, RI=H; bR=H, RI=COCH~; C R=Rt=H

A c o n f i r m a t i o n of the indicated s c h e m e is the p r e p a r a t i o n of Vb f r o m p - h y d r o x y a c e t o p h e n o n e . When

the r e a c t i o n is c a r r i e d out in the c a s e of phenol, o - a c y l a t i o n of the hydroxyl group of the phenolic r e s i d u e
is o b s e r v e d (by the p r e s e n c e in the IR s p e c t r a of an absorption band at 1760 c m - i ) . C r y s t a l l i z a t i o n of Vb
f r o m acetic acid (boiling for 2-3 min) leads to hydrolytic splitting out of the acetoxy g r o u p to give the p e r -
c h l o r a t e (Vc). The indicated t r a n s f o r m a t i o n is accompanied by a change in the c o l o r of the s a l t undergoing
c r y s t a l l i z a t i o n , by the d i s a p p e a r a n c e in the IR s p e c t r u m of the band at 1760 c m -l, and by the a p p e a r a n c e
of an a b s o r p t i o n band of an OH group (3320-3330 c m -1) [7].
2 - M e t h y l - 4 , 6 - d i ( 4 - h y d r o x y p h e n y l ) p y r i d i n e is o b t a i n e d in 90% yield by t r e a t m e n t of p e r c h l o r a t e s Vb,c
in e x c e s s dilute a m m o n i a solution.

EXPE RIME NTA L

The IR s p e c t r a of m i n e r a l oil s u s p e n s i o n s of the compounds w e r e r e c o r d e d with a UR-20 s p e c t r o m -
e t e r . The individuality of the compounds obtained was v e r i f i e d by c h r o m a t o g r a p h y in a thin l a y e r of g y p s u m
in b e n z e n e - c h l o r o f o r m (7 : 8) [8]. The IR s p e c t r a of all of the p y r y l i u m s a l t s obtained contain the a b s o r p -
tion bands c h a r a c t e r i s t i c for the p y r y l i u m cation and the C10~ anion [9].
4 , 7 - D i m e t h y l - 2 - ( 2 - h y d r o x y - 4 - m e t h y l p h e n y l ) b e n z o p y r y l i u m P e r c h l o r a t e (IVa) and 2 - H y d r o x y - 4 -
methylacetophenone. A solution of 10.8 g (0.1 mole) of m - c r e s o l in 30.6 g (0.3 mole) of acetic anhydride
was cooled, and 10 m l (0.1 mole) of 70% p e r c h l o r i c acid was added d r o p w i s e . The r e a c t i o n m i x t u r e w a s r e -
fluxed c a r e f u l l y at 120-130 ~ for 30-40 min, a f t e r which it was diluted with a tenfold excess of e t h e r and
allowed to stand in a r e f r i g e r a t o r f o r 2-3 h. The p r e c i p i t a t e d c r y s t a l s w e r e r e m o v e d b y filtration to give
1 0 g (55~c) of IVa with mp 2 4 5 - 2 4 T (dec.).
The e t h e r solution was washed with ice w a t e r and d r i e d o v e r sodium sulfate. The solvent was r.e-
m o v e d by distillation, and the r e s i d u e was s t e a m distilled. The usual t r e a t m e n t of the distillate gave 4 g
(27~0) of 2 - h y d r o x y - 4 - m e t h y l a c e t o p h e n o n e (Ha) with bp 107 ~ (7 nlm). The o - h y d r o x y ketches (IIb-d,
Table 1) and p e r c h l o r a t e s (IVb-e, Table 2) w e r e s i m i l a r l y obtained.
4 - M e t h y l - 2 - ( 2 - h y d r o x y p h e n y l ) b e n z o p y r y l i u m Salts (We). A__: A 0.68 g (0.005 mole) s a m p l e of o -
hydroxyacetephenone was refluxed c a r e f u l l y at 120-135 ~ for 20 m i n in a m i x t u r e of 1.5 ml (0.015 mole) of
acetic anhydride and 0.5 m l (0.005 mole) of 70% p e r c h l o r i c acid. The m i x t u r e was cooled, diluted with
ether, and f i l t e r e d to give 0.35 g(41.6%) of IVe with m p 230-231 ~ (glacial acetic acid).
B. A 0.68 g s a m p l e of o-hydroxyacetophenone was refluxed at 120-135 ~ for 30 min in a m i x t u r e with
2 m l of acetic acid and 0.5 ml of 70% p e r c h l o r i c acid. The m i x t u r e was cooled and diluted with e t h e r to
give 0.084 g (10%) of a product; no m e l t i n g - p o i n t d e p r e s s i o n was o b s e r v e d for a m i x t u r e of this product
with p e r c h l o r a t e IVe, and t h e i r IR s p e c t r a w e r e identical.

156
 4 - M e t h y l - 7 - a c e t o x y - 2 - ( 2 , 4 - d i a c e t o x y p h e n y l ) b e n z o p y r y l i u m P e r c h l o r a t e (IVf). A 0.5 ml (0.05 mole)
s a m p l e of 70% HCIO 4 was added dropwise c a r e f u l l y with cooling to 1.1 g (0.01 mole) of r e s o r c i n o l dissolved
in 6 m l (0.06 mole) of acetic anhydride, and the m i x t u r e was heated at 90-95 ~ for 15-20 rain. An e x c e s s of
e t h e r was added, and the m i x t u r e was allowed to stand i n a r e f r i g e r a t o r f o r 3-4 h. The p r e c i p i t a t e d oil was
r e p r e c i p i t a t e d two to t h r e e t i m e s f r o m acetone solution by the addition of ether, a f t e r which the addition o f
a s m a l l amount of acetone (1.5-2 ml) gave 0.31 g (12.4%) of c o l o r l e s s c r y s t a l s of IVf with mp 181-182 ~
R e s a c e t o p h e n o n e . A 1.1 g (0.01 mole) s a m p l e of r e s o r c i n o l was dissolved in 3.1 m l (0.03 mole) of
acetic anhydride, a f t e r which the solution was cooled and 1 ml (0.01 mole) of 70% p e r c h l o r i c acid was
added d r o p w i s e . The m i x t u r e was heated at 90-95 ~ for 40-50 rain, a f t e r which it was diluted with w a t e r to
give 1.06 g (70%) of r e s a c e t o p h e n o n e with mp 146 ~ (rap 146 ~ [10]).
2 - M e t h y l - 4 , 6 - d i ( 2 - m e t h y l - 4 - h y d r o x y p h e n y l ) p y r y l i u m P e r c h l o r a t e Wa) and 2 - M e t h y l - 4 - h y d r o x y a c e t o -
phenone. A 10.8 g (0.1 mole) s a m p l e of m - c r e s o l was dissolved in 30.6 ml (0.3 mole) of acetic anhydride,
a f t e r which the m i x t u r e was cooled, and 5 ml (0.05 mole) of 70% p e r c h l o r i c acid was added. The m i x t u r e
was then heated at 90-95 ~ for 30-40 rain. The r e s u l t i n g p y r y l i u m s a l t was p r e c i p i t a t e d with a tenfold e x c e s s
of e t h e r as a p a r t i a l l y c r y s t a l l i z e d oil. R e p r e c i p i t a t i o n of the oil f r o m n i t r o m e t h a n e or acetic acid gave
1.55 g (7.6Vc) of p e r c h l o r a t e Va with mp 250-252 o (glacial acetic acid). Found,%: C 59.0; H 4.8; C1 8.5.
C20H19C107. Calculated, %: C 59.1; H 4.7; C1 8.7. IR s p e c t r u m : 1120, 1534, 1590, 1620, 3250-3270 c m - l .
The e t h e r e x t r a c t was washed with water, and the e t h e r was r e m o v e d by distillation. The r e s i d u e was
s t e a m distilled, and the new r e s i d u e was allowed to stand to give 3 g (20%) of 2 - m e t h y l - 4 - h y d r o x y a c e t o -
phenone with mp 127 ~ (rap 128 ~ [10]).
2 - M e t h y l - 4 , 6 - d i ( 4 - a c e t o x y p h e n y l ) p y r y l i u m P e r c h l o r a t e (Vb). A. As in the p r e p a r a t i o n ov Va, Vb was
obtained f r o m 0.94 g (0.01 mole) of phenol, 3.06 ml of acetic anhydride, and 0.5 ml (0.005 mole) of p e r -
chloric acid by heating the m i x t u r e at 95-100 ~ f o r 10-15 rain. The p r o d u c t [0.18 g (8%)] was yellow and had
mp 223 ~ (glacial acetic acid). Found, %: C 5 7 . 0 ; H 4.3; C1 7.6. C22H19C109, Calculated, %: C 57.1; H 4.2;
C 1 7 , 7 . IR s p e c t r u m : 1090, 1540, 1595, 1630, 1760 c m -i,
B. A 3.1 ml (0.03 mole) s a m p l e of acetic anhydride and 0.3 ml (0.003 mole) of 70% p e r c h l o r i c acid
w e r e added to 1.36 g (0.01 mole) of p-hydroxyacetophenone, and the m i x t u r e was heated on a w a t e r bath for
1-2 rain, a f t e r which it was allowed to stand at r o o m t e m p e r a t u r e for 10-15 min. Cooling and dilution with
e t h e r p r e c i p i t a t e d 0.69 g (30%) of a p e r c h l o r a t e with mp 223 ~ (glacial acetic acid). No m e l t i n g - p o i n t d e -
p r e s s i o n was o b s e r v e d for a m i x t u r e of this product with p e r c h l o r a t e Vb, and t h e i r IR s p e c t r a w e r e identical.
2 - M e t h y l - 4 , 6 - d i ( 4 - h y d r o x y p h e n y l ) p y r y l i u m P e r c h l o r a t e (Vc). A 0.4 g s a m p l e of p e r c h l o r a t e Vb was
refluxed for 2-3 rain in g l a c i a l acetic acid in the p r e s e n c e of a drop of 70% p e r c h l o r i c acid. The m i x t u r e
was cooled, diluted with ether, and f i l t e r e d to give 0.30 g of the p e r c h l o r a t e (Vc) with mp 264-265 ~ (glacial
acetic acid). Found: C 57.2; H 4.2; C 1 9 . 2 . CisHisC107. Calculated, %: C 57.1; H 4.0; C 1 9 . 4 . IR s p e c t r u m :
1120, 1600, 1630, 3320-3330 c m - l .
2 - M e t h y l - 4 , 6 - d i ( 4 - h y d r o x y p h e n y l ) p y r i d i n e . An excess (4-5 ml) of a 22% a m m o n i u m hydroxide s o l u -
tion was added to 0.46 g (0.001 mole) of 2 - m e t h y l - 4 , 6 - d i ( 4 - a c e t o x y p h e n y l ) p y r y l i u m s a l t Vb, and the m i x t u r e
was allowed to stand for s e v e r a l h o u r s . The r e a c t i o n product was r e m o v e d by f i l t r a t i o n and dried to give
0 2 5 g (90%) of c o l o r l e s s c r y s t a l s with mp 276 ~ (from n i t r o m e t h a n e ) . Found, %: C 78.2; H 5.8; N 4.9.
C18HtsNO 2. Calculated, %: C 78.0; H 5.4; N 5.1. IR s p e c t r u m : 1520, 1590, 1605, 3380, 3420 c m -1.

LITERATURE CIT]~D
1. O. Diels and K. Alder, B e r . , 60, 716 (1927).
2. G . N . Dorofeenko and S~ V. Krivun, U k r . Khim. Zh., 2_99, 1058 (1963).
3. A . T . Balaban, W. Schroth, and G. F i s c h e r , Adv. H e t e r o c y c l . C h e m . , 10, 310 (1969).
4. G . N . Dorofeenko, Zh. Obshch. Khim., 3_11, 994 (1961).
5. V . V . M e z h e r i t s k i i and G. N. Dorofeenko, Zh. Organ. Khim., 5, 515 (1968).
6. G . A . Reynolds, J . A. Van Allan, and D. Daniel, J . H e t e r o c y c l . Chem., 7, 1395 (1970).
7. L. Bellamy, I n f r a r e d S p e c t r a of Complex Molecules, 2nd ed., Methuen (1958).
8. Yu. Zhdanov, G. N. Dorofeenko, and S. V. Z e l e n s k a y a , Zh. Obshch. Khim., 3_66(1964).
9. A . T . Balaban, G. D. Mateescu, and M. glian, T e t r a h e d r o n , 18, 1053 (1962).
10. D i c t i o n a r y of Organic Compounds, V o l s . 1-3 [Russian translation], IL, Moscow (1949).

157
2-BENZOPYRYLIUM SALTS
XV.* SYNTHESIS OF 4,5,8,9-TETRAMETHOXY-11-ARYL-11H-
INDE NO [t,2-c ]-2-BENZ OPYRYLIUM SALTS

E. V. Kuznetsov, D. V. Pruchkin, UDC 547.814' 833.07

A. V. Bicherov, a n d G . N. D o r o f e e n k o

-Veratrylindanones were obtained by reaction of ~-veratrylcinnamic acid with verat rol e in

polyphosphoric acid (PPA). A method for the synthesis of indeno-2-benzopyrylium salts
based on acylation of the indanones with the free acids and their anhydrides was developed.
It was shown that indeno-2-benzopyrylium salts can be converted to the little-studied indeno-
[1,2-c]isoquinoline bases.

Currently one of the most convenient methods for the synthesis of isoquinolines is based on the ability
of 2-benzopyrylium salts to exchange an oxygen heteroatom for nitrogen and undergo conversion to the c o r -
responding nitrogen bases [2, 3]. In connection with the fact that this s o r t of transformation does not gener-
ally cause serious difficulties, the effectiveness of this method depends primarily on the accessibility of
the starting 2-benzopyrylium salts.
In the present paper we describe the synthesis of the previously practically unknown indeno[1,2-c]-2-
benzopyrylium salts by acylation of a-veratrylindanones (II).
It is known that in the reaction of a,13 -unsaturated acids with aromatic compounds [4] or cyclic olefins
[5] in the presence of polyphosphoric acid (PPA) cycloaddition may also occur immediately after acylation.
In fact, ~-veratrylindanones (II) are formed in yields close to quantitative when ~-veratrylcinnamic acids
are heated with ve r at r ol e in PPA.

COOH Ar'~ H CHa F Ar~'CH~(~'~--"Y/OCH:~"

CM30 /C~cooH
CH~O~ (C2Hs)3N PPA ~c.~o,~.~ r
la, b L
~ocu~ ^r\ oc.~ C6Ns.].____~OCH3.
CH~O OCH3 RCO"1"X- C H 3~ 0 C HN3H:ICH~O
p . [ ~jC ~H ~Ao ~j TN~
~~ ~ OCH~I
---c,~o.X.~j o c"~~ ~ x- c,~
II a, b lit IV

II 9 Ar=CBHs;b Ar=O,4-(CHsO)2C6Ha

We have obtained indeno-2-benzopyrylium salts (III) as brightly colored high-melting substances by

acylation of indanones II with aliphatic acid anhydrides in the presence of 70% HC104 and aromatic or
aliphatic-aromatic acids in PPA. Like the spectra of 3-aryl-2-benzopyrylium salts [3], the spect ra of the
products contain a number of char a c t e r i s t i c bands at 1610-1620, 1540-1546, 1470-1480, and 1230-1240 ~m -l.

* See [1] for communication XIV.

Rostov State University. ScienUfic-Research Institute of Physical and Organic Chemistry, Rostov-on-
Don. Translated from Khimiya Geterotsiklicheskii Soedinenii, No. 2, pp. 181-183, February, 1974. Original
article submitted November 22, 1972.

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, IV. Y. 10011. No part o f this publication may be reproduced,
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158
 Like 3-aryl-2-benzopyrylium salts [3], the indeno-
[1,2-c]benzopyrylium salts exchange the oxygen hetero-
atom for a nitrogen only on treatment with alcoholic am-
O monia solution under pressure. This method was used
to give 1 - m e t h y l - 4 , 5 , 8 , 9 - t e t r a m e t h o x y - l l - p h e n y l - l l H -
indeno- [1,2-c]isoquinoline in quantitative yield. This
sort of structure is a component of the opium alkaloid
cryptopine [6]. The synthesis of llH-indeno[1,2vc]iso-
quinolines was previously realized by double cycliza-
tion of benzylhomophthalic acid and conversion of the
resulting isocoumarins to the corresponding isocarbo-
c~ styrils [7], by accidental synthesis from o-phthalaldehyde
9 [8], and recently from 4-benzylisoquinolines [6, 9].
O
EXPERIMENTAL
The IR spectra of the compounds in mineral oil
O were recorded with a UR-20 spectrometer.
~-(3,4-Dimethoxyphenyl)cinnamic Acid. This
compound was obtained by a method similar to that in
[10]. The product was obtained in 51% yield as light-
O yellow crystals with mp 182-183 ~ (alcohol). IR s p e c -
trum: 1690, 1630, 1608, and 1550 cm -1. Found, %:
C 71.6; H 5.9. CITHI604. Calculated, %: C 71.8; H 5.6.
~0
0000000 (~- (3,4-Dimethoxy-2 - (3,4-dimethoxyphenyl) -3,4 -
dimethoxycinnamic Acid. This compound was similarly
obtained in 50~c yield and had mp 213-214 ~ (from alcohol)
(rap 215-217 ~ [11]). IR spectrum: 1692, 1630, 1610,
and 1552 cm -i.
~D
5,6-Dimethoxy-2- (3,4-dimethoxyphenyl) -3-
phenylindanone (IIa). A mixture of 1.42 g (0.005 mole)
f of ~-vcratrylcinnamic acid, 0.7 g of veratrole, and 10
g of PPA was heated at 100~ with vigorous stirring for
10 min. After hydrolysis of the reaction mixture, the
O resulting precipitate was removed by filtration and
dried to give 1.8 g (90~c) of colorless crystals with mp
u i ,~ : =" o.~.~
170-171 ~ (fromalcohol). Found, ~c: C 74.4; H 6.1.
C25H2405. Calculated, %: C 74.3;H 5.9. IRspectrum:
1670, 1600, and 1530 cm -i.

44 5,6-Dimethoxy-2,3-di(3,4-dimethoxyphenyl)-
indanone (IIb). This compound was similarly obtained
9
in 80% yield as colorless crystals with mp 120~ (from
alcohol). Found,%: C 69.4; H 6.2. C27H2807. Calcu-
lated, %: C 69.8; H 6.0. IR spectrum: 1674, 1610, and
1532 cm -l .
1-Methyl-4,5, 8,9-tetramethoxy-11-phenyl-llH-
indeno[l,2-c]-2-benzopyrylium Perchlorate. A 0.5 ml
sample of 70~ perchloric acid was added dropwise with
cooling and stirring to a solution of 0.4 g (0.001 mole)
of (~-veratryl-fl -phenylindanone (IIa) in 5 ml of acetic
anhydride. The resulting precipitate was removed by
A filtration and washed with acetic acid and ether to give
O O
0.5 g (95%) of orange crystals with mp 229-230 ~ (after
recrystallization from acetic acid and reprecipitation
from nitromethane by the addition of ether). Salts Nos.
2, 3, and 4 (see Table I) Were similarly synthesized.

159
 1 - B en zy l-4, 5, 8, 9- t e t r am e t hoxy- l l - ph enyl -l l H -i ndeno[1,2-e]-2-benzopyrylium Perchl orat e. A mix-
ture of 0.4 g (1 mmole} of ~-veratryl-~ -phenylindanone (Ha} and 0.14 g (1.2 mmole) of phenylacetic acid in
5 g of PPA was heated with vigorous s t i r r i n g at 120 ~ for 1 h. The mixture was poured into cold water, and
the aqueous mixture was acidified with 30% HC104. The precipitated product was removed by filtration,
dried, and reprecipitated from a small amount of acetic acid containing a few drops of 70% HC104 by the ad-
dition of ether to give 0.44 g (73%} of bright-red crystals with mp 236-237 ~ (after reorystallization from
acetic acid and rep~ecipitation from nitromethane by the addition of ether}. Salts Nos. 6 and 7 (see Table 1)
were similarly obtained.
1-Methyl-4,5,8,9-tetramethoxy-ll-phenyl-llH-indeno[1,2-c]isoquinoline (IV). A suspension of 0.53 g
(0.001 mole} of 1-methyl-4,5,8,9-tetramethoxy-ll-phenyl-llH-indeno[1,2-c]-2-benzopyryliumperchlorate
in 10 ml of alcohol in an ampule was cooled to -10 ~ and saturated with ammonia. The sealed ampule was
heated at 100 ~ for 6 h, after which it was cooled, and the solvent was removed at reduced p r e s s u r e . The
residue was treated with 25 ml of water, and the resulting precipitate was removed by filtration and dried
to give 0.36 g (84%) of colorless needles with mp 199-200 ~ (from benzene) and R f 0.6 [A1203, c h l o r o f o r m -
benzene (3:2)]. Found, %: C 75.6; H 5.8; N 3.3. C27H25NO4. Calculated, %: C 75.9; H 5.6; N 3.3. IR spec-
trum: 1625, 1610, and 1590 cm -l.

LITERATURE CITED
1. G . N . Dorofeenko, S. V. Krivun, and V. G. Korobkova, Khim. Geterotsikl. Soedin., 1458 (1973).
2. G . N . Dorofeenko, L. V. Dulenko, V. I. Dulenko, and S. V. Krivun, Zh. Organ. Khim., 1, 1971 (1965).
3. G . N . Dorofeenko and E. V. Kuznetsov, Khim. Geterotsikl. Soedin., No. 2, 207 (1970).
4. F . H . Marquardt, Helv. Chim. Acta, 488, 1476 (1965).
5. L. Sukh Dev, J. Indian Chem. Soc, 34, 169 (1957).
6. S . F . Dyke and D. W. Brown, Tetrahedron, 2__55,5375 (1969).
7. I . N . Chatterjea and B. Mukherjee, J. Indian Chem. Sot., 37, 379 (1960).
8. S. Wawzonek, I. K. Stowell, and R. E. Karll, J. Org. Chem., 3__11,1004 (1966).
9. W . J . Gensler, K. T. Shamasunder, and S. Marburg, J. Org. Chem., 3__33,2861 (1968).
10. Organic Syntheses, Vol. 5, Wiley.
11. I . H . Russel and H. Hunziker, Tetrahedron Lett., 4035 (1969).

160
2-DICHLOROMETHYLENE-1,3-DIOXOLANE IN THE
DIELS-ALDER REACTION WITH a,fl-UNSATURATED ALDEHYDES

A. N. Mirskova, T. S. P r o s k u r i n a , UDC 547.811.813.729:542.953

V. K. Voronov, a n d A . S. A t a v i n

1 , 4 , 9 - T r i o x a - 5 , 5 - d i c h l o r o s p i r o [ 4 , 5 ] - 7 - d e c e n e and 1 , 4 , 9 - t r i o x a - 6 - m e t h y l - 5 , 5 - d i c h l o r o s p i r o -
[4,5]-7-decene w e r e s y n t h e s i z e d by condensation of 2 - d i c h l o r o m e t h y l e n e - l , 3 - d i o x o l a n e with
a c r o l e i n and c r o t o n i c aldehyde.

Cyclic acetals of dichloroketene display a dual r e a c t i v i t y that is due to polarization of molecules with
the f o r m a t i o n of a heteroenoid s y s t e m of conjugated bonds. Depending on the attacking agent, they r e a c t with
retention of the dioxolane ring [1] o r with cleavage of it at the C - O bond [2].
In the p r e s e n t r e s e a r c h we have investigated the condensation of 2 - d i c h l o r o m e t h y l e n e - l , 3 - d i o x o l a n e
(I) with a c r o l e i n and crotonic aldehyde. The reaction proceeds on heating to 100-150~ to give dihydropyran
derivatives with retention of the 1,3-dioxolane ring:
R
] /O--CH-
UB /o--ctt~ /CCl2--CQ.o_ c H
CH + cO~=C j -- R--C.3 /~ "
CH " \O--CH.~ \CH~CH
'NN..~. - 2
0
1 II, Ill

II R=H: Ill R=CH a

Condensation with acrolein proceeds m o r e readily than with ketene dimethylacetal [3]. In the c a s e of
crotonic aldehyde, m o r e s e v e r e conditions a r e r e q u i r e d to obtain a high yield of the adducts, but an i n c r e a s e
in the heating time and t e m p e r a t u r e leads to partial decomposition and res inification.
The s t r e t c h i n g vibrations of the c i s - e t h y l e n e bond in the IR s p e c t r a of II and III lie at 1647 and 1662
c m -1. A s e r i e s of bands at 1080-1252 c m -I c h a r a c t e r i z e s the acetal grouping of the dioxolane ring. The
absence of a carbonyl group band in the s p e c t r u m is evidence for 1,4-addition.
Allylic constant Jia > J2a in the PMR s p e c t r u m of III. It is known [4] that Jall ranges f r o m 1.3 to 3.1
Hz if 0 -~ 60-110 ~ (Scheme 1). At the s a m e time, according to the Karplus equation, J2a = 1.8 Hz if go = 65 ~

TABLE 1. P a r a m e t e r s of the PMR Spectra of 1 , 4 , 9 - T r i o x a - 5 , 5 - s p i r o -

[4,5]- 7 - d e c e n e s

Coro-
Chemical shift, 5, ppm Spin-spin coupling
t constant, Hz (absolute
pound I-H ~-H 3-H 4-H CHz--CH.~ valtles)

I
II 6,13 In*[ 4,72m 3,02g 4,25 m /12=6,0; /in= 1,7;
]2s = 3,6
IIi 5,99m ! 4,41g 3,08m 1,24, d 4,19 m /~2=6,2; 7ts=2,8;
f J~a= 1,8; 1a4=7,C~

* Abbreviations : m, multiplet; q, quartet; d, doublet.

Irkutsk Institute of Organic C h e m i s t r y , Siberian Branch, A c a d e m y of Sciences of the USSR. T r a n s -

lated f r o m Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 184-185, F e b r u a r y , 1974. Original article
submitted July 28, 1972.

9 19 75 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

161
(Scheme 2 ) . Analysis of the s t r uct ur e of the molecule with B r i e g l e b - S t u a r t models showed that the hexene
and dioxolane rings are in mutually perpendicular planes. Moreover, free rotation of the CH s group occurs
if 0 proves to be g r e a t e r than half the angle for the sp3-hybridized carbon atom (about 60-65~

. 8~77~--c/
.k~--- l\ H
H3~" C~ Cs

EXPERIMENTAL
The PMR s pe c t r a of CC14 solutions of the compounds were recorded with a BS487B s p e c t r o m e t e r (80
MHz) with hexamethyldisiloxane as the internal standard. The integral intensities of the signals were calcu-
lated with an accuracy up to 2%. The IR spectra were recorded with a UR-10 s p e c t r o m e t e r .
Anhydrous and freshly distilled acrolein [bp 51-52 ~ (720 mm), r ~ 1.3990] and crotonic aldehyde [bp
101-102 ~ (720 mm), n~ 1.4380] were used. The 2-dichloromethylene-l,3-dioxolane (I) was obtained by the
method in [5] and had the following constants: bp 72-73 ~ (2 mm) and mp 55-56 ~ (mp 55.5-57 ~ [5]). IR spec-
trum: 1710, 1104, 1103, and 1150 cm - l .
1,4,9-Trioxa-5,5-dichlorospiro[4,5]-7-decene (II). A mixture of 11.65g (0.07 mole) of I and 4.8 g
(0.07 mole) of acrolein was heated in a sealed ampule at 100 ~ for 8 h. Distillation of the contents yielded
11 g (68%) of II with bp 104-105 ~ (6 mm), d 2~ 1.4100, and n~ 1.5020. Found, %: C 39.8; H 3.8; C1 33.7; MRD
44.17. C7H8C1203. Calculated, %: C 39.9; H 3.8; C1 33.7; MRD 44.54. Chromatography in a thin l aye r on
activity II aluminum oxide gave one spot with R f 0.5 [benzene-hexane (5 : 1), development with iodine].
1,4,9-Trioxa-6-methyl-5,5-dichlorospiro[4,5]-7-decene (III). A 4 g (0.05 mole) sample of crotonic
aldehyde was added to 8 g (0.05 mole) of I, and the mixture was heated in a sealed ampule at 150 ~ for 12 h.
Distillation yielded 8.1 g (70o/0) of III with mp 65~ (from benzene) and bp 125 ~ (3 mm). Found, %: C 42.6; H
4.3; C1 31.5. C8H10C1203. Calculated, %: C 42.7; H 4.4; C1 31.5.

LITERATURE CITED
1. A. N. Mirskova and A. S. Atavin, in: Chemistry of Acetylenes [in Russian], Nauka, Moscow {1968),
p. 7.
2. A. S. Atavin, A. N. Mirskova, N. N. Chipanina, and R. A. Prelovskaya, Zh. Organ. Khim., 1, 2077
(1965).
3. S. M. McElvain, E. R. Degginger, and J. D. Behum, J. Amer. Chem. Soc., 76, 5736 (1954).
4. N. Bhacca and D. Williams, Applications of Nuclear Magnetic Resonance in Organic Chemistry
[Russian translation], Mir, Moscow (1966), pp. 70, 142.
5. S. M. McElvain and M. J . Curry, J. Am. Chem. Soc., 70, 3781 (1948).

162
SYNTHESIS OF 1,3-DIOXOLANE DERIVATIVES

V. V. Dovlatyan and D. A. Kostanyan UDC 547.729.07

Chloral c y a n o m e t h y l h e m i a c e t a l is c o n v e r t e d t o 2 - t r i c h l o r o m e t h y l - 4 - i m i n o - l , 3 - d i o x o l a n e under
the influence of hydrogen chloride or pyridine. Acetone cyanohydrin r e a c t s with c h l o r a l to
give 2 - t r i c h l o r o m e t h y l - 4 - i m i n o - 5 , 5 - d i m e t h y l - l , 3 - d i o x o l a n e , the h y d r o c h l o r i d e of which in
w a t e r gives 2 - t r i c h l o r o m e t h y l - 4 - o x o - 5 , 5 - d i m e t h y l - l , 3 - d i o x o l a n e .

The r e a c t i o n of hydroxynitriles with chloral has not been studied. We have found that formaldehyde
cyanohydrin r e a c t s with c h l o r a l to give c y a n o m e t h y l h e m i a c e t a l I [1], which decomposes during vacuum
distillation.
Compound I r e a c t s with hydrogen chloride to give 2 - t r i c h l o r o m e t h y t - 4 - i m i n o - l , 3 - d i o x o l a n e h y d r o -
chloride (]I), but is c o n v e r t e d to b a s e III, the hydrochloride of which is identical to II, in the p r e s e n c e of
catalytic amounts of pyridine.

O---CH 2
o:-c. j
O ~ C ~ N H - HCI
II

CI.aCCHOHCH2CN ~HCI
,. /O---C H 2

O~C~N H
II!

Compound H is readily h y d r o l y z e d to give a viscous s y r u p y liquid, which decomposes even at the t e m -

p e r a t u r e of a boiling-water bath with c h l o r a l liberation.
Ketone cyanohydrins r e a c t v e r y sluggishly with chloral. Heating of a m i x t u r e of the s t a r t i n g sub-
stances for many hours did not give any positive r e s u l t s . However, if an equimolecular mixture of acetone
cyanohydrin and c h l o r a l is allowed to stand at r o o m t e m p e r a t u r e for 2.5-3 months, the liquid solidifies al-
m o s t c o m p l e t e l y because of the f o r m a t i o n of c r y s t a l l i n e 2 - t r i c h l o r o m e t h y l - 4 - i m i n o - 5 , 5 - d i m e t h y l - l , 3 - d i -
oxolane (IV). Cyclization can be s h a r p l y a c c e l e r a t e d by the addition of t r a c e s of pyridine [2J.

H H H
1
c[ O: - - C ( C H 3 ) 2 C ~ N ~ -H+ CI3 C - ' ~ - O c ( c H 3 ) 2 C N ~ H+ II
CI3C--C--OC (CH3)2C ~ N
Cl3C--~) H---N CSHs -C5H5N
O- OH

H o--c(cH ) o--c(cH ) O-~(CHD=

{ -CsHsN ~ S2 ; a 2 /
c'~c-c-oc(c"3): -=N - c,3c-c, I,~ ~ c , : - r } ----c,3c-c, l
i
O--H--NCsH 5 -"+ o_.c--- N 'o--~:=N- ." b--~=N.

The catalytic action of pyridine is apparently due to the formation of a p y r i d i n e - c y a n o h y d r i n activated

complex in which the oxygen atom of the cyanohydrin is m o r e nucleophilic owing to the development of a
hydrogen bond and t h e r e f o r e readily attacks the carbonyl group of chloral. The adduct that forms in this
m a n n e r undergoes subsequent h e t e r o c y c l i z a t i o n , probably also through a step involving the formation of an
activated complex.
The catalytic action of hydrogen chloride is apparently due to protonation of the nitrile group and con-
v e r s i o n of it to a nitrile cation, which also attacks the f r e e pair of electrons of the hydroxyl group:
A r m e n i a n Agricultural Institute, Yerevan. T r a n s l a t e d f r o m Khimiya Geterotsiklicheskikh Soedinenii,
No. 2, pp. 186-188, F e b r u a r y , 1974. Original a r t i c l e submitted D e c e m b e r 12, 1972.

9 1975PlenumPublishing Corporation, 227 West 17th Street, New York, iV..Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
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163
 11
I
H+ C I 3 C - - C - ' O - - ' C H2 -H + HE!
| " " ( {A ~ 111 - " II
HO:,q..._..C~N H

Bands of s t r e t c h i n g v i b r a t i o n s of OH and C ~--- N groups a r e absent in the IR s p e c t r a of II, III, and IV,
but the s p e c t r a do contain intense a b s o r p t i o n at 1100-1130 ( C - O ) , 1705-1714 ( O - C = N ) , and 3210-3260
cm-i (NH).
The hydrochloride of IV is hydrolyzed on dissolving in water to give the completely stable 2-trichloro-
methyl-4-oxo-5,5-dimethyl-l,3-dioxolane (V); bands of C - O stretching vibrations (1100-1130 cm-I) and of
C = O groups in five-memberedlactones at 1775-1785 cm-i are displayed distinctly in the IR spectrum of V.

O--r 2
I v - HCi ~ .~o c%c-c'. I ~ cc,~c.o + (c.~)=clomcoo.
O--C=O
Y

Compound V was also obtained by condensation of c h l o r a l with c~-hydroxyisobutyric acid.

EXPERIMENTAL
The IR s p e c t r a of m i n e r a l oil s u s p e n s i b n s of the compounds w e r e r e c o r d e d with a UR-10 s p e c t r o m e t e r .
2 - T r i e h l o r o m e t h y l - 4 - i m i n o - l , 3 - d i o x o l a n e Hydrochloride (II). A m i x t u r e of 14.8 g (0.1 mole) of chloral
and 5.7 g (0.1 mole) of f o r m a l d e h y d e c y a n o h y d r i n [bp 81-83 ~ (5 ram)] was heated on a w a t e r b a t h for 1 h and
allowed to stand at r o o m t e m p e r a t u r e for 2 d a y s . Absolute e t h e r (50 ml) was added to the r e s u l t i n g I, and
the m i x t u r e was cooled to - 1 0 ~ with s t i r r i n g and s a t u r a t e d with d r y hydrogen chloride. After 2 h, the p r e -
cipitate was r e m o v e d by filtration, washed with absolute ether, and dried in a d e s i c c a t o r o v e r c o n c e n t r a t e d
sulfuric acid to give 16.8 g (70%) of a product with mp 112-113 ~ (dee.}. Found, %: C1 14.7; C1 68.0; N 6.9.
C4HsCI4N. Calculated, %: C1 14.8; C1 67.9; N 6.7.
2-Trichloromethyl-4-imino-l,3-dioxolane (III). A 0.05 g sample of pyridine was added with stirring
at -10~ to a mixture of 7.4 g (0.05 mole) of chloral, 2.9 g (0.05 mole) of formaldehyde eyanohydrin, and 25
ml of dry petroleum ether. The mixture was allowed to stand in a refrigerator overnight. The next day,
the petroleum ether was decanted, and the solid was treated several times with new portions of dry
petroleum ether. The mixture was then filtered, and the solid was air dried to give 9.8 g (96%) of a product
with mp 95-96~ Found, %: C1 52.3; N 6.9. C4H4CI3NO~. Calculated, ~: CI 52.0; N 6.8. The hydrochloride
had mp 112-113~ No melting-point depression was observed for a mixture of the product with a sample of II.
Hydrolysis of 2-Triehloromethyl-4-imino-l,3-dioxolaneHydroehloride. Water (10 ml) was added
dropwise with stirring and cooling to a mixture of 10 g of II and 25 ml of diethyl other, after which stirring
was continued for another 30 rain. The aqueous layer was then separated and extracted with ether. The
ether was removed, and the residue was distilled at 95-97~ to give 5 g of chloral hydrate with mp 56-57~
(rap 57-58~ according to the literature). No melting-point depression was observed for a mixture of this
product with a sample of chloral hydrate.
2-Trichloromethyl-4-imino-5,5-dimethyl-l,3-dioxolane(IV). A 0.05 g s ample of pyridine was added
to a water-cooled mixture of 6.9 g (0.047 mole) of chloral, 3.8 g (0.047 mole) of acetone cyanohydrin, and
25 ml of dry petroleum ether. A copious precipitate began to form immediately. The reaction mixture was
allowed to stand overnight and was f i l t e r e d the following day. The solid was washed with p e t r o l e u m e t h e r
and air d r i e d to give 9.5 g (88%) of a product with mp 133 ~ (after r e p r e c i p i t a t i o n f r o m acetone by the addi-
tion of w a t e r ) . Found, %: C1 46.2; N 6.3. C6H3C13NO2. Calculated, %: C1 45.8; N 6.0. The compound had
~ 0.4 [activity II A1203, h e x a n e - a c e t o n e (60:40), development with 2% AgNO 3 and 0.4% b r o m p h e n o l blue].
e h y d r o c h l o r i d e had mp 172-173 ~
2 - T r i c h l o r o m e t h y l - 4 - o x o - 5 , 5 - d i m e t h y l - l , 3 - d i o x o l a n e (V). A.: A 3.5 g s a m p l e of the h y d r o c h l o r i d e of
IV was d i s s o l v e d in a s m a l l amount of w a t e r and s t i r r e d thoroughly for 1 h. The r e s u l t i n g p r e c i p i t a t e was
r e m o v e d by filtration and a i r d r i e d to give 3.2 g (98.6~ of c o l o r l e s s c r y s t a l s with m p 72 ~ Found, %: C
31.1; H 3.2; C1 45.8. C6HTCI~O3. C a l c u l a t e d , %: C 30.8; H 3.0; C1 45.6. The p r o d u c t had R f 0.7 [activity
II A1203, h e x a n e - a c e t o n e (98:2), d e v e l o p m e n t with 2~ AgNO 2 and 0.4% b r o m p h e n o l blue].
B. A m i x t u r e of 2.21 g (0.015 mole) of c h l o r a l and 1.56 g (0.015 mole) of h y d r o x y l i s o b u t y r i c acid
(mp 78-79 ~ was heated at 120 ~ on an oil bath for 3 h. The m i x t u r e was cooled, and the r e a c t i o n product
was t r e a t e d with w a t e r . The p r e c i p i t a t e was r e m o v e d by filtration, dissolved in acetone, and p r e c i p i t a t e d

164
with water to give 2.6 g (74%) of a product with mp 72~ No melting-point depression was observed for a
mixture of this product with a sample of the material described above.

LITERATURE CITED
lo V. V. Dovlatyan and D. A. Kostanyan, Arm. Khim. Zh., 2_22,598 (1969).
2. V. V. Dovlatyan and D. A. Kostanyan, USSR Author's Certificate No. 266,776 (1968); Byul. Izobret.,
No. 3, 140 (1973).

165
QUANTUM-CIIEMICAL INVESTIGATION OF SOME
OLIGOMERIC HETEROAROMATIC COMPOUNDS
V.* OXAZOLES

G. I. Kagan, V. A. Kosobutskii, UDC 541.67' 632:547.787:543.422.6

V. K. Belyakov, and O. G. Tarakanov

The c h a r a c t e r i s t i c s of the electronic s t r u c t u r e s of a number of model aromatic oxazoles

r e a l i z e d in aromatic polyoxazoles w e r e obtained within the f r a m e w o r k of the P a r i s e r -
P a r r - P o p l e method. The UV s p e c t r a of most of them w e r e i n t e r p r e t e d . The s t e r e o -
i s o m e r i s m of dibenzoxazoles is examined.

Continuing our r e s e a r c h on the establishment of a c o r r e l a t i o n between the strength c h a r a c t e r i s t i c s of

bonds (during the degradation of the compounds) and the c h a r a c t e r i s t i c s of the electronic s t r u c t u r e s of a
number of molecules of h e a t - r e s i s t a n t polymers [1, 2], we have investigated model aromatic oxazoles and
s o m e fragments r e a l i z e d in aromatic polyoxazoles [3]. The c h a r a c t e r i s t i c s of the electronic s t r u c t u r e s
w e r e obtained within the f r a m e w o r k of the P a r i s e r - P a r r - P o p l e method; the details of the calculation and
the p a r a m e t e r s used w e r e r e p o r t e d in [2]. Thus we calculated oxazole (I), its 2-phenyl and 2,5-diphenyl
derivatives [(II) and (III), respectively], benzoxazole (IV), 2-phenylbenzoxazole (V), dibenz [b,e]oxazole (VI),
2,5-diphenyldibenz [b,e]oxazole (VII), a d i m e r of an aromatic oxazole based on dihydroxydiaminobenzene
(VIII), 5,5'-bis (2,2'-diphenylbenzoxazole) (IX), and some models containing differently connected benzoxazole
rings (X-XII). The indicated compounds a r e p r e s e n t e d in Figs. 1 and 2.
The calculated rings w e r e assumed to be r e g u l a r polyhedra with bond lengths of 1.38 ~ in the c a s e of
oxazole and condensed rings and 1.40 ~ in the c a s e of t e r m i n a l aromatic r i n g s . The C - C bond lengths be-
tween the rings were 1.50 A.
In addition to the usual quantum-chemical characteristics, we calculated the total (Etot), 7r-bond (E~rb),
and resonance (EvR) energies, the resonance energy per Irelectron (EVR/n) , the energy of interaction of
the heterorings with one another (Eint/m), and the energies of the upper occupied (Suo) and lower vacant
(~ Iv) molecular orbitals for the investigated heterocycles. The indicated values are presented in Table I.
Table 1 also includes information on the position of the m a x i m a of the long-wave absorption bands.
Molecular Diagrams. The molecular diagrams of the ground states of the investigated compounds are
presented in Figs. 1 and 2. Analysis of the electronic distribution in oxazole I indicates great nonuniformity
of the distribution of the ~ electrons (~ ~rtalc ~ 3.0 D) caused by the presence in the ring of heteroatoms of
different nature. Moreover, one of the carbon atoms (C2) is the electrophilic center of the molecule, while
two of the others (C 4 and C 5) are nucleophilic centers. The bonds between the carbons and the heteroatoms
have the lowest order. It is precisely at these bonds that one should primarily expectdisintegration of the
heteroring via a homolytic mechanism, and we will therefore subsequently define them as "weak bonds ."
Comparison of the molecular diagrams of I and imidazole [I] shows that the oxygen atom in the
oxazole ring is a weaker electron donor than the N H group of imidazole. 'In addition, we direct attention to
the facts, first, that the C 4 - N bond in I has a lower order, while,the C 2 - N bond has a higher order than in
imidazole, i.e., the "weak" C - N bond is m o r e r e s i s t a n t to homolytic disintegration
+
in the imidazole ring
than in the oxazole ring; second, that oxazole already has a dipositive C - ~ bond at which its hydrolytic
splitting m o s t likely o c c u r s .
##

* See [I] for communication IV.

All-Union S c i e n t i f i c - R e s e a r c h Institute of Synthetic Resins, V l a d i m i r . T r a n s l a t e d f r o m Khimiya
Geterotsiklicheskikh Scedinenii, No. 2, pp. 189-195, F e b r u a r y , 1974. Original article submitted October 16,1972.

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of thispublication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy o f this article, is available from the publisher for $15.00.

166
 -0~013 -(}tOO0 --0~38 -0f039 . . . . . 000 K ~ n h n t
+0,328 +0t323 r, =~. -0,007 O ~-0,0~,6+0,279 - 0 0 ~ ~ O.~P, v ' J +0~73 ' " n ~--J=
r'"
~,.~'~n o ^,.,-~ ~ s ,o ~'~C.t~.o _.~/'~~ ~ n _ ~ ~.~-.C a o.~0 % :.,~?

~I +o,o~).~ ~I +o,o3sh-=----E,-ozz+o,oos) $1 ~I +o.o9s3 ~l {~+o,0%.,-.,----~ )

o k" ' ~ ~ o~ " ~, o o ~'~

T ii +0017 + 0 0 0 5 +0003 t - ' - ~ +0001 ' - ~ +0t023 +0~006

-o,,,,.___+~176 o,,.~, .o,oo, +o,o. -~176 ~ %, ~o o,,,,

.o,,o, / ~ ~o ",t.% / \ / 3"-o,oo,"#-~" ~ \~- #2/ '9,-
+o.,oo< I E- 2,~- ~*~176176176176
~~176176
I I~I ~I ~ )
\ / 0"Co, o~'~-./__~ ~-'~~'0 . o -oo , ,,,,e -'Co,o~"-....,/-o,oo~ o , ~ ~,~0~ -~,~..._._/~
L-----/+o o~o +o,26s -o.o~ ~ -,~ - ~ , ~ +o,~7~ " - o , o ~ ~ ~ oW o,~75
"o_/~-~N ' ~% _ -o,o%,r oo~ ,,,

oX" /,~ ~ I~ \ - o,mo'~7. . . . \" +o,oos +0,0~,- -0,~9~ - %0000=. 0,~7~

N 0 ~./~^.. ~"-0,00~ +0,317 0,6?4

.o' o,o/
\ .... 7 \"'" I
"C
I /,.~ o\ /.
o.'I~ % oI-,-o,oo~ Io' - -oo, * o,ooo \ / \ ~ J.._ ~?~ ~r /~
'~ ~'~ ).~-o,o~, -o,ooo -o,oo~ .o,~ ' - o,o~" . . . . . o,s~s ,
-- . - 0,003 ~o. ~ ' % , ~ % ....
+ 0~001
-0~02~ O~2 o~ . +O, OOZ -0~ 289 + 0,028. . . . . O~ "
N +0,0o8 ~..~*0,oo8 N ,,-~L~to-. IMU~o~.~'~L.~ o2l ,b,~ M ~ f~ -0,671 O

n nan n nn~ ~"~---0~037 V - 0 , 0 3 8 ~ ~.------Jlb'~ ~ ,~J~.~o.~9.V_~'~,.'~J68u ~" -~.-..--~

v .... -~,~ * 0,25' -0~090 4. 0t25 , 0~684 '~1" ~'v~ "~ ~ " 0.,675
- o~oo~ Vll'-'i

Fig. 1. Molecular d i a g r a m s of a r o m a t i c oxazoles in the ground s t a t e .

- 0f28 z" - 0,285

+o,ogsjN,~ ..... o56o_~,~,N'~ 7 . o , o 9 3 / N \ . +o,ooo ~om5 ~
I .n~.,x,--~ vv" ,0,'I-~-~/o / ~ 't +o.oIo;~--'--x ,,,'/----vo'_
o---.(-o,_%%~ ~ o o~
.o,.o \ - o . * / o~ /~,,,o .o,,. k":o':oo,~-~.,
C . J %\---L~,~'--o~,o
- 0,0z,0- 0,008 --0"n6 - o,03S - 0,004 __ 0,S61 ~-~ N~,N~-
~
X _X~
+ 0,279 -- + 0,260

N-...J+0,011 ~ \-~ _.N o N ...~/+o;0,_..~ okj.~.~

-ore4 \ %~176 o~ /T,~u -o,=~ \ - ~ ' " " 7 ~\ ./~-Nc
*o,oo~ o,oo~_ o,~,~ o,~..,~o~ ~
..... o/'~0 ~,. -0,0rt -%00:~ ~ . N ' - ~ s +0,094~'~ N ~ . *0po~ -0,00,

a~ ..._~/+0.0,1 ~ 0 , 2 , 6 / - 0 , 0 0 8 _ ._~\~..~ O o " ~'0-..~-0.047 \0,2,5/-0o003 '~x463

. _'~046,
.~~F-~ - ~176 O~3"t~ 0)378' ~ - ,~176
+o.,d'~'~ ~ "* o,o,,/~ o

-0~012 -u?UUo -O,,U37 -0~039 -0~009 -U,041 o" U O~'l

Xl/ Xl/i * o~27~

F i g . 2. Molecular d i a g r a m s of s t e r e o i s o m e r i c dibenzoxazoles in the ground

s t a t e (X 5 , 5 ' - c i s , Xi 5 , 5 ' - t r a n s , XI 6 , 6 ' - c i s , XIi 6 , 6 ' - t r a n s , XII 5 , 6 ' - c i s , and
XIIi 5, 6 - t r a n s .

The oxazole and benzene rings in 2-phenyloxazole have identical e l e c t r o n e g a t i v i t i e s , of c o u r s e , with

a c e r t a i n tendency f o r e l e c t r o n - d o n o r c h a r a c t e r of the benzene ring with r e s p e c t to the oxazole ring. A
m o r e detailed e x a m i n a t i o n of the distribution of c h a r g e s in II attests to a c e r t a i n r e d i s t r i b u t i o n of the ~r-
e l e c t r o n cloud of the h e t e r o c y c l e in the d i r e c t i o n of equalization of the c h a r g e s on the atoms and of the bond
o r d e r s . M o r e o v e r , the o r d e r s of the "weak" bonds r e m a i n p r a c t i c a l l y unchanged, while the bonds of that
c a r b o n a t o m to which the phenyl group is attached a r e m o s t significantly weakened. The e l e c t r o p h i l i c i t y of
the C 2 a t o m in II is s o m e w h a t d e p r e s s e d .

167
 2,5-Diphenyl-substitution of oxazole (III) is acc pmpanied
by a further d e c r e a s e in the o r d e r of the c a r b o n - c a r b o n multiple
bond of the h e t e r o c y c l e , the c h a r g e density f r o m wilichSnigrates
to the adjacent benzene r i n g . We note a difference in the e l e c -
0 tronic effects of benzene rings attached to the 2 and 5 positions.
.o The f i r s t acts as an electron donor with r e s p e c t to the oxazo-le--
ring (empirical c h a r g e Q is +0.005), while the second displays
2 an e l e c t r o n - a c c e p t o r effect (Q = - 0 . 0 2 7 ) . As c o m p a r e d with I
o and II, the "weak" C - O bond in III is somewhat weakened,
while the "wea~+ + :' C - N bond is strengthened. The electrophili-
city of the C - C bond in III r e m a i n s the s a m e as in II.
Annelation of the oxazole and a r o m a t i c rings (IV) c o n -
S
s i d e r a b l y d e c r e a s e s the o r d e r s of the "weak" bonds. The e l e c -
trophilicity of the C - O bond in this c a s e i n c r e a s e s and is the
g r e a t e s t of all of the investigated oxazoles. Of the investigated
%0*'9 ~00 300 ~.00 500 600 h e t e r o c y c l e s , IV should apparently undergo nucleophilic attack
most readily.
Fig. 3. Calculated s i n g l e t - s i n g l e t ( ~ )
and S i n g l e t - t r i p l e t ( - - - ) transitions in 99 The effect of 2-phenyl-substitution of benzoxazole (V) is
aromatic oxazoles. s i m i l a r to the effect of substitution of the oxazole ring.
The formation of dibenz [b,e]oxazole s t r u c t u r e VI is accompanied by a still g r e a t e r d e c r e a s e in the
o r d e r s of the "weak" bonds and, generally, the bonds between the carbon+atoms + of the benzene ring and the
h e t e r o - a t o m s of the r i n g . With r e s p e c t to the electrophilicity of the C - O bond, IV occupies a middle p o s i -
tion among all of the investigated compounds.
I s o m e r i c dibenz[b,e]oxazole Vii has a l m o s t the s a m e c h a r a c t e r i s t i c s of c h a r g e distribution as VI. A
Comparison of t h e i r e n e r g y c h a r a c t e r i s t i c s (Table I) indicates the advantageousness of the "transoid" c o n -
figuration.
2 , 2 ' - D i p h e n y l - s u b s t i t u t i o n in V] (see VII) leads to the s a m e shift in e l e c t r o n density as in III and V.
F u r t h e r lengthening of the m o l e c u l a r chain (see VIII) has p r a c t i c a l l y no effect on the c h a r a c t e r i s t i c s of the
c h a r g e distribution in the h e t e r o c y c l e .
It is interesting to c o m p a r e the c h a r a c t e r i s t i c s of the electronic s t r u c t u r e of VII with those of IX,
since the f i r s t compound is a model of a polybenzoxazole based on dihydroxydiaminobenzene, while the
second is a model of a polybenzoxazele based on dihydroxybenzidine. It was found that the bonds in the
heturocycles in IX have higher o r d e r s ; however, the e l e c t r o p h i l i c i t y of the C 2 atom is somewhat lower. This
means that, according to the results of the q u a n t u m - c h e m i c a l calculations, the polybenzoxazole based on di-

TABLE 1. E n e r g y and Spectral C h a r a c t e r i s t i c s of Oxazoles

~max, nrn
Coin- Etot, E~, !t
pound
eV
Ejr eV /in : 7 0 ' :VLV' caloJ
I 100,703 8,833 3,957 0,6595 9,913 0,317 0,367 201
II 178,305 19,475 79,75 0,6646 0,5"84 9,356 i,701 0,358 267
26O
III 255;933 30,143 12,019 0,6677 0,597 8,941 1,983 0,359 296 303~
IV 151,007 14,497 6,300 0,6300 -- 9,528 1,484 0,374 281 -- 2765
243 -- 231s
V 227,441 23,971 9,990 0,6244 0,536 9,227 2,147 0,362 286 "v-, 2994
VI 224,915 18,855 8,941 0,6386 8,962 1,798 0,365 298 B~
VI i 224,945 18,885 8,971 0,6408 -- 8,909 1,863 0,371 301 ] B:~'
VII 376,782 36,802 16,040 0,6169 0,515 8,795 2,339 0,361 3171 ~
VIII 678,141 65,141 29,041 0,6313 0,514 [ 8,772 2,668 0,347 321 Be
IX 455,415 48,475 20,513 0,6410 0,536 ] ~,,928 2,101 0,360 294 B~
o,~31
X 302,547 I 29,527 13,133 0,6567 0,533 ]9,013 1,576 0,373 273 B2
302,551 [ 29,531 13,137 0,6569 0,537 19215 1,613 0,373 274 B
xXli ! 302,555 ] 29,535 13 141 0,6571 0,541 ]8,899 1,941 0,372 292 B~
Xli~ 302,566 J 29,546 13,152] 0,6576 0,552 ] 8,882 1,934 0,375 290 B,., D

XII ~ 302,562 I 29,542 13,148 0,6574 0,548 8,938 1,766 0,373 282 -- :
Xlli i 302,552 .[ 29,532 13,136 0,6569 0,538 8,932 I,T77 0,374 281 i --~

168
 +0,308 - 0~,118 "e0,034 -0,,009 -0~,084r +O,2BI
+ 0"264~' ~ ~ -r 0~046* - 0,051'~ - Oj,O02'~- 0,008"'0 0/-0~+ O,258 * -0,100 ^~/. - 01056 + 01009
+0,218 '~ ~ 0,510 x ~- = o,~0,106+'u'`~" 0,725

~,,'%~ *ouo*~~E.~2,~'Z. ~ ~.~.,.~j:)x-~Co~/~ ,~-- ~ /~ -To,, -/~

- ~ - -u~.=:,. -0106'* +0~036" "01008*+01067+0,047*'0,262 - ~/-W"=-O, 318 iO 014" -0 010

I -o, zs6 ~ +5',IO~ -O,O~B+0,o2~-O,OS~*O,O6S-O,Z69 -u,u~ V ' '
0 -0,103 -- (-V
9 - ,307 0,~ -0,,002 +0,006 -0f320- -0,0430010 - ~-~- 0696
M +0,087 /'~<'? ^ %'J" M n ~ ~ ,.. +0~.070 ~ " ~ -%U~ O~ '5%3 r ~ ~ ~' o

A i-0,o45( I ~ I 3 (-o,o,~ ,,~---...--~+Op6,:, I I "T'l ~l "~'~Z,E..:..;-/ h

0+0,2,, ._o1
oo \ \ / \ J
\x,(~" / +0~256 " ~.2< ~ -utuu= -u~v,= +0,265" -0.()56 " ~ - ~'/ -(~P' " 01696
k------q + 0~057 -v,,~. VI +0~026 -0~015 ~ ' Ix
/ \ ~0,267 -- ~ 0,714 o "~ -

~\ /,~ .-i | \ ' 0 479 ~'y \~- -0.001 r -u,332 0~ 0~,701 _

-~ v, ~ t,,% ' *0095 "~ 5%% o ,~
h'---'t~. +o,ou ~~ L~'~' /:,~ 9X /~ / X / ""r" ~ \% ~.,/ \e.,

- 0~001
+0;006 +0~025 -01294 '~0r025 -0~300 - 0 r 0 0 7 0 751 - ,.% 06;, 0 672
kl +0.012 A + 0 . 0 7 1 " " ~' o -- . , u , 5 2 2 r ~t,,'1 . . o
/ \ /"-<~ " - < ~ " \~, / ~% #,,'"-"---,-,F" ''--~,~--",'% ~,o/ -t'" = 0
'~%

9 0,000 +0,006 _ _ ~ulu,~ V - U ; u , , u -0,0330752 ~ U01~0~6"22~'~ ~'~'va U 0676 ~"

+U#Z73 .0,071 + 0 240 ~ -- " -'
r VIII

Fig. 4. Molecular d i a g r a m s of a r o m a t i c oxazoles in the f i r s t and second (*) singlet excited s t a t e s .

hydroxybenzidine should have higher heat r e s i s t a n c e b e c a u s e

of the g r e a t e r homolytic and h e t e r 0 c y c l i c s t a b i l i t y of the o x -
azole ring. We also note the identical s t r e n g t h s of the C - C
C, Ii ;r;
bonds between the rings of the diphenyl f r a g m e n t and between
the benzoxazole and benzene ring and a c e r t a i n tendency for
9O~
4 L I i
weakening of the t e r m i n a l C - C bond as the chain of the m o l e -
OJ
cule is lengthened.
C h a r a c t e r i s t i c s of the Excited States. The c a l c u l a t e d
e l e c t r o n i c a b s o r p t i o n s p e c t r a of the investigated compounds
a r e s c h e m a t i c a l l y r e p r e s e n t e d in Fig. 3; the A m~x values of
the long-wave a b s o r p t i o n a r e also p r e s e n t e d in Table 1. The
m o l e c u l a r d i a g r a m s of the compounds in s t a t e s c o r r e s p o n d i n g
to the long-wave excitation a r e p r e s e n t e d in Fig. 4. C o m p a r i -
s o n of t h e m with the m o l e c u l a r d i a g r a m s of the ground s t a t e
Im
I00 200 300 400 500 lead to the following r e s u l t s .
Excitation in oxazole is a c c o m p a n i e d by a c o n s i d e r a b l e
Fig. 5. Calculated s i n g l e t - s i n g l e t ( ~ )
d e c r e a s e in the o r d e r s of all of the bonds except the N - C a bond,
and s i n g l e t - t r i p l e t ( - - - ) t r a n s i t i o n s in
s t e r e o i s o m e r i c dibenzoxazoles. and e s p e c i a l l y of the multiple bonds. The e l e c t r o n density was
shifted to such an extent f r o m the C ~ C bonds that the atoms
tha% f o r m it w e r e c o n v e r t e d f r o m c e n t e r s of addition of e t e c -
trophilic agents to s i t e s of p o s s i b l e attack of nucleophilic agents. M o r e o v e r , a l a r g e excess of ~ - e l e c t r o n
dens ity is f o r m e d on C 2.
The l o n g e s t - w a v e excitation in H ( ~ ~ 267 nm, f -~ 0.07) is r e l a t e d to the phenyl f r a g m e n t of the
m o l e c u l e with p a r t i a l p a r t i c i p a t i o n of the C = C bond of the oxazole ring. However, the intense t r a n s i t i o n
with AE -~ 260 nm is a c c o m p a n i e d b y c h a r g e t r a n s f e r (about 0.2 e) f r o m the oxazole ring to the benzene
ring with c o n s i d e r a b l e strengthening of the bond between t h e m . In other words, the e l e c t r o n - a c c e p t o r
p r o p e r t i e s of the phenyl group a r e a p p r e c i a b l y intensified in the excited s t a t e .

169
 The s a m e p o l a r i z a t i o n of the v - e l e c t r o n cloud is also noted for the excited s t a t e of III. In this c a s e ,
the nonequivalence of the benzene ring is r e t a i n e d - the ring in the 2 position has the g r e a t e r e l e c t r o n -
a c c e p t u r effect. A m o r e detailed examination of the m o l e c u l a r d i a g r a m of III indicates that the o r d e r s of
all of the bonds of the oxazole ring d e c r e a s e during excitation, while the o r d e r s of the N ~ C bonds i n c r e a s e .
The bonds between the rings a r e a l s o s t r e n g t h e n e d .
Two bands of different intensity with k max 276 and 231 nm [4] a r e o b s e r v e d in the long-wave region
of the UV s p e c t r u m of benzoxazole IV. They a r e s a t i s f a c t o r i l y r e p r o d u c e d by our calculations (see Table 1).
M o r e o v e r , it turns out that the low-intensity band c o r r e s p o n d s to p r i m a r y m i g r a t i o n of the ~r-electron
density through the benzene ring, while the intense long-wave a b s o r p t i o n is a c c o m p a n i e d by c h a r g e r e d i s -
tribution throughout the entire m o l e c u l e .
As in all of the 2 - p h e n y l - s u b s t i t u t e d oxazoles, the excited s t a t e of V is c h a r a c t e r i z e d by a shift of the
- e l e c t r o n density f r o m the h e t e r o r i n g s to the benzene r i n g s . This shift is a c c o m p a n i e d by strengthening
of the bond between the r i n g s . M+or$over, the o r d e r s of the "weak" bonds r e m a i n p r a c t i c a l l y unchanged,
while the e l e c t r o p h i l i c i t y of the O - C bonds turns out to be c o n s i d e r a b l y reduced.
The long-wave excitation of dibenz [b,e]oxazole is of a nature that indicates involvement of the e n t i r e
m o l e c u l e . M o r e o v e r , the c h a r g e s on the c a r b o n atoms (the nucleophilicities of C 2 and C 2, d e c r e a s e as the
e l e c t r o p h i l i c i t i e s of C~ and C A, i n c r e a s e ) and.the o r d e r s of all of the bonds except the C - O bond change
m o s t significantly.
Substituent effects s i m i l a r to those d e s c r i b e d above a r e o b s e r v e d in the excited states of VH-IX (see
their molecular diagrams).
S t e r e o i s o m e r i s m of Dibenzoxazoles. The m o l e c u l a r d i a g r a m s and calculated e l e c t r o n i c absorption
s p e c t r a of v a r i o u s s t e r e o i s o m e r i c dibenzoxazoles a r e p r e s e n t e d in F i g s . 2 and 5.
A c o m p a r i s o n of the m o l e c u l a r d i a g r a m s of the i s o m e r s shows insignificant d i f f e r e n c e s in the c h a r -
a c t e r i s t i c s of the e l e c t r o n distribution. The examined i s o m e r s also differ only insignificantly with r e s p e c t
to energy c h a r a c t e r i s t i c s (Table 1). However, t h e i r c o m p a r i s o n m a k e s it p o s s i b l e to note that the cis
o r i e n t a t i o n of the oxazole rings p r o v e d to be s o m e w h a t m o r e advantageous than the t r a n s configuration only
in the cas e of XII.
The data in Fig. 5 make it p o s s i b l e to expect identical c h a r a c t e r of the long-wave a b s o r p t i o n of di-
benzoxazoles with cis o r t r a n s orientation of the oxazole rings and a c e r t a i n difference in t h e i r UV s p e c t r a
in the s h o r t - w a v e r e g i o n . S t e r e o i s o m e r s with different fusions of the benzoxazole rings (5,5'-, 6 , 6 ' - , or
5,6'-) a r e s p e c t r a U y different.

LITERATURE CITED
1. G. I. Kagan, V. A. Kosobutskii, V. K. Belyakov, and O. G. T a r a k a n o v , Khim. G e t e r o t s i k l . Soedin.,
1396 (1973).
2. G. I. Kagan, V. A. Kosobutskii, V. K. Belyakov, and O. G. T a r a k a n o v , Khim. G e t e r o t s i k l . Soedin.,
794 (1972).
3u R. Hirohashi, I. Hishiki, and S. Ishikawa, Polymer, 11,297 (1970).
4. D. G. Oft, F. N. Hayes, E. Hansbury, and V. N. Kerr, J. Amer. Chem. See., 79, 5448 (1957).
5. A. R. Katritzky, ed., Physical Methods in Heterocyclic Chemistry, 2 Vols., Academic (1963).

170
SYNTHESIS OF CYANOAMINOTHIOPHENES WITII
ACTIVE FUCTIONAL GROUPS

L. G. Sharanina and S. N. Baranov UDC 547.733'853.7.07

2 - A m i n o - 3 - c y a n o - 4 - N - a r y l c a r b a m o y l - 5 - m e t h y l t h i o p h e n e s w e r e obtained by condensation of
a r y l a m i d e s of a c e t o a c e t i c acid with s u l f u r and m a l o n o n i t r i l e in absolute alcohol. 4 - A m i n o - 6 -
N - a r y l c a r b a m o y l - 5 - m e t h y l t h i e n o [2,3-d]pyrimidines a r e f o r m e d by r e a c t i o n of the c o n d e n s a -
tion products with f o r m a m i d e .

2-Aminothiophenes containing alkyl o r a r y l groups in the 3,4 positions w e r e obtained by Knoevenagel

condensation of c a r b o n y l compounds with s u l f u r and nitriles containing an active methylene g r o u p [1, 2].
We have c a r r i e d out a condensation of the Knoevenagel type using anilides of a c e t o a c e t i c acid, m a l o n o -
n i t r i l e , and sulfur in ethanol. One might h a v e expected the f o r m a t i o n of 2 - a m i n o - 3 - c y a n o t h i o p h e n e s of the
I o r II type:

ArHN..,TT_~_~CN ArNHCO /CN ArNHCO-..~CN

CH3CO ~CN
II I a-d
a Ar=C~Hs; b Ar=4-CH3C6H4;c Ar=4-CICoH4;d Ar=2,$-CI2C6H3

We have shown that the r e a c t i o n leads p r i m a r i l y to d e r i v a t i v e s of the I type (Table 1). A s m a l l

amount of 3 - c y a n o - 4 - m e t h y l - 5 - a n i l i n o - 2 - p y r i d o n e was isolated as a side product; the s t r u c t u r e of the side
p r o d u c t was c o n f i r m e d by a l t e r n a t i v e synthesis by a known method f o r the p r e p a r a t i o n of pyridone [3] f r o m
a c e t o a c e t i c acid anflide and m a l o n o n i t r i l e in d i m e t h y l f o r m a m i d e in the p r e s e n c e of an organic b a s e .
The IR s p e c t r a of 2 - a m i n o - 3 - c y a n o t h i o p h e n e s I, contain four a b s o r p t i o n bands of f r e e and bonded
amino groups at 3200-3500 c m -t [4, 5]. The a b s o r p t i o n band at 2220 c m -I is affiliated with the s t r e t c h i n g
v i b r a t i o n s of a nitrile group bonded to an a r o m a t i c h e t e r o c y c l e [4, 5]. The intense b r o a d a b s o r p t i o n band
with two m a x i m a at 1610 and 1645 and a s h o u l d e r at 1660 c m -1 a p p a r e n t l y c o r r e s p o n d s to the d e f o r m a t i o n
v i b r a t i o n s of the a r o m a t i c r i n g s , the s t r e t c h i n g vibrations of the oxo group, and the d e f o r m a t i o n vibrations
of the amino group [4, 5].
The p r e s e n c e of vicinal functional amino and nitrile groups made it p o s s i b l e to c a r r y out the r e a c -
tion of substituted thiophene with f o r m a m i d e . 4 - A m i n o t h i e n o [ 2 , 3 - d ] p y r i m i d i n e s III (Table 2) w e r e isolated
in quantitative yields. On the basis of the available data [2, 6, 7], the following s c h e m e can be a s s u m e d for
the r e a c t i o n :

I a-d + ~ H2
o~C\~ CH:3f~.S/~-N=C HNH2 ~

i|l a-d

To choose between s t r u c t u r e s of the I o r II t y p e s , we c a r r i e d out the h y d r o l y s i s of both the 2 - a m i n o -

thiophene d e r i v a t i v e s and the 4 - a m i n o t h i e n o [2,3-d]pyrimidines. The h y d r o l y s i s of compounds of the I type
by refluxing in alcoholic alkali a p p a r e n t l y p r o c e e d s with c l e a v a g e of the thiophene ring, and the r e a c t i o n

Donetsk State U n i v e r s i t y . T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 2, pp. 196-

198, F e b r u a r y , 1974. Original a r t i c l e s u b m i t t e d O c t o b e r 2, 1972.

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No p~rt o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is avaflable from the publisher for $15.00.

171
 T A B L E 1. 2 -Amino-3-cyano-4-N-arylcarbamoyI-5-methylthiophenes
(Ia-d)

Com- Ar
Mp,.d t Empirical for-
pOUnd ";C_~] muia" . . . . . . Ill
la C6Hs 199 CI3HnN~OS I 60,414,4 16,2] 12,4 60,7 4,3 16,3 12,5 70
60,614,2 16,5 i 12,3I
Ib 4-CH~C6H4 232 CI4HI~N3OS 62,0 4,8 15,31 I 1,9162,0 4,8 15,5 tl,8 63
61,8 4,9 15,6111,71
Ic 4-CIC8H4 226 CmHmC1N3OSa 53,5[3,6 14,0]11,0153,5 3,5 14,4 11,0 60
t53,4i3,6
14,3110,8I
ld 2,5-C12C8H~ 312 ClsHgCI2NsOSb t 47,5 [ 2,8 12,6 9,7 47,9 2,8 12,9 9,8 68
147,612,6 12,7 9,8
a F o u n d , %: C1 12.3, 12.1. C a l c u l a t e d , %: C1 12.2.
b F o u n d , %: C1 21.7, 21.5. C a l c u l a t e d , %: C1 21.4.

T A B L E 2. 4 - A m i n o - 5 - N - a r y l c a r b a m o y l - 6 - m e t h y l t h i e n o [ 2 , 3 - d ] -
pyrimidines (Ula-d)
Found, % Calc., %
Corn-
pound Ar
MCp, ' Empirical for-
mula H N C H N ii S

Ilia CsHs 314 CI~H~zN4OS 59,3 4,5 19,g 10,9 59,t 4,3 19,7 :~11,3
59,1 4,5 20,C 11,1
Illb 4-CHaC6H4 315 CIsHI4N4OS 60,7 5,1 18,5 10,4 60,4 4,7 18,8 /i 10,7
60,2 4,9 18,5 10,6 i
IIlc 4-CIC61-I4 316 C~4HIICIN4OSa 52,9 3,3 17,4 9,9 52,7 3,5 17,6 10,o
52,3 3,4 17,7 9,8 [
l I I d 2,5-C12C6H3 345 C:4H,oCI2N4OSb 47,5 3,0 15,4 8,9 47,6 2,9 15,9 ! 9,1
47,3 2,7 15,7 8,8

a F o u n d , %: C1 11.0, 1 1 . 0 . Calculated, %: C1 11.1.

bFound, %: C1 19.8, 20.1. C a l c u l a t e d , %: C1 20.1.

p r o d u c t s could not be i d e n t i f i e d . H y d r o l y s i s in a c e t i c acid leads to 2 - a c e t a m i d o - 3 - c y a n o - 4 - c a r b o x y - 5 -

m e t h y l t h i o p h e n e (IV); the n i t r i l e g r o u p is not involved in this r e a c t i o n , in a c c o r d a n c e with the data in [8].
4 - A m i n o t h i e n o [ 2 , 3 - d ] p y r i m i d i n e IIIa is h y d r o l y z e d to 4 - a m i n o - 5 - c a r b o x y - 6 - m e t h y l t h i e n o [2,3-d]-
p y r i m i d i n e (V) in an alcohol s o l u t i o n of p o t a s s i u m h y d r o x i d e .
Thus the p r e s e n c e of an N - a r y l c a r b a m o y l g r o u p i n g in the p r o d u c t s of c o n d e n s a t i o n of a c e t o a c e t i c
acid anilides with m a l o n o n i t r i l e and s u l f u r is c o n f i r m e d ; this is e v i d e n c e in f a v o r of s t r u c t u r e s of the I and
III type f o r the p r o d u c t s .
EXPERIMENTAL
The individualities of all of the s y n t h e s i z e d c o m p o u n d s w e r e c o n f i r m e d by t h i n - l a y e r c h r o m a t o g r a p h y
(TLC) on a fixed l a y e r of s i l i c a g e l - g y p s u m in c h l o r o f o r m - a c e t o n e - c a r b o n t e t r a c h l o r i d e (3 : 3 : 5). The IR
s p e c t r a of K B r pellets of the c o m p o u n d s w e r e r e c o r d e d .
2 - A m i n o - 3 - c y a n o - 4 - N - p h e n y l c a r b a m o y l - 5 - m e t h y l t h i o p h e n e (Ia, Table 1). A 3.6 g (0.02 mole) s a m p l e
of a c e t o a c e t i c acid anilide and 0.8 g (0.025 g - a t o m ) of s u l f u r w e r e d i s s o l v e d in 10 m l of a n h y d r o u s ethanol
while heating on a w a t e r bath, a f t e r which the s o l u t i o n was c o o l e d to r o o m t e m p e r a t u r e , and 1.32 g (0.02
mole) of m a l o n o n i t r i l e and 2 m l of m o r p h o l i n e w e r e added. The r e a c t i o n m i x t u r e b e g a n to d a r k e n and
w a r m e d up to 60-65~ it was h e a t e d at 60 ~ f o r 30 min. It was then c o o l e d to r o o m t e m p e r a t u r e , during which
a b r i c k - r e d p r e c i p i t a t e f o r m e d ; the alcohol s o l u t i o n was diluted with a twofold to t h r e e f o l d a m o u n t of w a t e r
for c o m p l e t e p r e c i p i t a t i o n . The p r e c i p i t a t e was r e m o v e d b y f i l t r a t i o n and w a s h e d with ethanol. C r y s t a l -
lization f r o m ethanol ( c h l o r o f o r m ) gave a s m a l l a m o u n t (0.1-0.2 g) of insoluble 3 - c y a n o - 4 - m e t h y l - 6 - p h e n y l -
a m i n o - 2 - p y r i d o n e with m p 266 ~ Dilution of the alcohol s o l u t i o n with w a t e r gave 3.6 {70%) of Ia.
Thiophene d e r i v a t i v e s I b - d (Table 1) w e r e s i m i l a r l y obtained.
4 - A m i n o - 5 - N - p h e n y l c a r b a m o y l - 6 - m e t h y l t h i e n o [ 2 , 3 - d ] p y r i m i d i n e (IIIa, T a b l e 2). A m i x t u r e of 0.73 g
(0,28 m01e) of Ia and 5 ml of f o r m a m i d e was h e a t e d at 190 ~ on an oil bath f o r 15 m i n . It was then cooled,

172
and IIIa was crystallized to give 0.8 g (about 100%) of shiny colorless plates with mp 314 ~ (from dioxane).
IR spectrum: v NH2 3512, 3406; 5NH 2 1625; vC= O 1680 cm -1.
4-Aminothieno[2,3-d]pyrimidine derivatives IIIb-d (Table 2) were similarly obtained.
2-Aeetamido-2-cyano-3-carboxy-5-methylthiophene (IV). A 0.52 g (0.002 mole) sample of Ia was r e -
fluxed in a mixture of 5 ml of concentrated hydrochloric acid and 5 ml of glacial acetic acid for 4 h. The
mixture was then cooled to room temperature and worked up to give 0.24 g (50~) of a white precipitate of
IV with mp 324 ~ (from dioxane). IR spectrum: 2220 (C-------~N), 1720 cm -1 (COOH). Found, %: C 48.1, 48.0;
H 3.7, 3.5; N 12.3, 12.5; S 14.0, 14.1. CgHsN203S. Calculated, %: C 48.2; H 3.6; N 12.5; S 14.3.
4-Amino-5-carboxy-6-methylthieno [2,3-d]pyrimidine (V). A 0.4 g (0.014 mole) :sample of IIIa was
refluxed in alcoholic potassium hydroxide solution for 4 h. The reaction mixture was treated with hydro-
chloric acid until it was weakly acidic, and the mixture was filtered to give 0.075 g (26~ of V with mp 333 ~
(from dioxane). Found, ~c: C 46.2, 45.9; H 3.2, 3.1; N 20.0, 19.7; S 15.3, 15.4. CsHTN302S. Calculated, %:
C 46.0; H 3.4; N 20.2; S 15.4. IR spectrum: a number of absorption bands at 3200-3500 cm-1; 6 NH2 1630
cm-1; ~COOH 1720 cm -l,
LITERATURg CITED
1. K. Gewald, g . Schinke, and H. BiJtteher, Bet., 99, 94 (1966).
2. E . C . Taylor and I. l~. Berger, Angew. Chem., 78, 144 (1966).
3. U. Basu, J. Indian Chem. Soc., 7, 815 (1930).
4. A . R . Katritzky and A. P. Ambler, in: Physical Methods in Heterocyclic Chemistry, Chap. 10,
Academic (1963).
5. K. Nakanishi, Infrared Spectra and Structure of Organic Compounds [Russian translation], Mir,
Moscow (1965).
6. g . C . Taylor and A. Abul-Husn, J. Org. Chem., 31, 342 (1966).
7. E . C . Taylor, A. McKillop, and R. V. Pavindrathan, Angew. Chem., 78, 332 (1966).
8. Yu. A. Sharanin, Dissertation [in Russian], Leningrad (1967).

173
 SYNTHESIS OF 2-BENZAMIDOTHIAZOLINES

I. N. Azerbaev, L. A. Tsei, UDC 547.789.1,07:543.422.25.4.6

L. T. Kalkabaeva, and N. N. Alekseeva

2 - B e n z a m i d o - 5 - m e t h y l e n e - 2 - t h i a z o l i n e s w e r e obtained by r e a c t i o n of ~ - e t h y n y l a m i n e s with
benzoyl isothiocyanate. The resulting acylaminothiazolines have imino s t r u c t u r e s , while
t h e i r hydrochlorides have amino s t r u c t u r e s .

In developing our r e s e a r c h [1] involving a study of the r e a c t i o n of acetylenic amines with isothio-
c y a n a t e s , we d e s c r i b e d the r e a c t i o n of ~ - e t h y n y l a m i n e s with acyl isothiocyanates, p a r t i c u l a r l y with benzoyl
isothiocyanate. Since acyl isothiocyanates a r e m o r e r e a c t i v e compounds than alkyl and a r y l isothiocyanates,
acetylenic amines r e a c t with benzoyl isothiocyanate m o r e v i g o r o u s l y to give good yields of I a - f (Table 1).
The 2 - b e n z a m i d o - 2 - t h i a z o l i n e s a r e weak b a s e s , and t h e i r hydrochlorides a r e hydrolyzed on dissolving in
water.
I n t r a m o l e c u l a r cyclization at the triple bond to give a f i v e - m e m b e r e d ring is c o n f i r m e d by the PMR
s p e c t r a : two doublets at 5.0-5.4 ppm with J = 1.5-2 Hz a r e c h a r a c t e r i s t i c for the nonequivalent geminal
protons of an exocyclic methylene group (Table 2), the p r e s e n c e of which attests to the f o r m a t i o n of a five-
m e m b e r e d ring [2]. The absorption bands at 2100 and 3300 c m -1 that a r e c h a r a c t e r i s t i c for the C ~ C and
C - H s t r e t c h i n g v i b r a t i o n s a r e absent in the IR s p e c t r a of Ia-f, but the s p e c t r a do contain a b s o r p t i o n at
860-870 c m -1, which also indicates the p r e s e n c e of an exocyclic methylene group [3].
Sheinker and c o - w o r k e r s [4, 5] have found that the introduction of e l e c t r o n e g a t i v e substituents into
the exocyclic nitrogen atom shift the t a u t o m e r i c a m i n e - i m i n e equilibrium to favor p r e d o m i n a n c e of the
imine f o r m s : in p a r t i c u l a r , the acyl d e r i v a t i v e s of 2-aminothiazolines e x i s t in the imine f o r m in solution.
An investigation of the IR s p e c t r a of c r y s t a l s of the acylaminothiazolines that we obtained showed a c o n -
s i d e r a b l e shift in the a b s o r p t i o n bands of the C = O (1600-1610) and C = N (1550 c m -1) groups; this is due
to conjugation of t h e s e groups in imine s t r u c t u r e I. T h e s e data c o n f i r m the conclusions in [4, 5] r e g a r d i n g
the imine s t r u c t u r e of 2 - a c y l i m i n o t h i a z o l i n e s and a r e applicable to the 2 - b e n z a m i d o - 5 - m e t h y l e n e t h i a z o l i n e s
(I) that we obtained. The absorption band of a n amide c a r b o n y l group is o b s e r v e d at 1700 c m -l, and ab-
s o r p t i o n of a C = N group is o b s e r v e d at 1618-1627 c m -1 in the IR s p e c t r a of the hydrochlorides ( I I a - 0 of
the compounds obtained. The changes in the IR s p e c t r a of the hydrochlorides can be explained by the fact
that s a l t f o r m a t i o n p r o c e e d s through f o r m a t i o n of a cation at the ring nitrogen.

R~_.~,~C H2 R\ xCH~ R\ ~CH.

RR'~-c~c.+ c0.~coNcs ~ R"'I ( ~ R'-"'F---F :_...R'/F:--F "
i
; N HCOEBH s NCO%H s N HCOC~H~ "
l II

T h r e e a b s o r p t i o n m a x i m a a r e noted in the UV s p e c t r a of the 2-benzamidothiazolines (Table 3); a

m a x i m u m , c h a r a c t e r i s t i c for the thiazoline ring, is o b s e r v e d at 197 nm and below [6]. A b a t h o c h r o m i c
shift of the m a x i m u m by 10 nm and higher with no changes in the positions of the two other m a x i m a (270
and 235 nm) a r i s e s during the f o r m a t i o n of the h y d r o c h l o r i d e s . A s i m i l a r shift in the m a x i m a in the UV
s p e c t r a during the f o r m a t i o n of hydrochlorides is also observed" in the c a s e of thiazolidines with a fixed
s t r u c t u r e , while the a b s o r p t i o n m a x i m a of thiazolines and t h e i r hydrochlorides coincide [1]; this c o n f i r m s
the a s s u m p t i o n r e g a r d i n g the amine s t r u c t u r e of hydrochlorides I I a - f .

Institute of C h e m i c a l Sciences, A c a d e m y of Sciences of the Kazakh SSR, A l m a - A t a . T r a n s l a t e d f r o m

Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 2, pp. 199-201, F e b r u a r y , 1974. Original a r t i c l e s u b m i t t e d
S e p t e m b e r 25, 1972.
I 9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, N.Y. 10011. No part of this publication m~y be reproduced,
I stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
|[ recording or otherwise, without written permission of the publisher. A copy of this article isavailable_ from the publisher for $15.00.

174
 TABLE I. P h y s i c a l C o n s t a n t s and Y i e l d s of I
I
Com-i mp of ~i T Found, % tale,, % [.'d
pound R" mp? ~ i!the by- !
droehlo- Empirical
t.~
ride, ~ f0rmula ci.} s c n sl~

Ia CHa CHa 110 187--188 0,36 C13Hx4N~OS 634 61 127 634 57(130 756
Ib CHa C2Hs
Ir CHa Call?
130126t31 188--190 9,38
21S--2~0 / 0,34
6,:16:4112:7 64:616:211:3 92:5
CasHm,N~OS 65,916,61II,2165,716,61 II,7 82,4
l d C2Hs, C2Hs 91--92 114--115 ] 0,32 C~,~HmN2OS165,116,5111,8165,716,61 II,7180,2
Ie - - (CH2) 4-- 99---100 154--156 0,30 C~sH~sN2OS {66,2 6,1 I 1,4166,215,9111,8170,0
If , - - ( C H 2 ) s - - 134--135 209--210 0~39 CIsHIBN2OS[673 63] ll,l I 67 1 6,3 11 2 i 88 t

* T h e c o m p o s i t i o n of h y d r o c h l o r i d e s I V a - f was c o n f i r m e d b y d e t e r m i n a -
t i o n of the p e r c e n t a g e of n i t r o g e n .
T The a d s o r b e n t w a s A1203, the e l u e n t was b e n z e n e ; a n d the d e v e l o p e r
was iodine.

T A B L E 2. P M R S p e c t r a of I

Com- Chemical shifts of the \ . ~/H~ protons,

Solvent 5, ppm /'~=~ \H:- A6, ppm I, H z
pound
HL H=

CC14 ! 5,16 5,08 0,08 1,7

Ib CCh l 5,10 4,90 0,20 2,0
Ic CC]4 I 5,14 5,07 0,07 2,0
Id CS2 i 5,08 4,88 0,20 2,0
Ie CS2 i 5,00 5,00
If CSz t 5,00 5,00

T A B L E 3. D a t a f r o m the IR and UV S p e c t r a of I and II

IR spectra, v, em -I U V spectra of I
Com-
pound bases hydrochlorides
Zma x,
C=O C=N C=O C=N

la 1625 1550 1700 1615 197,5 240 279 2,02 1,65 t,79
Ib 1605 1530 1700 1610 -- 240 279 1,78 1,91
Ic 1600 1550 t700 1610 97,--5 241 28O 1,72 1,91
Id 1610 I545 1700 1600 1 242 280 2,14 1,87 2,06
le 1635 1550 1700 1610 198,0 241 280 2,12 1,79 1,93
If 1630 1550 1700 1605 -- 242 280 1,71 1,85

EX Pt~RIME NTA L
The IR s p e c t r a w e r e r e c o r d e d w i t h a U R - 2 0 s p e c t r o m e t e r . The P M R s p e c t r a of CC14 and CS 2 s o l u -
t i o n s w e r e r e c o r d e d w i t h a Z K R - 6 0 s p e c t r o m e t e r w i t h h e x a m e t h y l d i s i l o x a n e (HMDS) as t h e s t a n d a r d . T h e
UV s p e c t r a of a l c o h o l s o l u t i o n s w e r e r e c o r d e d w i t h a H i t a c h i E P S - 3 T s p e c t r o p h o t o m e t e r w i t h a d e u t e r i u m
lamp.

2-Benzamido-4,4-dimethyl-5-methylenethiazoline (Ia). A 3.26 g (0.02 m o l e ) s a m p l e of b e n z o y l i s o -

t h i o c y a n a t e was a d d e d d r o p w i s e w i t h s t i r r i n g and c o o l i n g to 1.66 g (0.02 m o l e ) of 3 - a m i n 0 - 3 - m e t h y l - 1 -
b u t y n e ; t h e t e m p e r a t u r e of t h e m i x t u r e was k e p t b e l o w 50 ~ (the r e a c t i o n was e x e t h e r m i c ) . T h e m i x t u r e was
c o o l e d , and the p r e c i p i t a t e d Ia w a s p u r i f i e d by r e c r y s t a l l i z a t i o n f r o m d r y p e t r o l e u m e t h e r to g i v e 3.72 g
(76.5%) Of a p r o d u c t w i t h m p 110 ~ and R f 0.36 ( a c t i v i t y rrI A1203, e l u t i o n w i t h b e n z e n e ) . F o u n d , ~ : C 63.4;
H 6.1; S 1 2 . 7 . Ct3H14N2OS. C a l c u l a t e d , %: C 63.4; H 5.7; S 13.0.

The h y d r o c h l o r i d e of IIa w a s o b t a i n e d b y a d d i t i o n of an e t h e r s o l u t i o n of HC1 to an e t h e r s o l u t i o n of

I a . The l u m i n o u s p r e c i p i t a t e was r e m o v e d b y f i l t r a t i o n a n d w a s h e d w i t h e t h e r to g i v e a p r o d u c t with m p
1 8 7 - 1 8 8 ~ F o u n d , %: N 10.0. CI3HI4N2OS 9 HC1. C a l c u l a t e d , %: N 9.9.
C o m p o u n d s I b - f w e r e s i m i l a r l y o b t a i n e d ( T a b l e 1).

T h e a u t h o r s t h a n k V. I. A r t y u k h i n f o r h i s a s s i s t a n c e in t h e r e c o r d i n g and i n t e r p r e t a t i o n o f the IR and

PMR spectra.

175
 LITERATUR~ CITED
1~ I. N. Azerbaev, L. T. Kalkabaeva, M. Zh. Aitkhozhaeva, and L . A . Tsoi, Khim. GeterotsiM. Soedin.,
471 (1972).
2. V. F. Bystrov, Usp. Khim., 41, 512 (1972).
3. L. Bellamy, New Data from the IR Spectra of Complex Molecules [Russian translation], Mir, Moscow
(1971), p. 46.
4. E. M. Peresleni, Yu. N. Sheinker, N. P. Zosimova, and Yu. I. Pomerantsev, Zh. Fiz. Khim., 37, 2713
(1963).
5. E. M. Peresleni and Yu. N. Sheinker, Zh. Fiz. Khim., 38, 2152 (1964).
6. C. Rao, Chemical Application of Infrared Spectroscopy, Academic (1963).

176
SYNTHESIS IN THE PHENOTHIAZINE SERIES
XXXV.* SOME TRANSFORMATIONS OF BROMOAMINOPHENOTHIAZIN~S

Z. I. Ermakova, A. N. Gritsenko, UDC 547.869.2.07

and S. V. Zhuravlev

The c o r r e s p o n d i n g a m i n e s w e r e obtained by reduction of 1 - n i t r o - 3 - b r o m o p h e n o t h i a z i n e and

2 - b r o m o - 4 - n i t r o p h e n o t h i a z i n e . 1 - A m i n o - 3 - b r o m o p h e n o t h i a z i n e r e a c t s with f o r m i c acid to
give 4 - b r o m o i m i d a z o [ 4 , 5 , 1 - k , / ] p h e n o t h i a z i n e and with c a r b o n dis~zlfide to give 4 - b r o m o - l , 2 -
d i h y d r o i m i d a z o [ 4 ; 5 , 1 - k , / ] p h e n o t h i a z i n e - l - t h i o n e . 4-Aminophenothiazine r e a c t s with s u l f u r
and c a r b o n disulfide to give 2 , 3 - d i h y d r o t h i a z o l o [ 5 , 4 - c ] p h e n o t h i a z i n e - 2 - t h i o n e .

Within our plan to s e a r c h f o r biologically active s u b s t a n c e s , 1 - n i t r o - 3 - b r o m o - and 2 - b r o m o - 4 - n i t r o -

phenothiazine [2] w e r e r e d u c e d with h y d r a z i n e h y d r a t e in the p r e s e n c e of a Raney nickel c a t a l y s t to 1 - a m i n o -
3 - b r o m o p h e n o t h i a z i n e (I) and 2 - b r o m o - 4 - a m i n o p h e n o t h i a z i n e (II). In addition to I, 1-aminophenothiazine
was also isolated f r o m the reduction of 1 - n i t r o - 3 - b r o m o p h e n o t h i a z i n e as a r e s u l t of r e d u c t i v e d e h a l o g e n a -
tion.
Compound I, like 1-aminophenothiazine, undergoes r e a c t i o n s c h a r a c t e r i s t i c f o r o - a r y l e n e d i a m i n e s .
Heating of I with f o r m i c acid leads to 4 - b r o m o i m i d a z o [4,5,1-k,/]phenothiazine (III). Its IR and UV s p e c t r a
differ little f r o m those of unsubstituted imidazophenothiazine [3].
Compound I r e a c t s with c a r b o n disulfide in alcoholic p o t a s s i u m hydroxide solution to give 4 - b r o m o -
1 , 2 - d i h y d r o i m i d a z o [ 4 , 5 , l - k , / ] p h e n o t h i a z i n e - l - t h i o n e (IV).
The IR s p e c t r u m of IV in c h l o r o f o r m contains a band at 3425 crn -1, which is c h a r a c t e r i s t i c for the
N - H group, and a band at 1055 c m -l, which is c h a r a c t e r i s t i c for the C : S group, while bands c h a r a c t e r -
istic for the S - H group (2500-2600 c m -1) a r e absent. This indicates thione f o r m IV.

NH2 HN C~S
iNO2

HC~N
H
V
II / Ill Sl NH,

NO 2 NH 2 S=~C--N H
I IV

Reaction of II with sulfur and c a r b o n disulfide did not give 4 - b r o m o - l , 2 - d i h y d r o t h i a z o l o [ 5 , 4 - c J p h e n o -

t h i a z i n e - 2 - t h i o n e , while 4 - a m i n o p h e n o t h i a z i n e under s i m i l a r conditions f o r m s 2,3-dihydrothiazolo [5,4-c ]-
p h e n o t h i a z i n e - 2 - t h i o n e (V), which is identical to the compound p r e v i o u s l y obtained by a different method [4].
The IR s p e c t r u m of V in m i n e r a l oil does not contain a b s o r p t i o n bands c h a r a c t e r i s t i c for the S - H group
but does contain a band at 1050 c m -1 (C : S). The c o m p a r a t i v e data show that.the introduction of b r o m i n e
into the benzene ring hinders c y c l i z a t i o n of the thiazole r i n g .

* See ['1] for c o m m u n i c a t i o n XXXIV.

Institute of P h a r m a c o l o g y , A c a d e m y of Medical Sciences of the USSR, Moscow. T r a n s l a t e d f r o m
K h i m i y a G e t e r o t s ikliches kikh Soedinenii, No. 2, pp. 202-203, F e b r u a r y , 1974. Original a r t i c l e s u b m i t t e d
S e p t e m b e r 28, 1972.

9 19 75Plenum Publishing Corporation, 22 7 West 17th Street, New York, N.. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available.from the publisher for $15.00.

177
 EXPERIMENTAL
The IR and UV s p e c t r a w e r e r e c o r d e d with UR-10 and SF-4 s p e c t r o m e t e r s , r e s p e c t i v e l y .
1 - A m i n o - 3 - b r o m o p h e n o t h i a z i n e (I). A solution of 0.5 g (10 mmole) of h y d r a z i n e h y d r a t e in 2 ml of
alcohol was added d r o p w i s e to a w a r m solution of 0.81 g (2.5 mmole) of 1 - n i t r o - 3 - b r o m o p h e n o t h i a z i n e in
20 ml of ethanol and 5 m l of t e t r a h y d r o f u r a n containing 1 g of Raney nickel c a t a l y s t . The solution was d e -
c o l o r i z e d during the reduction. A f t e r the addition of h y d r a z i n e hydrate, the r e a c t i o n m i x t u r e was s t i r r e d
at 50 ~ for 1 h, and the c a t a l y s t was r e m o v e d by filtration. Water was added to the f i l t r a t e until it b e c a m e
turbid, and the m i x t u r e was allowed to stand at 5-7 ~ for 10 h. The p r e c i p i t a t e d amine was r e m o v e d by
filtration to give 0.45 g (62%) of a c r y s t a l l i n e s u b s t a n c e with mp 126-127 ~ (from aqueous alcohol) that
darkened in a i r . Found, %: Br 27.1; N 9.7. C~HgBrN~S. Calculated, ~c: B r 27.2; N 9.6.
2 - B r o m o - 4 - a m i n o p h e n o t h i a z i n e (II). A s i m i l a r r e a c t i o n with 0.8 g (2.5 mmole) of 2 - b r o m o - 4 - n i t r o -
phenothiazine gave 0.5 g (70%) of II with mp 169-170 ~ (from aqueous alcohol); the c o l o r l e s s c r y s t a l l i n e s u b -
stance darkened in a i r and was soluble in m o s t organic solvents but insoluble in w a t e r . Found, ~ : Br 27.6;
N 9.4. Ci2HgBrN2S. Calculated, %: Br 27.2; N 9.6.
4 - B r o m o i m i d a z o [ 4 , 5 , 1 - k , l ] p h e n o t h i a z i n e (HI). A m i x t u r e of 0.8 g (3 mmole) of I and 3 ml of 85~
f o r m i c acid was refluxed for 5 h. The m i x t u r e was then poured into 5~c sodium hydroxide solution, and the
resulting p r e c i p i t a t e was r e m o v e d by filtration and washed with w a t e r to give 0.64 g (80~) of III with mp
217-218 ~ (from toluene) ; the c o l o r l e s s c r y s t a l l i n e product was soluble in alcohol but insoluble in e t h e r .
Found, %: B r 26.10; S 10.75. Ct~HTBrN2S. Calculated, %: B r 26.36; S 10.55. UV s p e c t r u m (in alcohol),
Xmax, nm (log e): 232 (4.52), 334-336 (3.90}.
4 - B r o m o - l , 2 - d i h y d r o i m i d a z o [ 4 , 5 , 1 - k , l ] p h e n o t h i a z i n e - l - t h i o n e (IV). A 0.6 g (2 mmole) s a m p l e of I
was d i s s o l v e d in 10 ml of alcohol, and 0 2 g (2.1 mmole) of c a r b o n disulfide and 0.135 g (2.2 mmole) of
p o t a s s i u m hydroxide in 2 m l of w a t e r w e r e added with s t i r r i n g . The m i x t u r e was refluxed for 5 h, cooled,
and acidified with dilute h y d r o c h l o r i c acid. The light-yellow p r e c i p i t a t e was r e m o v e d by filtration to give
0.3 g (44%) of IV with mp > 360 ~ (from aniline). Found, %: B r 23.6; S 19.3. Ct3I-I7BrN2S2. Calculated, %:
Br 23.8; S 19.1.
2,3-Dihydrothiazolo[5,4-c]phenothiazine-2-thione (V). A 1.07 g (5 mmole) s a m p l e of 4 - a m i n o p h e n o -
thiazine, 0.18 g (5.5 mmole) of powdered sulfur, and 1 ml of c a r b o n disulfide w e r e added to an ampule, and
the ampule was s e a l e d and placed in a h e r m e t i c a l l y s e a l e d s t e e l c y l i n d e r and heated at 180-190 ~ for 3 h. At
the end of the r e a c t i o n , the excess c a r b o n disulfide was evaporated, and the r e s i d u e was d i s s o l v e d in 20 ml
of 15% sodium hydroxide solution (a portion of the r e s i d u e was insoluble). The alkaline f i l t r a t e was a c i d i -
fied with h y d r o c h l o r i c acid, and the r e s u l t i n g p r e c i p i t a t e was r e m o v e d by filtration to give 0.36 g (25%) of
V with mp 280-285 ~ (from toluene) (mp 285-290 ~ [4]). Found, %: N 9.3; S 33.1. C13HsN2S3. Calculated, %:
N 9.7; S 33.5.

LITERATURE CITED
1. G . A . Khutornenko, N. S. Panshina, and S. V. Zhuravlev, Khim. G e t e r o t s i k l . Soedin., 325 (1972).
2. A . N . Gritsenko, Z. I. g r m a k o v a , and S. V. Z h u r a v l e v , Khim. G e t e r o t s i k l . Soedin., 1337 (1970).
3. A . N . G r i t s e n k o , Z. I. E r m a k o v a , S. u Zhuravlev, and V. S. T r o i t s k a y a , Khim. G e t e r o t s i k l . Soedin.,
767 (1971).
4. V . V . Shavyrina and S. V. Zhuravlev, Khim. G e t e r o t s i k l . Soedin., 38 (1972).

178
INDOLES
XLII.* SYNTHESIS OF 1,2-DISUBSTITUTED TRYPTOPHOLS

I. I. Grandberg and G. P. Tokmakov UDC 547.752.755.07

A new method is p r o p o s e d for the s y n t h e s i s of 1,2-disubstituted tryptophols by r e a c t i o n of

N a - s u b s t i t u t e d a r y l h y d r a z i n e s with ( r - a c y l - y - b u t y r o l a c t o n e s by refluxing the c o m p o n e n t s
in an acidic aqueous alcohol m e d i a .

( ~ - A c y l - y - b u t y r o l a c t o n e s a r e the s t a r t i n g m a t e r i a l s f o r the p r e p a r a t i o n of the c o r r e s p o n d i n g y - a c y l

d e r i v a t i v e s of alcohols, which c a n be u s e d for the s y n t h e s i s of 2 - s u b s t i t u t e d tryptophols [2].
Continuing our r e s e a r c h on the s y n t h e s i s of tryptophols (II) [3], we have investigated the p o s s i b i l i t y of
p r e p a r i n g t h e m d i r e c t l y f r o m a c e t y l b u t y r o l a c t o n e and a r y l h y d r a z i n e s in acidic m e d i a . It s e e m e d likely
that the h y d r o l y s i s of the lactone ring and decarboxylation m a y p r o c e e d in p a r a l l e l with F i s c h e r indoliza-
tion b e c a u s e of the identical conditions u s e d in c a r r y i n g out both p r o c e s s e s . Refluxing a c e t y l b u t y r o l a c t o n e
with N a - s u b s t i t u t e d a r y l h y d r a z i n e s in a m i x t u r e of i s o p r o p y l alcohol and aqueous h y d r o c h l o r i c acids leads
to a n u m b e r of 1,2-disubstituted tryptophols (IIa-d).

~-~.~ ~O=C--CH
F 3 ~ - N ~I - ~ " ~ ~-~-~//~-~"~
I
-
R R R
I Ill

~1" tl
c.2(cno)2on ~
I " f~ I1
cn(c.2)oo. [a,3]
II " ~ (CH,J~OII

I I {
R R R
IV V VI
~/CH2CH2 OH
II a R=CH2%H~; b R=CsHs; C R=CH3; d R=i-C3H 7

I
R
II a - d

H y d r a z o n e III is a p p a r e n t l y f o r m e d in the f i r s t s t e p and is then c o n v e r t e d to h y d r a z o n e IV as a r e s u l t

of acid h y d r o l y s i s . A f t e r p r o t o t r o p i c t a u t o m e r i c c o n v e r s i o n of hydrazone IV to e n e h y d r a z i n e V, the latter,
as a consequence of a s i g m a t r o p i c [3.3] shift [4], is c o n v e r t e d to diimine VI, which subsequently gives
tryptophol II v i a the usual F i s c h e r s c h e m e . Hydrolytic opening of the lactone ring and decarboxylation m a y
also o c c u r a f t e r the s t e p involving the s i g m a t r o p i c [3.3] shift.
We u s e d only the acetyl group as the acyl group, s i n c e u n d e r t h e s e conditions c y e l i z a t i o n p r o c e e d s at
the CH 2 group but not at CH 3. When other a c y l b u t y r o l a c t o n e s a r e used, m i x t u r e s of 2- and 3 - h y d r o x y a l k y l -
indoles a r e f o r m e d ; we will deal with this m a t t e r in s u b s e q u e n t p a p e r s .
Only 1 - p h e n y l - 3 - m e t h y l - 4 - ( 2 - h y d r o x y e t h y l ) - 5 - p y r a z o l o n e was isolated in 65% yield in an a t t e m p t to
u s e phenylhydrazine to obtain 1-unsubstituted tryptephol under the s a m e conditions [5].

* See [1] for c o m m u n i c a t i o n X L I .

K. A. T i m i r y a z e v Moscow A g r i c u l t u r a l A c a d e m y . T r a n s l a t e d f r o m K h i m i y a G e t e r o t s i k l i c h e s k i k h
Soedinenii, No. 2, pp. 204-206, F e b r u a r y , 1974. Original a r t i c l e s u b m i t t e d J a n u a r y 15, 1973.

9 1975 PlenumPublishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

179
 EXPERIMENTAL
The UV s p e c t r a of isopropyl alcohol solutions of the compounds w e r e r e c o r d e d with a Hitachi E P S - 3 T
s p e c t r o p h o t o m e t e r . The IR s p e c t r a of CC14 solutions w e r e r e c o r d e d with a UR-20 s p e c t r o m e t e r . The PMR
s p e c t r a of CC14 solutions w e r e r e c o r d e d with a V a r i a n T-60 s p e c t r o m e t e r with hexamethyldisiloxane (HMDS)
as the internal s t a n d a r d , C h r o m a t o g r a p h y was c a r r i e d out in a thin l a y e r of A1203 (activity II) in b e n z e n e -
isopropyl alcohol (20 : 1). The individuality of the compounds was also c o n f i r m e d by g a s - l i q u i d c h r o m a t o g -
r a p h y (GLC) with a Yanaco G-800 c h r o m a t o g r a p h with a 2-m-; long column filled with SE-30 silicone (5%) on
c h e z o s o r b (0.25-0.35 m m ) ; the column t e m p e r a t u r e was 240 ~ and the c a r r i e r gas (H2) flow r a t e was 36.5
ml/min.
C o m m e r c i a l g r a d e ~ - b e n z y l - ~ - p h e n y l - , ~ - m e t h y l - ~ - p h e n y l - , and c~, ~ - d i p h e n y l h y d r a z i n e s a l t s w e r e
u s e d . a - I s o p r o p y l - a - p h e n y l h y d r a z i n e h y d r o c h l o r i d e was obtained by the method in [6].
G e n e r a l Method for the P r e p a r a t i o n of TryptolShols I I a - d . A solution of 0.05 m o l e of ~ - a c e t y l - y -
butyrolactone and 0.05 mole of a r y l h y d r a z i n e s a l t in a m i x t u r e of 55 ml of i s o p r o p y l alcohol, 30 ml of water,
and 5 ml of c o n c e n t r a t e d h y d r o c h l o r i c acid was refluxed for 8 h, a f t e r which the solvents w e r e e v a p o r a t e d
on a r o t a r y e v a p o r a t o r , and the r e s i d u e was t r e a t e d with 30 ml of benzene and 50 ml of w a t e r . The benzene
l a y e r was washed s e v e r a l t i m e s with w a t e r , s e p a r a t e d , and dried. The benzene was e v a p o r a t e d , and the
r e s i d u e was v a c u u m distilled. The c r u d e product was additionally purified by passing 2 g of it through a
column (20 c m l o n g and 3 c m in d i a m e t e r ) fillwed with activity II A1203 with s u c c e s s i v e elution with hexane,
h e x a n e - b e n z e n e (1:1), and benzene. The yield of p u r e s a m p l e was 1.3-1.5 g.
1 - B e n z y l - 2 - m e t h y l t r y p t o p h o l (IIa). This compound, with mp 80-80.5 ~ (from hexane) and R f 0.51, was
obtained in 58% yield.* UV s p e c t r u m : h m a x 226, 285 nm (Iogs 4.48, 3.83). IR s p e c t r u m : 3637 (OH), 1618,
1496 c m -! (ring s t r e t c h i n g v i b r a t i o n s ) . PMR s p e c t r u m , t 6, ppm: 1.67 s (OH), 2.20 s (2-CH3) , 2.86 t (J =
7 Hz, 3ka-CH2) , 3.63 t (J = 7 Hz, 3-fl-CH2) , 5.12 s (1,CH2) , 6.70-7.50 m (aromatic protons). Found, ~ : C
81.1; H 7.1. CIsH19NO. Calculated, %: C 81.5; H 7.2.
1 - P h e n y l - 2 - m e t h y l t r y p t o p h o l (Hb). This compound, with bp 195-210 ~ (1 ram), mp 69-70 ~ and R f 0.46,
was obtained in 57~c yield. UV s p e c t r u m : ~ max 223,267, 285 nm (log s 4.65, 4.14, 4.08). IR s p e c t r u m :
3637 (OH), 1600, 1505 c m -1 (ring s t r e t c h i n g v i b r a t i o n s ) . PMR s p e c t r u m , 5 , ppm: 1.83 s (OH), 2.19 s (2-
CH3), 2.90 t (J = 7 Hz, 3-~-CH2), 3.70 t (J = 7 Hz, 3-~ -CH2), 6.90-7.50 m (aromatic p r o t o n s ) . Found, %:
C 80.3; H 6.6. C17H17NO. Calculated, %: C 81.2; H 6.8.
1,2-Dimethyltryptophol (IIc). This compound, with bp 170-180 ~ (1 mm) and Rf 0.47, was obtained in
41% yield. UV s p e c t r u m : k m a x 229, 284 nm (log s 4.61, 3.87). IR s p e c t r u m (liquid film): 3400 (OHbonded),
1610, 1480 c m -1 (ring s t r e t c h i n g v i b r a t i o n s ) . PMR s p e c t r u m , 6 , ppm: 2.03 s (OH), 2.23 s (2-CH3) , 2.77 t
(J = 7 Hz, 3-c~-CH2) , 3.47 (1-CH3), 3.56 t (J = 7 Hz, 3-fl-CH2), 6.8-7.3 m (aromatic protons). Found, %:
C 74.8; H 8.0; N 7.3. C12H15NO. Calculated, %: C 76.2; H 8.0; N 7.4.
1 - I s o p r o p y l - 2 - m e t h y l t r y p t o p h o l (IId). This compound, with Rf 0.49, was obtained in 55% yield. UV
s p e c t r u m , ~ max: 230,284 nm (log s 4.53, 3.81). IR s p e c t r u m : 3600 (OH), 1600, 1500 c m -I (ring s t r e t c h -
ing v i b r a t i o n s . PMR s p e c t r u m , 5, ppm: 1.53 d [J = 8 Hz, (CH3)2C], 1.79 s (OH), 2.30 s (2-CH3) , 2.81 t (J =
7 Hz, 3-~-CH2) , 3.61 t (J = 7 Hz, 3-fl-CH2) , 4.58 m (1-CH), 6.8-7.4 m ( a r o m a t i c protons). Found, %. C
77.2; H 8.8. Ct4H19NO. Calculated, %: C 77.4; H 8.8.
1 - P h e n y l - 3 - m e t h y l - 4 - ( 2 - h y d r o x y e t h y l ) - 5 - p y r a z o l o n e . This compound was obtained f r o m phenyl-
hydrazine h y d r o c h l o r i d e . A f t e r r e m o v a l of the solvent f r o m the r e a c t i o n m i x t u r e , the r e s i d u e was dissolved
in h y d r o c h l o r i c acid (1 : 1), and the solution was washed s e v e r a l t i m e s with c h l o r o f o r m . It was then made
alkaline with KOH until the initially f o r m e d e m u l s i o n had dissolv.ed, a f t e r which it was washed s e v e r a l t i m e s
with c h l o r o f o r m . The alkaline solution was n e u t r a l i z e d with acetic acid and e x t r a c t e d with c h l o r o f o r m . The
solution of the p y r a z o l o n e in c h l o r o f o r m was f i l t e r e d through a l a y e r of aluminum oxide, the solvent was
evaporated, and the r e s i d u e was obtained in 65qc yield as a c h r o m a t o g r a p h i c a l l y p u r e s a m p l e with bp 209-
211 ~ (2 mm) (dec.) and R f 0 2 3 [ b e n z e n e - i s o p r o p y l alcohol (9:1)]. UV s p e c t r u m : ~ max 248 nm (log s 4.23).
IR s p e c t r u m (in KBr): 3400 (OHbonded), 1700 c m -1 (C = O ) . Found, %. C 65.2; H 6.3. C12H14N202. C a l c u -
lated, %: C 66.0; H 6.5.

* H e r e and e l s e w h e r e , the yields indicated a r e for the products obtained a f t e r distillation.

r The abbreviations u s e d h e r e and e l s e h w e r e a r e as follows : s , singlet; d, doublet; t, t r i p l e t ; m, multiplet.

18o
 LITERATURE CITED
1. L . B . Dmitriev and I. I. Grandberg, Izv. Sel'skokhoz. Akad. imeni Timiryazeva, 5, 206 (1973).
2. I . I . Grandberg, A. N. Kost, and A. P. Terent'ev, Zh. Obshch. Khim., 2/7, 3342 (1957).
3. I . I . Grandberg and T: P. Moskvina, Khim. Geterotsikl. Soedin., 1366 (1972).
4. I . I . Grandberg, Izv. Sel'skokhoz. Akad. imeni Timiryazeva, 5, 188 (1972).
5. H. Wamhoff and F. Korte, Bet., 99, 2962 (1966).
6. I . I . Grandberg and S. N. Dashkevich, I<him. Geterotsild. Soedin., 342 (1971).
7. I . I . Grandberg, D. V. Sibiryakova, and L. V. Brovkin, Khim0 Geterotsikl. Soedin., 94 (1969).

181
INDOLE DERIVATIVES
XC .* PREPARATION OF INDOLES WITH A SUBSTITUENT IN THE
BENZENE RING FROM THE CORRESPONDING 2-NAPHTHOLS

G . N. P e t r o v a , V. F. Shner, UDC 547.757:542.943

L . M. A l e k s e e v a , a n d N. N. S u v o r o v

7-Nitroindole, 5-methoxyindole, and 6-methoxyindole were synthesized by oxidation of 2-

naphthol derivatives with hydrogen peroxide to the corresponding o-carboxycinnamic acids
and cyclization of their amides under the conditions of the Hofmann reaction.

We have previously reported [2] a new method for the preparation of indole and 5-bromoindole by
oxidative opening of the hydroxyl-containing ring of the corresponding 2-naphthols with subs equent closing
of the heterocycle. This method seems of promise to us in connection with the accessibility of naphthalene
derivatives and the possibility of obtaining indoles with a strictly determined position of the substituent by
this method.
In the present r e s e a r c h we have studied the possibility of extending the method, having selected as
starting materials 6-, 7-, and 8-substituted 2-naphthols with substituents {nitro and methoxy groups) that
differ sharply with r es pe c t to their electronic effect on the aromatic system.
The oxidative cleavage of 8-nitro-2-naphthol (Ia) with hydrogen peroxide in acetic acid proceeds
smoothly. Acid IIa, which is converted to lactone Va only on heating, is formed in high yield. Previously
[2], in an attempt to obtain the isomeric 6-nitro acid we isolated only the corresponding lactone; this indi-
cates the substantial s t e r i c strain [3] in the molecules of this acid because of disruption of the coplanarity
of the s y s tem, Oxidation of methoxynaphthols (Ib, c) does not proceed so unambiguously. The yields of the
corresponding acids (Hb, c} are low, although they may be raised somewhat if the reaction is c a r r i e d out
at lower t e m p e r a t u r e s . A low yield for 2,6-dihydroxynaphthalene and its monomethyl ether was also noted
in [4]. The presence of electron-donor substituents in the naphthol molecule apparently hinders the pro-
duction of the corresponding o-carboxycinnamic acids.
Two doublets from vinyl protons with the s p i n - s p i n coupling constant (J = 16 Hz) characteristic for
trans-o-carboxycinnamic acids [3] are observed in the PMR spect ra of Ha, c.
When acids IIa,b,c are fused with phosphorus pentachloride and then treated with ammonia, they are
converted to trans-diamides (IIIa,b,c), which cyclize to indoles (IVa,b,c) under the conditions of the Hofmann
reaction. This transformation can also be realized through a step involving the urethane (VI). In the suc-
ceeding steps of the synthesis, i.e., in the II--~ IV conversion, we did not note a substantial effect of the sub-
stituent on the course of the p r o c e s s .
Thus the proposed method for the synthesis of substituted indoles from 2-naphthols is sufficiently
general for the preparation of indoles with different substituents in the 5, 6, and 7 positions. The possi-
bility of its practical realization depends pri m ari l y on the ease of formation of o-carboxycinnamic acids
by oxidative cleavage of the naphthols. There are also quite convenient methods [5] for the synthesis of 5-
and 7-substituted indoles, but the proposed method is simpler than the known methods [5, 6] in the synthesis
of 6-substituted indoles. The question of the use of this method for the preparation of 4-substituted indoles

* See [1] for communication LXXXIX.

D. I. Mendeleev Moscow Chemical-Engineering Institute. Translated from Khimiya Getarotsikli-
cheskikh Soedinenii, No. 2, pp. 207-210, February, 1974. Original article submitted January 22, 1973.

9 19 75Plenum Publishing Corporation, 227 West 17th Street, New York, N.Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, o r transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy of this article is availablefrom the publisher for $15.00.

182
 ~::OOH H /CONH}
H,
.~'--...~c=c~,~ ~"-~c=c<~ H _ _ ~
X
X-- H ~ ~,.CON H2

I a-C II a - C III a-C IV a - C

~ . . c . . ( c " c c~176 c~-~c.=c.~.cooc.~

~

Ya VI C

I a X=8--NO~. b X=c-OCH3. c X=7-OCH3; II m X = 3 - N O 2, b X = 5 - O C H 3, c X=4-OCH$;

III I X=3-NO2. bX=5-OCH~ ' cX=4-OCH~; IVa X = 7 - N O 2, b X ~ 5 - O C a 3, c X=6-OCH3;

V a X=3-NO2; VI c X=4-OCH~;

r e m a i n s open despite an u n s u c c e s s f u l attempt [2] to s y n t h e s i z e 4-nitroindole and will be the subject of s p e -

cial investigations.
As d e m o n s t r a t e d by our e x p e r i m e n t s , in c o n t r a s t to the l i t e r a t u r e data [7], not only 5- and 8 - n i t r o - 2 -
naphthylamines but also 4 - n i t r o - 2 - n a p h t h y l a m i n e and 4 , 5 - d i n i t r o - 2 - n a p h t h y l a m i n e are f o r m e d in the n i t r a -
tion of 2-naphthylamine.

EXPIgRIMENTAL
The IR s p e c t r a of mineral oil suspensions were r e c o r d e d with a UR-10 s p e c t r o m e t e r . The PMR
s p e c t r a of deuterodimethyl sulfoxide solutions were r e c o r d e d with a C - 6 0 - H L s p e c t r o m e t e r with an o p e r a t -
ing frequency of 60 MHz with t e t r a m e t h y l s i l a n e as the internal s t a n d a r d .
3 - N i t r o - 2 - c a r b o x y c i n n a m i c Acid (Ha). A total of 40 ml of 40~c H202 was added to a solution of 3.8 g
(0.02 mole) of Ia and 60 mg of Na2MoO4 in 50 ml of acetic acid, and the mixture was allowed to stand at 40 ~
for 4 d a y s . It was then v a c u u m e v a p o r a t e d at 30 ~ to 5 ml, 40 ml of w a t e r was added, and after 30 min at
about 0~ as in [2], 2.7 g (57~ of IIa with mp 193-194 ~ was obtained. IR s p e c t r u m : 1670, 1740 (CO) c m -l.
PMR s p e c t r u m : doublet at 6.5 ppm (1 H, J = 16 Hz) and doublet at 8.1 ppm (1 H, J = 16 Hz). Found, %: C
50.5; H 3.2; N 6.0. CIoH7NO 6. Calculated, %: C 50.6; H 3.0; N 5.9. According to [4], this compound has
mp 188-189 ~ .
N - L a c t o n e of 3 - N i t r o - 2 - c a r b o x y c i n n a m i c Acid (Va). A solution of 0.2 g (0.001 mole) of acid IIa in
10 ml of acetic acid was heated at 55-60 ~ for 1 h, after which it was vacuum evaporated to 3 ml and filtered
to give 0.13 g (63~c) of Va with mp 157-158 ~ (from water). IR s p e c t r u m : 1750, 1780 (CO) cm -1. Found, %:
C 50.4; H 2.8; N 6.0. C~0HTNO6. Calculated, %: C 50.6; H 3.0; N 5.9.
5 - M e t h o x y - 2 - c a r b o x y c i n n a m i c Acid (IIb). As in the preceding experiment, 7 ml of 93% H202 in 7 ml
of acetic acid was added to a solution of 2.8 g (0.016 mole) of Ib in 40 ml of acetic acid, after which the
mixture was allowed to stand at 25 ~ for 3 days and worked up to give 1.4 g (40%) of IIb with mp 206-207 ~
IR s p e c t r u m : 1675, 1695 (CO) c m -1. Found, %: C 69.6; H 4.5. CHH~005. Calculated, %: C 59.5; H 4.5.
According to [4], this compound has mp 186-187 ~

4 - M e t h o x y - 2 - c a r b o x y c i n n a m i c Acid (1]c). As in the preceding experiment, 6 g (0.037 mole) of Ic was

oxidized with 15 ml of 93% H202, and the reaction mixture was allowed to stand at 25-28 ~ f o r 3 days and
worked up to give 3.3 g (43~c) of IIc with mp 195-196 ~ (dec.). IR s p e c t r u m : 1690, 1710 (CO) c m -I. PMR
s p e c t r u m : doublet at 6.3 ppm (1 H, J = 16 Hz) and doublet at 8.3 ppm (1 H, J = 16 Hz). Found, %: C 59.3;
H 4.3. C~lHl005. Calculated, %: C 59.5; H 4.5.

Diamide of 3 - N i t r o c a r b o x y c i n n a m i c Acid (IIIa). This compound, with mp 306-308 ~ (dec., f r o m alcohol),

was obtained in 81% yield by the method in [2] 12y fusing IIa with PC15 at 110 ~ IR s p e c t r u m : 1630, 1675
(CO), 3370, 3405, 3180 (NH) c m -1. Found, ~c: C 50.8; H 4.0; N 17.6. Ct0HgN~O4. Calculated, %: C 51.0; H
3.9; N 17.9.

Diamide of 5 - M e t h o x y - 2 - c a r b o x y c i n n a m i c Acid (IIIb). This compound, with mp 237.5-238 ~ (from

water)', was obtained in 66v/c yield by fusing IIb with PC15 at 115 ~ IR s p e c t r u m : 1670, 1695 (CO), 3200,
3330, 3410 (NH) c m - l . PMR s p e c t r u m : doublet at 6.6 ppm (1 H, J = 16 Hz) and doublet at 7.9 ppm (1 H,
J = 16 Hz). Found, %: C 60.0; H 5.5; N 12.5. CIIHI2N203. Calculated, ~ : C 60.0; H 5.5; N 12.7.

183
 D i a m i d e of 4 : M e t h o x y - 2 - c a r b o x y c i n n a m i c Acid (IIIc). This compounds, with mp 224-225 ~ (from water),
was obtained in 86% yield by fusing IIc with PC15 at 80~ IR s p e c t r u m : 1665, 1695 (CO), 3200, 3330, 3400
(NH) c m -1. PMR s p e c t r u m : doublet at 6.4 p p m (1 H, J = 16 Hz) and doublet at 7.7 ppm (1 H, J = 16 Hz).
Found, %: C 60~2; H 5.5; N 12.8. CllHI~N203. Calculated, %: C 60.0; H 5.5; N 12.7.
4 - M e t h o x y - N , N ~ - d i c a r b o m e t h o x y - 2 , w - d i a m i n o s t y r e n e (VIc). As in [2], 0.3 g (0.001 mole) of IIIc gave
0.08 g (30%) of VIc with mp 180-181 ~ (from w a t e r ) . IR s p e c t r u m : 1710, 1720 (CO), 3330, 3410 (NH) c~/h-~.
Found, %: C 55.5; H 5.74; N 10.2. C13H16N205. Calculated, %: C 55.7; H 5.8; N 10.0.
7-Nitroindole (IVa). This compound, with mp 95-97 ~ was obtained in 60% yield by the method in [2].
IR s p e c t r u m : 3400 (NH) c m -~. According to [7], this compound has mp 95-97 ~
5-Methoxyindole (IVb). This compound was obtained f r o m IIIb by the method in [2]. Compound IVb
could be isolated f r o m the r e a c t i o n m a s s a f t e r t r e a t m e n t with NaOC1 by s t e a m distillation or e x t r a c t i o n
with c h l o r o f o r m or b e n z e n e . The yield was 42%. The product did not d e p r e s s the melting point of an
authentic s a m p l e and had a c o m p l e t e l y identical IR s p e c t r u m : 3400 (NH) c m -~ .
6-Methoxyindole (We). This compound, with mp 91.5-92 ~ was obtained in 36~c yield f r o m IIIc as in
the p r e c e d i n g e x p e r i m e n t . IR s p e c t r u m : 3400 (NH) c m -1 . According to [9], this compound has mp 92 ~
6-Methoxy-2-naphthol (Ib). Absolute t e t r a h y d r o f u r a n (20 ml) and 4.74 g (0.02 mole) of 6 - b r o m o - 2 -
naphthol methyl e t h e r w e r e added s u c c e s s i v e l y to 0.61 g (0.025 mole) of Mg activated with iodine, a f t e r
which the m i x t u r e was heated until an e x o t h e r m i c r e a c t i o n began. At the end of spontaneous refluxing, the
m i x t u r e was h e a t e d for another 15-20 min, cooled to - 8 to - 1 0 ~ Air, purified by passing through g r a n u -
latedKOH, was then p a s s e d through the m i x t u r e for 2 h, and it was then poured into 150 m l of w a t e r . The
aqueous m i x t u r e was acidified with HC1 and e x t r a c t e d with e t h e r . The e t h e r e x t r a c t was e x t r a c t e d r e -
peatedly with 5% KOH, and CO 2 was bubbled into the alkaline e x t r a c t s until the pH was about 8. The m i x -
t u r e was f i l t e r e d to give 1.2 g (36%) of Ib with mp 147-148 ~ (from alcohol) (mp 145-147 ~ [10], mp 150-151 ~
[111).
7-Methoxy-2-naphthol (Ic). A 6.25 ml (0.064 mole) s a m p l e of dimethyl sulfate was added dropwise
to a solution of 10 g (0.063 mole) of 2,7-dihydroxynaphthalene in 36 ml of w a t e r and 65 ml of 1 N NaOH,
a f t e r which the m i x t u r e was s t i r r e d for 6 h and allowed to stand overnight. The p r e c i p i t a t e was r e m o v e d
by filtration and s t i r r e d with 5% KOH. The alkaline m i x t u r e was filtered, and the alkaline f i l t r a t e was
acidified. The p r e c i p i t a t e was r e m o v e d by filtration and dried to give 5.08 g (47~c) of Ic with bp 189 ~ (3 mm)
and mp 117-117.5 ~ (aqueous alcohol) (mp 117 ~ [12]).
8 - N i t r o - 2 - n a p h t h a l e n e , 4 - N i t r o - 2 - n a p h t h y l a m i n e , and 4 , 5 - D i n i t r o - 2 - n a p h t h y l a m i n e . The sulfuric
acid m o t h e r liquor a f t e r s e p a r a t i o n of the p r e c i p i t a t e d 5 - n i t r o - 2 - n a p h t h y l a m i n e obtained by nitration [2] of
5 g of 2 - n a p h t h y l a m i n e was n e u t r a l i z e d at 0~ with 25% NH4OH. The p r e c i p i t a t e was r e m o v e d by filtration
and e x t r a c t e d with 0.1 N HC1. The acid e x t r a c t was n e u t r a l i z e d with a m m o n i a , and the p r e c i p i t a t e (1.2 g)
was placed in a column filled with 70 g of A120 ~ and eluted s u c c e s s i v e l y with e t h e r - p e t r o l e u m e t h e r (10:1)
to give 0.6 g ( 8 ~ c ) of 8 - n i t r o - 2 - n a p h t h y l a m i n e with mp 103-104 ~ (the acetyl d e r i v a t i v e had mp 195.5~
0 9 g (overall yield 21.2%) of 5 - n i t r o - 2 - n a p h t h y l a m i n e with mp 144-145 ~ (the acetyl d e r i v a t i v e had mp
185.5), 0.1 g (1.5%) of 4 - n i t r o - 2 - n a p h t h y l a m i n e with m p 96-98 ~ (the acetyl d e r i v a t i v e had mp 241~ and
0.15 g (2.3%) of 4 , 5 - d i n i t r o - 2 - n a p h t h y l a m i n e had mp 230-232 ~ (the acetyl d e r i v a t i v e had m p 296-297~ A c -
cording to [13], 8 - n i t r o - 2 - n a p h t h y l a m i n e has mp 103.5-105 ~ (the acetyl d e r i v a t i v e has mp 195.5~ 4 - n i t r o -
2-naphthylamine has mp 98.5 ~ (the acetyl d e r i v a t i v e has mp 241"), and 4 , 5 - d i n i t r o - 2 - n a p h t h y l a m i n e has mp
232 ~ (the acetyl d e r i v a t i v e has mp 296~
8 - N i t r o - 2 - n a p h t h o l (Ia). This compound, with mp 143-144.~ (mp 144-145 ~ [13]), was obtained in 70%
yield by the method in [14]. -
LITERATURE CITED
1. V . P . Gorbunova and N. N. Suvorov, Khim. G e t e r o t s i k l . Soedin., 1519 (1973).
2. G . N . P e t r o v a , V. F. Shner, L. M. A l e k s e e v a , and N. N, Suvorov, Khim. G e t e r o t s i k l . Soedin., 753
(1973).
3. G . A . Elvidge and D. g . Jones, J. Chem. Soc., C, 2059 (1967).
4. D . F . Dewining and D. Woodcock, J . C h e m . Soc., 531 (1958).
5. R . J . Sundberg, The C h e m i s t r y of Indoles, A c a d e m i c P r e s s (1970).
6. M . N . P r e o b r a z h e n s k a y a , Usp. Khim., 36, 1760 (1967).
7. H: H. ttodgson and W. Davey, J . C h e m . Soc., 348 (1939).

184
 8. J. Thesing, G. Semler, and G. Mohr, Chem. Bet., 9.55,2205 (1962).
9. K . G . Blaikie and W. H. Perkin, J . Chem. Soc., 12__55,296 (1924).
10. R . L . Kidwel and D. S. Darling, Tetrahedron Left., 531 (1966).
11. H . E . French and K. Sears, J. Am. Chem. Soc., 7___00,1279 (1948).
12. O. Fischer and F. Hammerschmidt, J . P r a k t , Chem., 94{2____),24 (1916).
13. N. Donaldson, Chemistry and Technology of Compounds of the Naphthalene Series [Russian transla-
tion], Moscow (1963).
14. H . H . Hodgson and F. Walker, J. Chem. Soc., 1620 (1933).

185
I N D O Llg D E R I V A T I V E S
XCI.* 3-INDOLYLPHENYLACETIC ACID

V. N. Rusinova, Yu. I. Smushkevich, UDC 547.757:542.958,3.4:630.54

O. V. Telenkova, M. V. Vasin, and N. N. Suvorov

Reaction of 3 - ( e - m e t h y l a m i n o b e n z y i ) i n d o l e (I) with p o t a s s i u m cyanide in a s t r e a m of c a r b o n

dioxide g a v e 3-indolylphenylacetenitrile (II), which was c o n v e r t e d to 3-indolylphenylacetic
acid (r~I) by alkaline h y d r o l y s i s . The acid has h e r b i c i d a l action but does not have an anti-
b a c t e r i a l effect.

R e p l a c e m e n t of one of the phenyl groups by a h e t e r o a r o m a t i c group in diphenylacetic acid d e r i v a t i v e s

m a y lead to f a v o r a b l e changes in the s p e c t r u m of p h a r m a c o l o g i c a l action [2]. In this connection, we have
c a r r i e d out the s y n t h e s i s of 3-indolylphenylacetic acid (III).

C6H~CH=N__CH3
NHCH3 ~ ~[~N~J CN
H H H
I II

tt It
I|l |V

As we have p r e v i o u s l y shown, amine I r e a c t s with KCN in the p r e s e n c e of a i r oxygen to give only in-
significant amounts of n i t r i l e II [3, 4]. C a r r y i n g out the r e a c t i o n in a s t r e a m of c a r b o n dioxide made it p o s -
sible to exclude contact with oxygen and r e d u c e the alkalinity of the m e d i u m ; this enabled us to obtain II in
quantitative yield [5]. (The u s e of the adipate r a t h e r than the f r e e b a s e and c a r r y i n g out the r e a c t i o n in a
s t r e a m of nitrogen or a r g o n r a i s e d the yield of II only to 41% .) Nitrile II was c h a r a c t e r i z e d by s p e c t r a l
data and reduction to the known ~ - p h e n y l t r y p t a m i n e (IV) [6] by the action of sodium b o r o h y d r i d e in m e t h -
anol in the p r e s e n c e of Raney nickel [7]. Alkaline h y d r o l y s i s of II in ethylene glycol leads 'to acid III in 9(fie
yield (in a s t r e a m of an i n e r t g a s to exclude the f o r m a t i o n of oxidation products [4]). Acid III was c h a r a c -
t e r i z e d by the p r e p a r a t i o n of d e r i v a t i v e s .
T e s t s showed that the sodium s a l t of acid III does not s t i m u l a t e the growth of plants but has h e r b i c i d a l
activity. According to the data of T. N. Zykova and T. A. G u s ' k o v a ( D e p a r t m e n t of C h e m o t h e r a p y of the
S. Ordzhonikidze All-Union S c i e n t i f i c - R e s e a r c h P h a r m a c e u t i c a l - C h e m i s t r y Institute), acid III in c o n c e n t r a -
tions of 1000 / 4 g / m l does not inhibit the growth of t u b e r c u l a r bacilli (H-37 RV strain) and does not have
fungicidal action.
- P h e n y l t r y p t a m i n e IV does not have r a d i a t i o n - p r o t e c t i o n p r o p e r t i e s .

EXP~RIME NTAL
The IR s p e c t r a of m i n e r a l oil s u s p e n s i o n s or c h l o r o f o r m solutions w e r e r e c o r d e d with a UR-10 s p e c -
t r o m e t e r . The UV s p e c t r a of alcohol solutions w e r e r e c o r d e d with an SF-4A s p e c t r o p h o t o m e t e r .
* See [1] for c o m m u n i c a t i o n XC.
D. I. Mendeleev Moscow C h e m i c a l - E n g i n e e r i n g Institute. T r a n s l a t e d f r o m K h i m i y a G e t e r o t s i k l i c h e s k i k h
Soedinenii, No. 2, pp. 211-213, F e b r u a r y , 1974. Original a r t i c l e s u b m i t t e d D e c e m b e r 20, 1972.

9 1975Plenum Publishing Corporation, 227 West 17th Street, New York, N.Y. lOOI1. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy of this article is availablefrom the publisher for $15.00.

186
 3-Indolylphenylacetonitrile (II). A 9,6 g (0.04 mole) s a m p l e of a m i n e I [3] was d i s s o l v e d in 100 ml of
ethanol and 5 m l of w a t e r , and the solution was s a t u r a t e d at 70-80 ~ with c a r b o n dioxide. A solution of 6.5 g
(0.1 mole) of p o t a s s i u m cyanide in 20 ml of w a t e r was added, and the m i x t u r e was s t i r r e d in a gentle s t r e a m
of c a r b o n dioxide for 4 h and then allowed to stand f o r 12 h. The inorganic p r e c i p i t a t e was r e m o v e d by fil-
t r a t i o n and washed with alcohol. Nitrile II was p r e c i p i t a t e d by adding w a t e r to the alcohol f i l t r a t e . The
yield of p r o d u c t with mp 113-114 ~ ( e t h e r - c y c l o h e x a n e ) was quantitative. Found, %: C 82.8; H 5.2; N 12.0.
CI6H12N2. Calculated, %: C 82.7; H 5.2; N 12.16. UV S p e c t r u m , A max, nm ( l o g e ) : 272 (4.084), 278 (4.092),
288 (4.020). IR s p e c t r u m : 3390 ( N - H ) , 2270 ( C ~ N) c m - t .
2 - ( 3 ' - I n d o l y l ) - 2 - p h e n y l e t h y l a m i n e (IV). A solution of 0.59 g of NaBH 4 in 2.23 ml of 8 N NaOH was
a d d e d in the c o u r s e of 10 rain at 40-45 ~ to a m i x t u r e of 3 g (0.013 mole) of nitrile II, 1.01 g of Raney nickel,
and 11.4 ml of methanol, a f t e r which the m i x t u r e was s t i r r e d for another 30 min, and the c a t a l y s t was r e -
m o v e d by f i l t r a t i o n and washed with methanol. The f i l t r a t e was e v a p o r a t e d to d r y n e s s , and the r e s i d u e was
e x t r a c t e d with methylene c h l o r i d e until the e x t r a c t gave a negative t e s t with E r l i c h ' s r e a g e n t . The solvent
was r e m o v e d by distillation, and the r e s i d u e was c r y s t a l l i z e d f r o m benzene to give 2.15 g (70~c) of amine IV
with mp 131-132 ~ (mp 130.5-131.5 ~ [6]). Found, %: C 81.4; H 6.8; N 11.5. C16H16N2. Calculated, %: C 81.3;
H 6.8; N 11.9. UV s p e c t r u m , k m a x , n m (log e ): 222 (4.52), 280 (3.745), 290 (3.680). The h y d r o c h l o r i d e of
a m i n e IV was obtained by the action of a 5% alcohol solution of HC1 on a solution of amine IV in anhydrous
benzene (pH 6.5-7.0). The yield of h y d r o c h l o r i d e with mp 225-226 ~ (dec.) was quantitative. Found, ~ : C
70.5; H 6.3; N 10.5; C1 13.01. ClsHi6N 2 9 HC1. Calculated, ~c: C 70.5; H 6.3; N 10.2; C1 13.0.
3-Indolylphenylacetic Acid (liD. A. A 2.5 g s a m p l e of p o t a s s i u m hydroxide and 5 g of nitrile II w e r e
d i s s o l e d in 80 ml of ethylene glycol, and the solution was heated at 150-160 ~ in a s t r e a m of nitrogen until
a m m o n i a evolution c e a s e d {18-20 h). It was then diluted with a double volume of w a t e r and e x t r a c t e d with
e t h e r to r e m o v e the oily p r o d u c t s . The aqueous solution was cooled and acidified with h y d r o c h l o r i c acid,
and the p r e c i p i t a t e d acid was r e m o v e d by filtration, washed with water, dried, and r e c r y s t a l l i z e d f r o m
b e n z e n e - e t h y l a c e t a t e to give 4.8 g (90%) of acid III with mp 175-176.5 ~ Found, %: C 76.3; H 5.3; N 5.7.
C16Hi3NO 2. Calculated, ~c: C 76.5; H 5.2; N 5.6. IR s p e c t r u m : 1710 (COOH), 3450 ( N - H ) c m -~.
B. A solution of 0.5 g of KOH in 3 ml of w a t e r was added to a solution of 0.25 g of II in 10 m l of
ethanol, and the m i x t u r e was refluxed until a m m o n i a evolution c e a s e d (33 h). The s o l v e n t was r e m o v e d by
distillation, 10 ml of w a t e r was added to the r e s i d u e , and the aqueous m i x t u r e was e x t r a c t e d with e t h e r .
The aqueous solution was acidified with h y d r o c h l o r i c acid, and the p r e c i p i t a t e was r e m o v e d by filtration
and t r e a t e d with s odium b i c a r b o n a t e solution. Acidification with h y d r o c h l o r i c acid gave 0.23 g (85%) of
acid III. The solid [0.03 g (10.5%) ] that was isoluble in sodium b i c a r b o n a t e solution was found to be 2 - e t h o x y -
3-benzoylindole [4J. The e t h e r solution yielded 0.01 g (4.2%) of 3-benzoylindole.
Methyl 3-Indolylphenylacetate (V). A 2.5 g (10 mmole) s a m p l e of acid III was added in portions with
s t i r r i n g and cooling to an e t h e r solution containing 15-20 m m o l e of diazomethane. The m i x t u r e was then
s t i r r e d f o r another hour, a f t e r which p e t r o l e u m e t h e r was added. The p r e c i p i t a t e was r e m o v e d by f i l t r a -
tion and r e c r y s t a l l i z e d f r o m e t h e r - p e t r o l e u m e t h e r to give 2.2 g (83%) of methyl e s t e r V with mp 69-70 ~
Found, %: C 77.2; H 5.9; N 5.3. Ci7HisNO2. Calculated, %: C 77.0; H 5.7; N 5.3. IR s p e c t r u m (CHC13, c o n -
c e n t r a t i o n 0.5~c, d = 1.0 m m ) : 1740 (C ~-~O), 3490 ( N - H ) c m - t .

Ethyl 3-Indolylphenylacetate (VI). A solution of 1 g of III in 25 ml of ethanol was refluxed with s t i r -

r i n g for 19 h with 0.5 g of KU-2 r e s i n in the H f o r m . The r e a c t i o n was m o n i t o r e d by c h r o m a t o g r a p h y in a
thin l a y e r of a l u m i n u m oxide. At the end of the r e a c t i o n , the KU-2 r e s i n was s e p a r a t e d by filtration, the
solvent was r e m o v e d by distillation, and the r e s i d u e was r e c r y s t a l l i z e d f r o m e t h e r - c y c l o h e x a n e to give
0.77 g (69%) of VI with mp 92-93 ~ Found, ~ : C 77.6; H 6,2; N 5.1. CisH17NO 2. Calculated, ~ : C 77.6; H
6.1; N 5.0. IR s p e c t r u m : 1715 (C----~O), 3370 ( N - H ) c m -~.
3-Indolylphenylacetic Acid Diothylamide (VIII). A 0.7 ml (5 mmole) s a m p l e of t r i e t h y l a m i n e was added
with s t i r r i n g at 0~ to a solution of 1.25 g (5 mmole) of III in 20 ml of absolute t e t r a h y d r o f u r a n (THF), a f t e r
which the m i x t u r e was s t i r r e d for 10 min, and 5 ml of a 1 M solution of ethyl c h l o r o c a r b o n a t e in absolute
t e t r a h y d r o f u r a n was added at this t e m p e r a t u r e . The m i x t u r e was then s t i r r e d f o r 15-20 min, a f t e r which
0.6 ml (5 mmole) of diethylamine in 3 m l of absolute THF was added. This m i x t u r e was s t i r r e d at r o o m
t e m p e r a t u r e for 1 h, a f t e r which the p r e c i p i t a t e d t r i e t h y l a m i n e h y d r o c h l o r i d e was r e m o v e d by filtration and
the solvent was r e m o v e d by distillation. The r e s i d u e was t r e a t e d with 15 m l of m e t h y l e n e c h l o r i d e . The
methylene chloride solution was washed with sodium b i c a r b o n a t e solution and w a t e r and dried with MgSO 4.
The s o l v e n t was r e m o v e d by distillation, and the r e s i d u e was r e C r y s t a l l i z e d f r o m benzene to give 0.54 g of
a m i d e VIII with mp 160-162 o. Found, %: C 78.8; H 7.2; N 8.9. C20H22N20. Calculated, %: C 78.5; H 7.2; N
9 2 . IR s p e c t r u m : 1630 (C -----O, amide band), 3290 ( N - H ) c m -1.

187
 LITERATURE CITED
lo G. P. Petrova, V. F. Shner, L. M. Alekseeva, and N. N. Suvorov, Khim. Geterotsikl. Soedin., 208 (1974).
2. S. S. Liberman and L. N. Yakhontov, Khim.-Farmats. Zh., 5, 7 (1971).
3. V. N. Rusinova, Yu. I. Smushkevich, and N. N. Suvorov, Trudy MKhTI imeni D. I. Mendeleeva, 6_66,125
(1970).
4o V. N. Rusinova, Yu. I. Smushkevich, T. A. Kozik, and N. N. suvorov, Zh. Organ. Khim., _8, 1735 (1972).
5. N. N. Suvorov, Yu. I. Smushkevich, and V. N. Rusinova, USSR Author's Certificate No. 355,164; Byul.
Izobr., No. 31, 79 (1972).
6. W. E. Noland, G. M. Christensen, G. E. Sauer, and G. S. Dutton, J. Am. Chem. Soc., 77, 456 (1955).
7. R. A. Egli, Helv. Chim. Acta, 5_33,47 (1970) o

188
IODONIUM DERIVATIVES OF HETEROCYCLIC COMPOUNDS
III.* P R E P A R A T I O N AND P R O P E R T I E S OF IODONIUM DERIVATIVES OF INDOLN

B. Ya. Karele, L. E. Treigute, S. V. Kalnin', UDC 547.755.756:541.651

I. P. Grinberga, and O. Yao Neiland

Reaction of indole with phenyl i o d o s o a c e t a t e in alkaline m e d i a leads to the unstable {~- p h e n y l -

iodonioindole betaine, the m o r e s t a b l e t o s y l a t e and fluoborate of which w e r e used for the in-
troduction of a pyridine, quinoline, and isoquinoline molecule into t h e / ~ - p o s i t i o n of indole to
give the c o r r e s p o n d i n g t o s y l a t e s and fluoborates of fl - ( N - p y r i d i n i o ) - , fl-(N-quinolinio)-, and
t3-(N-isoquinolinio)indole. I n t r a m o l e c u l a r c h a r g e t r a n s f e r f r o m the donor indole s y s t e m to
the a c c e p t e r onium s y s t e m s is detected f r o m the UV s p e c t r a l data. The acidity constants of
a n u m b e r of fi - o n i u m d e r i v a t i v e s of indole w e r e d e t e r m i n e d by s p e c t r o p h o t o m e t r y .

In previous p a p e r s one of us [2] mentioned the p o s s i b i l i t y of obtaining fl-phenyliodonioindole betaine

(I). In the p r e s e n t r e s e a r c h we have m a d e a m o r e detailed study of the phenyliodonation of indole and have
studied s o m e p r o p e r t i e s of phenyliodonium d e r i v a t i v e s of indole.
Reaction of indole with phenyl i o d o s o a c e t a t e gave, in good yield, the unstable 13-phenyliodonioindole
betaine (I), which is inclined to undergo e l e c t r i f i c a t i o n and spontaneous d e c o m p o s i t i o n (even explosively on
grinding). T r e a t m e n t of betaine I with e q u i m o l a r amounts of p-toluenesulfonic acid and fluoboric acid gives
the r e l a t i v e l y m o r e s t a b l e fi-phenyliodonioindole t o s y l a t e and fluoborate (IIa, b), which can be s t o r e d for
s e v e r a l days in the cold in the d a r k .
+ @

tl H
I , Ila, b

H
III a-f

a B=N-pyridylx=rso: b B=N-pyr/dyl x=sF,; c B=N-isgquino X=TsO; d B=N-'isoquinolyI

X=BF,; e B=N-quinolyl X=BF,;f s~ N-quinolyl X=clo,.
One should have anticipated that electrophilic attack would o c c u r in the fl - p o s i t i o n of the indole m o l e -
cule [3]. In fact, t r e a t m e n t of IIb with sodium a c e t a t e and s u b s e q u e n t alkaline h y d r o l y s i s of acyloxy d e r i v a -
tive IV gives indoxyl (3-hydroxyindole) (V), which gives indigo (VI) on oxidation b y a i r oxygen; this un-
a m b i g u o u s l y p r o v e s the f o r m a t i o n of I during phenyliodonation of indole.

H H
IV Y Vl

Substitution of the phenyliodonium g r o u p to give the c o r r e s p o n d i n g t o s y l a t e s and fluoborates (IIIa-e)

o c c u r s in the r e a c t i o n of II with nucleophilic r e a g e n t s - pyridine, isoquinoline, and quinoline, fl -(N-qui n-

* See [1] for c o m m u n i c a t i o n II.

Riga P o l y t e c h n i c a l Institute. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 2, pp.

214-219, F e b r u a r y , 1974. Original a r t i c l e s u b m i t t e d J a n u a r y 9, 1973.

9 1975 PlenumPublishing Corporation, 227 West 17th Street, New York, iV. Y. 10011. No part o f this publication may be reproduced, 11
stored in a retrieval system, or transmitted,, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is availablefrom the publisher for $15.00.

189
 olino)indole t o s y l a t e was c o n v e r t e d , without isolation, to p e r c h l o r a t e
IIIf. Thus it was shown to be p o s s i b l e to p r e p a r e a n u m b e r of/~ -
onium d e r i v a t i v e s of indole through its iodonium d e r i v a t i v e s . We
w e r e unable to obtain a sulfonium d e r i v a t i v e in the r e a c t i o n of II with
dimethyl sulfide. Attempts to obtain the c o r r e s p o n d i n g onium b e t -
aines f r o m s a l t s HI w e r e also u n s u c c e s s f u l , s i n c e r e s i n i f i c a t i o n o c -
curs on t r e a t m e n t of t h e m with alkali solution. A s i m i l a r phenomenon
~ c~ +1+1 is also known in the h y d r o l y s i s of c~-pyridinium s a l t s of indole [4],
which a r e obtained by r e a c t i o n of ~ - s u b s t i t u t e d indoles with N-
b r o m o s u c c i n i m i d e and pyridine.
The band of the s t r e t c h i n g v i b r a t i o n s of the N - H bond of the
onium d e r i v a t i v e s in the IR s p e c t r a (Table 1) a r e shifted to the low-
g frequency r e g i o n as c o m p a r e d with unsubstituted indole [5] (3390
c m - i ) ; this is due to the e l e c t r o n - a c c e p t e r p r o p e r t i e s of the onium
groupings, s i n c e it is known that e l e c t r o n - a c c e p t o r substituents,
p a r t i c u l a r l y in the fl - p o s i t i o n of the indole ring, m a r k e d l y l o w e r the
a b s o r p t i o n frequency of the N - H group [5].
~ O
B e onium d e r i v a t i v e s of indole w e r e also c h a r a c t e r i z e d by the
UV s p e c t r a of the compounds in aqueous and aqueous ethanol s o l u -
tions in m e d i a with various pH values (Figs. 1-4). As c o m p a r e d
with the s p e c t r a of indole and its d e r i v a t i v e s [6, 7], the introduction
~mommm of onium groupings into the ~ - p o s i t i o n of indole c a u s e s the a p p e a r -
ance of new a b s o r p t i o n m a x i m a at 300-500 nm, The c h a r a c t e r i s t i c
a b s o r p t i o n bands of the pyridinium, quinolinium, and isoquinolinium
m~mm~au~ s y s t e m s [7] a r e changed. The a b s o r p t i o n m a x i m a of III at 350-400
nm (Figs. 2-4) a r e m a i n l y a s s o c i a t e d with e l e c t r o n t r a n s f e r f r o m the
C donor indole s y s t e m to the pyridinium, quinolinium, and isoquinolini-
u m s y s t e m s . The absorption m a x i m a in the long-wave region (at
NNN N ~dd 450-550 nm} of the a m m o n i u m d e r i v a t i v e s of indole in s t r o n g l y a l -
kaline m e d i a (pH > 12), in which the betaine f o r m s of t h e s e compounds
(VII) a r e f o r m e d , a r e a s s o c i a t e d with i n t r a m o l e c u l a r t r a n s f e r of
c h a r g e f r o m the indole anion to the onium s y s t e m . In the c a s e of
betaine I, the absorption m a x i m u m at 344 nm is evidence for i n t r a -
@ molecular charge transfer.

OH- ~ B~"
o HX

0
Judging f r o m the a b s o r p t i o n m a x i m a , the onium s y s t e m s that
we investigated a r e a r r a n g e d in the following o r d e r with r e s p e c t to
t h e i r a c c e p t o r p r o p e r t i e s : quinolinium (492 n m ) > isoquinolinium
0 (48"6) > ,pyridinium (453) > phenyliodonium (344). The s a m e o r d e r is
0 also o b s e r v e d for the onium betaines of fi - d i c a r b o n y l compounds [8-
10], only in this c a s e the quinolinium betaines display a g r e a t e r "
b a t h o c h r o m i c shift of the gong-wave m a x i m u m than the isoquinolinium
d e r i v a t i v e s (on the a v e r a g e , a shift of 16 nm). The VII s y s t e m is
evidently c o p l a n a r , and the indole portion of the molecule i n t e r a c t s
m o r e with the onium portion.
The o n i u m b e t a i n e s of indole display s o l v a t o c h r o m i s m : the
long-wave m a x i m u m is shifted b a t h o c h r o m i c a l l y as the p o l a r i t y of
the solvent d e c r e a s e s (Table 2).
The acidity constants of s o m e onium d e r i v a t i v e s of indole in
aqueous ethanol solutions (Table 1 ) w e r e d e t e r m i n e d by a s p e c t r e -
p h o t o m e t r i c method [8]. The values of the constants o f IIb and IIIc
a r e a p p r o x i m a t e , s i n c e t h e s e compounds a r e unstable in alkaline

190
 ~gC

3~E

2.5[ . , , , I\ , , , ~
,2,5 ~ ~ ' -~ !
200 ~50 300 350 400 450 X,. 200 250 300 350 400 z60 .500 ks I l r n

Fig. 1. UV s p e c t r a of IIb in 50~c ethanol: Fig. 2. UV s p e c t r a of IIIa in 50~ ethanol:

1) pH 1-10; 2) pH "~ 14. 1) pH 0-10; 2) pH > 14; 3) p H ~ 14.

'goI tgr
4,5
"\

%~,j. %

%S l \ 3,E

"%~r.2 3,C %k "%

2,-~ , I i r ~9 t ,%
200 2~ 300 3so ~oo ~o eco 550 A, n m 200 250 300 350 400 z.50 500 550 ?., "rim

Fig. 3. UV s p e c t r a of IIIf in 50~c ethanol: Fig. 4, UV s p e c t r a of IIIc in 50~ ethanol:

1) pH 0-10; 2) pH ~ 14; 3) pH 12.2. 1) pH 0-11; 2) pH ~ 14.

TABLE 2. Solvatochromis m of fi -Onium Betaines of Indole"

~'rna~, [l.m(ig e)

Compound 1 N K O H in water 1 N K O H in 50% I N K O H in 90%

ethanol ehhanol

IIb I 333 (3,50)* 344 (3,63) 360 (3,65)

IIIa 427 (3,93) 453 (4,07) 476 (4,08)

*Contains 2% ethanol.

m e d i a . Since t h e r e a r e no data in the l i t e r a t u r e r e g a r d i n g the acidity of indole and one cannot d e t e r m i n e it

by a s i m p l e s p e c t r o p h o t o m e t r i c method (pK > 14), we cannot draw any a c c u r a t e conclusions r e g a r d i n g the
effect of onium groupings on the NH acidity of indole. It is known that the acidity of p y r a z o l e s i n c r e a s e s by
4.7-5 o r d e r s of magnitude [11] when a phenyliodonium group is introduced into the 4 position. A s s u m i n g a
s i m i l a r effect for indole, one can roughly e s t i m a t e the acidity of indole in 50~c ethanol as PKa ~ 17.

EXPERIME NTAL
The IR s p e c t r a of Nujol s u s p e n s i o n s of the compounds w e r e r e c o r d e d with an IKS-14A s p e c t r o m e t e r .
The UV s p e c t r a w e r e r e c o r d e d with SFD-2 and Specord UV-vis s p e c t r o p h o t o m e t e r s . The pH values of
b u f f e r e d solutions w e r e m e a s u r e d with an L P M - 6 0 M pH m e t e r by m e a n s of a glass e l e c t r o d e p a i r e d with
a s i l v e r chloride flow e l e c t r o d e . The optical densities of IIb and IIIc in alkaline m e d i a w e r e e x t r a p o l a t e d
to "zero" t i m e .
fl -Phenyliodonioindole Betaine (I). A solution of 4.7 g (0.04 mole) of i ndole and 11.2 g (0.2 mole) o~
p o t a s s i u m hydroxide in 40 ml of methanol was cooled to 0-5 ~ and 12.9 g (0.04 mole) of finely ground phenyl
i o d o s o a c e t a t e [13] was added in s m a l l portions with vigorous s t i r r i n g in the c o u r s e of 1.5 h. A f t e r all of
the phenyl i o d o s o a c e t a t e had been added, s t i r r i n g at 0-5 ~ was continued for another 1.5 h. Betaine I (a y e l -
low c r y s t a l l i n e substance) was then r e m o v e d by filtration, washed s u c c e s s i v e l y on the f i l t e r with a s m a l l
amount of c o l d methanol and c h l o r o f o r m , and a i r d r i e d (do not grind - it m a y d e c o m p o s e e x p l o s i v e l y ' ) . It
is r e c o m m e n d e d that the p r o d u c t be used i m m e d i a t e l y for the s u b s e q u e n t r e a c t i o n s , s i n c e it d e c o m p o s e s
rapidly on s t o r a g e . In w o r k with s i z e a b l e amounts of betaine I, it should not be dried c o m p l e t e l y but u s e d
i m m e d i a t e l y a f t e r washing with c h l o r o f o r m . The yield was 9.0 g (70~c).

191
 -Phenyliodonioindole T o s y l a t e (Ha). A s u s p e n s i o n of 9.6 g (0:03 mole) of I in 30 m l of ethanol was
cooled in ice w a t e r , and 5.7 g (0.03 mole)"of p-toluenesulfonic acid m o n o h y d r a t e was added in portions with
s t i r r i n g . C o l o r l e s s I I a gradually p r e c i p i t a t e d f r o m the yellow solution. The r e a c t i o n m i x t u r e was diluted
with 30 m l of absolute e t h e r , and the p r e c i p i t a t e was r e m o v e d by filtration and washed on the filter with
e t h e r to give 12.5 g of a p r o d u c t with mp 94-95 ~ (dec.).
/~ -Phenyliodonioindole F l u o b o r a t e (IIb). A 3.2 g (0.01 mole) s a m p l e of betaine I was added in portions
with s t i r r i n g to 10 m l of an ice w a t e r - c o o l e d 1 N solution of fluoboric acid in ethanol. The r e s u l t i n g d a r k
solution was diluted with 50 m l of absolute e t h e r and allowed to stand at 0-5 ~ for 1 h for c r y s t a l l i z a t i o n .
The c o l o r l e s s c r y s t a l s of IIb w e r e washed with e t h e r to give 3.3 g of a product with mp 91 ~ (dec .).
- ( N - P y r i d i n i o ) - a n d fi-(N-Isoquinolinio)indole Tosylates (IIIa,c) and fi-(N-Quinolinio)indole P e r -
c h l o r a t e (I~f). A m i x t u r e of 2.45 g (0.005 mole) of IIa and 4 ml of pyridine, isoquinoline, or quinoline was
h e a t e d on a w a t e r bath f o r 15 min, a f t e r which the cooled solutions w e r e diluted with 30 m l of absolute
e t h e r and allowed to stand at 0-5 ~ f o r 12 h. The p r e c i p i t a t e d Ilia and lIIc w e r e r e m o v e d by filtration and
washed on the f i l t e r with e t h e r . The e t h e r l a y e r was poured off f r o m the oily ~-(N-quinolinio)indole t o s y l -
ate, and 15 ml of w a t e r and 2 ml of p e r c h l o r i c acid w e r e added to the r e s i d u e . The r e a c t i o n m i x t u r e was
allowed to stand for another day, a f t e r which it was heated to the boiling point, t r e a t e d w i t h activated c h a r -
coal, and refluxed for 5 min." The hot solution was filtered, and the f i l t r a t e was cooled. The b r i g h t - y e l l o w
p r e c i p i t a t e of IIIf was r e m o v e d by filtration.
- ( N - P y r i d i n i o ) - , ~ -(N-Isoquinolinio)-, and fl-(N-Quinolinio)indole Fluoborates (IIIb,d,e). A m i x t u r e
o f 2.0 g (0.005 mole) of I Ib and 3-4 m l of pyridine, isoquinoline, or quinoline was heated on a b o i l i n g - w a t e r
bath for 10 rain. The solutions of IIIb and liIe w e r e cooled and diluted with 15 ml of absolute e t h e r . C o m -
pound IIIb was allowed to stand at 0-5 ~ for 12 h, a f t e r which the light-yellow c r y s t a l l i n e p r e c i p i t a t e , with
mp 144-153 ~ was r e m o v e d by filtration. Compound IIIe was isolated as a d a r k oil; the e t h e r was decanted,
the r e s i d u e was t r e a t e d with 5 m l of absolute ethanol, and the g r e e n i s h - y e l l o w p r e c i p i t a t e of IIIe was r e -
m o v e d by filtration a f t e r 2 h. A g r e e n i s h - y e l l o w p r e c i p i t a t e with mp 180-185 ~ was isolated f r o m the s o l u -
tion .of Hid a f t e r cooling.
C o n v e r s i o n of IIb to Indigo. A m i x t u r e of 0.82 g (0.002 mole) of lib and 0.16 g (0.002 mole) of sodium
a c e t a t e was refluxed in 5 m l of ethanol for 30 rain, a f t e r which 0.11 g (0.002 mole) of p o t a s s i u m hydroxide
was added, and the m i x t u r e was refluxed for 5 min. It was then cooled, and 20 m l of w a t e r was added to the
solution. A i r was bubbled through the solution to a c c e l e r a t e oxidation. The r e s u l t i n g blue p r e c i p i t a t e was
r e m o v e d by filtration to give 0 2 g (76%) of a product with m p 389 ~ (from nitrobenzene) (mp 390-392 ~ [14]).

LITERATURE CITED
1. B. Ya. K a r e l e , S. V. Kalnin', I. P . G r i n b e r g a , and O. Ya. Neiland, Khim. G e t e r o t s i k l . Soedin., 553
(1973).
2. O. Neiland and G. V a n ~ , Dokl. Akad. Nauk SSSR, 141, 872 (1961).
3. R . H . Hinman and J . Lang, T e t r a h e d r o n Lett., 2_11, 12 (1960).
4. T. Kobayashi and N. Inokuchi, T e t r a h e d r o n , 2_00, 2055 (1964).
5. F. Millich and E. I. B e c k e r , J . Org. Chem., 2_33, 1096 (1958).
6. G, M. Badger and B. J . C h r i s t i e , J . C h e m . Soc., 3438 (1956).
7. S . F . Mason, in: P h y s i c a l Methods in H e t e r o c y c l i c C h e m i s t r y , A c a d e m i c (1963).
8. O. Ya. Neiland and S. V. Kalnin', Zh. Organ. Khim., _4, 140 (1968).
9. S . V . Kalnin' and O. Ya. Neiland, Izv. Akad. Nauk LatvSSR, Set. Khim., 43 (1972).
10. S . V . Kalnin' and O. Ya. Neiland, Zh. Organ. Khim., 7, 1605 (1971).
11. B. Ya. K a r e l e , S. V. Kalnin', I. P . G r i n b e r g a , and O. Ya. Neiland, Khim. G e t e r o t s i k l . Soedin., 245
(1973).
12. Ya. L i n a b e r g and A. Veis, Izv. Akad. Nauk L a t v S S R , S e r . Khim., 213 (1962).
13. B. Ya. K a r e l e and O. Ya. Neiland, Izv. Akad. Nauk LatvSSR, Ser. Khim., 587 (1970).
14. Handbook for C h e m i s t s , Vol. 2 [in Russian], Goskhimizdat, M o s c o w - L e n i n g r a d (1951), p. 466.

192
REACTION OF 5 - H Y D R O X Y I N D O L E DERIVATIVES WITH
o-NITROBENZENESULFE NYL CHLORIDE

A . N. G r i n e v , A , K , C h i z h o v , UDC 547.755.756
V. I. Shvedov, and T. F. Vlasova

In the reaction of o-nitrobenzenesulfenyl chloride with 5-hydroxyindole derivatives, electro-

philic substitution occurs in the 3 position. When there is a carbethoxy group in the 3 posi-
tion, the o-nitrobenzenesulfenyl residue enters the 6 position. The corresponding 5-hydroxy
derivatives, the aminomethylation of which leads to 4-dimethylaminomethyl derivatives, were
obtained by hydrolysis of the 5-acetoxy derivatives of o-nitrophenyl 3-indolyl sulfides.

5-Hydroxyindole derivatives undergo electrophilic substitution with o:nitrobenzenesulfenyl chloride

to give o-nitrophenyl 6-indolyl and o-nitrophenyl 3-indolyl sulfides.
Compounds I and II were obtained by heating equimolecular amounts of o-nitrobenzenesulfenyl chlo-
ride and 1,2-dimethyl-3-carbethoxy-5-methoxy- or 1,2-dimethyl-3-carbethoxy-5-hydroxyindole in dioxane.

R " O ~ COOC2H~' ~ S C t R"O~ ~ OOC~'H5

9 ~"-NO 2 . [N(CHa)2]~CH 2
~.N~ ~CH,~ S / " , , ~ / ~ N . / ~CH3
I I I
R' ~ N O ~ R'
I-H

CH2N(CH3)2
R"O~COOC2H
I H202
CH3COOH

~,
O= S ' ~ / " ~'N"/~'CHa
1 I
~ NO2 R' NO2 R'

XI

SC:

'~f~" N/"~CH3 NO 2
I }
R' R'
Ill-IX

CH2N(CH~) ~

=i C
I
R'

I R'=CH3~ N'~CH3; II R"=CHs, R'=~H; IIt R'='CH3, R"=OCHs; IV R'=CH3, R"=

=OCOCH3; V R'=CHa; R"=OH; VI R'~C~Hs, R"=OCOCH~; VII R'=C6H~ R'=OH.
VIII R =CH2C6H~, R =OCOCHs; IX R =CH2C~Hs R"=OH. X I~'=CHo' D"-CH"
R,';/=UH ' . ' ' -- , -- -- ~ o a,

S. Ordzhonikidze All,Union Scientific-Research Pharmaceutical-Chemistry Institute, Moscow. T r a n s -

lated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 220-223, February, 1974. Original article
submitted March 7, 1973.

9 19 75 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N.Y.. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available j~om the publisher for $15.00.

193
 T A B L E 1. o - N i t r o p h e n y l Indolyl Sulfide D e r i v a t i v e s
9 ... ,, i~, ", ,,, ,,

9Calc..,
COrn" x,. ~ i Empirical - {

. *-,r, ~ /,formUi a .
C H N, S

222,4--223,1 C2oH2oN2OsS
I 59,7 5,2 7,2 8,3 602 5,0 7,0 8,0 30
269--270
II C19HIsN2OsS 59,2 4,8 7,2 8,0 59,1 4,7 7,2 I 8,3 34
157,8---158,8 CtrHi6NsOaS
III 61,9 4,9 8,6 9,9 52,2 4,9 85 t 9,8 34
157,7--158,2 CIsHI,N~O4S
IV 80,5 4,9 7,7 9 8,6 60,7 4,5 7,9 { 9,0 60
!83,4--184,0 C,6H~N~OsS
V 60,9 _4'4 ~,8 10,0 61,1 4,5 -- I 10,2 75
143,5--144,5 C=aH~8N~O4S
VI 7,5 -- -- 6,7 [ 7,7 42
VII165--168 C2iHI~NeOaS 7,6 7,7 7,4 8,5 9 5
" dec.,!
VIII 17Zt~I73d C~4H2oN.~O*S 6,5 7,4 6,5 7,4 26
IX 13o,8.--131,3T C22HIsN20~S 74
X 216,6--217,3 C2oH2oN206S 77 T, z 77! 53

* C o m p o u n d s I and III w e r e c r y s t a l l i z e d f r o m alcohol, 1I was c r y s t a l l i z e d

f r o m d i m e t h y l f o r m a m i d e - b e n z e n e , and I V - X w e r e c r y s t a l l i z e d f r o m
acetone.
t T h i s c o m p o u n d was u s e d in t h e t r a n s f o r m a t i o n s w i t h o u t a d d i t i o n a l p u r i -
fication.

T A B L E 2. 4 - D i m e t h y l a m i n o D e r i v a t i v e s of o - N i t r o p h e n y l Indolyl
Sulfides
Corfl
o Found_,~/5 Calc., % !Yield,
pound Mp, "C Empirical formula

Xl 189,2--189,8 C=~H24NaOsS 59,6 5,6

5--- --~ 9,517,5 59,7' 5,5 -- i 9,5i 7,3]
'7.1Z 66
~II 195,5--196,5 C1,H=~NaOaS 61,3 11,2 - [ 6 1 , 4 5,7 - 11,3!- 72
XIIl 190,0--191,0 C24H2aNaOaS lO, l 71 -- -- --I 97i74 98
XIV 187,4--188,4 C2sH2sNaOaS - ;4! 9,317:0 - I - - 9,4 7 2 87
XV 225,6--226,6 CmH~vNaOaS9HC1 101175 I - -- 8,7 10,3 7,9
X,VI 170,0--171,0 C24H=aNaOaS9HCI __ 7,31 89 6 4 , - - -- 7,5 8,9 6,8
XVII 229,5--230,5 C'2sH2sNaOsS9HCl -- 73 881651_ 1--]7'31 8'716'61

* C o m p o u n d s XI, XII, and X I V - X V I I w e r e c r y s t a l l i z e d f r o m a l c o h o l .

The r e a c t i o n of 1 , 2 - d i m e t h y l - 5 - m e t h o x y i n d o l e and v a r i o u s 2 - m e t h y l - 5 - a c e t o x y i n d o l e s with o - n i t r o b e n z e n e -

s u l f e n y l c h l o r i d e in dioxane leads to H I - I X . Sulfides of 5 - h y d r o x y i n d o l e s V, VII, and IX a r e f o r m e d in high
yields in the h y d r o l y s i s of IV, VI, and V I I I with alcoholic alkali. T r a n s i t i o n f r o m a c e t o x y d e r i v a t i v e s IV,
VI, and VIII to 5 - h y d r o x y d e r i v a t i v e s V, VII, and IX is a c c o m p a n i e d by the d i s a p p e a r a n c e of the band of
c a r b o n y l a b s o r p t i o n o f the a c e t o x y g r o u p at 1750-1755 c m -i and the a p p e a r a n c e of the band of a phenolic
h y d r o x y l g r o u p at 3400-3700 c m -1 . 4 - D i m e t h y l a m i n o m e t h y l d e r i v a t i v e s (XI-XIV) and t h e i r h y d r o c h l o r i d e s
(XV-XVII) w e r e obtained by a m i n o m e t h y l a t i o n of 5 - h y d r o x y i n d o l e d e r i v a t i v e s II, V, VII, and IX. o - N i t r o -
phenyl 1 , 2 - d i m e t h y l - 3 - c a r b e t h o x y - 5 - m e t h o x y - 6 - i n d o l y l sulfide f o r m s sulfoxide X on heating with 30%
h y d r o g e n p e r o x i d e in a c e t i c a c i d .
Two s i n g l e t s c o r r e s p o n d i n g to the p a r a p r o t o n s (4-H and 7-H) of the b e n z e n e p o r t i o n of the indole
r i n g a r e o b s e r v e d in the P M R s p e c t r u m of II in (CD3)2SO. This indicates that the o - n i t r o b e n z e n e s u l f e n y l
g r o u p e n t e r s the 6 p o s i t i o n . In addition to the s i g n a l s of the phenyl r i n g , doublets of the 7-H (J7,6 = 8.5 Hz)
and 4 - H (J4,6 = 2.5 Hz) protons and a quartet:of the 6-H proton (J6J = 8.5 Hz, J6,4 = 2.5 Hz) a r e o b s e r v e d in
the a r o m a t i c p o r t i o n of the P M R s p e c t r u m of IV in (CDa)2CO. The s t r u c t u r e s of t h e s e s i g n a l s and the a b -
s e n c e of the s i n g l e t of the 3 - H p r o t o n u n a m b i g u o u s l y p r o v e that the o - n i t r o p h e n y l m e r c a p t o g r o u p o c c u p i e s
the 3 p o s i t i o n in IV. A doublet of the 7-H p r o t o n at 6 7,20 ppm (JT,s = 8.5 Hz), a doublet of the 4-H p r o t o n
at 5 7.11 p p m (J4,? = 2.5 H z ) , a q u a r t e t of a 6-H p r o t o n at 6.74 ppm {J6,7 = 8.5 Hz, J6,4 = 2.5 Hz), and a
s i n g l e t of the 3 - H p r o t o n at 6.15 p p m a r e o b s e r v e d in the P M R s p e c t r u m in (CD3)2CO of 1 , 2 - d i m e t h y l - 5 -
a c e t o x y i n d o l e , u s e d as the s t a r t i n g c o m p o u n d in the s y n t h e s i s of IV.

EXPgRIME NTAL*
The P M R s p e c t r a of the c o m p o u n d s w e r e r e c o r d e d with a J E O L CO J N M - 4 H - 1 0 0 s p e c t r o m e t e r w i t h
t e t r a m e t h y l s i l a n e as the i n t e r n a l s t a n d a r d . The IR s p e c t r a w e r e r e c o r d e d with a P e r k i n - E l m e r 457 s p e c -
t r o m e t e r . The p h y s i c a l c o n s t a n t s and yields of the c o m p o u n d s a r e p r e s e n t e d in T a b l e s 1 and 2.

* The e x p e r i m e n t a l p o t i o n of t h i s r e s e a r c h was a c c o m p l i s h e d with the p a r t i c i p a t i o n of R . A . Z i n o v ' e v a .

194
 0 - N i t r o p h e n y l 1 , 2 - D i m e t h y l - 3 - c a r b e t h o x y - 5 - m e t h o x y - 6 - i n d o l y l Sulfide (D. A mixture of 2.6 g (10.5
mmole) of 1 , 2 - d i m e t h y l - 3 - c a r b e t h o x y - 5 - m e t h o x y i n d o l e [1], 2.0 g (10.5 mmole) of o-nitrobenzenesulfenyl
chloride [2], and 5 ml of dioxane was heated at 100 ~ for 2 h, after which it was cooled to r o o m t e m p e r a t u r e
and filtered to r e m o v e the precipitated I. The p r o d u c t was washed on the filter with cold acetone and dried
in a vacuum d e s i c c a t o r over c a l c i u m c h l o r i d e .

o-Nitrophenyl 1 , 2 - D i m e t h y l - 3 - c a r b e t h o x y - 5 - h y d r o x y - 6 - i n d o l y l Sulfide (]I). A mixture of 6.7 g (28.7

mmole) of 1 , 2 - d i m e t h y l - 3 - c a r b e t h o x y - 5 - h y d r o x y i n d o l e [3], 5A g (28.7 mmole) ~f o-nitrobenzenesulfenyl
chloride, and 11 ml of dioxane was heated at 100 ~ for 1 h, after which it was cooled to r o o m t e m p e r a t u r e
and filtered to r e m o v e the precipitated II. The product was washed on the filter with acetone and dried in a
vacuum d e s i c c a t o r over c a l c i u m chloride. PMR s p e c t r u m , 6, ppm: s* 9.63 (5-OH), 7.74 (7-H), 7.65 (4-H),
3,71 (1-CH3) , 2.73 (2-CH3) , t 1.4 (CH3) , q 4.31 (3-COOCH2CH3) , m 6.79, 7.39, 8.24 (6-o-NO2CsH4S).
o-Nitrophenyl 1 , 2 - D i m e t h y l - 5 - m e t h o x y - 3 - i n d o l y l Sulfide (HI). This compound was obtained by the
method u s e d to p r e p a r e I.

o-Nitrophenyl 1 , 2 - D i m e t h y l - 5 - a c e t o x y - 3 - i n d o l y l Sulfide (IV). A mixture of 1.7 g (8.23 mmole) of 1,2-

d i m e t h y l - 5 - a c e t o x y i n d o l e [4], 1.6 g (8.23 mmole) of o - n i t r o b e n z e n e s u l f e n y l chloride, and 5 ml of dioxane
was heated at 100 ~ for 15 min, and the mixture was then cooled to r o o m t e m p e r a t u r e . The precipitated IV
was r e m o v e d by filtration, washed with a s m a l l amount of cold acetone, and dried in a vacuum d e s i c c a t o r
o v e r c a l c i u m c h l o r i d e . PMR s p e c t r u m , 6 , ppm: s 3.83 (1-CH3) , 2.50 (2-CH3) , 2.18 (5-OCOCH~) t d 7.07
(4-H), 7.47 (7-H), q 6.91 (6-H), m 6.80, 7.30, 8.20 (6 o-NO2CsH4S). IR s p e c t r u m (in m i n e r a l oil): !755 c m -i
(C ~ 0 ) .

Compounds VI and VIII were obtained by the method used to p r e p a r e IV.

o-Nitrophenyl 1 , 2 - D i m e t h y l - 5 - h y d r o x y - 3 - i n d o l y l Sulfide (V). A mixture of 6.8 g {19.1 mm01e) of IV

and 133 ml of 10% p o t a s s i u m hydroxicIe solution in methanol was refluxed at 70~ for 1 h. The solution was
then poured into a threefold volume of water, and the mixture was filtered to r e m o v e a s m a l l amount of a
suspension. The filtrate was acidified with acetic acid until it was weakly acidic (pH ,~ 6), and the V was
r e m o v e d by filtration, washed on the filter with distilled water until it was neutral, and dried in a vacuum
d e s i c c a t o r over P205 at 90 ~ for 24 h. IR s p e c t r u m (in m i n e r a l oil): 3300 c m - l (OH).
Compounds VII and IX were obtained by the method used to p r e p a r e V (Table 1).
o-Nitrophenyl 1 , 2 - D i m e t h y l - 3 - c a r b e t h o x y - 5 - m e t h o x y - 6 - i n d o l y1 Sulfoxide (X). A 3 g (7.49 mmole)
s a m p l e of I was dissolved at 115 ~ with s t i r r i n g in 68 ml of glacial acetic acid, a n d 2 ml of 30% aqueous
hydrogen peroxide with d 2~ 1.1122 (19.62 mmole) was added dropwise, after which the mixture was s t i r r e d
for 1 h and poured into 90 ml of w a t e r . A 6.5 ml s a m p l e of 25% a m m o n i u m hydroxide was added to the m i x -
ture, and the precipitated X was r e m o v e d by filtration.

o-Nitrophenyl 1 , 2 - D i m e t h y l - 4 - c a r b e t h o x y - 4 - d i m e t h y l a m i n o m e t h y l - 5 - h y d r o x y - 6 - i n d o l y l Sulfide (X-t).

A mixture of 0.5 g (1 ~9 mmole) of II, 0.4 g (3.91 mmole) of bisdimethylaminomethane, and 5 ml of d i m e t h y l -
f o r m a m i d e (DMF) was s t i r r e d at 105 ~ for 4 h , a f t e r which it was vacuum evaporated to dryness at 70~. The
r e s i d u e was t r e a t e d with absolute ether, and the c r y s t a l l i n e precipitate of XI was r e m o v e d by filtration.
o-Nitrophenyl 1 , 2 - D i m e t h y l - 4 - d i m e t h y l a m i n o m e t h y l - 5 - h y d r o x y - 3 - i n d o l y l Sulfide (XII). A mixture of
2.0 g (6.36 mmole) of V, 0.9 g (9.19 mmole) of bisdimethylaminomethane, 5 ml of dioxane, and 2 mI of DMF
was heated at 100 ~ for 2.5 h, after which it was vacuum evaporated to d r y n e s s at 70~ Water was added to
the residue, and the precipitated XII was r e m o v e d by filtration and washed with w a t e r .
Compounds XIII and XIV w e r e obtained f r o m VII and IX by the method used to p r e p a r e XII (Table 2).
Hydrochloride of XII (XV). Base XII was dissolved in the m i n i m u m amount of acetone, and a solution
of hydrogen chloride in absolute ether was added. The mixture w a s then t r e a t e d with absolute ether until
the precipitation of h y d r o c h l o r i d e XV was c o m p l e t e . The precipitate was r e m o v e d by filtration, washed on
the filter with absolute ether, and dried over P205 at 10 m m ( m e r c u r y standard) and 90~ for 6 h.
The h y d r o c h l o r i d e s of bases XIII, XIV (XVI and XVII) were s i m i l a r l y obtained (Table 2).

* H e r e and e l s e w h e r e , s is singlet, d is doublet, t is triplet, q is quartet, and m is multiPlet.

195
 LITERATURE CITED
lo A. N. Grinev, I. A. Zaitsev, V. I. Shvedov, and A. P. Terent'ev, Zh. Obshch. Khim., 2_88,447 (1958}.
2. Organic Syntheses, Vol. 2, Wiley (1946}, p. 455.
3. A. N. Grinev, N. K. Kul'bovskaya, and A. P. Terent!ev, Zh. Obshch. Khim., 2_55,1355 (1955).
4. A. N. Grinev, V. I. Shvedov, E. K. Panisheva, N. S. Bogdanova, I. S. Nikolaeva, and G. N. Pershin,
Khim.-Farmats. Zh., 9, 9 (1969).

196
RESEARCH ON T H l g C H E M I S T R Y OF PYRAZOLIDINE
XXI.* PRODUCTS OF THE REACTION OF 4 - A R Y L I D E N E - 1 , 2 - D I P H ~ N Y L -
3,5-DIOXYPYRAZOLIDINES WITH ALKOXIDES AND ALKYLATION OF THEM

B. L. Moldaver and M. E. Aronzon UDC 547.775

Sodium alkoxides r e a d i l y add to the exocyclic double bond of v a r i o u s l y substituted 4 - b e n z y l -

idene d e r i v a t i v e s of 1 , 2 - d i p h e n y l - 3 , 5 - d i o x o p y r a z o l i d i n e to give the sodium s a l t s of 4-{1-
a l k o x y b e n z y l ) - l , 2 - d i p h e n y l - 3 , 5 - d i o x o p y r a z o l i d i n e s , the methylation of which leads to 4-
m e t h y l - 4 - ( 1 - a l k o x y - b e n z y l ) - l , 2 - d i p h e n y l - 3 , 5 - d i o x o p y r a z o l i d i n e s . This c o n f i r m s the p r e -
viously e x p r e s s e d a s s u m p t i o n that the r e a s o n for the s t a b i l i t y of the N - N bond and the e x o -
cyclic double bond of 4 - b e n z y l i d e n e - l , 2 - d i p h e n y l - 3 , 5 - d i o x o p y r a z o l i d i n e in alkaline m e d i a
with r e s p e c t to catalytic h y d r o g e n o l y s i s is the f o r m a t i o n u n d e r t h e s e conditions of a stable
enolate.

We have p r e v i o u s l y e x p r e s s e d the a s s u m p t i o n [2] that the r e a s o n for the r e s i s t a n c e of the N - N bond

and the exocyclic double bond of 4 - a r y l i d e n e - l , 2 - d i p h e n y l - 3 , 5 - d i o x o p y r a z o l i d i n e s in ethanol containing KOH
to catalytic h y d r o g e n o l y s i s is the addition of a hydroxyl group to the exocyclic double bond to give s t a b l e
enolate anions [3]. This s o r t of direction of the r e a c t i o n might have been expected considering the ability
of these compounds [4] to add various nucleophilic reagents to the exocyclic double bond. The c h a r a c t e r of
the UV s p e c t r a of 4-benzylidene d e r i v a t i v e s in alkaline ethanol [2, 5] was also in a g r e e m e n t with the in-
dicated a s s u m p t i o n . However, the products of the addition of alkali o r alkoxide to 4 - b e n z y l i d e n e d i o x o -
pyrazolidines w e r e not isolated. The p r e p a r a t i o n and s o m e p r o p e r t i e s of compounds of this s o r t a r e d e -
s c r i b e d in the p r e s e n t p a p e r .
g n o l s a l t s (V-X, Table 1), which can be isolated in quantitative yield by the addition of excess a b -
solute ether, a r e f o r m e d in the r e a c t i o n of 4-benzylidene d e r i v a t i v e I and its substituted d e r i v a t i v e s (H-IV)
with an e q u i m o l e c u l a r amount of sodium alkoxide in the c o r r e s p o n d i n g absolute alcohol (methanol, ethanol,
and butanol).
0
R O N_C6H5

Na + OAIk

I-IV V-X X l - XIV

I R=C6Hs, R'~H; 11 R=p-O2NC6H4, R'=H; Ill R~p-CH3OC6H4, R'=H; IV R=R':C61t s

The IR s p e c t r a of V-X a r e in good a g r e e m e n t with the s t r u c t u r e a s s i g n e d to t h e m . An a b s o r p t i o n

band with a m a x i m u m at 1665-1675 c m -~ of m e d i u m or weak intensity and an intense b r o a d band with
m a x i m a at 1610 and 1580 c m -t a r e o b s e r v e d in the s p e c t r a of the addition products in place of the c h a r a c -
t e r i s t i c [for the s t a r t i n g dioxopyrazolidines (I-IV)] dicarbonyl doublet with m a x i m a at 1680-1720 c m - l . The
position of the a b s o r p t i o n m a x i m a is a l m o s t the s a m e as in the IR s p e c t r u m of the p o t a s s i u m s a l t of 4-
b u t y l - l , 2 - d i p h e n y l - 3 , 5 - d i o x o p y r a z o l i d i n e (1664, 1596, and 1570 c m - t ) ; this is additional p r o o f in f a v o r of
the chelate anion s t r u c t u r e of V - X . The signal of a single benzyl proton ( s - H ) is o b s e r v e d in the PMR
s p e c t r a of V - V I I at 5 5.26-5.40 ppm, along with the signals of the protons of-the c o r r e s p o n d i n g alkoxy
groups (Table 2).
* See [I] for communication XX.

Leningrad P h a r m a c e u t i c a l - C h e m i s t r y Institute. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h

Soedinenii, No. 2, pp. 224-226, F e b r u a r y , 1974. Original a r t i c l e s u b m i t t e d J a n u a r y 29, 1973.

9 19 75Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced, I
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy of this article is availablefrom the publisher for $15.00.
J
197
 TABLE 1. C h a r a c t e r i s t i c s of the P r o d u c t s of the Addition of Sodium
Aikoxides to 4 - A r y l i d e n e - l , 2 - d i p h e n y l - 3 , 5 - d i o x o p y r a z o l i d i n e s

Com-[. " '"[ . . . . " ' : , N,% m spectrum,

l~t~d R R; Ark Empirical for- found eale, cm.X
nmla ' I

v C~5 CHa IC~H1.N~OaNa 7,4: 7,1 t580, 1610, 1675

Vl C~H5 i C,,Hs /C2~"t~lbl'~:O#Na 7.0 6,9 1580, 1610, 1670
VII C6H5 C4H~ IC~H~N2OaNa 6,4 6,4 1585, 1610, 1665
VlIl CsH4NO~-p b

CH~ IC2sHlsN3OaNa 9,8 9,5 1346, 1528, 1585,

1605, 1667
IX 3,4-(CHsO)2C6H3 H "C~sH~N~OvNa 5,9 6,2 1585, 1605, 1665
X C6H5 C6Hs CH: C.H~N,O3Na 6,0 6,0 1580, 1608, 1670

TABLE 2. PMR S p e c t r a (in 6 units) of'the Protons of the P r o d u c t s

of the Addition of Alkoxides to 4 - A r y l i d e n e - l , 2 - d i p h e n y l - 3 , 5 - d i o x o -
p y r a z o l i d i n e s and of the Alkylation P r o d u c t s (XI-XIV)
z"
, % i=
.i C o m - 8. ppm
p~ Recording coriditiom*
(z-H 4-CHa OAlk

V CDaOD,, HMDS 100 MHzF 5,26 3,37

VI CD3OD,': HMDS t00 :MHz; 5,37 3,57; t,21
VII CD.~OD~;)'HM,_DS. 100 MHz / 5,40 3,50; 1,6; 0;91
Xt CC[4,,HNIDS 5(l M H z ; 4;37 1,17 3,04
XII CCb, "T1VIB60 MHz~.- 4,56 1,26 3,17
XIII CCh. TMS 40 MHg==. 4,45 1,31 3,27t
XIV CDCI~HMDS -B0 MHzl 4,72 1,31 3,31; 1,02

* A b b r e v i a t i o n s : HMDS is hexamethyldisiloxane, and TMS is t e t r a -

methyls itane.
The signals of the methoxy groups in (CH30)2C6H~ a r e o b s e r v e d at
3.91 and 3.79 p p m .

In o r d e r to obtain neutral compounds containing an alkoxy group fixed in the a - p o s i t i o n , we studied

the alkylation of pyrazolidines I-IV in ethanol in the p r e s e n c e of sodium methoxide. 4 - M e t h y l - 4 - ( 1 - m e t h -
o x y b e n z y l ) - l , 2 - d i p h e n y l - 3 , 5 - d i o x o p y r a z o l i d i n e (XI) was isolated in 47~c yield f r o m the r e a c t i o n of methyl
iodide with I. Alkylation products of the s a m e s t r u c t u r e (XII, XIII) a r e also f o r m e d with II and III, but the
yields a r e low (8-13%), and a l a r g e p a r t of the s t a r t i n g m a t e r i a l s a r e r e c o v e r e d . In the c a s e of IV, no
alkylation product at all could be isolated. Steric f a c t o r s a p p a r e n t l y play a substantial r o l e in the a l k y l a -
tion of I-IV, as indicated by the negative r e s u l t s of alkylation with other bulkier (than methyl iodide) alkyl
h a l i d e s , p a r t i c u l a r l y ethyl iodide, propyl iodide, and butyl b r o m i d e . Alkylation product XIV containing an
ethoxy group in the a - p o s i t i o n was also obtained when sodium methoxide was r e p l a c e d by sodium ethoxide
in the c a s e of II.
A doublet with m a x i m a at 1750-1 765 and 1710-1730 c m -~ , which is c h a r a c t e r i s t i c for the f l - d i c a r b o n y l
f o r m of 3 , 5 - d i o x o p y r a z o l i d i n e s , is o b s e r v e d in the IR s p e c t r a of XI-XIV.
The a b s o r p t i o n m a x i m u m in the UV s p e c t r a of all of the compounds is at 238 nm and does not change
its position on p a s s i n g f r o m n e u t r a l to acidic or alkaline media. The PMR s p e c t r a of XI-XIV (Table 2) also
confirm their structures.
Thus the data obtained c o n f i r m the p r e v i o u s l y e x p r e s s e d a s s u m p t i o n that the r e a s o n for the r e s i s t a n c e
of 4 - a r y l i d e n e - l , 2 - d i p h e n y l - 3 , 5 - d i o x o p y r a z o l i d i n e s in alkaline m e d i a to catalytic hydrogenation is the f o r m -
ation of a s t a b l e enolate under these conditions.

EXPERIMENTAL
The UV s p e c t r a w e r e r e c o r d e d as p r e v i o u s l y indicated in [2]. The IR s p e c t r a of suspensions in
m i n e r a l oil w e r e r e c o r d e d with a UR-10 s p e c t r o m e t e r .
Sodium Salts of 4 - ( 1 - A l k o x y b e n z y l ) - l , 2 - d i p h e n y l - 3 , 5 - d i o x o p y r a z o l i d i n e s (V-X, Tables 1 and 2). An
e q u i m o l e c u l a r amount of I-IV was added to a f r e s h l y p r e p a r e d solution of sodium alkoxide in the m i n i m u m
amount of the c o r r e s p o n d i n g alcohol, and the m i x t u r e was s t i r r e d in the cold until a c o l o r l e s s solution had
f o r m e d . An excess of absolute e t h e r was then added, and the finely c r y s t a l l i n e p r e c i p i t a t e was r e m o v e d by
filtration and d r i e d . The yield was c l o s e to quantitative.
 4-Methyl-4- (1-methoxybenzyl)-l,2-diphenyl-3,5-dioxopyrazolidine(XI). A 1.7 g (0.005 mole) s ample
of I was added to 20 ml of freshly prepared 1% solution of sodium methoxide in absolute methanol, and 7.1 g
(0.05 mole) of methyl iodide was added. The mixture was stored in a dark place for 4 days, after which it
was diluted with water and extracted wifh ether. Acidification of the aqueous solution yielded 0.74 g (42%)
of starting I with mp 163-164 ~ The ether extract was washed successively with a weak alkali solution and
water until it was neutral, and it was then dried with anhydrous sodium sulfate and evaporated to dryness.
Recrystallization of the residue from aqueous methanol gave 0.9 g (47~c) of a colorless crystalline sub-
stance with mp 127-128 ~ and R f 0.59 [activity II aluminum oxide, c h l o r o f o r m - b e n z e n e (3:1)]; development
in UV light. UV spectrum (neutral, acid, and alkaline solutions in ethanol)- ~max 238 nm (log r 4.30). IR
spectrum. 1750, 1711, 1600 cm -1. Found, %. C 74.7; H 5.9; N 7.4. C24H2~N203. Calculated, %: C 74.8; H
5.5; N 7.3.
4-Methyl-4- (1-methoxy-4:nitrobenzyl)-l,2-diphenyl-3,5-dioxopyrazolidine (XII). This compound was
obtained as in the preceding experiment in 8% yield ( 8 ~ of the starting II was recovered). The colorless
product had mp 159-160 ~ (from aqueous methanol) and R f 0.59 [Silufol, petroleum e t h e r - c h l o r o f o r m -
methanol ( 9 : 4 : 1 ) ] . UV spectrum (neutral, acid, and alkaline solutions in ethanol): ~max 238 nm (logr 4.25).
I R s p e c t r u m : 1 7 5 5 , 1 7 2 2 , 1 6 0 0 , 1 5 3 0 c m -1. Found,%.. N9.6. C24H21N30~. Calculated,~c: N9.8.
4-Methyl-4-(1-methoxyveratryl)-l,2-diphenyl-3,5-dioxopyrazolidine(XIII). This compound was ob-
tained in 13% yield (85% of the starting III was recovered) by the method used to prepare XI. The light-
yellow crystalline product had mp 156-157 ~ {from methanol) and R f 0.12 [alkaline aluminum oxide, b e n z e n e -
chloroform (13:2)]. UV spectrum (neutral, acid, and alkaline solutions in ethanol): ~ max 238 nm (log r
4.3). IR spectrum: 1758, 1732, 1600 cm -1. Found, %: C 69.9; H 6.4; N 6.4. C26H26N205. Calculated, ~:
C 69.9; H 5.9; N 6.3.
4:Methyl-4-(1-ethoxy-4-nitrobenzyl)-l,2-diphenyl-3,5-dioxopyrazolidine(XIV). This compound was
obtained in 30% yield by the method used to prepare XII, except that sodium ethoxide in ethanol was used.
The colorless crystalline product had mp 133-134 ~ and Rf 0.76 [Silufol, petroleum e t h e r - c h l o r o f o r m -
methanol ( 9 - 4 : 1 ) ] . Found, %. N 9.8. C2~H23N30~. Calculated, ~: N 9.5. UV spectrum (neutral, acid, and
alkaline solutions in ethanol).. Amax 238 nm (log e 4.26). IR spectrum- 1764, 1730, 1600, 1530 cm -~.

LITgRATURE CITED
1. B. L. Moldaver, M. P. Papirnik, V. V. Zverev, and Yu. P. Kitaev, Khim. Geterotsikl. Soedin., 781
(1973).
2. B. L. Moldaver and M. E. Aronzon, Khim. Geterotsikl. Soedin., 804 (1970).
3. B. L. Moldaver, M. E. Aronzon, and M. P. Papirnik, Khim. Geterotsikl. Soedin., 407 (1970).
4. A. Mustafa, A. Sammour, M. Kira, M. K. Hilmy, M. Anwar, and S. N. Nakhla,. Arch. Pharm., 298,
516 (1965).
5. B. L. Moldaver and M. E. Aronzon, Khim. Geterotsikl. Soedin., 657 (1971).

199
RIgACTION OF NITRILES OF gNYNE ACIDS WITH HYDRAZINES.
SYNTH]gSIS OF CYANO D~gRIVATIVES OF 2-PYRAZOLINES

K. G. Golodova, S. I. Yakimovich, UDC 547.396+547.339.2+547.772.2

and F. Ya. Perveev

The r e a c t i o n of nitriles of enyne acids with hydrazine, a l k y l h y d r a z i n e s , and phenylhydrazine

gives 5 - c y a n o m e t h y l - 2 - p y r a z o l i n e s . The p o s s i b l e m e c h a n i s m of the cyclization is examined.

g n y n e nitriles [1,2] a r e compounds that have an activated C ---~C bond in which the activating cyano
group is s e p a r a t e d f r o m the C ~---C bond by an additional multiple bond. V e r y little study has been devoted
to the r e a c t i o n s of compounds of this s o r t with nucleophilic reagents [3].
In the p r e s e n t r e s e a r c h we have investigated the r e a c t i o n of nitriles I-III with hydrazine, a l k y l a -
h y d r a z i n e s , and p h e n y l h y d r a z i n e . The r e a c t i o n products w e r e pyrazolines IVa-i (Table 1).

RC.C_~=CI.IC N WNHNH2. R ~ H 3
CH3 "''I~/ '~CH2CN
R'
I-Iii IVa

I R=CHa; II R=n-C4Hg; III R=C~H5

IV: a R=CHa, R'=H; b R=R'=CHa; e R=CHa, R'=n-CaHr; r R=CHa, R'=CsHs;
e R=n-C4Hg, R'=H; f R=n-C4I-]9, R'=CHa; g R=n-C4Hg, R'=n-CaHr; h R=C6Hs, R'=H;
i R =CsHs, R'=CHa,

The IR s p e c t r a of IV a r e c h a r a c t e r i z e d by an absorption band of m e d i u m intensity at 2255-2260 c m -~,

w h i c h is r e l a t e d to the v i b r a t i o n s of an unconjugated C ----N o r C ------C bond, and an a b s o r p t i o n band at 1630
c m -1, which is due to the vibrations of C = N , C = C , o r N = N bonds. The p r e s e n c e of a nitrile group was
shown by c h e m i c a l m e a n s in the c a s e of the product of the r e a c t i o n of nitrile I with m e t h y l h y d r a z i n e (on the
b a s i s of p r o o f p r e s e n t e d f u r t h e r on, it has the 1 , 3 , 5 - t r i m e t h y l - 5 - c y a n o m e t h y l - 2 - p y r a z o l i n e s t r u c t u r e ) . The
nitrile group was c o n v e r t e d to an a m i d e group via the R a d z i s z e w s k i r e a c t i o n by h y d r o l y s i s in the p r e s e n c e
of alkali and hydrogen p e r o x i d e [4].

H20 CII~"~C /
Iyb H2OJNaOH Ha
2CONH 2
CH 3
V

The a b s o r p t i o n at 2260 c m -~ is absent in the IR s p e c t r u m of V, but it does contain absorption bands

at 1625, 1660, 3100, 3310, and 3400 c m -1, which a r e c h a r a c t e r i s t i c for p r i m a r y amides (amide I and II
bands, and s t r e t c h i n g vibrations of the NH 2 group of an amide) [5]. A b s o r p t i o n of the C = N bond of the
p y r a z o l i n e ring is s u p e r i m p o s e d on the amide II a b s o r p t i o n band (1625 c m - l ) .
Thus addition of h y d r a z i n e s to enyne nitriles p r o c e e d s at the C ~---C bond with subsequent c y c l i z a t i o n
at the C = C bond to give p y r a z o l i n e s that have an unconjugated C =-- N group in the side chain.

- ~N/ \CH2CN /
R'
VI VII

A . A . Zhdanov Leningrad State U n i v e r s i t y . T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii,

No. 2, pp. 227-232, F e b r u a r y , 1974.

9 19 75Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, meehanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy of this article is availablefrom the publisher for $15.00.

200
 The r e a c t i o n of hydrazine with enyne nitriles may lead to s u b -
stituted 1- (VI}, 2- (IV, R' = g ) , and 3 - p y r a z o l i n e s (VII, R' = R" = H).
The r e a c t i o n of monosubstituted h y d r a z i n e s with nitriles I-III
m a y c o m m e n c e with attack at the C ----C bond by the substituted n i t r o -
gen a t o m . In this c a s e , the f o r m a t i o n of only 3 - p y r a z o l i n e s VII (R' =
H, R" = Alk, C6H5) is p o s s i b l e . If the r e a c t i o n c o m m e n c e s at the
C -- C bond by the unsubstituted nitrogen atom, the products m a y have
2 - (IV, R T = Alk, C6H 5) and 3 - p y r a z o l i n e (Vii, R" = H, R' = Alk, C6H ~)
s t r u c t u r e s . The IR s p e c t r a of the products of the r e a c t i o n of nitriles
with h y d r a z i n e s (IVa,e,h) contain an absorption band in the region of
the stretching vibrations of the NH bond at 3280-3330 cm-~; this e x -
eludes the p o s s i b i l i t y that they e x i s t as l - p y r a z o l i n e s (VI). Except
~ M M ~ M M ~ M for IVd,h,i, absorption at 3000-3100 c m -~, which should have been e x -
peered if these compounds had the s t r u c t u r e of 3 - p y r a z o l i n e s (VII)

!'i
~N
(stretching vibrations of the -----C-I-J bond), is absent in the s p e c t r a of
~N all of the compounds except for IVd,h,i. In addition, absorption in
the r e g i o n of the stretching vibrations o f the NH bond is absent in the
IR s p e c t r a of all of the compounds except IVa,e,h; this is also e v i -
denee in favor of the 2 - p y r a z o l i n e s t r u c t u r e (IV).
00 The absorption band of low intensity at 1625-1630 c m -~ in the
IR s p e c t r a of I v a - c , e - g should be a s s i g n e d to the vibrations of the
C ----N bond. The band of medium intensity at 1610 c m -~ in the s p e c -
c~ trum of IVd is due to the s u p e r i m p o s i t i o n of absorption bands of the
C = N bend and the phenyl ring. The absorption bands at 1595 and
1570 e m -1 in the s p e c t r a of IVh,i are due to the vibrations of the
phenyl ring and the C = N bond. It should be noted that the IR s p e c t r a
--!
O of IVa-i in the region of the stretching vibrations of the double bonds
N
have the f o r m c h a r a c t e r i s t i c for the s p e c t r a of 3-substituted 2-
C~ p y r a z o l i n e s [6].
~z~zzzzz ~D
The definitive s t r u c t u r e of the products of the r e a c t i o n of the
enyne nitriles with h y d r a z i n e s was proved by the PMR s p e c t r a and by
c o m p a r i s o n with the data in the literature regarding the PMR s p e c t r a
CD
of 2 - p y r a z o l i n e s [7, 8]. F i r s t of all, one should note the a b s e n c e of
o

~ I~ I~ O the signal of a proton attached to the C ----C bond in the PMR s p e c t r a .

Consequently, the investigated compounds cannot have the 3 - p y r a z o l -
ine s t r u c t u r e (VII). The signal that might have been a s s i g n e d to the
proton of the methylidyne group of the ring in the l - p y r a z o l i n e s t r u c -
>
ture (VI) is absent in the s p e c t r a of I v a , e , h .
o) <D O
~ o9 c~ o9 The PMR s p e c t r a of all of the investigated compounds (Table 1)
contain singlets of the protons of a methyl group (5 1.30-1.50 ppm)
0
~7
lllItIlt and a m e t h y l e n e group (5 2.40-2.55 ppm) attached to a saturated
.c-m carbon a t o m . In addition, the s p e c t r a of all of the compounds are
I c h a r a c t e r i z e d by two broad singlets at 8 2.40-2.90 ppm (each with an
intensity, of one proton), which should be a s s i g n e d to the protons of
the ring CH 2 group. Such a low position of the signal of a ring CH 2
group is not ifl a g r e e m e n t with the p o s s i b l e l - p y r a z o l i n e s t r u c t u r e
0
C
(VI) for the products of the reaction of nitriles I-III with h y d r a z i n e .
The signal at l o w e r field is probably affiliated with the proton of the
I
ring m e t h y l e n e group in the c i s position r e l a t i v e to the CH2CN group.
u~
O The s t r u c t u r e of the carbon s k e l e t o n of the 2 - p y r a z o l i n e s was
obtained for Ivb by exhaustive methylation and s u b s e q u e n t Hofmann
~D
c l e a v a g e of the p y r a z o l i n e ring via the method in [9].
O
The i s o l a t e d h y d r a z o n e (IX) was also obtained by r e a c t i o n of
nitrile I with d i m e t h y l h y d r a z i n e . The IR and PMR s p e c t r a of the
h y d r a z o n e s obtained by both methods w e r e c o m p l e t e l y identical. We
p r e s e n t e d the proof of the s t r u c t u r e o f h y d r a z o n e IX in [10].

201
 c.~I.~ CH3~
"~-~--'~c.~ N~#O3 CH3CCH2C:CH2CN
IV
N-~CH~C N | I
/\ N CHa
CH3 CH s I- (CH3)2N,'/
VIII IX

The investigated enyne nitriles were obtained as mixtures of the cis and trans i s o m e r s [2]. Both
i s o m e r s of nitrile t w e r e isolated and subjected to reaction with methylhydrazine. In both c a s e s , pyrazoline
IVb was obtained. The f o r m a t i o n of pyrazolines IV in all of the investigated reactions of enyne nitriles I-III
with h y d r a z i n e s means that the r e a c t i o n c o m m e n c e s with interaction of the nucleophilic reagent with the
.triple bond, apparently with the formation of a conjugated enehydrazine. The subsequent formation of the
pyrazolines may o c c u r d i r e c t l y by cyelization of the enehydrazine or through tautomeric transition to the
h y d r a z o n e f o r m and c o n v e r s i o n of it to the pyrazoline. In o r d e r to a s c e r t a i n this, we made a detailed in-
vestigation of t h e r e a c t i o n of nitrile I with methylhydrazine. The r e a c t i o n o c c u r s with heat liberation and
the addition of m e t h y l h y d r a z i n e to nitrile I is p r a c t i c a l l y complete after 2 h, according to t h i n - l a y e r c h r o m -
atography ( T I ~ ) . Two absorption bands - an intense band at 1600 c m -i and a band of medium intensity in
the region of s t r e t c h i n g vibrations of double bonds at 1635 c m -1 - are o b s e r v e d in the IR s p e c t r u m of the
r e a c t i o n mixture of equimolecular amounts of the reagents r e c o r d e d 2 h after mixing. The f o r m of the ab-
sorption in the region of vibrations of the C ~ N bond is complex. There is a v e r y intense absorption band
at 2210 c m -1 and bands at 2235 and 2260 c m -1, which p r o j e c t as shoulders of the f i r s t band. The intensity
of the band at 2235 c m -i is higher than that of the band at 2260 c m -~. The intensity of the band at 1600 c m -1
gradually d e c r e a s e s with time, while the intensity of the band at 1635 cm -1 initially remains approximately
c o n s t a n t and then begins to i n c r e a s e ; in the region of vibrations of the C -~- N bond, the intensity of the ab-
sorption at 2210 c m -1 d e c r e a s e s , and the intensity of the absorption at 2260 c m -1 i n c r e a s e s . The a b s o r p -
tion at 2235 c m -I initially i n c r e a s e s and then d e c r e a s e s . In the s p e c t r u m of the reaction mixture r e c o r d e d
after 11 h, t h e absorption at 1600, 2210, and 2235 c m -i p r a c t i c a l l y vanishes, while the low-intensity bands
at 1635 and 2260 c m -1 r e m a i n . According to T L C , the reaction is complete after 11 h, and only pyrazoline
IVb is p r e s e n t . The results can be i n t e r p r e t e d as follows. In the reaction of nitrile I with methylhydrazine,
the addition p r o d u c t - enehydrazine X - which has an extended s y s t e m of multiple bonds, is f o r m e d quite
rapidly. In its IR s p e c t r u m , it is apparently c h a r a c t e r i z e d by absorption bands at 1600 and 2210 c m -I .
T a u t o m e r i c t r a n s i t i o n to the hydrazone f o r m of addition product XI, which is c h a r a c t e r i z e d by absorption
bands at 1635 and 2235 c m -1, gradually o c c u r s . The final product of the r e a c t i o n of nitrile I with m e t h y l -
h y d r a z i n e - p y r a z o l i n e IVb - to which the low-intensity bands at 2260 and 1635 c m -1 in the IR s p e c t r u m are
related (the l a t t e r is overlapped by the absorption of the C = N bond of the hydrazone form}, forms s i m u l -
taneously. The r a t e of c o n v e r s i o n of enehydrazine f o r m X of the addition product to hydrazone XI is higher
than the r a t e of formation of pyrazoline IVb. This explains the initial i n c r e a s e in the intensity of the ab-
sorption at 1635 and 2235 c m -~. It is m o s t likely that p r e c i s e l y the hydrazone f o r m is converted to the
final pyrazoline, since an i n c r e a s e in the e l e c t r o n density in the reaction zone due to the inclusion of the
u n s h a r e d pair of the p r i m a r y nitrogen atom in the conjugation s y s t e m will hinder attack of the s e c o n d a r y
nitrogen atom at the C : C bond in the enehydrazine f o r m . However, the results do not make it possible to
c o m p l e t e l y exclude the possibility of cyclization of enehydrazine form X to a pyrazoline.

CH3NHNH~ CHaC=CHC=CHCN ~ CH3CCfl2C=CI'ICN ~ IVb

I CH3NHNH CH3 ~ ~H3
CH3N/

X Xl

The i n t e r m e d i a t e a p p e a r a n c e of the hydrazone f o r m was also fixed by means of PMR s p e c t r o s c o p y .

Signals" r e l a t e d to the hydrazone (XI) and enehydrazine (X) f o r m s of the initial addition product can be noted
in addition to the signals of pyrazoline IVb in the s p e c t r u m of an equimolecular mixture of nitrile I and
methylhydrazine r e c o r d e d 4 h after mixing. Thus, for example, the group of signals at 5 2.80, 2.86, 2.98,
and 3.05 ppm can, on the basis of a c o m p a r i s o n with the s p e c t r u m of the product of the r e a c t i o n of nitrile I
with dimethylhydrazine [10], be assigned to the signals of the protons of the CH 2 group of hydrazone XI; the
s i g n a l at 5.16 ppm apparently belongs to the proton of the NH group of this f o r m [11]. The signals at 4.48
and 5.38 ppm should be assigned to the protons attached to the double bonds o f t h e enehydrazine a n d h y d r a z o n e
forms.
The effect of a solvent on the c o u r s e of the r e a c t i o n was examined in the c a s e of the r e a c t i o n of
methylhydrazine with nitrile I by means of TLC. The addition and subsequent cyclization to a pyrazoline
o c c u r rapidly in dimethyl sulfoxide (DMSO), m o r e rapidly, in fact, than when nitrile I is mixed directly

202
with excess m e t h y l h y d r a z i n e . Cyclization is s lowed down in CC14 and proceeds most slowly in alcohol. The
i n c r e a s e in the r e a c t i o n r a t e in DMSO is explained by the fact that both addition of methylhydrazine to the
enyne nitrfle and c y c l i z a t i o n at the double bond proceed through zwitter ion transition states, which are
stabilized by a dipolar aprotic solvent. The nucleophilicity of hydrazine is apparently reduced in alcohol
due to the f o r m a t i o n of a hydrogen bond with the solvent, which reduces the r a t e of addition at the C -- C
bond. The c y c l i z a t i o n p r o c e s s in this solvent can be slowed down due to an i n c r e a s e in the stability of the
enehydrazine f o r m also as a consequence of the formation of i n t e r m o l e c u l a r hydrogen bonds, which de-
c r e a s e s the c o n c e n t r a t i o n of the h y d r a z o n e f o r m through which the formation of the pyrazolines m o s t likely
proceeds.
gXPERIMENTAL
The IR s p e c t r a of the pure compounds, m i n e r a l oil suspensions (thin layer), and c a r b o n t e t r a c h l o r i d e
solutions (1-1.5%, thin l a y e r , 603 #m) were r e c o r d e d with a UR-20 s p e c t r o p h o t o m e t e r . The PMR s p e c t r a
of 10% solutions of the compounds in c a r b o n t e t r a c h l o r i d e were r e c o r d e d with a V a r i a n HA-100 D / 1 5 s p e c -
t r o m e t e r with hexamethyldisiloxane (HMDS) as the internal standard.
2 - M e t h y l - l - p e n t e n - 3 - y n e c a r b o n i t r i l e (I). This compound was obtained in 70% yield by the method in
[1] and had bp 46-48 ~ (3 ram), d~U 0.9032, and n~ 1.5025.
2 - M e t h y l - l - o c t e n - 3 - y n e c a r b o n i t r i l e (II). This compound was s i m i l a r l y obtained in 75% yield and had
bp 83-84 ~ (4 mm), d~~ 0.8726 and r ~ 1.4912.
2 - M e t h y l - 4 - p h e n y l - l - b u t e n - 3 - y n e c a r b o n i t r i l e (III) [2]. This compound was obtained in 65~ yield by
vacuum distillation of 2 - h y d r o x y - 2 - m e t h y l - 4 - p h e n y l - 3 - b u t y n e c a r b o n i t r i l e over P205 and had bp 124-125 ~ (3
mm), d 2~ 1.0054 and n~ 1.6110. The cis and trans i s o m e r s of nitrile I were isolated by means of p r e p a r a -
tive TLC on activity II aluminum oxide [2]. g t h e r - p e t r o l e u m ether (1 : 5) was used as the eluent, and the
c h r o m a t o g r a m s were developed with a UV lamp. The s e p a r a t i o n of the cis and trans i s o m e r s was achieved
by three to four repetitions of the s e p a r a t i o n o p e r a t i o n s .
c i s - 2 - M e t h y l - l - p e n t e n - 3 - y n e c a r b o n i t r i l e . This i s o m e r had bp 50.5-51 ~ (3 mm), d] ~ 0.9043, n~ 1.4987.
trans-2-Methyl-l-denten-3-ynecarbonitrile. This is o m e r had bp 39.5-40 ~ (3 mm), d 2~ 0.9018, n~
1.5102.

3 , 5 - D i m e t h y l - 5 - c y a n o m e t h y l - 2 - p y r a z o l i n e (IVa). A 10.5 g (0.1 mole) sample of nitrile I was mixed at

r o o m t e m p e r a t u r e with 3.8 g (0.12 mole) of anhydrous h y d r a z i n e . The t e m p e r a t u r e of the mixture r o s e
spontaneously t o 50-60 ~ after which it was held at r o o m t e m p e r a t u r e for 5 h. The c o u r s e of the r e a c t i o n
was monitored by TLC on activity II A1203 in e t h e r - p e t r o l e u m ether ( 2 : 1 ) . Vacuum distillation yielded
12.3 g (90%) of pyrzoline IVa with bp 125.5-126 ~ (4 mm); the liquid c r y s t a l l i z e d on standing to give a solid
with mp 45-46 ~ The product was unstable and d e c o m p o s e d in air; this is c h a r a c t e r i s t i c for 1-unsubstituted
pyrazolines [12]. IR s p e c t r u m (l~c solution in CCla, cm-1): 865 w, 890 m, 910 m, 960 m, 1045 m, 1095 w,
1110 w, 1135 w, 1160 w, 1175 w, 1200 rn, 1225 m, 1245 w, 1270 w, 1280 w, 1330 s, 1380 s, 1420 s,
1440 s, 1460 s, 1630 m, 2255 m, 2850 m, 2920 s, 2950 s, 2970 s, 3270 s, 3330 s. The physical constants and
results of analysis of the p y r a z o l i n e s obtained are p r e s e n t e d in Table 1.
1 , 3 , 5 - T r i m e t h y l - 5 - c y a n o m e t h y l - 2 - p y r a z o l i n e (Wb). Mixing of 10.5 g (0.1 mole} of nitrile I and 5.3 g
(0.12 mole) of m e t h y l h y d r a z i n e for 13 h gave, after vacuum distillation, 14.3 g (95%) of pyrazoline IVb. IR
s p e c t r u m (1~ solution in CC14, cm-1): 850 w, 890 w, 910 w, 928 m, 960 m, 1015 w, 1090 m, 1120 s, 1145 m,
1180 s, 1190 s, 1230 s, 1245 s, 1280 m, 1295 m, 1330 s, 1375 s, 1390 s, 1420 s, 1432 s,1440 s,1475 s , 1 6 2 5 r n ,
2255 m, 2800 s, 2850 s, 2870 s.

3 , 5 - D i m e t h y l - l - p h e n y l - 5 - c y a n o m e t h y l - 2 - p y r ~ t z o l i n e (IVd). A mixture of 2.1 g (0.02 mole) of nitrile I

and 2.5 g (0.022 mole) of phenylhydrazine was heated in a test tube with a s t o p p e r at 100 ~ for 120 h. The r e -
action product was isolated by p r e p a r a t i v e TLC on activity II aluminum oxide in e t h e r - p e t r o l e u m ether
(1:1) to give 0.9 g (41~ of p y r a z o l i n e IVd with mp 60-60.5 ~ IR s p e c t r u m (1% solution in CC14, cm-1): 1020
m, 1045 m, 1090 w, 1115 w, 1140 w, 1165 w, 1185 w, 1210 m, 1230 m, 1280 s, 1290 s, 1305 s, 1355 s, 1400 s,
1445 s, 1465 m, 1505 s, 1610 s, 2260 m, 2850 w, 2860 w, 2920 m, 2950 m, 2985 m, 2995 m, 3035 w, 3050 w,
3075 w.

5 - M e t h y l - 3 - p h e n y l - 5 - c y a n o m e t h y l - 2 - p y r a z o l i n e (IVh). A 5 g (0.03 mole) s a m p l e of nitrile III was

mixed with 1 2 g (0.032 mole) of anhydrous h y d r a z i n e . P r o n o u n c e d heating of the mixture was o b s e r v e d .
A f t e r 15 h [monitoring by T I C on aluminum oxide in e t h e r p e t r o l e u m ether (9:1)], 5 g (80%) of pyrazoline

203
IVh, with mp 69.5-70.5 ~ (from e t h e r ) , was isolated. IR s p e c t r u m (thin l a y e r in m i n e r a l coil, cm-~): 835 s,
855 s , 900 s , 915 s , 960 w, 980 w, 1020 m: 1065 m, 1085w, l l 1 0 w, 1160 m, 1185 w, 1225 m, 1275 s, 1315 m,
1360 s , 1385 s, 1420 s , 1460 s, 1505 m, 1575 m, 1595 m, 2260 m, 2880 m, 2935 s, 2975 s, 3030 m, 3070 m,
3260 s, 3320 s.
1 , 3 , 5 - T r i m e t h y l - 5 - c y a n o m e t h y l - 2 - p y r a z o l i n e (VIID. A m i x t u r e of 5 g (0.033 mole) of p y r a z o l i n e IVb,
7 g (0-05 mole) of m e t h y l iodide, and 60 m l of benzene was heated at 65 ~ for 4 h. The p r e c i p i t a t e d VIII was
c r y s t a l l i z e d f r o m ethyl a c e t a t e - m e t h a n o l (2:1) to give 8.6 g (90~c) of a product with mp 157 ~ . Found, ~ :
C 36.9; H 5.6; N 14.0. CgH16IN3. C a l c u l a t e d , %: C 36.8; H 5.4; N 14.2.
4 - D i m e t h y l h y d r a z o n o - 2 - m e t h y l - l - p e n t e n e c a r b o n i t r i l e (IX). A__:.A m i x t u r e of 8 g (0.026 mole) of
methi0dide VII, 5 g (0.04 mole) of Na2CO3, and 10 m l of w a t e r was heated at 50 ~ for 4 h. The r e a c t i o n m i x -
t u r e was e x t r a c t e d with c h l o r o f o r m , the c h l o r o f o r m e x t r a c t s w e r e d r i e d with MgSO 4, and the solvent was
r e m o v e d . The r e s i d u e was s e p a r a t e d by p r e p a r a t i v e TLC on activity II aluminum oxide in e t h e r - p e t r o l e u m
e t h e r (1 : 1) to give 1.8 g (40%) of nitrile IX with d~~ 0.9354 and n~ 1.4885. IR s p e c t r u m (thin l a y e r , c m -i) :
800 m, 820 m, 860 w, 970 m, 1025 m, 1050 m, 1075 w, 1095, w, 1160 m, 1200 m, 1250 w, 1300 w, 1370 s,
1390 s, 1445 s, 1470 s, 1570 w, 1630 s, 2190 w, 2225 s, 2780 s, 2820 s, 2860 s, 2900 m, 2920 m, 2970 s,
2990 s, 3060 w. Found, %: C 65.5; H 9.2; N 2 5 . 5 . C9HisN ~. Calculated, %: C 65.4; H 9.1; N 25.4.
B. A m i x t u r e of 2.1 g i0.02 mole) of nitrile I and 2 g (0.033 mole) of d i m e t h y l h y d r a z i n e was heated in
a t e s t tube with a g r o u n d - g l a s s s t o p p e r at 40 ~ for 70 h. The e x c e s s d i m e t h y l h y d r a z i n e was r e m o v e d in
vacuo to give 3.1 g (100%) of nitrile IX with d 2~ 0.9341 and n~ 1.4885. The IR s p e c t r u m was identical to the
s p e c t r u m of the h y d r a z o n e obtained by degradation of methiodide VIII.
1 , 3 , 5 - T r i m e t h y l - 5 - a m i d o m e t h y l - 2 - p y r a z o l i n e (V). A 10-g s a m p l e of NaOH was added gradually with
s t i r r i n g to 100 m l of 30% h y d r o g e n p e r o x i d e , a f t e r which 1 g of p y r a z o l i n e IVb was added d r o p w i s e . The
solution was n e u t r a l i z e d and e x t r a c t e d r e p e a t e d l y with e t h e r . The e t h e r e x t r a c t s w e r e dried with MgSO4,
and the e t h e r was r e m o v e d to give 0.5 g (45qc) of a m i d e V with mp 238-240 ~ (dec.). IR s p e c t r u m (KBr pellet,
cm-1): 740 m, 760 w, 840 w, 950 s, 1020 m, 1040 m, 1090 m, 1235 m, 1320 m, 1390 s, 1430 s, 1505 m , 1 5 3 0 s ,
1625' s, 1660 s, 2760 m, 2870 m , 2940 m,3100 s, 3310 m, 3400 m . Found, %: C 56.9; H 8.7; N 24.1.
CsH15NzO. Calculated, %: C 56.8; H 8.9; N 24.2.

LITERATURE CITED
I. F. Ya. P e r v e e v and K. G. Golodova, Zh. Obshch. Khim., 32, 2092 (1962).
2. F . Ya. P e r v e e v , K. G. Golodova, and S. I. Yakimovich, Zh. Organ. Khim., 7, 2059 (1971).
3. E. Winterfeldt, Angew. C h e m . , 7__99,389 (1967).
4. B. R a d z i s z e w s k i , B e r . , 1_88, 355 (1885).
5. L. B e l l a m y , I n f r a r e d Spectra of Complex Molecules, 2nd ed., Methuen (1958).
6. B . V . Ioffe, Khim. G e t e r o t s i k l . Soedin., 1089 (1968).
7. G. Gloss and H. Heyn, T e t r a h e d r o n , 22, 463 (1966).
8. V . S . Stopskii, V. B. Lebedev, B. V. Ioffe, and A~ A. P e t r o v , Dokl. Akad. Nauk SSSR, 166, 399 (1966).
9. B . V . Ioffe and K. N. Zelenin, Dokl. Akad. Nauk SSSR, 154, 864 (1964).
10. K . G . Golodova and S. I. Yakimovich, Zh. Organ. Khim., 8, 2019 (1972).
ll. B. ,~. Arbuzov, Yu. Yu. Samitov, and Yu. P. Kitaev, Izv. Akad. Nauk SSSR, Otd. Khim. Nauk, 56 (1966).
12. N . V . Kupletskaya, A. N. Kost, and I. I. G r a n d b e r g , Zh. Obshch. Khim., 26, 3135 (1956).

204 ,
DIPYRAZOLODIAZOCINES

M. A. Mikhaleva, L. N . ll'chenko, UDC 542.953:547.779.895.853

and V. P. Mamaev

Substituted dipyrazolo[3,4--d:4',3~-g][1,3]diazoeines - r e p r e s e n t a t i v e s of a new h e t e r o c y c l i c

s y s t e m - w e r e obtained by r e a c t i o n of m e t h y l e n e b i s u r e a and b e n z a l b i s u r e a with 1 - R - a m i n o -
pyrazoles.

We have p r e v i o u s l y [1] shown that p y r a z o l o [ 3 , 4 - d J p y r i m i d i n e s (I) a r e f o r m e d in the r e a c t i o n of 1 - s u b -

stituted 5 - a m i n o p y r a z o l e s with m e t h y l e n e b i s u r e a in acetic acid when the r e a g e n t r a t i o is I : 2.

Nit 2

R R 6
I |1
I, II 9 R=C6Hs;b R=CH~s 5
A compound that differed f r o m I was isolated when this condensation was c a r r i e d out with an equi-
m o l e c u l a r r a t i o of the r e a g e n t s . Absorption bands at 1665 and 3260 c m -1 (NH) w e r e p r e s e n t in the IR s p e c -
t r u m of this compound; m o r e o v e r , judging f r o m the negative qualitative r e a c t i o n , the compound did not c o n -
tain an NH 2 group. The UV s p e c t r u m of the compound was s i m i l a r to the UV s p e c t r u m of the s t a r t i n g
p y r a z o l e . Signals of m e t h y l e n e protons at 3.53 (s),* of p y r a z o l e ring protens at 7.74 (s), and of a r o m a t i c
protons at 7,43 ppm (m) with an intensity r a t i o of 1 : 1 : 5 w e r e p r e s e n t in the PMR s p e c t r u m . On the basis
of the data p r e s e n t e d above, the d e t e r m i n a t i o n of the m o l e c u l a r weight, and the r e s u l t s of e l e m e n t a r y
a n a l y s i s , the 1, 7 - d i p h e n y l - 9 - o x o d i p y r a z o l o [ 3 , 4 - d : 4 ' , 3 ' - g ] [1,3]diazocine s t r u c t u r e (Ha) was a s s i g n e d to the
compound obtained.

Condensation of e q u i m o l e c u l a r amounts of l - b e n z y l - 5 - a m i n o p y r a z o l e with m e t h y l e n e b i s u r e a p r o c e e d s

s i m i l a r l y to give d i p y r a z o l o d i a z o c i n e lib, the s t r u c t u r e of which was also p r o v e d by analytical and s p e c t r a l
data and d e t e r m i n a t i o n of the m o l e c u l a r weight.
It has been r e p o r t e d [2] that 1 - p h e n y l - 3 - a m i n o p y r a z o l e r e a c t s with b e n z a l b i s u r e a to give a c o m p l e x
m i x t u r e , one of the components of which is l - p h e n y l - 3 - u r e i d o p y r a z o l e , which is r e a d i l y f o r m e d f r o m l -
p h e n y l - 3 - a m i n o p y r a z o l e and the u r e a p r e s e n t in the r e a c t i o n m e d i u m . In a f u r t h e r investigation of this r e -
action, we i s o l a t e d y e t another compound, which, judging f r o m the qualitative reaction, does not have an
NH2 g r o u p but contains NH (3420 c m -i) a n d C O (1700 c m -~) g r o u p s . On the basis of these data and the
e m p i r i c a l f o r m u l a , as well as in analogy with the p r e c e d i n g c a s e , we a s s i g n e d t h e 2 , 4 , 6 - t r i p h e n y l - 9 - o x o d i -
p y r a z o l o [ 3 , 4 - d : 4 ' , 3 ' - g ] [1,3]diazocine s t r u c t u r e (III) to this compound.

I
C+H 5
c+.+-]N~g+]/+'~'~ym
w,~p,,]m~.%.+
0
Ill

* T h e following abbreviations a r e used h e r e and e l s e w h e r e : s is singlet and m is multiplet.

N o v o s i b i r s k Institute of Organic C h e m i s t r y , Siberian Branch, A c a d e m y of Sciences of the USSR.
T r a n s l a t e d f r o m K h i m i y a G e t e r o t s i k l i c h e s k i k h Seedinenii, No. 2, pp. 233-234, F e b r u a r y , 1974. Original
a r t i c l e s u b m i t t e d J a n u a r y 16, 1973.
I......
9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, A~.Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is availablefrom the publisher for $15.00.

205
 Of the condensed derivatives of diazocines that have been described, most of the compounds are di-
benzo [1,5]- and dibenzo [1,3]diazocines [3;4]; dipyrido [3,2-b:3 TfiT_f] [1,5]diazocine [5] was synthesized f r o m
h e t e r o c y c l i c compounds including a diazocine ring. Pyrazolodiazocines have not been described, and H and
III consequently a r e m e m b e r s of a n e w h e t e r o c y c l i c s y s t e m - dipyrazolo [1,3]diazecine.

EXPNRIMgNTAL
The IR s p e c t r a of KBr pellets (c 0.25qc) w e r e r e c o r d e d with a UR-20 s p e c t r o m e t e r . The PMR s p e c t r a
of ds-dimethyl sulfoxide solutions w e r e r e c o r d e d with a Varian A56/60A s p e c t r o m e t e r with hexamethyldi-
siloxane (HMDS) as the internal standard, The m o l e c u l a r weights were d e t e r m i n e d with an MS-902 mass
spectrometer.
1,7-Diphenyl-9-oxodipyrazolo [3',4-d:4 T,3'-g] [1,3]diazocine (IIa). A 1.0 g (6.3 mmole) s ample of 1-
p h e n y l - 5 - a m i n o p y r a z o l e was refluxed for 2 h with 0.83 g (6.3 mmole) of m e t h y l e n e b i s u r e a [6] in 10 ml of
glacial CH3COOH. The m i x t u r e was cooled, and the precipitate was r e m o v e d by filtration, washed with
acetic acid, and dried over NaOH to give 0.13 g of IIa with mp 358-362 ~ Found, ~: C 67.2; H 4.5; N 23.3.
Mol. wt. 356. C20H16NsO. Calculated, %: C 67.4; H 4.5; N 23.6. Mol. wt. 356.
The filtrate was poure.d into water, and the aqueous mixture was neutralized with NaHCO 3 and ex-
t r a c t e d with CHCI~. The c h l o r o f o r m extracts w e r e dried with MgSO4, and the c h l o r o f o r m was r e m o v e d by
distillation to give 0.1 g of Ia [1].
1,7-Dibenzyl-9-oxodipyrazolo [3,4-d:4',3'-g] [1,3]diazocine (iIb). This compound was obtained in 10~
yield by the method used to p r e p a r e Ha by reaction of 1 - b e n z y l - 5 - a m i n o p y r a z o l e and m e t h y l e n e b i s u r e a .
The product had mp 359-359 ~ Found, %: N 21.6. Mol. wt~ 384. C22H20N~O. Calculated, ~ : N 21.8.
Mol. wt. 384. IR s p e c t r u m : 1650 c m -i (CO). PMR s p e c t r u m , 5, ppm: 3.44 (4-CH 2, s), 5.84 (1,7-di-CH2, s),
7A0 (3-H, s ) , ' 7 2 0 (1,7-di-CsHs, m) with an intensity ratio of 1 : 2 : 1 : 5.
2 , 4 , 6 - T r i p h e n y l - 9 - o x o d i p y r a z o l o [3,4-d:4' ,3'-g] [1,3]diazocine (III). A 1.59 g (0.01 mole) s ample of 1-
p h e n y l - 3 - a m i n o p y r a z o l e and 2.08 g (0.01 mole) of b e n z a l b i s u r e a w e r e refluxed for 2 h with 20 ml of glacial
CH~COOH. The yellowish solution was poured into 300 ml of water, and the precipitate was r e m o v e d by
filtration, dried, and washed thoroughly with ether to give 1.6 g of a substance with mp 160-170 ~. Four r e -
c r y s t a l l i z a t i o n s f r o m 50% alcohol gave HI with mp 223-225 ~ Found, %: C 67.8; H 4.9; N 19.7. Mol. wt.
432. C2sH20NsO. Calculated, %: C 67.6; H 4.5; N 19.4. Mol. wt. 432.

LITERATURE CITED
1. M. A. Mikhaleva and V. P. Mamaev, Khim. G e t e r o t s i k l . Soedin., 1696 (1972).
2. u P. Mamaev and M. A. Mikhaleva, Khim. G e t e r o t s i k l . Soedin., 535 (1971).
3. N. J . H a r p e r and J . M. Sprake, J . Chem. Soc., C, 882 (1969).
4. J . G. Topliss, E, P . Shapiro, and R. J . T a b e r , J . Med. Chem., 1_O0,642 (1967).
5. V. Oakes and H. N. Rydon, J . Chem. Soc., 204 (1958).
6. Hiroaki Kadowaki, Bull. Chem. Soc. Japan, 1_~1,248 (1936); Chem. Abstr., 3__00,5944 (1936).

206
SYNTHESIS OF SUBSTITUTED 1-ISOPROPENYL- AND
1-ALKYLBN NZ IMIDA Z OLON/~ S

A. T. Ayupova, Ch. Sh. Kadyrov, UDC 547.785.5.07:542.951:541.67

and K. Seitanidi

1 - I s o p r o p e n y l b e n z i m i d a z o l o n e s , the alkylation of which with alkyl halides and 7 - b u t y r o -

lactone p r o c e e d s in the 3 position, wore obtained by r e a c t i o n of o - p h e n y l e n e d i a m i n e and
its a r o m a t i c r i n g - s u b s t i t u t e d d e r i v a t i v e s with a c e t o a c e t i c e s t e r .

B e n z i m i d a z o l e and its d e r i v a t i v e s a r e traditional objects in the s e a r c h for pesticides [1, 2], but 1-
monosubstituted b e n z i m i d a z o l o n e s have not been i n v e s t i g a t e d as h e r b i c i d e s .
We have u s e d the condensation of o-phenylenediamine and its d e r i v a t i v e s with acetoacetic e s t e r for
the s y n t h e s i s of b e n z i m i d a z o l o n e s . It is known that the p r o c e s s m a y go in s e v e r a l d i r e c t i o n s , depending on
the conditions [3, 4]. In the p r e s e n t r e s e a r c h , the condensation of o - p h e n y l e n e d i a m i n e and its 4 - c h l o r o , 3,5-
dimethyl, 3,5-dichloro, and 4 , 5 - d i c h l o r o d e r i v a t i v e s with acetoacetic e s t e r was c a r r i e d out under conditions
for which one might have expected the f o r m a t i o n of 1 - i s o p r o p e n y l b e n z i m i d a z o l o n e s (l-V). The highest
yields could be obtained when the condensation was c a r r i e d out in reflu_xing xylene in neutral m e d i a with r e -
m o v a l of the l i b e r a t e d w a t e r and alcohol by distillation. In addition to benzimidazolones I-V (Table 1), we
isolated ethyl/3 - ( o - a m i n o a n i l i n o ) c r o t o n a t e s :
R~ R~ R~ R~ "
p : : _~...hsN
I H2 Ctl3COCIt2CO2C2H~ R 2 . . ~ N H . ~=O R ' X R~, ~ / N t
R/ ~ N H ~
_ RS~ / ~ J / ~ ' N R .~~ - " ' - ~ / , " - ~ N~0 - -

I I.
CH3--C:CH 2 CH3--C=CH ~
I-V

R, R~
-2 I i
20 N H2SO4 v, ~ N \
O
R;~-~.N/) =
H
VI-X

The 5 - c h l o r o - l - i s o p r o p e n y l b e n z i m i d a z o l o n e s t r u c t u r e (II) was c o n f i r m e d by alkylation and subsequent

h y d r o l y s i s to the known 6 - c h l o r o - l - e t h y l - and , 1 - a l l y l b e n z i m i d a z o l o n e s [5], and also by the PMR s p e c t r a .
The 4 , 6 - d i m e t h y l - (III) and 4 , 6 - d i c h l o r o - l - i s o p r o p e n y l b e n z i m i d a z o l o n e (IV) s t r u c t u r e s w e r e p r o v e d by
p r e p a r a t i o n of 3 - a c y l d e r i v a t i v e s and c o m p a r i s o n of the PMR s p e c t r a . The signals of the protons of the
a r o m a t i c ring of III and IV a r e found at 6 6.71 and 6.66 ppm. The position of the signals of the a r o m a t i c
protons is r e t a i n e d f o r the 3 - a c y l d e r i v a t i v e s . This means that the allyl group does not e n t e r the 1 p o s i -
tion, o t h e r w i s e one should have expected an a p p r e c i a b l e anisotropic effect of the acyl C = O group on the
shift of 7-H. The p r e s e n c e of signals of allyl methyl groups at 2.15 and 2.20 ppm and of the signals of vinyl
protons at 5,05-5.20 ppm in the f o r m of two doublets with J = 1.5-2 Hz in the PMR s p e c t r a of b e n z i m i d a z o l -
ones I-V p r o v e s the f o r m a t i o n of 1 - i s o p r o p e n y l b e n z i m i d a z o l o n e s and excludes the s t r u c t u r e of substituted
d i h y d r o b e n z o - 2 - d i a z e p i n o n e s , in the s p e c t r a of which the protons of the methylene g r o u p r e s o n a t e at s t r o n g
field at 3.07 ppm [6]. Signals of a r o m a t i c protons at 6.7-7.3 p p m a r e o b s e r v e d in all of the s p e c t r a . The
signals of the protons of the two a r o m a t i c methyl groups f o r IH f o r m two sir~glets at 2.30-2.34 ppm.

Institute of the C h e m i s t r y of Plant Substances, A c a d e m y of Sciences of the Uzbekh SSR, Tashkent.

T r a n s l a t e d f r o m K h i m i y a G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 2, pp. 235-237, F e b r u a r y , 1974. Original
a r t i c l e s u b m i t t e d D e c e m b e r 25, 1971; r e v i s i o n s u b m i t t e d F e b r u a r y 13, 1973.

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

207
 TABLE 1. Substituted 1 - I s o p r o p e n y l b o n z i m i d a z o l o n e s and T h e i r
Alkylation P r o d u c t s
il '
mp~deg Empirical
O ~ Rt R2 R~ R4 formula

It.
II H
III 1CH3 I
119--1203
186-.-189
215--218
CloH,oN~O
CIoH~CIN20 [ 56,914,31 13,8 57,5 4,3 13,4 41
Ct2Htv'N~O [ 60,116,8113,7 59,4 6.9 13,8143
60
IV t Cl H CI ! 240--242 CIoHsCI~N20I 49,013,0/12,1 ,9,3 3,311,5/57
C1 C! 220--222 CIoHsCIsN20/ 50,3[ 3,6/ 11,5 49,3 3,3 11,51 52
C1
CI
H
H
CH3
C2H5
190--192
184--1855
CsHTC1,N20 ~ t / !5,7
CgH~CIN20 ] ] [,
115,31
69
68
vm / n C1 H E3H7 180--182 CaoH~2CITN20[ [ / 13,3 13,3] 60
1xlg C1 H C4H9 120--121 CnHI~C1N20~. ] t 12,6 12,4/53
C1 H CH~CH=CH2 172--1735 CtoHIoC1N20[ ]
H H (CH2)3COOH 8*--86 CvtHloN~O3 / 64,0 5,9110,1 64,6 6,1:I0,7 50 61

The e s t a b l i s h m e n t of the s t r u c t u r e of unknown compounds II-V showed that in the c a s e of m o n o s u b -

stituted o - p h e n y l e n e d i a m i n e , the r e a c t i o n p r o c e e d s at the m o r e basic amino group through an i n t e r m e d i a t e
a r y l a m i n o c r o t o n a t e , which is c y c l i z e d to the c o r r e s p o n d i n g 1 - i s o p r o p e n y l b e n z i m i d a z o l o n e under the r e a c -
tion conditions. The r e a c t i o n p r o c e e d s at the l e s s basic amino group f o r 3,5-disubstituted compounds,
p r o b a b l y b e c a u s e of s t e r i c h i n d r a n c e c r e a t e d by the s u b s t i t u e n t adjacent to the m o r e b a s i c amino group.
The a b s e n c e of dihydrobenzodiazepinones is p o s s i b l y explained by d i r e c t c y c l i z a t i o n of the a r y l a m i n o c r o t o n -
ate to 1 - i s o p r o p e n y l b e n z i m i d a z o l o n e without i s o m e r i z a t i o n to the amide of acetoacetic acid.
6 - C h l o r o - l - a l k y l b e n z i m i d a z o l o n e s VI-X (Table 1) w e r e obtained by alkylation of b e n z i m i d a z o l o n e II
with alkyl halides, as in [5].
We w e r e able to i s o l a t e 1 - i s o p r o p e n y l - 3 - ( 3 - c a r b o x y p r o p y l ) b e n z i m i d a z o l o n e (XI) by r e a c t i o n of 1 - i s o -
p r o p e n y l b e n z i m i d a z o l o n e with 9/-butyrolactone in d r y d i m e t h y l f o r m a m i d e (DMF) :
CH2CH~CH2COOH

CH3--t=CH 2
Xi

A b s o r p t i o n bands of the C = O group of the imidazolone ring (1680-1725 c m -l) and absorption bands of
1,2,4- (810-820 cm-1), 1,2,4,5- (850-855 c m - l ) , and 1,2,3,5-substituted (840 c m -l) benzene rings a r e ob-
s e r v e d in the IR s p e c t r a of I - X I and the 3 - a c y l d e r i v a t i v e s .
Some of the s y n t h e s i z e d compounds have s e l e c t i v e h e r b i c i d a l action [7, 8].

EXPERIMENTAL
The PMR s p e c t r a of c h l o r o f o r m (I-HI, XI) and deuteropyridine (IV, V) solutions w e r e r e c o r d e d with a
JNM-4H-100 s p e c t r o m e t e r with t e t r a m e t h y l s i l a n e as the internal s t a n d a r d .
5 - C h l o r o - l - i s o p r o p e n y l b e n z i m i d a z o l o n e (II). A solution of 1.52 ml (0.012 mole) of a e e t o a c e t i c e s t e r
(purified by the method in [9]) in 1 ml of xylene was added dropwise to a refluxing solution of 1.42 g (0.01
mole) of 4 - c h l o r o - l , 2 - p h e n y l e n e d i a m i n e in 12 m l of xylene, and the m i x t u r e was heated until the w a t e r had
been c o m p l e t e l y r e m o v e d by distillation (2 h, with a D e a n - S t a r k trap), a f t e r which it was cooled to 35-40 ~
and t r e a t e d with 15 m l of 10% aqueous p o t a s s i u m hydroxide solution. The sodium s a l t of the condensation
product p r e c i p i t a t e d on standing. The p r e c i p i t a t e was s e p a r a t e d and dissolved in w a t e r , and the solution
was acidified to give 1.13 g (41%) of bonzimidazolone II with mp 186-189 ~ {from benzene). Acidification of
the alkaline f i l t r a t e gave an additional 0.1-0.15 g of II.
Compounds I and III-V w e r e s i m i l a r l y obtained (Table 1).
6 - C h l o r o - l - m e t h y l b e n z i m i d a z o l o n e (VI). A 2.08 g (0.01 mole) s a m p l e of d r y benzimidazolone II was
added t o a solution of sodium ethoxide, p r e p a r e d f r o m 0.23 g (0.01 g - a t o m ) of sodium and 10 ml of absolute
ethanol, a f t e r which 7.6 ml (0.12 mole) of methyl iodide was added d r o p w i s e with s t i r r i n g . The m i x t u r e was
then refluxed f o r 4 h, cooled, t r e a t e d with 20 N sulfuric acid (1.4 ml), and allowed to stand at r o o m t e m p e r a -
t u r e for 3 h. An equal v o l u m e of w a t e r was added, and the m i x t u r e was e v a p o r a t e d to half its volume on a
w a t e r bath to p r e c i p i t a t e 1.2 g (60%) of benzimidazolone VI with m p 190 ~ (from aqueous alcohol).

208
 Compounds VII-X w e r e s i m i l a r l y obtained (Table 1).
1 - I s o p r o p e n y l - 3 - ( 3 - c a r b o x y p r o p y l ) b e n z i m i d a z o l o n e (XI). A m i x t u r e of 9.8 g (0.05 mole) of d r y , finely
ground s o d i u m s a l t of 1 - i s o p r o p e n y l b e n z i m i d a z o l o n e , 4.75 g (0.055 mole) of f r e s h l y distilled 7 - b u t y r o l a c t o n e ,
and 7-10 ml of d r y d i m e t h y l f o r m a m i d e was heated with s t i r r i n g at 150-155 ~ for 2 h, a f t e r which it was
cooled to about 100 ~ and d e c o m p o s e d with an equal volume of hot w a t e r . The solution was cooled and made
weakly acidic with h y d r o c h l o r i c acid, and the r e a c t i o n product was e x t r a c t e d with e t h e r . The e x t r a c t was
washed with w a t e r and t r e a t e d t h r e e t i m e s with s a t u r a t e d sodium b i c a r b o n a t e solution. The alkaline e x -
t r a c t s w e r e combined and acidified with h y d r o c h l o r i c acid to give 6 g (50%) o f b e n z i m i d a z o l o n e X I w i t h mp
84-86 ~ (from aqueous alcohol). PMR s p e c t r u m : 6 3.91 (triplet, J = 6 Hz, a - c H 2 ) , 2.33 (triplet, J = 6 Hz,
-CH2), 2.00 (multiplet, fl -CH2) , 10.54 ppm (singtet, C OOH).

L I T I i ~ R A TU R E CITgD
I. A. M. l~fros and M. P . F e d o s e e v a , Dokl. Akad. Nauk SSSR, 146, 236 (1962).
2. J . J . S i m s , H. Mee, and D, C. Erwin, Phytopathology, 5__99,1775 {1969).
3. G. A. A r c h e r and L. H. Sternbach, C h e m . Rev., 6._88, 747 (1968).
4. A. N. Kost, Z. F . Solomko, N. P . P r i k h o d ' k o , and S. S. T e t e r y u k , Khim. G e t e r o t s i k l . Soedin., 1556
(1971).
5. J . Davoll, and D. H. Laney, J . C h e m . Soc., 308, 314 (1960).
6. A. N. Kost, Z. F. Solomko, N. P . P r i k h o d ' k o , and A. P . T e r e n t ' e v a , Khim. G e t e r o t s i k l . Soedin., 787
(1971).
7. Ch. Sh. Kadyrov,A. T. Ayupova, and A. A. Rakhimov, USSRAuthor's Certificate No. 235,510 (1969);
Byul. Izobr., No. 5 (1969).
8. Ch. Sh. Kadyrov,M. N. Kosyakovskaya,A. T. Ayupova, A. A. Rakhimov, A. Khikmatov, and
K. Akbarov, Agrokhimiya,1_~I,161 (1969).
9. S. Coffey,J. K. Thomson, and F. J. Wilson, J. Chem. Soc., 856 (1936).

209
REACTIVITiES OF D I A N I O N S OF PYRIDYL PHENYL KETONES*

T. R. Strelets and D. V. Ioffe UDC 547.823.828

Substituted pyridylphenylcarbinols are formed in the reaction of the dianions of isomeric

pyridyl phenyl ketones with alkyI halides, aldehydes, and benzonitrile. The reaction of the
dianlon of 3-pyridyl phenyl ketone with benzophenone, in contrast to the analogous reaction
of the dianion of 2-pyridyl phenyl ketone, gives 5-benzoyl-2-diphenylhydroxymethyl-l,2-
dihydropyridine. It is assumed that the observed reaction includes one-electron t ransfer
and the formation of two anion radicals. Recombination of the anion radical of 3-pyridyl
phenyl ketone leads to 5, 5' -dibenzoyl-2,2'-di(1,2-dihydropyridyl).

In contrast to the dianions of the carb0cyclic s e r i e s , very little study has been devoted to the re a c tiv i-
ties of the diauions of heterodyclic ketones. Only the preparation of the dianions of pyridyl phenyl ketones
and their alkylation has been described [3]. It is also known that the reduction of isomeric pyridine deriva-
tives containing e l e c t r o n - a c c e p t e r groups may proceed differently. Thus the reduction of 3-cyanopyridine
with sodium borohydride gives di- and tetrahydropyridine derivatives, while the nitrile group is reduced in
t h e analogous reaction of 2- and 4-cyanopyridines [4]. In this connection, it seemed of interest during a
study of the reactivities of the dianions to compare the properties of the dianions and anion radicals of iso-
meric pyridyl phenyl ketones.
The reaction of all three isomeric pyridyl phenyl ketones with two equivalents of lithium or sodium in
liquid ammonia gives dianions, the alkylation of which with alkyl halides leads to alkylpyridylphenylcarbinols,
while reaction with aromatic aldehydes and benzonitrile leads to glycols and keto alcohols.
{PyCOC6a5]2-2M C6HsCN
I-Ill C6Hs Nil %f15. O

Py(~(OH)CH(OHIAr PyCI~(OH) C6Hs

C~H~
I Py=2-pyridyl II Py= 3-pyridyl III Py= 4-pyridyl
A difference in the reactivities of dianions I-Ill was observed in the reaction with benzophenone. While
reaction of dianion I with benzophenone gave 1,1,2-triphenyl-2-(2-pyridyl)ethanediol, the analogous reaction
of dianion II gave 5-benzoyl-2-diphenylhydroxymethyl-l,2-dihydropyridine(IV) in 93% yield. This same
compound was obtained by reaction of two anion radicals - those of benzophenone and 3-pyridyl phenyl
ketone (V) - and by reaction of the dianion of benzophenone with 3-pyridyl phenyl ketone. The structure of
dihydropyridine IV was proved by spectral methods and also by chemical transformations. The UV sp e c -
trum of IV contains two bands, which is characteristic for 5-substituted 1,2-dihydropyridine [5]. Oxidation
of IV gave 5-benzoyl-2-diphenylhydroxymethylpyridine(VI), the Haller cleavage [6] of which gave the known
2-pyridyldiphenylc arbinol.
The formation of dihydropyridine IV i s p o s s i b l y due to st eri c hindrance arising during the reaction of
dianion II with benzophenone. It has been shown [7] that ambident c h a r a c t e r of the dianion is displayed in the
reaction of the dianion of benzophenone with st eri cal l y hindered alkyl halides. Atkylation of dianion II with

*Communication XV of the s e r i es "Reductive Metallation of C arbonyl Compounds 7 See [1] for communica-
tion XIV. See [2] for the preliminary communication.
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 238-242, February, 1974.
Original article submitted December 7, 1972.

9 19 75Plenum Publishing Corporation, 227 West 17th Street, New York, N.Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher..4 copy o f this article is availablefrom the publisher for $15.00.

210
 6 ~ o c. z
9 ~2-~ ~co\ L J --.
[~c~"0~176/
9 ~,cY4~
~>~6 v --~

IV I1 Vll

C 6 H 5 C ~ .,.~"-,. ...~",.. / CC6 H 5

V| VIII

the s t e r i c a l l y hindered t e r t - b u t y l bromide gave a product of substitution of the pyridine ring in addition to
t e r t - b u t y l - 3 - p y r i d y l p h e n y l c a r b i n o l (in 707c yield). Although we were unable to isolate this compound be-
cause of its e x t r e m e instability, the s p e c t r a l c h a r a c t e r i s t i c s c o n f i r m that it has the dihydropyridine s t r u c -
t u r e . However, in c o n t r a s t to the quantitative yield of dihydropyridine IV, the yield of this compound was
low. In addition, it can be a s s u m e d that the s t e r i c difficulties are identical in the r e a c t i o n of benzophenone
with dianions I and II, but, n e v e r t h e l e s s , these reactions lead to c o m p l e t e l y different r e s u l t s .
In our opinion, the r e a c t i o n of dianion II with benzophenone, in c o n t r a s t to the reaction of II with alkyl
halides, includes o n e - e l e c t r o n t r a n s f e r . This s o r t of m e c h a n i s m is o b s e r v e d in a number of anion r e a c -
tions [8]. O n e - e l e c t r o n t r a n s f e r is c o n s i d e r e d to be one of the alternative m e c h a n i s m s for the reaction of
benzophenone with a z a h e t e r o c y c l e s in the p r e s e n c e of lithium metal [9]. As a r e s u l t of o n e - e l e c t r o n t r a n s -
fer, two anion radicals - t h o s e of benzophenone and 3 - p y r i d y l phenyl ketone--" which also interact, are
f o r m e d in the investigated r e a c t i o n . Anion radicals and dianions can differ substantially with r e s p e c t to
their reactivities [10]. Calculation of the distribution of the spin density in anion radicals of the s i m i l a r
compounds 3,3-dipyridyl ketone [11] and 3-pyridyl methyl ketone [12] leads to a m a x i m u m value of the den-
s i t y of the unpaired e l e c t r o n in the 6 position of the pyridine ring. Analysis of the ESR s p e c t r u m of the
anion r a d i c a l of 3 - p y r i d y l phenyl ketone, which was p e r f o r m e d by V. M. Kazakova and c o - w o r k e r s in the
D e p a r t m e n t of P h y s i c a l C h e m i s t r y of the Moscow Institute of P r e c i s i o n Chemical Technology, also showed
that the m a x i m u m value of the spin density is in the 6 position of the pyridine ring.
In addition to the reactions of dianions I-III, we also studied the recombination reactions of the anion
radicals of the three i s o m e r i c pyridyl phenyl ketones. Recombination of two anion radicals of 2 - p y r i d y l
phenyl ketone leads to 1 , 2 - d i p h e n y l - l , 2 - d i ( 2 - p y r i d y l ) e t h a n e d i o l . Only an e q u i m o l e c u l a r mixture of the c o r -
responding carbinol and the s t a r t i n g ketone was isolated f r o m the analogous reaction of 4 - p y r i d y l phenyl
ketone. U n s u c c e s s f u l attempts to obtain pinacol f r o m 4 - p y r i d y l phenyl ketone are d e s c r i b e d in the l i t e r a t u r e

TABLt~ 1. PyC (OH)RCsH 5

i N, % i 9
Empirical
py rap, deg :C (solvent) formula ~
' found !yield,
%

2-Py C2H5 78--79 !spetroleum :iC14HIsNO i95

ether) ' i
2-Py
2-Py
i-CzH7
t-C'4H9
65 (hexane)I~
81--83 (2-propanol)
CznHlrNO
C16HIgNO 5S i90
.97
2=Py CH(OH)C6H5 167--169 (dioxane) C19HtrNO2 4,7 4,8 !75
2-Py C(OH) (C6Hs)2* 113--115 (hexane) C26H21NO2 3,91 3,84 88
3-Py C2Hs 104--105 (eyclohexane 16 CI,HIsNO ~85
3-Py i-C3H7 127--129 (hexane) CI~HITNO 196
3-Py !C6HsCH2 153--154 (2-propanol)I~ lCtgHIzNO 194
3-Py CH(OH)CsHs 184--186 (chloroform) IC'19HIzNO~ 4,7 4,8 ~50
3-Py CH(OH) (p-CH3OC6H,) 173--174 (chloroform) 'IC20H19NO3 . 4,3 4,3 r64
3-Py C(NH)C~Hs 140~141 (ethanol) iC~gH]6N~O 9,8 9,7
3-Py COC6H~I" 116--118 (2-propane1) iC]gHI~NO2 4,7 4,8
4-Py C2H5 152--153 (dichloroethane)2~ICt4HIsNO 70
4-Py i-CsH7 138 (heptane)~l iC,sHI~NO

* The r e a c t i o n m a s s was poured into a solution of an excess of a m -

monium chloride in liquid a m m o n i a for neutralization.
Obtained by saponification of the preceding compound with 5% h y d r o -
c h l o r i c acid at 50~

211
[13]. The r e c o m b i n a t i o n of two anion r a d i c a l s V gave 5 , 5 ' - d i b e n z o y l - 2 , 2 ' - d i ( 1 , 2 - d i h y d r o p y r i d y l ) (VII). The
s t r u c t u r e of the l a t t e r was p r o v e d by s p e c t r a l methods and also by oxidation to the known 5 , 5 ' - d i b e n z o y l -
2 , 2 ' - d i p y r i d y l (VIII) [14]o It is e s s e n t i a l to note that dihydropyridyl VII is f o r m e d in the r e a c t i o n of sodium
amide in liquid a m m o n i a with 1 , 2 - d i p h e n y l - l , 2 - d i ( 3 - p y r i d y l ) e t h a n e d i o l .
The r e c o m b i n a t i o n of two anion r a d i c a l s of a r o m a t i c ketones c a n lead to the f o r m a t i o n of t h r e e types
of d i m e r s - one with a new bond between the c a r b o n y l c a r b o n s , one with a new bond between the c a r b o n y l
c a r b o n and the ring c a r b o n , and one with a new bond between two c a r b o n atoms of different r i n g s . D i m e r s
of the f i r s t type - pinacols - a r e m o s t often f o r m e d . The f o r m a t i o n of d i m e r s of the second type, which is
a s s o c i a t e d with d e a r o m a t i z a t i o n of one a r o m a t i c ring, is c o n s i d e r a b l y r a r e r [15, 16]. Finally, d e a r o m a t i z a -
"tion of two rings and f o r m a t i o n of a bond between two c a r b o n a t o m s of t h e s e rings has been noted only in the
c a s e of e l e c t r o c h e m i c a l reduction [17]. This s o r t of r e c o m b i n a t i o n has been o b s e r v e d for the f i r s t t i m e
during the c h e m i c a l reduction of ketones.

EXPERIMENTAL
Substituted P y r i d y l p h e n y l c a r b i n o l s (Table 1). A solution of 0.01 mole of alkylating agent in 10 ml of
e t h e r was added to a violet solution of the dianion, p r e p a r e d f r o m 0.01 m o l e of pyridyl phenyl ketone and
0.022 g - a t o m of s o d i u m in 5~ ml of liquid a m m o n i a via the method in [3]. After 10-15 min, 0.02 mole of
a m m o n i u m c h l o r i d e was added, and the a m m o n i a was r e m o v e d by distillation. The r e s i d u e was diluted with
w a t e r , and the r e a c t i o n product was r e m o v e d by filtration and c r y s t a l l i z e d . Alkyl b r o m i d e s , benzyl c h l o -
ride, benzaldehyde, p - m e t h o x y b e n z a l d e h y d e , benzonitrile, and benzophenone w e r e u s e d as r e a g e n t s .
( 3 - P y r i d y l ) p h e n y l - t e r t - b u t y l c a r b i n o l . A 1.37 g (0.01 mole) s a m p l e of t e r t - b u t y l b r o m i d e was added
to dianion II, obtained f r o m 1.83 g (0.01 mole) of 3 - p y r i d y l phenyl ketone in liquid a m m o n i a . After 15 min,
1.1 g (0.02 mole) of a m m o n i u m chloride was added, and the a m m o n i a was r e m o v e d by distillation. W a t e r
was added to the r e s i d u e , and the light-yellow p r e c i p i t a t e was s e p a r a t e d . Column c h r o m a t o g r a p h y (activity
III aluminum oxide, ether) gave ( 3 - p y r i d y l ) p h e n y l - t e r t - b u t y l c a r b i n o l , with mp 153-154 ~ (isopropyl alcohol),
in 70% yield. IR s p e c t r u m (CHC13): 3620 c m -1 (OH). Found, %: N 6.0. C16H19NO. Calculated, ~c: N 5.8.
In addition to the c a r b i n o l , 13% of a s u b s t a n c e , the IR s p e c t r u m of which contained bands at 1670 (C O) and
3455 c m -1 (NH), was isolated.
5 - B e n z o y l - 2 - d i p h e n y l h y d r o x y m e t h y l - l , 2 - d i h y d r o p y r i d i n e (IV): A__=A 1.82 g (0.01 mole) s a m p l e of
benzophenone was added to dianion II, obtained f r o m 1.83 g (0.01 mole) of 3 - p y r i d y l phenyl ketone in liquid
a m m o n i a . The usual workup gave IV, with mp 103-104 ~ (from benzene), in 97~c yield. IR s p e c t r u m (CHC13):
1650 (CO), 3435 (NH), 3550 and 3620 c m -t (OH). UV s p e c t r u m in alcohol, ~ m a x nm (log e): 304 (3.84),
360 (3.95). Found, ~c: C 82.0; H 6.1. C25H21NO2. Calculated, %: C 81.7; H 5.8.
B. A 0.01 m o l e s a m p l e of 3 - p y r i d y l phenyl ketone was added to 0.01 mole of the dianion of benzo-
phenon~'in liquid a m m o n i a . The usual workup gave IV, with mp 103-104 ~ (from benzene), in 92~ yield.
C.: A solution of anion r a d i c a l V, obtained f r o m 1.83 g (0.01 mole) of 3 - p y r i d y l phenyl ketone and
0.25 g (0.011 g , a t o m ) of sodium in liquid a m m o n i a , was added to a solution of the anion r a d i c a l of benzo-
phenone, obtained f r o m 1.82 g (0.01 mole) of benzophenone and 0.25 g (0.011 g - a t o m ) of sodium in liquid
a m m o n i a . The usual workup gave IV, with m p 99-101 ~ in 98~c yield.
5 ' B e n z o y l - 2 - ( d i p h e n y l h y d r o x y m e t h y l ) p y r i d i n e (VI). A solution of 0.37 g (1 mmole) of IV and 0.11 g
(1 mmole) of p-benzoquinone in 20 ml of benzene was refluxed for 4 h, a f t e r which it was cooled and washed
with 10% sodium hydroxide solution, 5~c h y d r o c h l o r i c acid, and w a t e r . The benzene was then r e m o v e d by
distillation to give 0.28 g (75%) of VI with mp 123-124 ~ (from heptane). IR s p e c t r u m (CHC13): 1670 (CO),
3240 and 3620 c m -1 (OH). Found, %: C 81.8; H 5.3; N 3.8. C25HI~NO2. Calculated, %: C 82.2; H 5.2; N 3.8.
Diphenyl(2-pyridyl)carbinol. A solution of 1 g (2.7 mmole) of VI in 10 ml of toluene was added to a
s u s p e n s i o n of s o d i u m amide in 40 m l of toluene. The m i x t u r e was cooled, and 1 m l of alcohol and 20 m l of
w a t e r w e r e added. The toluene l a y e r was s e p a r a t e d and washed with w a t e r . Removal of the solvent by
distillation gave 0.3 g of diphenyl(2-pyridyl)carbinol with mp 102-105 ~ (from ethanol); the product did not
d e p r e s s the melting point of an authentic s a m p l e [18].
1 , 2 - D i p h e n y l - l , 2 - d i ( 2 - p y r i d y l ) e t h a n e d i o l . A 1.83 g (0.01 mole) s a m p l e of 2 - p y r i d y l phenyl ketone was
added to 0 2 3 g (0.01 g - a t o m ) of sodium in liquid a m m o n i a . The r e s u l t i n g blue solution of the anion r a d i c a l
was poured, a f t e r 15 min, into a solution of 3 g of a m m o n i u m chloride in liquid a m m o n i a . The a m m o n i a
was e v a p o r a t e d , and w a t e r was added. The p r e c i p i t a t e was r e m o v e d by filtration to give 1 , 2 - d i ( 2 - p y r i d y l ) -
ethanediol, with mp 138-139 ~ in 80% yield [23].

212
 5,5'-Dibenzoyl-2,2'-di(1,2-dihydropyridyl) (VII). A. A 1.83 g (0.01 mole) sample of 3-pyridyl phenyl
ketone was added to 023 g (0,01 g-atom) of sodium in 50 ml of liquid ammonia. The resulting green solu-
tion of anion radical V was neutralized with ammonium chloride, and the ammonia was removed by distilla-
tion. Water was added, and the yellow precipitate was removed by filtration to give VII, with mp 86-89 ~
(from benzene), in 98gc yield. IR spectrum (CHC13): 1665 (CO) and 3430 cm -1 (NH). Found, %: N 7.2.
C24II20N202. Calculated, %: N 7.6.
B_.: A 0.9 g (2.5 mmole) s ample of 1,2-diphenyl-l,2-di (3-pyridyl) ethanediol, obtained photochemically
[22], was added to a suspension of sodium amide in 30 ml of liquid ammonia, obtained from 0.12 g (5 rag-
atom) of sodium. The green solution that formed during the addition was neutralized with ammonium chlo-
ride. The usual workup gave VII, with mp 69-75 ~ in 90% yield. The IR spect ra of the compounds obtained
by methods A and B were identical.
5,5'-Dibenzoyl-2,2'-dipyridyl {VIII). A solution of 0.5 g (1.4 mmole) of VII and 0.15 g (1.4 mmole) of
p-benzoquinone in 10 ml of benzene was refluxed for 2 h. It was then cooled and washed with 10~ sodium
hydroxide solution, 5% hydrochloric acid, and water. Removal of the benzene by distillation gave VIII, with
mp 211-212 ~ (from alcohol-benzene), in 40~c yield [14].

LITERATURg CITgD
1. D . V . Ioffe and V. N. Chursina, Zh. Organ. Khim,, 8, 806 (1972).
2. D . V . Ioffe and T. R, Strelets, Khim. Geterotsikl. Soedin., 129 {1972).
3. M. Miocque and C. Fauran, Compt. Rend., C, 25___99,408 (1964); Bull. Soc. Chim. France, 3162 (1965).
4. S. Yamada, M. Kuramoto, and J. Kikugawa, Tetrahedron, 3_.66,3104 (1969).
5. R. Lyle and P. Anderson, Adv. Heterocycl. Chem., 6, 57 (1966).
6. K . E . Hamlin and A. W. Weston, Organic Reactions, Vol. 9 [Russian translation], IL (1959), p. 7.
7. M . I . Mostova and D. V. Ioffe, Zh. Organ. Khim., 8, 1547 {1972).
8. K . A . Bilevich and O. Yu. Okhlobystin, Usp. Khim., 3__.77,2162 (1968).
9. C . E . Crawforth, C. A. Russel, and O. Meth-Cohn, Chem. Commun., 1406 (1970); J. Chem. Soc.,
Perkin I, 1176 (1972).
10. W. Remers, G. Gibs, R. Ridaeks, and M. Weiss, J. Org. Chem., 3__66,279 (1971).
11. I . D . Morozova and M. ~ . Dyatkina, Zh. Strukt. Khim., 6, 278 (1965).
12. P . T . Cottrell and P. H. Rieger, Mol. Phys., 1._.22,149 (1967).
13. g . V . B r o w n and M. B. Shambu, J. Heterocycl. Chem., 8, 967 (1971).
14. W .H. Sasse and C. P. Whittle, J . Chem. Soc., 1347 (1961).
15. J. Morizur and J. Wieman, Bull. Soc. Chim. France, 1619 (1964).
16. J . Grim_shaw and E. Rea, J . Chem. Soc., C, 2628 (1967).
17. K . M . Johnston, Tetrahedron Left., 837 (1967).
18. C . H . Tilford, R. S. Shelton, and M. G. Van Campen, J. Am. Chem. Soc., 7__00,4001 (1948).
19. M. Protiva and M. Borovicka, Czechoslovakian Patent No. 85,411 (1955); Chem. Abstr., 6_0, 10,798
(1956).
20. A . G . Davies, J . Kenyon, and K. Thaker, J. Chem. Soc., 3394 (1956).
21. K. Thaker and U. S. Pathak, J. Indian Chem. Soc., 4..~1, 555 (1964).
22. M . R . Kegelman and E. V. Brown, J. Am. Chem. Soc., 755, 4649 {1953).
23. F . F . Ebetino and E. D. Amstutz, J. Org. Chem., 2_88,3249 {1963).

213
REACTIONS OF 1,5-DIKETONES
X.* REACTION OF ALICYCLIC 1,5-DIKETONES WITH
PRIMARY ALIPHATIC AMINES

A. N. Saverchenko, Z, R. Bekkerova, UDC 547.835

V. A. Kaminskii, and M. N. Tilichenko

N - R - 9 - R ' - D e c a h y d r o a c r i d i n e s , which a r e f o r m e d as a r e s u l t of the r e a c t i o n of alicyclic 1,5-

diketones with p r i m a r y aliphatic a m i n e s , s p l i t out a substituent f r o m the nitrogen atom and
a hydrogen a t o m f r o m the 9 position to give 9 - R ' - s y m - o c t a h y d r o a c r i d i n e s . On the basis of
the IR s p e c t r a , it was concluded that the N - ~ - h y d r o x y e t h y l ) - 9 - R ' - d e c a h y d r o a c r i d i n e s c y c l i z e .

The l i t e r a t u r e data on the r e a c t i o n of 1,5-diketones with p r i m a r y aliphatic amines a r e m e a g e r [2, 3].

In p a r t i c u l a r , it is indicated that 2 , 2 ' - m e t h y l e n e d i c y c l o h e x a n o n e (I) f o r m s the c o r r e s p o n d i n g N - a l k y l d e c a -
h y d r o a c r i d i n e s with m e t h y l a m i n e and its homologs [3].
We s e l e c t e d I and the product of i n t r a m o l e c u l a r aldolization of 2,2'-benzylidenedicyclohexanone -
4 - p h e n y l - 2 , 3 - t e t r a m e t h y l e n e b i c y c l o [ 3 . 3 . 1 ] n o n a n - 2 - o l - 9 - o n e (II) - as the diketones for our study. The p r i m -
a r y amines u s e d w e r e m e t h y l a m i n e (IIIa), ethanolamine (nIb), b e n z y l a m i n e {IIIc), and glycine ethyl e s t e r
(Hid).

A tendency f o r splitting out of substituents f r o m the nitrogen a t o m and a hydrogen a t o m f r o m the 9

position of the r e s u l t i n g N - R - 9 - R ' - d e c a h y d r o a c r i d i n e s (IV, V) was o b s e r v e d when the r e a c t i o n was c a r r i e d
out in a nonpolar s o l v e n t (benzene, m - x y l e n e ) ; this leads to the c o r r e s p o n d i n g s y m - o c t a h y d r o a c r i d i n e
d e r i v a t i v e s (Via, b).
R'

R' tl / R - - H +

II R
VII a-C, VIII b-d

IV, V, VII, VIII a R=CH3; b R=CH2CH2OH; C R=CH2C6Hs; d R=CH2COOC2Hs, |V,Vll R'=H;

V,VII! R'=E6tts; VI a R'=H; b R'=C6H s

The e a s e of a r o m a t i z a t i o n depends on the r e a c t i o n t e m p e r a t u r e (the r e a c t i o n p r o c e e d s to a g r e a t e r e x -

tent in xylene than in benzene) and on the nature of group R, and the e a s e of c l e a v a g e d e c r e a s e s in the o r d e r
CH2COOC2H 5 > CH2C6H ~ > CH~ > CH2CH2OH. Thus only o c t a h y d r o a c r i d i n e Via is obtained in the r e a c t i o n
of ketone I with a m i n e IIId even in b e n z e n e . Compounds IVc, Vc, and Vd a r e f o r m e d in a m i x t u r e with
a r o m a t i z e d Via o r , r e s p e c t i v e l y , VIb. Compound IVa contains only a s m a l l amount of Via; IVb and Vb a r e
f o r m e d without contamination b y Via o r Vlb. Ketot II and IIIa do not f o r m products of the h y d r o a c r i d i n e
s e r i e s ; in this c a s e , 9-phenyloctahydroxanthene was isolated [4]. All IV and V a r e s m o o t h l y c o n v e r t e d to

* See [1] for c o m m u n i c a t i o n IX.

F a r - E a s t e r n State U n i v e r s i t y , Vladivostok. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii,
No. 2, pp. 243-246, F e b r u a r y , 1974. Original a r t i c l e s u b m i t t e d October 31, 1972.

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

214
Via or, r e s p e c t i v e l y , VIb on heating to 240-280 ~ The s a m e r e s u l t is o b s e r v e d in the t h e r m o l y s i s of N - R -
9 - R ' - l l , 1 4 - d i c y a n o p e r h y d r o a c r i d i n e s VII and VIII.

There are no data on a r o m a t i z a t i o n proceeding with splitting out of an alkyl group f r o m the nitrogen
atom of dihydropyridine in the review l i t e r a t u r e [5]. Only a single c a s e of this s o r t of reaction is d e s c r i b e d
[2]; an assumption r e g a r d i n g the possibility of a r o m a t i z a t i o n of N - m e t h y l d e c a h y d r o a c r i d i n e is stated in [6].
A c o m p a r i s o n of the data that we obtained with the p r e v i o u s l y detected exceptionally facile a r o m a t i z a t i o n of
N - a m i n o d e c a h y d r o a c r i d i n e derivatives rl] makes it possible to conclude that a r o m a t i z a t i o n is quite g e n e r a l
in the d e c a h y d r o a c r i d i n e s e r i e s .
The d e c a h y d r o a c r i d i n e s that we isolated in the individual state (IVb, Vb, and Vc) add two molecules
of HCN to give dicyanides VIIb, VIIIb, and VIIIc. Dicyanides VIIa, VIIc, and VIIId, respectively, were i s o -
lated by t r e a t m e n t with HCN of mixtures of IVa and IVc with Via and of a mixture of Vd with VIb. The ab-
s o r p t i o n of an OH group at 3050-3700 c m -1 is absent in the IR s p e c t r a of N-(fl - h y d r o x y e t h y l ) d e c a h y d r o -
acridines IVb and Vb. In place of the two bands at 1670-1700 cm -t that are c h a r a c t e r i s t i c for d e c a h y d r o -
acridines [7] {this s o r t of doublet is o b s e r v e d in the s p e c t r u m of Vc), there is only one peak at 1670 cm-1;
this is c h a r a c t e r i s t i c for d o d e c a h y d r o a c r i d i n e s [8]. At the s a m e time, the IR s p e c t r a of dicyanides VIIb
and VIIIb contain the absorption band of an OH group at 3600 c m -l. This makes it possible to a s s u m e r e -
v e r s i b l e c y c l i z a t i o n of IVb and Vb of the type involving nucleophilic addition to 1 , 4 - d i h y d r o p y r i d i n e s :
1" 1'

/ ,
CH 2 OH

As p r e v i o u s l y established [9], c a r r y i n g out of the r e a c t i o n of diketone I with p r i m a r y aliphatic amines

in the p r e s e n c e of CC14 leads to a s y m - o c t a h y d r o a c r i d i n i u m salt only in the c a s e of amine IIIc. However,
when a m o r e active oxidizing agent - b r o m o f o r m - was used, we w e r e able to obtain N - R - s y m - o c t a h y d r o -
a c r i d i n i u m salts with amines IIIb and IIId (but not with IIIa). The r e a c t i o n of diketone I with amine Bib is
accompanied by r e p l a c e m e n t of the OH group by bromine under the influence Of the HBr f o r m e d during the
decomposition of b r o m o f o r m ; the reaction product is an N - ( f i - b r o m o e t h y l ) - s y m - o c t a h y d r o a e r i d i n i u m salt
(IX). An N - m e t h y l - s y m - o c t a h y d r o a c r i d i n i u m salt (X) is f o r m e d in the r e a c t i o n of diketone I with amine IIId
in the p r e s e n c e of b r o m o f o r m . This is apparently the r e s u l t of hydrolysis of the e s t e r group by the w a t e r
liberated in the condensation of I and IIId with subs equent decarboxylation of the N - e a r b o x y m e t h y l - s y m -
octahydroac ridinium salt.

~XPgRIM~ NTAL
The IR s p e c t r a of m i n e r a l oil suspensions of the compounds were r e c o r d e d with a UR-20 s p e c t r o m -
e t e r . In all c a s e s , Via and VIb were identical to genuine samples [10, 11J according to the results of thin-
l a y e r c h r o m a t o g r a p h y (TLC) [activity II A12Oi, in e t h e r - e t h y l acetate ( 7 . ! ) ; R f 0.7 for Via and 0.4 for VIb].
The pierate of Via and base VIb did not d e p r e s s the melting points of genuine s a m p l e s .
Reaction of Diketones I and II with P r i m a r y Aliphatic A m i n e s . A mixture of 0.02 mole of I o r II and
0.02 mole of amine in 30-40 ml of benzene or m - x y l e n e was refluxed with a D e a n - S t a r k trap until water
liberation c e a s e d (4-6 h) ; in the r e a c t i o n with 1I, the catalytic addition of p-toluenesulfonic acid was n e c e s -
s a r y . The solvent was then vacuf~m evaporated.

Reaction of Diketone I with Amine IIId (I + IIId). The residue c o n s i s t e d a l m o s t entirely of o c t a h y d r o -

acridine Via.

I + I I I c . When the r e a c t i o n was c a r r i e d out in xylene, the residue w a s ' a mixture of d e c a h y d r o a c r i d i n e

IVc and o e t a h y d r o a c r i d i n e Via with p r e d o m i n a n c e of the latter (according to TLC). When the r e a c t i o n was
c a r r i e d out in benzene, when IVc > Via, the mixture was t r e a t e d with a solution of KCN in acetic acid, and
N - b e n z y l - l l , 1 4 - d i c y a n o p e r h y d r o a c r i d i n e (V]Ic) (52~c yield) was r e m o v e d by filtration after 2 h; it was
identical to a genuine s a m p l e [81 a c c o r d i n g to the IR s p e c t r u m . A r o m a t i z a t i o n of IVe o c c u r r e d during
vacuum distillation of the mixture of IVc and Via, and pure Via, with bp 125-127 ~ (2 ram), was obtained in
the distillate.

I + i I i a and I + IIIb. The r e s i d u e was vacuum distilled to give, r e s p e c t i v e l y , d e c a h y d r o a c r i d i n e IVa

[with a s m a l l amount of o c t a h y d r o a c r i d i n e Via (according to TLC)], with bp 140-154 ~ (2 mm), in 73~c yield

215
 T A B L E I. N - R - 9 - R ' - D e c a h y d r o a c r i d i n e s (IV, V) and N'R-9-Phenyl-
1 1,14-dic yanoperhydr oa'cridines (VIII)

Com- Found, Calc., ~o Yield,

mp, deg ~'C Empirical
pound formula c H N C H N I%
IVb 152--154 (2)* CIsH23NO 77,0 9,9 6,6 77,2 9,9 6,0 70
yb 93--94 C21H27N0 81,l 9,3 5,0 81.6 8,7 4,5 74
ve 101--102 C26HmN 87.6 8,6 3,8 87,9 8,2 3,9 60
Vlllb 168--169 C2~H29N~O 76,8 8,5 11,2 76,0 7.9 11,5 70
VIIIc 233--234 C2sHsIN3 81,6 8,1 10,3 82,1 7,6 10,3 70
IIld 172--174 C2~HsINs02 74,0 8,5 9,8 74,1 7,6 10.4 7G

* This is the boiling point (nm, m e r c u r y standard).

(the product could not be f r e e d f r o m Via on r e p e a t e d distillation) and pure IVb (see Table 1). N - M e t h y l - l l ,
1 4 - d i c y a n o p e r h y d r o a c r i d i n e (VIIa}, which was identical to a genuine s a m p l e [12] according to the IR s p e c -
t r u m , was s i m i l a r l y obtained f r o m the mixture of IVa and Via obtained by distillation.
II + I I I a and II + IIIb. The r e s i d u e was t r e a t e d with alcohol and r e m o v e d by filtration: in the c a s e of
IIIa, 9-phenyloctahydroxanthene (in 34% yield), which was identical to a genuine s a m p l e [4] according to the
IR s p e c t r u m , was obtained, while Vb (see Table 1) was isolated in the c a s e of IlIb. T r e a t m e n t of Vb with
KCN in acetic acid gave dicyanide VHIb.
II + IIIb. The r e s i d u e was t r e a t e d with acetone, the mixture was cooled to -50 ~ and Vb (Table 1) was
r e m o v e d by filtration. Dicyanide VIIIb was obtained f r o m Vb.
II + IIId. When the r e a c t i o n was c a r r i e d out in xylene, the r e s i d u e c o n s i s t e d p r i m a r i l y of VIb; in b e n -
zene t}le r e s i d u e contained p r i m a r i l y Vd, which could not be isolated. The residue was t r e a t e d with KCN in
acetic acid, and dicyanide VIIId was r e m o v e d by filtration. IR s p e c t r u m : 2230 (CN) and 1760 (ester c a r -
bonyl) c m -1 .

A r o m a t i z a t i o n of N - R - 9 - R ' - D e c a h y d r o a c r i d i n e s and N - R - 9 - R ' - 1 1 , 1 4 - D i c y a n o p e r h y d r o a c r i d i n e s . A

0 ~2 g s ample of d e c a h y d r o a c r i d i n e Vb or Vc was heated at 240-250 ~ for 1 h to give pure o c t a h y d r o a c r i d i n e
VIb. Similarly, Via containing s t a r t i n g IVb (according to TLC) was obtained f r o m 1 g of IVb after 3 h at
260-280 ~ . D e s t r u c t i v e distillation of 2.3 g of VIIc gave 0.6 g of Via. The volatile t h e r m o l y s i s products
were collected in a trap cooled with d r y ice; toluene was detected in the products by g a s - l i q u i d c h r o m -
atography. A 0.2 g s a m p l e of VIIId was heated at 240 ~ for 1 h to give pure VIb.
Reaction of IVb with B r o m o f o r m . A solution of 1 g of IVb in 2 ml of b r o m o f o r m was refluxed for 3 h,
after which it was diluted with 15 ml of water, shaken, and extracted with ether. The aqueous l a y e r was
t r e a t e d with NH4C104 solution, and the mixture was filtered to give 0.8 g (47~c) of IX with mp 234 ~. Found, %:
C 45.9; H 5.7; Br 20.1; CI 8.9; N 4.0. C15H21BrCINO 4. Calculated, %: C 45.5; H 5.3; Br 20.3; CI 9.0; N 3.5.
IR s p e c t r u m : 1100 c m -i (CIO4); no absorption at 3000-3700 c m -i.
Reaction of I with [lib and [lid in B r o m o f o r m . A mixture of 0.02 mole of I, 0.02 mole of IIIb or [lid,
and 0.04 mole of b r o m o f o r m in 20 ml of benzene was refluxed for 4 h, after which it was worked up as in
the preceding method. In the c a s e of IIIb, IX was isolated in 47~c yield, while X, which was identical to a
genuine s a m p l e [8] according to the IR s p e c t r u m , was isolated in 33% yield in the c a s e of IIId.

LITERATURE CITED
1. T. V. Moskovkina, V. A. Kaminskii, V. I. Vysotskii, and M. N. Tilichenko, Khim. Geterotsikl. Soedin.,
826 (1973).
2. K. W, Merz and H. Richter, A r c h . P h a r m . , 275, 2941 (1937); C h e m . A b s t r . , 3_!1, 70, 597 (1937).
3. L . R. F r e i m i l l e r and I. W. Nemec, US Patent No. 3,326,917; C h e m . A b s t r . , 68, 49, 469 (1968).
4. A. N. Saverchenko, V. A. Kaminskii, and M. N. Tilichenko, Khim. Geterotsikl. Soedin., 384 (1973).
5. U. E i s n e r and J . Kuthan, C h e m . Rev., 7_.22, 1 (1972).
6. R. S. Monson, D. N. P r i e s t , and I. C. Ullrey, T e t r a h e d r o n Lett., 929 (1972).
7. A. N. Saverchenko, V. A. Kaminskii, and M. N. Tilichenko, Khim. Geterotsikl. Soedin., 1232 (1972).
8. V. A. Kaminskii, A. N. Saverchenko, and M. N. Tilichenko, Khim. Geterotsikl. Soedin., 1538 (1970).
9. V. A. Kaminskii, A. N. Saverchenko, and M. N. Tilichenko, Zh. Organ. Khim., 6, 404 (1970).
10. N. S. Gill, K. B. J a m e s , F. Lions, and K. T. Potts, J . Am. C h e m . Sot., 74, 4923 (1952}.
11. M. N. Tilichenko and V. G. Kharchenko, Zh. Obshch. Khim., 3.0, 2283 (1960).
12. V. A. Kaminskii, L . N. Donchak, and M. N. Tilichenko, Khim. Geterotsikl. Soedin., 1134 {1969).

216
INVI~STIGATION OF NAPHTHYRIDINgS
IV.* ARYLAMID]~S OF 2-ANILINONICOTINIC ACID AND CYCLIZATION OF
THEM TO 4-ARYLAMINO-2,3-B]gNZO-1,8-NAPHTHYRIDINES

V. P. Chesnokov and M . ]g. K o n s h i n UDC 547.834.2.07

The c o r r e s p o n d i n g a r y l a m i d e s were obtained f r o m methyl 2-anilinonicotinate and d i m a g n e s y l -

amines, and the amides were converted to 4 - a r y l a m i n o - 2 , 3 - b e n z o - l , 8 - n a p h t h y r i d i n e s by the
action of phosphorus oxychloride. The pKa values of the 2-anilinonicotinic acid a r y l a m i d e s
were determined.

Substituted 4 - a m i n o - 2 , 3 - b e n z o - 1 , 8 - n a p h t h y r i d i n e s - analogs of the widely known 9 - a m i n o a c r i d i n e s -

a r e of interest as potential physiologically active s u b s t a n c e s . Such compounds have not been d e s c r i b e d in
the l i t e r a t u r e . The p r e s e n t r e s e a r c h is devoted to the synthesis of 4 - a r y l a m i n o - 2 , 3 - b e n z o - l , 8 - n a p h t h y r i d -
ines f r o m 2-anilinonicotinic acid a r y l a m i d e s .
NHC6H4R NHCsH4R
t [
~ . ~ COOCH2
~N~"~NHC6H~ RC~H~.N(MgX)&~ ; ~
H
I-X XI - XVII

2-Anilinonicotinic acid a r y l a m i d e s (I-X, Table 1) were obtained in good yields by r e a c t i o n of a r y l d i -

m a g n e s y l a m i n e s with methyl 2-anilinonicotinate. A vCO band at 1638 + 2 c m -I is o b s e r v e d in the IR s p e c -
t r a of I - X . The UV s p e c t r a contain two m a x i m a at 290-294 and 353-357 rim. The pKa values of a r y l a m i d e s
I-VII in ethanol a r e c l o s e to one another and range f r o m 2.48 to 2.72 PKa units. Because of the r e m o t e n e s s
of the radical of the a r y l a m i d e portion of the molecule f r o m the nitrogen atom of the pyridine ring, its ef-
fect on the b a s i c i t y is insignificant.

4 - A r y l a m i n o - 2 , 3 - b e n z o - l , 8 - n a p h t h y r i d i n e s (XI-XVII, Table 2) are f o r m e d in s a t i s f a c t o r y yields when

I-V, VIII, and IX are refluxed in excess phosphorus oxychloride. It should be noted that 2-anilinonicotinic
acid a r y l a m i d e s , in c o n t r a s t to N-phenylanthranilic acid anilide [2], undergo c y c l i z a t i o n with much g r e a t e r
difficulty. This is apparently a s s o c i a t e d with the d e c r e a s e in the e l e c t r o n density on the phenyl group (the
nucleophilic c e n t e r of the reaction) due to the e l e c t r o n - a c c e p t o r p r o p e r t i e s of the protonated pyridine ring.
The s t r u c t u r e of naphthyridines XI-XVII was c o n f i r m e d by the IR s p e c t r a , in which the band of a
s e c o n d a r y amino group is o b s e r v e d at 3426-3449 c m -I and, in c o n t r a s t to the s p e c t r a of a r y l a m i d e s I-X,
the band of a c a r b o n y i g r o u p is absent.

EX PERIM],~ NTA L
The IR s p e c t r a of 0.005 M solutions of the compounds in c a r b o n t e t r a c h l o r i d e were r e c o r d e d with an
IKS-14 s p e c t r o m e t e r .

The ionization constants of the 2-aniltnonicotinic acid a r y l a m i d e s were determined potentiometrically

by titration, with an 0.1 N ethanol solution of p e r c h l o r i c acid, of 0.01 M solutions of I-VII in ethanol (with an
LPM-60M potentiometer). The PKa values were calculated b y t h e method in [3].

*See [1] for communication Ill.

P e r m P h a r m a c e u t i c a l Institute. T r a n s l a t e d f r o m Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp.

247-248, F e b r u a r y , 1974. Original a r t i c l e submitted F e b r u a r y 14, 1973.

9 19 75 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

217
 T A B L E 1. 2 - A n i l i n o n i c o t i n i c A c i d A r y l a m i d e s (I-X)

Corn= ~ mp, deg "~iC Empirical fox,= -:T-'- ~ =

POUnd] mula found oalc) i pKa, in eth=.
anol
J
I H 185--187 C,sH15N~O 14,6 14,5 2,56__0,06 62
II m-CHa 173--174 CIgHtTN30 13,9 13.9 2,62+_0,04 64
IiI p-C1 168--170 ClsH14CIN~O 12,9 13,0 2,48+_0,06 78
IV p-CH30 170--172 C,~HLTNsO2 13,2 13,2 I 2,52+_0,05 46
V m-CHaO 163--164 CIgHtTNsO2 13,3 13,2 2,68+_0,02 83
VI m-C1 206--207 CtsHt4Cl~sO 12,9 132 2,58+_024 44
VII p-CH8 170--172 CtgH17NaO 14,0 13,9 2,72+_0,03 50
VIII o-CI 174--176 Ct~Ht4C1NaO 13,0 13,0 72
IX p-Br 183---184 CI~HI4BrNaO 11,5 11,4 69
X o-CH30 138--140 Ct~HI~NBO2 13,3 13,2 42

T A B L E 2. 4 - A r y l a m i n o - 2 , 3 - b e n z o - l , 8 - n a p h t h y r i d i n e s (XI-XVII)
N,%
Com-
pound rap, deg ~C Empirical for- found CaIc.
mula

XI H 274--276 C,sHI*N3 15,6 15,5 47

~II m-CH3 269--270 C19HlsNs 14,8 14,7 44
XIII p-C1 278--280 CIsHI~C1Na 13,6 13,7 27
XIV p-CHsO 225--228 C19HisN30 13,7 13,9 24
XV m-CH30 290--292 C19HtsN30 13,9 13.9 23
XVI o-C1 276--279 C18HI2CIN~ 13,9 13,7 21
XVJI p-Br 280--283 CIsHI2BrNa t 1,9 12,0 19

2 - A n i l i n o n i c o t i n i c A c i d A r y l a m i d e s (I-X). A s o l u t i o n of 0.02 m o l e of m e t h y l 2 - a n i l i n o n i c o t i n a t e in 30
ml of a b s o l u t e e t h e r was added to 0,05 m o l e of d i m a g n e s y l a m i n e , and the m i x t u r e was h e a t e d f o r 1.5 h. It
was t h e n d e c o m p o s e d with a s a t u r a t e d a m m o n i u m c h l o r i d e solution, and the e t h e r l a y e r was w o r k e d up b y
s t e a m d i s t i l l a t i o n . The r e s i d u e was c r y s t a l l i z e d f r o m ethanol. A r y l a m i d e s I - X w e r e obtained as c o l o r l e s s
c r y s t a l l i n e s u b s t a n c e s that w e r e s o l u b l e in the u s u a l o r g a n i c s o l v e n t s {Table 1).
4 - A r y l a m i n o - 2 , 3 - b e n z o - l , 8 - n a p h t h y r i d i n e s (XI-XVII). A 0.005 m o l e s a m p l e of a r y l a m i d e I-V, VIII,
o r IX was added to 5 ml of p h o s p h o r u s o x y c h l o r i d e , and the m i x t u r e was r e f l u x e d f o r 10 h. The e x c e s s
p h o s p h o r u s o x y c h l o r i d e was r e m o v e d by v a c u u m distillation, and 1 0 - 1 5 ml of ice w a t e r was added to the
r e s i d u e . The aqueous m i x t u r e was n e u t r a l i z e d with 10~c s o d i u m h y d r o x i d e solution, and the p r e c i p i t a t e was
r e m o v e d by f i l t r a t i o n and c r y s t a l l i z e d f r o m aqueous p y r i d i n e . N a p h t h y r i d i n e s X I - X V I I w e r e obtained as
y e l l o w i s h c r y s t a l l i n e s u b s t a n c e s that w e r e only s l i g h t l y soluble in the u s u a l o r g a n i c s o l v e n t s {Table 2).

LITERATURE CITED
. M. E . Konshin and V. P . C h e s n o k o v , Khim. G e t e r o t s i k l . Soedin., 119 (1973).
2. P . A. P e t y u n i n , N. G. P a n f e r o v a , and M. E . Konshin, Khim. G e t e r o t s i k l . Soedin., 257 (1965).
3. A . A l b e r t and E . S e r j e a n t , I o n i z a t i o n C o n s t a n t s of A c i d s and B a s e s , Methuen (1962).

218
CYANINE DYES BASI~D ON 2 - P H E N Y L - 3 , 4 - D I M g T H Y L -
5,6-BENZ OQUINOLINE

N. S . K o z l o v , O. D. Zhikhareva, UDC 668.8.547.832.5

"and I. P. Stremok

It is shown that the only product in the condensation of benzylidene-2-naphthylamine with

methyl ethyl ketone is 2-phenyl-3,4-dimethyl-5,6-benzoquinoline, on the basis of the quat-
e r n a r y s a l t of which cyanine dyes w e r e synthesized.

In our c u r r e n t r e s e a r c h we have investigated the condensation of benzylidene-2-naphthylamine (I) with

methyl ethyl ketone. According to the p r e v i o u s l y e x p r e s s e d [t] concepts r e g a r d i n g the r e a c t i o n mechanism,
one might have expected the f o r m a t i o n of two products - 2-phenyl-4-ethyl-5,6-benzoquinoline and 2-phenyl-
3,4-dimethyl-5,6-benzoquinoline - t h e o r e t i c a l l y as a r e s u l t of the condensation and subsequent cyclization.
However, the only r e a c t i o n product proved to be 2-phenyl-3,4-dimethyl-5,6-benzoquinoline (II). Consequent-
ly, the condensation of methyl ethyl ketone at the azomethine bond occurs with the participation of the m e t h y l -
ene group. The p r e s e n c e in the PMR s p e c t r a of benzoquinoline II of signals of two nonequivalent methyl
groups at 2.41 and 2.92 ppm confirms the proposed s t r u c t u r e .

/N:CHC6H5 CH3COC2Hs
~ N or ~ N

I II

Cyanine dyes, the c h a r a c t e r i s t i c s of which a r e p r e s e n t e d in Table 1, w e r e synthesized f r o m 2-phenyl-

3,4-dimethyl-5,6-benzoquinoline methiodide (HI).
The absorption m a x i m a of the dyes obtained a r e shifted to the long-wave region of the s p e c t r u m as
c o m p a r e d with analogous dyes - derivatives of other h e t e r o c y c l i c bases; this is apparently associated with
the introduction of phenyl and methyl groups into the dye m o l e c u l e s .

EXPERIMENTAL
The absorption s p e c t r a of alcohol solutions of the dyes w e r e r e c o r d e d with a Specord UV-vis s p e c t r o -
p h o t o m e t e r . The PMR s p e c t r a of CC14 solutions were r e c o r d e d with an HA-100 s p e c t r o m e t e r with t e t r a -
methylsilane as the internal standard.
2 - P h e n y l - 3 , 4 - d i m e t h y l - 5 , 6 - b e n z o q u i n o l i n e (II). A 5.4 ml (0.06 mole) s a m p l e of methyl ethyl ketones,
0.6 ml of concentrated HC1, and 0.6 ml of nitrobenzene were added to 4.6 g (0.02 mole) of I in 35 ml of alco-
hol, and the m i x t u r e was refluxed on a w a t e r bath for 2 h. It was then cooled and neutralized with NH4OH.
The resulting oil was washed r e p e a t e d l y with water, dissolved in alcohol, and precipitated with ether to give
10~ (twice f r o m alcohol) of c o l o r l e s s needles with mp 142-144 ~ Found, ~ : C 89.2; H 6.0; N 5.0. C21H17N.
Calculated, %: C 89.0; H 6.0; N 4.9. UV s p e c t r u m , h m a x (logs 258 (4.63), 340 (3.66), 356 (3.71) nm.
2.-Phenyl-3,4-dimethyl-5,6-benzoquinoline Methiodide (III). This compound was p r e p a r e d by heating
1.25 g of benzoquinoline H with 3 ml of methyl iodide and 3 m l o f acetic anhydride in a s e a l e d ampule at

Institute of P h y s i c a l Organic C h e m i s t r y , Academy of Sciences of the B e l o r u s s i a n SSR, Minsk. T r a n s -

lated f r o m Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 249-250, F e b r u a r y , 1974. Original article
submitted June 27, 1972.

9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of tins publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy of this article is availablefrom the publisher for $15.00.

219
 TABLE 1. C h a r a c t e r i s t i c s of the Cyanine Dyes
Com- N,%
Yield.
pound mp, deg ~C Empirical formula lg8
found I calc. %

IV 181--183 C~H37N~I 3,86 3,82 780 4.75 11

V 274--275 CssHaIN21 4,91 4,62 608 5,40 10
VI 166~-167 C3~H29N21 4,78 4,82 620 4,94 34
VII 243--245 C31HszN21S* 539 4,49 34
VIII 234--235 C~sH24N2OS, 630 4,86 43
IX 165--t67 CsIH29N21 :542 9 4,14 50
X 143--145 C3oH24NO21 2,52 2,51 380 4,06 50

*Found, %: S 5.60. Calculated, %: S 5.46.

t Found, %: S 13.79. Calculated, %: S 13.69.

100~ The yield of yellow p r i s m s with mp 190-192 ~ (from alcohol) was 90%. Found, ~c: N 3.0. C22H20NI.
Calculated, %: N 3.3.
The dyes w e r e obtained by s t a n d a r d methods for the p r e p a r a t i o n of this type of compound (for ex-
a m p l e , s e e [2]).
B i s ( 1 , 3 - d i m e t h y l - 2 - p h e n y l - 5 , 6 - b e n z o - 4 - q u i n o l y l ) t r i m e t h y t i d y n e c y a n i n e Iodide (IV). A m i x t u r e of 0.42
g (0.001 mole) of methiodide III, 1 m l of ethyl o r t h o f o r m a t e , 3 ml of pyridine, and t h r e e drops of acetic an-
hydride was h e a t e d at 140 ~ for 3 h. The dye was p r e c i p i t a t e d with e t h e r , c h r o m a t e g r a p h e d in c h l o r o f o r m on
A1203, and c r y s t a l l i z e d f r o m alcohol to give g r e e n needles (Table 1).
(3-Dimethy-2-pheny-56-benz-4-quinoy)-(-ethy-2-quinoy)trimethyidynecyanine Iodide (V).
A m i x t u r e of 0-21 g (0.5 mmole) of III, 0.21 g (0.5 mmole) of 2-(~ -acetanilinovinyl)quinoline, 0.23 g of
sodium a c e t a t e , and 3 m l of acetic anhydride was heated at 130 ~ f o r 1.5 h. The p r e c i p i t a t e was r e m o v e d by
filtration, washed with w a t e r , and c r y s t a l l i z e d f r o m alcohol to give 0.02 g of shiny g r e e n needles.
3-Dimethy-2-pheny-4-[(-ethydihydro-4-quinoyidene)methy]-56-benzoquinoinium Iodide (VI).
A m i x t u r e of 0.21 g of III, 0.28 g (0.001 mole) of quinoline ethiodide, 0.14 g (0.001 mole) of anhydrous K2CO3,
and 4 m l of absolute alcohol was heated f r o m 1.5 h on a w a t e r bath. The dye was p r e c i p i t a t e d with aqueous
KI solution, washed with w a t e r , c h r o m a t o g r a p h e d in c h l o r o f o r m on A1203, and c r y s t a l l i z e d f r o m alcohol to
give 0.1 g of violet c r y s t a l s .
1 , 3 - D i m e t h y l - 2 - p h e n y l - 4 - [(3-ethylbenzo-2-thiazolinylidene)methyl]-5,6-benzoquinolinium Iodide.__ This
compound was s i m i l a r l y obtained f r o m 0.21 g of III and 0.17 g of 2 - m e t h y l m e r c a p t o b e n z o t h i a z o l e ethiodide
in the p r e s e n c e of sodium a c e t a t e . The p r e c i p i t a t e that f o r m e d on cooling was r e m o v e d by filtration, washed
with w a t e r , and c r y s t a l l i z e d f r o m alcohol to give 0.1 g of v i o l e t - b r o n z e needles.
3-E thyl- 5- [ 1 , 3 - d i m e t h y l - 2 - p h e n y l - 5 , 6 - b e n z o d i h y d r oquinolylidene-4-ethylidene ]thiazolidene-2-thion-
4 - o n e (VIii). A m i x t u r e of 0.21 g of IlI, 0.15 g (0.5 mmole) of 3 - e t h y l - 5 - N - p h e n y l a c e t a m i d o m e t h y l e n e r h o d -
anine, and 0.2 g of sodium a c e t a t e in 4 m l of alcohol was refluxed for 2 h. The p r e c i p i t a t e was r e m o v e d by
filtration, washed with w a t e r , and c r y s t a l l i z e d f r o m alcohol to give 0.1 g of shiny g r e e n needles.
4 - ( p - D i m e t h y l a m i n o s t y r y l ) - 2 - p h e n y l - 3 - m e t h y l - 5 , 6 - b e n z o q u i n o l i n e Methiodide (IX): This compound
was ot~tained f r o m 0.21 g of III and 0.1 g of p , d i m e t h y l a m i n o b e n z a l d e h y d e by heating for 1.5 h in 3 ml of a l -
cohol in the p r e s e n c e of t h r e e drops of piperidine. The dye was p r e c i p i t a t e d by ether, washed with w a t e r ,
and c r y s t a l l i z e d f r o m alcohol {with the addition of ether) to give 0.14 g of fine violet c r y s t a l s .
4 - ( 3 , 4 - M e t h y l e n e d i o x y s t y r y l ) - 2 - p h e n y i - 3 - m e t h y l - 5 , 6 - b e n z o q u i n o l i n e Methiodide (X). This compound
was s i m i l a r l y obtained as yellow needles f r o m 0 21 g of III and 0.12 g of p i p e r o n a l .

LITERATURE CITED

1. N. S. Kozlov and V. V. Misenzhnikov, Khim. G e t e r o t s i k l . Soedin., 866 (1968).

2. G. T. Pilyugin and O. E . P e t r e n k o , Khim. G e t e r o t s i k l . Soedin., 143 (1965).

220
COMPARATIVE MASS-SPECTROMETRIC INVESTIGATION OF
QUINOLIZIDINE ALKALOIDS AND CYTISINE, SPARTEINE,
AND MATRIDINE DERIVATIVES

N. S. Vul'fson, Z. S. Ziyavidinova, UDC 547.944/945:543.51

and V. G. Zaikin

The low- and h i g h - r e s o l u t i o n m a s s s p e c t r a of p a c h y c a r p i n e , t e t r a h y d r o d e s o x o c ~ i s i n e ,

mat~kline, a - i s o l u p a n i n e , t e t r a h y d r o c y t i s i n e , m a t r i n e , d - t h e r m o p s i n e , cytisine, and i s o s o -
p h o r a m i n e , as well as s o m e of t h e i r s t e r e o i s o m e r s and deutero analogs, m a k e it p o s s i b l e
with a high d e g r e e of p r o b a b i l i t y to r e l a t e the investigated compounds to one o r another
group of quinolizidine alkaloids.

The m a s s s p e c t r a of the thoroughly studied c y t i s i n e and s p a r t e i n e d e r i v a t i v e s [1-3] and the c o n s i d e r -

ably l e s s well studied m a t r i d i n e d e r i v a t i v e s [4-6] have m a n y f e a t u r e s in c o m m o n . On the basis of an
analysis of the l i t e r a t u r e and our own e x p e r i m e n t a l investigations c a r r i e d out in the c a s e of p a c h y c a r p i n e
(Ia), m a t r i d i n e (IIIa), a l l o m a t r i d i n e (]]l-b), isosophoridan (TIIc), s o p h o r i d a n (IIId), ~ - i s o l u p a n i n e (IVa), lup-
anine (IVb), m a t r i n e (Via), a l l o m a t r i n e (VIb), isosophoridine (VIc), s o p h o r i d i n e (VId), d - t h e r m o p s i n e (VIIa),
c y t i s i n e (VIIIa), is o s o p h o r a m i n e (IXa), s o p h o r a m i n e (IXb), and a n u m b e r of ~ e i r d e u t e r o analogs, we a t -
t e m p t e d to m a k e a c o m p a r a t i v e m a s s - s p e c t r o m e t r i c investigation of alkaloids of these t h r e e types with the
a i m of p o s s i b l y identifying t h e m . Since d i f f e r e n c e s in the m a s s s p e c t r a of s t e r e o i s o m e r s a r e m a n i f e s t e d
in m o s t c a s e s in a change in only the r e l a t i v e intensities of the individual peaks, we will d i s c u s s the p e c u l i -
a r i t i e s of the m a s s s p e c t r a in the c a s e s of s t r u c t u r a l i s o m e r s - alkaloids Ia (Fig. l a ) , IIa, lIIa (Fig. lc),
IVa (Fig. 2a), Va, Via (Fig. 2c), and VIIa, VIIIa, IXa {Fig. 3a-c) o The s p e c t r a of alkaloids Tla and Va a r e
p r e s e n t e d in [1, 3].
14

7 16 S 7~NR 5

X X

I a , b , I Y a, b Ila,b, Ya, b 111 a - d , VI a - d

X = H2, Ia p a c h y c a r p i n e ; Ib s p a r t e i n e ; X = O, IVa a - i s o l u p a n i n e ; IVb lupanine; X = H2, IIa d e s o x o t e t r a h y d r o -

c y t i s i n e (R = H); IIb N - m e t h y l d e s o x o t e t r a h y d r o c y t i s i n e (R = CH3); X = O, Va t e t r a h y d r o c y t i s i n e (R = H); Vb
N - m e t h y l t e t r a h y d r o c y t i s i n e (R = CH3); X = H2, IIIa m a t r i d i n e ; I]]b a l l o m a t r i d i n e ; IIIc isosophoridan; IIId
sophoridan; X = O, Via m a t r i n e ; VIb a l l o m a t r i n e ; VIc isosophoridine; VId s o p h o r i d i n e .

9 n " I[
O O
VII a, b V I I I a. b " IX a, b

M. M. Shemyakin Institute of the C h e m i s t r y of N a t u r a l Compounds, A c a d e m y of Sciences of the USSR.

A. V. Topchiev Institute of P e t r o c h e m i c a l Synthesis, A c a d e m y of Sciences of the USSR, Moscow. T r a n s -
l a t e d f r o m K h i m i y a G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 2, pp. 251-260, F e b r u a r y , 1974. Original a r t i c l e
s u b m i t t e d J u l y 94, 1973.

9 19 75Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy of this article is availablefrom the publisher for $15.00.

221
VIIa d - t h e r m o p s i n e ; VIlb anagyrine; VIIIa cytisine (R = H); VIIIb N - m e t h y l c y t i s i n e (R = CH3); IXa i s o s o -
phoramine; IXb s o p h o r a m i n e .
Only in individual c a s e s , p r i m a r i l y in the examination of alkaloids of the HI and VI type, will we deal
with p r o b l e m s a s s o c i a t e d with the s t e r e o c h e m i c a l peculiarities of the m o l e c u l e s .
According to the data in [1-4], ion peaks with m / e 84 (a), 96 (b), 97 (b'), 98 (b"), 136 (c), 137 (c'), and
150 (d), which apparently c h a r a c t e r i z e the quinolizidine s y s t e m [7], are typical for almost all of the quinol-
izidine alkaloids. The origin of the ions, the peaks of which a r e situated in the h i g h - m o l e c u l a r - w e i g h t r e -
gion of the s p e c t r a , has not been adequately discussed.

~'~H ~N+~cH 2
b' .,/~ o7

b" m/~ 98 .... /r 13e c' m/e 137

One should f i r s t note that the affiliation of the alkaloids w i t h the group of cytisine alkaloids (II, V, VIII)
can usually be established f r o m the m o l e c u l a r weight b e c a u s e of the absence of a ]3 ring in them. The task
is somewhat complicated if the substituent attached to the nitrogen atom of the C ring is l a r g e r than a
methyl group o r if the alkaloid is dimeric (as, for example, argentine, octahydroargentine [8], or dimeth-
amine [9]). But h e r e also, as a r e s u l t of a cleavage and elimination of a large portion of the substituent
f r o m the nitrogen atom o r disintegration of the m o l e c u l a r ion of the dimeric alkaloid, the l o w - m o l e c u l a r -
weight regions of the s p e c t r a a r e p r a c t i c a l l y identical to the s p e c t r a of the c o r r e s p o n d i n g cytisine d e r i v a -
tives.
In the c a s e of alkaloids of the I type with a f o r m a l l y s y m m e t r i c a l s t r u c t u r e , it might be expected that
the a, b - b " , c, and c' ions are f o r m e d equally probably as a r e s u l t of cleavage of the bonds in the B and C

r
1~176176176~-' ~ N a

| ..

'~1 96 ~ Z05 I
100 150 200 250 role

100 l~ 136

J/~lll -~
Illu ,,,,,al,,,u,, I,,
.o
,,,, h, I,~~ . . . . .
19s
.,,I, 207 ,
M
23"-6
,I,
100 150 200 250 mle
~~176176
so] 23&
i.
~~ 191 2os
t . . . .
b'r
'~60
I, ,11
~]
dg
~
J,k
15o
,~2
I. ,. .I. . . . [I. . . . 2 5 o , w ~
" 260 . . . . .

'~176 i;-; ~
N M
d
ooi ]P 136 190
t
100 150 200 2'50 rnle

Fig. I . Mass s p e c t r a : a) paehycarpine; b) 3,3-D2-pachycarpine; c) m a t r i -

dine; d) 5,17-dehydroallomatridine.

222
rings and contain A and D o r AB and CD rings, r e s p e c t i v e l y . However, in the c a s e of s p a r t e i n e [1], these
ions contain chiefly an A ring (or AB ring, r e s p e c t i v e l y ) ; N e u n e r - J e h l e and c o - w o r k e r s [1] explain this by
the effect of the s t e r e o c h e m i s t r y of the fusion of the A / B and C / D r i n g s . A s i m i l a r situation is also r e -
tained in p a e y c a r p i n e Ia, which is the d - i s o m e r of s p a r t e i n e (Ib) and has the s a m e s t e r e o c h e m i s t r y of fusion
of the A / B and C / D r i n g s . In fact, the peaks of the a, b - b " , c and c' ions in the m a s s s p e c t r u m of 3,3-D~-Ia
(Fig. lb) a r e shifted b a s i c a l l y by 2 a m u . The f o r m a t i o n of t h e s e ions for alkaloids II is also p r i m a r i l y a s -
s o c i a t e d with c l e a v a g e of the bonds in the B o r C ring and with localization of the c h a r g e on the f r a g m e n t
containing the A o r AB ring, r e s p e c t i v e l y .
On the b a s i s of an analysis of the m a s s s p e c t r u m of the 15,15-D~- analog of m a t r i d i n e (IIIa), Yunusov
and c o - w o r k e r s [4] a r r i v e d at the conclusion that the a and b - b " ions f o r IIIa contain A o r B rings and a r i s e
as a r e s u l t of t h r e e C - C bonds in the A (or B) and C rings with m i g r a t i o n of two hydrogen a t o m s . However,
this r e q u i r e d s u b s e q u e n t r e f i n e m e n t , s i n c e the f o r m a t i o n of ions with localization of the c h a r g e on the D
ring should p r o c e e d v i a a s i m p l e r m e c h a n i s m with c l e a v a g e of only two C - C bonds in the C ring, just as in
the c a s e of alkaloids I. We t h e r e f o r e studied the m a s s s p e c t r a of 14,14-D 2 analogs of alkaloids IIIa-c .* It
has b e e n shown [10] that, depending on the s t e r e o c h e m i c a l p e c u l i a r i t i e s of the investigated alkaloids, the a
and b - b " ions m a y contain both an A (or B) ring and a D ring. Thus, for e x a m p l e , in the c a s e of IIIb, the
b" ion p r i m a r i l y includes a D ring, while an A o r B ring is included in the c a s e of IIIa and IIIc.
In this connection, it is i n t e r e s t i n g to note that the peaks of the a, b', and b" ions in the m a s s s p e c -
t r u m of 6 , 1 7 - d e h y d r o a l l o m a t r i d i n e (X) (Fig. ld), which contains a double bond in the C ring, a r e p r a c t i c a l l y
* The t h r e e - d i m e n s i o n a l s t r u c t u r e s of t h e i r c a r b o n y l - c o n t a i n i n g d e r i v a t i v e s (Via-c) a r e p r e s e n t e d in Table 1.

1001%

. . . . .,,I, A
~,~~

100
d,r, J,, I,II,
,~, i,~-0 o

,Ill
150
, I~111,
177
]II,
'2o

I'
200
l Ill, II I I
,II"
"100] ~ 1361 b
&l -I-

2~

/ t,~ ,,o / h,, o o 3,3-o=-~o .

64 137 --

100 150 200 250 m/e

N i0',_)
205

, ,, Ill .... II ,,,,i ,I.... ,1,1,,, , , , , .ll, , , , r ,

100 150 200 250 m/e
100 %
o ~ o d

1OO] o/'o
,I, d,!, ,!1,,, ...,,,, ,,,.,,, !,],l,, ,,, l,. , .I, .lit,.
100
-

150
I~"?
,,,, .., ,.
.200
~ O
221
,k .
e
. .,till,
250 role
O D

11,12,13314- DZ- ~.~1b

100 150 200 250 role

Fig. 2. Mass s p e c t r a : a) ~ - i s o l u p a n i n e ; b) 3,3-D2-c~-isolupanine; c)

m a t r i n e ; d) 14,14-D~-matrine; e) 11,12,13,14-D4-allomatrine.

223
 x b, ~le 95 c, ,~/e ,35 c I m/~ ,37

absent, while the ion p e a k with m / e 95, to which s t r u c t u r e b i can be assigned, is a m a x i m u m .

I n s o f a r as ions with m / e 136 and 137 a r e concerned, for alkaloids III they f o r m e x c l u s i v e l y as a r e -
.suit of c l e a v a g e of the bonds in the C ring with localization of the c h a r g e on the f r a g m e n t containing the A
and B r i n g s . In c o n t r a s t to the analogous f r a g m e n t s of alkaloids I and II, these ions a p p a r e n t l y have ci and
cl' s t r u c t u r e s , r e s p e c t i v e l y . The intensity of the peaks of these ions is naturally c o n s i d e r a b l y r e d u c e d in
the s p e c t r u m of X (Fig. ld}.
According to the data in [1], the f o r m a t i o n of a d ion with m / e 150 in the c a s e of alkaloids I does not
depend on the s t e r e o c h e m i s t r y of fusion of the A / B and C / D rings, and ion d is due a p p r o x i m a t e l y to an
equal d e g r e e to localization of the c h a r g e on both nitrogen a t o m s . This conclusion is also in a g r e e m e n t with
our o b s e r v a t i o n that the intensities of the peaks with m / e 150 and 152 in the m a s s s p e c t r u m of the 3,3-D 2
analog of Ia a r e a p p r o x i m a t e l y equal (Fig. lb}.

cl m/e 150

In the c a s e of the s t e r e o i s o m e r s of alkaloids Ill, ions d a r e f o r m e d e x c l u s i v e l y through c l e a v a g e of

the bond in the C ring and as a consequence of localization of the c h a r g e on the nitrogen atom of the A and
B r i n g s . This is indicated by the absence of a shift in their peaks in the m a s s s p e c t r a of the 14,14-D 2
analogs [10].
The m a s s s p e c t r a of Ilia and HIe contain r a t h e r intense ion peaks with m / e 162, the intensity of which
in the s p e c t r a of la,b is c o n s i d e r a b l y l o w e r (Fig. l a , c ) . However, this ion can s c a r c e l y have s u b s t a n t i a l
diagnostic value, s i n c e the intensity of its peak in the s p e c t r u m of d e r i v a t i v e IIIb is also s o m e w h a t lowered
[10]. It is difficult to f o r m a judgment r e g a r d i n g the nature of the ion with m / e 162, and one can only note
that it does not include the C-14 [10] and C-15 [4] a t o m s , but, according to the data f r o m the h i g h - r e s o l u t i o n
m a s s s p e c t r u m of HIc, has the c o m p o s i t i o n CiIHi6N.
The m a s s s p e c t r a of alkaloids I and HI contain low intensity N-43 and M-29 ion peaks with m / e 191
and 205, r e s p e c t i v e l y . Since the f i r s t of t h e s e peaks in the s p e c t r a of the 14,14-D 2 analogs of III [10] a r e
only p a r t i a l l y shifted to m / e 192 and 193, it can be supposed that they a r e f o r m e d due to ejection of a propyl
r a d i c a l o r an ethyleneimine m o l e c u l e . The f o r m a t i o n of ions with m / e 205 is a s s o c i a t e d with ejection of
an ethyl r a d i c a l f r o m the A o r B r i n g s . The peaks of these ions in the s p e c t r a of the deutero analogs of III
a r e c o m p l e t e l y shifted to m / e 207.
The m o s t s u b s t a n t i a l (from a diagnostic point of view) difference between the m a s s s p e c t r a of alkaloids
o f the I and III type is the p r e s e n c e in the s p e c t r a of I of r a t h e r intense M-41 ion peaks with m / e 193, which
a r e p r a c t i c a l l y absent in the s p e c t r a of III (Fig. 1, s p e c t r a a and c). In the c a s e of alkaloids of the I type,
this ion is a p p a r e n t l y f o r m e d as a r e s u l t of elimination f r o m the m o l e c u l a r ion of a c y c l o p r o p y l r a d i c a l d u r -
ing c l e a v a g e of the bonds in the B and C r i n g s . This is c o n f i r m e d by the shift in its peak by 2 ainu (to m / e
195) in the m a s s s p e c t r u m of the 3,3-D 2 analog of la (Fig. lb), and also by the shifts of 16 ainu to m / e 209
in the m a s s s p e c t r a of 1 3 - h y d r o x y - I b [1] and 1 4 - h y d r o x y - I b [2]. E j e c t i o n of a c y c l o p r o p y l r a d i c a l f r o m the
m o l e c u l a r ion is l e s s likely in the c a s e of alkaloids III.
The p r e s e n c e of a l a c t a m c a r b o n y l group in alkaloids IV-VI has a substantial effect on the c h a r a c t e r
of the d i s i n t e g r a t i o n of t h e i r m o l e c u l a r ions under e l e c t r o n impact; this c o n s i d e r a b l y f a c i l i t a t e s d i f f e r e n t i a -
tion of t h e i r m a s s s p e c t r a (Fig. 2, s p e c t r a a and c).
The m o s t c h a r a c t e r i s t i c p e c u l i a r i t i e s of the m a s s s p e c t r a of alkaloids VI a r e the e x t r e m e l y intense
M + and M-1 ion p e a k s ; the dominant ion peak in the c a s e of Via is M +, while M-1 ions dominate in the c a s e
of V I c - d (Table 1). The intensities of t h e s e peaks a r e c o n s i d e r a b l y l o w e r in the s p e c t r a of alkaloids IV
and V.

224
 TABLE 1. Data f r o m the Mass Spectra of Alkaloids VI (the intensities
a r e given in p e r c e n t of the m a x i m u m )
Spp.ho-
Ma'trine, (VI) Allomatrine I Isosophoridine (VIc) rl(~lne ,
(VIb) _
(VIb) ~ _.

0
ra/'e

249 19 10 13 9
248 I00 59 86 53
247 92 100 100 100
22O 14 1 7 1
219 16 3 7 3
206 25 3 12 4
205 58 6 26 7
192 33 3 8 2
178 5 9 5 3
177 16 49 20 10
164 5 1 3 1
163 6 2 4
162 14 4 10 3
161 12 3 7
151 10 7 14 5
150 27 39 36 24
149 10 19 12 10
148 17 14 15 8
138 11 7 8 17
137 20 10 12 6
136 14 21 17 16
135 5 4 4 2
134 7 7 5 3
122 9 8 8 8
120 l0 3 5 3
ll0 6 5 4 8
12

l
98 17 7 ,
7
96 33 10 25 3O
86 5 1
85 l 7 I
84 7 5 4 7
83 7 6 5 8
82 9 7 4 7

* The s t e r e o c h e m i s t r y has not been definitively e s t a b l i s h e d .

The intensities of the peaks of ions a and b - b " in the s p e c t r a of alkaloids IV and VI a r e g e n e r a l l y
l o w e r than in the s p e c t r a of I - I I I . In the c a s e of alkaloids IV, t h e s e ions contain e x c l u s i v e l y a D ring, as
a t t e s t e d to by the a b s e n c e of a shift in t h e i r peaks in the s p e c t r u m of the 3,3-D 2 analog of IVa (Fig. 2b).
However, in the c a s e of alkaloids VI, t h e s e ions a r e f o r m e d due to the A o r B rings; this is c o n f i r m e d by
the absence of a shift in t h e i r peaks in the s p e c t r u m of the 14,14-D 2 analog of Via (Fig. 2d).
In addition, the s p e c t r u m of d e r i v a t i v e s IVa (Fig. 2a) is c h a r a c t e r i z e d by a peak of medium intensity
with m / e 110, which is absent in the s p e c t r u m of Va and is of insignificant intensity in the s p e c t r u m of Via.
According to the data f r o m the h i g h - r e s o l u t i o n m a s s s p e c t r u m of alkaloids IVa, this ion has the C7H12N c o m -
position and, a c c o r d i n g to the ass~umption in [3], m a y have the e or e' s t r u c t u r e . The ions with m / e 110 in
the c a s e of alkaloids J - I I I p r o b a b l y also have a s i m i l a r s t r u c t u r e .

According to the data in [3], a c h a r a c t e r i s t i c p e c u l i a r i t y of the m a s s s p e c t r u m of alkaloid VA is the

p r e s e n c e of a r a t h e r intense ion peak with m / e 82 and a m a x i m u m peak with m / e 95, while the peaks of
the a and b - b " ions a r e of low intensity. The ions with m / e 82 and 95 contain a C ring, s i n c e t h e i r peaks
a r e shifted by 14 ainu (to m / e 96 and 109) in the m a s s s p e c t r u m of N - m e t h y l t e t r a h y d r o c y t i s i n e (Vb) [3].

225
 leo]ore ir
a

S~ "I o v_ao ~-~,

I ~I r ~ ~ I I
l., ............
. . . . .
,,,84 9~,III, .,., ,,Jl,
16o . . . .
J,:~ ,II
~o . . . . 260
, 1
11250
r,,le

I
1111,A, II,Li 100
L ,,t,, ,,, ',11[
150
:,, 200 250 m/e

5O
Q ~
(t"
c ~ 1 Nc~
" -- -- I1
~3s ~4e. ~{ -- . 215. . . . II

.':,, ,,I,,,, IJ!..,,:1,1 .... I,,~11 ~J,h, ,,[, !, ,ll .h, I hi. IlL ,I, ,, .,ill
100 150 200 250 m#,

F i g . 3. Mass s p e c t r a : a) d - t h e r m o p s i n e ; b) cytisine; c) i s o s o p h o r a m i n e .

The m a s s s p e c t r a of alkaloids IV-VI differ substantially with r e s p e c t to the intensities of the peaks
of the c and c' ions. In the s p e c t r u m of IVa, the peak of ion c is a m a x i m u m , while the peak of ion c' is in-
significant. The peaks of t h e s e ions in the s p e c t r a of Va,b a r e p r a c t i c a l l y absent [3], while they a r e of
m e d i u m intensity in the s p e c t r u m of Via (the c' peak is g r e a t e r than the c peak). The p r e s e n c e in the
s p e c t r a of I v a and Via of peaks of m e t a s t a b l e ions with m* = 74 (calculated 73.7) and 75 (calculated 74.9),
r e s p e c t i v e l y , is evidence that in the f i r s t c a s e ion c is f o r m e d d i r e c t l y f r o m the m o l e c u l a r ion, while in the
second c a s e ion c' a r i s e s f r o m the M-1 ion.
The ion peak with m / e 150 in the s p e c t r u m of IVa is of m e d i u m intensity and, judging f r o m its i n s i g -
nificant shift in the s p e c t r u m of the 3,3-D 2 analog, IVa contains p r i m a r i l y C and D rings and has a s t r u c -
t u r e of the b type. A distinctive c h a r a c t e r i s t i c of the s p e c t r u m of IVa is the p r e s e n c e of a c o n s i d e r a b l y
m o r e intense ion peak with m / e 149, to which the d' s t r u c t u r e is assigned [3].
~ H2

0
d' ,~/c 149 i :,~/e tso

The peak with m / e 150 in the m a s s s p e c t r a of alkaloids V is of low intensity and, f r o m its nature,
differs s h a r p l y f r o m ion b, since it contains A and B r i n g s , as a t t e s t e d to by the absence of its shift in the
s p e c t r u m Of Vb [3]. It a p p a r e n t l y has the f s t r u c t u r e .
In the c a s e of alkaloid Via, the ion with m / e 150 f o r m s d i r e c t l y f r o m the M-1 ion; this is c o n f i r m e d
by the p r e s e n c e of a p e a k with m* = 91.3 (ealculated 91.1). According to the data of the h i g h - r e s o l u t i o n
m a s s s p e c t r a of Via and Vie, the peak with m / e 150 is a c o m p o s i t e and is c a u s e d by i s o b a r i c CIoHI6N and
CgHI2NO ions in a r a t i o of 65 : 35. The dominant ion a p p a r e n t l y has a s t r u c t u r e of the b type, while the
second has a s t r u c t u r e of the f type. However, it should be noted that t h e s e data do not a g r e e with the r e -
sults obtained f r o m the m a s s s p e c t r a of the 14,14-D 2 and 11,12,13,14-D 4 analogs of Via (Fig. 2, s p e c t r a d
and e), in which s u c h a l a r g e shift in the peak with m / e 150 is not o b s e r v e d . This places in doubt the.data
on the quantitative r a t i o of the i s o b a r i c ions with m / e 150.
The h i g h - m o l e c u l a r - w e i g h t region of the m a s s s p e c t r a of alkaloids IV (from m / e 150 up to M +) c o n -
tains only low intensity p e a k s , in c o n t r a s t to the s p e c t r a of alkaloids VI (Fig. 2, s p e c t r a a and c; Table 1).
According to the data of the h i g h - r e s o l u t i o n m a s s s p e c t r u m of Via, the peak wi~da m / e 161 is due to
the CIoHIINO ion, while the peak with m / e 162 is a c o m p o s i t e and c o r r e s p o n d s to CIoHI2NO and C11Ht6N ions
in a r a t i o of 5 5 : 4 5 . According to the s a m e data, the peak with m / e 177 is due to an ion with the c o m p o s i -
tion C11HI6N2. The c o m p l e t e shift of this peak by 1 ainu to m / e 178 in the s p e c t r u m of 11,12,13,14-D 4 analog

226
of VIb (Fig. 2e) indicates that it contains A = C rings and a p p a r e n t l y has the g s t r u c t u r e . According to the
data of the h i g h - r e s o l u t i o n m a s s s p e c t r u m of IVa, the l o w - i n t e n s i t y p e a k with m / e 177 is also due to the
ion with c o m p o s i t i o n ClIHlTN~ , which p o s s i b l y has the g' s t r u c t u r e .
Ejection of a portion of the D ring f r o m the m o l e c u l a r ion as C3H40 l e a d s , in the c a s e of alkaloid Via,
to a r e l a t i v e l y s t a b l e CI2H2ON2 ion r a d i c a l , which p r o b a b l y has the h s t r u c t u r e .

One of the m o s t intense peaks in the s p e c t r u m of Via with m / e 205 (Fig. 2c) is c o m p l e t e l y shifted by
2 amu to m ~ e 207 in the s p e c t r u m of the 14,14-D 2 analog (Fig, 2d), According to the data of the h i g h - r e s o l u -
tion m a s s s p e c t r u m , the ion c o r r e s p o n d i n g to this peak has the c o m p o s i t i o n C~2H17N20. Consequently, it is
f o r m e d as a r e s u l t of ejection of a C3Hs p a r t i c l e (most likely f r o m the A o r B ring) and m i g r a t i o n of two
hydrogen atoms f r o m the C ring and has the i or i' s t r u c t u r e .

Ok

i t~l/e 205 i'

In c o n t r a s t to this, the peak with m / e 206 is a c o m p o s i t e (of i s o m e r i c ~ons of the c o m p o s i t i o n

CI~H18N20 and C14H21N); this is c o n f i r m e d by the p a r t i a l s h i f t in this peak in the s p e c t r u m of the 14,14-1) 2
analog of Via (Fig. 2d).
The peaks with m / e 219 and 220 in the s p e c t r u m of Via a r e c o m p l e t e l y shifted to m / e 221 and 222 in
the s p e c t r u m of its 14,14-D 2 analog. The second of these peaks is due to the C14H24N2 ion, which is f o r m e d
as a r e s u l t of elimination of a CO group f r o m the m o l e c u l a r ion, while the f i r s t is a c o m p o s i t e and is due
to M - C 2 H 5 (C13H19N20) and M - C O - H (Ci4H23N2) ions. In the f o r m a t i o n of the f i r s t of these, an ethyl
r a d i c a l is a p p a r e n t l y e l i m i n a t e d f r o m the A o r B rings, and it has the j or j' s t r u c t u r e .

j ,,,/e ~9 j"

The introduction of two double bonds into the l a c t a m ring of alkaloids IV-VI leads to the a p p e a r a n c e
of s u b s t a n t i a l d i f f e r e n c e s in the m a s s s p e c t r a of the c o r r e s p o n d i n g alkaloids (VII-IX) (Fig. 3, s p e c t r a a - c ) .
As in the c a s e of alkaloids VI, the dominant peaks in the s p e c t r a of alkaloids IX a r e those of the M + and
M-1 ions, while peaks of b" ions with m / e 98, which a r e f o r m e d with r e t e n t i o n of the D ring, p r e d o m i n a t e
in the s p e c t r u m of VII. The peaks of b" ions in the s p e c t r a of IX a r e of insignificant intensity, while they
a r e c o m p l e t e l y a b s e n c e in the s p e c t r a of alkaloids VIII (Fig. 3, s p e c t r a a - c ) .
The p e a k of the b ion with m / e 96 is r e l a t i v e l y intense in the s p e c t r u m of IXa, while the r e m a i n i n g
peaks of the l o w - m o l e c u l a r - w e i g h t region a r e of low intensity (Fig. 3, s p e c t r u m c).
Low intensity of the peaks of the c ion ( m / e 136), which contain C and D rings, and of ions with m / e
146 and 160, which have the k and l s t r u c t u r e s , i s c h a r a c t e r i s t i c for alkaloids of the VII type: These ions
contain A and B r i n g s , s i n c e they a r e not shifted in the s p e c t r u m of 1 3 - h y d r o x y - V I I a (argentamine) [11],
while the p e a k of ion c is shifted by 16 amu to m / e 152.
The p e a k of ion k in the s p e c t r u m of Villa is a m a x i m u m , while the intensity of the peaks of ions l
is low (Fig. 3, s p e c t r u m b).
It should be noted that the s p e c t r a of the homologs of VllIa and ViiIb differ s u b s t a n t i a l l y . The m a x i -
m u m p e a k with m / e 58 in the s p e c t r u m of VIIIa is due to the M e 2 ] ~ C H 2 ion, the intensity of the m o l e c u l a r
ion i n c r e a s e s s h a r p l y , and the r e m a i n i n g peaks a r e of insignificant magnitude.

227
 CH2.

O
k role ,4, , m/~ ,6o

The peaks of ions c, k, and I are small in the spectrum of IEa. A distinctive peculiarity of the spec-
trum of this compound is the r a t h e r significant intensity of the ion peak with m / e 149, which probably has
the d" s t r u c t u r e , and the p r e s e n c e of a peak with m / e 215, which, according to the data of the h i g h - r e s o l u -
tion m a s s s p e c t r u m , is a c o m p o s i t e caused by i s o b a r i c CI3H15N20 and Ci4H19N2 ions, the f i r s t of which is
~ormed as a r e s u l t of elimination of an ethyl r a d i c a l f r o m the m o l e c u l a r ion (apparently f r o m the A o r B
r i n g s , as in the f o r m a t i o n of ion j o r j.'), while the second is f o r m e d by elimination of a CO group and a
hydrogen a t o m . The ion with m / e 201 is s i m i l a r to the i or i' ions, differing f r o m t h e m only with r e s p e c t
to the p r e s e n c e of two double bonds in the D r i n g .

d" role 149

Thus the data a r e evidence that it is possible, with a high d e g r e e of r e l i a b i l i t y , to r e l a t e an i n v e s t i -
gated compound to one o r another group of quinolizidine alkaloids, as was u s e d to e s t a b l i s h the s t r u c t u r e of
. a r g e n t a m i n e [1.1].
EXPI~RIME NTAL*
The l o w - r e s o I u t i o n m a s s s p e c t r a w e r e r e c o r d e d with an MKh-1309 s p e c t r o m e t e r with d i r e c t introduc-
tion of the s a m p l e into the ion s o u r c e at an ionization e n e r g y of 70 eV and s a m p l e - v o l a t i l i z a t i o n t e m p e r a -
t u r e s of 30 ~ (Ia, IIIa-d) and 50-70 ~ (IVa,b, Via-d, VIIa, VIIIa, and lEa,b). The h i g h - r e s o l u t i o n m a s s s p e c t r a
of IIIc, IVa, and IXa w e r e r e c o r d e d with an M8-3301 s p e c t r o m e t e r , while the h i g h - r e s o l u t i o n m a s s s p e c t r a
of VIa,e w e r e r e c o r d e d with a JMS-01-S s p e c t r o m e t e r .
3,3-D~-d-Lupanine. A 3 - m g s a m p l e of Na and 20 mg of d-lupanine (IVb) w e r e dissolved in a m i x t u r e
of 3 m l of absolute t e t r a h y d r o f u r a n (THF), 1 ml of D20, and 1 m l of C2HsOD , and the solution was refluxed
for 6 h, a f t e r which it was cooled and e v a p o r a t e d . The r e s i d u e was e x t r a c t e d with c h l o r o f o r m , and the ex-
t r a c t was dried o v e r Na2SO 4 and f i l t e r e d . The f i l t r a t e was e v a p o r a t e d to d r y n e s s , and the c r y s t a l s of 3,3-
D2-IVb , with mp 50 ~ w e r e used without f u r t h e r purification for the r e c o r d i n g of the m a s s s p e c t r u m . The
isotopic purity of the product was 97~c D 2, 2~ D1, and 1~ D o analogs. A s i m i l a r method was u s e d to obtain
3 , 3 - D 2 - ~ - i s o l u p a n i n e (3,3-D2-IVa), with m p 49 ~ (ether), and 3 , 3 - D 2 - m a t r i n e (3,3-D2-VIa), with mp 79~
(petroleum ether), the m a s s s p e c t r a of which a r e p r e s e n t e d in Fig. 2 ( s p e c t r a b and d).
l l , 1 2 , 1 3 , 1 4 - D 4 - A l l o m a t r i n e (ll,12,13,14,D4-VIb). A solution of 20 nag of i s o s o p h o r a m i n e IXa in 3 ml
9of ethanol was h y d r o g e n a t e d with gaseous d e u t e r i u m o v e r Raney Ni, a f t e r which the c a t a l y s t was r e m o v e d
by filtration, and the f i l t r a t e was e v a p o r a t e d (with the addition of acetone) to give 15 mg of a product with
mp 105-106 ~ which was used to r e c o r d the m a s s s p e c t r u m (Fig. 2, s p e c t r u m e). According to the m a s s
s p e c t r u m , the p r o d u c t contains 4.3% D 0, 5.4% D 1, 7.5~0 D 2, 40.8% D 3, 20.5Tc D4, and 21.5~c D 5 analogs. The
p r e s e n c e of the D5 product is evidence f o r p a r t i a l d e u t e r i u m exchange of one of the hydrogen atoms of the
A - C rings in the hydrogenation o v e r Raney Ni. This effect has been p r e v i o u s l y o b s e r v e d [12].
3 , 3 - D ~ - P a c h y c a r p i n e (3,3-D2-Ia). A solution of 14 mg of 3,3-D2-d-lupanine in 1 ml of THF was added
dropwise to a s u s p e n s i o n of LiA1H4 in absolute THF, and the m i x t u r e was refluxed for 3 h. It was then
cooled, and the LiA1H 4 was d e c o m p o s e d with ethyl a c e t a t e . The m i x t u r e was filtered, and the f i l t r a t e was
e v a p o r a t e d to give 3 , 3 - D 2 - p a c h y c a r p i n e , the m a s s s p e c t r u m of which is p r e s e n t e d in Fig. 1 ( s p e c t r u m b).

LITERATURE CITED
91. N. N e u n e r - J e h l e , N. Nesvadba, and G. Spiteller, Monatsh., 95, 687 (1964).
2. N . N e u n e r - J e h l e , D. Schumann, and G. SpiteUer, Monatsh., 98, 836 (1967).
3. D. Schumann, N. N e u n e r - J e h l e , and G. Spiteller, Monatsh., 99, 390 (1968).

* The authors s i n c e r e l y thankA. S. Sadykov, Kh. A. Aslanov, and Yu. K. K u s h m u r a d o v for kindly providing
us with s a m p l e s f o r the investigation, and A. Sulem, V. G. M e r i m s o n , V. L. Sadovskaya, and V. M a i r a n o v -
s k i i f o r r e c o r d i n g the m a s s s p e c t r a .

228
 4. S. Iskandarov and S. Yu. Yunusov, Khim. Prirodn. Soedin., 106 (1968).
5. S. Iskandarov, Ya. V. Rashkes, D. Dzh. Kamalitdinov, and S. Yu. Yunusov, Khim. Prirodn. Soedin.,
331 (1969).
6. S. Iskandarov, B. Sadykov, Ya. V. Rashkes, and S. Yu. Yunusov, Khim. Prirodn. Soedin., 347 (1972).
7. M. Hussain, J. S. Robertson, and T. R. Watson, Austr. J. Chem., 2_33, 773 (1970).
8. Pham Khoang Ngok, Yu. K. Kushmuradov, Kh. A. Aslanov, and A. S. Sadykov, Khim. Rastit.
Vestmhestva, 3, 99 (1968).
9. S. Iskandarov, V. I. Vinogradova, R. A. Shaimardanov, and S. Yu. Yunusov, Khim. Prirodn. Soedin.,
218 (1972).
10. N.S. Vul'fson (Wulfson), Z. S. Ziyavidinova (Zijavidinova), and V. G. Zaikin, Org. Mass Spectrometry,
7, 1313 (1973).
11. Pham Khoang Ngok, Yu. K. Kushmuradov, Kh. A. Aslanov, A. S. Sadykov, Z. S. Ziyavidinova, V. G.
Zaitkin, and N. S. Vul'fson, Khim. Prirodn. Soedin., 111 (1970).
12. H. Budzikiewicz, C. Djerassi, and D. H. Williams, Structure Elucidation of Natural Products by
Mass Spectrometry, Vol. 1 (1964), p. 24.

229
~r ' E L E C T R O N STRUCTURE AND R E A C T I V I T I E S OF
ISOMERIC PYRROLO-s ym- TRIAZ OLES

L. I. Savranskii, V. A. Kovtunenko, UDC 547.759' 792.9:541.67

and F. S. Babichev

The ~ ~electron s t r u c t u r e s and energies of the singlet ~ --* ~ * transitions of a n u m b e r of

i s o e l e c t r o n i c analogs of indolizine w e r e calculated by the MO LCAO method within the s e m i -
e m p i r i c a l s e l f - c o n s i s t e n t field (SCF) approximation. In c o n t r a s t to the calculations made by
the simple MO LCAO method, the ~r, e l e c t r o n density distribution obtained is in b e t t e r a g r e e -
ment with the direction of electrophilic substitution. On the basis of an analysis of the e l e c -
tronic s p e c t r a , it was concluded that the 6-phenyl group is not coplanar.

Replacement of the -H'C (7) ~ C (8)H- group of indolizine (I) by the - N ( R ) - grouping makes it possible
to d e r i v e the f o r m u l a of the is oelectronic c o m p o u n d - 1 H - p y r r o l o [1,2-a]imidazole (II) - in which a s y s t e m
of 10 electrons is provided by the joining of two f i v e - m e m b e r e d rings. The e l e c t r o n i c s t r u c t u r e of indol-
izine (I) has been studied by methods of different a c c u r a c y [1-9], while 1H-pyrrolo[1,2-a]imidazole has been
s t u d i e d only by the s i m p l e MO method [8]. The e m p i r i c a l values of the coulombic (~) and r e s o n a n c e (fl)
integrals have been v a r i e d o v e r wide limits by various investigators [1, 3, 8, 9]. The distribution of the ~r
e l e c t r o n densities (q~) in 1 H - p y r r o l o [1,2-a]imidazole [8] and in 4 H - p y r r o l o [1,2-a]benzimidazole (V) [9, 10]
in calculations by the simple MO method does not c o r r e s p o n d to the direction of electrophilic substitution.
A distribution of the 7r~ e l e c t r o n density in a c c o r d with the direction of electrophilic substitution reactions
was obtained f o r indolizine only in the calculation in [1] by the simple MO method. The conclusions r e l a t i v e
to the r o l e of the energies of electrophilic localization of the c a r b o n atoms (Lr) obtained in [3, 8] are c o n t r a -
dictory, despite the identical methods of calculation. The L~r values obtained in [8] for indolizine (I) and
p y r r o l o i m i d a z o l e (ID c o r r e l a t e with the e x p e r i m e n t a l data on electrophilic substitution, but c o r r e l a t i o n is
absent in [3]. Only the distribution of the boundary e l e c t r o n densities ( f r~) r e f l e c t the c o r r e c t direction of
the SE reactions in all of the known calculations by the simple MO method [2, 8].
5 5

I II Ill IV V

We have investigated the e l e c t r o n i c s t r u c t u r e s of indolizine (I), 1 H - p y r r o l o [ 1 , 2 - a ] i m i d a z o l e (lI), and

its aza derivatives - 1 H - p y r r o l o [ 1 , 2 - b ] - s y m - t r i a z o l e (III) [11] and 1 H - p y r r o l o [ 2 , 1 - c ] - s y m - t r i a z o l e (IV) [12].
It might have been hoped that the use of a m o r e thorough method of calculation of the e l e c t r o n i c s t r u c t u r e s
and the s p e c t r a would make it possible to avoid the c o n t r a d i c t o r y conclusions obtained by various authors
within the f r a m e w o r k of the s i m p l e MO method. We p e r f o r m e d the calculations of the electronic s t r u c t u r e s
and s p e c t r a of neutral molecules and protonated cations of indolizine (I) and a l a r g e group of its i s o e l e c -
tronic analogs by the MO LCAO method within the s e m i e m p i r i c a l s e l f - c o n s i s t e n t field (SC F) approximation.
The ionization potentials of the valence orbitals of the atoms w e r e taken f r o m [13]. The ionization potential
of the p~ orbital of the protonatod nitrogen atom was taken to be - 1 7 . 8 eV [14]. The calculations w e r e made
both without s e l f - c o n s i s t e n c y of the ionization potentials with r e s p e c t to the atomic charges (the p r o g r a m s
in [16] w e r e used) and with s e l f - c o n s i s t e n c y w i t h t h e aid of the p r o g r a m in [15]. The calculations w e r e c a r -
r i e d out with b r o a d v a r i a t i o n o f the e m p i r i c a l values of the r e s o n a n c e integrals. C o n c r e t e examples of the
effect of the selection of the values of the r e s o n a n c e integrals a r e p r e s e n t e d in Table 2.

T. G. Shevchenko Kiev State University. T r a n s l a t e d f r o m Khimiya GeterotsikUcheskikh Soedinenii,

No. 2, pp. 261-267, F e b r u a r y , 1974. Original a r t i c l e submitted November 28, 1972.

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

230
TABLE 1. Bond Orders (Pr_s), and Chargeson the Atoms ( q ~r ) f o r I s o m e r i c Pyrrolo-sym-triazoles *
,, , ,

Gem- ft-Electron charges (q jr) Bond orders (Pr.s)

pound R ~t, 1 '
7 6 5 4 3 2 I 9 8 7--6 5--6 4--5 3--4 2--3 I--2 I --8 4--8 7--8 1--9
f

0,02 --O,Ol --0,04 I 0,34 --0,I0 --0,04 --0,08 ---0,01 0,01 0,49 0,84 0,33 0,43 0,78 0,58 0,4( O,36 ', 0,80 0,71
l -- --0,01 --0,10 --0,25 0,30 0,12 --0,02 0,08 0,06 --0,17 0,65 0,61 0,28 0,32 0,72 0,61 0,5( 0,39 0,53 0,53
]I H - 0,11 - 0,05 - 0,12 0,32 - 0,09 - 0,05 0,19 - 0,08 0,55 0,80 0,40 0,29 0,91 0,33 0,3( 0,41 0,76
0,09 -0,02 -0,10 0,36 -0,16 -0,26 0,35 -_0,16 0,58 0,66 0,27 0,40 0,62 0,28 0,36 0,38 0,56

III H -.0,11 -0,06 -0,10 0,34 -0,32 0,12 0,22 t -0,10 0,55 0,79 0,43 0,25 0,86 0,42 0,28 0,42 0,76
0,12 -0,04 0,15 0,35 -0,58 0,41 0,35 0,06 0,61 0,71 0,36 0,20 0,44 0,23 0,45 0,47 0,56
I

IV H -0,11 -0,04 -0,13 0,33 0,08 0,27 0,20 i --0,07 0,54 0,80 0,38 0,35 0,87 0,30 0,32 0,38 0,76
0,12 -0,04 0,11 0,32 -0,37 0,62 0,44 I 0,05 0,59 0,73 0,35 0,26 0,44 0,20 0,49 0,43 0,58
E
-0,10 -0,05 :-0,11 0,30 -0,05 0,02 0,16 i -0,08 0,,53 0,81 0,39 0,25 0,28 0,40 0,77
9V H. -- F 0,00 -0,06 -0,05 0,31 -0,06 0,00 0,37 } -0,09 0,56 0,76 0,35 0,31 0,35 0,40 0,68
G --0,10 --0,05 -0,11 0,33 -0,08 0,05 0,24 --0,09 0,51 0,75 0,42 0,29 0,29 0,40 0,77
lie C6H6 C6H5 F 0,11 --0,10 --0,16 0,34 -0,04 0,13 0,45 --0,14 0,53 0,66 0,28 0,39 0,37 0,39 0,61
iIIa H C6H5 G --0,10 -0,06 -0,10 0,35 --0,32 0,12 0,22 --0,10 0,52 0,75 0,44 0,25 0,28 0,41 0,77
F 0,09 -0,04 0,16 0,36 -'0,54 0,35 0,28 0,07 0,57 0,62 0,39 0,22 0,42 0,45 0,56
G -0,11 -0,04 -0,11 0,34 -0,30 0,12 0,27 --0,10 0,56 0,79 0,41 0,25 0,29 0,43 0,74
]lib C6H~ H, F 0,14 -0,04 0,12 0,37 -0,51 -0,34 0,36 0,04 0,61 0,72 0,33 0,26 0,40 0,50 0,53
G -0,I0 -0,06 -0,09 0,35 -0,31 0,12 0,27 -0,I0 0,52 0,75 0,44 0,25 0,27 0,41 0,77
H 1c c 8 H 5 c61zi5 F o, 11 -0,05 o, 14 0,36 - 0,50 - 0,33 0,39 0,04 0,57 0,66 0,38 0,2,4 0,41 0,47 0,59
G --0,11 -0,04 --0,12 0,34 0,08 -0,27 0,21 --0,0," 'i 0,51 0,76 0,40 0,35 0,33 0,38 0,77
lVa H CsH~ F 0,12 -0,06 0,09 9 -0,27 --0,57 0,34 0,06 0,56 0,63 0,36 3,32 0,47 0,42 0,5.7
' G --0,12 -0,03 -0,14 0,33 0,10 --0,27 0,26 -+0,07 0,55 0,80 0,37 0,36 0,33 0,39 0,75
IVb CsHs H F 0,12 -0,05 0,05 0,34 -0,24 - 0,55 0142 0,00 0,60 0,72 0,32 0,35 0,44 0,44 0,55
G -0,10 -0,04 -0,12 0,34 0,09 --0,27 0,26 --0,08 0,51 0,76 0,40 0,35 0,31 0,38 0,77
IVe CsHs C6H~ F 0,10 -0,06 0,03 0,34 -0,21 -0,54 0,46 -0,02 0,56 0,67 0,36 0,35 0,43 0,42 0,62

9 The calculation was carried out within variant A. Abbreviations : G is the ground state, and F is the first excited state.
1" P8-9"
$ P4-9"
 TABLE 2. Reactivity,Imdexes of i - V *

Com.- I " '

pound --E~, eV

-0,i0 " o,~i ~ 12,37

9137,93
I 1 -o,o8 O20 13,26
5 --0,12 - o J7 -o,14 0,25 22,24
II 148,80
7 --0,11 --0,16 --O,l 1 0,23 923,28
5 --0,I0 -- O,15 -- 0,23 0,30 22,45
III 151,59
7 --0,I1 --0,15 --0,10 0,22 23,5I,
5 -0:13 -0,17 -0,25 0,26 22,35
151,4fi
IV -0.16 -0,11 0,22 23,42
7 --0,11
1 -0;11 0,25 22,09
V 200,24
3 -0,I0 0,19 23,11

* The qr~ values a r e the c h a r g e s on a t o m r , f r is the boundary 7r

e l e c t r o n density on a t o m r , and L $r is the ener.gy of electrophilic
l o c a l i z a t i o n of a t o m r .

The ~ e l e c t r o n densities (qr~) and bond o r d e r s (Pr-s) inthe ground and f i r s t excited s t a t e s of the c o m -
pounds that we i n v e s t i g a t e d a r e p r e s e n t e d in Table 1, while the r e a c t i v i t y indexes of the m o s t active p o s i -
tions with r e s p e c t to electrophilic attack a r e p r e s e n t e d in Table 2.
A comp~trison of the data shows that the m a x i m u m ~ e l e c t r o n densities of all of the examined c o m -
pounds (I-V) a r e l o c a l i z e d on the C0) and CO) a t o m s for indolizine I and 4 H - p y r r o l o [ 1 , 2 - a ] b e n z i m i d a z o l e
(V) and on C(5) and C(7) for H - I V . An exception to this is HI, in which the r e l a t i v e magnitude of the c h a r g e s
on C(5) and C(7) p r o v e d to be v e r y s e n s i t i v e to the s e l e c t i o n of the values of the e m p i r i c a l p a r a m e t e r s . In
p y r r o l o - s y m - t r i a z o l e s HI and IV, the g r e a t e r ~ - e l e c t r o n densities a r e localized on the nitrogen atoms of
the pyridine type. The c h a r a c t e r of the distribution of the ~r e l e c t r o n density is r a d i c a l l y changed in the
f i r s t excited s t a t e . The introduction of phenyl r i n g s into the 1 and 6 positions of p y r r o l o - s y m - t r i a z o l e s III
and IV, j u s t as in the c a s e of introduction of two phenyl groups at once, has p r a c t i c a l l y no effect on the
q~ and P r - s values of the t w o - r i n g compounds. Aza substitution in the imidazole portion of the 1 H - p y r r o l o -
[1,2-a]imidazole m o l e c u l e (It) in the 2 position does not s u b s t a n t i a l l y change the distribution of ~ e l e c t r o n
density and the bond o r d e r s of the t w o - r i n g s y s t e m , but the introduction of a nitrogen atom of the pyridine
type into the 3 position (II ~ III) leads to equalization of the c h a r g e s in the 5 and 7 positions of the III m o l e -
c u l e . In s o m e v a r i a n t s of the calculation, q7~ b e c o m e s s o m e w h a t g r e a t e r than ~ . T h r e e v a r i a n t s of the
calculation of qr~ with different values of the r e s o n a n c e i n t e g r a l (fl) for the C - N and N - N : bonds a r e p r e -
sented in Table 2: in v a r i a n t A, the fl values a r e calculated f r o m the f o r m u l a s in [15]; in v a r i a n t B, the fl
values a r e - 2 . 3 eV. In v a r i a n t C, s e l f - c o n s i s t e n c y of the coulombic integrals was not r e a l i z e d with r e s p e c t
to the c h a r g e s [16]. The values of the r e m a i n i n g indexes a r e p r e s e n t e d for v a r i a n t A. A c o m p a r i s o n of the
total conjugation e n e r g i e s (g~) of the i s o m e r i c p y r r o l o - s y m - t r i a z o l e s (IH and IV) shows r e l a t i v e l y high
s t a b i l i t y of 1 H - p y r r o l o [ 1 , 2 - b ] - s y m - t r i a z o l e s (HI). It follows f r o m an analysis of the data in Table 2 that
all of the m o s t i m p o r t a n t r e a c t i v i t y indexes (qr~ , f r~ , and L@) r of indolizine (I), 1 H - p y r r o l o [1,2-a]imidazole
(II), and 4 H - p y r r o l o [ 1 , 2 - a ] b e n z i m i d a z o l e (V} indicate that the C3(5)I a t o m s of I, II, and V will p r i m a r i l y
undergo e l e c t r o p h i l i c attack, followed only by the Clg)s a t o m s , r e s p e c t i v e l y . T h e s e conclusions a r e in
c o m p l e t e a g r e e m e n t with the e x p e r i m e n t a l data for all of the compounds listed above [17-19]. In the c a s e
of p y r r o l o - s y m - t r i a z o l e s (III, IV), the calculations p r e d i c t the g r e a t e s t r e a c t i v i t y of the c a r b o n atoms in
the 5 position in electrophilic substitution r e a c t i o n s . A c o m p a r i s o n of the data in Table 2 on the r e a c t i v i t y
indexes of the investigated compounds indicates an i n c r e a s e in r e a c t i v i t y on passing f r o m I to II, which was
p r e v i o u s l y noted in [8]. However, it i s i m p o s s i b l e to draw conclusions r e l a t i v e to the r e l a t i v e r e a c t i v i t i e s
in the s e r i e s of compounds II-IV f r o m the calculations b e c a u s e of the c l o s e n e s s of the values of the r e a c t i v -
ity indexes.
Thus, in c o n t r a s t to the r e s u l t s calculated p r e v i o u s l y by the s i m p l e MO LCAO method, we have ob-
tained s e l f - c o n s i s t e n t c onclus ions r e l a t i v e to the p r e f e r r e d d i r e c t i o n of electrvphilic substitution both with
r e s p e c t to the qr~ values and the L~r values f o r I, II, and V.

232
 TABLE 3. Charges on the Atoms (qr~) of the Monocations of Pyrrolo-
s ym-triazoles
l>toton
Monoeation,, of pyrrolo-sym-triazoles
r
added to III Illa llIb Illc IV IVa IVb IVc

2 (3) +0,13 +0,13 +0,12 +021[ + 0,07 + 0,06 + 0,07

N(9)or N(2) 5 --0,21 --0,10 --0,21 --0,21 - - 0,25 --0,15 --0,25
7 --0,10 -- 0,09 -0,10 -0,09 --0,12 --0,11 -0,I0
2 +0,06 +0,05 ' +0,03 -0,17 --0,18 --0,19 --0,20
C(5> 3 -0,18 - 0,20 --0,20 +0,05 +0,04' +0,04 +0,03
7 :-0,01 -0,06 - 0,05 --0,01 - 0,06 --0,13 --0,05
2 +0,07 + 0,06 +0,04 +0,03 --0,16 -0,.17 --0,20 --0,t9
C(7) 3 --0,19 -0,21 --0,191 --0,21 +0,04 +0,02 +0,05 +0,02
5 -0,13 -- 0,09 -0,t3 1 --0,19 --0,13 -0,10 0,00 --0,20

T A B L E 4. C a l c u l a t e d P o s i t i o n s of the A b s o r p t i o n Band M a x i m a in the

UV S p e c t r a of P y r r o l o - s y m - t r i a z o l e s (III, IV)
theor _ I. exp
Base kma x tot the eatiom, am ~max
Com-
pound theor~ exp mon~--~-m ~ ~tions ~_i of the
cations,
~ i )~max 5-H 7 T4
"-'"
/flN-H
-- , 5-H+NH
g 7-H+NH
]" II nm

I[I 307 302 297 321 323 296

234 220 234 248 244 232
220
IIIa 288 407 425 332 404 435
270 358 349 281 364 363
262 250 287 276 304
III b 328 322 323 342 339
272 269 319 266 321
248 271 256 289
1II 333 sh 300-- 426 4O8 341 419 440 315
--340 350 336 292 356 353
273 264 316 306 266 312 309
IV 316 300 296 346 320 289
240 218 237 251
IVa 311 308 4O5 426 355 399 436 306
262 266 357 344 280 362 348
253 297 283 341
IVb 340 319 329 344 370 363 349 325
275 242 324 34O 264 356 334 272
258 270 279 262 273 277
IVc 343 328 430 404 376 319
273 270 351 330 288
327 " 316 272

The c a l c u l a t i o n s of the e l e c t r o n i c s t r u c t u r e s of the 5-H and 7-H m o n o c a t i o n s of p y r r o l o - s y m - t r i a z o l e s

show t h a t s i g n i f i c a n t n e g a t i v e c h a r g e s a r e l o c a l i z e d on the n i t r o g e n a t o m s of the p y r i d i n e type i n the m o n o -
c a t i o n s . This i n d i c a t e s the p o s s i b i l i t y of the f o r m a t i o n of the c o r r e s p o n d i n g d i c a t i o n s . The v e l e c t r o n
c h a r g e s on the a t o m s in the m o n o c a t i o n s of t h e i n v e s t i g a t e d c o m p o u n d s , w h i c h w e r e o b t a i n e d w i t h i n v a r i a n t
C, a r e p r e s e n t e d i n T a b l e 3. It is a p p a r e n t f r o m T a b l e 3 t h a t t h e r e a r e c o n s i d e r a b l e n e g a t i v e c h a r g e s o n
the C(5) and C(7 ) a t o m s i n the N - c a t i o n s and t h a t t h e s e c h a r g e s d i f f e r l i t t l e f r o m the c h a r g e s i n the m o l e -
c u l e s of the b a s e s . The high n e g a t i v e c h a r g e on the p y r i d i n e n i t r o g e n a t o m of the s y m - t r i a z o l e r i n g is r e -
t a i n e d i n the C - c a t i o n s d u r i n g p r o t o n a t i o n of the 5(7) c a r b o n a t o m s , and is r e d u c e d c o n s i d e r a b l y on the 7(5)
c a r b o n a t o m s . The ~ - e l e c t r o n d e n s i t y on C(7 ) i n t h e 5-H c a t i o n s is p a r t i c u l a r l y r e d u c e d ; t h i s a l s o i n d i c a t e s
the p r e f e r r e d c h a r a c t e r of the f o r m a t i o n of the 5-H c a t i o n s . The c a l c u l a t e d p o s i t i o n s of the a b s o r p t i o n b a n d
~ theor~
m a x i m a v - m a x , t o g e t h e r with t h e e x p e r i m e n t a l v a l u e s ( k ~ x ) f o r i s o m e r i c p y r r o l o - s y m - t r i a z o l e s (III, IV)
and t h e i r p r o t o n a t e d c a t i o n s a r e p r e s e n t e d i n T a b l e 4. In a g r e e m e n t with the e x p e r i m e n t a l r e s u l t s , the c a l -
c u l a t i o n s h o w s a c o n s i d e r a b l y l o w e r i n t e g r a l i n t e n s i t y of the l o n g - w a v e b a n d as c o m p a r e d with the s h o r t -
w a v e b a n d i n the s p e c t r a of the n e u t r a l m o l e c u l e s . In the o b s e r v e d s p e c t r a , this l e a d s to the f a c t t h a t the
l o n g - w a v e b a n d is o f t e n o b s e r v e d o n l y as a s h o u l d e r . A c o m p a r i s o n of the c a l c u l a t e d and e x p e r i m e n t a l
p o s i t i o n s of the a b s o r p t i o n b a n d m a x i m a of t h e n e u t r a l m o l e c u l e s shows t h a t t h e y c o i n c i d e s a t i s f a c t o r i l y .

233
 The data presented in Table 4 make it possible to make the following observations:
1. The positions of the ~ t h e o r values of the monocations formed by protonation of a nitrogen of the
"" m a x
pyridine type do not correspond a t a l l to the experimentally observed values. Consequently, monocations
of this type are not formed on protonation.
2. According to the calculations, any variants of the formation of the monocations of 6-phenyl- or
1,6-diphenylpyrrolo-sym-triazoles (III, IV) lead to long-wave bands wlm . . . . ^ theor
max > 400 nm; this contradicts
the experimental data (a deviation of more than 100 nm). The accuracy in the calculation of the position of
uleor
9~max can be estimated at 20-30 nm. The assumption regarding disruption of the planarity of the system
.on passing from the base to the cation may s e r v e as a possible explanation of this contradiction; the 6-phenyl
group deviates from the plane, since the calculated xtl~m~r values for the mon0cations of phenylpyrrolo-sym-
triazoles are in satisfactory agreement with the experimentally observed values. In these cases, the ob-
s e r v ed absorption bands are due to the 7r s ys t em of IIIb, IV, and IVb.
. . . . theor
3. The caicum~ea Area .
x values for the 5-H and 7-H cations are v e r y close; this does not enable one
to draw a conclusion regarding the direction of protonation from the position of k exp
max"

4. Closeness of the calculated ""~ tmha xe o r values for the dications formed by protonation a t the carbon
atoms and the nitrogen atom~ of the pyridine type and of the 5-H and 7-H monocations and the experimental
)t exp values is observed in most c a s es . This does not make it possible to form a judgment regarding the
max
formation of the corresponding dications from the experimentally observed spectra, although the Xmea~~
values for dications are somewhat c l o s e r to the experimental values.

LITERATURE CITED
1o C. A. Coulson and H. C. Longuet-Higgins, Trans. Faraday Soc., 4_~3,87 (1947).
2. K. Fukui, T. Yonezawa, C, Nagata, and H. Shingu, J. Chem. Phys., 22, 1433 (1954).
3. A. Galbraith, T. Small, R. A. Barnes, and V. Boekelheide, J. Am. Chem. Soc., 8__33,453 (1961).
4. A. Streitwieser, J . Am. Chem. Soc., 82, 4132 (1960).
5. A. Gamba and G. Favini, Gazz. Chim. Ital., 9__88,167 (1968).
6. V. Galasso, G. de Alti, and A. Bigoto, Theor. Chim. Acta, 9, 222 (1968).
7. V. Galasso, Gazz. Chim. Ital., 9__99,1078 (1969).
8. L. M. Alekseeva, G. G. Dvoryantseva, I. V. Persianova, Yu. N. Sheinker, A. A. Druzhinina, and P. M.
Kochergin, Khim. Geterotsikl. Soedin., 492 (1972).
9. L. M. Alekseeva, G. G. Dvoryantseva, I. V. Persianova, Yu. N. Sheinker, R. M. Palei, and P. M.
Kochergin, Khim. Geterotsikl. Soedin., 1132 (1972).
10. M. Yu. Kornilov, G. G. Dyadyusha, and F. S. Babichev, Khim. Geterotsikl. Soedin., 905 (1968).
11. V. A. Kovtunenko and F. S. Babichev, Ukr. Khim. Zh., 38, 1142 (1972).
12. F. S. Babichev, V. A. Kovtunenko, and L. N. Didenko, Ukr. Khim. Zh., 40, No. 2 (1974).
13. J. Hinze and H. H. Jaffe, J. Am. Chem. Soc., 84, 545 (1962).
14. L. I. Savranskii, Zh. Prirodn. Soedin., 1_.33,1084 {1970)
15. G. I. Kagan, I. N. Fundyler, and G. M. Kagan, Teor. i Eksperim. Khim., 2, 589 (1966}.
16. Yu. A. Kurglyak, G. G. Dyadyusha, V~ A. Kuprievich, L. M. Podol'skaya, and G. I. Kagan, Methods
for the Calculation of the Electronic Structures and Spectra of Molecules [in Russian], Naukova
Dumka, Kiev (1969), p. 175.
17. W. L. Mosby, Heterocyclic Systems with Bridgehead Nitrogen Atoms, Vol. 1, New York-London
(1961), p. 239.
18. A. A. Druzhinina, P. M. Kochergin, and L. M. Alekseeva, Khim. Geterotsikl. Soedin., 405 (1972).
19. F. S. Babichev, G. P. Kutrov, and M. Yu. KornUov, Ukr. Khim. Zh., 34, 1020 (1968).

234
TE TRAZOLE DERIVATIVES
IX.* 1 - ( 5 - T E T R A Z O L Y L ) - 3 - P H E NYL-5-ARYLFORMAZANS
WITH ELEC TRON-DONOR SUBSTITUENTS

V. P. Shchipanov and G. F, Grigor'eva UDC 547.796.1'556.9

A s e r i e s of 1 - ( 5 - t e t r a z o l y l ) - 3 - p h e n y l - 5 - a r y l f o r m a z a n s , which a r e readily oxidized to

brightly c o l o r e d 2 - ( 5 - t e t r a z o l y l ) - 3 - a r y l - 5 - p h e n y l t e t r a z o l i u m betaines in alkaline media,
a r e obtained by coupling of arenediazonium salts containing strong e l e c t r o n - d o n o r groups
with 5 - t e t r a z o l y l h y d r a z o n e s . The f o r m a z a n s f o r m deeply colored complexes with Ni 2+,
Cu 2+, and Co 2+ s a l t s .

To a s c e r t a i n the g e n e r a l principles in the p r o p e r t i e s of f o r m a z a n s , it s e e m e d of i n t e r e s t to s y n t h e s i z e

a s e r i e s of compounds with s t r o n g e l e c t r o n - d o n o r substituents.
H H
N--N
I, ,, ...~H - +
CIN~:C6H4
R N--N [O] N--N +

N--N N,,.~.~N,
C6H~ C6H~
I II-V VI-IX"

Considerable difficulties a r e always encountered in the p r e p a r a t i o n of formazans containing e l e c t r o n -

donor groupings [2]. However, the high r e a c t i v i t y of benzaldehyde 5 - t e t r a z o l y l h y d r a z o n e (I) in azo coupling
w i t h arenediazonium salts in aqueous alkaline media makes it possible to obtain such compounds (II-V,
Table 1) in high y i e l d s . The introduction of a s t r o n g e l e c t r o n donor into the t e t r a z o l y l f o r m a z a n molecules
changed t h e i r p r o p e r t i e s substantially: the substances b e c a m e e x t r e m e l y sensitive to the action of oxidizing
agents, p a r t i c u l a r l y in alkaline media, in which formazans III-V readily undergo autooxidation. The oxida-
tion of II proceeds under the influence of K3Fe(CN) s.
F o r m a z a n s II-V have deep c o l o r in the c r y s t a l l i n e state and in solution and a r e readily soluble in aque-
ous alkali with deepening of the c o l o r , Dissolving of II in 0.1 N sodium carbonate solution leads to a con-
s iderable hypsochromic shift of the absorption maximum to
387 nm; in m o r e alkaline media (0.1 N NaOH), k m a x is 480
O rim. The family o~ c u r v e s of the UV s p e c t r a of f o r m a z a n II
2,~
at different pH values p a s s e s through an isopiestic point
2,0 (Fig. 1); this makes it possible to conclude that equilibrium
between two forms - the monoanion and the dianion - exists
in alkaline solution.
N--N N--
0,8- - ~--NH ,N_CsH4R.p .NaOH'- _~)__N N--CsH.R- p
, / , I, I / I\ --11
N--N N~N 2 Na +
[
C 6 Hs H5

.220 240 2CO ' 320 ~0 4OO ~ ~80 ~O' ff~O )., BITI
In c o n t r a s t to II, f o r m a z a n s that contain s t r o n g e r e l e c -
Fig..1. UV s p e c t r a of II at various solu- t r o n - d o n o r groups of the NH~ and N(CH3) 2 type absorb at
tion pH values: 1) pH 11.0; 2) pH 11.6; 3)
pH 12.0; 4) pH 12.3. * See [1] for communication VIII.

Tyumen, State Institute. T r a n s l a t e d f r o m Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 2 6 8 -

2 72, F e b r u a r y , 1974. Original a r t i c l e submitted J a n u a r y 22, 1973.

9 1975Plenum Publishing Corporation, 227 West 17th Street, New York, N. y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. ,4 copy o f this article is availablefrom the publisher for $15.00.

235
 T A B L E 1. 1 - ( 5 - T e t r a z o l y l ) - 3 - p h e n y l - 5 - a r y l f o r m a z a n s (II-V)

f~rnula I ] ' 1' [ [ complexes in' [~:

II OCHa 156
C,1gl4gs
3 ~ t 9Os , ) 3 4 ,t8[~.430
o-~,o t~l ]i (4..85)~
,480,1 (4:59)387"570 610 ]I640 ji96
' C H NO ~
. o,~,l~]h',~' ' [ 472 I 490 560 615 640 72
III NHOH 188 ,, t, a or, ~,~t(:?iv2) ] (4h6~6)~1(4/36) . "
C H N /407 , , , I"J~-" I 496 I 436 560 456 1666 155
14 w 9 , ~u,t "*Qo (4,66) (4,25)
IV 200--202 C H N 1333 ~ ~ !44'.;~5_!580 480 1684 t81
"V N(CHz)s 135---136 .~6t~:Oh.b , co,,[(~77) ~(4,44, (4,26, [ /

Note. a w i t h d e c o m p o s i t i o n ; II, III, and V w e r e r e c r y s t a l l i z e d f r o m

ethanol, while IV was r e c r y s t a l l i z e d f r o m 70% ethanol, bFound, %:
C 56.4; H 5.7. C a l c u l a t e d , %: C 56.7; H 6.1.

T A B L E 2. 2 - (5- T e t r a z o l y l ) - 3 - a r y l - 5 - p h e n y l t e t r az olium B e t a i n e s
(Vl-X)

Com- mp (dec.): Empirical formula ifoun~-N" % - - _ i Yield, %b

pound deg 'C a ? ! talc. i

VI OCH3 188 CIsH,,N80 34.7 35,0 1 94

VII OH 238 C14HIoNsO 37,0 i 36,6! 72
VIII NH2 230 C,4HI,N9 41.6 i 41,3 i 88
IX N(CHs), 193 C16HI~N9 38,0 t 37,8 94
X NHCOCH3 213 CI6H18NgO9H20 c 34,0 q 34,5 }I --

Note. a c o m p o u n d s VI, IX, and X w e r e r e c r y s t a l l i z e d f r o m ethanol,

while VII and VIII w e r e r e c r y s t a l l i z e d f r o m aqueous d i m e t h y l f o r m -
a m i d e (1 : 1). b B e t a i n e VIII was o b t a i n e d by autooxidation, while the
r e m a i n i n g b e t a i n e s w e r e obtained by m e a n s of K3Fe(CN) 6. CFound,
%: C 52.5; H 4.0. C a l c u l a t e d , %: C 52.5; H 4.1.

T A B L E 3. E l e c t r o n i c S p e c t r a of B e t a i n e s V I - X m u c h l o n g e r w a v e l e n g t h s (436 and 480 nm, r e s p e c t i v e -

ly) inNa2CO 3 s o l u t i o n . We s u p p o s e that this is a c o n -
Corn-
pound Medium ~'ma$, n m (lg ~}
s e q u e n c e of e q u a l i z a t i o n of the e l e c t r o n - d o n o r c h a r a c -
t e r i s t i c s of the s u b s t i t u e n t s a t t a c h e d to the 1 - N and
VI a 235 (4,26), 250d('4~23), 345 (3,67) 5 - N a t o m s ; this leads to an i n c r e a s e in the s y m m e t r y
c 240 (4,34), 260 (4,40), 370 (3,92) of the e l e c t r o n d e n s i t y on the f o r m a z a n g r o u p i n g .
VII a 240 (4,40), 350 (3,78), 485 (2,68)
b 255 (4,46), 280d(4,24), 490 (4,43) H y d r o x y d e r i v a t i v e HI, in which the OH g r o u p m a y be
C 245 (4.41), 360 (3,81) ionized in addition to the t e t r a z o l e r i n g u n d e r t h e s e
VIII a 245 (4,42), 440 (3,98)
C 250 (3,87) conditions, should also be c o n s i d e r e d f r o m t h e s e s a m e
IX a 245 (4,37), 460 (4,10) positions.
C 247 (4,35)
X a 255 (4,73), 350 (3,98)
c 257 (5,02), 350 (4,23) F o r m a z a n s II-V r e a d i l y f o r m deeply c o l o r e d
c o m p l e x e s with the cations of t r a n s i t i o n m e t a l s ; c o m -
Note: a E t h a n o l , b0.1 N alcohol s o l u t i o n of plexing of IV and V with Cu 2+ , a c c o m p a n i e d b y an in-
NaOH. c 6 N HC1. d S h o u l d e r . c r e a s e in the c o l o r , s t a n d s out s i g n i f i c a n t l y in the
e x a m i n e d s e r i e s of f o r m a z a n s and m e t a l c a t i o n s .
The t e t r a z o l i u m s a l t s (betaines) obtained by oxidation of f o r m a z a n s II-V h a v e c o l o r s f r o m light yellow
(VI, VII) to i n t e n s e r e d (IX) (Table 2). This d i s t i n g u i s h e d t h e m f r o m the c o l o r l e s s t e t r a z o l i u m b e t a i n e s c o n -
taining a c c e p t e r o r w e a k l y donor g r o u p i n g s in the phenyl g r o u p a t t a c h e d to 3 - N [1]. It should be noted that
e x a m p l e s of b r i g h t l y c o l o r e d s a l t s [3,4] and b e t a i n e s [5,6] a r e known a m o n g t e t r a z o l i u m s a l t s that a r e d e -
r i v a t i v e s of a r y l - and h e t a r y l f o r m a z a n s , m o s t of which a r e c o l o r l e s s o r p a l e - y e l l o w ; e x c e p t for [6], the
r e a s o n s f o r the c o l o r of the c o m p o u n d s h a v e not b e e n e s t a b l i s h e d .
In c o n t r a s t to t e t r a z o l i u m b e t a i n e s with a c c e p t e r g r o u p i n g s , w h i c h a r e r e a d i l y r e d u c e d in alkaline
m e d i a [1], c o m p o u n d s V I - X a r e e x t r e m e l y r e s i s t a n t to r e d u c t i o n . T h e i r r e d u c t i o n to a f o r m a z a n , the a p -
p e a r a n c e of which is d e t e c t e d f r o m a p o s i t i v e t e s t f o r c o m p l e x i n g with COC12, o c c u r s only on h e a t i n g in an
a l k a l i n e aqueous alcohol s o l u t i o n in the p r e s e n c e of h y d r o q u i n o n e .

236
 Only one band at 250 nm (loge 4.4) is o b s e r v e d in the e l e c t r o n i c s p e c t r a of c o l o r l e s s t e t r a z o l i u m
betaines [1] of the VI-IX type (R = H, CH3). In c o m p a r i s o n with this, a band at 345-350 nm (Table 3) ap-
p e a r s in the s p e c t r a of betaines that contain OH and OCH 3 groups; a b s o r p t i o n is o b s e r v e d at still longer
wavelengths (440-460 nm) in compounds with NH 2 and N(CH3) 2 groupings.
Heating betaine VIII in acetic anhydride gives the c o r r e s p o n d i n g acyl d e r i v a t i v e (X), the second band
in the UV s p e c t r u m of which is shifted to the s h o r t e r - w a v e region (350 nm) as c o m p a r e d with s t a r t i n g VIII.
Dissolving of betaines VIII and IX in c o n c e n t r a t e d m i n e r a l acids d e c o l o r i z e s them and leads to the d i s a p -
p e a r a n c e of the l o n g - w a v e band; this is a p p a r e n t l y due to protonation at the amino group. In acidic media,
the long-wave band in the s p e c t r a of VI and VII undergoes a s m a l l b a t h o c h r o m i c shift. The nitrogen atom
of the f e t r a z o l i u m ring is p r o b a b l y protonated in this c a s e to give the n o r m a l t e t r a z o l i u m s a l t A. In the
c a s e of protonation at the oxygen atom, one should have expected the d i s a p p e a r a n c e of this band. S i m i l a r
b e h a v i o r in acidic m e d i a is also c h a r a c t e r i s t i c for betaine X. The s t a r t i n g c o l o r e d s a l t s a r e isolated un-
changed when solutions of VI-X in acid a r e diluted with w a t e r .
D i s s o l v i n g of betaine VII in aqueous or alcoholic alkali leads to a s h a r p deepening of the c o l o r (h max
490 nm) with a c o n s i d e r a b l e i n c r e a s e in the extinction. If one c o n s i d e r s that betaine VII in neutral alcohol
solution displays weak a b s o r p t i o n in the s a m e region (485 nm), the connection between this band and the
ionized hydroxyl group is obvious. It might be a s s u m e d that the long-wave band in the s p e c t r a of V I - X is
due to a t r a n s i t i o n of the l --* au type, which is usually displayed when an e l e c t r o n - d o n o r substituent c o n -
taining u n s h a r e d p a i r s of e l e c t r o n s is introduced [7]. However, additional studies a r e n e c e s s a r y to d i s -
c o v e r the nature of this phenomenon in the c a s e of c o l o r e d t e t r a z o l i u m s a l t s .

~XP~RIM~NTAL *
The UV s p e c t r a w e r e r e c o r d e d with SF-4A and SF-10 s p e c t r o p h o t o m e t e r s . The IR s p e c t r a of K B r
pellets of the compounds w e r e r e c o r d e d with a UR-20 s p e c t r o m e t e r .

Method f o r the Recording of the UV S p e c t r a at Different Solution pH V a l u e s . A solution of f o r m a z a n

II (3 23 9 10 'z~ M) in 0.1 N Na2CO 3 was t i t r a t e d with a 1 N NaOH s o l u t i o n a t 20 ~ during which the pH of the
solution was d e t e r m i n e d with an LPM-60M t i t r o m e t e r . Samples for s p e c t r o p h o t o m e t r y w e r e s e l e c t e d at
definite solution pH v a l u e s .

1-(5-Tetraz~ (II) (Table 1). A diazonium s a l t solution ob-

tained f r o m 1.2 g (0.01 mole) of p-anisidine, 2.6 ml of c o n c e n t r a t e d h y d r o c h l o r i c acid, 40 ml of water, and
0.7 g of NaNO 2 in 8 ml of w a t e r , was added at 0-2 ~ to a solution of 1.88 g (0.01 mole) of h y d r a z o n e I in 100
ml of 1.6~ NaOH, a f t e r which the m i x t u r e was filtered, and the f i l t r a t e was acidified with 10 ml of acetic
acid to give 3.1 g of d a r k - c h e r r y - r e d p r e c i p i t a t e of f o r m a z a n II. Compound V (Table 1) was s i m i l a r l y ob-
tained.

! - _ ( 5 - T e t r a z o l y l ) - 3 - p h e n y l - 5 - ( p - h y d r o x y p h e n y l ) f o r m a z a n (III) and 2 - ( 5 - T e t r a z o l y l ) - 3 - ( p - h y d r o x y -
p h e n y l ) - 5 - p h e n y l t e t r a z o l i u m Betaine (VII) (Tables 1 and 2). Coupling of a diazonium s a l t solution o b t a i n e d
f r o m p-aminophenol h y d r o c h l o r i d e with h y d r a z o n e I under the conditions of the preceding synthesis gave
2.65 g of a product f r o m which 2.2 g of f o r m a z a n III (fine r e d - b r o w n p r i s m s ) and 0.25 g of betaine VII (light-
yellow needles, only slightly soluble in ethanol) w e r e isolated by f r a c t i o n a l c r y s t a l l i z a t i o n .
1- !5- T e t r az o l y l ) - 3 - p h e n y l - 5- (p-aminophenyl) f o r m a z a n (IV) and 2- (5- Tetrazolyl) - 3 - (p-aminophenyl)-
5 - p h e n y l t e t r a z o l i u m Betaine (VIII) (Tables 1 and 2). A solution of 0.69 g of NaNO 2 in 8 ml Of w a t e r was --
added at 6-8 ~ to a solution of 1.08 g (0.01 mole) of p - p h e n y l e n e d i a m i n e in 3 ml of c o n c e n t r a t e d h y d r o c h l o r i c
acid and 30 ml of w a t e r . The diazonium solution was added at 0-2 ~ to 1.88 g o f h y d r a z o n e I i n 100 ml of 1.6~c
NaOH, and the p r e c i p i t a t e d VIII was s e p a r a t e d (0.52 g of light y e l l o w - o r a n g e needles). The f i l t r a t e was
acidified with acetic acid to give 1.68 g of f o r m a z a n IV ( d a r k - b r o w n plates).- IR s p e c t r u m (cm-l): IV rNH
3380 s, 3320 s, 3190 m, 5NH 1630 s, rC=N,N=N [8, 9] 1605 s, ~[520 m, 1450 w, 1355 m, ~C-N [9] 1310 s,
1240 m, 1150 s; v i b r a t i o n s of the t e t r a z o l e ring [8, 10] at 1080 m , 1020 m, 990 m, 845 m, 780 w, 700 w;
VIII ~NI/3400 s , 3340 m, 3220 m, 5NH 1650 m, VC=N,N= N [8, 11] 1530 m, 1515 m, 1490 w, 1460 m, 1415 w,
1390 w, 1355 m, YC-N [11] 1270 w, 1175 m, 1150 m; v i b r a t i o n s of the t e t r a z o l e ring [8-11] at 1010 w, 990
m, 840 m, 7 8 5 w , 720 w, 690 w.

2---(5-Tetraz~ Betaine (IX) (Table 2). A solution

of 0.5 g of f o r m a z a n V in 50 m l of 1 N NaOH was allowed to stand in a P e t r i dish overnight. The r e s u l t i n g
* With the p a r t i c i p a t i o n of M. A. K u r m a e v a .

237
precipitate was removed by filtration to give 0.45 g (9.2%) of betaine IX with mp 193 ~ (dec.) (bright-red
needles from alcohol). Formazans III and IV were similarly oxidized.
2-(5-Tetrazolyl)-3-(p-methoxyphenyl)-5-phenyltetrazoliumBetaine (VI) (Table 2). A solution of 1.65
g (5 mmole) of K~Fe(CN) 6 in 10 ml of water was added to a solution of 0.8 g (2.5 mmole) of formazan II in
50 ml of 1 N NaOH, and the precipitate was removed by filtration and washed with water and alcohol to give
0.75 g of betaine VI (pale-yellow needles from alcohol). Compounds IX and VII (Table 2) were similarly
obtained. To isolate betaine VII, the reaction mixture was acidified with concentrated hydrochloric acid.
2-!5-Tetrazolyl)-3-(p-acetamidophenyl)-5-phenyltetrazoliumBetaine (X) (Table 2). A 0.5-g sample
9of betaine VIII in 10 ml of acetic anhydride was refluxed for 1 h, after which the solution was cooled, and
the precipitated light-orange X was removed by filtration to give 0.32 g {56%) of yellow-orange needles. The
product was only slightly soluble in alcohol and dimethylformamide. IR spectrum, ~, cm -l : NH 3225 m,
3120 m; C-~O 1710 s .

LITERATUR~ CITED
1, V. P. Shchipanov, K. I. Krashina, and A. A. Skachilova, Khim. Geterotsikl. Soedin., 1570 (1973).
2. A. P. Novikova, Master's Dissertation [in Russian], Sverdlovsk (1967).
3. J . N. Ashley, B. M. Davis, A. W. Nineham, and R. Slack, J. Chem. Soc., 3881 (1953).
4. H. Beyer and T. Pyl, Ber., 8_!, 1505 (1954).
5. H. Pechmann and E. Wedel(ind, Ber., 2__88,1688 (1895).
6. J . W. Ogilwie and A. H. Corwin, J . Am. Chem. Sot., 8_33,5023 (1961).
7. R. N. Nurmukhametov, Absorption and Luminescence of Aromatic Compounds [in Russian], Khimiya,
Moscow (1971), p. 61.
8. V. P. Shchipanov, S. L. Portnova, V. A. Krasnova, Yu. N. Sheinker, and I. Ya. Postovskii, Zh. Organ.
Khim., 1, 2236 (1965).
9. G. Arnold and C. Schiele, Spectrochim. Acre, 25A," 685 (1969).
10. c . w. Roberts, G. F. Fanta, and J . D. Martin, J. Org. Chem., 24, 654 (1959).
II. G. Arnold and C. Schiele, Spectrochim. Acta, 25A, 671 (1969).

238
LETTERS TO THE EDITOR

NATURE AND PROPERTII!:S OF TETRACYANOQUINODIMETHAN~

COMPLEXES WITH AZOLES

A. D. Garnovskii, L. S. Utkina, UDC 541.49:547.772.781.791

V. N. Sheinker, and O. A. Osipov

We have found that m o l e c u l a r c o m p l e x e s (A max 470 nm) a r e initially f o r m e d in the r e a c t i o n of t e t r a -

cyanoquinodimethane (TCQD) with azoles (imidazole, 1 - m e t h y l i m i d a z o l e , 3 , 5 - d i m e t h y l - and 1 , 3 , 5 - t r i m e t h y l -
p y r a z o l e s , and 1 - m e t h y l t r i a z o l e ) in dioxane. The c o m p o s i t i o n (1:1) was d e t e r m i n e d d i e l c o m e t r i c a l l y by the
i s o m o l a r s e r i e s method. T h e s e c o m p l e x e s acquire i o n - r a d i c a l s t r u c t u r e s (A max 744, 760, 845 nm) on
standing for 2 d a y s . The f o r m a t i o n of an i n t e r m e d i a t e m o l e c u l a r complex in methylene chloride solutions
can be detected only when solutions of the components cooled to - 8 0 to -90~ a r e mixed. I o n - r a d i c a l c o m -
plexes a r e f o r m e d p r a c t i c a l l y instantaneously at r o o m t e m p e r a t u r e . Thus the r a t e of t r a n s i t i o n of the
m o l e c u l a r c o m p l e x to an i o n - r a d i c a l c o m p l e x i n c r e a s e s as the p o l a r i t y of the solvent i n c r e a s e s and as the
temperature rises.

Rostov State U n i v e r s i t y , R o s t o v - o n - D o n . T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii,

No. 2, p. 273, F e b r u a r y , 1974. Original a r t i c l e s u b m i t t e d July 9, 1973.

9 19 75 Plenum Publishing Corporation, 22 7 West 1 7th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

239
SYNTHESIS O F A NEW H E T E R O C Y C L I C SYSTEM
THE THIONAPHTHENO[2,3-c]PYRYLIUM ION

V. I. Dulenko, V. I. Volbushko, UDC 547.735'812'821.07

L . V. D u l e n k o , and G. N. D o r o f e e n k o

We have accomplished the synthesis of thionaphtheno[2,3-c]pyrylium salts by acylation of 3-acetunyl-

thionaphthene with carboxylic acid anhydrides in the presence of perchloric acid.

The crystalline thienaphtheno N,3-c]pyrylium perehlorates were isolated in 75-80~ yields. They are
-converted to thionaphtheno[2,3-c]-pyridines by the aet~onof ammonia. The latter are of interest in Nat they
are isosteres of ~ -carbolines found in nature (the alkaloids harman and harmine) and have physiological
activity. P r elimi nar y tests have shown that they are actually of promise for the search for both active anti-
depressants and tranquilizers.
It should be noted that the thionaphtheno ['2,3-e]pyrylium cation is a new heteroaromatie system.

EXPERIMENTAL
2,4-Dimethylthionaphtheno[2,3-c]pyrylium Perchlorate. This compound, with mp 194-195 ~ (from alco-
hoD, was obtained in 80% yield. Found, %: C 49.8; H 3.8; C1 10.9; S 10.0. CI3HllC105S. Calculated, ~: C
49.6; H 3.5; C1 11.3; S 1 0 2 . IR spectra: 1623, 1550, 1115, 790, 750, 630 cm -l.
2-Ethyl-4-methylthionaphtheno[2,3-c]pyrylium Perchl orat e. This compound, with mp 199-200 ~ (from
alcohol), was obtained in 75~c yield. Found, ~: C 50.7; H 3.7; C1 10.6; S 9.7. C14H13C105s. Calculated, ~:
C 51o2; H 3.9; C1 10.7; S 9.8.
2,4-Dimethylthionaphtheno [2,3-c]pyridine. This compound, with mp 94-95 ~ was obtained in 95% yield.
Found, %: C 72.6; H 5A; N 6.4; S 15.3. C13HllNS. Calculated, ~: C 73.2; H 5.2; N 6.6; S 15.0.

Donetsk Physical Organic Chemistry Branch, Institute of Physical Chemistry, Academy of Sciences
of the Ukrainian SSR. Rostov State University, Scientific-Research Institute of Physical and Organic
Chemistry, Rostov-on-Don. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 2 73-2 74,
February, 1974. Original article submitted July I0, 1973.

9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 100II. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy o f this article is available from the publisher for $15.00.

240
ADDITION OF HYDROGEN SELENIDE TO DIACETYLENIC KETONES

A. I. Tolmachev and M. A. Kudinova UDC 547.739~

Up until now, s e l e n o p y r o n e s w e r e unknown. We have found that 2,5-heptadiym-4-one (Ia) adds h y d r o -

gen selenide in the p r e s e n c e of b a s e s to give 2 , 6 - d i m e t h y l - l - s e l e n o - T - p y r o n e (IIa). The addition of H2Se to
1 , 5 - d i p h e n y l - l , 4 - p e n t a d i y n - 3 - o n e (Ib) gives a m i x t u r e of 2 , 6 - d i p h e n y l - l - s e l e n o - T - p y r o n e (IIb) and 2 - b e n z y l -
i d e n e - 3 - o x o - 5 - p h e n y l - 2 , 3 - d i h y d r o s e l e n o - p h e n e (liD, in yields of 17 and 28~c, r e s p e c t i v e l y .

.C~H.
/ R=CH3(a) ~ S R MnO2 ~ e ~
(RCmC)2(;O
la, b Ila, b

C6H5 CHC6H5
II!

A 0 . 3 - m l s a m p l e of a 10~ solution of t r i e t h y l a m i n e was added to a solution of 3 g (28 mmole) of ketone

Ia (R = CH 3) in 30 ml of methanol, and H2Se was bubbled into the m i x t u r e f o r 20 rain in such a way that the
t e m p e r a t u r e did not exceed 35~ Half of the methanol was r e m o v e d by v a c u u m distillation (with a w a t e r
a s p i r a t o r ) , and 25 ml of w a t e r was added. Selenopyrone IIa was c r y s t a l l i z e d f r o m w a t e r to give 2.8 g (57%)
of product. Vacuum s u b l i m a t i o n g a v e c o l o r l e s s needles with mp 88-89 ~ UV s p e c t r u m , ~ max, ~m (log ~):
236 (3.86), 310 (4.36). IR s p e c t r u m : 1625 c m - l . PMR s p e c t r u m : singlets at 6.73 (2H) and 2.47 p p m (6H).
Found, %: Se 42.0. C7HsOSe. Calculated, %: Se 42.2.
Hydrogen selenide was added as in the p r e c e d i n g e x p e r i m e n t to 0.92 g (4 mmole) of ketone lb. The
resinous p r e c i p i t a t e was e x t r a c t e d with 30 m l of boiling methanol, and the methanol solution was decanted
and diluted with w a t e r . The r e a c t i o n p r o d u c t was r e m o v e d by filtration, dried, and d i s s o l v e d in 100 ml of
d r y benzene, and h y d r o g e n chloride was bubbled through the solution. The p r e c i p i t a t e d s a l t was r e m o v e d
by filtration and t r e a t e d with aqueous sodium c a r b o n a t e solution to give 0.21 g (17~'c) of s e l e n o p y r o n e IIb as
yellowish needles with mp 145-146 ~ [from b e n z e n e - c y e l o h e x a n e (1:1)]. UV s p e c t r u m , :~max, nm (log a ) :
280 (4.22), 317 (4.27). IR s p e c t r u m : 1608 c m -i (CO). PMR s p e c t r u m : s i n g l e t at 7.22 ppm (2H) and m u l t i -
plet at 7.60 ppm (10H). Found, ~ Se 25.5. C17Hi2OSe. Calculated, %: Se 25.4.
The benzene solution r e m a i n i n g a f t e r p r e c i p i t a t i o n of the s e l e n o p y r o n e s a l t was washed with w a t e r
and dried. The benzene was r e m o v e d by distillation, and the r e s i d u e was c r y s t a l l i z e d f r o m b e n z e n e - e y c l o -
hexane (1:1) and twice f r o m methanol to give 0.34 g (28~c) of III as d a r k - y e l l o w needles with mp 130-131 ~
UV s p e c t r u m , X max, nm (log 8): 338 (4.42), 438 (3.72). IR s p e c t r u m : 1660 c m -~ (CO). PMR s p e c t r u m :
singlet at 6.98 (1H), multiplet at 7.58 (10H), and singlet at 8.05 ppm (1H). Found, ~ : 25.2 Se. CtTHI2OSe.
Calculated, %: Se 25.4.

Compound IIb was also obtained by heating 0.395 g (1 mmole) of 2 , 6 - d i p h e n y l s e l e n o p y r y l i u m p e r -

c h l o r a t e and 1.9 g (20 mmole) of active m a n g a n e s e dioxide in 10 ml of a c e t o n i t r i l e f o r 10 rain. The m i x t u r e
was e x t r a c t e d with ether, and the e x t r a c t was washed with w a t e r and dried. The e t h e r was r e m o v e d by d i s -
tillation, and the r e s i d u e was c r y s t a l l i z e d twice f r o m b e n z e n e - e y e l o h e x a n e (1 : 1) to give 0.096 g (32%) of
a p r o d u c t that was identical to that d e s c r i b e d above.

Institute of Organic C h e m i s t r y , A c a d e m y of Sciences of the Ukrainian SSR, Kiev. T r a n s l a t e d f r o m

Khimiya G e t e r o t s i l d i c h e s k i k h Soedinenii, No. 2, pp. 274-275, F e b r u a r y , 1974. Original a r t i c l e s u b m i t t e d
August 14, 1973.

9 1975 Plenum Publishing Corporation. 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy o f this article is available from the publisher for $15.00.

241
SYNTHESIS OF 1,1',3,3'-TETRAETHYL-5,5i-BIS(TRIFLUORO-
ME THYLSU LF ONY L) IMIDATRICARBOC YA NI NE

V. I. Troitskaya and L. M. Yagupol'skii UDC 547.785.5'221.07+541.651

I m i d a c a r b o c y a n i n e with SO2CF 3 groups in the 5 and 5' positions (I, n = 1) proved to be an effective
p h o t o s e n s i t i z e r [1]. In the imidacyanine dye s e r i e s , t r i c a r b o c y a n i n e s could not be obtained up until now.
We have found that t r i c a r b o c y a n i n e I (n = 3) is f o r m e d ff a s u s p e n s i o n of 1.8 g of 1 - e t h y l - 5 - t r i f l u o r o -
methylsulfonylbenzimidazolium ethiodide, 0.56 g of glutaconic aldehyde anilanilide hydrochloride, and 0.2 g
of t r t e t h y l a m i n e in 10 m l of pyridine is allowed to stand for 20 days at 20-24 ~ in the d a r k . F i l t r a t i o n of the
m i x t u r e gave 0.33 g (74~c) of the s t a r t i n g q u a t e r n a r y salt, which was washed with pyridine. The pyridine
solution was diluted with w a t e r , and the dye was e x t r a c t e d with c h l o r o f o r m . The c h l o r o f o r m solution was
washed with w a t e r , the c h l o r o f o r m Was e v a p o r a t e d to a volume of 5 ml, and hexane was added. The p r e -
c i p i t a t e d dye was r e m o v e d by filtration and washed with hexane and e t h e r . It was c r y s t a l l i z e d f r o m alcohol
and washed with alcohol until the m o t h e r liquor b e c a m e p u r e blue in c o l o r . This p r o c e d u r e gave 0.07 g
(16%) of a product with mp 212-213 ~ (dec.). Found, %: F 13.7. C31H~3F6INaO4S2. Caiculated, %: F 13.7.

I C2115 CiH ~
. |

Lengthening of the c h r o m o p h o r e of the dye by one C H = C H group c a u s e s a b a t h o c h r o m i c shift of

about 100 nm in the absorption m a x i m u m (Amax is 519, 622, and 728, r e s p e c t i v e l y , for n = 1, 2, and 3).

LITERATURE CITED
1. I. I. Levkoev, ]~. B. Lifshits, L. M. Yagupol'skii, and A. V. Borin, USSR Author's C e r t i f i c a t e No.
118,091; Byul. I z o b r . , No. 4, 55 (1959).

Institute of Organic C h e m i s t r y , A c a d e m y of Sciences of the Ukrainian SSR, Kiev. T r a n s l a t e d f r o m

Khimiya Geterots iklicheskikh Soedinenii, No. 2, p. 2 75, F e b r u a r y , 19 74. Original a r t i c l e s u b m i t t e d
August 16, 1973.

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy of this article is available from the publisher for $15.00.

242
ANOMERS IN THE SYNTHESIS OF IMIDAZOLI~
NUCLNOSIDES BY THE SHAW METHOD

V. V. Alenin and V. D. Domkin UDC 547,963.32' 781.07:541,63:543.422.25

A c c o r d i n g to t h e d a t a in [1], c l o s i n g of the i m i d a z o l e r i n g in the r e a c t i o n of r i b o s y l a m i n e I w i t h i m i d -

a t e I I a p r o c e e d s w i t h the f o r m a t i o n of o n l y t h e fl - a n o m e r of i m i d a z o l e n u c l e o s i d e I l i a .
A
l
(HOCH2)2CHO--C--H
t
CH2OH
"~176 ~ nOCH2.~~ s vii ( from v)

oN/o
7~ N
HCOOR
CHsONa

O O
HA

HO OH
HA

[I
/\ CHOC2Hs v ( from m)
CH a CH 3 CHa CHs
! H II! 9
Jt~'anomer~
v vt ( from Iv)
H
iv (a.anomer) (HO.CH2)2CHO_C~ A
N---r-'
( ~ COOR t
CH20H
a R = cH.; b R=c~t~s; Ts=p-tosyl A= girl (from vl)
NH2

We h a v e found t h a t t h e r e a c t i o n b e t w e e n a m i n e I and i m i d a t e s II g i v e s both a n o m e r s Il and IV. A s c o m -

p a r e d w i t h t h e s i g n a l of t h e s a m e p r o t o n in I I I a , b , t h e s i g n a l of the a n o m e r i c p r o t o n in n u e l e o s i d e s I V a , b is
s h i f t e d to w e a k e r f i e l d ( c o m p a r e w i t h [2]). W h e n t h e p a i r of a n o m e r s is t r e a t e d w i t h a c i d , b o t h a r e c l e a v e d
to r i b o s e and t h e s a m e b a s e . C o m p o u n d s VHb and VIIIb, o b t a i n e d f r o m n u c l e o s i d e s V b and VIb b y the m e t h o d
in [3], h a v e [ a ] ~ +53 ~ and - 6 3 ~ r e s p e c t i v e l y . T h e s e d a t a p r o v e t h e a - a n o m e r i c s t r u c t u r e of n u c l e o s i d e s IV.

T A B L N 1. P r o p e r t i e s of N u c l e o s i d e s III and IV

Com- rap, deg c Empirical for-I ~=~, nm(~)b 81.H, Yield,

pound at d %
mula a I ppm c
i
IIia 159--160 e CI3HIgN306 269 (12800) 5,77 0,73 r 18 '
IVa 191 CIaHIgN~O6 269 (12700) 5,87 9 0,58 ~ 19
IIlb I71--172 , CHH21NaO6 269 (13200) 5,76 0,76 i 20
IVb I78--179 j C:~H21N~O6 269 (13800) 5,89 0,63 i 22
Note, a T h e r e s u l t s of e l e m e n t a r y a n a l y s i s c o r r e s p o n d t o t h e c o m p o s i t i o n s
give----~, b i n w a t e r . CIn d i m e t h y l s u l f o x i d e , d S i l u f o l U V - 2 5 4 , c h l o r o f o r m -
m e t h a n o l (4:1). e A c c o r d i n g to t h e d a t a in [41, t h i s c o m p o u n d h a s mP 16I ~

EXPERIMENTAL
S y n t h e s i s of N u c l e o s i d e s III a n d IV. A t o t a l of 8.0 m l of an 0.5 N s o l u t i o n of s o d i u m m e t h o x i d e in
m e t h a n o l and a s o l u t i o n of 1 g (0.006 m o l e ) of i m i d a t e II [4] in 20 m l of e t h e r w e r e a d d e d s u c c e s s i v e l y to a
s o l u t i o n o f 1.44 g (0.004 m o l e ) of a m i n e I [1] in 60 m l of m e t h a n o l , a f t e r w h i c h t h e m i x t u r e w a s h e a t e d a t
50 ~ f o r 30 m i n and a l l o w e d to s t a n d o v e r n i g h t . A m i x t a r e of a n o m e r s III and IV, w h i c h was s e p a r a t e d b y
c h r o m a t o g r a p h y on s i l i c a g e l ( s e e T a b l e 1), was i s o l a t e d on the O H - f o r m of D o w e x 1 2 (by t h e m e t h o d
i n [5J).

A. A. Zhdanov Leningrad State University. Translated from Khimiya Geterotsiklicheskikh Soedinenii,.

No. 2, p p . 2 7 5 - 2 7 6 , F e b r u a r y , 1974. O r i g i n a l a r t i c l e s u b m i t t e d M a y 3, 1973.

9 !975Plenum Publishing Corporation, 227 West 17th Street, New York, iV. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy o f this article is available from the publisher for $15.00.

243
 LITgRATURE CITIgD
1. N . J . Cusack and G. Shaw, Chem. Commun., 1114 (1970).
2. J~ A. Montgomery and H. J . Thomas, J . Am. Chem. Soc., 8_77,5442 (1965).
3. R . S . Wright, G. M. T e n e r , and H. G. Khorana, J . Am. Chem. Soc., 8__00,2004 (1958).
4. G~ Shaw and D. V. Wilson, J . Chem. Soc., 2937 (1962).
5. C. A~ Dekker, J . Am. Chem. Soc., 8_77,4027 (1965).

244
 'HRONICLES

EUROPEAN CONFERENCE ON THE CHEMISTRY OF

HETEROCYCLIC COMPOUNDS

A. N. Kost

A c o n f e r e n c e on the c h e m i s t r y of h e t e r o c y c l i c compounds, o r g a n i z e d by the E u r o p e a n A s s o c i a t i o n of

C h e m i s t s (EUCHEM), was held f r o m A p r i l 24 to April 27, 1973, in the L a Grande Metre health r e s o r t on the
s e a c o a s t 9 km f r o m Montpelier. This a s s o c i a t i o n holds annual or biennial c o n f e r e n c e s on the various
fields of c h e m i s t r y . T r a d i t i o n a l l y the c o n f e r e n c e s a r e functional in c h a r a c t e r , i.e., s p e a k e r s f r o m various
countries a r e invited to s p e a k on a s e l e c t e d p r o b l e m in o r d e r to s e t f o r t h the status of the p r o b l e m and
f o r m u l a t e the t h e m e s for d i s c u s s i o n . R e p r e s e n t a t i v e s of the s c i e n t i f i c - r e s e a r c h organizations, who pay for
p a r t i c i p a t i o n in the c o n f e r e n c e but do not p r e s e n t p a p e r s or r e p o r t s , a r e invited to the c o n f e r e n c e . A c c o r d -
ing to tradition, the c o - w o r k e r s of the o r g a n i z e r institution, who c a r r y out the h e a v y o r g a n i z a t i o n a l work,
a r e p r e s e n t at the c o n f e r e n c e f r e e of c h a r g e . Thus, the c o n f e r e n c e s a s s e m b l e about 100-150 participants
and, in addition, 15-20 s p e a k e r s . No one p r e s e n t s any a b s t r a c t s w h a t s o e v e r , and the d i s c u s s i o n s a r e not
p r i n t e d . The p a p e r s take up (at the d e s i r e of the s p e a k e r ) f r o m 20 minutes to 1 hour. Each p a p e r is fol-
lowed by a d i s c u s s i o n , which s o m e t i m e s b e c o m e s quite prolonged. Thus these c o n f e r e n c e s r e c a l l o u r
scientific schools with r e s p e c t to the s t y l e of their o p e r a t i o n .
The 1973 c o n f e r e n c e was o r g a n i z e d by the U n i v e r s i t y of Montpelier and consequently was headed by
the dean of the c h e m i s t r y faculty of this u n i v e r s i t y , P r o f e s s o r R. J a c q u i e r . T h e r e w e r e 18 s p e a k e r s , in-
cluding six f r o m F r a n c e , t h r e e f r o m G r e a t Britain, one each f r o m D e n m a r k and Belgium, and two f r o m the
F e d e r a l Republic of G e r m a n y . In addition, the o r g a n i z e r s invited s p e a k e r s f r o m the United States (three),
the USSR {one), and the G e r m a n D e m o c r a t i c Republic (one). T h e r e w e r e about 60 p a r t i c i p a n t s with about
another 30 c o - w o r k e r s of the U n i v e r s i t y of Montpelier. Thus t h e r e w e r e little m o r e than 100 p e r s o n s , and
s i n c e not all of them w e r e p r e s e n t f o r each p a p e r (we note that the s p e a k e r s w e r e at all p l e n a r y s e s s i o n s ) ,
about 50 p e r s o n s w e r e p r e s e n t at one t i m e ; this made it e a s y to c a r r y out the d i s c u s s i o n s . Of the 60 p a r -
ticipants mentioned above, t h e r e w e r e r e p r e s e n t a t i v e s f r o m G r e a t B r i t a i n (four), the United States (three),
Spain (two), Italy (two), Switzerland (three), Thailand (two), B u r m a (one), Holland (seven), and Belgium (one),
while the r e s t w e r e f r o m F r a n c e . Most of the p a r t i c i p a n t s w e r e r e p r e s e n t a t i v e s of f i r m s . F o r e x a m p l e ,
the leading c h e m i s t s f r o m the f i r m s C i b a - G e i g y , Sandoz, and H o f f m a n - L a R o c h e c a m e f r o m Switzerland.
The p r i m a r y group of p a p e r s was c o n c e n t r a t e d around two p r o b l e m s : h e t e r o c y c l i z a t i o n leading to
nitrogen h e t e r o c y c l e s , and the p h o t o c h e m i s t r y of h e t e r o a r o m a t i c compounds. The g r e a t e r portion of the
p a p e r s was linked with the i n t e r e s t s of m e d i c i n a l c h e m i s t r y , although the biological action of the s u b s t a n c e s
obtained was not d i r e c t l y d i s c u s s e d in any of t h e m . The synthesis of i n t e r e s t i n g s t r u c t u r e s was of p r i m a r y
concern.

Professor A. Lattes (University of Toulouse) was the first speaker and reviewed his research on the
u s e of a m i n o m e r c u r a t i o n and h y d r o x y m e r c u r a t i o n in the s y n t h e s i s of h e t e r o c y c l e s . It is known that m e r c u r y
s a l t s add to olefins to give an active c a r b o n i u m ion that is c a p a b l e of attacking the u n s h a r e d p a i r of e l e c -
trons of the oxygen o r nitrogen atom to give, r e s p e c t i v e l y , fl - m e r c u r a t e d alcohols or a m i n e s . The m e r c u r o
group is then r e a d i l y r e m o v e d by the action of s o d i u m b o r o h y d r i d e ; if the m e r c u r y a t o m is bonded to an
a s y m m e t r i c a l c a r b o n atom, it is r e m o v e d with r e t e n t i o n of the configuration.

Hg X2----~ .~--~-- Hg X R2NH BH~-

H e t e r o c y c l i z a t i o n is p o s s i b l e when a double bond and an amino group a r e p r e s e n t in the s a m e m o l e -

c u l e . Thus, the c o r r e s p o n d i n g p y r r o l i d i n e (II) is obtained f r o m 5 - a m i n o p e n t e n y l b e n z e n e (I), but up to 30~ of

T r a n s l a t e d f r o m K h i m i y a G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 2, pp. 277-285, F e b r u a r y , 1974.

9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

245
 HgX2 BH Z

("liHsCH=CH(CH2)3NHR7 " ~ " C6H5CH~ " C6H5CH2~t t C6H5"~1

T HgX R ~" R [~ R

piperidine d e r i v a t i v e III is f o r m e d s i m u l t a n e o u s l y with ring expansion. The ring expansion p r o c e e d s during

d e m e r c u r a t i o n , since, judging f r o m the PMR s p e c t r u m , the i n t e r m e d i a t e m e r c u r o compound has a f i v e -
m e m b e r e d r i n g . The f o r m a t i o n of f i v e - and s i x - m e m b e r e d rings was also noted in the m e r c u r a t i o n and
subsequent reduction of 6 - m e t h y l - 2 - p r o p y l a m i n o - 5 - h e p t e n e . However, if t h e r e a r e no substituents at the
end of the double bond, the p r o c e s s takes place without i s o m e r i z a t i o n of the r a d i c a l . Thus 1 - p r o p y l a m i n o -
3-butene and 1 - p r o p y l a m i n o - 5 - h e x e n e a r e cyc[ized to 1 - p r o p y l p y r r o l i d i n e and 2 - m e t h y l - l - p r o p y l p i p e r i d i n e ,
respectively.
The r e a c t i o n depends substantially on s t e r i c f a c t o r s . Thus c y c l i z a t i o n of amine IV gives only i s o m e r

9'
HXNHR
V, while amine VI f o r m s a m i x t u r e of f i v e - and s i x - m e m b e r e d r i n g s .

~.~//7-,,,,
H
--N\R

The s p e a k e r also examined the photochemical cyclization of u n s a t u r a t e d n i t r i t e s .

h'q O O h"~
( R=CH3) ( R=H )
R' R R'
If a triple bond r a t h e r than a double bond undergoes attack, the i n t e r m e d i a t e is cleaved as in the Beckmann
rearrangement.

R-C=_C(CHz)3ONO
R

S i m i l a r h e t e r o c y c l i z a t i o n s p r o c e e d during initiation with peroxides to give c a r b o n - c a r b o n o r c a r b o n -

h e t e r o a t o m bonds.
The H o f m a n n - L S f f l e r r e a c t i o n , which is b a s e d on the decomposition of N - c h l o r o a m i n e s , is the m o s t
developed r e a c t i o n in this direction. H e r e , the r a t i o of r e a c t i o n products depends s u b s t a n t i a l l y on the
solvent.

NHR
Cl R R R

H e t e r o c y c l i z a t i o n of u n s a t u r a t e d m e r c a p t a n s occurs s i m i l a r l y during photochemical initiation.

P r i m a r i l y a s e v e n - m e m b e r e d ring is f o r m e d f r o m 5-hexenethiol at -65~ while a s i x - m e m b e r e d

ring is f o r m e d a l m o s t exclusively at +80 ~ . The synthesis of bicyclic s t r u c t u r e s could be c a r r i e d out
similarly.
P r o f e s s o r R. C a r r i e (University of Rennes} r e p o r t e d that aziridine d e r i v a t i v e s with s t r o n g e l e c t r o n -
a c c e p t e r groups attached to the c a r b o n atoms a r e capable of r e a d i l y undergoing c l e a v a g e at the C - C bond
r a t h e r than at the C - N b o n d . Actually, such s t r u c t u r e s r e a c t as yUdes, interacting with both nucleophiles
and e l e c t r o p h i l e s . F o r example, e s t e r VII is stabilized as ylide VIII by the action of benzoic acid. Ylide

246
 VIII r e a d i l y r e a c t s with Wittig r e a g e n t s to give p y r r o l i n e s . Azetidines a r e obtained with ylides of t e t r a -
valent s u l f u r .
RI
A\ C"/ Rj. COOCH3
-COOCH3 ~ 4- /COOCH3 B S = "R
H ? COOCH3 ? COOCH3 C H~/'IL--"N~cH
C6H5 C6H5 6 5 6 5 .
via v.._A

P r o f e s s o r C. W. Rees (University of Liverpool) d i s c u s s e d a t t e m p t s to s y n t h e s i z e s u p e r a r o m a t i c

s t r u c t u r e s of the benzoazetidine and cyclobutenopyridine type and the r e l a t e d c h e m i s t r y of 1 , 2 , 3 - t r i a z a n a p h -
thalene. Attempts to obtain a f o u r - m e m b e r e d ring in the benzene s e r i e s by p y r o l y s i s of o - a z i d o ketones led
to opening of the benzene ring, while oxidation of the c o r r e s p o n d i n g h y d r a z o n e s gave t r i a z a n a p h t h a l e n e d e -
rivatives.
The p a p e r p r e s e n t e d by O. Buchardt (Copenhagen) was devoted to the photochemical t r a n s f o r m a t i o n s
of N-oxides of the pyridine and benzopyridine s e r i e s . He e x a m i n e d the m e c h a n i s m s of r e a c t i o n s with ring
c o n t r a c t i o n (formation of acylindoles f r o m quinoline N-oxides) or ring expansion (formation of 1 , 3 - o x a z e p -
ines). In p a r a l l e l fashion, he e a s t a b l i s h e d the f o r m a t i o n of d i r e c t s , quinolone d e r i v a t i v e s , etc., for b e n z o -
pyridine d e r i v a t i v e s . He also e s t a b l i s h e d that the oxazepine model is an i n t e r m e d i a t e in the photochemical
f o r m a t i o n of the p y r r o l e ring. S i m i l a r p r o c e s s e s w e r e followed in the p y r i d a z i n e s e r i e s .

-- Co +
O H H

In a c o m p a r a t i v e l y b r i e f p a p e r , P r o f e s s o r N. Lozach (University of C aen) examined the instances of

the ambiguous occurre'nce of r e a c t i o n s of s u l f u r analogs of i s o c o u m a r i n . As in the c a s e of the oxygen c o m -
pounds, t h e i r h y d r o l y s i s p r o c e e d s with p a r t i a l ring expansion.

Ar O
X:O;S
N2H4 [ ~ A r

O
NH2 4-
~N/NH

O
/N
An

The c o r r e s p o n d i n g thione (IX) undergoes r e p l a c e m e n t of the thione g r o u p on r e a c t i o n with aniline, but

r e p l a c e m e n t of the ring sulfur a t o m o c c u r s during proton c a t a l y s i s ,
9 A;~

N\ S H5 C6H5
C6H5 ~ C6H~

The r e a c t i o n p r o c e e d s s i m i l a r l y but in a m o r e c o m p l e x m a n n e r if another h e t e r o a t o m is introduced

into the r i n g .

Surzur and M e t z g e r f r o m the U n i v e r s i t y of M a r s e i l l e s d i s c u s s e d the synthesis of f i v e - and s i x -

m e m b e r e d sulfur rings with two h e t e r o a t o m s (one of t h e m being a nitrogen atom) as a method for r a d i c a l
cycloaddition and as a method for c h e m i c a l t r a n s f o r m a t i o n of an a l r e a d y existing r i n g . In p a r t i c u l a r ,
M e t z g e r focused attention on the s t e r i c r e q u i r e m e n t s of substituents during the alkylation of thiazolidone-
thiones, evaluating the s t r u c t u r e s of the molecules both f r o m the PMR s p e c t r a and by m e a n s of x - r a y dif-
f r a c t i o n a n a l y s i s ; this m a d e it p o s s i b l e to have independent information r e g a r d i n g the s t r u c t u r e s in the
solid s t a t e and in solution.

H. Dorn f r o m the Institute of Organic C h e m i s t r y of the A c a d e m y of Sciences of the G e r m a n D e m o -

c r a t i c P epublic p r e s e n t e d a detailed p a p e r that s u m m a r i z e d his r e s e a r c h on the s y n t h e s i s of a m i n o p y r a z o l e s
and their cyclization to p y r i d o - and p y r i m i d o p y r a z o l e s . He dealt s e p a r a t e l y with this method of a r o m a t i z a -
tion of p y r a z o l i n e s and pyrazolidones by c l e a v a g e of the c o r r e s p o n d i n g tosyl d e r i v a t i v e s .
The A m e r i c a n s c i e n t i s t G, Stork p r e s e n t e d a s h o r t r e p o r t on a t t e m p t s to u s e the known method of
alkylation of enamines (Stork alkylation) f o r the synthesis of yohimbine and its analogs. S t e r e o s p e c i f i c
routes f o r the s y n t h e s i s of two i s o m e r i c p e r h y d r o i s o q u i n o l i n e s , one of which is b a s e d on the p a r t i a l r e d u c -
tion of the b e n z e n e ring by the B i r c h method, w e r e found:

247
 9 CH3OOC~CH~'-C"-O
CH30"--~CH~HR
R CH3OOC--CH. 0 /
I

= OH- O~ ' - - C H~-'N--R

CH30~C~.H
o
The A m e r i c a n c h e m i s t L. A. Paquette found a quite g e n e r a l method for the synthesis of h o m o a r o m a t i c
compounds in the h e t e r o c y c l i c s e r i e s . The ability to undergo p o l a r o g r a p h i c reduction was taken as the
c r i t e r i o n of a r o m a t i c i t y . Dianion XI, which fulfills the r e q u i r e m e n t s of a r o m a t i c i t y , was obtained by the
action of p o t a s s i u m m e t a l on a z a c y c l o o c t a t e t r a e n e (X). It displays a potential that c o r r e s p o n d s to t w o - e l e c -
t r o n reduction and r e a d i l y r e a c t s with acids (to give 3,4- and, in p a r t , 7,8-dihydro derivatives) and other
electrophfles.

- - " " 2. , -
OCH3 THF OCH 3

,Q
OCH 3 OCH 3

Ion XI r e a d i l y adds benzophenone and then undergoes spontaneous c o n v e r s i o n to cyclobutenopyridine

{XII).

C6H5C OC6H 5

C6H5'-CI - C6H5
-o

H o m o a r o m a t i c s t r u c t u r e XIII was s i m i l a r l y s y n t h e s i z e d and c h a r a c t e r i z e d .

OCH 3
xlt_~1

Doubly-charged ions condensed with the benzene ring can be s t a b i l i z e d with ring c o n t r a c t i o n .

H O - OCP~3 H

A. K a t r i t z k y (University of g a s t Anglia), whose r e s e a r c h on t a u t o m e r i s m is well known to us in the

Soviet Union, at this t i m e s e l e c t e d for his p a p e r the ability of 3 - h y d r o x y p y r i d i n e s and t h e i r benzo analogs
to r e a c t in the dipolar ion f o r m . He was able to show the 3 - h y d r o x y p y r i d i n e methiodide, a f t e r d e p r o t o n a -
rich, f o r m s ylide XIV, which is capable of giving adducts with strong dienophiles (acrylic and m a l e i c acid
d e r i v a t i v e s and dehydrobenzene). The subsequent t r a n s f o r m a t i o n s of the adducts p r o v e d to be a new method
f o r the s y n t h e s i s of t r o p o l o n e s . The r e a c t i o n s p r o c e e d s i m i l a r l y for 3-hydroxyisoquinolines, 1 - p h e n y l - 3 -
hydroxypyridinium ions, etc.

O-- N--CH3 (CH3)2N ~ HO O

CH~CHCN
.c o 2.o.- .-

I NC
CH 3

In passing, it was a s c e r t a i n e d that the compound d e s c r i b e d in the l i t e r a t u r e as a 1 - ( d i n i t r o p h e n y l ) - 3 -

hydroxypyridinium s a l t (XV) has ether s t r u c t u r e XVI, into which this s a l t is v e r y rapidly c o n v e r t e d in the

248
 NO2 0 O

NO2 (C2H5)3 N
C6H5
~ NO2 C6H5
xv__.j
NO2
XV

p r e s e n c e of protic s o l v e n t s . P u r e XV gives adducts with, for example, s t y r e n e . In a number of c a s e s ,

quaternization of the pyridine ring is not n e c e s s a r y , for example:

N--CH2CH2CN

,~OH CH{CHCN (mixture of

isomers)

I CN
CH2CHzCN
Similar reactions p r o c e e d for hydroxy compounds of the pyridazine, phthalazine, and cinnoline s e r i e s .

(CH3)2 NCSCL + Ctz'--'~(CH3) 2 NCCt3~'r-~(CH3) 2 N=CC~z Cl,-
xvl--'T xg~u

The Belgian s c i e n t i s t H. Viehe examined the synthetic possibilities that are offered by the use of the
s o - c a l l e d "phosgenimmonium s a l t s " as applied to h e t e r o c y c l i z a t i o n . In 1957, N. N. Yarovenko r e p o r t e d that
unstable substance XVII is f o r m e d by the action of chlorine on c a r b a m o y l chloride. It was found that s u b -
stances of the XVII type actually have s a l t s t r u c t u r e XVIII, They spontaneously liberate CH3C1 on s t o r a g e ,
even at -180 ~ but one ,can work with them in situ just as easily as with o r d i n a r y r e a g e n t s . Salt XVIII proved
to be a m o r e energetic r e a g e n t than the salt of B r o d e r i c k and V i l s m e i e r . It r e a c t s readily with various CH-
acid c o m p o u n d s .

4 0 _ 6 0o (CH3)2NN /CN CH3NHNH2 H2N ._..~_/.~C N

XVIII~ -r- CH2(CN)2 C---~C
CL \CN I N(CH3)2
CH3
Under more s e v e r e conditions, even the ~ - m e t h y l e n e group of acid d e r i v a t i v e s reacts to give an ion of the
X I X type, f r o m which d i v e r s e heterocycles can be synthesized:
R R
X~ ~.. R'C(:NH) NH2 (CH3)2N "~,v~N(CH3)2
.RCH2CON(CH3)2~(CH3)2N-~C"~-"~%--N(CH3)z ,~ flN
I"~T~N
Cl CL R'

Difunctional compounds f o r m h e t e r o c y c l e s with salt XVIII, for example.

N--N
R_C~N--NH~ XV,, R_JLXy__
N(C%)2
\XH
X=O~S~NR'
While Buchardt spoke on the photochemical transformations of N-oxides, A. Lablache-Combier
(University of Lille) examined in detail the photochemical t r a n s f o r m a t i o n s of h e t e r o c y c l e s of the pyridine,
quinoline, and p y r a z i n e type. It was found that i r r a d i a t i o n of acridine brings about its reduction with partial
alkylation by solvent molecules and d i m e r i z a t i o n . When the solvent was ether, he was able to fix the i n t e r -
mediate f o r m a t i o n of free r a d i c a l s . It is a s s u m e d that an n ~ 1r * transition in the pyridine molecule (or its
analogs) is o b s e r v e d initially, and an ion r a d i c a l is f o r m e d and is also attacked by a solvent r a d i c a l . This
is in a g r e e m e n t with the q u a n t u m - c h e m i c a l calculations.

OCH2CH3 ~I,,~.,,,~L,.N.~J'-C
'- H-- O 02H5

If the molecule is initially protonated, the p r o c e s s is facilitated, and alkylation proceeds even with
methanol m o l e c u l e s .

249
 The r e a c t i o n s of i s o p y r a z o l e s (i.e., pyrazolenines) w e r e examined in a p a p e r by M. F r a n k - N e u m a n n
(University of S t r a s b o u r g ) . During the synthesis of these compounds by the usual method - r e a c t i o n of
aliphatic diazo compounds with the c o r r e s p o n d i n g olefins or acetylenes - he was able to find e x p e r i m e n t a l l y
convenient methods for the p r e p a r a t i o n of s t r u c t u r e s with functional groups in the side chain. Special a t t e n -
tion was d i r e c t e d to the synthesis of the c o r r e s p o n d i n g compounds with a s t e r o i d grouping. He was able to
s y n t h e s i z e 1 H - p y r a z o l o [ 3 , 4 - d ] p y r i d a z i n e s (XXV) f r o m diketones of the i s o p y r a z o l e s e r i e s .

C6H 5
(CH3)2 CN2 N--'---r-- CO C6H 5 N2H/. N~ N~
C=H~C-- C~C-- CC~H= ~ II IJ ~ II I
"ll II ~ ~ N > ~ COC6H 5 NX, K~N
o o
CH 3 CH 3 CH 3 CH3 C6H5
xxv

Migration of one of t h e geminal CH 3 groups to give p y r a z o l e s usually o c c u r s in the t h e r m o l y s i s of i s o -

p y r a z o l e s (it is i n t e r e s t i n g that the COOC2H ~ group m i g r a t e d when t h e r e was c o m p e t i t i o n between it and CH 3
groups). If this s o r t of s t r u c t u r e is subjected to i r r a d i a t i o n , nitrogen is p r e f e r a b l y eliminated to give c y c l o -
propene d e r i v a t i v e s .
R
:~20 ~ N R ~.x/CH3
RJ,-F'~-FII R .
N'?/I'~CH3 X "R R/~ COOC2H
5
H3C COOC2H5
cOoC2H s

The A m e r i c a n A. I. M e y e r s d i s c u s s e d a new method f o r the synthesis (including the s t e r e o s p e c i f i c

synthesis) of aliphatic aldehydes, ketones, and acids. Strictly speaking, this was not within the theme of the
c o n f e r e n c e , but the r e s e a r c h was of i n t e r e s t to synthetic c h e m i s t s ; f o r m a l l y , the method is b a s e d on the
use of h e t e r o c y c l e s , and it was t h e r e f o r e included in the p r o g r a m . 1,3-Oxazine d e r i v a t i v e s of the XXI type
a r e alkylated r e l a t i v e l y r e a d i l y through the lithium d e r i v a t i v e s and f o r m aldehydes a f t e r reduction and
h y d r o l y s i s . The yields with o r g a n o m a g n e s i u m compounds a r e s o m e w h a t l o w e r . However, the yield can be
r a i s e d substantially if the nitrogen atom is quaternized and the r e a c t i o n is then c a r r i e d out in h e x a m e t a p o l
(hexamethylphos phoric t r i a m i d e ) .

O RLI "~O R'X ,. 9 R,CH2CHO

THF,
-78= CH2L~ CH2R'
XXI
Good results were also obtained in the synthesis of branched structures ; this made i t possible to de-
velop a new method for the preparation of branched ketones.

., H~ PCHO
1 R

The method p r o v e d to be suitable in the terpenoid and s t e r o i d s e r i e s .

o

~::~/[-- CH2 2. H20/CH3OH CH3OOCCH

2
I

A s e a r c h for methods for s t e r e o s p e c i f i c synthesis was made on the b a s i s of the s a m e p r i n c i p l e .

Optically active norephedrine, f r o m which an active oxazolidine was s y n t h e s i z e d by reaction with propionic
acid imino e s t e r , was u s e d initially. Subsequent alkylation and h y d r o l y s i s gave an optically active acid with
an overall purity of only 29%. The use of optically active 2 - a m i n o - l - p h e n y l - l , 3 - p r o p a n e d i o l , which is a by-
product in the m a n u f a c t u r e of synthomycin, was c o n s i d e r a b l y m o r e s u c c e s s f u l . This made it possible to ob-
tain 2-methylhexanoic acid with a high d e g r e e of optical purity.
o o o o
RXN~, N'h/R R\N]J. N"~ .R ] ~Nl
R-. N4 R

CH30 CH 3 CH3

250
 The e s t a b l i s h m e n t of the s t r u c t u r e s of various N-oxides that a r e f o r m e d in the d i r e c t oxidation of
pteridines was the s u b j e c t of the l e c t u r e b y W. P f l e i d e r e r (University of Konstanz). It was found that the
nitrogen a t o m that is not shielded by a methyl group bonded to the nitrogen atom of the adjacent ring is
oxidized p r e f e r a b l y .
The joint application of the v a r i o u s s p e c t r a and a l t e r n a t i v e s y n t h e s i s made it p o s s i b l e to also e s t a b -
lish a n u m b e r of principles of alkylation f o r both p t e r i d i n e s and s i m p l e r model s t r u c t u r e s of the p y r i m i d i n e
and pyridazine type. A s e r i e s of data on the d i r e c t i o n of r e a r r a n g e m e n t of s u c h N-oxides by the action of
acetic anhydride was p r e s e n t e d .
A long p a p e r by the English Nobel L a u r e a t e D. Barton was devoted to s y n t h e s e s by m e a n s of phenyl-
s u l f e n a m i n e s . T r i s (phenylsulfenyl)-amine (XXII), which is r e l a t i v e l y r e a d i l y obtained by the action of
C6HsSC1 on a m m o n i a , r e a d i l y t h e r m a l l y f o r m s r a d i c a l XXIII, which is c a p a b l e of undergoing n u m e r o u s r e -
a c t i o n s . Thus, it gives quinonimine d e r i v a t i v e s on r e a c t i o n with phenols o r a r o m a t i c a m i n e s .

~ --OH 4- N(SC6H5) 3 . ~>::N--SC6H 5 + tracesofthe

1,4-isomer
xxl--~ O
.to
N(SC6H5) 3 ., . N(SC6H5) 3 -4- - SC6H 5 (~ C6H55SC6H 5)
xx,__~J

S t e r i c a l l y hindered phenols a r e attacked by this r e a g e n t with r e p l a c e m e n t of the group in the p a r a

position r e l a t i v e to the hydroxyl group. The r e a c t i o n with 2,6-dialkylanilines p r o c e e d s s i m i l a r l y .
OH O" 0 0

R R R N(SC6H5)2 NSCsH5
The r e a c t i o n s with f i v e - m e m b e r e d h e t e r o c y c l e s a r e i n t e r e s t i n g . Reagent XXII (or, m o r e p r e c i s e l y ,
r a d i c a l XXIII) is a quite s t r o n g e l e c t r o p h i l e and attacks the G - c a r b o n a t o m of furan or p y r r o l e even if t h e r e
is a s u b s t i t u e n t attached to it; r e p l a c e m e n t of the ring oxygen by nitrogen or ring expansion m a y o c c u r .

C6H5 C6H5 X-'~=~ C-'6HS'~N

5C'6H
C6Hs~'~C6H5 ~QO""C6H5~ CH6 H 5 C6Hs~N~'~Cb.H~
C6H5 C6H5

C6Hs~_~C6H5 C6H5 C6H5 "

N(SC6Hw2 HO

S i m i l a r l y , compounds of the indole s e r i e s undergo oxidative amination with e n t r y of the s u b s t i t u e n t

into the 3 position.

C6~5 ,, -C6H5 C6 .~

In addition to r a d i c a l p r o c e s s e s , r e a g e n t XXII m a y r e a c t via the s c h e m e of ionic r e a c t i o n s with s t r u c -

t u r e s in which t h e r e is a p a i r of ~ e l e c t r o n s , and a bond is f o r m e d with the sulfur atom (enamines, f o r
e x a m p l e , r e a c t t h i s way), o r in which t h e r e is an u n s h a r e d p a i r of p e l e c t r o n s , in which c a s e a bond is
f o r m e d with the nitrogen a t o m .

o[ ~ 1. XX.!.! , 20 = -~
2o H30"I"
SCBH5

P (C6H5)3 20= (C6H5~3P~NSC"6H5

251
 Thus the unusual oxidative amination r e a c t i o n developed by Barton p r o c e e d s with a s o m e w h a t d i f f e r -
ent orientation (for e x a m p l e , p r e f e r r e d entry of substituents into the ortho position even in the naphthol
s e r i e s ) than other r e a g e n t s give and is d e s e r v i n g of the s e r i o u s attention of c h e m i s t s doing r e s e a r c h in the
synthesis of h e t e r o c y c l i c s t r u c t u r e s .
A. N. Kost (Moscow University), on behalf of A. K. $heinkman (Donetsk University) and h i m s e l f , p r e -
sented a r e v i e w of h e t a r y l a t i o n r e a c t i o n s , i.e., a r e v i e w of methods for the d i r e c t introduction into an o r g a n -
ic molecule of the r e s i d u e of a h e t e r o a r o m a t i c compound of the pyridine type and its benzo d e r i v a t i v e s .
The basic positions a s s o c i a t e d with the p r o b l e m of h e t a r y l a t i o n w e r e touched upon in a p a p e r by A. K.
Sheinkman, which was published in Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii [Khim. G e t e r o t s i k l . Soedin.,
No. 1 (1974)]. It is also p r o p o s e d that the texts of s o m e other p a p e r s , which the authors have s e n t to the
editorial s t a f f of this journal, be published in m o r e c o m p l e t e f o r m .

252
MASS SPECTROMETRY OF INDOLE COMPOUNDS
(REVIEW)

R. A. Khmel'nitskii UDC 547.751.07:543.51

The b e h a v i o r of the s i m p l e s t indole s y s t e m s upon e l e c t r o n i m p a c t is examined. The r e -

a r r a n g e m e n t s o c c u r r i n g during the f i r s t s t a g e s of the disintegration a r e d i s c u s s e d , and t h e
effect of t h e s e p r o c e s s e s on d i s s o c i a t i v e ionization is d e m o n s t r a t e d . The p o s s i b l e d i s i n t e -
gration m e c h a n i s m s w e r e c o n f i r m e d in a n u m b e r of c a s e s by investigation of labeled c o m -
pounds and by the application of h i g h - r e s o l u t i o n m a s s s p e c t r o m e t r y , kinetic methods, and
low-voltage mass spectrometry.

The p r e s e n t r e v i e w is devoted to an examination of the b e h a v i o r of the s i m p l e s t indole s y s t e m s during

e l e c t r o n impact. R e s e a r c h on the m a s s s p e c t r o m e t r y of p o s i t i v e l y c h a r g e d ions is d i s c u s s e d . Special a t -
tention is d i r e c t e d to the r e a r r a n g e m e n t p r o c e s s e s o c c u r r i n g in the f i r s t s t a g e s of the disintegration of the
m o l e c u l a r ion, since it is p r e c i s e l y t h e s e p r o c e s s e s that usually lead to the development of the m o s t intense
c h a r a c t e r i s t i c peaks. Studies devoted to the quantitative c h a r a c t e r i s t i c s of d i s s o c i a t i v e ionization a r e not
c o n s i d e r e d in this review.
The cited l i t e r a t u r e e n c o m p a s s e s publications that have a p p e a r e d up to October 1972.

Indole and Methylindoles

The disintegration of indole under the influence of e l e c t r o n impact p r o c e e d s e x t r e m e l y s e l e c t i v e l y :
t h e r e a r e only t h r e e intense p e a k s with m a s s e s of 116, 90, and 89 in its m a s s s p e c t r u m , in addition to t h e
m o l e c u l a r ion (mass 117) and the c o r r e s p o n d i n g doubly c h a r g e d ion [1-3]. Metastable peaks c o r r e s p o n d i n g
to the following p r o c e s s e s w e r e o b s e r v e d in the m a s s s p e c t r u m of indole [3]: 117+---90++27, a p p a r e n t m a s s
69.2; 90+---89++1, a p p a r e n t m a s s 88.0; 89+--63++26, apparent m a s s 44.5.

7t 7+

_HCz,117139,~3)NZ 116 (3tl --CN,

]?

90 (13,~0)
-',K, I-H~

89 ( 8~1 )
C2H2 I "~
C5H 3
S5(3~5)

K. A. T i m i r y a z e v ~ A g r i c u l t u r a l A c a d e m y , Moscow. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h
Soedinenii, No. 3, pp. 2 9 ! - 3 0 9 , March, 1974. Original a r t i c l e submitted July 24, 1973.

9 19 75 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permisdon o f the publisher. A copy o f this article is avaiTable from the publisher for $15.00.

253
 The m e t a s t a b l e ions make it possible to r e p r e s e n t the disintegration of indole by means of the s c h e m e p r e -
sented above. *
The ions with m a s s e s 90 and 89 a r e p r o b a b l y d e h y d r o t r o p y l i u m ions. The m e t a s t a b l e ion, which indi-
cates detachment of C~H2, indirectly c o n f i r m s the p r e s e n c e of a s e v e n - m e I r l b e r e d h y d r o c a r b o n s t r u c t u r e ,
for which this s o r t of disintegration is e x t r e m e l y c h a r a c t e r i s t i c . However, the p o s s i b i l i t y of the existence
of other s t r u c t u r e s is not excluded [4].
The p r e s e n c e of an alkyl substituent leads to cleavage of the fl-bond with r e s p e c t to the a r o m a t i c s y s -
t e m and to the f o r m a t i o n of an intense p e a k of ( M - 1 ) + ions for the methylindoles. As for m e t h y l p y r r o l e s ,
as well as the O and S analogs, it is a s s u m e d that this s o r t of cleavage leads to expansion of the f i v e - m e m -
b e r e d r i n g of the indole s y s t e m to a s i x - m e m b e r e d r i n g and to the f o r m a t i o n of a quinolinium cation [1, 5-7].

7 .+

130

~ . . . ~ , - - HCN

130 103

Ring expansion may be realized either with migration of the C - C bond (path A_) or miEs of the
C - N bond (path B). Marx and b j e r a s s i [8], in a study of the isotopic distribution in the ( M - H - H C N ) + ion
with m a s s 103 in the m a s s s p e c t r u m of 2-methylindole labeled with C t3 at the methyl group and in the 2 p o -
sition, concluded that p a t h A is p r e f e r r e d , but ~ 14% of the ions with m a s s 103 a r e f o r m e d via a path other
than paths A and B; f r o m all a p p e a r a n c e s , cleavage of the phenyl r i n g o c c u r s h e r e .
The disintegration of s e v e n i s o m e r i c methylindoles was c o r r e l a t e d by P o w e r s [9]. During d i s s o c i a t i v e
ionization, C - m e t h y l i n d o l e s initially l o s e hydrogen with subsequent expansion of one of the r i n g s and f o r m a -
tion of ions b o f f , which in t u r n l o s e HCN and give the CsH~ + ion with m a s s 103. The l a t t e r l o s e C2142 and
f o r m the CsH5 + ion. N-Methylind01es undergo disintegration in a s i m i l a r m a n n e r , but another r o u t e is also
possible [equation (3)].
The use of a kinetic method of analysis [11, 12] for methyltndoles [10] with application of the m e t a -
stable ions showed that the ( M - l ) + ions in the m a s s s p e c t r a of 4-, 5-, 6-, and 7-methylindoles have v e r y
close e n e r g y distributions and s t r u c t u r e s . This is evidence for r a n d o m i z a t i o n (intermixing) of the s u b s t i -
tuent i n t h e ( M - 1 ) + i o n . The r e s u l t s do not enable one to draw any concrete conclusions w h a t s o e v e r r e g a r d -

--H. ~ -HCN CsH7 --C2H2 C6H: (1)

CH3 .- . .
H H
O 131 b 130 c 103 d 77

{ ~ -H" { ~ -HCN + -C2~ 2

CH3 ~ CsH 7 C6H5 (2)

H H
. e 131 f 130 C 103 d 77

[ ~ --CH 39 ~- -HCN
i,- CsHsN ~ C?H 5 (3)

I
CH 3 116 Sg

* H e r e and e l s e w h e r e , the n u m b e r s under the f o r m u l a s r e p r e s e n t the r a t i o of the m a s s to the charge ( m / e ) ,

the n u m b e r s in p a r e n t h e s e s r e p r e s e n t the intensity of the p e a k of the c o r r e s p o n d i n g ion in p e r c e n t of the
total ion c u r r e n t , the n u m b e r s i n b r a c k e t s r e p r e s e n t s the intensity of the ion p e a k in p e r c e n t of the m a x i m u m
p e a k in the s p e c t r u m , and an a s t e r i s k indicates the p r e s e n c e of the c o r r e s p o n d i n g m e t a s t a b l e ion.

254
ing the s t r u c t u r e of the ions; they m a y be e i t h e r a z a a z u l e n i u m ions (ion b) o r s o m e other type of ion (for
e x a m p l e , l i n e a r and polyunsaturated ions).
The close intensity r a t i o s of the m e t a s t a b l e and c o r r e s p o n d i n g daughter ions for 2- and 3 - m e t h y l i n -
doles and t h e i r c o n s i d e r a b l e difference f r o m the r e m a i n i n g i s o m e r s make it p o s s i b l e to a s s u m e another
s t r u c t u r e for the ( M - 1 ) + ions, for e x a m p l e , a quinolinium ion ( s t r u c t u r e f ) , which is in a g r e e m e n t with the
conclusions drawn by Marx and D j e r a s s i [8]. According to the kinetic investigations, the s t r u c t u r e of the
( M - 1) +ion in the m a s s s p e c t r u m of 1- methyl indole differs c o n s i d e r a b l y f r o m the s t r u c t u r e of the ( M - l ) +
ions f o r m e d in the disintegration of 2- and 3 - m e t h y l i n d o l e s .
The intensity r a t i o s of the m e t a s t a b l e p e a k and the p e a k of the daughter ion obtained for the p r o c e s s
ion c (mass 103) -Hon d (mass 77) a r e close for the m a s s s p e c t r a of all of the i s o m e r s except for N - m e t h y l -
indole. This fact p r o v i d e s evidence that detachment of HCN f r o m two e n e r g i e a l l y different CBH~N+ ions is
a c c o m p a n i e d b y intensive s k e l e t a l r e a r r a n g e m e n t and leads to the f o r m a t i o n of C8H7+ ions, which a r e s t r u c -
t u r a l l y and e n e r g i c a l l y s i m i l a r for all of the C - m e t h y l i n d o l e s .
The data a r e c o n f i r m e d [10] by an a n a l y s i s of the s p e c t r a of the kinetic e n e r g i e s of the ions [13, 14].
T h r e e types of r e a r r a n g e m e n t p r o c e s s e s leading to expansion of the r i n g s a r e fundamentally p o s s i b l e
for di-, t r i - , and polymethylindoles [15-18].
1. L o s s of a hydrogen a t o m of the methyl group in the 1, 2, and 3 positions of indole with subsequent
expansion of the p y r r o l e r i n g and f o r m a t i o n of a quinoline s t r u c t u r e . This s a m e p r o c e s s is p o s s i b l e when
at l e a s t two adjacent methyl groups a r e p r e s e n t with l o s s of one of t h e m and hydrogen migration.
2. L o s s of two h y d r o g e n a t o m s by two methyl groups in the p y r r o l e r i n g of indole or l o s s of a h y d r o -
gen a t o m of the methyl group of the methylquinolinium ion (which is f o r m e d e a r l i e r ) with subsequent e x -
pansion of it to an a z e p i n i u m ion. The l a t t e r on losing a hydrogen a t o m can be c o n v e r t e d to an a z a t r o p y l i u m
ion. The l o s s of CH~ and H is also p o s s i b l e when t h r e e methyl groups a r e p r e s e n t in the p y r r o l e r i n g of in-
dole.
3: L o s s of a hydrogen a t o m (one of the two Vicinal methyl groups) of the methyl group in the benzene
r i n g of the indole with its subsequent expansion to the c o r r e s p o n d i n g t r o p y l i u m s t r u c t u r e :

C H 3 ~ - ~ c~r -cHr ,._ c H 3 ~

H CH3 ~'~N~'
H
15g ( 2 3 , 5 ) 144 C11~S )

~ CH 3 or

--H. -H.

7t ~
or 143 (2~7)

H H
L 157 (2,7, [

H
156 (2~,6)
The intensity of the p e a k s of the ( M - 1 5 ) + ion in d i m e t h y l - , t r i m e t h y l - , t e t r a m e t h y l - , and p e n t a m e t h -
ylindoles [17] i n c r e a s e s l i n e a r l y as the n u m b e r of methyl substituents i n c r e a s e s . However, the r a t i o of the
intensities of the peaks of the ( M - 15) + ions to the n u m b e r of m e t h y l groups in the indole s y s t e m r e m a i n s
constant and is independent of this n u m b e r and of the o r i e n t a t i o n of the methyl groups. In other w o r d s , the
methyl groups in the e x t r e m e l y u n s y m m e t r i c a l indole s y s t e m behave as if t h e y w e r e under absolutely iden-
t i c a l conditions, and the p r o b a b i l i t y of t h e i r detachment is independent of the position. This fact p r o v i d e s
indirect evidence of r a n d o m i z a t i o n of the methyl substitutent o v e r the entire indole s y s t e m in the c a s e of
di-, t r i - , and polysubstitus systems.

255
 The dissociative ionization of alkylindoles [5, 7, 18] with substituents l a r g e r than methyl is realized
with predominant cleavage of the C - C bond of the alkyl chain in the fl-position relative~ the indole s y s -
tem; this process is often accompanied by migration of a hydrogen atom and formation of a pseudomolecu-
l ar r e a r r a n g e d ion.

1,7-Dimethylene- and 1,7-Trimethyleneindoles

Ions formed via three principal directions can be isolated in the disintegration of 1,7-dimethylene-
2,3-dimethylindole in the first stages under the influence of electron impact. First, r e a r r a n g e d ions that
are formed with the expansion of the pyrrole ring during detachment from the starting molecule of one or
two hydrogen atoms or a methyl group are similar to the ions observed in the disintegration of 2,3-dimeth-
ylindole. Second, since there is a saturated five-membered ring condensed with the aromatic system of in-
dole in the molecule, it undergoes extremely intensive dehydrogenation, both in the stage involving disinte-
gration of the molecular ion and in the stage involving formation (without disintegration of the saturated
ring) of fragment ions. Finally, r a t h e r intensive disintegration of the saturated ring with splitting out of C2H2,
C2H3, and C2H 4 particles occurs in the molecule under the influence of electron impact.
The disintegration of 1,7-trimethylene-2,3-dimethyl- and -1,3,5-trimethylindole is basically similar,
but there are substantial differences associated with replacement of the five-membered saturated ring by a
six-membered ring.

Phenyl- and Benzylindoles

The mass spectra of phenylindoles were examined in [9, 19]. The principal act of the dissociative ion-
ization of isomeric 2- and 3-phenylindoles [19] is the formation of an ion with mass 165, which corresponds
to the fluorenyl cation structure, which may be formed both during splitting out of CH2N from the molecular
ion and during detachment of a hydrogen cyanide molecule from the ( M - 1)+ ion; the detachment of the above-
indicated groupings from 2-phenylindole without r e a r r a n g e m e n t is unlikely.
The metastable peak with mass 141.5, which corresponds to the process 192+-~165++27 in the mass
spectra of phenylindoies, attests to probable r e a r r a n g e m e n t of the ( M - I ) + ion with subsequent splitting out
of HCN, although one cannot exclude the possibility of r e a r r a n g e m e n t of the molecular ion.
The introduction of a m~thyl group into the phenylindole molecule (3-methyl-2-phenylindole, 2-methyl-
3-phenylindole, and 2-methyl-7-phenylindole) leads to great differences in the mass spectra of the isomeric
compounds [19]. The r e a r r a n g e d ( M - H ) + ion, which apparently has the qulnoline structure, and the other two
r e a r r a n g e d ions basically determine the paths of the subsequent disintegration.
q -t-

191 ( 0~,5 )

I H I H
t I
--211 9

207 (2G,61 206 (22,8) 204 (5,4)

1- C6H5 " I-C6H5 '

I-C6H

H
!30 (5~5) 129 ( 0 , 6 ) 128 (3~,3)

Cleavage Of the bond between the phenyl and indole rings, which corresponds to the formation of the
(M-77) + ion, while being absolutely uncharacteristic for phenylindoles, is real i zed to a considerable degree
in the case of 3-methyl-2-phenyl- and 2-methyl-3-phenylindole. It might be assumed that the driving force

256
of t h e s e p r o c e s s e s is r i n g expansion and the f o r m a t i o n of quinolinium ions. If this p r o c e s s is unlikely, the
intensity of the ( M - 7 7 ) + p e a k d e c r e a s e s s h a r p l y [19].
Detachment of a methyl group, a c c o m p a n i e d by splitting out of a hydrogen a t o m to f o r m a new bond
between the phenyl substituent and the indole s y s t e m c o m p e t e s with detachment of a phenyl group. In the
c a s e of 2 - m e t h y l - 7 - p h e n y l i n d o l e , cyclization with the p a r t i c i p a t i o n of the n i t r o g e n a t o m and the f o r m a t i o n
of a stable f i v e - m e m b e r e d r i n g is e n e r g i c a l l y m o r e f a v o r a b l e .
Methylphenylindoles a r e c h a r a c t e r i z e d by an e x t r e m e l y significant dehydrogenation p r o c e s s [19]. In
addition to the peaks of the e x a m i n e d ( M - 1) +, ( M - 2)+and ( M - 3 ) + ions, t h e r e a r e also ( M - 4 ) + peaks [and
s o m e t i m e s even up to ( M - 8 ) + p e a k s ] in the m a s s s p e c t r a .
The disintegration of 1-benzylindole [20] and 2 , 3 - d i m e t h y l - l - b e n z y l i n d o l e [18] p r o c e e d s with r i n g ex-
pansion and p r e d o m i n a n t l o c a l i z a t i o n of the p o s i t i v e c h a r g e on the phenyl ring; this leads to the m o s t p r o b -
able f o r m a t i o n of the C7H7+ ion. The ( M - 7 7 ) + ions which c o r r e s p o n d to detachment of a phenyl group, a r e
absent. The f o r m a t i o n of ( M - H ) +, ( M - 1 5 ) +, andCTHTe ions f r o m the m o l e c u l a r ion and of the C5H5+ ion f r o m
the t r o p y l i u m ion is c o n f i r m e d b y the c o r r e s p o n d i n g m e t a s t a b l e peaks. The introduction of four fluorine
a t o m s into the benzene r i n g of 1-benzylindole changes the direction of disintegration only slightly [21].

Tryptamine and Methyltryptamines

The disintegration of t r y p t a m i n e [6] under the influence of e l e c t r o n impact p r o c e e d s p r i m a r i l y at the
fi-bond with the splitting out of a CH2NH2 group and f o r m a t i o n of an t m m o n i u m ion with m a s s 130, which can
r e a r r a n g e to a stable quinolinium ion, as d e s c r i b e d for 2- and 3 - m e t h y l i n d o l e s . The f o r m a t i o n of this ion
is also p o s s i b l e f r o m the ion with m a s s 131, which is obtained in the splitting out of a CHNH 2 group f r o m
the s t a r t i n g molecule [6].
-NH 2 K~-~..~ C H C H3

H
14.4 (3~,5)

]+.
~ C.2C.~NH2I t --CHN~2 ~
H
CH3
H
131 (18~7)
160 ( 3,7 )

I-H.

H H
130 ( 3 t ~ 0 )

The disintegration of m e t h y l t r y p t a m i n e s [22-24] is b a s i c a l l y analogous to the disintegration of t r y p t a -

mine. Disintegration at the fl-bond with m i g r a t i o n of a hydrogen a t o m and f o r m a t i o n of an ( M - 2 9 ) + l o n , s i m -
i l a r to the ion with m a s s 131 in the s p e c t r u m of t r y p t a m i n e , is c o n f i r m e d by the p r e s e n c e of the c a r r e -
sponding m e t a s t a b l e p r o c e s s e s . Competition in the f o r m a t i o n of these ions and t h e ( M - 3 0 ) + ions, which
have the quinolinium ion s t r u c t u r e and a r e obtained during cleavage of this s a m e f l - b o n d without hydrogen
m i g r a t i o n , is o b s e r v e d in the m a s s s p e c t r a of t r y p t a m i n e and m e t h y l t r y p t a m i n e s . The p r o b a b i l i t y of the
o c c u r r e n c e of t h e s e p r o c e s s e s depends m a r k e d l y on the e n e r g y of the ionizing e l e c t r o n s [2].

Phenyltryptamine s
The introduction of a phenyl substituent into the 1 position of the 2 - m e t h y l t r y p t a m i n e , t r y p t a m i n e , and
m e t h y l t r y p t a m i n e molecules [6, 25] has p r a c t i c a l l y no effect on the intensity of the disintegration p r o c e s s e s
of the aminoethyl side chain at the fl-bond with splitting out of CH2NH2 and CHNH 2 groups. As b e f o r e , the
m o s t intense p e a k s in the m a s s s p e c t r a c o r r e s p o n d to t h e s e p r o c e s s e s , which a r e c o n f i r m e d b y the c o r r e -
sponding m e t a s t a b l e ions.
The c h a r a c t e r i s t i c (for phenylindoles) p r o c e s s e s of f o r m a t i o n of ions c o r r e s p o n d i n g to subsequent
splitting out of hydrogen a t o m s in the m a s s s p e c t r a of p h e n y l t r y p t a m i n e a p p e a r only a f t e r disintegration of
the side chain.

257
 The behavior of 1,2-diphenyltryptamine is similar to the behavior of the corresponding phenylindoles.
Just as in phenylindole, disruption of conjugation, which is associated with the noncoplanarity of the molec-
ular ion, leads to a decrease in the stability of the p r i m a r y ion, and, as a consequence, to the occurrence of
disintegration via a large number of paths. The most intense peaks correspondto ions associated with dis-
integration at the fl-bond of the side chain and the formatinn of r e a r r a n g e d ions with subsequent dehydro-
genation, which leads to ions with aromatic structures.
The disintegration of benzyltryptamines reflects the competition in the possibility of localization of
the charge on various portions of the molecule.
Thus the disintegration of aryltryptamines to a considerable degree is in agreement with the dissocia-
tive ionization of the corresponding indoles. However, the processes characteristic for the analogous indole
derivatives proceed only after disintegration of the side aminoethyl chain of tryptamine. As in phenylin-
doles, the ions formed by successive dehydrogenation correspond to aromatic structures.

Homotryptamines
An increase in the length of the aminoalkyl side chain as compared with tryptamines (dimethylhomo-
tryptamine) changes the behavior of these systems only relatively little under the influence of electron im-
pact [6]. Just as in tryptamines, the p r i m a r y act of disintegration is cleavage of the side chain with split-
ting out of CH2NH2 and CHNH2 groups, although the second process becomes less intense. However, disin-
tegration paths absent or uncharacteristic for tryptamines begin to manifest themselves in these com-
pounds. As seen f~om the scheme for the disintegration of 2,7-dimethylhomotryptamine, the disintegration
of the C - N bond with splitting out of ammonia, which is not too intense in the spectrum of tryptamine and
is almost completely absent in the spectra of methyltryptamines, leads to a third (with respect to intensity)
Ion in the mass spectrum. P r o c e s s e s involving cleavage at the T-bond relative to the indole system, which
are activated by the effect of an amino group [the characteristic (for amines) disintegration at the ~-bond
with r es p ect to the amine nitrogen], also are quite intensive. However, the possibility of complete splitting
out of an aminoalkyl group with migration of hydrogen from the adjacent methyl substituent and ex-
pansion of the p y r r o l e ring of the indole system is most characteristic for homotryptamines. This
p ro ces s was not realized in tryptamines, inasmuch as the coordinated effect of the aromatic system
and of the amino group leads only to cleavage of the /3-bond. The subsequent disintegration of the
resulting ions is similar to that described for methylindole and methyltryptamines.

Stability of Alkyl- and Aryl-Substituted Indoles and Tryptamines

Compounds of the indole s e r i es are extremely resi st ant to electron impact. In the dissociative ion-
ization of indole, ~40% of the total ion current (WM) goes into the production of the molecular ion fraction,
and the peak corresponding to it is a maximum in the mass spectrum. The introduction of the first methyl
substituent reduces the resistance of the molecule to electron impact by a factor of almost two. The intro-
duction of the second and third methyl groups also lowers WM, but to a considerably l e s s e r extent; the ad-
dition of a fourth and fifth substituent leads to an increase in the stability [26]. A similar picture is also
observed in the disintegration of tryptamine [26].

H o,, Y
185 (6~1) ~'~Ai~ 144 (/-,,,O)

,."CH2CH2CH2NHz7 f

~H CH3
CH 3 ~ C'~/
20;~ (6~3) ""~ s~

H
CHo
CH 3 h
158 (17t2)
172 ( 2 t 2 )

258
 The o b s e r v e d i n c r e a s e in W M as the volume of the molecule i n c r e a s e s can take place only in the case
of s o m e r e a r r a n g e m e n t s of the m o l e c u l a r ion itself. This m a y be r e f l e c t e d in a change in the s t r u c t u r e of
the f r a g m e n t ions of identical m a s s that a r e f o r m e d in the f i r s t s t a g e s of the disintegration of the m o l e c u l a r
ion [27].
Monophenylindoles [9] differ c o n s i d e r a b l y with r e s p e c t to t h e i r s t a b i l i t y as a function of the position
of the phenyl group. The i n c r e a s e d e l e c t r o n density in the 3 position of the indole s y s t e m , due to the opti-
m u m conditions for its conjugation with the phenyl substituent, leads to an i n c r e a s e in W M of 60 r e l a t i v e %
for 3-phenylindole as c o m p a r e d with 2-phenylindole and even to a slight i n c r e a s e as c o m p a r e d with indole.
The introduction of yet another phenyl group (2,7-diphenylindole) l e a d s to an i n c r e a s e in W M as a r e s u l t of
stabilization of the m o l e c u l a r ion due to the e l e c t r o n - d o n o r phenyl substituents. One might have expected
a c e r t a i n f u r t h e r i n c r e a s e in W M in triphenylindoles. However, a g r e a t e r than twofold d e c r e a s e in the s t a -
bility, c a u s e d by two adjacent phenyl groups which disrupt the c o p l a n a r i t y of the m o l e c u l a r ion and the con-
jugation of the phenyl groups with the indole s y s t e m , is o b s e r v e d in 2,3,7-triphenylindole. The p o s s i b i l i t y
of the o c c u r r e n c e of profound disintegration via a l a r g e n u m b e r of paths is a consequence of this.

Carbazoles and Tetrahydrocarbazoles

In comparison with the corresponding aromatic hydrocarbons, carbazoles have extremely high resis-
tances to electron impact [28, 29]. The mass spectra of these compounds are simple: the maximum peak
corresponds to the molecular peak in the spectrum, and disintegration of the compound takes place ex-
tremely selectively. Apart from the molecular ion peak with mass 167 (CI2HgN) + in the mass spectrum of
carbazole itself, only ion peaks with masses 139 (CIIHT) + and 140 (Ci0II~N)+have adequate intensities. The
elementary compositions of these ions were established on the basis of a precise measurement of the
m a s s e s [29].
The d e t a c h m e n t of C2H3 f r o m the m o l e c u l a r ion is o b s e r v e d only in the m a s s s p e c t r u m of c a r b a z o l e ;
substituted c a r b a z o l e s e l i m i n a t e only H2CN fro m the m o l e c u l a r ion, while N - m e t h y l - s u b s t i t u t e d c a r b a z o l e s
also e l i m i n a t e a methyl group. Detachment of a substituent is not o b s e r v e d in the c a s e of N - a r y l - s u b s t i -
tuted c a r b a z o l e s ; detachment of H2CN is a l s o blocked in this case.
The m a s s s p e c t r a of t e t r a h y d r o e a r b a z o l e and m e t h y l - , phenyl-, and b e n z y l - s u b s t i t u t e d t e t r a h y d r o -
c a r b a z o l e s [30] a r e c h a r a c t e r i z e d by intense, s u c c e s s i v e dehydrogenation of the s y s t e m , both in the stage
involving the m o l e c u l a r ion and in the stage involving the ions f o r m e d a f t e r splitting out of the substituent.
A c o n s i d e r a b l e portion of the ions f o r m e d as a r e s u l t of dehydrogenation a r i s e f r o m the ( M - l ) + ion, The
intensity of the p e a k s of the ( M - l ) + ions depends to a c o n s i d e r a b l e d e g r e e on the nature of the substituent
in the indole ring.
In addition to dehydrogenation, disintegration at the fl bonds with r e s p e c t to the indole s y s t e m with
splitting out of an ethylene m o l e c u l e , p o s s i b l y with the following r e a r r a n g e m e n t , is c o m m o n for all of the
tetrahydrocarbazoles:

_ C2H 4 ~ ~-

H H
171 ( 3 2 ~ , 2 )

Indole-Containing Condensed Systems

The o v e r w h e l m i n g m a j o r i t y of compounds of this type, p a r t i c u l a r l y compounds with an indole r i n g
condensed with n i t r o g e n - c o n t a i n i n g r i n g s , a r e indole alkaloids and t h e r e f o r e a r e beyond the scope of the
p r e s e n t r e v i e w . However, an examination of r e l a t i v e l y s i m p l e s y s t e m s that do not enter into the indicated
c l a s s e s of natural compounds is of undoubted i n t e r e s t .
The m a s s s p e c t r a of benzindole and dihydrobenzindole w e r e d e s c r i b e d by Pandit and c o - w o r k e r s [31,
32] and L e e h [33]. An i n v e s t i g a t i o n o f 2 , 3 - p h e n y l e n e d i h y d r o i n d o l e s showed [34] that the m o s t p r o b a b l e p r o -
c e s s involves elimination of CH2N and f o r m a t i o n of an ion with m a s s 165, which c o r r e s p o n d s to the fluorenyl
cation s t r u c t u r e . It is i n t e r e s t i n g to note that s i m p l e disintegration of the f o u r - m e m b e r e d r i n g does not o c -
cur during e l e c t r o n impact of this compound.

259
 CH2N ' ~,,

165

A m a s s - s p e c t r o m e t r i c method was used by B e r g m a n and c o - w o r k e r s [35, 36] for the identification of

the products of m a c r o c y c l i c condensation of indoles and s i m p l e aldehydes. Thus the r e a c t i o n of 1- methyl in-
dole With formaldehyde gave a t r i m e r , the m a s s s p e c t r u m of which has a m o l e c u l a r ion p e a k of s e c o n d a r y
intensity. Indolo [3,2-b]carbazole was identified in the c a s e of the condensation of indole and formaldehyde.

9 o C.~o

The m a s s s p e c t r a of methylindolylearbaT.oles f o r m e d during t h e r m a l and catalytic d i m e r t z a t i o n of

vinylindole w e r e examined in [37]. The m a s s s p e c t r a of [ndolylmethylpiperidines w e r e also d e s c r i b e d [38].
An investigation of the m a s s s p e c t r a of N - s k a t y l b e n z i m i d a z o l e , N - s k a t y l - 2 - m e t h y l - and N - s k a t y l - 2 -
benT.ylber~im[dazole, and N-skatyl-l,2,3-benT.otriazoles showed that the disintegration of t h e s e compounds
during e l e c t r o n impact is r e a l i z e d via the expected paths and leads to r e a d i l y identified f r a g m e n t s that a r e
f o r m e d f r o m the methylindole or tmidazole (triazole) portions of the molecule. The m o l e c u l a r p e a k s a r e
intense, and an ion with m a s s 130 with the probable s t r u c t u r e of the quinolinium cation c o r r e s p o n d s to the
m a x i m u m p e a k in all of the m a s s s p e c t r a [39].
In the dissociative ionization of m e t h y l - s u b s t i t u t e d 3 , 3 ' - a z o i n d o l e s [40], disintegration at the fl-bond
with the f o r m a t i o n o f ( M - l ) + ions is s u p p r e s s e d b y other p r o c e s s e s . The m a x i m u m p e a k c o r r e s p o n d s t o a n
ion with m a s s 159; this ion is f o r m e d as a r e s u l t of m i g r a t i o n of a hydrogen of the methyl group to the ni-
t r o g e n a t o m of the azo group with subsequent cleavage of the N - N bond. Charge localization on the n i t r o -
gen a t o m of the azo group p r o b a b l y p r e c e d e s the indicated p r o c e s s .

CH 3

C H 2::;:~/N

CH3
/
316 [.67] 1 NH

I CH]
CH 3
~59 ~_1oo]
The m a s s s p e c t r a of hexahydroazepine [2,3-b]indoles w e r e investigated b y H e s t e r [41], and the s i m -
p l e s t d e r i v a t i v e s of pyridoindoles w e r e studied in [42-47].
Biemann [42] found that the disintegration of 1 - a l k y l - f i - c a r b o l i n e s with an alkyl chain containing m o r e
than two c a r b o n a t o m s p r o c e e d s with M c L a f f e r t y r e a r r a n g e m e n t .
Coutts and c o - w o r k e r s [46] investigated 12 substituted f l - c a r b o l i n e s using d e u t e r i u m - l a b e l e d c o m -
pounds and h i g h - r e s o l u t i o n m a s s s p e c t r o m e t r y .
The disintegration of 1 - a l k y l - l , 2 , 3 , 4 - t . e t r a h y d r o - f l - c a r b o l i n e s is r e a l i z e d in the f i r s t stage with de-
t a c h m e n t of an alkyl r a d i c a l (It) or with elimination of RNH. The r e s u l t i n g ( M - R ) + i o n with m a s s 171 c o r -
r e s p o n d s to the m a x i m u m p e a k in the s p e c t r u m . This ion on disintegration giv.es a n u m b e r of intense peaks.
The use of h i g h - r e s o l u t i o n m a s s s p e c t r o m e t r y showed that in the disintegration of 1 - m e t h y l - l , 2 , 3 , 4 - t e t r a -
h y d r o c a r b o l i n e , 67% of the ions with nominal m a s s 117 a r e CsHTN+ ions, while 33% a r e C9H9+ ions. The
second path of disintegration leads to ions with m a s s 156, which subsequently eliminate CHsCN and f o r m
ions with m a s s 115.

260
 Rather little study has been devoted to the m a s s s p e c t r a of compounds with the e s e r t n e and h o m o e s e r -
ine s k e l e t o n s [48-51]. The m o s t probable p r i m a r y paths of d i s s o c i a t i v e ionization of the e s e r o l i n e s axe d i s -
integration of the pyrrolidine ring, detachment of a methyl group, and f o r m a t i o n of ions with m a s s 30 (CH2=
NH2).
N l+' -~' "

I=NH
H F~ H
171 [100..]
~R NH- t'~"
--HCN I ~

~ H
CH3

'!5& 143
t --C2H2 -HCN
+
CgH9
H

115 117 117

The disintegration of the pyrrolidine ring with detachment of a CH2CH2NH particle f r o m the m o l e c u l a r ion
l e a d s to the f o r m a t i o n of one of the m o s t intense ion peaks in the m a s s s p e c t r a of e s e r o l i n e s - ( M - 4 3 ) + .
The s t r u c t u r e of the ( M - 4 3 ) + tons probably c o r r e s p o n d s to the structure of the p s e u d o m o l e c u l a r tons of
2 , 3 - d i m e t h y l i n d o l e d e r i v a t i v e s . Detachment of a methyl group f r o m the m o l e c u l a r tons l e a d s to a structure
with p o s s i b l e charge d e l o c a l i z a t i o n between two nitrogen a t o m s [51].
-~- R1~ -t-

C H2=NH2

~r~--CH 3"

--CH3"[~"
~2 !3 "c% I CH3 F? CH,~

-H.

{ M - 4 4 ) "~"

Just as in the c a s e of the e s e r o l i n e s t h e m s e l v e s , in the e a s e of d i s s o c i a t i v e ionization of h o m o e s e r o -

l i n e s [51] the m o s t intense peaks in the m a s s s p e c t r a c o r r e s p o n d to the f o r m a t i o n of p s e u d o m o l e c u l a r ions
of 2 , 3 - d i m e t h y l i n d o l e derivatives - ( M - 5 7 ) +. An interesting peculiarity of the m a s s s p e c t r a of h o m o e s e r o -
line is the p r e s e n c e [n t h e m of intense ion peaks c o r r e s p o n d i n g to the protonated f o r m of tndole.

Oxygen-Containing Indole Compounds

The m a s s s p e c t r a of 2 - k e t o i n d o l i n e s have been investigated by a number of authors [9, 52-58]; the
general s c h e m e of the f i r s t stages of the disintegration can be illustrated in the following manner:

[~ ~ 0 -CO
H
105 104

-- HCN I "~ --HCNI~

-t-
C6H; C6H5
78 77

261
 It has been a s s u m e d that the carbon in the HCN eliminated f r o m ions with mass 105 and 104 is r e -
moved f r o m the methylene group of the 2-keto-tndoline. In c o n f o r m i t y with this, a m e c h a n i s m for the r e -
moval of HCN with hydrogen migration to the a r o m a t i c ring has been proposed. This m e c h a n i s m c o n t r a -
dicts the data of Brown and Butcher [59], who investigated the mechanism of the pyrolysis of carbon-labeled
2-ketotndolines at 850 ~ and 0.7 m m . P r o c e e d i n g f r o m this, Brown and Butcher [59] investigated the high-
resolution mass s p e c t r a of (3-C13)-2-ketoindoline. It was o b s e r v e d that in the ease of the M - C O - H C N p r o -
c e s s , detachment of HClaN c o r r e s p o n d s only to a small portion of the ions (-,30%), while a l a r g e portion of
the ions (~70%) c o r r e s p o n d to elimination of HC12N. The fractions of the c o r r e s p o n d i n g ions for the
M - C O - H - H C N p r o c e s s a r e 25 and 75%. Thus it can be supposed that the prevailing p r o c e s s is elimination
of unlabeled HCN, probably with r e m o v a l of carbon f r o m the 7a position.

The mass s p e c t r a of 4-, 5-, 6-, and 7-hydroxyskatoles are e x t r e m e l y s i m i l a r [60]. An investigation
of the disintegration p r o c e s s e s by means of high-resolution mass s p e c t r o m e t r y led to the conclusion that
all four i s o m e r s f o r m an ion with mass 118 principally due to elimination of CO f r o m the ( M - H ) + ion; a
total of 5-20% of ions with the s a m e nominal mass is f o r m e d during the detachment of H2CN f r o m the mo-
l e c u l a r ion. According to a kinetic method for the investigation of metastable ions, the ( M - H ) ~-ions have
identical s t r u c t u r e s ; this indicates r a n d o m i z a t i o n of the substituent in the investigated i s o m e r s .
The maximum peak in the mass s p e c t r u m of isatin [52, 61] is f o r m e d in the elimination of CO f r o m
the molecular ion. Subsequent disintegration is r e a l i z e d via t h r e e alternative paths: one of them is a s s o -
ciated with r e m o v a l of HChr with subsequent detachment of CO, while the second is a s s o c i a t e d with r e m o v a l
of CO and subsequent detachment of HCN; detachment of CONH leading to an ion with mass 76 is also p o s -
sible. Thus all three h e t e r o a t o m s of [satin are eliminated in the formation of these p r i m a r y ions [52].

The disintegration of the i s o m e r i c formylindole [9, 62] is r e a l i z e d via a c o m m o n s c h e m e with the f o r -

mation of qualitatively s i m i l a r mass spectra.
"- CO --IICN --C~H2
M+ ~ 144+ ~ 116+----89 + . 63+

The incomplete m a s s s p e c t r a of 1- and 3-acetylindoles have been published; the formation of a m a x i -

mum peak (mass 117), which c o r r e s p o n d s to detachment of ketene, is c h a r a c t e r i s t i c for 1-acetylindole [7,
63].

o-]+-
-- CO
o] +. C//O 7"+'"
0
H /
1~7 [ss]
r
cO~.,/" 119 [lOO]
-CO l /-HCN
7-1-~
It c~O]"
9 C .
76 [80] oi [2~] 92 [77.]
-c~z1 --.... -1- .//
Q
50 [15] 64 [ . 3 3 ]
The m a x i m u m peak in the mass s p e c t r u m of 3-acetylindole c o r r e s p o n d s to the (M-CH3CO)+ ion with mass
116.
].+ 7+
~ CH2CO
I
COCH3 717
H

"]~" + .M
IQ~'COCH3
/ -CH3CO" ~
H
An investigation of 10-substituted 1-acyl-2-indolinols showed that the predominant f o r m for all of the
investigated compounds in the gas phase is the open f o r m [64].

262
 R4 R3 R4 R3

NH 0
1 I
R --C~O

The disintegration of i s o m e r i c indoleearboxylie acids [9] p r o c e e d s with s u c c e s s i v e elimination of OH,

CO, and HCN, but an ortho effect is m a n i f e s t e d in the c a s e of the 7 - s u b s t i t u t e d i s o m e r , and w a t e r is r e -
moved in the f i r s t step.
-IV i:

COOH

The disintegration of n i t r i l e s , a m i d e s , e s t e r s , and other d e r i v a t i v e s of indolecarboxylic acid [9, 32,

62, 65-67] p r o c e e d s in a c c o r d a n c e with the g e n e r a l p r i n c i p l e s of the b e h a v i o r of a r o m a t i c acid d e r i v a t i v e s
during e l e c t r o n i m p a c t and t h e r e f o r e does not r e q u i r e additional consideration.
Chizhov and c o - w o r k e r s [68-70] have d e s c r i b e d the s o - c a l l e d oxygen r e a r r a n g e m e n t in e s t e r s of a l i -
p h a t i c - a r o m a t i c and u n s a t u r a t e d acids, which is induced by e l e c t r o n impact and c o n s i s t s in the m i g r a t i o n
of one of the oxygen a t o m s of the c a r b o x y l group to the t m s a t u r a t e d portion of the molecule. It has been
shown [70] that this r e a r r a n g e m e n t also o c c u r s in the c a s e of d i s s o c i a t i v e ionization of the [ndole analog of
f l - p h e n y l - p r o p i o n i c acid e s t e r s .

H HH H

The introduction of a methyl group into the a - p o s i t i o n of the p y r r o l e r i n g hinders r e a r r a n g e m e n t .

Shortening of the chahu length also l e a d s to c o m p l e t e s u p p r e s s i o n of the r e a r r a n g e m e n t . Consequently, r e -
a r r a n g e m e n t in the 4 - p o s i t i o n of the indole r i n g does not occur.
A l a r g e n u m b e r of r e p r e s e n t a t i v e s of o t h e r types of oxygen-containing d e r i v a t i v e s of indoles have
a l s o been i n v e s t i g a t e d by m a s s s p e c t r o m e t r y : methoxyindoles [9], m e t h o x y t r y p t a m i n e s [22], methyl, benzyl,
and methoxy d e r i v a t i v e s of tryptophols and homotryptophols [1], carbonyl d e r i v a t i v e s of [satin [72], 2 - s u b -
stituted d e r i v a t i v e s of 3-benzoylindoles [73], methoxybenzylindoles [74], [ndolylpyruvic acid [75], h y d r o x y -
[ndoloindolizines [76], and 2 - p h e n y l i s a t o g e n [77].

Indole Compounds with Other Functional

Subst[tuents. Systems with Several Substituents
The p r e s e n c e of two different substituents in the [ndole r i n g m a y lead to a s h a r p change in the m a s s
s p e c t r u m as c o m p a r e d with the s p e c t r a of monosubstituted d e r i v a t i v e s p r i m a r i l y b e c a u s e of the p o s s i b i l i t y
of c h a r g e localization on different groups of the molecule. The interaction of t h e s e groups in the excited
molecule or hu the m o l e c u l a r ion has a l e s s e r but s o m e t i m e s substantial effect (especially when the two
groups a r e adjacent). In a n u m b e r of c a s e s , one of the substitutents d e t e r m i n e s the p a t t e r n of d i s i n t e g r a -
tion during e l e c t r o n i m p a c t of the disubstituted s y s t e m s [9, 78].
An i n c r e a s e in the length of the aminoalkyl group, b r a n c h i n g of it, or r e p l a c e m e n t of nitrogen a t o m s
of the amino group b y alkyl groups or acyl groups leads to the development of new p r o c e s s e s that a r e not
typical for the disintegration of t r y p t a m i n e s and h o m o t r y p t a m i n e s . Thus the m a s s s p e c t r u m of 3 - ( 6 - d i -
methyaminobutyl)indole i l l u s t r a t e s the p o s s i b i l i t y of c h a r g e localization in both the indole s y s t e m s and on
the nitrogen of the dimethylamino group, with p r e d o m i n a n c e of the second p r o c e s s [18, 78].

/CH 3
~ J CH3 [ ~ ~ N CH2CH2CH2CH2N,
CHiN --~
\CH 3 CH3
H H
58 { 39,5 ) "~30 ( 3 ~ 8 )

The m a s s s p e c t r u m of 1 - ( 4 - c h l o r o b e n z o x y ) - 2 - m e t h y l i n d o l e attests to cleavage of the alkyl-oxygen

bond in the m o l e c u l a r ion [58]. The c h a r g e is l o c a l i z e d with g r e a t e r p r o b a b i l i t y on the acyl portion of the

263
molecule (mass 139), which subsequently disintegrates with elimination of CO (mass 111) and C1 (mass 75).
Disintegration of the indole-containing fragment (mass 146) is realized with elimination of O (mass 130);
the subsequent path is analogous to the disintegration of 2-methylindole.
The disintegration of tryptophan ethyl ester at the #-bond leads to a quinolinium ion with mass 130
(the maximum peak ia the spectrum); onty aa msignificg_at portion of the ions (2%) /s formed ~n the case of
alternative charge localization on the substituent (ions with mass 102) [7, 79]; 4,7-dihydrotryptophan dis-
integrates similarly [80].
The identical character of the mass spectra of 5-, 6-, and 7-hydroxyindole-3-carboxylic acids is a
consequence of the randomization of one of the substituents [60].. The sharp contrast between these spectra
and the mass spectrum of the 4-isomer is due to 3,4-trans-interaetion, which leads in this case to suppres-
sion of the elimination of OH and an increase in the probability of the removal of HzO.
The mass spectra of 2-ketoindolh~yl-3-methines [55} differ markedly from the mass spectrum o[ t-
methyl-2-ketoindol/ne with respect to the low intensity of the molecular ion peak; in some cases, the doubly
charged molecular ion corresponds to the peak of seeondat7 intensity in the mass spectrum. The dlsinte-
gration of 2-ketoindolinyl-3-methines, in addition to the usual transformations of indole compounds during
electron impact, proceeds with condensation and the formation of a rearranged 1-methylbenz [b]azepinium
ion.

[ -b
CH 3 CH3273
274

/t N

245

The mass sl~etra of l-ethyl-5-hydroxy-6-methoxy- and 5-hydroxy-6-methoxyindole, 1- (3-acetoxy-

benzyl)-5,6-diaeetoxyindole [81], 1,5-dimethoxy-3- (dimethylamtnomethyl)indole [821, 6-hydroxy-, 5,6-di-
hydroxy-, and 6-methoxy.2-earbethoxyindoles, 6-hydroxy-5,7-dibromo-2-aeetamidomethylindole [83], 6-
hydroxy-5-methoxy-3-(acetamidoethyl)indole [84], indolimicinic acid [85], peracetyltryptamine [471, acetyl-
tryptophan derivatives [86- 88], N-mesidino-2-methyl-ALpyrroline [18], 3-inclolyl acetic acid derivatives
[89I, 5- and 7-nitro-2-keto[ndoltnes, 2~hydroxy-5,7-dinitroiadote [90 i, l~3-dtmethyl-Z-p~cryl ~ratno~ndole
[91], N- [2- (3-indolyl)ethyl]pyrrolidinomaleinimide [92], products of the autooxidattve dimerizatton of vari-
ous alkylindoles [93, 94], indodidthiones [57, 95], benzodithihaindoles [96], 2-ethylthioindole derivatives [15,
97], indolyl toluene sulfonates [98], and 3-indolyl thiocyanates [99] have also been studied.

Selenium-Containing Indole Compounds

An extremely specific group of selenium-containing ~ndoles was the subject of the steadfast attention
of Agenaa~ [100-1037 aad, in part, Bergman [I04],
An investigat(on of the mass spectra of 3-selenocygnatolndole and its 1- and 3-methyl-substituted de-
rivatives and of 3,3'-diindolyl diselenide and its methyl-substituted derivatives showed that selenoeyanate
compounds, like aromatic selenocyanates, disintegrate in the first step with removal of Se and CN.

l
H H
2~o [2o3 142 [ l ooJ

1 1
H H
196 p~.) 116 [ l o ]

264
The selenium-containing indole fragment subsequently disintegrates to form either selenium-containing
fragments o r indole fragments [100].
The disintegration of diindolyl diselenides is also similar to that of the corresponding aromatic ana-
logs, and the principal peaks in the mass spectrum are formed during the elimination of Se.

3 9 2 [1 ] 312 [ 1 8 , ]

- CsH6NSe -Se

Se f

H H H H
116 E2Q] 232 [100_]

3,3-Diindolyl selenides also undergo simultaneous disintegration of both S e - C bonds and "recombin-
ation" of the fragments [104].
se 7 +' ! +"

I I ' 1

This type of disintegration is probably a general one for aryl selenides [100]. A similar process ap-
parently also occurs during electronic impact of diphenyl sulfide, diphenyl disulfide, benzophenone, and azo-
benzene, although the intensity of the C12H10+ ion peak is lower. It is interesting to note that this peak is not
present in the mass spectrum of diphenyl ether.
A comparison of the mass spectra of 3-indolylmethyl benzyl selenide, di(3-indolyl)methyl selenide,
and di(3-indolyl)methyl diselenide with the spectra of the corresponding sulfur analogs provides evidence
[103] that the p r i m a r y paths of disintegration and the intensity of the overwhelming number of peaks of
analogous ions are similar for the S and Se indole compounds. However, in each pair of mass spect ra there
are differences that make it possible to readily distinguish between the indicated compounds. These dif-
ferences show up particularly distinctly in r e a r r a n g e m e n t p r o c e s s e s , for example, those associated with
migration of a hydrogen atom during cleavage of the S - S e or C - S bonds.
The mass spectra of 5-selenocyanatoindoles, 5,5'-diindolyl diselenides, and the corresponding indoline
analogs have been studied [101]. The disintegration of these compounds, which have intense molecular ion
peaks, is realized with elimination of Se, HSe, and CN from the selenocyanate group. The presence of a
saturated f iv e- m em be r ed ring in the ease of indoline derivatives leads to the appearance of additional chan-
nels for disintegration.

LITERATURE CITED
I. H. Budzikiewicz, C. Djerassi, and D. H. Williams, Mass Spectrometry of Organic Compounds, Holden-
Day (1967).
2. Catalog of Mass Spectral Data, American Petrol. Inst. Research Project 44, Pittsburgh (1952).
3. V. I. Vysotskii, R.A. Khmel'nitskii, and I. I. Grandberg, Izv. Timiryazev. Sel'skokhoz. Akad., 5,204
(1970).
4, J. L. Oeeolowitz and G. L. White, Austral. J. Chem., 21, 997 (1968).
5. J. H. Beynon and A. E. Williams, Appl. Spectr., 1___3,i01 (1959).
6. A. A. Polyakova and R. A. Khmel'nitskii, Mass Spectrometry in Organic Chemistry [in Russian],
Khimiya, Moscow- Leningrad (1972).
7. Q. hl. Porter and J. Baldas, Mass Spectrometry of Heteroeyclic Compounds, WHey Interscience
(1971).
8. M. Marx and C. Djerassi, J. Am. Chem. Soe., 90, 678 (1968).
9. J. C. Powers, J. Org. Chem., 33, 2044 (1968).
i0. S. Safe, W. D. Jamieson, and O. Hutzinger, Org. Mass Speetr., 6, 33 (1972).
ii. M. M. Bursey and F. W. McLafferty, J. Am. Chem. Soc., 8-3, 529 (1966).

265
12. D.H. Williams, S. W. Tam, and R. G. Cooks, J. Am. Chem. Soc., 9_00,2168 (1968).
13. J . H . Beynon, J. W. Amy, and W. E. Baitinger, Chem. Commtm., 723 (1968).
14.' E.M. Chait and W. B. Askew, Org. Mass Spectr., 5, 149 (1971).
15. J. Bey-non, Mass Spectrometry and Its Application to Organic Chemistry, American Elsevier (1960).
16. J . H . Beynon, R. A. Saanders~ and A. E. Williams, The Mass Spectra of Organic Molecules, Elsevier
(.1968).
17. V-~!. Vysotskii, R. A. Khmel'nitskii, I. I. Grandberg, and V. A. Budylin, Izv. Timiryazev. Sel'skokhoz.
Akad., 4, 221 (1970).
18. A.H. Jackson and P. Smith, Tetrahedron, 2_44,2227 (1968).
19. R . A . Khmel'nitskii, V. I. Vysotskii, I. I. Grandberg, A. N. Kost, and V. A. Budylin, Zh. Organ. Khim.,
7, 1514 (1971).
20. A . J . Namis, E. Cortes, O. Coliera, and F. Walls, Bol. Inst. Quim. Univ. Nac. Autom Mexico, 18, 64
(1966).
21. V.S. Kobrin and M. I. Gorfinkel', Zh. Obshch. Khim., 40, 1120 (1970).
22. R . A . Khmel'nitskii, V. L Vysotskii, and I. I. Grandberg, Zh. Organ. Khim., _5,417 (1969).
23. I . I . Grandberg, N, M. Przheval'skii, V. I. Vysotskii, and R. A. Khmel,nitskii, Khim. Geterotsikl.
Soedin., 477 (1970).
24. R.W. W~ker, H. S. Ahn, L. R. Mandel, and I. A. Vandenhenvelw, Anal. Biochem., 47,228 (1972).
25. R . A . Khmel'nitskii, N. A. Klyuev, A. F. Dolgikh, N. I. Bobrova, and I. I. Grandberg, Izv. Timiryazev.
Sel'skokhoz. Akad., 1, 176 (1974).
26. R . A . Khmel'nitskii, A. P. Krasnoahehek, and V. I. Vysotskii, Izv. Timiryazev. Sel'skokhoz. Akad., 6,
178 (1969).
27. R . A . Khmel'nitskii (Khmelnizky), Third International Congress of Heterocyclic Chemistry, Sendal
(Japan) C-4-8 (1971), p. 399.
28. K.G. Das, P. T. Fanke, and A. K. Bose, J. Amer. Chem. Soc., 86, 3729 (1964).
29. W. Riepe and Z. Zander, Naturforsch. ~, 24a, 2017 (1969).
30. V.I. Vysotskii, R. A. Khmel'nitskii, I. I. Grandberg, and G. V. Fridlyandskii, Izv. Timiryazev. Sel'-
skokhoz. Almd., 3,206 (1971).
31. U.K. Pandit, t{. J. Hofman, and H. O. Hutsman, Tetrahedron, 20, 1679 (1964).
32. U.K. Pandit and H. O. Huisman, Ree. Tray. Chim., 83, 50 (1964).
33. B. Leeh, Tet:=ahedron, 2_44, 6663 (1968).
34. M.E. Kuehue and T. Kitagawa, J. Org. Chem., 29, 1270 (1964).
35. J. Bergman, S. Hogberg, and J. Lindstrom, Tetrahedron, 26, 3347 (1970).
36. J. Bergman, Tetrahedron, 26, 3353 (1970).
37. F . E . Ziegler, E. B. Spitzner, and C. K. Wilkins, J. Org. Chem., 36, 1759 (1971).
38. L . J . Dolby and G. W. Gribble, Tetrahedron, 24, 6377 (1968).
39. A. Kamal, A. A. Qureshi, I. H. Qureshi, M. Aujum, and J. P a k . , Sci. Ind. Res., 13,341 (1970).
40. A.S. Bailey and J. J. Meter, J. Chem. Soc., C, 1345 (1966).
41. J . B . Hester, J. Org. Chem., 3__5.5, 875 (1970).
42. K. Biemann, Mass Spectrometry, McGraw-Hill, New York (1962).
43. L . D . Antonaccio and H. Budzikiewiez, Monatsh., 93, 962 (1962).
44. S. Agurell, B. Holmstedt, and J. E. Lindgren, Amer. J. Phaxm., 140, 148 (1968).
45. S. Agurell, B. Holmstedt, J. E. Lindgren, and R. E. Schultes, Biochem. Pharmacol., 17, 2487 (1968).
46. R . T . Courts, R. A. Locock, and G. W. A. Clywka, Org. Mass Spectr., 3, 7879 (1970).
47. A. Hollerbach, Dissertation, Gottingen (1972).
48. E. Clayton and R. I. Reed, Tetrahedron, 19, 1345 (1963).
49. I.G. Spiteller and M. Spiteller-Friedman, Tetrahedron Lett., 147 (1963).
50. R . A . Khmel'nitskii, V. I, Vysotskii, T. A. Ivanova, and K. K. Zhigulev, Second F a r - E a s t e r n Sympo-
sium on Bioorgantc Chemistry [in Russian], Vladivostok (1969), p. 60.
51. K.K. Zhigulev, R. A, Khmel'nitskii, I. I. Grandberg, and V. I. Vysotskii, Khim. Geterotsikl. Soedin.,
1065 (1972).
52. J. Ballantine, R. Fenwick, and M. Alam, Org. Mass Speetr., 1, 467 (1968).
53. P. Fruit, R. Gantron, and C. Audic, Bull: Soc. Chim. France, 2237 (1968).
54. J. Bottvdats, Bull. Soc. Chim. France, 1506 (1968).
55. R. Hodges, J. S. Shannon, W. D. Jamieson, and A. Taylor, Can. J. Chem., 46, 2189 (1968).
56. S. Ghosol and S. K. Durra, Indian J. Chem., 7, 1095 (1969).
57. T. Hino, M. Nakagawa, K. Tsuneoka, S. Misawa, and S. Akaboski, Chem. Phaxm. Bull. (Tokyo), 17,
1651 (1969).

266
 58. R . M . Acheson, R. G. Bolton, and I. Hunter, J. Chem. Soc., C, 1067 (1970).
59. R . F . C . Brown and M. Butcher, Austral. J. Chem., 25, 149 (1972).
60. R. Marehelli, W. D. Jamieson, S. Safe, O. Hutzinger, and R. A. Heacock, Can. J. Chem., 49, 1296
(1971).
61. K. Yamada, T. Konakahara, and H. Iida, Kogo Kagaku Zasshi, 73, 98 (1970).
62. N.S. Vul'fson, V. I. Zaretskii, A. V. Kisin, N. N. Suvorov, and Zh. D. Ovehinnikova, Khim. Geterotsikl.
Soedin., 502 (1967).
63. O. Buchardt, J. Becher, C. Lahse, and J. Moller, Acta Chem. Seand., 20, 262 (1966).
64. O. Buchardt, A. M. Duffield, and C. Djerassi, Acta Chem. Scand., 22, 3329 (1968).
65. Yu. S. Nekrasov, P. A. Sharbatyan, R. S. Sagitullin, V. A. Puchkov, A. N. Kost, and N. S. Vul,fson,
Izv. Akad. Nauk SSSR, Set. Khim., 2181 (1969).
66. U.K. Pandit and H. O. Huisman, Rec. Tray. Chim., 85,311 (1966).
67. A . B . Lerner, J. D. Case, K. Biemann, R. V. Heinzelman, J. Szmuskovisz, W. C. Onfhony, and A.
Kirvis, J. Am. Chem. Soc., 81, 5264 (1959).
68. V.I. Kadentsev, B. M. Zolotarev, O. S. Chizov (Chizow), Kh. Shakhidayatov (C. Shachidayatov), L. A.
Yanovskaya, and V. F. Kucherov, Org. Mass. Spectr., 1, 839 (1968).
69. V.I. Kadentsev, O. S. Chizhov, L. A. Yanovskaya, V. F. Kucherov, and Kh. Shakhidayatov, Izv. Akad.
Nauk SSSR, Ser. Khim., 2207 (1971).
70. V.I. Kadentsev, O. S. Chizhov, L. A. Yanovskaya, and V. F. Kucherov, Izv. Akad. Nauk SSSR, Set.
Khim., 2440 (1972).
71. R. A, Khmel'nitskii, N. A. Klyuev, A. F. Dolgikh, T. P. Moskvina, and I. I. Graadberg, Izv. Timirya-
zev. Sel'skokhoz. Akad., 3, 192 (1973).
72. J . A . Ballantine, R. G. Tenwick, and F. D. Popp, Org. Mass Spectr., 5, 1003 (1971).
73. R . A . Khmel'nitskii, N. A. Klyuev, T. A. Kozik, V. N. Rusinova, and N. N. Suvorov, Khim. Geterotsikl
Soedin. (1974) (in press).
74. K. 55. Biswas and A. H. Jackson, Tetrahedron, 25, 227 (1969).
75. O. Hutzinger and W. D. Jamieson, Anal. Biochem., 35, 351 (1970).
76. E. Winterfelot and J. M. Nelke, Bet., 103, 1174 (1970).
77. D.R. Eckroth, Chem. Commun., 465 (1970).
78. R . A . Khmel'nitskii, K. K. Zhigulev, I. I. Grandberg, and V. I. Vysotskii, Third All-Union Colloquium
on the Chemistry and Pharmacology of Indole Compounds [in Russian], Kishinev (1971), p. 60.
79. K. Biemann, J. Seibl, and F. Gapp, J. Am. Chem. Soc., 83, 3795 (1961).
80. O. Yomemitsu, P. Cerutti, and B. Witkop, J. Am. Chem. Soc., 88, 3941 (1966).
81. T. Kametani, C. Sieno, I. Noguchi, M. Shibuya, K. Fukumoto, T. Kohno, and S. Takano, J. Chem. Soc.,
C, 1803 (1971).
82. S.R. Jatms, J. A. Lamberton, and J. L. Occolowitz, Austral. J. Chem., 20, 1737 (1967).
83. M. Wilchek, T. Spande, G. Milne, and B. Witkop, Biochemistry, _7, 1777 (1968).
84. D . E . Hall and A. H. Jackson, J. Chem. Soc., C, 1681 (1967).
85. yon M. S. Wittenan and H. Els, J. Am. Chem. Soe., 85, 3425 (1963).
86. S. OhM and T. Nagasaka, Chem. Pharm. Bull. (Tokyo), 19, 545 (1971).
87. H. Budziktewicz, C. Djerassi, and D. H. Williams, Structure Elucidation of Natural Products by Mass
Spectrometry, Holden-Day, San Francisco (1964).
88. T. Nagasaka and S. OhM, Chem. Phaxm. Bull. (Tokyo), ~ 603 (1971).
89. L. Berlisson and L. Palmer, Science, 177, 74 (1972).
90. R. T. Coutts, K. W. Hindmarsh, and E. Mah, Can. J. Chem., 48, 3747 (1970).
91. A. S. Bailey, W. A. Wart, G. B. Allison, and C. K. Prout, J. Chem. Soc., C, 956 (1970).
92. E. Winterfeldt and J. M. Nelke, Bet., 101, 3163 (1968).
93. G. Berry, A. Da Settimo, G. Colo, and E. Nannipieri, J. Chem. Soc., C, 2703 (1969).
94. S. McLean and G. I. Dmitrienko, Can. J. Chem., 49, 3642 (1971).
95. T. Hino, M. Nakagawa, T. Suzuki, S. Takeda, N. Kano, and Y. Istmii, Chem. Commun., 836 (1971).
96. N. P. Buu-Hoi, P. Jacquignon, L. Lederert, A. Ricci, and D. Balcaai, J. Chem. Soc., C, 2196 (1969).
97. M. Nakagawa and T. Hi,o, Tetrahedron, 26, 4491 (1970).
98. A. H. Jackson and B. Naidoo, Tetrahedron, 25, 4843 (1969).
99. L. B. Agenas, Arkiv Kemi, 3_~0,465 (1969).
100. L. B. Agenas, Acta Chem. Scand., 2_22, 1773 (1968).
101. L. B. Agenas, Arkiv Kemi, 31, 159 (1969).
102. L. B. Agenas, Arkiv Kemi, 3.0, 471 (1969).
103, L. B. Agenas, Arkiv Kemi, 3_11,31 (1969).
104. J. Bergman, Acta Chem. Scand., 22, 1883 (1968).
267
RESEARCH ON UNSATURATED LACTONES
XXV.* REACTION OF 3-ACETYL-A3-BUTENOLIDES
WITH PHOSPHORUS PENTACHLORIDE

A. A. Avetisyan, A . N. D z h a n d z h a p a n y a n , UDC 547.722.724 : 542.944.1 : 543.422.4

L. E. Astsatryan, and M. T. Dangyan

Chloroalkenes a r e obtained in 55-70% yields in the r e a c t i o n of e q u i m o l a r amounts of 3 - a c y l -

A3-butenolides with phosphorous pentachloride; dtchloroalkenes a r e f o r m e d in the p r e s e n c e
of a twofold e x c e s s of phosphorus pentachloride. The ability of chloroalkenes to undergo
p o l y m e r i z a t i o n is shown.

It is known that 2-chloroalkenylphosphorus t e t r a c h l o r i d e s a r e f o r m e d in addition to g e m - d i c h l o r o a l -

kanes and chloroalkenes in the r e a c t i o n s of phosphorus pentachloride with ketones; this is explained by
phosphorylation of the chloroalkenes obtained [2, 3].
A study of the r e a c t i o n of 3-acetyl-A3-butenolides with phosPhorus pentachloride showed that the only
r e a c t i o n products in the p r e s e n c e of equimolar amounts of the s t a r t i n g components a r e c h l o r o a l k e n e s , which
0
CH3\f--"---~ C-oH3 PCI~ CH R 3 ~ CCI2--C1"13 CH3\F~----------~CCI=
~R
-- CH2

I--III IV-VI

1,1~, P=P'=CH 3 II, IY R=CH 3, R'=C~H~,; Ill, Vl R--R'=(CH2) 5

a r e obtainedin 55-70% y i e l d s . The chloroalkenes a r e n o t p h o s p h o r y l a t e d , apparently b e c a u s e of the a b s e n c e o f
e x c e s s PC15.
3 - ( ~ , f l r D i c h l o r o v i n y l ) - 4 , 5 , 5 - t r i m e t h y l - A 3 - b u t e n o l i d e (VII} is obtained in 56% yield in the r e a c t i o n of
I with a twofold e x c e s s of phosphorus pentaehloride.
The c h a r a c t e r i s t i c frequencies of the a b s o r p t i o n of the carbonyl group of an unsaturated T-lactone at
i760 c m -1 and of a conjugated double bond at 1645-1650 c m -~ a r e found in the IR s p e c t r a of the compounds
obtained {IV-VII).
The production of a dichloroalkene in the indicated r e a c t i o n is evidently a consequence of destruction
of the i n t e r m e d i a t e p h o s p h o r u s - c o n t a i n i n g product (VIII); this was also p r e v i o u s l y noted by Fokin and co-
w o r k e r s [2].

CH3~.[~___/CCI =CH PCI4

CHz ~0 / ~0
~111

Dichloro d e r i v a t i v e VII is also obtained in the r e a c t i o n of butenolide IV with an e q u i m o l a r amount of

phosphorus pentachloride.

*See [1] for commtm[cation XXIV.

Yerevan State University. T r a n s l a t e d f r o m Khimiya G e t e r o t s t k l i c h e s k i k h Soedinenii, No. 3, pp. 310-

311, March, 1974. Original a r t i c l e submitted March 26, 1973..

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, N.Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy of this article is available from the publisher for $15.00.

268
 The 3 - ( a - c h l o r o v i n y l ) - A 3 - b u t e n o l i d e s that we s y n t h e s i z e d p o l y m e r ize and undergo c o p o l y m e r i z a t i o n
r e a c t i o n s with vinyl m o n o m e r s in the p r e s e n c e of f r e e - r a d i c a l initiators. Thus, for e x a m p l e , we subjected
3 - ( ~ - c h l o r o v [ n y l ) - 4 , 5 , 5 - t r i m e t h y l - A ~ - b u t e n o l t d e to h o m o p o l y m e r i z a t i o n and c o p o l y m e r i z a t i o n with a c r y l -
onitrile and methyl a c r y l a t e in the p r e s e n c e of 2 , 2 ' - a z o b i s i s o b u t y r o n i t r i l e (AIBN). The r e s u l t i n g h o m o p o l y -
m e t and c o p o l y m e r s differ f r o m one another with r e s p e c t to t h e i r solubilities and a p p e a r a n c e . "
Bands of the a b s o r p t i o n of the CO group of a f i v e - m e m b e r e d lactone r i n g at 1745-1760 c m -1 and a b -
s o r p t i o n at 1650-1660 c m -1 a r e found in the IR s p e c t r a of the p o l y m e r s . The IR s p e c t r u m of the c o p o l y m e r
with a c r y l o n i t r i l e also contains an a b s o r p t i o n band at 2244 c m -1, which is c h a r a c t e r i s t i c for the C = N bond.

EXPERIMENTAL
The IR s p e c t r a of m i n e r a l oil s u s p e n s i o n s w e r e r e c o r d e d with an IKS-14 s p e c t r o m e t e r .
Reaction of 3 - A c e t y l - 4 , 5 , 5 - t r i m e t h y l - A 3 - b u t e n o l i d e (I) with P h o s p h o r u s P e n t a c h l o r i d e . A) An 11.9 g
(0.06 mole) s a m p l e of PC15 was added in s m a l l portions with s t i r r i n g to a solution of 10.08 g (0.06 mole) of
butenolide I in 40 ml of absolute benzene, a f t e r which the r e a c t i o n mixture was refluxed at 40-50 ~ until the
PCI5 had dissolved c o m p l e t e l y (30 min). The benzene was r e m o v e d by distillation, and the r e s i d u e was
v a c u u m distilled to give 7.75 g (70%) of butenolide IV with bp 116-1190 (3 mm) and n ~ 1.4990. Found: C 57.5;
H 6.1; C1 19.4%. CaHllC102. Calculated: C 57.9; H 5.9; C1 19.0%.
B) A 21 g (0.1 mole) s a m p l e of PC15 was added in s m a l l portions with s t i r r i n g to a solution of 8.5 g
(0.05 mole) of I in 40 ml of absolute benzene. The r e a c t i o n m i x t u r e was then heated at 45 ~ for 6-7 h. The
benzene was r e m o v e d b y distillation, and the r e s i d u e was v a c u u m distilled twice. The f r a c t i o n with bp
86-92 ~ (1 mm) was collected and r e c r y s t a l l i z e d to give 4.9 g (44.5%) of butenolide VII with mp 62-63 ~ (from
p e t r o l e u m ether). Found: C48.4; H 4.5; C1 31.8%. C9H10C1202. Calculated: C 49.0; H 4.6; C1 32.1%.
3 - ( ~ - C h l o r o v i n y l ) - 4 , 5 - d i m e t h y l - 5 - e t h y l - A 3 - b u t e n o l i d e (V). A 5.95 g (0.03 mole) s a m p l e of PC15 was
added with s t i r r i n g to a solution of 5.46 g (0.03 mole) of butenolide II in 20 ml of absolute benzene, a f t e r
which the r e a c t i o n mixture was heated at 500 for 45 min. The benzene was then r e m o v e d by distillation, and
the r e s i d u e was washed with w a t e r to r e m o v e the phosphorus oxychlortde and unchanged PC15. The r e a c t i o n
product was e x t r a c t e d with ether and dried with m a g n e s i u m sulfate. The e t h e r was r e m o v e d , and the r e s i -
due was v a c u u m distilled to give 3.28 g (55%) of V with bp 94-96 ~ (1 ram) and n ~ 1.4950. Found: C 59.9;
H 6.9; C1 17.1%. C10H13C102. Calculated: C 59.8; H 6.5; C1 17.7%.
3 - ( ~ - C h l o r o v i n y l ) - 4 - m e t h y l - 5 , 5 - p e n t a m e t h y l e n e - A 3 - b u t e n o l i d e (VI). S i m i l a r l y , 6.24 g (0.03 mole) of
III in 40 m l of absolute benzene and 5.95 g (0.03 mole) of PC15 gave 3.94 g (59~o) of butenolide VI with mp 74 ~
(from acetone). Found: C 63.1; H 4.1; C1 16.0%. C12H15C102. Calculated: C 63.5; H 4.4; C1 16.1%.
3 - ( ~ , f l - D i c h l o r o v i n y l ) - 4 , 5 , 5 - t r i m e t h y l - A 3 - b u t e n o l i d e (VII). A 5.95 g (0.03 mole) s a m p l e of PC15 was
added to a solution of 5.04 g (0.03 mole) of IV in 30 ml of absolute benzene, a f t e r which the r e a c t i o n m i x -
t u r e was heated at 60-70 ~ for 6-7 h. The benzene was r e m o v e d by distillation; the r e s i d u e was v a c u u m d i s -
tilled twice. The f r a c t i o n with bp 86-90 ~ (1 ram) was collected and r e c r y s t a l l t z e d to give 3.85 g (58%) of a
s u b s t a n c e with mp 62-63 ~ (from hexane); no melting-point d e p r e s s i o n was o b s e r v e d for a mixture of a s a m -
ple of this product with dichloralkene VII.
P o l y m e r i z a t i o n of 3 - ( ~ - C h l o r o v i n y l ) - 4 , 5 , 5 - t r i m e t h y l - ~ 3 - b u t e n o l i d e . A 1 g (5.4 mmole) s a m p l e of b u -
tenolide I and 0.0088 g (1 mole %) of AIBN w e r e placed in a n a m p u l e , and the mixture was heated in a t h e r -
m o s t a t at 80 ~ for 10 h. The r e s u l t i n g p o l y m e r was purified by dissolving in c h l o r o f o r m and r e p r e c i p i t a t i o n
with ether. A viscous brown m a s s was obtained in 34.7% yield. Found: C1 18.3%. C9HllC102. Calculated:
C1 19.0%.
C o p o l y m e r i z a t i o n of I with A c r y l o n i t r i l e and Methyl A c r y l a t e . This r e a c t i o n was also c a r r i e d out in
the p r e s e n c e of 1 mole % AIBN in s e a l e d a m p u l e s at 80 ~ for 10 h. The c o p o l y m e r s w e r e taken in e q u i m o l a r
amounts. The c o p o l y m e r with a c r y l o n i t r i l e was purified by r e p r e c i p i t a t i o n with ether f r o m acetone s o l u -
tions to give a white powder with mp 228-232 ~ (dec.) in 32.3% yield. The c o p o l y m e r with methyl a c r y l a t e
was p r e c i p i t a t e d by CC14 f r o m d i m e t h y l f o r m a m i d e solutions and was obtained as yellow c r y s t a l s with mp
220-225 ~ (dec.) in 29% yield.

LITERATURE CITED
1. Ao A. Avetisyan, K. G. Akopyan, and M. T. Dangyan, Khim. Geterotsikl. Soed[n., 1604 (1973).
2. A. V. Fokin, A. M. Kolomiets, and V. S. Shchennikov, Zh. Obshch. Khim., 4_22, 801 (1972).
3. K. N. Anisimov, Izv. Akad. Nauk SSSR, Otd. Khim. Nauk, 803 (1954).

269
 ISOMERISM OF 5-ARYLFURFURAL OXIMES
(ACCORDING TO PMR SPECTROSCOPIC DATA)

N. P . K o s t y u c h e n k o , A. F. Oleinik, UDC 547.724.2

T. I. Vozyakova, K. Yu. Novitskii,
a n d Y u . N. S h e t n k e r

The s t e r e o c h e m i s t r y o f 5 - a r y l f u r f u r a l s and t h e i r O - a c e t y l d e r i v a t i v e s was studied by PMR

s p e c t r o s c o p y . The configurations of each of the i s o m e r s w e r e d e t e r m i n e d for the oximes of
p - b r o m o : and p - c b l o r o p h e n y l f u r f u r a l s , which w e r e isolated as two g e o m e t r i c a l i s o m e r s , and
also for their O - a c e t y l d e r i v a t i v e s . The anti and syn configurations w e r e e s t a b l i s h e d for the
oximes of phenylfurfural and p - n i t r o p h e n y l f u r f u r a l , r e s p e c t i v e l y , which w e r e obtained as
single i s o m e r s . Conclusions r e g a r d i n g the p r e f e r r e d conformation of the side chain r e l a t i v e
to the plane of the f u r a n r i n g in all of the investigated i s o m e r s w e r e drawn on the b a s i s of an
analysis of the of the l o n g - r a n g e s p i n - s p i n coupling constants (JHoH4).

The individual r e p r e s e n t a t i v e s of a r y l f u r f u r a l o x i m e s that a r e d e s c r i b e d in the l i t e r a t u r e w e r e i s o -

l a t e d by the authors in the f o r m of one i s o m e r without e s t a b l i s h m e n t of the s t r u c t u r e [1-3].
In an investigation of v a r i o u s conditions for the p r e p a r a t i o n of o x i m e s , we o b s e r v e d that, depending
on the concentration of the r e a c t i o n m i x t u r e , either a h i g h - m e l t i n g i s o m e r or a m i x t u r e of the h i g h - m e l t i n g
and l o w - m e l t i n g i s o m e r s (the amount of l o w - m e l t i n g i s o m e r in the mixture r a n g e d f r o m 50 to 8070) is
f o r m e d . Under these conditions, phenylfurfural and p - n i t r o p h e n y l f u r f u r a l o x i m e s f o r m only one i s o m e r
(Table 1). The s y n t h e s i z e d oximes w e r e c o n v e r t e d to t h e i r O - a c e t y l d e r i v a t i v e s , which w e r e obtained either
in the f o r m of the individual i s o m e r s (VIb, VIIa, b, and VIl/b) or in the f o r m of m i x t u r e s of the i s o m e r s (V,
VI, and VIII).
In o r d e r to e s t a b l i s h the configuration of the i s o m e r s of the 5 - a r y l f u r f u r a l o x i m e s and t h e i r O - a c e t y l
d e r i v a t i v e s and to study the c o n f o r m a t i o n of the side chain r e l a t i v e to the furan ring, we examined t h e i r
PMR s p e c t r a .
The e s t a b l i s h m e n t of the configuration was b a s e d on a c o m p a r i s o n of the c h e m i c a l shifts of the , a l d e -
hyde proton" (H 0) in both g e o m e t r i c a l f o r m s . It is known [4] that owing to the deshielding effect of the NOH
group, the H 0 signal in the s p e c t r u m of the syn i s o m e r is found at w e a k e r field b y 0.5-0.6 p p m than in the
s p e c t r u m of the anti i s o m e r . The signals of the H 0 proton of the l o w - m e l t i n g i s o m e r s of II, III, VI, and VII
a r e situated at w e a k e r field than the signals of the c o r r e s p o n d i n g h i g h - m e l t i n g i s o m e r s , and the difference
in the c h e m i c a l shifts is 0.51-0.56 p p m (Table 1). This m a k e s it p o s s i b l e to r e l a t e the h i g h - m e l t i n g i s o -
m e r s (a) to the anti f o r m s and the l o w - m e l t i n g i s o m e r s (b) to the syn f o r m s . We w e r e able to obtain

,-r'g.,-~[-c=N/~ , . , , g , , - ~ - / c = nXo"
' lto I~o
anti syn
I a - I l l a, V a-Viii a II b - v i i i b

R = R'-- H: I I R = H. R" = e l : I I I R = H, R ' = Br : I v R = It, R ' = NO2; v R = COCHa, R ' = H :

VI R=COCH3, R ' = C I : Vii R = C O C f l a. R ' = B r : VIII R = C O C H 3, R'=NO:2

S. Ordzhonikidze All-Union S c i e n t i f i c - R e s e a r c h P h a r m a c e u t i c a l - C h e m i s t r y Institute, Moscow. T r a n s -

l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 3, pp. 312-318, March, 1974. Original a r t i c l e s u b -
mitted F e b r u a r y 9, 1973.

9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, iV. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy of this article is available from the publisher for $15.00.

270
 T A B L E I. Chemical Shifts ( 8 , ppm), Long-Range Spin-Spin Cou-
pling Constants (J, Hz),* and Melting Points of I-IX

~COCH3 ~ Sol~ent mp, ~C

oo=

I a 7,61 7,37 7,07 -- 194--195

7,5917,35 7,14 -- 033" 0,72 -- DCON(CD3)2 159--161
11 8,10 ! 6,83 [ 7,08 [ -- 0[39 0,09 -- DCON(CD~)a ] 137~138
a 7,58] 7,36 7,16 -- 0,30 0~72 r --JDCON(CD3)~J i69--170
II1 b 809 683]7,09] - - 0,30 /0,09 -- DCON(CD~)2 I 159,5--160
IV b [8,14!693 7 , 3 8 ] - !0,39 0,15~ -- DCON(CD3)~ 173--174
a? !7,78 17,32 6,79 - - 2,26 %30 ' 0,66 / -- ]r CD CI3 ,i
V b~ ]8,19 6,95 6,71 - - 2,17 0,36031~ / --[CDC13 I
2,27 033 066 [ -- [CDCI~ t
V i 2,19 10,360:271't -- CDCI~ 142,5--145,0
8481715i7151 -
2,20 !$ ~t -- DCON(CD3)2 ] 1 4 2 , 5 - - 1.45,~)
a 7741782 679 -- 2,27 0,33 0,64 -- CDCI3 I 125--126
VII 8:18 6195 16:721 - - 2,19 0,360,27 ~' -- CDC13 I 149--150
7,2l - 2,19 :]: :]: -- DCON(CD3)~ I 1,49---150
a-* 7,8417,41]7,01[ -- 2,29 10,3010,66 / -
VIII 8,2516,9617,04 [ -- 2,20 0,30 0,27bJ -- CDCI3 161--163
b 8,60 7,28 7,49 / -- 2,2D 0,37 0,20[ -- [DCON(CD3)2 I I ~ I - - 1 6 3
i 7,7417,29 16,57 t7,58 2, 7 033 0.66 o.o:i I
a't '7,99 7,42 6,7"3 7,89 2,27 [0,30 0,67 0,09 DCON(CD3)2
IX
8,20 6,90 6,53 7,57 2,19 I0,361027 0371CDCI~
bi" 8,50 7,10 6,67]7,89 2,14 I 4,0 3 0I 0,2 2 t 046
~ DCON(CD3)2.
'" I!

* See the experimental section.

The compounds could not be isolated in the f o r m of individual
geometrical isomers; fractions enriched in one of the isomers
were investigated.
The 4JH2H3 and 5JH2H4 constants could not be evaluated f r o m the
spectra, inasmuch as the H 3 and H 4 protons f o r m an A 2 system.
* * C o m p o u n d Villa w a s obtained in a mixture with VIIlb after a
solution of VIIlb in C D C I a had stood for a w e e k at r o o m temperature.

o n l y o n e i s o m e r e a c h f o r I, I V , a n d VIII, b u t b y c o m p a r i n g t h e H 0 c h e m i c a l s h i f t s o f t h e s e i s o m e r s w i t h t h e
c o r r e s p o n d i n g d a t a f o r t h e o t h e r i s o m e r i c p a i r s w e f o u n d it w a s p o s s i b l e t o u n a m b i g u o u s l y a s s i g n t h e a n t i
c o n f i g u r a t i o n to o x i m e I a a n d t h e s y n c o n f i g u r a t i o n to o x i m e s IVb a n d V I I l b .
A d o u b l e s e t of s i g n a l s w a s p r e s e n t in t h e P M R s p e c t r u m o f V, w h i c h i n d i c a t e d t h e p r e s e n c e of t w o
geometrical isomers. It f o l l o w s f r o m an a n a l y s i s o f t h e H 0 c h e m i c a l s h i f t s in b o t h f o r m s t h a t t h e a n t i f o r m
is predominant. A s t u d y o f t h e PIVIR s p e c t r a of t h e i s o m e r s of VI s h o w e d t h a t one o f t h e m (VIb) is t h e i n -
d i v i d u a l s y n i s o m e r , w h i l e t h e o t h e r (Via) i s a m i x t u r e of e q u a l a m o u n t s of t h e s y n a n d a n t i i s o m e r s .
T h e s e a s s i g n m e n t s a r e in g o o d a g r e e m e n t w i t h t h e k n o w n d a t a on the m e l t i n g p o i n t s o f t h e s y n a n d a n t i
i s o m e r s , in a c c o r d a n c e w i t h w h i c h t h e a n t i i s o m e r s a r e t h e h i g h e r - m e l t i n g c o m p o u n d s .
W e e s t a b l i s h e d t h a t t h e a n t i f o r m of t h e a r y l f u r f u r a l o x i m e s c a n b e i s o l a t e d f r o m t h e r e a c t i o n w i t h o u t
a d m i x t u r e o f the s y n i s o m e r , w h i l e t h e s y n i s o m e r a l w a y s c o n t a i n s t h e s e c o n d i s o m e r . T h e i s o m e r s o f t h e
oximes are capable of intereonversion on storage [in the solid state and in solution in DCON(CD~)2] , and the
conversion of the syn form to the anti f o r m occurs m o r e rapidly than the reverse process. O n the basis of
the spectra, a mixttlre containing ,~ 500/0of each isomer corresponds to the equilibrium state. The isomers
of the O-acetyl derivatives of the oximes also undergo interconversion on storage. Thus solutions of the
individual isomers VII), VIL%, b and of a nonequilibrinm mixture of V in C D C ] 3 have reached the equilibrium
state with about identical amounts of the geometrical forms after a week. A mixture of the syn and anti
forms (Villa, b) was formed as a result of isomerization w h e n a solution of VIIlb in C D C I s was allowed to
stand.
A n investigation of the antitubercular activity (in vitro) of the oximes of 5-(p-bromophenyl)- and 5-
(p-chlorophenyl)fnrfurals in the chemotherapy laboratory of the Ordzhonikidze All-Union Scientific-Re-
search Phsrmaceutical-Chemistry Institute showed that the activity of the anti isomers is higher than that
of the corresponding syn isomers.

271
 TABLE 2. ~ o and Z[ Values [for solutions In o r d e r to investigate the conformations of I-VIII,
in DCON(C DS)2] we used the l o n g - r a n g e s p i n - s p i n coupling constants
Position
(SSCC) 5JH4H0 . The s t e r e o s p e c i f i c i t y of t h e s e l o n g - r a n g e
Parameter Isomer R' SSCC in furfural oximes was r e c e n t l y used [5] to e s t a b l i s h
the r e l a t i v e p e r c e n t a g e s of the s - c i s or s - t r a n s c o n f o r m a -
6a, ppfn Isyn 6,70 6,54 tions in solutions. An analysis of the e x p e r i m e n t a l data on
(oxirne) Ianti 7,96 6,60 the magnitudes of the l o n g - r a n g e SSC C showed that the anti
80, ppm isyn 7,10 6,67
(acetate) ianti 7,42 6,73 i s o m e r of f u r f u r a l oxime exists a l m o s t e n t i r e l y inthe s - c i s
ZI, ! 0,12 0,48 c o n f o r m a t i o n in CDC1 a solution (SJHsH0 = 0 Hz, 5JH4H0 = 0.7
ppm I 0~12 0,50 Hz), while the syn i s o m e r under t h e s e conditions is p r e s e n t
Br 0,14 0,56
NO2 0,26 0,86 as a p r a c t i c a l l y equal mixture of the s - c i s and s - t r a n s con-
f o r m a t i o n s (SJH~H0 = 0.35 Hz, 5JH4H 0 = 0.25 Hz).
The s - e i s and s - t r a n s conformations a r e also p o s s i b l e
for e a c h of the i s o m e r i c f o r m s of the compounds that we

syn

Ar~.O/'-C=N \ ~ Ar1%.OJ'--C/Ho,
ffl OR fl
N\OR
S-cis S-trans
A B
H4 H3 anti n4.~_~Hs
Ar~=N..OR ~ ArJ<,x~,,,C/H
-... o
.o/
RO/
S -cis $ -trans
C D

investigated. I n a s m u c h as the 5 position of the furan ring is substituted in these compounds, one can f o r m a
judgment r e g a r d i n g the conformational p r e f e r a b l e n e s s only f r o m the 5JH4H0 value. In this connection, it
b e c a m e n e c e s s a r y to unambigously assign the signals of the H3 and ~ protons; this was r e a l i z e d by means
of a c o m p a r i s o n of the calculated and e x p e r i m e n t a l l y obtained c h e m i c a l shifts of the H3 and H4 protons.* The
H3 and ~ H4 values w e r e calculated via an additive s c h e m e with the use of the equation

6H~--'6o+Zi,
where ~ 0 a r e the values of the chemical shifts of the H 3 or H 4 protons for f u r f u r a l oxime or its O - a c e t y l de-
r i v a t i v e , and Z i a r e the i n c r e m e n t s of the effect of the substituted aryl r i n g s on the c h e m i c a l shifts of the
H3 and H 4 protons of the fttran r i n g , which we found f r o m the s p e c t r a of the c o r r e s p o n d i n g 5-phenylfurans
( s e e Table 2).
The calculated and e x p e r i m e n t a l ~ Hs and 6 H4 values a r e p r e s e n t e d in Table 3. The l a r g e difference
in the calculated c h e m i c a l shifts of the H~ and H 4 protons and the good a g r e e m e n t b e t w e e n e a c h of the c a l -
culated shifts and one of the e x p e r i m e n t a l values made it possible to make a r e l i a b l e a s s i g n m e n t of the s i g -
nals of the H 3 and H~ protons in the P M R s p e c t r a of the a r y l f u r f u r a l o x i m e s . In the a s s i g n m e n t of the Haand
H 4 protons, it was a s s u m e d that the conformational s t a t e s of the model and investigated compounds coin-
eided. As shown below, this is not always the c a s e , owing to which a c e r t a i n d i s a g r e e m e n t between the c a l -
culated and e x p e r i m e n t a l c h e m i c a l shifts is o b s e r v e d . However, these deviations a r e n e v e r t h e l e s s suffi-
ciently s m a l l and do not i n t e r f e r e with the unambiguous a s s i g n m e n t of the signals of the H a and H 4 protons.
A s i m i l a r calculation was made for O - a c e t y l d e r i v a t i v e s V-VIII. As in the c a s e of the o x i m e s , the
o b s e r v e d difference /n the c h e m i c a l shifts of the H 3 and He protons d e c r e a s e s as the e l e e t r o n - a c c e p t o r c h a r -
a c t e r of the substituent in the a r y l r i n g i n c r e a s e s , and for the syn i s o m e r of VIII this difference changes
sign (the H 4 signal i s shifted to w e a k e r field than II3 signal). In DCON(CDa) 2 solution, only the syn f o r m of
the O - a c e t y l d e r i v a t i v e s could be investigated (the anti f o r m s p r o v e d to be unstable in this solvent). The
calculated 6 Hg and 6 H4 values for the syn f o r m s p r o v e d to be in quite good a g r e e m e n t with the e x p e r i m e n t a l
values.

*The a s s i g n m e n t of the signals of the H3 and H4 protons on the b a s i s of multiplicity is i m p o s s i b l e , inasmuch

as 4JHsH0' arid 5JH4H0 a r e c o m p a r a b l e in absolute value.

272
 TABLE 3. Calculated and Experimental Values of the Chemical
Shifts of the H8 and Ha P r o t o n s (ppm)
i 6
Pro-
toll
Corn- l IC~ i Ie
~
)ound icalc, iexptl.! ~,6 !pourid ?alc. DCON(CDs)~
ati
DCON(CD~)~
~exp
[
H8 |a 7,38 7.37 ! 0.01 Va
7,54 7,32
H4 7,08 7.07 0,01 7,21 6,79
H~ Vb 7,22 6,95
H4 7,15 6,71
H3 IIa 7,38 7.35 0,03 Via 7.54 7,33
H4 7,10 7.14 -0,04 7,25 6,78
H~ IIb 6,82 6.83 --0,01 ~ VIb 7,22 7,15 0,07 6,96
H4 7,04 7,08 --0,04 ] 7,17 7,15 0,02 6,7I
H3 IIla 7,40 7.36 0,04 VIIa 7.56 7,32
H4 7,16 7,16 ' 0,00 7,29 6,79
H3 IIIb 6,84 6,83 0,01 i VIIb 7,24 7,21 0,03 6,95
H4 7,1(1 7,09 0,01 7,23 7,21 0,02 6,72
H3 -- 'VIIIa 9 7,41
H4 7,59 F 7,01
H~ IVb 6,96 6,93 0.03 ! VIIIb 7,36 7,28 0,08 6,96
H4 7140 7.38 0,02 j 7,53 7,49 0,04 7,04

R e c o r d i n g of the s p e c t r a of V-VIII in CDC13 showed that in this solvent r e g u l a r i t i e s are o b s e r v e d for

Hs and H4, but the values t h e m s e l v e s of the chemical shifts differ appreciably f r o m the values calculated
f r o m the i n c r e m e n t s found for solutions in DCON(CD3) 2 (see Table 3). At the same time, this did not p r e -
vent the reliable a s s i g n m e n t of the H3 and H4 signals in the PMR s p e c t r a .

The values of the l o n g - r a n g e SSCC !JH4H0 for all of the investigated compounds were d e t e r m i n e d
f r o m the signals of the H4 protons. F o r anti i s o m e r s In-ilia, 5JHaH0 is 0.66-0.72 Hz, while 5JH4I-]0 is close
to z e r o for syn i s o m e r s ]/b-IVb. Consequently, the anti i s o m e r s axe p r e s e n t in solution p r i m a r i l y in the
s - c i s conformation C (as also in the case of the anti i s o m e r of furfural oxime) [5], while the syn i s o m e r s
a r e p r e s e n t p r i m a r i l y in s - t r a n s conformation B (in c o n t r a s t to the syn i s o m e r of furfural oxime).
The position of the VOH band is p r a c t i c a l l y the s a m e in the IR s p e c t r a of Lrla and IIIb (3220 c m -1 in
the c r y s t a l s and 3585 c m - i in solutions), and dilution does not affect the position of the band. I n a s m u c h as
an i n t r a m o l e c u l a r hydrogen bond cannot exist in the syn i s o m e r by virtue of g e o m e t r i c a l considerations, the
data p r e s e n t e d above negate the p r e s e n c e of this s o r t of bonding in the anti i s o m e r ; this is to a g r e a t degree
in a g r e e m e n t with conformation C of the l a t t e r i s o m e r .

The data obtained show that the introduction of an aryl substituent into the 5 position of the furan ring
does not affect the conformational equilibrium of the anti i s o m e r s , while for the syn i s o m e r s it p r o m o t e s
g r e a t p r e f e r a b l e n e s s of the s - t r a n s form,
In o r d e r to investigate the conformations of O - a c e t y l derivatives V-VIII, we used model compounds

~ " ~ C Ha=NOCOCHa
~Xa, b

IX (a is anti, and b is syn). F r o m t h e values of the 5JH H and 5JH4H0 l o n g - r a n g e SSSC (see Table 1), it was e s t a b -
5 4 5
l i s h e d t h a t s - c i s c o n f o r m a t i o n C ( JH4H0 ~ 0.66-0~ ~z, JHhH0 ~ 0.06-0.09 Hz) is p r e f e r a b l e for the anti
i s o m e r , while the syn i s o m e r is r e p r e s e n t e d by a mixture of the s - c i s and s - t r a n s conformations (A and B)
(hjH4H ~ N 0.22-0.27 Hz, 5JHhi_[0~ 0.37-0.45 Hz). F r o m a c o m p a r i s o n of the l o n g - r a n g e SSCC, it follows that
in CDC13 solutions the syn i s o m e r is a mixture with p r a c t i c a l l y identical amounts of conformations A and
B, while this equilibrium is shifted to a c e r t a i n d e g r e e in DCON(CD3)2 solution to favor conformStion B.
This situation is different f r o m the case of the syn i s o m e r of furfural oxime in which the effect of solvents
on the conformational state of the investigated compound is absent [5].
F o r Va-VIIIa, 5JH.H0 is 0.66-0.64 Hz which indicates p r e d o m i n a n c e of s - c i s conformation C in these
compounds. For the s ~ i s o m e r s of V-VIII, 5JH4H0 ~ 0.27-0.30 Hz (CDCla) and 0.20 I-Lz [VII, DCON(CD3)2].
These data show that the syn i s o m e r s , as .in the case of model compound Ixb, are p r e s e n t in CDC13 solution

273
 in the f o r m of a mixture with a p p r o x i m a t e l y identical amounts of the s - c i s and s - [ r u n s c o n f o r m a t i o n s , while
s - t r a n s conformation B a p p a r e n t l y b e c o m e s somewhat m o r e p r e f e r a b l e in DCON(CD3) 2 solution.
Thus in solutions the ant[ i s o m e r s of the entire s e r i e s of investigated and model compounds a r e p r e s -
ent in the s - c t s conformation. The s y n i s o m e r s of furfural ox[me and its O - a c e t a t e and of the O - a c e t y l de-
r i v a t i v e s of 5 - a r y l - f u r f u r a l oximes a r e r e p r e s e n t e d in solution by m i x t u r e s with a p p r o x i m a t e l y equal
amounts of the s - e i s and s - t r a n s conformations, while the equilibrium is shifted to favor the s - [ t a n s con-
f o r m a t i o n for the syn i s o m e r s of 5 - a r y l - f u r f u r a l o x i m e s .

EXP ERIME NTAL

The PMR s p e c t r a w e r e r e c o r d e d with JNM-4H-100 and C - 6 0 - H L s p e c t r o m e t e r s with t e t r a m e t h y l s i l a n e
(TMS) as the internal standard. The IR s p e c t r a w e r e r e c o r d e d with a P e r k i n E l m e r 457 s p e c t r o m e t e r . The
solvent was CC14.
The difference in the widths of the H 4 signal (at half its height) m e a s u r e d under m o n o r e s o n a n c e con-
ditions and under conditions involving decoupling of the H 0 proton was taken for the 5JHtH 0 SSCC for lib and
VIlIb ( c ) ( T a b l e 1). The differences in the widths of the H 4 or H 3 signals at half t h e i r heights and the values
that take into account the natural width of the line and the coupling of a given proton with the a r o m a t i c r i n g
protons w e r e taken for the 5JHtH0 and ~JH3H 0 SSCC, denoted b y a; the s u m of the l a t t e r two values was de-
t e r m i n e d f r o m H 0 decoupling e x p e r i m e n t s for rib and VIIIb (c). The 5JH4H0 SSCC values, denoted by b, w e r e
d e t e r m i n e d f r o m the H 0 signal with allowance for all of the interactions of the "aldehyde" proton. The n a t -
ural width of the line, which was d e t e r m i n e d f r o m the CH2C12 signal for a d e g a s s e d s a m p l e [0.15 Hz in CDC13
and 0.20 Hz in DCON(CD3)2] , was taken into account in the evaluation of ~JH H0 of IXa (d and e). The SSCC
values denoted by a w e r e d e t e r m i n e d with an a c c u r a c y of 0.06 Hz, while tee r e m a i n i n g values w e r e d e t e r -
mined with an a c c u r a c y of 0.03 Hz (degassed s a m p l e s w e r e investigated).
5 - ( p - B r o m o p h e n y l ) f u r f u r a l Oxime, ant[ I s o m e r lIIa. See [1] for the synthetic method and the physical
constants.
O-Acetyl Derivative Vlla. A mixture of 1.08 g of IIIa and 4.5 ml of acetic anhydride* was refluxed on
a w a t e r bath for 30 min, after which it was p o u r e d into water. The p r e c i p i t a t e was r e m o v e d by filtration to
give 0.83 g (70%) of a product with mp 125-126 ~ (from alochol). Found: C 51.0; H 3.3; Br 25.5%.
C~Hi0BrNO 3. Calculated: C 50.7; H 3.3; Br 25.8%.
5-0p-Bromophenyl)furfural Ox[me, syn I s o m e r IIIb. A mixture of 7.5 g (29 mmole) of 5 - ( p - b r o m o -
phenyl)furfural, 2.3 g (33 mmole) of hydroxylamine hydrocbloride, and 2.7 g (33 mmole) of s o d i u m acetate
in 58 ml of 36% alcohol was refluxed for 4 h. The mixture was cooled, and the r e s u l t i n g p r e c i p i t a t e was r e -
moved by filtration and r e c r y s t a l l i z e d two or t h r e e t i m e s f r o m 95% alcohol. The yield of IIIb in s e p a r a t e
e x p e r i m e n t s r a n g e d f r o m 4.2 to 6.0 g (53-77%). The product had mp 159.5-160 ~ Found: C 50.1; H 3.0;
Br 29.9%. CllHsBrNO 2. Calculated: C 49.7; H 3.0; Br 30.0%.
O-Acetyl Derivative VIIb. This compound was obtained in the s a m e way as O - a c e t y l d e r i v a t i v e VIIa.
The yield of product with mp 149-150 ~ (from alcohol) was 59%. Found: C 50.8; H 3.2; Br 25.5; N 4.4%.
CI3H10BrNO3. Calculated: C 50.6; H 3.3; Br 25.8; N 4.5%.
5-(p-Chlorophenyl)furfural Oxime, anti I s o m e r IIa. See [1] for the synthetic method and the physical
constants.
O-Acetyl Derivative Via. This compound was obtained by the method used to p r e p a r e O - a c e t y l d e r i v a -
tive VIIa. The yield of product with mp 108-120 ~ (from alcohol) was 53%. Composition. 50% syn i s o m e r
and 50% anti i s o m e r . Found: C 59.2; H 3.8%. ClsHi0C1NO 3. Calculated: C 59.2; H 3.8%.
5-(p-Chlorophenyl)furfural Oxime, syn I s o m e r lib. This compound was p r e p a r e d by the method used
to obtain IlIb. The yield of product with mp 137-138 ~ (from ethyl acetate) was 50-89%. Found: C 59.4;
H 3.6; C1 15.7; N 6.6%. CliHsC1NO 2. Calculated: C 59.6; H 3.6; C1 16.0; N 6.3%.
O-Acetyl Derivative VIb. This compound was p r e p a r e d by the method used to obtain O - a c e t y l d e r i v a -
tive VIIa. The yield of product with mp 142.5-145 ~ (from alcohol) was 65%. Found: C 59.2; H 3.7; C1 13.0%.
C13H10C1NO3. Calculated.. C 59.2; H 3.8; C1 13.5%.

*The a c e t a m i d e s of 5 - a r y l f u r a n - 2 - c a b o x y l i c acids a r e f o r m e d during the acetylation of the a r y l f u r f u r a l

o x i m e s with acetic anhydride. See our following communications for details of t h e s e s o r t s of t r a n s f o r m a -
tions.

274
 5-Phenylfurfural Oxime, anti Isomer Ia, See [3] for the synthetic method and the physical constants.
O-Acetyl Derivative Va. This compound was prepared by the method used to obtain O-acetyl deriva-
tive VEa. The yield of product with mp 85-100 ~ (from alcohol) was 70%. Composition: 3070 of the syn iso-
mer and 7070 of the anti isomer. Found: C 68.1; H 4.7; N 6.170. C13HllNO3. Calculated: C 68.1; H 4.8; N
6.1%.
5-(p-Nitrophenyl)furfural Oxime, syn Isomer IVb. See [2] for the synthetic method and the physical
constants.
O-Acetyl Derivative VIIIb. This compound was obtained by the method used to prepare VIIa. The
product had mp 161-163 ~ (from alcohol). Found: C 56.7; H 3.8; N 10.670. C13H10N205. Calculated: C 56.9;
H 3.7; N 10.270.
O-Acetyl Derivative of Furfural Oxime (anti and syn isomers IXa, b). This compound was prepared
by the method used to obtain O-acetyl derivative VIIa from the syn isomer of furfural oxime. Fractions ~
with bp 107-109 ~ (3 mm) and n ~ 1.5339 (5070 syn and 5070 anti isomers) and bp 113-114 ~ (3 mm) and n~
1.5379 :(..90%sya and 107o anti isomers) were isolated. The results of analysis of both fractions were close
and correspond to the empirical formula IX.

LITERATURE CITED
1. A. F. Oleinik, T. I. Vozyakova, G. A. Modnikova, and K. Yu. Novitskii, Khim. Geterotsikl. Soedin.,
1448 (1972).
2, R. Frimm, S. Kovac, and S. A. Giller, Chem. Zvesti, 2.33, 916 (1969).
3. C. Davis and G. Zougheed, J. Heterocycl. Chem., 4, 153 (1967).
4. E. Lustig, J. Phys. Chem., 65,491 (1961).
5. R. Wasylishen and T, Schaefer, Can. J. Chem., 50, 274 (1972),

275
RESEARCH ON FURAN ACETAL COMPOUNDS
VII.* PIVIR SPECTRA, CONFIGURATION, AND CONFORMATIONS
OF SUBSTITUTED 2- (~-FURYL)-I,3-DIOZANES

Yu. Yu. Samitov, Z. I. Zelikman, UDC 547.722.2'841 : 541.63 : 543.422.25

A. I. Shkrebets, and V. G. Kul'nevich

The configuration and p r e f e r r e d conformations of a n u m b e r of s t e r e o i s o m e r i c 2 - ( ~ - f u r y l ) -

1,3-dioxanes w e r e e s t a b l i s h e d by PMR s p e c t r o s c o p y . It is shown that eis orientation of the
NO 2 groups with r e s p e c t to the furyl ring is p r i m a r i l y r e a l i z e d for 2 - ( a ' - n i t r o - ~ - f t t r 3 r l ) - 5 -
ethyl-5-nitro-l,3-dLoxanes.

In o r d e r to investigate the s t e r e o c h e m i s t r y of 1,3-dioxanes of the furan s e r i e s [2], we synthesized

~ ' - s u b s t i t u t e d 2 - ( ~ - f u r y l ) - 5 - e t h y l - 5 - n i t r o - (A), ~ ' - s u b s t i t u t e d 2- ( a - f u r y l ) - 5 , 5 - d i m e t h y l - (B), and a t - s u b -
stituted 2 - ( ~ - f u r y l ) - 4 - m o n o methyl[or 4 , 4 - d i m e t h y l - (C)]-l,3-dioxanes [3, 4].
R
o

A B C
I-IV, V a.b vI-VIII IX-XI

I X=H,aiS-: II X = C H z , a i s - :
III X = B r , a i S - ; IV X = I.CiS-: V a X= N O : ~ i S - : v b X = ~ o ~ , t r a n s - ;
Ph
VI X = l t ; VII X=NO2; VIII X = C - - O H . IX X = H , RI=R2=CH3; x X = H . R;=H. R2=CH3~
I
Ph
Xl X=Br RI=H, R2=CH~

The p r e s e n t communication is devoted to the p r o o f of the configuration and e s t a b l i s h m e n t of the p r e -

f e r r e d conformations of 1,3-dioxanes of s e r i e s A, B, and C by P1Vllq s p e c t r o s c o p y .
The proton c h e m i c a l shifts (8) and the s p i n - s p i n coupling constants (JHH') of compounds I - X I a r e
s u m m a r i z e d in Table 1.
As will be shown below, the p r e f e r r e d c h a i r c o n f o r m a t i o n for the 1,3-dioxane r i n g is r e a l i z e d in all
of the investigated s y s t e m s , and the methylene protons in the 4 and 6 positions a r e t h e r e f o r e denoted as HA
(axial) and HB (equatorial) in Table 1. In a p r e c e d i n g communication [2], it was shown that the r e l a t i v e
magnetic nonequivalence of t h e s e protons (ASAB) m a y s e r v e as a t e s t sign of both the configuration and the
c o n f o r m a t i o n of the 1,3-dioxane s y s t e m . I n a s m u c h as proton vicinal s p i n - s p i n couplings a r e absent in
s e r i e s A and B b e c a u s e of the p r e s e n c e of two substituents attached to the C(5) a t o m , we judge the config-
uration of the substituents and the conformation of the s i x - m e m b e r e d h e t e r o r i n g b y r e l y i n g on the t h e o r e t -
ically expected r e l a t i v e changes in the nuclear magnetic shielding constants (AcrZ). These e s t i m a t e s show
that in the c a s e of 5 , 5 - d i m e t h y l - l , 3 - d i o x a n e the HA and H B protons for a c h a i r c o n f o r m a t i o n should have
g r e a t r e l a t i v e nonequivalence (AaABth~- 0.8 ppm), should be p r a c t i c a l l y equivalent for a s y m m e t r i c a l boat
conformation (AaABth -~ 0.004 ppm), and that the nonequivalence should be s m a l l for the u n s y m m e t r i c a l b o a t
conformation (AcrABth~ 0 . 1 4 p p m f o r 4-CH2and 0.22 p p m for 6-CH2). Turning to Table 1, we see that the

~See [1] for communication VI.

K r a s n o d a r Polytechnical Institute. V . I . U l ' y a n o v - L e n i n Kazan State University. T r a n s l a t e d f r o m

KhimLya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 3, pp. 319-323, March, 1974. Original article s u b m i t t e d April
10, 1973.

9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy o f this article is available from the publisher for $15.00.

276
 J "o
~ ~ mp'~ 'H. HB
Eq.5-CH~
Ax, t a'-CHa UaB, HZ~
E>
1,57 5,24 -- - 12.6
99 / 3,o8 4,68 1,60 5,2fi 1,92 - - I2,3
In 116 / 2,98 4,6O 1,62 5,06 0,32 0,89 - - -- -- - 13.0
1:5 3,03 2,10 5,15 0,33 0,92 -- - 12.7
139 / 3,o4 4,6(3 1,56 4,93 0,34 0,93 -- - 12.7
107 / 3,55 3,94 0,39 4,72 0,57 1,84 -- -11,5
VI 1t2 (2)*[3,40 3,57 0,17 5,37 0.70 1.21 -- - 10.8
VII 19094 3,51 3,68 0,17 5,44 0.731,21 -- - 12.0
-- 5,34 0,70 1.19 --
109 (7)* -- 379 / 5,64 1,30 1.37
420 -- / 5,45 1,20 1.30
xXli 11546(6)* 3,97 5,47 -- -- 1,24 1.34

* Boiling point (mm, mercury standard).

t T h e c h e m i c a l s h i f t s (6) w e r e d e t e r m i n e d w i t h an a c c u r a c y o f
=~ 0 . 0 0 5 p p m .
$ The J H H ' c o n s t a n t s w e r e d e t e r m i n e d w i t h an a c c u r a c y o f + 0.1 Hz.

HA Ho H

O2N - NO2
I HB-
-- CH~
HB H~ C2H5 low-melting

- - CH2-

H~ Ho H

--CH.
IH B
HB H~. NO2
He ~ 2 0 A B . - - 1 2 , 7 Hz ~ high-melting -- CH2--

t p
4 3 2 O $~ppm

F i g . 1. P M R s p e c t r a of 2 - ( a ' - n t t r o - c ~ - f t L r y t ) - 5 - e t h y l - 5 - n i t r o - l , 3 -
d i o x a n e s : l o w - m e l t i n g i s o m e r ( t r a n s f o r m ) and h i g h - m e l t i n g i s o m e r
(cis f o r m ) .

A S A B v a l u e s ( c o l u m n 5) f o r I - V a c o n s i d e r a b l y e x c e e d t h e A e A B t h ~ 0.8 p p m v a l u e a n d r a n g e f r o m 1.56 to
2.10 p p m . T h i s f a c t , f i r s t o f a l l , a t t e s t s to t h e c h a i r c o n f o r m a t i o n o f the 1 , 3 - d i o x a n e r i n g a n d , s e c o n d , i n -
d i c a t e s a n a x i a l c o n f o r m a t i o n of t h e n i t r o g r o u p , i n a s m u c h a s when t h e n i t r o g r o u p h a s a n e q u a t o r i a l c o n -
f o r m a t i o n , t h e e x p e r i m e n t a l l y o b s e r v e d A 6 A B v a l u e , a s s h o w n in [2], c o r r e s p o n d s to t h e e s t i m a t e d A ~ A B t h
v a l u e . T h e c h e m i c a l s h i f t s o f t h e CH 2 a n d CH 3 g r o u p s of the e t h y l g r o u p i n g a l s o i n d i c a t e the a x i a l o r i e n t a -
t i o n o f t h e NO 2 g r o u p and, c o n s e q u e n t l y , t h e e q u a t o r i a l c o n f o r m a t i o n o f t h e e t h y l g r o u p . The P M R s p e c t r a
o f two s t e r e o i s o m e r s o f V a x e p r e s e n t e d in F i g . 1. F r o m t h e l o w e r s p e c t r u m , w h i c h c o r r e s p o n d s to t h e
h i g h - m e l t i n g i s o m e r , it is s e e n t h a t t h e p r o t o n s of t h e CH 2 and CH 3 g r o u p s r e s o n a t e at " a n o m a l o u s l y " h i g h

277
 5,15
HA Ho H
r~B --CH
C2H5 ,[
t~J!~~,e 2 ~ 12,7
HA NO 2

Hz
i~ - CHf-

I i I I I I I I I I
4 3 2 1 0 $~pprn
Fig. 2. P ~ s p e c t r a of 2 - ( a ' - i o d o - a - f u r y l ) - 5-ethyl- 5 - n i t r o - l , 3- dioxane.

magnetic field values; this is possible in s i x - m e m b e r e d cyclic ethers and e s t e r s , as shown in a paper by
one of the co-authors [5], for an equatorial orientation of, for example, the C2Hs group. However, if the ethyl
group occupies an axial position, the line of the CH 2 group is shifted to lower field (5 =1.84 ppm), and the
magnitude of the nonequivalence of the HA and HB protons d e c r e a s e s to ZX5 = 0.39 ppm. The equatorial con-
formation of the furan ring in I-XI can be judged f r o m the magnitude of the chemical shift of the singlet of
the proton attached to C (2) [2]; this shift is 4.72-5.70 ppm in all of the investigated compounds.
In general f e a t u r e s , the PIVIR s p e c t r a of I-IV duplicate the f o r m of the s p e c t r u m of the high-melting
s t e r e o i s o m e r Va (Fig. 1), as can be judged f r o m the s p e c t r u m of, for example, IV (Fig. 2).
Thus we a r r i v e at the conclusion that the molecules of I-Va have cis orientation of the NO 2 groups
with r e s p e c t to the faryl group, i.e., they can be called cis i s o m e r s , while Vb is a t r a n s i s o m e r with diequa-
torial orientation of the polar substituents. If one considers that the volume of the C2H5 group is g r e a t e r
than the volume of the NO 2 group, it can be seen that the s t e r e o s p e c i f i c i t y of the condensation r e a c t i o n s of
diols with aldehydes of the furan s e r i e s is regulated by the effective volumes of the substitutents attached
to the C (5) atom r a t h e r than by t h e i r m a s s e s .
In addition, the p r e f e r a b l e n e s s of the axial conformation of the nitro group in most of the compounds
of s e r i e s A can be r e a d i l y understood f r o m a qualitative point of view if one considers that the axial position
of the C(5) atom is unique. The fact is that the axial conformation of the nitro group both in the diol itself,
in wMch a quasichair conformation is r e a l i z e d because of intramolecular hydrogen bonding (see the s c h e m e
below, conformation a ) in the transition state, and, doubtlessly, in the final product should be stabilized by
e l e c t r o s t a t i c interaction (attraction) between the nitrogen atom bearing a positive charge and the endoeyclic
oxygen atoms (conformation b).

o I.-.';--:.~' %m-;-~f.... o
II ~e
o a o b

The PM~ s p e c t r a of compounds' of s e r i e s B contain a radical difference in the c h a r a c t e r of the r e s o -

nance of the the 4,6-CH 2 groups, which consists in the considerably l e s s e r nonequivalence of the HA and HB
protons (see Table 1).
It would s e e m that tMs indicates a cl~nge in the conformation of the 1,3-dioxane ring if the r e s o n a n c e
of the protons of the methyl groups of the gem-dimethyl grouping did not have featttres peculiar to the chair
conformation. The s p e c t r u m of VII, f r o m which the c h a r a c t e r i s t i c difference in the amplitude of the methyl
lines is seen, is p r e s e n t e d in Fig. 3. This difference is due to the unresolved multiplet s t r u c t u r e of the line
at lower field. It is known that the shielding constants of the methyl groups attached to C (5) undergo i n v e r -
sion [5] and that consequently the line at weak field must be assigned to the axial methyl group if one adopts
the chaLr conformation. -Its additional multiplicity is then understood as a consequence of the l o n g - r a n g e
s p i n - s p i n coupling (4JHH,) with the axial HA protons of the 4,6-CH 2 groups. This s o r t of coupling is always
r e a l i z e d with a lower 4JHH, constant for an equatorial proton. The magnitudes of the r e l a t i v e nonequivalence

278
 HA HQ Hp c~
oH;
HS~AO~/fH p'
J Hs NO~ HAHs
cH~
2j -
AB.--11,5 HZ

_~3=6 Hz H~

~ - ~ 3 2 1 o
5, ppm
Fig. 3. PMR s p e c t r u m of 2 - ( a ' - n i t r o - a - f u r y l ) - 5 , 5 - d i -
methyl-l,3-dioxane.

of the protons of the g e m - d i m e t h y l grouping [A6ae(CH3) 0.48-0.51 ppm] a r e typical [5] for the c h a i r con-
f o r m a t i o n in cyclic e t h e r s and e s t e r s . However, the r e a s o n for the low nonequivalence of the HA and HB
protons in s e r i e s B r e m a i n s unclear and r e q u i r e s f u r t h e r study. It s e e m s p r e m a t u r e to consider it to be
the r e s u / t of c o m p r e s s i o n of the chair.
Compounds X and XI in s e r i e s C m a y be s t e r e o i s o m e r i c , but, according to the PMR s p e c t r a , the in-
v e s t i g a t e d s a m p l e s a r e p u r e cis i s o m e r s with diequatorial o r i e n t a t i o n of the substituents. This can be
judged f r o m the lone 4-CH 3 doublets (JHH' --6 Hz) with c h e m i c a l shifts 5 =1.29 p p m in both compounds.
This s o r t of shift is c h a r a c t e r i s t i c for an equatorial methyl group attached to the C (4) or C (6) atom. T a k -
ing into account the p o s s i b i l i t y of a s t r o n g 1 , 3 - i n t e r a c t i o n of the axial furyl grouping, we a s s i g n an e q u a t o r -
ial c o n f o r m a t i o n to it.
In conclusion, it must be noted that d o n o r - a c c e p t o r substituents in the u - p o s i t i o n of the furan ring -
CH3, I, Br, and NO 2 - have p r a c t i c a l l y no effect on the c o n f o r m a t i o n of the s i x - m e m b e r e d r i n g , as can be
judged f r o m the a b s e n c e of definite tendencies in the s m a l l changes in the c h e m i c a l shifts of the protons of
the 1,3-dioxane ring.

EXPERIMENTAL
The p r e p a r a t i o n of the 2 - ( c e - f u r y l ) - l , 3 - d i o x a n e s studied in this r e s e a r c h was d e s c r i b e d in [1, 3, 4].
The PMR s p e c t r a of 5-10 vol. % solutions of I - V in benzene and of 10 vol. % solutions of VI-XI in CCI4 w e r e
r e c o r d e d with Varian HA-100D and Varian T - 6 0 s p e c t r o m e t e r s at r o o m t e m p e r a t u r e . T e t r a m e t h y l s i l a n e
was used as the internal standard.

LITERATURE CITED
1. V. G. Kul'nevich, Z. I. Z e l i k m a n , A. I. S h k r e b e t s , B. A. T e r t o v , and M. M. Ketslakh, Khim. G e t e r o t -
sild. Soedin., 595 (1973).
2. Yu. Yu. Samitov, Z. I. Z e l i k m a n , and V. G. Kul'nevieh, Zh. Strukt. Khim., 1_0, 234 (1969).
3. Z. I. Zelikman, A. I. Shkrebets, V. G. Kul'nevich, and B. A. T e r r o r , tc2tim. G e t e r o t s i k l . Soedin., 438
(1971).
4. A. I. S h k r e b e t s , Z. I. Z e l i k m a n , V. G. Kul'nevieh, G. N. Soltovets, and R. Z. Fakhrutdinov, Khim.
G e t e r o t s i k l . Soedin., 1159 (1972).
5. Yu. Yu. Samitov, Dokl. Akad. Nauk SSSR, 164, No. 2 , 3 4 7 (1965).

279
~-ELECTRONIC STRUCTURE OF THE NITROFURAN SYSTEM
IV.* ESR SPECTRA OF ANION RADICALS OF 2-VINYLENE
DERIV~T~VES O F 5-NITROFURAN

R. A. Gavar, L. Kh. Baumane, UDC 543.422.27 + 541.515' 138 + 547.722.5

Ya. P. Stradyn', and S. A. Giller

Anion r a d i c a l s of 2-vtnylene d e r i v a t i v e s of 5 - n i t r o f u r a n w e r e obtained by e l e c t r o c h e m i -

cal generation. The hyperfine s t r u c t u r e (tffs) of the ESR s p e c t r a of t h e s e anion r a d i c a l s
indicates delocalization of the unpaired e l e c t r o n o v e r t h e i r entire v - e l e c t r o n s y s t e m .
The effect of the vinylene grouping on the distribution of the unpaired electron in the an-
ion r a d i c a l s and on the distribution of the unpaired e l e c t r o n in the vinylene grouping itself
was examined on the b a s i s of the lffs constants. It was found that the vinylene grouping by
localizing m o r e than 10% of the density of the unpaired e l e c t r o n on i t s e l f r e d u c e s , by a f a c -
t o r of 1.4, the effect of substituents in the 2 position of 5 - n i t r o f u r a n on the distribution of
the spin of the unpaired e l e c t r o n in the n i t r o f u r a n f r a m e w o r k .

T h e e l e c t r o c h e m i c a l reduction of s i m p l e 5 - n i t r o f u r a n d e r i v a t i v e s in d i m e t h y l f o r m a m i d e (DMF) p r o -
ceeds through a step involving the f o r m a t i o n of anion r a d i c a l s of the s t a r t i n g compounds [1, 2]. The p r e s -
ence of a hyperfine s t r u c t u r e (hfs) in the ESR s p e c t r a made it p o s s i b l e to not only p r o v e the s t r u c t u r e s of
t h e s e r a d i c a l s but also to investigate the distribution of e l e c t r o n s o v e r the v - s y s t e m and the p r i n c i p l e s of
the interaction of s i m p l e substituents with the furan ring [3]. A t t e m p t s to obtain this s o r t of information
f o r m o r e complex compounds, f o r example, 2-vinylene d e r i v a t i v e s of furan, did not give definite r e s u l t s
[4-6]. In the p r e s e n t r e s e a r c h we t h e r e f o r e made a s y s t e m a t i c study of 5 - n i t r o f u r a n d e r i v a t i v e s in which
the substituent is s e p a r a t e d f r o m the f u r a n ring by a vinylene grouping.
By m e a n s of e l e c t r o c h e m i c a l reduction in DMF we w e r e able to obtain, in a o n e - e l e c t r o n step of the
p r o c e s s , anion r a d i c a l s I - V I I of vinylene d e r i v a t i v e s of 5 - n i t r o f u r a n that w e r e sufficiently stable f o r r e -
cording by ESR s p e c t r o s c o p y . Consequently, the anion r a d i c a l s a r e f o r m e d during the following reaction:

I--VII

I It~II'=H, X=.COOH; II II=Br. I t ' = t l , X=COOH: Ill II=H. R'=CI, X=COOH;

IV II~H. I~'=CH 3, X~COOH; V ll=R'=tt, X=CHO: VI R = R ' = t t , X=COOC2H~

v i i I I = l l ' = b l , X~COOCtt 3

F o r c o m p a r i s o n of the hfs constants of the ESR s p e c t r a , the hfs constants of anion r a d i c a l s VIII-XI,
which do not contain a vinylene grouping, w e r e d e t e r m i n e d m o r e p r e c i s e l y u n d e r the s a m e e x p e r i m e n t a l
conditions.

*See [1] f o r communication HI.

Institute of Organic Synthesis, A c a d e m y of Sciences of the Latvian SSR, Riga. T r a n s l a t e d f r o m K h i m -

iya Geterotsiklieheskikh Soedinenii, No~ pp. 324-329, March, 1974. Original a r t i c l e submitted M a r c h 14,
1973.

9 1975Plenum Publishing Corporation, 227West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy o f this article is available from the publisher for $15.00.

280
 L ~III Xl

Vlll X=COOH, IX X=COOCH 3, X X=COOC2Hs; Xl X=CHCl

The anion r a d i c a l s of the vinylene s e r i e s (I-VII} do not differ substantially in stability f r o m anion
r a d i c a l s VIII-XI. The n a t u r e of substituent X has the principal effect on the stability of all of the investi-
gated anion r a d i c a l s . The ESR s p e c t r u m of anion r a d i c a l I (Fig. 1) has splitting of the 3 N 92 H 92 H 92 H 92 H
type. The m e a s u r e d hfs constants have the following values: a N = 7 . 9 5 Oe, and a i l = 4 . 9 6 , 3.06, 1.37, and
0.93 Oe. Constant a N is close in value to the a N values p r e v i o u s l y obtained for the anion r a d i c a l s of the
n i t r o f u r a n s e r i e s (VIII-XI) [7], and this splitting is due to interaction of the unpaired electron with the ni-
t r o g e n atom of the nitro group. It is impossible on the basis of only the single s p e c t r u m obtained to assign
the r e m a i n i n g hfs constants to definite p r o t o n s . For this, we also studied anion r a d i c a l s 1I, III, and IV, in
which, in contrast to anion r a d i c a l I, the individual protons of the vinylene grouping are substituted by other
a t o m s . The absence of a proton attached to the a - a t o m of the vinylene grouping in anion radical II leads
to simplification of the hfs of the ESR s p e c t r u m (Fig. 2). Almost all of the s p e c t r a l lines (the splitting
is of the 3N "2H ~ "2H type}, except for two, a r e resolved. By comparing the hfs constants of this s p e c -
t r u m ( a N = 8 . 6 Oe, and a l l = 4 . 9 , 1.2, and 2 . 3 0 e ) with the values c o r r e s p o n d i n g to anion radical I, we see
that in the case of anion r a d i c a l I the aI_I constant of 0.93 Oe is due to the proton of the a - p o s i t i o n of the
vinylene grouping. Interpretation of the ESR s p e c t r u m of anion r a d i c a l HI (hfs of the 3 N 92H 92 H 9214 type),
in which the proton in the fl -position of the vinylene grouping is replaced by a chlorine atom, led to t h e
following values of the hfs constants: a N = 8 . 3 0 e , and a H =4.7, 1.3, and 1 . 3 0 e . On the basis of a c o m -
p a r i s o n of this set of hfs constants with the hfs constants f o r anion radical I, it can be a s s e r t e d that the a H
hfs constant of anion r a d i c a l I (3.06 Oe) is due to the p r o t o n of the/~ - c a r b o n atom of the vinylene grouping.
The r e m a i n i n g two hfs constants of this anion radical a r e evidently, as usual [7], due to the interaction of
the unpaired electron with the p r o t o n s of the furan ring, namely, a H = 4.96 Oe f r o m interaction with the p r o -
ton in the 4 position and a H = 1.37 Oe f r o m interaction with the proton in the 3 position.

In c o n t r a s t to the anion r a d i c a l s with COOCH 3 and COOC2H5 substituents, in the ESR s p e c t r a of which
one o b s e r v e s splitting due to the protons of this substituent, the ESR s p e c t r a of the free r a d i c a l s obtained
f r o m compounds with a COOil substituent do not have this sort of hfs constant, although q u a n t u m - c h e m i c a l
calculations provide evidence for a c e r t a i n density of the unpaired electron on the oxygen atom of the Oil
grouping of this substituent [3]. This p r o v e s that in the c a s e of compounds with a COOil substituent, the

i
~, ~! ,i! ;LU;LJl~JU.,JJ~ JLUJ! I ~J,.]]~,JJ! j~II]! J L JkJo.,~
i; ) Y TT f it )i i 3T ) i~: ill ~ Ji ~ i: 1o~.,
?i
"I( i;
;J '~i '_J..... C
"; "I'T-L,~
o;O.
50e
6 I

F i g . 1. ESR s p e c t r u m of dianion r a d i c a l I, r e c o r d e d in
the f o r m of the s e c o n d d e r i v a t i v e , and i t s l i n e a r r e e o n -
struction.

281
 T A B L E 1. H y p e r f i n e S t r u c t u r e P a r a m e t e r s of the ESR S p e c t r a
of Anion R a d i c a l s of the 5 - N i t r o f u r a n S e r i e s
S"ectralv Splitting constants, Oe
R' X Type of splitting length, ]~ Ia 1
~zN
Oe I!aH4' %,31 H.~ %.1~!a H . X

COO- 3N:21i'2H'2n'21[ 26,38 7,95 4,96 1,37 0,93 3,06

COO- 3~ "2H"~t '2H 25,8 8.6 4,9 1,2 -- 2,3
Ill i H ,CI COO- 3N"2n'2~'2H 2&9 8,3 4,7 1,3 1,3
IX
v COO- 3N"2It"2H'21:"4I[
CHO 3N .2~'2~-2H '21: "2H
COOC2H 3N'2H "2H"2H"3It
34,0
18,72
20,89
9,0
5,02
5,79
5,0
3,37
3,72
1,6 1,6 25
3,89 0,89 3,19
1,20 -- 3,72 0.,30
v11i _~ H COOCHs 3N'2n-2n'2H-4:i 21,42 3,84
"5,80 1,19 3,84 0,34
COO-: 3N .2n .2~ 26,03 9,9t 5,18 1,02
COOCH3 3N '2H-2H ~0,7'2 7,07 4,18 1,08 0,42
COOC2H~ 3N"2H'2H 20.40 7,t4 ~,,i8 1,o7 0,36
] CHO 3N'2~'2H'2U 1753' 15,65 ~,43 ~,~ 2,05

f r e e r a d i c a l s r e c o r d e d in DMF a r e dianion r a d i c a l s with a

COO- substituent. B e c a u s e of the s p e c i f i c hfs, a s , f o r e x -
a m p l e , in the c a s e of anion r a d i c a l VII (Fig. 3}, the identi-
fication of the constant c a u s e d by the p r o t o n s of s u b s t i t u -
ent X is not difficult.
A s i m i l a r a s s i g n m e n t of the hfs c o n s t a n t s was a l s o
m a d e f o r the r e m a i n i n g r e c o r d e d anion r a d i c a l s .
F r o m the r e s u l t s p r e s e n t e d in T a b l e 1, one can fol-
low the change in the hfs c o n s t a n t s and t h e r e b y a l s o the
r e d i s t r i b u t i o n of the d e n s i t y of the u n p a i r e d e l e c t r o n in the
anion r a d i c a l s , w h i c h c h a r a c t e r i z e s the r e l a t i v e e l e c t r o -
p h i l i c i t y of the v a r i o u s p o s i t i o n s of the s t a r t i n g 5 - n i t r o -
Ill )ijji][} !JIj Jr)J I{ J~ ,
]" Y'I:T : l:] '! ] : f u r a n c o m p o u n d s as a function of the c h a r a c t e r of the s u b -
stituent. T r a n s i t i o n f r o m anion r a d i c a l s VIII-XI to t h e i r
:. 3. r.. J.o,,, a n a l o g s with a vinylene g r o u p i n g in the side chain (I, VII,
VI, and V) c a u s e s a d e c r e a s e in the hfs c o n s t a n t due to the
T _J~ n i t r o g e n a t o m of the n i t r o g r o u p . I n a s m u c h as the hfs c o n -
i stant and the d e n s i t y of the u n p a i r e d e l e c t r o n in the n i t r o
g r o u p a r e i n t e r r e l a t e d [8], this a t t e s t s to at least a d e -
F i g . 2. ESR s p e c t r u m of dianion r a d i c a l
c r e a s e in the d e n s i t y of the u n p a i r e d e l e c t r o n on the n i t r o -
II, r e c o r d e d in the f o r m of its f i r s t d e r i v a -
gen a t o m . The s a m e p h e n o m e n o n is a l s o o b s e r v e d f o r the
tive, and its l i n e a r r e c o n s t r u c t i o n .
all, 4 constant; this is a c l e a r indication of a d e c r e a s e in
the d e n s i t y of the u n p a i r e d e l e c t r o n in the 4 p o s i t i o n of the
f u r a n ring. The opposite effect is o b s e r v e d f o r the aI_], 3 constant; the p r e s e n c e of a vinylene g r o u p i n g in-
c r e a s e s the value of the aN, 3 constant. H o w e v e r , c a l c u l a t i o n s show that in this c a s e the n e g a t i v e s p i n d e n -
s i t y of the r - e l e c t r o n s m a k e s the p r i n c i p a l contribution, and it is t h e r e f o r e i m p o s s i b l e to f o r m a d i r e c t
j u d g m e n t r e g a r d i n g the d e n s i t y of the u n p a i r e d e l e c t r o n in the f i r s t vacant m o l e c u l a r o r b i t a l f r o m the value
of only this hfs constant.
The hfs constant due to the p r o t o n s of substituent X a l s o d e c r e a s e s in the p r e s e n c e of the v i n y l e n e
grouping. This effect is r e i n f o r c e d as the e l e c t r o p h i l i c i t y of substituent X i n c r e a s e s , and in the c a s e
X =CHO in the p r e s e n c e of a vinylene g r o u p i n g the a H constant, due t o the p r o t o n of the aldehyde grouping)
d e c r e a s e s by a f a c t o r of about f o u r (Table 1, V and XI). The d e c r e a s e in the d e n s i t y of the u n p a i r e d e l e c -
t r o n in the n i t r o f u r a n r i n g and in substituent X is c a u s e d by d e l o c a l i z a t i o n of the u n p a i r e d e l e c t r o n o v e r the
vinylene grouping, within the l i m i t s of which the d e n s i t y of the u n p a i r e d e l e c t r o n constitutes a c o n s i d e r a b l e
value, m o r e than 10% of the e l e c t r o n . The d e n s i t y of the u n p a i r e d e l e c t r o n in the vinylene g r o u p i n g is d i s -
t r i b u t e d n o n u n i f o r m l y , and the e l e c t r o p h i l i c i t y of the/3 - p o s i t i o n is m o r e than t h r e e t i m e s that of the c~-
position. R e p l a c e m e n t of the p r o t o n in the/3 - p o s i t i o n of the vinylene g r o u p i n g by a c h l o r i n e a t o m o r a
m e t h y l g r o u p (R' = C H v C1) i n c r e a s e s the r e l a t i v e e l e c t r o p h i l i C i t y of the ~ - p o s i t i o n , but r e p l a c e m e n t of the
p r o t o n in the a - p o s i t i o n by a b r o m i n e a t o m d e c r e a s e s the e l e c t r o p h i l i c i t y of the fi - p o s i t i o n . Substitutions
in the vinylene g r o u p i n g (in both the ~ - and/3 -positions} i n c r e a s e the r e l a t i v e e l e c t r o p h i l i c i t y of the n i t r o
group; this is m a n i f e s t e d in an i n c r e a s e in the m a g n i t u d e of the a N c o n s t a n t . In the e x a m i n e d c a s e s of s u b -
stitution, the e l e c t r o p h i l i c i t y of the 4 and 3 p o s i t i o n s of the 5 - n i t r o f u r a n f r a m e w o r k c h a n g e s only slightly.

282
 "(. I. "(j i:i. '(..3' J._
50e

Fig. 3. ESR s p e c t r u m of anion radical VII, r e c o r d e d in the

f o r m of the second derivative, and its linear r e c o n s t r u c -
tion.

It has been shown that the a N and a H,4 hfs constants of anion r a d i c a l s d e c r e a s e r e g u l a r l y as the e l e c -
trophilicity of the substituent in the 2 position of 5-nitrofuran i n c r e a s e s [7]. It follows f r o m a c o m p a r i s o n
of t h e s e hfs constants for anion radicals I and V-VII that when t h e r e is an intermediate grouping in the sub-
stituent of the vinylene type this sort of general principle of the effect of substituent X is retained. This is
confirmed, for example, by the l i n e a r interrelationship between the aNvin and a H,4 vin constants of anion
r a d i c a l s I and V ' V I I and the c o r r e s p o n d i n g a N and a H,4 constants of t h e i r analogs, VIII-Xh avin = 0.92 +
0.71a (r = 0.993) o
It follows f r o m the value of the reproducibility coefficient (Z = 0.71) in the equation that the inclusion
of a vinylene grouping d e c r e a s e s the effect of substituent X on the hfs constants caused by the nitrogen atom
of the nitro group and the proton of the 4 position of the 5 - n i t r o f u r a n f r a m e w o r k by a f a c t o r of 1.41. This
s o r t of estimate for the starting 5 - n i t r o f u r a n molecules was p r e v i o u s l y made in [9], in which the potentials
of the p o l a r o g r a p h i c reduction of t h e s e compounds were c o m p a r e d , and it was found that the vinylene group-
ing r e d u c e s the effect of substituent X on the r e a c t i o n center by a f a c t o r of 1.67. It should be emphasized
that in our case the attenuation was determined f r o m the s t e r i c c h a r a c t e r i s t i c s of the unpaired electron in
the anion radicals, w h e r e a s in [9] it was d e t e r m i n e d from the e n e r g y c h a r a c t e r i s t i c s of the f i r s t vacant o r -
bital of the s t a r t i n g compounds. The c l o s e n e s s of the found values of the " e l e c t r o n i c conductivity" of the
vinylene grouping indicates that the p a r a m e t e r s of the ~r-electron s y s t e m and the interrelationship between
them do not change significantly with the addition of one electron to the starting m o l e c u l e s .

EXPERIMENTAL

The anion radicals of the investigated compounds were obtained by electrochemical generation on the
surface of a mercury drop in a microcell [I0] mounted in the resonator of an ESR spectrometer. When the
rectangular resonator (Hl02) of an ER 9 ESR spectrometer (Karl Zeiss, Jena) was used, the reactor of the
cell [10] was flat in the near-cathode portion with a test-solution layer thickness of ~ 0.4 ram. The solu-
tions of the investigated substances were prepared in DMF (concentrations of 10 -3 to 5 9 10 -3 M) and con-
tained an inert salt [(C3HT)4NBr ] in a concentration of 0.I M. The electrochemical generation of the anion
radicals was realized at potentials of the plateau of the limiting current of the first polarographic wave at
-0.6 to -I.0 V relative to the anode - mercury sludge. The ESR spectra of the anion radicals were re-
corded with RIP-1301 (with a cylindrical resonator and a resolution of ~ 0.40e) and ER 9 (Karl Zeiss, Jena)
(with a rectangular resonator and a resolution of better than 0.30e) spectrometers. The magnetic field
scan was calibrated from the ESR spectrum of nitrobenzene anion radicals [II].

The samples of the starting compounds from which anion radicals I-XI were obtained by electroreduc-
tion were given to us by K. K. Venter, for which we sincerely thank hLrn. According to the PMR data, start-
ing compounds I-VII are the trans isomers.

283
 LITERATURE CITED
1. R.A. Gavar, L. Kh. Baumane, Ya. P. Stradya', and S,A. Giller, Khim. Geterotsikl. Soedin., 435 (1972).
2. Ya. A. Kastron, G.A.Veinberg, R. A. Gavar, and S. A. Giller, Khim. Geterotsikl. Soedin., 863 (1966).
3. R.A. Gavar, V. A. Zilitis, Ya. P. Stradya', and S. A. Giller, Khim. Geterotsikl. Soedin., 294 (1970);
3 (1971}.
4. G.O. Reikhman, Ya. P. Stradyn', R. A. Gavar, and S. A. Giller, Zh. Obsheh. Khim., 4_!I,906 (1971}.
5. A.I. Prokof'ev, V. M. Chibrikin, O. A. Yuzhanova, and R. G. Kostyanovskii, Izv. Akad. Nauk SSSR,
Set. Khim., 1105 (1966).
6. A. Berndt, Angew. Chem., 7_~9,240 (1967).
7. R.A. Gavar, V. K. Grin', G. O. Reikhman, and Ya. P. Stradyn', Teor. i Eksperim. Khim., _6, 685 (1970).
8. J.H. Freed, P. H. Rieger, and G. K. Fraenkd, J. Chem. Phys., 3_~7,1881 (1962).
9. Ya. P. Stradyn', I. Ya. Kravis, G. O. Reikhman, and S. A. Giller, Khim. Geterotsikl. Soedin., 1309
(1972}.
I0. R.A. Gavar, Ya. P. Stradyn', and S.A. Giller, Zavod. Lab., 31, 41 (1965).
ii. L. H; Piette, P. Ludwig, and R.N. Adams, Anal. Chem., 3_~4,916 (1962}.

284
DIHYDROPYRAN DERIVATIVES
I. 2- (H YDROXYALKOX Y),3,4-DIHYDRO PYRANS

M . G. V o r o n k o v , A. S. A t a v i n , UDC 547.81.811 : 543.422.25.4

V. I. Lavrov, V. K . Stankevieh,
and I. D. Kalikhman

A n u m b e r of 2 - ( h y d r o x y a l k o x y ) - 3 , 4 - d i h y d r o p y r a n s w e r e s y n t h e s i z e d by diene c o n d e n s a -
tion of m o n o v i n y l e t h e r s of g l y c o l s with a c r o l e i n , and s o m e of t h e i r c h e m i c a l t r a n s f o r m a -
t i o n s w e r e studied. T h e y w e r e a l s o s u b j e c t e d to initial p h a r m a c o l o g i c a l e x a m i n a t i o n .

C o m p o u n d s of the p y r a n s e r i e s a r e w i d e l y u s e d in o r g a n i c s y n t h e s i s and find a p p l i c a t i o n a s g l u e s , l u -

b r i c a n t s , p l a s t i c i z e r s , and m o n o m e r s in c o p o l y m e r i z a t i o n [1, 2].
2 - A l k o x y ( a r y l o x y ) - 3 , 4 - d i h y d r o p y r a n s w e r e p r e v i o u s l y o b t a i n e d by c o n d e n s a t i o n of vinyl alkyl [ 3 ] ( a r y l
[4]) e t h e r s with a , f i - u n s a t u r a t e d a l d e h y d e s or k e t o n e s . We have i n v e s t i g a t e d the diene c o n d e n s a t i o n of
m o n o v i n y l e t h e r s of g l y c o l s with a c r o l e i n , which l e a d s to t h e f o r m a t i o n of the p r e v i o u s l y unknown 2 : ( h y -
d r o x y a l k o x y ) - 3 , 4 - d i h y d r o p y r a n s . T h e r e a c t i o n p r o c e e d s in 4-5 h in the a b s e n c e of a s o l v e n t and a c a t a l y s t
at 145-155~ via the s c h e m e

HC~CH2
HE CH--OROIt
%o
I-V

I R=(CIt2)2; II R~(CH~)3; Ill R=CH2Cfl(CH3); IV R=(CH2)4; V R=(CH2)20(EH2) 2

All of the s y n t h e s i z e d c o m p o u n d s (I-V, T a b l e 1) a r e h i g h - b o i l i n g c o l o r l e s s liquids that a r e s t a b l e on

storage.
T h e IR s p e c t r a of I - V contain f r e q u e n c i e s at 1180 and 1215 c m -1, which i n d i c a t e the p r e s e n c e of C -
O - C g r o u p i n g in t h e i r m o l e c u l e s . T h e s t r e t c h i n g v i b r a t i o n s of the C =C bond a p p e a r d i s t i n c t l y at 1654 e m -1,
while the s t r e t c h i n g v i b r a t i o n s of the = C H - bond a p p e a r at 3065 e m -~. T h e v i b r a t i o n s of the CI-I2 g r o u p in
the d i h y d r o p y r a n ring a r e c h a r a c t e r i z e d by b a n d s at 2840-2860 and 2920 and 2940 c m -~ (v CH} and at
1460 ~= 20 c m -1 (6 CH}. The p r e s e n c e of a h y d r o x y l g r o u p is c o n f i r m e d b y a b r o a d band at 3430 c m -1.

T A B L E 1. 2 - ( H y d r o x y a l k o x y ) - 3 , 4 - d i h y d r o p y r a n s (I-V)

~ROH
' I I
] MRD ].~ ~ tFound, i Calc., ~

I --CH2CH2-- ! 70(3) I 1,1129 1,4720!36,31136,67

I I IC=H203 o8~4] 8,4' 58 3[ 8 4 71 a-
II --CH~CHzCH2-- i107(8) 1,0797 1,4706'~4092 !41,29 ICsHI4Oz[ 60,619,1 i 60,7[ 8,9i 76,1
]II:--CH2CH(CHs)-- i 69(5) 10650 1,464040 99 i41,291CsH~403 605 88607 89512
IV --CH2CH2CHzCH~-- 1123 10671 14719 45,61145,91 CgH~O~ 62"0 9'5 62'8 94 68'0
! (10) jI1,1166]L1,472614725
V --CH2CH2OCH~CH~--'103(4) i 47551CH I ' I ' / ' i8,6
, ! 9 ,~O4157,5i8,5157,4 [ i58,0
] '

I r k u t s k I n s t i t u t e of O r g a n i c C h e m i s t r y , S i b e r i a n B r a n c h , A c a d e m y of S c i e n c e s of the USSR. T r a n s -
l a t e d f r o m K h i m i y a G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 3, pp. 330-332, M a r c h , 1974. O r i g i n a l a r t i c l e s u b -
m i t r e d A p r i l 17, 1973.

9 1975PlenumPublishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

285
 TABLE 2. P a r a m e t e r s of the PMR Spectra of the Synthesized
Compounds
I Spin - spin coupling con-
,-ol Chemical shifts, 6, ppm ~stants, J, Hz
H5 DMSO'or_her,gr.0UPS.__
i
I 607,6~,8714,05
II 1 6 | 5 i 4 6 7 1 4,921 3,69
i a,ro
3,80 4,46
|,77
'
4,64
i
6,0
! 6,2 2,9
2,9 3,0
[
4,2 1,6
3,0 4,2 1,7
III 16,3i I4,95 3,49
4,70 l 3,20 -- 3,80 -- CH 6,2
1,10 CHa i
2,8 3,0 4,0 1,8
:~4,1
IV 6,12 i 4,67 4,90 3,51 1,57 4,20 4,43 i 6,2 2,8 3,0 1,7
V 4,68 4,62 i6'2 2,9 3,0 4,01 1,8
VI 675 4,56 3,60 3,o 3,o
VII 4,7, ,,86 4,97 3,66 2,54 6,3 2,9 3,0 i;

The p a r a m e t e r s of the PMR s p e c t r a of the synthesized compounds a r e p r e s e n t e d in Table 2. The

change in the length and c h a r a c t e r of the side chain is r e f l e c t e d in the magnitude of the chemical shifts, but
the s p i n - s p i n coupling constants r e m a i n p r a c t i c a l l y unchanged. The OCH 2 and CH 2 signals a r e weakly
r e s o l v e d multiplets. The signal splitting o b s e r v e d for H-2 is c h a r a c t e r i s t i c f o r the coupling of two equa-
t o r i a l and a x i a l - e q u a t o r i a l vicinal protons [5], and the 2 ' - h y d r o x y a l k o x y group in all of the studied c o m -
pounds consequently occupies the axial position.
The e x t r a p o l a t e d (to infinite dilution) c h e m i c a l shifts of the hydroxyl protons of I - V in dimethyl sulf-
oxide (DMSO) a r e p r e s e n t e d in T a b l e 2. It is known [6] that t h e s e shifts can s e r v e as a m e a s u r e of the a c i d -
,

b a s e p r o p e r t i e s of hydroxyl-containing compounds. Withdrawal f r o m the c.2c, 2 s y s t e m l o w e r s the

acid p r o p e r t i e s of the hydroxyl group. The acidities of the hydroxyl hydrogens in I and V a r e p r a c t i c a l l y
identical.
Hydrogenation of the compounds d e s c r i b e d above in the p r e s e n c e of Raney nickel or palladium on
BaSO 4 gives the c o r r e s p o n d i n g t e t r a h y d r o p y r a n d e r i v a t i v e s (VI). Cyanoethylation p r o c e e d s with the p a r t i -
cipation of the hydroxyl group:

NCCH2CHzOCH2CH~OO Clt2=CltCN ! 1t2~ Q~o~OClt2CIt2Ott

VII V[

A p r e l i m i n a r y study of the physiological activity of the compounds showed that they a r e not toxic for
white m i c e (LDs0 =1.5 g/kg}. Except for a c e r t a i n reduction in m o t o r activity, e x p r e s s e d ataxia, a c e r t a i n
amount of salivation, and difficulty in breathing, no special changes w e r e o b s e r v e d in the b e h a v i o r of the
t e s t a n i m a l s . No effect on the c a r d i o v a s c u l a r s y s t e m was noted.

EXPERIMENTAL

The IR s p e c t r a of m i c r o l a y e r s of the compounds w e r e r e c o r d e d with a UR-20 s p e c t r o m e t e r (with

NaC1 and L i F p r i s m s ) . The PMR s p e c t r a of 5% solutions in CC14 w e r e r e c o r d e d with a T e s l a BS 487B
s p e c t r o m e t e r with an operating f r e q u e n c y of 80 MHz at 20 ~ Hexamethyldisiloxane (HMDS} was used as the
internal standard. The s t a r t i n g hydroxyalkyl vinyl ethers w e r e obtained by r e a c t i o n of acetylene with the
a p p r o p r i a t e glycols under p r e s s u r e in an autoclave [7].
Ethylene glycol monovinyl e t h e r had bp 138 ~ (715 ram) and nD2~ 1.4300. 1 , 2 - P r o p y l e n e glycol m o n o -
vinyl ether had bp 47 o (15 ram) and n D 20 1.4312. Trimethylene glycol monovinyl ether had bp 164 (755 ram) o

and no2~ 1.4390. T e t r a m e t h y l e n e glycol monovinyl e t h e r had bp 182 ~ (755 mm} and no2~ 1.4458. Oiethylene
glycol monovinyl ether had bp 96 ~ (12 ram) and nD2~ 1.4480. The a c r o l e i n was distilled p r i o r to the r e a c t i o n s
and had bp 52-53 ~ (720 ram) and nD2~ 1.3998. Hydroquinone (1%) was added to it as a p o l y m e r i z a t i o n in-
hibitor.
2 - ( 2 ' - H y d r o x y e t h o x y } - 3 , 4 - d i h y d r o p y r a n (D. A 0 . 2 5 - l i t e r rotating s t e e l autoclave was c h a r g e d with
11.2 g (0.2 mole} of aerolein, 0.1 g of hydroquinone, and 17.6 g (0.2 mole} of ethylene glycol monovinyl
ether, and the m i x t u r e was heated at 145 ~ for 4 h, a f t e r which it was distilled initially at a t m o s p h e r i c p r e s -
s u r e (during which 0.4 g of a c r o l e i n with bp 53 ~ and riD2~ 1.4010was isolated) and then in vaeuo to give 20.6
g (71.5%) of I.

286
 The r e m a i n i n g compounds (H-V) w e r e s i m i l a r l y s y n t h e s i z e d .
2 - ( 2 ' - H y d r o x y e t h o x y ) t e t r a h y d r o p y r a n (VI). A hydrogenation v e s s e l was c h a r g e d with 3.6 g (0.025
mole) of I, 20 m l of alcohol, and 0.02 g of p a l l a d i u m on BaSO 4. After 600 m l (0.026 mole) of hydrogen had
been a b s o r b e d , the m i x t u r e was filtered, the alcohol was r e m o v e d by distillation, and the r e s i d u e was f r a c -
tionated in vacuo to give 3.4 g (92.7%) of VI with bp 83 ~ (5 m m ) , d4201.0774, and nD2~ 1.4565. Found: C
57.5; H 9.7%; MR D 36.91. CTHitO 3. Calculated: C 57.5; H 9.6%; MR D 37.14.
2 - ( 2 ' - C y a n o e t h o x y e t h o x y ) - 3 , 4 - d i h y d r o p y r a n (VII). A m i x t u r e of 7.2 g (0.05 mole) of I, 2.65 g (0.05
mole) of a c r y l o n i t r i l e , and 0.05 g of sodium methoxide was placed in a g l a s s ampul and heated at 140 ~ f o r
8 h. It was then cooled and washed with w a t e r . The w a t e r l a y e r was e x t r a c t e d with ether, a n d the ether
e x t r a c t was dried o v e r K2CO 3. The ether was r e m o v e d by distillation, and the r e s i d u e was vacuum distilled
to give 3.7 g (37.2%) of VII with bp 144 ~ (7 ram), d42~ 1.0900, and nD2~ 1.4682. Found: N 7.2%; MR D 50.32.
C10H15NO3. Calculated: N 7.1%; MR D 50.46.

LITERATURE CITED

1. N. W. Flodin, US Patent No. 2,443,496 (1948); Chem. Abstr., 4__22,7576 (1948).

2. J. Dazzi, US Patent No. 2,943,473 (1960); Chem. A b s t r . , 5..~5,4531 (1961).
3. R. J. Longley and W. S. E m e r s o n , J. Am. Chem. Soc., 72, 3079 (1950).
4. M. F. Shostakovskii, G. G. Skvortsova, K. V. Zapunnaya, and V. G. K o z y r e v , Khim. G e t e r o s t i k l .
Soedin., 652 (1966).
5. N. S. Z e f i r o v , N. M. Shekhtman, and K. A. Karakhanov, Zh. Organ. Khim., 3, 1925 (1967).
6. A. G. Brook and K. H. Pannel, J. O r g a n o m e t . Chem., 8_._66,179 (1967).
7. M. F. Shostakovskii, M. I. Batuev, P. V. Tyupaev, and A. D. Matveeva, Dokl. Akad. Nauk SSSR, 8__9,
93, 501 (1953).

287
 DIHYDRO PYRAN DERIVATIVES
II.* BIS(3,4-DIHYDRO-2-PYRANYL) ETHERS OF GLYCOLS

V. I . L a v r o v , A . S. A t a v i n , UDC 547.811.813 : 543.422.4

a n d V. K . S t a n k e v i c h

A n u m b e r of glycol b i s ( 3 , 4 - d i h y d r o - 2 - p y r a n y l ) e t h e r s w e r e synthesized by diene condensa-

tion of glycol divinyl e t h e r s with a c r o l e t n . The physiological activity of the p r o d u c t s was
tested.

The l i t e r a t u r e contains only patent information r e g a r d i n g the p r e p a r a t i o n of a s i m p l e b i s ( 3 , 4 - d i -

h y d r o - 2 - p y r a n y l ) ether, and the r e a c t i o n conditions a r e not indicated [2].
A n u m b e r o f p r e v i o u s l y unknown glycol b t s ( 3 , 4 - d i h y d r o - 2 - p y r a n y l ) e t h e r s w e r e obtained by diene con-
densation of glycol divinyl e t h e r s with a c r o l e i n . The r e a c t i o n p r o c e e d s in 4-5 h in the a b s e n c e of a solvent
and a c a t a l y s t at 150-160~ via the s c h e m e
/~CH2

No
I-V
| R=(CH2). ; I1 R=(CH2)3; Ill R=(CH2)4; IV R=(CH2)2CH(CH3) ;
V R=(CH2)20(CH2) ~

The c h a r a c t e r i s t i c s of I - V a r e p r e s e n t e d ill Table 1. T h e i r s t r u c t u r e was p r o v e d by IR s p e c t r o s c o p i c data,

the r e s u l t s of e l e m e n t a r y a n a l y s i s , and by c h e m i c a l t r a n s f o r m a t i o n .
The bands at 1654 and 3065 c m -1 in the IR s p e c t r a of I - V indicate, r e s p e c t i v e l y , the p r e s e n c e of C = C
and =CH bonds in the d i h y d r o p y r a n rings. The vibrations of the C - O - C groupings a p p e a r at 1180 and 1215
cm -~. The absorption bands of an aldehyde group a r e absent.
The c o r r e s p o n d i n g glycol b i s ( t e t r a h y d r o - 2 - p y r a n y l ) e t h e r s (V) w e r e obtained by hydrogenation of the
synthesized compounds in alcohol in the p r e s e n c e of Raney nickel. Absorption bands at 1654 and 3065 cm -~

*See [1] for communication I.

TABLE 1. Glycol B i s ( 3 , 4 - d i h y d r o - 2 - p y r a n y l ) E t h e r s

o,o9
Corn- I bp, 1i -MRD
- EmpiricalFound, Calc., ~e.
pound i R ~ d,2~ formula % ~o
J
I (CH2)2 105(3) 1,109811,4824 58,17i 58,65 C,~H,sO4 63,8 8,1 63,7 8,0 62,4
II (CH2)a 141(9)] 1,0824[1,4790[ 62,95 ] 63,47 C18H2oO4 65,0 8,4[65,0/ 8,4[ 65,3
llI (CH~)4 120(2) ] 1,0717] 1,4803! 67,39 1 68,09 C14H=O4 66,l] 8,7t 66,1j8,7/ 72,8
IV (CH~)~CH(CH3)141(7) l 1,0561] 1,4771f 67,50 [ 68,09 C14H~O4 66,1l8,8 66,118,7178,1
V (CH2)20(CH2)2 133(2) 1t,1117 1,4820] 69,32] 69,73 C~4H2:O561,9 8,1 62,2 8,2 62,2

I r k u t s k Institute of Organic C h e m i s t r y , Siberian Branch, A c a d e m y of Sciences of the USSR. T r a n s -

lated f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 3, pp. 333-334, March, 1974. Original a r t i c l e sub-
mitted May 18, 1973.

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy of this article is available from the publisher for $15.00.

288
a r e absent in the IR s p e c t r a of VI; this indicates the c o m p l e t e n e s s of the hydrogenation and again c o n f i r m s
the p r o p o s e d s t r u c t u r e of I - V . As a r e s u l t of t e s t s on I - V for physiological activity it was a s c e r t a i n e d that
they a r e m o d e r a t e l y o r slightly toxic for white m i c e (LDs0 =0.7-1.5 g/kg). I n c r e a s e d excitability of the t e s t
a n i m a l s was noted in s o m e c a s e s . In the r e s t of the a n i m a l s , t h e i r b e h a v i o r r e m a i n e d without s p e c i a l signs,
and t h e i r r e f l e x e s w e r e retained; no effect on the c a r d i o v a s c u l a r s y s t e m and r e s p i r a t i o n was o b s e r v e d .

EXPERIMENTAL
The IR spectra of microlayers of the compounds were recorded with a UR-20 spectrometer (with NaCl
and LiF prisms).
The glycol divinyl ethers used as the dienophiles were obtained by direct vinylation of the appropriate
glycols with acetylene under pressure in an autoclave in the presence of alkaline catalysts [3].
Ethylene glycol divinyl ether had bp 126 ~ (748 ram) and nD2~ 1.4350. Trimethylene glycol divinyl ether
had bp 143 ~ (760 ram) and riD2~ 1.4332. Tetramethylene glycol divinyl ether had bp 167 ~ and nD2~ 1.4398.
1,3-Butylene glycol divinyl ether had bp 54 ~ (17 ram) and riD2~ 1.4348. Diethylene glycol divinyl ether had
bp 89 ~ (13 ram) and riD2~ 1.4465. Freshly distilled aerolein [bp 52-53 ~ (720 ram), nD2~ 1.3998] containing 1%
hydroquinone as a polymerization inhibitor was used.
Ethylene Glycol Bis(3,4-dihydro-2-pyranyl) Ether (1). A 0.25-1iter rotating steel autoclave was
charged with 11.4 g (0.I mole) of ethylene glycol divinyl ether and 11.2 g (0.2 mole) of aerolein, and the mix-
ture was heated for 4 h at 150 ~ The mixture was removed from the autoclave and distilled, initially at at-
mospheric pressure [during which I.I g of acrolein (bp 52 ~ nD2~ 1.4007) was isolated] and then in vacuo to
give 14.1 g (62.4%) of I.
Compounds II-V were similarly synthesized.
Diethylene Glycol Bis(tetrahydro-2-pyranyl) Ether (VI). A long-necked hydrogenation flask was
charged with 6.8 g (0.025 mole) of V, 30 ml of ethanol, and a catalytic amount of Raney nickel. A total of
1.2 liters ofhydrogenwas introduced with vigorous stirring. The mixture was filtered, the ethanol was re-
moved from the filtrate by distillation, and the residue was fractionated in vaeuo to give 5.8 g (84.6~) of
VI with bp 154 ~ (4 ram), d42~ 1.0755, and riD2~ 1o4649. Found: C 61.4; H 9.7%; MR D 70.51. C14H2605. Cal-
culated: C 61.3; H 9.6%; MR D 70.67.

LITERATURE CITED
1. M. G. Voronkov, A. S. Atavin, V. I. Lavrov, V. K. Stankevich, and I. D. Kalikhman, Khim. Geterotsikl.
Soenin., 330 (1974).
2. C. E. Smith, D. C~ Norton, and S. A. Ballard, US Patent No. 2,514,168 (1950); Chem. Abstr., 44, 8377
(1950).
3. M~ F. Shostakovskii and P. V. Tyupaev, Organic Syntheses, Vol. 2, Wiley.

289
 SOME PECULIARITIES OF THE CYCLIZATION

OF N- PO LYNITROALKY L-N- NITROSO AMINOA C ETIC

ACIDS AND THEIR NITRILES TO SYDNONES
AND SYDNONIMINES*

A. L. Fridman, F. M. Mukhametshin, UDC 547.793.1 : 543.422.4

V. S. Zalesov, and S. S. Novikov

The cyclization of N - p o l y n i t r o a l k y l - N - n i t r o s o a m i n o a c e t i c acids to sydnones o c c u r s only

under the influence of t r f f l u o r o a c e t i c anhydride. Closing to a sydnonimine ring does not
o c c u r in the case of N - ( 2 , 2 , 2 - t r i n i t r o e t h y l ) - N - n i t r o s o a m i n o a c e t o n i t r i l e , but N - ( 2 , 2 , 2 - t r i -
n i t r o e t h y l ) - N - n i t r o s o i m i n o a c e t i c acid imine e s t e r is f o r m e d . Removal of the nitro groups
in the ~/ position relative to the nitrosoamino group leads to n o r m a l o c c u r r e n c e of the r e -
action to give polynitroalkylsydnonimines.

The cyclization of N - n i t r o s o a m i n o a e e t i c acids and t h e i r nitriles to sydnones and sydnonimines has

been developed in quite some detail [2, 3]. However, such an important p r o b l e m as the effect of e l e c t r o n -
a c c e p t o r substituents on the r e a c t i v i t y of the N - N =O f r a g m e n t r e m a i n s unexplained.

In o r d e r to study the nucleophilic activity of the oxygen atom of the nitroso group as a function of the
c h a r a c t e r of the polynitroalkyl substituents, we investigated the cyclization of N - p o l y n i t r o a l k y l - N - n i t r o s o -
aminoacetic acids and their nitriles to sydnones and sydnonimines.
The starting acids were obtained via the Mannich reaction by reaction of 2,2,2-trinitroethanol with the
appropriate amino component in alkaline media with subsequent nitrosation of the condensation product with
sodium nitrite in h y d r o c h l o r i c acid.
R R R
I 1 I
(NO2)3CCH2OH+ H2NCHCOOH--~(NO~)3CCH~NHCHCOONar+(NO2)~CCH2NCHCOOH
NO
I R=H, II R=CHa I, 1I

N - ( 2 - H a l o - 2 , 2 - d i n i t r o e t h y l ) - N - n i t r o s o a m i n o a e e t i c acids (III and IV, Table 1) were obtained f r o m I as a r e -

sult of its denitration with potassium iodide and subsequent halogenation of the dipotassium salt of N-(2,2-
dinitro ehhyl)-N-nit ro soaminoac eric acid,
The s t r u c t u r e of I - I V was confirmed by nitration of them to the c o r r e s p o n d i n g N-(p01ynitroalkyl-N-
nitroaminoacetic acids (V-VIII, Table 1).
N - ( 2 , 2 , 2 - T r i n i t r o e t h y l ) - N - n i t r o s o a m i n o a e e t o n i t r U e (IX) was p r e p a r e d by the addition of n i t r o f o r m to
methyleneiminoacetonitrile and nitrosation of the reaction product in a mixture of sulfuric and acetic acids.

9HC(NO2)3+H2C=NCH2cN-+(NO2hCCH_~NHCH2CN--~(NO~J3CCH2NCH2CN
X I
NO
IX

*See [1] for the p r e l i m i n a r y communication.

P e r m State P h a r m a c e u t i c a l Institute. N. D. Zelinskii Institute of Organic Chemistry, Academy o f

Sciences of the USSR, Moscow. T r a n s l a t e d f r o m Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 335-
341, March, 1974. Original a r t i c l e submitted J a n u a r y 31, 1973.

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, N.Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy of this article is available from the publisher for $15.00.

290
 TABLE 1. N-Polynitroalkyl-N-nitroso(nitroaminocarboxylic Acids and Their Nitriles XC(NO2)2CH2NCI-IRR1
!
Xt
Corn- rap, ~ Empirical Found, % Calc, a]0 . . . . . . IR
. . s .p e. c .t r .u m
. ,. .c m
. .-1. . . . . Yield,

pound R, formula c H I N C ' FI N VC(NO2)~ VN--NO "r 1'4 ~"C= O

I - I - " C NO.. ~ N--NO~ '-- C~N

I NO2 NO H COOH 117--t18 a C4HsNsO9 L7,6 1,8 25,8 17,7 : 1,8 9 25,8 1600 1510 1018 1730 40
1305
ii NO2 NO CHz COOH 113--114 b CsHTN~Op' 21,2 2,3 24,8 21,4 2,5 24,9 1610 1480 1095 1725 17
i
1305
III CI NO tt COOH 91--92 a CaHsCIN4Or 18,5 1,9 21,7 18,7 1,9 21,7 1592 1495 1010 1735 9O
i 1310
IV Br NO H COOH 84--85 a C4HsBrN407 ..... 18,7 18,6 1590 1496 10181 1730 81
1310
V CI ,NQ H COOH 135--136 b C4H~CtN408 -- -- 20,8 20,6 1600 i580 1730 92
1305 i290
VI Br NO,~ H COOtl 137--138 b C4HsBrN408 ..... t7,6 ~7,7 1600 1570 1728 86
1310 1290
VII NO2 NO2 CH3 COOH 156--160 a CsHrNsOIo 20, I 2,3 23,4 20,2 2,4 23,6 1618 1565 1742 89
1310 1288
VIII NO~ NO2 H COOIt 145--147 b C4H~NsO~o 24,9 -- -- 24,7 1615 1570 173,5 92
13(18 1290
IX NO~ NO H" CN 59--60 c C4H4N607 19,2 1,5 29,4 19,4 1,6 29,6 1615 1507 1018 2260 68
1310
X NO2 H H CN 67-68d C4HoN~O6 21,3 2,.3 32,8 21,9 2,3 33,0 1600 2255 93
1305

Note: aFrom befizene, bFrom water. CFrom CHC13-CC14 (1:1). dFrom CC14.

['O
~D
t.a
 TABLE 2. Polynitroalkylsydnones
Found. % Calc., ~ fr-
Com- Empirical
pound x R rap, ~ formula H H i
C
Cl, Br
N C B-~7
cl. ! N o
J
X't NO: H 92--93* C4HzNsOs 18,7] 1.1 ]28,0 19,0 1,2 . I28,1 98
XII NO: ICH3 73--74 CsHsNsO8 22s 1,7 ~26,5 22,8 ! 1,9 !26,6 90
XlI] Ct H 70--71 CaH3C1N4Q -- 23.1 -- 1-5,0
i
I
23,3,96

XIV Br H 59--60 C4H3BrN406 -28~i- i9.8 - 19,8 86

*All of the sydnones melt with decomposition.

N - ( 3 , 3 , 3 - T r i n i t r o p r o p y h a m i n o a c e t o n i t r i l e (IXa) and the dinitrile of 3 , 3 - d i n i t r o - l , 5 - p e n t a n e - d i a m i n o a c e t i c

acid (IXb) were p r e p a r e d by condensation of the corresponding polynitroalkylamines with f o r m a l i n and po-
tassium cyanide.
(NOd3CCH2CH2NH~+ CH2O+ KCN-+(NO2)3CCH~CH2NHCH2CN
IXa
It is known that the eyclization of unsubstituted N - a l k y l - N - n i t r o s o a m i n o a c e t i c acids to sydnones in-
cludes i n t r a m o l e c u l a r reaction of the oxygen atom of the n i t r o s o group with the carbon atom of the carbonyl
group under the influence of a dehydrating agent - m o s t often acetic anhydride [2, 3].
We have established that I does not form a sydnone under the influence of acetic anhydride. The r e -
action p r o c e e d s with the liberation of oxides of nitrogen and resinification of the nitroso derivative.
P r o c e e d i n g f r o m concepts r e g a r d i n g the m e c h a n i s m of the cyclization [3], one should a s s u m e that the
negative result in our case is due to the lowered electron density on the oxygen atom of the n i t r o s o group
due to the inductive effect of the t r i n i t r o m e t h y l group (A and B).

CH~CH.,T..-NCH,,C/ / ~ O (NO2)aCCH2..TN
CH~C.~
''~
" "'~-i ~ ~OCOCHa ~J .~. "OCOCH
N- - 0 N- - 0
A B

In o r d e r to r e i n f o r c e the electrophilicity of the carbon atom of the carbonyl group in the mixed an-
hydrides of N - a l k y l - N - n i t r o s o a m i n o a c e t i c acids - the i n t e r m e d i a t e s in the cyelization [3, 4] - we chose a
dehydrating agent that has strong e l e c t r o n - a c c e p t o r p r o p e r t i e s - t r i f l u o r o a c e t i c anhydride. In fact, under
the influence of the latter, I-IV r e a c t smoothly to give high yields of sydnones (XI-XIV, Table 2).
It is c h a r a c t e r i s t i c that, in c o n t r a s t to the p r e v i o u s l y known types of sydnones, which a r e usually yel-
low [2, 3], the polynitroalkylsydnones a r e c o l o r l e s s . They also explode on r a p i d heating, are unstable

(F3CCO)~O XC (NO2)~CH2--N~CR~
XC(NO2)2CH2?CH(W)COOH -F3CCOOH N ~~_
/ C ~10 1
NO
XI-XIV
XI X=NO2, R ' = H ; Xll X = N O 2, R'=CH3; XII] X=Ci, R~ H; XIV X = B r , Rl=H

during storage, are sensitive to air moisture, a n d d e c o m p o s e in alcohols and acetone. T h e ring closing of
nitriles of N - n i t r o s o a m i n o a c e t i c acids is based on the polarity of the .C=N bond and the nueleophilicity of
the oxygen atom of the nitroso group [2-4].
As in the c a s e of sydnones, no attempts to experimentally establish the effect of polarization of the
nitroso group, on which the outcome of the reaction depends, are r e p o r t e d in the l i t e r a t u r e . In this r e s p e c t ,
a study of the behavior of the nitriles of N - p o l y n i t r o a l k y l - N - n i t r o s o a m i n o a c e t i c acids makes it possible to
obtain information of interest to us.
In analogy with the cyclization to sydnones of I-IV, in the case of nitrile IX one also should have ex-
pected a d e c r e a s e in r e a c t i v i t y on cyclization of it to a sydnonimine. In fact, under Conditions s i m i l a r to
those in the synthesis of sydn0nimines [2-4], we o b s e r v e d not only a d e c r e a s e in the reactivity of nitrile IX
but also a completely different reaction c o u r s e . Instead of the expected 3-(2,2,2-trinitroethyl)sydnonimine,
we isolated methyl N - ( 2 , 2 , 2 - t r i n i t r o e t h y l ) - N - n i t r o s o i m i n o a c e t a t e h y d r o c h l o r i d e (XV).

292
 /I ~ (NO2)oCCH2--N~CH
~ l I
Clt3OIt ; HCl N~(~C= N FI, HCI
IX

= (NO2)3CCH2NCH~C< NH'HC|
i OCH 3
NO
XV

Reactions of this sort have not been reported. The structure of imino ester X V was proved unambiguously
by a number of transformations via the scheme

( H20
XV : (NO2)3CCH2~CH2COOCH3 HNO-~--~3(NO2)3CCH2NCH2COOCH3 -- Vlll
N0 NO2

The initial step in the r e a c t i o n of XV with hydrogen chloride in methanol apparently includes attack
on the nitrogen atom of the nitrile group by a proton, as in the c a s e of the unsubstituted analogs. The r e s u l t -
ing e a r b o i m m e n i u m cation [RN(NO)CH2C =N H] + undergoes methanolysis, which competes with ring closing.
This is possible when the nucleophilic p r o p e r t i e s of the oxygen atom of the nitroso group a r e weakened un-
der the influence of a polynitroalkyl substituent.
In o r d e r to follow the effect of polynitroalkyl substituents on the N - N =O fragment, we studied the be-
havior of nitriles of N - n i t r o s o a m i n o a c e t i e acids containing a nitro group in the y - p o s i t i o n with respect to
the n i t r o s o a m i n o group. Under conditions identical to those in the synthesis of imino e s t e r XV, the h y d r o -
chloride of the c o r r e s p o n d i n g .sydnonimine (XVIII, Table 3) was obtained f r o m nitrile IXe, while the nitrate
salt of 3 - ( 3 , 3 , 3 - t r i n i t r o p r o p y l ) s y d n o n i m i n e (XX) is obtained f r o m nitrile IXa on t r e a t m e n t with nitrogen

N~C
N20~
- (NO2)3CCH2CH2 ~CH2CN N2Oa (NO2)3CCH2CH~:--"{,,E)'H
f

IX a
" N,<o/C=NH. HNOz
NO
- XX

oxides i m m e d i a t e l y without isolation of the nitroso derivative.

N - e x o - N i t r o s o derivatives (XIX and XXI, Table 3) are f o r m e d smoothly on t r e a t m e n t of sydnonimines
XVIII and XX with sodium nitrite in acid media; these derivatives a r e c h a r a c t e r i z e d by bright coloration
[2, 3]. Sydnonimine XX is converted to N - e x o - n i t r o derivative XXII under the influence of sulfuric acid.
As seen f r o m Table 1, the absorption of the nitroso group in the N - p o l y n i t r o a l k y l - N - n i t r o s o a m i n o -
earboxylic acids and t h e i r nitriles is shifted by 50 cm -1 to higher frequencies, while the same shift to lower
frequencies as c o m p a r e d with the unsubstituted analogs [5] c o r r e s p o n d s to the N - N bond. This confirms
our previous conclusion r e g a r d i n g the d e c r e a s e in the degree of p-~r conjugation in the n i t r o s o a m i n e f r a g -
ment due to the inductive effect of e l e c t r o n - a e c e p t o r substituents [4, 6].
An intense band at 3120-3175 cm -1, which is c h a r a c t e r i s t i c for the C - H group of the sydnone ring, is
observed in the IR s p e c t r a of polynitroalkylsydnones and polynitroalkylsydnonimines. An absorption band at
1690-1705 cm -~, which is c h a r a c t e r i s t i c for the C =N bond of the sydnonimine ring [2, 3], is o b s e r v e d in the
IR s p e c t r a of the sydnonimines.

TABLE 3. Polynitroalkylsydnonimines and T h e i r exo Derivatives

RCHeCH2--N--CH
1 i
N\(~C = NR~' Z

Corn-i ' ~ Empirical }Found, % talc., ~o I$

pound R R, z rap, ~ formula I
, ~lc IH x c H I N ~N*

XVIIIIC(NO~)~* H HC1 217--218t CgHt4C 2N806132,6 i 4A 33.7 ]327 4,2 33,9 i38
.XIXjC(NO2).,*NO ! i101--I03 ~cgn,oN,oOa 127,9
- - 2,4 36;2i2S:0 2,6 36,3 81
XXiC(NO~)3 !H H N O a ! l l 5 - - 1 1 6 CsHrNrO~0 {18,4 2,0 30, t 18,5 2,2 30,2 73
XXI C(NO2)~ ]NO -- 86--87 CsHsNTOs 120,4 1,6 33,5 20,6 1,7 33,7 86
XXIIjC(NO2)3, INO2[i - - 153--154 iC~HzN709 i19,5i 1:5 31,8119,5, 1,6 3! 9 [74

* The bissydnonimine; yet another sydnonimine residue is attached

to the dinitromethyl group.
All of the sydnonimines melt with decomposition.

293
 The absorption bands of the t r i n i t r o m e t h y l , dinitromethyl, and n i t r o a m i n o groups have the usual c h a r -
a c t e r i s t i c s [7, 8].

EXPERIMENTAL
N-(2,2,2-Trinitroethyl)-N-nitrosoaminoacetic Acid (i). A 40-g sample of glycine was dissolved in the
minimum amount of water at 90-95 ~ and the solution was treated with 44 g of sodium bicarbonate. The re-
sulting solution of the sodium salt of glycine was added at 20-25 ~ to 130 g of 70% solution of 2,2,2-trinitro-
ethanol [9]. After 30 rain, the reaction mixture was air evaporated to the pasty state and transferred in
small portions to 300 ml of cooled (to 0 ~ hydrochloric acid (sp. gr. 1.23). The mixture was nitrosated at
-5 to 0 ~ by the addition of 20 g of NaNO 2 in 40 ml of water. After 3 h, the crystalline product was sepa-
rated and washed with ice water (three 100-ml portions). The yield of I was 39.5 g.
Compound II was similarly obtained from ~-aminopropionic acid and 2,2,2-trinitroethanol.
N-(2-Halo-2,2-dinitroethyl)-N-nitrosoaminoacetic Acids (III, IV). A) Dipetassium Salt of N-(2,2-Di-
nRroethyi)-N-nitrosoaminoacetic Acid. A 2.7-g sample of I was dissolved in 50 ml of methanol, and 5 g of
potassium iodide was added slowly at 15-20 ~ After 1-1.5 h, the mixture was diluted with 30 ml of ether,
and the yellow precipitate was separated and washed with ether to give 2.05 g (68%) of a salt with mp II0-
III ~ (dec.). The salt was used for the subsequent syntheses without purification.
]3) Chlorination. A solution of 3 g of the dipotassium salt of N-(2,2-dinitroethyl)-N-nitrosoamino-
acetic acid in 30 ml of methanol was treated with chlorine gas at 10-15 ~ until the reaction mixture became
colorless. The inorganic precipitate was separated, and the filtrate was air dried to give 2.4 g of color-
less crystals of III.
C) Bromination. This reaction was carried out as in the case of chlorination. After bromination,
the reaction mixture was acidified with hydrochloric acid. The yield of IV was 1.65 g.
N-(2,2,2-Trinitroethyl)-N-nitroaminoacetic Acid (VIID. A 2-g sample of I was dissolved at 10-15 ~
in 15 ml of 98% nitric acid, and the solution was held at 20-25 ~ for 2 h. A large portion of the nitric acid
was then evaporated, and the residue was diluted with 30 ml of cold water. The resulting precipitate was
separated and washed with cold water to give 1.9 g of acid VIII. The product was identified by a mixed-
melting point determination with a genuine sample of the acid [I0].
N-[2-Chloro(bromo)-2,2-dinitroethyl]-N-nitroaminoacetic and N-2,2,2-trinitroethyl)-N-nitroamino-
~-methylpropionlc acids (V, VI, and VII) [I0, II] were similarly obtained from II, Ill, and IV.
3-(2,2,2-Trinitroethyl)sydnone (XI). A 5-g sample of I was dissolved in 50 ml of ether, and 8 ml of
trifluoroaeetic anhydride was added slowly dropwise to the solution. The mixture was stirred at 15-20 ~
for 1 h, after which it was cooled to 0 ~ and the resulting precipitate was removed by filtration and puri-
fied by precipitation from ethyl acetate by the addition of hexane. The yield was 4.8 g.
Sydnones XII-XIV were similarly obtained.
N-(2,2,2-Trinitroethyl)-N-nitrosoaminoacetonitrile (IX). A 9.5-g sample of methyleneiminoacetoni-
trile [12] was added to a 40% aqueous solution of 20 g of nitroform at 15-20 ~ After 30 min, the precipRate
was separated, washed with water, and dried to give 27,5 g of X. A 10-g sample of X was dissolved in a
mixture of 50 m l of acetic acid and 10 m l of sulfuric acid (sp. gr. 1.84), the solution was cooled to 0-5 ~ and
5 g of sodium nitrite was added with vigorous s t i r r i n g . After 2-2.5 h, the m i x t u r e was poured o v e r 150 g
of c r u s h e d ice, and the r e s u l t i n g p r e c i p i t a t e was s e p a r a t e d and washed with w a t e r to give 6.9 g of IX.
Methyl N - ( 2 , 2 , 2 - T r i n i t r o e t h y l ) - N - n i t r o s o i m i n o a c e t a t e Hydrochloride (XV). A 4-g s a m p l e of IX was
dissolved at 0-5 ~ in 75 m l of methanol s a t u r a t e d with hydrogen chloride, and the m i x t u r e was held at this
t e m p e r a t u r e f o r 2 days. Two-thirds of the alcohol was r e m o v e d by distillation at reduced p r e s s u r e (30-
40 ram, m e r c u r y standard), and 50 m l of e t h e r was added to the r e s i d u e . The p r e c i p i t a t e d substance was
s e p a r a t e d and washed with e t h e r to give 2.3 g (45%) of a product with rap 88-89 ~ (dec.). Found: C 18.9; H
2.8; N 26.4%. CsHgC1N608. Calculated: C 18.9; H 2.8; N 26.5%. IR s p e c t r u m : 1608, 1310 [vC(NO2)3]; 1488
(v N =O); I000, 1020 (VN_N), and 1710 (v C = N) cm-l-
A 0.5-g sample of XV was added slowly to 10 ml of water, and the resulting oil was extracted with
methylene chloride (two 5-ml portions). The extract was dried over magnesium sulfate, the solvent was
removed by distillation, and 5 ml of 98% nitric acid was added to the residue at 0-5% After 2 h, the mix-

294
t u r e was p o u r e d o v e r ice, and the p r e c i p i t a t e was s e p a r a t e d and dried. The yield of methyl e s t e r of acid
VIII was 0.4 g (80%). The e s t e r was saponified with a 1 : 1 m i x t u r e of acetic and h y d r o c h l o r i c acids to acid
VIH. The product was identified by m e a n s of a m i x e d - m e l t i n g - p o i n t d e t e r m i n a t i o n .
3 , 3 - D i n i t r o p e n t a m e t h y l e n e b i s ( s y d n o n i m i n e ) DLhydroehloride (XVI1D. A) Dinitrile of 3 , 3 - D i n i t r o - N , N ' -
d i n i t r o s o - l , 5 - p e n t a n e d i a m i n o a c e t i c Acid (IXc). A 3-g s a m p l e of 3 , 3 - d i n i t r o - l , 5 - p e n t a n e d i a m i n e [13] was
d i s s o l v e d in 50 m l of water, and 1.5 g of p o t a s s i u m cyanide in 10 ml of w a t e r and 3 m l of 36% f o r m a l i n w e r e
added s u c c e s s i v e l y at 10-15 ~ A f t e r 3 h, 30 m l of h y d r o c h l o r i c acid (sp. g r . 1.23) was added to the m i x t u r e .
It was then cooled to 0 ~ and t r e a t e d with an aqueous solution of 3 g of sodium n i t r i t e . The r e s u l t i n g oily
p r o d u c t was e x t r a c t e d with m e t h y l e n e chloride (three 3 0 - m l portions), and the e x t r a c t was dried o v e r m a g -
n e s i u m sulfate. The solvent was e v a p o r a t e d to give 2.5 g (70%) of IXe as a viscous yellow oil. The sub-
stance was subjected to f u r t h e r t r a n s f o r m a t i o n s without purification.
B) Sydnonimine XVIII. A 2-g s a m p l e of dinitrile IXc was dissolved in 30 m l of methanol s a t u r a t e d wit~
hydrogen chloride, and the m i x t u r e was allowed to stand at 15-20 ~ f o r 2 days. The p r e c i p i t a t e d dihydro-
chloride of sydnonimine XVIII was r e m o v e d by filtration, washed with ether, and dried to give 1.05 g of
product. IR s p e c t r u m : 1565, 1320 [vC(NO2)2]; 1690 (v C=N); 3150 (Vring CH) cm-1.
3 - ( 3 , 3 , 3 - T r i n i t r o p r o p y l ) s y d n o n i m i n e Nitrate (XX). A 2-g s a m p l e of N - ( 3 , 3 , 3 - t r i n i t r o p r o p y l ) a m i n o -
a c e t o n i t r i l e n i t r a t e (IXb), obtained f r o m 3 , 3 , 3 - t r i n i t r o p r o p y l a m i n e [14], p o t a s s i u m cyanide, and f o r m a l i n as
in the c a s e of IXa, was t r e a t e d at 0-5 ~ with 2 g of sodium nitrite (in 10 m l of water) in 20 m l of 57% nitric
acid. A f t e r 2 h, the p r e c i p i t a t e was s e p a r a t e d , a i r dried, and purified by p r e c i p i t a t i o n f r o m hot methanol
by the addition of ethyl a c e t a t e . The yield was 1.8 g. IR s p e c t r u m : 1595, 1305 [vC(NO2) ]; 1705 (VC=N);
3175 (v ring CH) era-l"
N - e x o - N i t r o s o D e r i v a t i v e of 3 - ( 3 , 3 , 3 - T r i n i t r o p r o p y l ) s y d n o n i m i n e (XXI). A 0.5-g s a m p l e of XX was
added at 0 ~ to a solution of 0.5 g of sodium nitrite in 5 ml of water, and the m i x t u r e was acidified with 0.5
m l of 57% n i t r i c acid and s t i r r e d f o r 1 h. The b r i g h t - r e d c r y s t a l s of XXI w e r e s e p a r a t e d and washed with
w a t e r to give 0.43 g of product. The compound was p u r i f i e d by p r e c i p i t a t i o n f r o m m e t h a n o l s o l u t i o n b y t h e
addition of w a t e r .
N - e x o - N i t r o s o d e r i v a t i v e XIX was s i m i l a r l y obtained f r o m XVIII.
N - e x o - N i t r o D e r i v a t i v e of 3 - ( 3 , 3 , 3 - T r i n i t r o p r 0 p y l ) s y d n o n i m i n e (XXII). A 4-g s a m p l e of sydnon-
i m i n e XX was added at 5-10 ~ to 20 m l of sulfuric acid (sp. gr. 1.84), and the m i x t u r e was heated to 20-25 ~
and held at this t e m p e r a t u r e for 4-5 h. It was then p o u r e d o v e r 150 g of c r u s h e d ice, and the p r e c i p i t a t e
was s e p a r a t e d and r e c r y s t a l l i z e d f r o m aqueous methanol to give 3.0 g of product.

LITERATURE CITED
1. F. M. Mukhametshin, A. L. F r i d m a n , and A. D. Nikolaeva, Khim. G e t e r o t s i t d . Soedin., 125 (1970).
2. W. B a k e r and W. Ollis, Quart. Rev., 2, 15 (1957).
3. F. Stewart, Chem. Rev., 64, 129 (1964).
4. A.L. Fridman, F. M. Mukhametshin, and S. S. Novikov, Usp. Khim., 40, 65 (1971).
5. R. Williams, R. Pace, and G. Jeacocke, Speetroehim. Acta, 2__0.0 , 225 (1964).
6. F.M. Mukhametshin and A.L. Fridrnan, Zh. Organ. Khim., 6, 928 (1970).
7. A.L. Fridman, V. P. Ivshin, and S. S. Novikov, Usp. Khim., 38, 1448 (1969).
8. V.I. Slovetskii, Us p. Khim., 40, 740 (1971).
9. N. IVIarans and R. Zelinsky, J. Am. Chem. Soe., 7_~2,5329 (1950).
I0. H. Feuer, G. Bachman, C. Coller, and W. Swarts, Tetrahedron, 19 (D, 165 (1963).
II. H. Ungnade and L. Kissinger, Tetrahedron, 19 (I), 143 (1963).
12. J. Bailey and D. Shyder, J. Am. Chem. Soe., 37, 935 (1915).
13. L. Herzog, M. Gold, and E. Geekler, J. Am. Chem. Soe., 7__3_3 , 749 (1951).
14. G. Gold, M. Frankel, G. Linden, and K. Klager, J. Org. Chem., 2_~7,334 (1962).

295
2-BENZOPYRYLIUM SALTS
XVI.* REACTION OF 3-CARBALKOXY-2-BENZOPYRYLIUM SALTS
WITH S~E DIAMINES

G. N. Dorofeenko and V. G. Korobkova UDC 547.814.833' 833.9' 834

The condensation of 1 - a l k y l - 3 - c a r b a l k o x y - 2 - b e n z o p y r y l i u m s a l t s with diamines leads to the

synthesis of piperazino [3,4-b]- and quinoxalino [3,4-b]isoquinolinium p e r c h l o r a t e s .

o n e of the m o s t important t r a n s f o r m a t i o n s of 2 - b e n z o p y r y l i u m s a l t s is t h e i r r e a c t i o n with nitrogen

b a s e s , which leads to the f o r m a t i o n of isoquinolines or isoquinolinium salts - c l o s e analogs of n a t u r a l a l -
kaloids [2]. Recently it has been shown [3] that 2 - b e n z o p y r y l i u m salts r e a c t with diamines ( h e x a m e t h y l e n e -
diamine, p-phenylenediamine, and benzidine) to give isoquinolinium b i s q u a t e r n a r y s a l t s .
We have studied the r e a c t i o n of 2 - b e n z o p y r y l i u m s a l t s that have two r e a c t i v e c e n t e r s with s o m e di-
a m i n e s . F o r this p u r p o s e , we c a r r i e d out the r e a c t i o n of 1 - m e t h y l - 3 - m e t h o x y c a r b o n y l - 6 , 7 - d i m e t h o x y - 2 -
benzopyrylium p e r c h l o r a t e (I) (which we synthesized in [4]) with an e q u i m o l e c u l a r amount of ethylenedi-
amine, which p r o c e e d s r e a d i l y to give one individual product~ The final products of the r e a c t i o n might have
been II-IV:

CHsO~y COOCH3
CH 3 0 ~ N ' ~ ' C H2'--CH2-- NH2
CH3 CIO~

0
II
CH30, , , . , ~ , 7 CO0CH3 NH2CH2CH2NH 2 CH30" ~ - ~ ~ "N H
+ I
c . ~ o ~ ; clo: CH30
CH3 CH3 CIO~"
I 9 III

CH30--~--~COOCH3 CH~OOC\~/OCH3
CH30~N~cH, CH.2/N~ocH3
CH3 CH3
2cto~-

A study of the IR s p e c t r u m [5-7] of the product showed that t h e r e is an a b s o r p t i o n band of the NH group
of a cyclic l a c t a m at 3200 c m -1 and a s t r o n g a b s o r p t i o n band at 1715 c m -1, which is c h a r a c t e r i s t i c f o r the
c a r b o n y l group of a cyclic imide (imide I band); however, t h e r e is no absorption band at 1735 c m -1 ( e s t e r
group). On the b a s i s of a study of the IR s p e c t r u m of the compound obtained, we decided in f a v o r of s t r u c -
t u r e HI. T h i s conclusion was also c o n f i r m e d by the PMR s p e c t r a . The c h e m i c a l shifts (5 scale) w e r e as
follows: singlet at 2.28 p p m (CH 3 group), singlet at 3..03 p p m (two OCH 3 groups), t r i p l e t s at 2.94 and 3.69
p p m (CH2CI-I2 group), and singlets at 5.78, 5.93, and 6.80 p p m ( a r o m a t i c protons). The a b s e n c e in the s p e c -
t r u m of signals of the p r o t o n s of another methox-y group c o n f i r m s p r o p o s e d s t r u c t u r e III [8].

*See [1] for communication XV.

Rostov S t a t e U n i v e r s i t y . S c i e n t i f i c - R e s e a r c h Institute of P h y s i c a l and Organic C h e m i s t r y , R o s t o v -

on-Don. T r a n s l a t e d f r o m Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 342-344, March, 1974. O r i g -
inal a r t i c l e submitted M a r c h 15, 1973.

9 19 75 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy o f this article is available from the publisher for $15.00.

296
 P e r c h l o r a t e I r e a c t s s i m i l a r l y with o - p h e n y l e n e d i a m i n e to give V:
O
II
C H 3 0 ~ N H
Cbl30 I~[ ~ / ~ f / I CIO~-

The data f r o m the PMR s p e c t r u m a r e as follows: 2.58 p p m (CH 3 group), 3.04 p p m (two OCH 3 groups),
and multiplet at 5.64-6.18 and 7.06 p p m ( a r o m a t i c protons). T h e s e data c o n f i r m s t r u c t u r e V, which was
p r o p o s e d on the b a s i s of the IR s p e c t r o s c o p i c data. Thus we have shown that this method can be used to
s y n t h e s i z e the p r e v i o u s l y unknown condensed b i s h e t e r o c y c l i c s y s t e m s - p i p e r a z i n o [ 3 , 4 - b ] - and quinoxaline-
[3,4-b- ]isoquinolinium s a l t s .
Only r e p l a c e m e n t of the h e t e r o c y c i f e oxygen a t o m by nitrogen without ring closing o c c u r s in the r e -
action of p e r c h l o r a t e I with 1,8-diaminonaphthalene or p - p h e n y l e n e d i a m i n e , and N - s u b s t i t u t e d isoquinoliniurz
s a l t s VI and VII a r e formed:

cn~o\~/coocu~ cu~~ c~176 N.~

clo: clo7
%/I VII
The IR spectra of ~ and VII contain absorption bands at 3455, 3370 (V~. and 3435, 3355 cm -I ( ~ D ,
which are related to the stretching vibrations of an unsubstituted p r ~ a r y amino group [6] [~S VI =345"53 +
(0.876 "3455) =3372.11; VS ~ = 3 4 5 o 5 3 +(0.876 "3435) =3354.59], and the absorption band of an ester group
(1730 cm-~).

EXPERIMENTAL
The IR s p e c t r a of m i n e r a l oil s u s p e n s i o n s of the compounds w e r e r e c o r d e d with a UR-20 s p e c t r o m -
e t e r . The PMR s p e c t r a of CF3COOH solutions w e r e r e c o r d e d with a T e s l a BS 487c s p e c t r o m e t e r at 80
MHz and 50%
1 - M e t h y l - 6 , 7 - d i m e t h o x y - 2 - k e t o p i p e r a z i n o [ 3 , 4 - b ] i s o q u i n o l i n i u m P e r c h l o r a t e (III). A m i x t u r e of 0.45
g (1.24 mmole) of p e r c h l o r a t e I, 0.14 g (2.8 mmole) of ethylenediamine, and 4 m l of alcohol was refluxed
f o r 30 rain, a f t e r which it was cooled and f i l t e r e d to give 0.3 g (65%) of c o l o r l e s s c r y s t a l s with mp 287 ~
(dec., f r o m a l c o h o l - n i t r o m e t h a n e ) . Found: C 48.2; H 4.7; C1 9.3; N 7.6%. C15HITN2OTC1. Calculated: C
48.3; H 4.6; C1 9.5; N 7.5%. IR s p e c t r u m , era-l: 3200 m, 1715 s, 1605 s, 1570 m, 1525 s, 1290 s, 1265 m,
1235 m, 1100 s, and 1000 s.
1 - M e t h y l - 6 , 7 - d i m e t h o x y - l H - 2 - k e t o q u i n o x a l i n o [ 3 , 4 - b ] i s o q u i n o l i n i u m P e r c h l o r a t e (V). This compound
was similarly obtained from 0.5 g (1.38 mmole) of perchlorate I, 0.12 g (I.Ii mmole) of o-phenylenediamine,
and 4 ml of alcohol. The yield of yellow crystals with mp 280 ~ (dec., from nitromethane) was 0.35 g (60%).
Found: C 53.9; H 4.2; C1 8.1%. C19HITN2OTCI. Calculated: C 54.2; H 4.0; C1 8.4%. IR spectrum, cm-1:
3270 m, 1695 s, 1595 s, 1555 m, 1520 w, 1500 w, 1275 s, 1230 s, II00 s, and 1020 m.
l-Methyl-2-(4-aminophenyl)-3-methoxycarbonyl-6, 7-dimethoxyisoquinolinium Perchlorate (VI). This
compound was s i m i l a r l y obtained f r o m 0.5 g (1.38 g mmole) of p e r c h l o r a t e I, 0.14 g (1.11 mmole) of p -
phenylenediamine, and 4 m l of alcohol. The yield of yellow c r y s t a l s with mp 226 ~ (dec., f r o m nitromethane)
was 0.3 g (50%). Found: C 52.7; tI 4.5; C1 7.6%. C20H2tN2OsC1. Calculated: C 53.0; H 4.6; C1 7.8%. IR
s p e c t r u m , era-t: 3455 m, 3370 m, 1730 s, 1610 s, 1560 m~ 1515 s, 1275 s, 1230 s, 1210 s, 1170 s, 1100 s,
and 1020 m .
1 - M e t h y l - 2 - [1-(8-aminonaphthyl) ] - 3 - m e t h o x y e a r b o n y l - 6 , 7 - d i m e t h o x y i s o q u i n o l i n i u m Perchlorate (VII).
This compound was s i m i l a r l y obtained f r o m 0.5 g (1.38 mmole) of p e r c h l o r a t e I, 0.19 g (1.2 mmole) of 1,8-
diaminonaphthalene, and 4 m l of alcohol. The yield of yellow c r y s t a l s with mp 247 ~ (dec., f r o m n i t r o m e t h -
ane) was 0.4 g (66%). Found: C 57.5; H 4.7; C1 7.2; N 5.6%. C24}]23N208C1. Calculated: C 57.8; H 4.6; C1
7.2; N 6.0%. IR s p e c t r u m , c m - l : 3355 m, 3435 m, 1730 s, 1640 w, 1605 s, 1580 s, 1515 s, 1275 m, 1235 s,
1210 s, 1100 s, and 1015 w.

297
 LITERATURE CITED
1. E.V. Kuznetsov, D. V. Pruchkin, A.N. Bicherov, and G.N. Dorofeenko, Khim. Geterotsikl. Soedin.,
181 (1974}.
2. G. N: Dorofeenko, E. I. Sadekova, S. V. Krivun, and Yu. A. Zhdanov, Dokl. Akad. Nauk SSSR, .181,
No. 2, 345 (1968}.
3. G.N. Dorofeenko, E. I. Sadekova, and V. M. Goncharova, Khim. Geterotsikl. Soedin., 1308 (1970}.
4. G.N. Dorofeenko, S. V. Krivun, and V. G. Korobkova, Khim. Geterotsikl. Soedin., 1458 (1973}.
5. A. R: Katritzky (editor}, Physical Methods in Heterocyclic Chemistry, 2 Vols., Academic (1963}.
6. K. Nakanishi, Infrared Spectra and Structure of Organic Compounds [Russian translation], Mir, Mos-
cos (1965}.
7. L. Bellamy, Infrared Spectra of Complex Molecules, 2nd ed., Methuen (1958}.
8. J. Brandt and G. Eglinton, Applications of Spectroscopy in Organic Chemistry [Russian translation],
Mir, Moscow (1967).

298
DISINTEGRATION OF 1-SILALACTONES UNDER
THE INFLUENCE OF ELECTRON IMPACT

V. N. Bochkarev, N . S. F e d o t o v , UDC 547.76'245 : 543.51

I. G. Rybalka, a n d V. F . M i r o n o v

It is shown that t h e paths of f r a g m e n t a t i o n of 1 - s i l a l a c t o n e s under the influence of e l e c t r o n

i m p a c t a r e d e t e r m i n e d by the ring size and r e m a i n v i r t u a l l y unchanged when the methyl
groups attached to the silicon a t o m a r e r e p l a c e d by a chlorine a t o m o r an ethyl group. The
p o s s i b i l i t y of the identification of i s o m e r i c s i l a l a c t o n e s on the b a s i s of t h e i r m a s s s p e c t r a
was e s t a b l i s h e d .

The p r e s e n t c o m m u n i c a t i o n is devoted to a study of the paths of disintegration of p r e v i o u s l y synthe-

s i z e d [1, 2] s i l a l a c t o n e s (I-III) under the influence of e l e c t r o n i m p a c t and to the e x p o s u r e of the p o s s i b i l i t y
of the identification of compounds of this c l a s s on the b a s i s of t h e i r m a s s s p e c t r a .

O_CO 3 O--CO o--CO

1 11 a - c Ill
lla R=R'=CH3;b R=CH3, R,=CI;C R=C2Hs, R,=CI

The m a s s s p e c t r a of all of the investigated compounds contain m o l e c u l a r ion peaks of low intensity
(~ 1%). The p e a k s of the ( M - l ) + ions have intensities of the s a m e o r d e r . The f r a g m e n t a t i o n of f i v e - m e m -
b e r e d lactone I is v e r y s i m p l e . Two of the m o s t intense p e a k s in the s p e c t r u m c o r r e s p o n d to ions f o r m e d
during ejection of a CO 2 m o l e c u l e f r o m the m o l e c u l a r ion and f r o m the ( M - M e ) + i o n with m / e 129 (the loss of
a m e t h y l group f r o m the silicon a t o m is c h a r a c t e r i s t i c f o r the methyl d e r i v a t i v e s of silicon-containing
h e t e r o c y c l e s [3, 4]). The f o r m a t i o n of the r e m a i n i n g ions in the s p e c t r u m of I (the s t r u c t u r e s , m / e values,
and r e l a t i i v e intensities of t h e s e ions a r e p r e s e n t e d in Scheme 1) r e q u i r e s no c o m m e n t a r y . The e l i m i n a -
tion of CO 2 f r o m the s i l a l a c t o n e s is s i m i l a r to the ejection of SO 2 f r o m s i l a s u l t i n e s during e l e c t r o n i m -
p a c t [5].
Scheme i~
(CH3]2Si-I-. (CH3)2 Si=CH2
,~/~ 58 <57 %)
o ~'~
~ ~ i-- ,./~ 72 (2o%)

(cnp2~io. ~..
(2e%)
../e 75
(cn3h
.

cd
c.; ?- (Cnp
cM-c,,
,'
i, M+,~/o ,44 (2%) ,,/~ ,oots,%)
l-c.;

CH3Si
+ c.3-*],--~.~ -co~ Cfl3 '+Si--CH2
,~/~ 43 (27%) ~ "~./-c.~
m/e z29 (2o%) ,,,/e ~ (Ioo%)

t The t r a n s i t i o n s denoted with an a s t e r i s k a r e c o n f i r m e d by the p r e s e n c e of the c o r r e s p o n d i n g m e t a s t a b l e

p e a k s . Ions of low m a s s n u m b e r s m a y a r i s e not only d i r e c t l y f r o m the m o l e c u l a r ion but also in s e v e r a l
steps.

T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 3, pp. 345-347, March, 1974. Original

a r t i c l e s u b m i t t e d F e b r u a r y 19, 1973.

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

299
 TABLE 1. m / e Values (relative intensities, %) of
the C h a r a c t e r i s t i c Ions in the Mass Spectra of
Six-Membered Silatactones I I a - c

loft" II& Itb* IIc

144 (1) 164 (2) 178 (1)

( M - t) + l~ (i) 163 (i) 177 (1)
a 129 (12) 149 (I) 149 (4)
b 129 (I) 143 (3)
C loo (35) 120 (riO) 134 (64)
d I05 (9) I05 (13)
85 (8)
e 85 (2) 99 (1)
f I16 (98) 136 (25) 150 (r
g 12t (15) 121 (52)
lOl (65)
h lOl (5) 115 (5)
i 75 (16) 95 (25) 109 (22)
i 72 (lOO) 92 (lO0) ~10~ 000)
* The m/e values for C135 are given for the c h l o r i n e -
containing ions. The ratios of the intensities of the
isotopic peaks are in agreement with the calculated
values in all c a s e s ,

All of the ions c h a r a c t e r i s t i c for I are p r e s e n t inthe m a s s s p e c t r u m of s i x - m e m b e r e d laetone Ita, which

is the i s o m e r of f i v e - m e m b e r e d laetone I. Despite this, i s o m e r i c lactones I and IIa can be reliably dis-
tinguished on the basis of the m a s s spectra, inasmuch as a new type of fragmentation a s s o c i a t e d with ejec-
tion of a neutral particle with m a s s 28 amu f r o m the m o l e c u l a r ion and the ( M - M e ) + ion with m / e 129 ap-
p e a r s in the case of IIa. This particle m a y be ethylene or CO. A s i m i l a r p r o c e s s was also o b s e r v e d in the
m a s s s p e c t r a of silacycloketones with no less than six links in the ring, and it was shown [6] by means of

Scheme 2
+ +
" "-" ' . %,-c.,:
O~CO O--CO
g f h b

1-., V
O - - - CO O--CO CH2-CH ~
rr,si~cHz +
o II. H + ' e

R"-~i--(:H? ,.-r RR'S[ + --CH2

I
CH2-CH ~, C H 2"-C H:~
d c

the Mgh-resolution m a s s s p e c t r a that this fragmentation path is due p r a c t i c a l l y completely to the elimina-
tion of ethylene. Inasmuch as lactone Ha is s t r u c t u r a l l y s i m i l a r to the silacycloketones studied in [6], we
a s s u m e that loss of an ethylene molecule is also o b s e r v e d in the m a s s s p e c t r a of lactones of the II type. A
c o m p a r i s o n of the m a s s s p e c t r a of I I a - c shows that a change in the nature of the substituents attached to
the silicon atom does not have a substantial effect on the fragmentation paths. The s t r u c t u r e s of the c h a r -
a e t e r i s t i c ions in the m a s s s p e c t r a of s i x - m e m b e r e d lactones I I a - c a r e p r e s e n t e d in Scheme 2, while the
m / e values and relative intensities a r e p r e s e n t e d in Table 1. In addition to the ions indicated in Table 1,
the s p e c t r u m of IIc contains monochloro f r a g m e n t s (i-C2I-I4) with m / e 81 (18%) and (j-C2H 4) with m / e 78
(2 8%), the development of which is a s s o c i a t e d with ejection of an ethylene molecule f r o m the ethyl substitu-
ent, i.e., with c o n v e r s i o n of the ethyl f o r m to the hydride f o r m . One should also note the p r e s e n c e in the
s p e c t r u m of IIc of the (M-15) + ion with m / e 163 (9%). Inasmuch as methyl substituents attached to the sili-
con atom a r e absent in this compound, while the loss of a methyl radical f r o m an ethyl substituent attached
to a silicon atom is usually not observed, the development of this ion should be explained by ring cleavage
with c o n v e r s i o n to s t r u c t u r e k (see S c h e m e 3). Ions of this type a r e probably also f o r m e d in the s p e c t r a
of Ha, b, but they are s u p e r i m p o s e d by ions a.

300
 Scheme 3
" , ~ ~ + -' C,~H.cIsIOCOEH~CN~
O - - C O " " " ~

nc ~ + k ,@- Is3(9~0)

CHo--Si--CH, CH~--SI--(Cfl~) -H(CHd~

I+- I " ~ ~ I+' I - io ~ (CH~)2SiOCO(C.I~I~)~ C H = C H :
O---CO 0 --CO

(CH3)2SIOH
.+;~, 7~ (17%)

;~=l, ,:e 227 (11%): n=Z m/e 213 (5%): n=3, ,n/e 199 (15%); n=4. m/e 185 (17~0):
1~=5 ,,!/e[71 (9%); t~=~ m/e 157 {4%}; n=7. role 143 (9%}; n=& m/e 129 (100%)

F r a g m e n t a t i o n with r i n g opening p r e v a i l s for m a e r o c y c l i c tactone t1I. Most of the f r a g m e n t tons in

the s p e c t r u m of III have s t r u c t u r e s d e s c r i b e d by general Iormula l (see Scheme 3). The s t r u c t u r e s , m / e
values, and relative intensities of the c h a r a c t e r i s t i c ions in the m a s s s p e c t r u m of HI are presented in
Scheme 3.
One should also note that the peak with m / e 2 2 7 is a composite: an ton of the Z type (n = 1) and an
(hi-Me} ~ ion, f o r m e d a~ a result of detachment of a methyl radical f r o m the silicon atom, are superimposed
The m a s s s p e c t r a were r e c o r d e d with an hiKh-1303 m a s s s p e c t r o m e t e r at 200~ and an ionizing volt-
age of 30 V.

LITERATURE CITED
1o V. F. Mironov and N, S. Fedotov, KhEm. GeterotsiM. Soedin., 179 (1967}.
2. V. F. Mironov, N. S. Fedotov, and I. G. Rybalka, Khim. Geterotsikl. soedtn., 440 (1969).
3. V. N. t~oehkarev, T, L. Krasnova, and E. A. Chernyshev, Zh. Obshch, Khim., 42, 1339 (1972).
4. V. N. Bochkarev, N. G. Komalenkova, S. A. Bashkirovu, and E. A. Chernyshev, Zh. Obshch. Khim.,
42, 2000 (1972).
5. I. Dubae, P. Mazerolles, hi. Joly, W. Kitching, C. W. Fong, and W. H, Atwell, J. Org. Chem., 34, 17
(1972).
6+ w . P. Weber, R . A . Felix, A. K. Wil[ard, and H. O. Boettger, J. Org. Chem., 36, 4060 (197B.

301
RESEARCH ON THE CHEMISTRY OF PHENOXAZINES
VII.* REACTIONS AND PROPERTIES OF RESORUFIN AND SOME
OF ITS :+DERIVATIVES

G. B. Afanas'eva, T . S. V i k t o r o v a , UDC 547.863.1 : 541.132

K. I. Pashkevich, and I. Ya. Postovskii

Resorufin (7-hydroxy-3-phenoxazinone) r e a c t s with thiophenols to give 2,8-di(arylthio)

d e r i v a t i v e s . The site of e n t r y of the nucleophilic r e s i d u e s indicates protonation of
r e s o r u f i n at the ring nitrogen atom. The changes in the absorption s p e c t r a of the a r y l -
thio d e r i v a t i v e s of r e s o r u f i n in the x~isible region as a function of the pH of the solution
a r e a s s o c i a t e d with the a c i d - b a s e dissociation of t h e s e compounds with r e s p e c t to the
hydroxyl group. The ionization constants of s o m e 2,8- and 2 , 4 , 6 , 8 - t e t r a s u b s t i t u t e d
resorufin derivatives were measured.

3-Phenoxazinone has two electrophilic c e n t e r s - one in the benzoid ring (in the p a r a position r e l a t i v e
to the nitrogen atom) and one in the quinoid ring [2]. In the p r e s e n t p a p e r we have examined the r e a c t i o n of
thioplienols with r e s o r u f i n (I), in which the position c h a r a c t e r i s t i c for nucleophilic attack in the benzoid ring
is occupied by a hydroxyl group; only the r e a c t i o n c e n t e r in the quinoid ring r e m a i n s open.
The r e a c t i o n of I with thiophenols o c c u r s only under acid c a t a l y s i s conditions, i.e., under the condi-
tion of p r i o r protonation of the r e s o r u f i n molecule.+ In this case, despite our expectations, di(arylthio)
r e s o r u f i n d e r i v a t i v e s I I - V (Table 1) r a t h e r than mono(arylthio) d e r i v a t i v e s w e r e isolated. An examination
of the r e s o n a n c e s t r u c t u r e s shows that activation of the 1 and 9 positions for nucleophilic attack can be ex-
pected when r e s o r u f i n is protonated at the exocyelie oxygen a t o m . Protonation at the ring nitrogen a t o m
will p r o m o t e r e a c t i o n at the 2, 4, 6, and 8 positions. The p r o b l e m of protonation p r e s e n t l y r e m a i n s un-
solved: thus, the addition of a proton to the earbonyl group is examined in [3, 4] (in [5] this p o s s i b i l i t y is
c o n s i d e r e d f o r the r e l a t e d 3-phenothiazone), while addition of a proton to the ring nitrogen a t o m is con-
s i d e r e d in [6, 7].

B r ~ B F ~ N ~ ] ~ BF C H 3 C 6 H 4 S ~ N ~ S C 6 H 4 G N ~
HO/'~"-/xOH HO/~x~.,.,~NO/~x~/- x~0 HO/ V "-O~ / ~ . ~

Br Br
g.ll I VIII

Br Br s S%H,CH 3
Xlll Vl VIl

*See [1] for communication VI.

S. M. K i r o v Ural Polytechnic Institute, Sverdlovsk. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h

Soedinenii, No. 3, pp. 348-353, March, 1974. Original a r t i c l e submitted D e c e m b e r 26, 1972.

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, N.Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy of this article is available from the publisher for $15.00.

302
 TABLE 1. Ar 4thio D e r i v a t i v e s of R e s o r u f i n
Corn-I mp, ~C Empirical Found, % ! Calc.,% i Yield,
pound formuta c : H N SIC H N s I~o
II 230--231 a C~HmNO~Se t 68,4 i 4,4 3[ 141 68,2 4,6 3,1 14,0 23
III 280--281 a C,24HIsNOzS2 : 67,0 3,6 3,3 14,8 6Z, l 3,5 3,3 14,8 20
IV 288--290~ C24HI~NaOTS2 ] 55,31 3,0 7,9 12,1 , 55,1 2,6 8,1 12,3 26
V 253--255 C26H15NOTS2 I - - i -- -- 12,9 i -- 12,5 25
VII 205--207 c C4oH31NO3S4 e 68,4 i 4,5 -- 18,3 i68,2 4,5 18,1 50
VIII 220--221 d C26HITBreNOsS2 50,0 2,8 -- 50,6 i 50,6 2,8 10,5 90
IX 201--202 a C2sH2~NO~S~g 69,3 i 4,8 - 113,0
- 169,3 4,8 13,2 30
XI 951~252~ Ca2HsBr *39,2 '. 1,5 4,0{ - - '38,9 114 ~,8 35
XIII 249--250P C~IHI~NO3S 69 2 i 4,7 - - ; 8,8 169,5 4.8 9~ 82
XVI 263---265]. C~Hz3NO3S2 I 69:2 ! 4,8 - - 113,1 !69,5 4,8 -- 13,2 89

Note: aFrom isoamyl alcohol, bFrom 80% alcohol. CFrom n-butyl

alcohol, dFrom n-butyl alcohol-isoamyl alcohol (I : i). eFound:
Br 25.5%. Calculated: Br 26.0%. fFrom dimethyl formamide.
gFound: Br 43.3%. Calculated: Br 43.1%. hFrom benzene or ethanol.
iFrom ethanol.

C'I0 -4 In the p r e s e n t paper, the position of the two

arylthio r e s i d u e s in the r e s o r u f i n d e r i v a t i v e s was
6'81 6" e s t a b l i s h e d by a s e r i e s of r e a c t i o n s , and the site of
protonation of I during the d e s c r i b e d r e a c t i o n w a s
5
thereby determined.
5,1
4 It is known [1] that the b r o m i n e a t o m in b r o m o -
phenoxazinones is only slightly labile and does not
undergo nucleophilic substitution. P r o c e e d i n g f r o m
3~4
this, one might have expected that the r e a c t i o n of
2 , 4 , 6 , 8 - t e t r a b r o m o - 7 - h y d r o x y - 3 - p h e n o x a z i n o n e (VI)
[8] with t h i o c r e s o l would give 1,9-di(tolylthio)-2,4,6,8-
117 t e t r a b r o m o r e s o r u f i n in the c a s e of protonation of the
m o l e c u l e at the oxygen a t o m of the c a r b o n y l group.
However, it was e s t a b l i s h e d that all of the b r o m i n e
a t o m s in t e t r a b r o m i d e VI a r e r e a d i l y exchanged by
420 500 600 7 ~ ~,rlm arylthio r e s i d u e s to give 2,4,6,8-tetra(tolylthio)-
r e s o r u f i n (VII). The b r o m i n a t i o n of II leads to di-
Fig. 1. Absorption s p e c t r a of alcohol solutions
b r o m o d e r i v a t i v e VIII, the r e p l a c e m e n t of the b r o m i n e
of II (1-6, c 10 -4 M, l a y e r t h i c k n e s s 5 mm):
a t o m s in which by arylthio groups gives a compound
15 pH 2.50; 25 pH 3.10; 3) pH 4.10; 45 pH 5.00; 55
that i s c o m p l e t e l y identical to VII. This excludes a c -
pH 5.95; 6) pH 7.10; 7) IX (e 5 910 -5 M, l a y e r
tivation of the 1 and 9 positions during the r e a c t i o n .
t h i c k n e s s 5 ram).
An additional confirmation is the f o r m a t i o n of di(tolyl-
thio) d e r i v a t i v e IX during the r e a c t i o n of 1 , 9 - d i m e t h y l -
r e s o r u f i n with t h i o c r e s o l .
F o r the definitive e s t a b l i s h m e n t of the s t r u c t u r e of di(tolylthio)resorufin II and, consequently, other
di(arylthio) d e r i v a t i v e s , one of the p o s s i b l e i s o m e r s - 2 , 8 - d i ( t o l y l t h i o ) - 7 - h y d r o x y - 3 - p h e n o x a z i n o n e - was
obtained by independent s y n t h e s i s . 2 , 4 - D i h y d r o x y b r o m o b e n z e n e (X) r e a c t s with sodium nitrite in acidic
m e d i a (a known method f o r the p r e p a r a t i o n of r e s o r u f i n f r o m r e s o r c i n o l [9]) to give 2 , 8 - d i b r o m o r e s o r u f i n
(XI) (35% yield), which has a known orientation of the b r o m i n e a t o m s . On heating with t h i o c r e s o l , the b r o m -
ine a t o m s in this compound a r e s m o o t h l y exchanged by arylthio r e s i d u e s to give 2 , 8 - d i ( t o l y l t h i o ) - 7 - h y d r o x y -
3-phenoxazinone, which is identical to II obtained d i r e c t l y f r o m r e s o r u f i n (see the above s c h e m e ) . Thus
the addition of thiophenols to resortifin p r o c e e d s at the 2 and 8 positions, and this in t u r n is evidence f o r
protonation at the ring nitrogen a t o m .
The e n t r y of two thiophenol r e s i d u e s into the r e s o r u f i n m o l e c u l e is p r o b a b l y a s s o c i a t e d with the p o s -
sibility of quinoidization of the benzoid ring, i n a s m u c h as only one thiophenol m o l e c u l e is added in the 2
position (in analogy with 3-phenoxazinone) in the c a s e of 7 - e t h o x y - 3 - p h e n o x a z i n o n e (XII).
Like phenoxazinones [10], H-IV, VI-VIII, and XI have two c h a r a c t e r i s t i c a b s o r p t i o n bands in the n e a r
UV region (210-220 and 230-245 nm), the p r e s e n c e and position of which a r e independent of the pH of the

303
 TABLE 2. Spectra and pK a Values of Resorufin Derivatives (50%
alcohol, 20~

Corn- krnax of the non-I kmax of the

', ionizedform, 9l g E P/<a
pound ionizednrnform, 1 , nm

I 481 3,78 576 5,14 6,85-0.03

ti 505 4,41 626 5,17 5,78-+0.03
Ill 494 3,98 624 5,21 5,75
IV 488 4,50 600 4,95 4,88
\'Ill 505 4,33 640 5,22 4.86_+0,02
XI 495 4,40 595 5,C6 4,38
VII 488 4,30 634 4,83 3,41
VI 492 4,36 @6 4,98 2,16

solution. These compounds have two m a x i m a in the visible region, the position and intensity of which de-
pend on the pH of the solution; this is, in all likelihood, a s s o c i a t e d with a c i d - b a s e dissociation with r e s p e c t
to a hydroxyl group of the phenol type. T h e r e is only a long-wave band (620-650 nm) in the s p e c t r a at
pH > 5 f o r II-IV and at pH > 3.5 f o r VI-VIII and XI, while t h e r e is only a short-wave band (482-506 nm) in the
s p e c t r a f o r II-IV at pH < 4 for VI-VIII and XI at pH < 2. Both of the indicated bands are o b s e r v e d in the s p e c -
t r a of all of the compounds at intermediate pH values.
If the assumption of a c i d - b a s e dissociation is c o r r e c t , the long-wave absorption maximum that ap-
p e a r s in the m o r e alkaline region is related to the absorption of a s y m m e t r i c a l anion, while the s h o r t - w a v e
absorption maximum that is observed in more acidic solutions is related to the absorption of the undisso-
ciated f o r m of the dye.
T o confirm this, we synthesized 2,8-di(tolylthio)resorufin ethyl ether (XV1) through the sodium (XIV)
and silver (XV) salts of II and subjected it to s p e c t r o s c o p i c investigation. The position of the absorption
maximum of an alcohol solution of XVI is independent of the pH of the solution (it r e m a i n s constant at ~ 500
nm) and is close to the position of the s h o r t - w a v e maximum of an aqueous alcohol solution of II (Fig. 15.
Inasmuch as XVI is incapable of a c i d - b a s e dissociation and exists only in the undissociated form, the s h o r t -
wave absorption maximum of II (and of III, IV, v I - v I I I , and XI) should be related to the absorption of a s y m -
m e t r i c a l anion. Thus the change in the s p e c t r a of solutions of the investigated Compounds as the pH in-
c r e a s e s is due to splitting out of the proton of the hydroxyl group.
To determine the effect of the nature of the substituents in the 2, 4, 6, and 8 positions of r e s o r u f i n on
the strengths of the investigated acids, we studied the ionization constants (PKa) of II-IV, VI-VIII, and XI
by the speetrophotometric method in [11]. The weakest acid is unsubstituted r e s o r u f i n (I, pK a 6.85, Table
25. The introduction of both bromine atoms and arylthio residues leads to an i n c r e a s e in the acid ionization
as c o m p a r e d with resorufin, i.e., the arylthio residues, like bromine atoms, display e l e c t r o n - a e c e p t o r p r o p -
e r t i e s with r e s p e c t to resorufin.
The higher acidity of IV in the 2,8-disubstituted resorufin s e r i e s is a s s o c i a t e d with the strong e l e c -
t r o n - a c c e p t o r effect of b r o m i n e atoms; the e l e e t r o n - a c c e p t o r effect of the arylthio residues is exerted to
a l e s s e r extent.
The value of the ionization constants of 2,8-di(arylthio) r e s o r u f i n derivatives is in good a g r e e m e n t
with the d o n o r - acceptor p r o p e r t i e s of substitutents in the p a r a position of the arylthio group. The i n t r o -
duction of a nitro group into the p a r a position relative to the thio group r e i n f o r c e s the e l e c t r o n - a c c e p t o r
effect of the arylthio residue and leads to an i n c r e a s e in the ionization of the IV molecule as c o m p a r e d with
III; the e l e c t r o n - d o n o r methyl group (ID induces only a slight r e v e r s e effect.
Bromine atoms have the g r e a t e s t effect on the pK a values in the investigated 2,4,6,8-tetrasubsituted
r e s o r u f i n derivatives and in 2,8-disubstituted r e s o r u f i n derivatives. Thus, for example, t e t r a b r o m o r e s o r u -
fin (VI, pK a 2.16, Table 25 is a strong acid, while the effect of the arylthio r e s i d u e s is less significant in the
case of the tetrasubstituted derivatives.

EXPERIMENTAL

The electronic spectra of If-IV, VI-VIII, and XI were obtained with an SF-10 spectrophotometer. So-
lutions of II, III, VI-VIII, and XI (1 9 10 -4 M in 96% ethanol5 and of IV (3 9 10 -5 M in 96% ethanol) were pre-
pared for the speetrophotometric measurements.
- The ionization constants were measured in 50% ethanol with anSF-4 spectrophotometer. Ammonia-ace-
tate buffers were used as buffer solutions. The starting solution for VI was a 0oi N solution in hydroehloric acid.

304
 2,8-Di(p-tolylthio)resorufin (II). A) A 0.8 g (0.006 mole) sample of p - t h i o e r e s o l and a few drops of
c o n c e n t r a t e d h y d r o c h l o r i c acid w e r e added to 1 g (0.005 mole) of r e s o r u f i n in 20 ml of ethanol. The teuco
compound began to f o r m gradually, and the solution b e c a m e green. In o r d e r to oxidize the leuco compound
to dithio derivative II, the mixture was allowed to stand in the air at room t e m p e r a t u r e for 3 days with p e r i -
odic s t i r r i n g . The m i x t u r e b e c a m e brown, and the c r y s t a l s were r e m o v e d by filtration and washed with
alcohol to give 0.3 g of II (Table 1) :
B) A total of 0.5 g (40%) of dithio derivative II was s i m i l a r l y obtained f r o m 1 g (0.003 mole) of di-
b r o m o r e s o r u f i n XI and 0.9 g (0.007 mole) of p - t h i o c r e s o l .
2,8-Di(phenylthio)resorufin (III), 2,8-Di(p-nitrophenylthio)resorufin (IV), and 2,8-Di(o-carboxyphenyl-
thio)resorufin (V). These compounds were s i m i l a r l y obtained by method A (Table 1).
2 , 4 , 6 , 8 - T e t r a ( t o l y l t h i o ) r e s o r u f i n (VII, Table 1). A) A 0.5 g (0.004 mole) sample of p - t h i o c r e s o l was
added gradually with s t i r r i n g and heating to 40-50 ~ to 0.5 g (0.001 mole) of t e t r a b r o m o derivative VI in 200
m l of alcohol containing 10 drops of concentrated h y d r o c h l o r i c acid. The mixture was h e a t e d at 50 ~ f o r an-
other 2.5 h, after which it was heated to the boiling point and then allowed to stand at r o o m t e m p e r a t u r e f o r
8 h. The p r e c i p i t a t e d c r y s t a l s were r e m o v e d by filtration and washed with alcohol to give 0.3 g of VII.
B) A total of 0.55 g of VII was s i m i l a r l y obtained f r o m 0.5 g (0.0009 mole) of VIII and 0.3 g (0.0025
mole) of p - t h i o c r e s o l .
2 , 8 - D i ( t o l y l t h i o ) - 4 , 6 - d i b r o m o r e s o r u f i n ( v i m . A 0.2 g (0.005 mole) sample of finely ground di(totyl-
thio)resorufin II was added to a solution of sodium ethoxide (0.3 g of sodium in 20 ml of alcohol), and the
mixture was s t t r r e d a t room t e m p e r a t u r e for 20 min. The precipitate was then r e m o v e d by filtration and
washed with alcohol. A total of 1 ml of bromine was added gradually with s t i r r i n g to the thus obtained s o -
dium salt of II in 15 ml of alcohol, a f t e r which the mixture was refluxed for 20 min and cooled. The p r e -
cipitated r e d - b r o w n c r y s t a l s w e r e r e m o v e d by filtration and washed with alcohol and ether to give 0.25 g
of VIII (Table 1).
1 , 9 - D i m e t h y l - 2 , 8 - d i ( p - t o l y l t h i o ) r e s o r u f i n (IX, Table 1). This compound was obtained, by the method
used to p r e p a r e tolylthio derivative II, f r o m 0.5 g (0.002 mole) of 1 , 9 - d i m e t h y l r e s o r u f i n [12] and 0.5 g (0.004
mole} of p - t h i o c r e s o l . The yield was 0.3 g.
2 , 8 - D i b r o m o r e s o r u f i n (XI, Table 1). An 11 g (0.058 mole) sample of 2,4-dihydroxybromobenzene [13]
was added in portions with s t i r r i n g at a mixture t e m p e r a t u r e of no higher than 60 ~ to a solution of 11 g (0.16
mole} of sodium nitrite in 70 ml of concentrated sulfuric acid. The mixture was held at 95-100 ~ for 4 h and
then poured into 0.5 liter of water. The precipitate was r e m o v e d by filtration and washed with water to neu-
t r a l i t y to give 4 g of XI.
2 - T o l y l t h l o - 7 - e t h o x y - 3 - p h e n o x a z i n o n e (XIII, Table 1). A 0.4 g (0.003 mole) sample of p - t h i o c r e s o l
and four drops of concentrated h y d r o c h l o r i c acid were added to a suspension of 0.5 g (0.0025 mole) of 7-
ethoxy-3-phenoxazinone (XID [14] in 15 ml of alcohol, and the mixture was s t i r r e d at room t e m p e r a t u r e un-
til phenoxazinone XII had dissolved completely and the solution color had changed to light-green. It was
then held at r o o m t e m p e r a t u r e for 1 h, after which 10 ml of a f r e s h l y p r e p a r e d 10% solution of f e r r i c chlo-
ride was added, and the mixture was s t i r r e d . The resulting c r y s t a l s were r e m o v e d by filtration, washed
with alcohol and ether, and dried to give 0.5 g of XIII.
2,8-Di(tolylthio)resorufin Sodium Salt (X-IV). A 0.5 g (0.001 mole} sample of II was added to a solu-
tion of sodium ethoxide (from 20 ml of alcohol and 0.2 g of sodium), and the suspension was s t i r r e d at room
t e m p e r a t u r e for 1.5 h. The g r e e n p r e c i p i t a t e was r e m o v e d by filtration and washed repeatedly with alcohol.
The yield was quantitative. Found: S 13.2%. C26H18NO3S2Na. Calculated: S 13.3%.
2,8-Di(tolylthio)resorufin Silver Salt (XV). A 0.2 g sample of s i l v e r n i t r a t e was added to a solution
of 0.5 g (0.001 mole) of sodium salt XIV in 0.3 liter of w a t e r . The flocculent brown precipitate was r e m o v e d
by filtration, washed with alcohol, and dried.
2,8-Di(tolylthio)-7-ethoxy-3-phenoxazinone (XVI, Table 1). A 0.7 ml sample of ethyl iodide was added
to a suspension of 0.4 g (0.007 mole) of s i l v e r salt XV in 10 ml of alcohol, and the r -'xture was refluxed for
1 h. The hot reaction m i x t u r e was filtered, and the precipitated s i l v e r iodide was washed on the filter with
hot alcohol. The filtrate was cooled, and the precipitate was r e m o v e d by filtration, dried, and purified with
a column filled with A1203 (elution with anhydrous c h l o r o f o r m ) . The orange fraction was evaporated to
give 0.23 g (80%) of XVI.

305
 LITERATURE CITED
1. G. B. Afanas'eva, K. I. Pashkevich, and I. Ya. Postovskii, Khim. Geterotsikl. Soedin., 1246 (1973}.
2. G. B. Afanas'eva, K. I. Pashkevich, I. Ya. Postovskii, V. G. Vykhristyuk, N. P. Shimanskaya, and
V. D. Bezuglyi, Khim. Geterotsikl. Soedin., 1344 (1972}.
3. V. Simanek, J. Lasovsky, V. Stuzka, and L. ttruban, Coll. Czech. Chem. Commun., 35, 3064 (1970}.
4o ~G. :B. Afanas'eva and I. Ya. Postovskii, Zh. Obshch. Khim., 34, 3041 (1964}.
5. C. Bodea and J. Silberg, Adv. Heterocycl. Chem., 9, 321 (1968).
6. H. Musso and H. Matties, Bet., 90, 1914 (1957).
7. D. P. Sevbo and o . G. Ginzburg, Zh. Organ. Khim., 6, 345 (1970}.
. P. Weselsky, Ber., 4, 613 (1871).
9. H. Eichler, J. Prakt. Chem., 139, 113 (1934).
10. W. Schafer, Progr. Org. Chem., 6, 135 (1964).
11. A. Albert and E. Serjeant, Ionization Constants of Acids and Bases, Methuen (1962).
12. R. Nietzky and H. Mackler, Bet., 23, 720 (1890).
13. Organic Syntheses, Vol. 2, Wiley.
14. E. .Ruzicka and J. Jurina, Monatsh., 97, 129 (1966).

306
SYNTHESIS OF SUBSTITUTED 2-AMINO-5,6-DIHYDRO-

4H-1,3-OXAZINES AND 2-IMINOTETRAHYDRO-1,3-OXAZINES

L. A. Ignatova, A. E. Gekhman, UDC 547.867.07

P. L. Ovechkin, a n d B . V. U n k o v s k i i

3 , 4 , 4 , 6 - T e t r a m e t h y l - 2 - a r y l i m i n o t e t r a h y d r o - l , 3 - o x a z i n e s were synthesized by i n t r a m o l e e u -
l a r cyclization of N - a r y l - N ' - m e t h y l - N ' - ( 2 - m e t h y l - 4 - h y d r o x y - 2 - p e n t y l ) - S - m e t h y l i s o t h i o -
u r e a s . 4 , 4 , 6 - T r i m e t h y l - 2 - ( N - m e t h y l - N - a r y l a m i n o ) - 5 , 6 - d i h y d r o - 4 H - 1 , 3 - o x a z i n e s were ob-
tained by methylation of 4 , 4 , 6 - t r i m e t h y l - 2 - a r y l a m i n o - 5 , 6 - d i h y d r o - 4 H - 1 , 3 - o x a z i n e s .

In our p r e c e d i n g communication [1] we d e s c r i b e d the synthesis of 4 , 4 , 6 - t r i m e t h y l - 2 - a l k y l ( a r y l ) a m i n o -

5 , 6 - d i h y d r o - 4 H - 1 , 3 - o x a z i n e s (D that a r e capable of existing in two t a u t o m e r i c f o r m s - amino f o r m IA and
imino f o r m IB. In o r d e r to study the amino f o r m - i m i n o f o r m t a u t o m e r i s m IA ~ I B , we synthesized model
oxazines that have fixed imino and amino s t r u c t u r e s .
We synthesized the imino-form models - 3 , 4 , 4 , 6 - t e t r a m e t h y l - 2 - a r y l i m i n o t e t r a h y d r o - l , 3 - o x a z i n e s
(V) - f r o m 2 - m e t h y l a m i n o - 2 - m e t h y l - 4 - p e n t a n o l (II). N - A r y l - N ' - m e t h y l - N ' - ( 2 - m e t h y l - 4 - h y d r o x y - 2 - p e n t y l ) -

c.3x./N.c/C"~ c.~.....I H(c.~ .., CH3\//.-... ~/C H3 _ CH3~/"~/CH3

cga/T x"N-OH OH ~ CH/I I
CH,INH H CHa/N~SCH3 CH3/N"~
I
II N
/N /\
N N~C6H4R
H C6H4R H C6H4R V
I-
III W

t h i o u r e a s (lID w e r e obtained by the reaction of amino alcohol II with substituted a r y l isothioeyanates in

e t h e r . In c o n t r a s t to N - a r y l - N ' - ( 2 - m e t h y l - 4 - h y d r o x y - 2 - p e n t y l ) t h i o u r e a s [1], III a r e unstable and decompose
even during t h e i r p r e p a r a t i o n and also on s t o r a g e and r e c r y s t a l l i z a t i o n to give aryl isothiocyanates, amino
alcohol iX, and other decomposition products. The r e a s o n for the lability of thioureas III is apparently the
s t e r t c interaction of the methyl groups attached to the nitrogen atom and the s - c a r b o n atom, inasmuch as
N - p h e n y l - N , N ' - d i m e t h y l t h i o u r e a , which is a simple model of thioureas III and which we obtained under
s i m i l a r conditions in 40% yield, has high stability on prolonged s t o r a g e and heating in various solvents at
50-80~

T A B L E 1. 3 , 4 , 4 , 6 - T e t r a m e t h y l - 2 - a r y l i m i n o t e t r a h y d r o - l , 3 - o x a z i n e s
(va-f)
Corn- :rap, ~ i gmpiri c al" Found, % i Calc.,~o Yield,
pound R i(from iformula i- ~o
ihexane) i C H N i C H N

\'a i
! p-OC2Hs 79.5--80 C~6H24N202 69,5 8,7 10,0 69,5 8,7 10,1 68
Vb ! p-CH3 99,5--100 C=~H2eN20 73,5 8,8 11,4 73,1 9,0 11,4 72
VC , m-CHa . 41--42 CIsH22N20 73,2 8,7 11,7 73,1 9,0 11,4 61
Vd rH 59,5--60 C~4H20N20 72,2 8,6 t2,4 72,4 8,7 12.l 73
Ve i p-Br 67--68 C~4H~gBrN~O 54,0 5,9 9,0 54,0 6,1 9,0 65
Ve ! m-Cl 78--79 ,!C14HIgC1N20
E
62,8 7,3 10,0 63,0 7,2 10,5 70

M. V. Lomonosov Moscow Institute of Fine Chemical Technology. T r a n s l a t e d f r o m Khimiya Geterot-

siklicheskikh Soedinenii; No. 3, pp. 354-356, March, 1974. Original a r t i c l e submitted M a r c h 2, 1973,

9 19 75 Plenum Publishing Corporation, 22 7 West 1 7th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher~ A copy of this article is available from the publisher for $15.00.

307
 TABLE 2. 4 , 4 , 6 - T r i m e t h y l - 2 - ( N - m e t h y l - N - a r y l a m i n o ) - 5 , 6 -
d i h y d r o - 4 H - 1 , 3 - o x a z i n e s (viIa-g)
i
Corn- I ;:rap, ~ Empirical Found,% Calc.. qo Yield,
I l(from formula
pound i r fiexane) N C H
C H N

VII a
vIIb
i! p-OCH3 1 47--47,5
p-OC~tls i 56,5--57
C15H22N~O2
Q6H24N202
68,6
69,4
8,4
8,6
11,0
10,3
68,7 8,4
69,5 8,7
10,7
10,1
91
94
VII c I p-CH3 65.5--66 CIsH~N20 73,8 9,0 11,5 73,1 9,0 11,4 90
vlld ,n-CH3 27--28 CIsH2~N20 73,3 &8 12,0 73,1 9,0 11,4 85
VII e /H 43--43,5 CI4H20N~O 72,1 8,7 125 72,4 8,7 12,1 96
Vllf Ip-Br 61,5--62 Ct4HIgBrN20 53,9
62,7
6,3
7,2
9.0 54,0 6,1 9,0 87
Im-Ct
Vt I g 163.5-- 165* CI4HmC1N20 I0,6 63,0 7,2 t0,5 82
*This is the melting point (with decom ~osition) of the hydriodide.

Thioureas III were methylated with excess methyl iodide immediately after isolation f r o m the r e a c -
tion mixtures. Methylation in acetone o r alcohol is accompanied by profound destruction of the starting III
and the methylation products. The resulting S - m e t h y l - N - a r y l - N ' - m e t h y l - N ' - ( 2 - m e t h y l - 4 - h y d r o x y - 2 - p e n t y l ) -
isothiourea hydriodides (IV) a r e also e x t r e m e l y labile, and their subsequent t r a n s f o r m a t i o n s were t h e r e -
f o r e accomplished without isolation and purification; IV a r e cyclized, with the liberation of methyl m e r -
captan, to iminooxazines V (Table 1) on reaction with 3 N alcoholic alkali solution.
We synthesized 4 , 4 , 6 - t r i m e t h y l - 2 - ( N - m e t h y l - N - a r y l a m i n o ) - 5 , 6 - d i h y d r o - 4 H - 1 , 3 - o x a z i n e s (VII), which
have a fixed amino s t r u c t u r e , by methylation of the corresponding oxazines (I) with methyl iodide in a c e t o n e .

C H 3 ~ " " ' ~ Ell3 CH3"~'''",~CH3 H CH3\ ~ .CH.

c'Ha" N ~ , O I } ~ HNvO
j <
HN~O
Y ~ . ~o ., -
H
23_tn~..,'OI
[I tl
N N N N
x/',r
. \r /~
CH3 R /NR
CH~
1A IB VI VII

The p r e s e n c e of two nucleophilic reaction centers - the endocyclic and exocyclic nitrogen atoms - in
I p r e s u p p o s e s the possibility of methylation via two directions; this is confirmed by the literature data on
the alkylation of h e t e r o c y c l i c s y s t e m s that contain an amidine f r a g m e n t . Thus, it is known that 2 - a m i n o -
quinazolines [2], 2-aminobenzothiazoles [3, 4], and 2-amtnothiazolines [5] a r e alkylated at the ring nitrogen
atom. The alkylation of 2 - a c y l a m i n o - l , 3 , 4 - o x a d i a z o l e s [6] and 2 - a r y l a m i n o - i m i d a z o l i n e s [7] p r o c e e d s at
the exocyclic nitrogen atom. There is no doubt that the direction of alkylation depends on the c h a r a c t e r of
the alkylating agent, the nature of the heterocycle, etc.
We have shown that methylation of aminooxazines IA ~-~IB p r o c e e d s at the exocyclic nitrogen atom to
give 4 , 4 , 6 - t r i m e t h y l - 2 - ( N - m e t h y l - N - a r y l a m i n o ) - 5 , 6 - d i h y d r o - 4 H - 1 , 3 - o x a z i n e hydriodides (VI) in almost
quantitative yields. Salts VI a r e converted to the c o r r e s p o n d i n g bases on t r e a t m e n t with aqueous p o t a s s i u m
carbonate solutions (Table 2). A p r o o f of the methylation of I at the exocyclic nitrogen atom is the differ-
ence in the p h y s i e o c h e m i c a l c h a r a c t e r i s t i c s of VII and IV, the s t r u c t u r e s of which a r e determined unam-
biguously by the methods used for their s y n t h e s i s .
Bands at 1610-1625 cm -~, which a r e related to the stretching vibrations of the exoeyclic C =N bond,
a r e observed in the IR s p e c t r a of the c r y s t a l l i n e iminooxazines V. The v C=N ring bands are observed at
1645-1650 e m , 1 in the IR s p e c t r a of Amino f o r m s VII. Substantial differences are also observed in the PMR
s p e c t r a of V and VII. The s p e c t r a l c h a r a c t e r i s t i c s of the synthesized model compounds will be examined
in detail in a discussion of the amino-imino t a u t o m e r i s m of aminooxazinones I.

EXPERIMENTAL

N - P h e n y l - N ' - m e t h y l - N ' - ( 2 - m e t h y l - 4 - h y d r o x y - 2 - p e n t y l ) t h i o u r e a (IIId, R =H). A 3.1 g (0.023 mole)

sample of phenyl isothiocyanate was added to a soltr~ion of 3.0 g (0.023 mole) of amino alcohol II in 10 ml
of d r y ether. The precipitate that f o r m e d after 2 h was r e m o v e d by filtration to give 5.3 g (87%7 of thiourea
IIId with mp 78-79 ~ Found: N 10.5; S 12.0%. C14H22N20S. Calculated: N 10.5; S 12.1%. A s i m i l a r method
was used to obtain IIIa-e, e, f, which were converted to iminooxazines V without additional purification.
3 , 4 , 4 , 6 - T e t r a m e t h y l - 2 - p h e n y l i m i n o t e t r a h y d r o - l , 3 - o x a z i n e (Vd). A solution of 5.0 g (0.019 mole) of
t h i o u r e a Hid in 10 ml of methyl iodide was allowed to stand at 20 ~ for 2-3 h. The e x c e s s methyl iodide was

308
then r e m o v e d b y distillation, and the r e s i d u a l IVd was t r e a t e d with 30 m l of a 3 N solution of KOH i n m e t h -
anol at 20 ~ After 4 h, the methanol was r e m o v e d b y distillation, and the residue was e x t r a c t e d with boiling
hexane; the hexane was r e m o v e d by distillation to give 2.9 g of iminooxazine Vd. Compounds Va-c, e, f
(Table 1) w e r e obtained by a s i m i l a r method.
4 , 4 , 6 - T r i m e t h y l - 2 - ( N - m e t h y l a n i l i n o ) - 5 , 6 - d i h y d r o - 4 H - 1 , 3 - o x a z i n e (VIIe). A 3.9 g (0.028 mole) s a m p l e
of m e t h y l iodide was added to 3.2 g (0.014 mole) of 4 , 4 , 6 - t r h n e t h y l - 2 - a n i l i n o - 5 , 6 - d i h y d r o - 4 H - 1 , 3 - o x a z i n e
(Ie) in 10 ml of acetone, and the m i x t u r e was allowed to stand at 20 ~ for 30 h. Absolute e t h e r (20 ml) was
added, and the p r e c i p i t a t e d c r y s t a l s w e r e r e m o v e d by filtration and dried to give 4.9 g (96~5 of Vie. The
product was d i s s o l v e d in 50 m l of water, and the solution was n e u t r a l i z e d with a s a t u r a t e d p o t a s s i u m c a r b -
onate solution. The organic portion was e x t r a c t e d with ether, and the e x t r a c t was dried with m a g n e s i u m
sulfate. The e t h e r was r e m o v e d by distillation, and the r e s i d u e was e h r o m a t o g r a p h e d on aluminum oxide
[ e t h e r - h e x a n e (1 : 1)]. The eluent was r e m o v e d by distillation to give 3.0 g of aminooxazine ViIe. A s i m i l a r
method was used to obtain VIIa-d, f (Table 25.

LITERATURE CITED

1. L. A. Ignatova, P. L. Ovechkin, M. Z. B r a n z b u r g , A. E. Gekhman, and B. V. Unkovskii, Khim. G e t e r o t -

sikl. Soedin., 1037 (19725.
2. D. Brown and B. England, A u s t r a l . J. Chem., 2._!, 2813 (1968).
3. Mo Conte, R. Guglielmetti, and J. M e t z g e r , Bull. Soc. Chim. France, 2834 (1967).
4. N. P. G r i n ' , A. N. K r a s o v s k i i , and P. M. Kochergin, Khim. G e t e r o t s i k l . Soedin., 1271 (19725.
5: E. M. P e r e s t e n i , Yu. N. Sheinker, N. P. Z o s i m o v a , and Yu. I. P o m e r a n t s e v , Zh. Fiz. Khim., 3._3 2713
(19635.
6, G. Heinz and M. Just, Ann., 703, 136 (1967).
7. H. Shahle and K. Pook, Ann~ 751, 159 (19715.

309
SYNTHESIS OF S U B S T I T U T E D
2 - A M I N O - 5 , 6 - D I H Y D R O - 4 H -1 , 3 - THIA ZINES
AND 2 - I M I N O T E TRAHYDRO- 1 , 3 - T H I A Z I N E S

P. L. O v e c h k i n , L. A. I g n a t o v a , UDC 547.869.07
A. E. G e k h m a n , and B. V. U n k o v s k i i

N-Aryl-N'-(2-methyl-4-hydroxy-2-pentyl)thioureas are cyclized in acidic media to 4,4,6-

trimethyl-2-arylimino-5,6-dihydro-4H-1,3-thiazines, the methylation of which with methyl
iodide gives 4,4,6-trimethyl-2-methylarylamino-5,6-dihydro-4H-1,3-thiazines. 3,4,4,6-
Tetramethyl-2-aryliminotetrahydro-l,3-thiazines were synthesized by cyclization of N-
aryl-N'-methyl-N'-(2-methyl-4-hydroxy-2-pentyl)thioureas.

2-Amino-5,6-dihydro-4H-1,3-thiazines are known compounds (for example, see [1-4]), but data on
the structure and tautomerism of these compounds are scanty and contradictory [1, 3].
In the present communication we describe the synthesis of 4,4,6-trimethyl-2-arylamino-5,6-dihydro-
4H-1,3-thiazines (IV), which was realized via the scheme in [2].

CH
3.3~/.... /C% H ~+ CHs\J',/~C./ C H s CH3\/""%/CHs OH- CH3~/'~CHs (R=H) CH3\/~"'/CH3

N N N N N
H/ \ CsH4X
9
H/ \ C6H~X H/ \ C6H4X \c6n4x
H/ \ C6H4X
I.V II, VI Ill,VII IVB VIII IVA

I-IV R=H; V-VIII R=CH S

N-Aryl-N'-(2-methyl-4-hydroxy-2-pentyl)thioureas (I) [5] are protonated at the sulfur atom in a sat-

urated alcohol solution of hydrogen chloride to give isothiourea cations (ID; this is attested to by the hypso-
chromic shift (by 40 nm) of the maximum of the absorption band in the UV spectra of I in 4 N HCI in meth-
anol as compared with the maximum of the absorption band in the UV spectra of I in methanol (~max 254
urn). This sort of shift of the maximum of the absorption band in acidic media is characteristic for the S-
protonated forms of compounds that contain a thioamide group [6, 7].
At high temperatures cations H are cyclized as a result of nuc]eophilic attack by the sulfur atom on
the carbinol carbon atom to give aminothiazine Salts III, which were converted to the bases of the corre-
sponding aminothiazines (IV, Table 1) as a result of treatment with saturated potassium carbonate solution.
In order to study the amino-imino tautomerism possible for IV, we also synthesized the correspond-
ing model compounds with fixed imino and amino structures. The starting compounds for the synthesis of
the imino models -3,4,4,6-tetramethyl-2-aryliminotetrahydro-l,3-thiazines(VIII)- w e r e N-aryl-N'-
mefhyl-N'-(2-methyl-4-hydroxy-2-pentyl)thioureas (V), which were cyclized in concentrated hydrochloric
acid through intermediate cations VI to 3,4,4,6-tetramethyl-2-aryliminotetrahydro-l,3-thiazinehydro-
chlorides (VID, from which bases VIII were isolated by the usual method.
The lability of N,N',N'-trisubstituted thioureas V, which we have previously noted [8], increases in
acidic media: aromatic amines, arylthioureas, and other unidentified products of the destruction of thio-

M. V. Lomonosov Moscow Institute of Fine Chemical Technology. Translated from Khimiya Geterot-
siklicheskikh Soedinenii, No. 3, pp. 357-359, March, 1974. Original article submitted March 9, 1973.

9 19 75 Plenum Publishing Corporation, 22 7 West 1 7th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available [rom the publisher for $15.00.

310
 T A B L E i. 4 , 4 , 6 - T r i i n e t h y l - 2 - a r y l a m i n o - 5 , 6 - d i h y d r o - 4 H - 1 , 3 -
thiazines (IVa-f)

Corn- i rap, ~ Empirical Found, % Calc.. % Yield,

pound : x (from formula qo
'~ 'alcohol) N S N S

IVa p-OCHa 177--178 C 14H2oNaOS 10.5 11.8 10.5 12,1 94

IVb p-CHa 147--1,48 C,~H~oNzS 11,2 12.6 11,3 12.9 96
IV c m-CHz i 117--117,5 CI4H2oN2S 11.2 12,7 I1,3 12,9 92
I\rd H , 150---151 ClaHlaNzS 12,1 13,5 12,0 13.7 90
IVe p-Br ! 185--186 CI3HITBrNeS 8,7 10,0 8.9 10~2 87
IVf i m-Ct 137--138 C~H~TCINeS 10,2 ti,8 10.4 11.9 85

TABLE 2. 4,4,6-Trimethyl-2-methylarylamino-5,6-dihydro-4H-
1,3-thiazines (Xa-f)
Con]- ! Empirical Found, % Calc., ~o Yield,
i
x rap, ~
pound i formula r i

C ]HI'I N 5 C ill' N S i

Xa ! p-OCH3 55--56 ClsH22NzOS 64,6~7,8 -- ll,5 64.718,0~ _I 11.5 91

Xb i p-CH3 43~44 CI~H~zN~S 68,5 8,5 10,5 -- 68,7]8,5 I0,7i - - i 93
Xc ! m-CHa 53--54 CIsH22N2S 68,6 8,4 -- 12,1 68,718,5; -- i 12,2 92
Xd In 105--106 CI4H~oNzS l l , 2 12,8 11,3:lZ,91
Xe I p-Br 81--81,5 CI4HmBrN2S 8.4 9,6 ~ - - ' 8,6 9,8 93
xf i m-Cl 31--32 C~4HmCIN2S 10,1 1t,0 9,9 11,3 95

u r e a s V w e r e d e t e c t e d in t h e r e a c t i o n m i x t u r e . F o r t h i s r e a s o n , t h e y i e l d s of i m i n o t h i a z i n e s VIII are sub-

s t a n t i a l l y l o w e r t h a n t h e y i e l d s o f t h e c o r r e s p o n d i n g IV.

Model compounds with a fixed amino structure -4,4,6-trimethyl-2-methylarylainino-5,6-dihydro-

4 H - 1 , 3 - t h i a z i n e s (X) - w e r e o b t a i n e d by m e t h y l a t i o n of a i n i n o t h i a z i n e s IV w i t h m e t h y l i o d i d e i n a c e t o n e .

tV A ~ C l i 3 \ ~ . / C H3 CH3~x.z/"~y/CH~.
! : c.~t c.(] I o.- c.(l !
',i " HN~S N.%./S
zvB i Ii !
N N
/\ /\
CH3 C6H4X CH3 C6H4X

IX a-f ~ a-f

I n t h i s c a s e , w e o b t a i n e d s i n g l e m e t h y l a t i o n p r o d u c t s in h i g h y i e l d s ( T a b l e 2); t h i s p r o v i d e s e v i d e n c e
that the reaction proceeds primarily at one of the two reaction centers. On t h e b a s i s o f t h e d i f f e r e n c e s in
the physicochemical characteristics o f t h e m e t h y l a t i o n p r o d u c t s a n d VIII, t h e i m i n o s t r u c t u r e o f w h i c h i s
d e t e r m i n e d by t h e s t r u c t u r e of t h e s t a r t i n g c o m p o u n d s , w e a s s u m e t h a t t h e I n e t h y l a t i o n o f a m i n o t h i a z i n e s
IV i s r e a l i z e d a t t h e e x o c y c l i c n i t r o g e n a t o m . T h e s p e c t r a l p a r a m e t e r s o f IV, V I I I , a n d X a n d t h e a m i n o -
imino tautoinerism IVA~WB w i l l be d i s c u s s e d in o u r n e x t c o m m u n i c a t i o n .

EXPERIMENTAL
4,4,6-Triinethyl-2-anilino-5,6-dihydro-4H-l,3-thiazine (IVd). A solution of i0 g (0.04 Inole) of thio-
urea Id in 50 Inl of ethanol was saturated with dry hydrogen chloride, after which the ethanol was removed
by distillation, and the residue was neutralized with a saturated potassium carbonate solution. The or-
ganic portion was extracted with ether, and the extract was dried with Inagnesium sulfate. The ether was
removed by distillation, and the residue was crystallized from alcohol to give 8.3 g of aminothiazine IVd.
A similar method was used to obtain IVa-c, e, f (Table i).
3,4,4,6-Tetrainethyl-2-phenyliminotetrahydro-l,3-thiazine (VIIIc). A mixture of 4.0 g (0.015 mole)
of thiourea V and 15 Inl of concentrated hydrochloric acid was heated at 90-95 ~ for i0 Inin, after which the
acid was removed by vacuum distillation, and the residue was neutralized with saturated potassium car-
bonate solution. The organic portion was extracted with ether, the ether was reinoved from the extract by
distillation, and the residue was recrystallized froin alcohol to give 2.4 g (63%) of VIIIc with nap 72-73 ~
Found: N 10.9; S 12.5%. CI4HmNzS. Calculated: N 11.3; S 12.9%.
A similar Inethod was used to obtain 3,4,4,6-tetrainethyl-2-(p-methoxyphenyl)iIninotetrahydro-l,3-
thiazine (VIIIa, 18% yield, mp 71.5-72 ~ Found: N 9.8; S 11.2%. CIsH2zN2OS. Calculated: N i0.i; S 11.5%)

311
and 3,4,4,6-tetramethyl-2-(p-tolyl)iminotetrahydro-l,3-thiazine (VIIIb, 23% yield, mp 116-117 ~ Found:
N 10.5; S 11.9%. C15H22NzS. Calculated: N 10.7; S 12.2~o).
4,4,6-Trimethyl-2-N-methylanilino-5,6-dihydro-4H-1,3-thiazine (Xd). A 4.8 g (0.034 mole) sample
of methyl iodide was added to a solution of 4 g (0.017 mole) of IVd in 15 ml of acetone, and the mixture was
allowed to stand at 20 ~ for 30 h. Dry ether (20 ml) was added, and the precipitated crystals of salt IXd
were removed by filtration and treated with a saturated potassium carbonate solution. The organic portion
was extracted with ether, and the ether extract was dried with magnesium sulfate. The ether was removed
by distillation to give 3.4 g of aminothiazine Xd. A similar method was used to obtain Xa-c, e, f (Table 2).

LITERATURE CITED
1. M. Tisler, Arch. Pharm., 293, 621 (1960).
2. H. Najer, R. Giudicelli, and J. Menin, Bull. S.c. Chim. France, 2120 (1965).
3. E. Cherbuliez, B. Baehler, O. Espeio, H. Jindra, B. Willhatm, and J. Rabinowitz, Helv. Chim. Acta,
50, 331 (1967).
4. L. Toldy, P. Sohar, K. Farago, Z. Toth, and L. Bartalits, Tetrahedron Lett., 2167 (1970).
5. L. A. Ignatova, P. L. Ovechkin, M. Z. Branzburg, A. E. Gekhman, and B. V. Unkovskii, Khim.
Geterotsikl. Soedin., 1037 (1972).
6. M. Janssen, Spectrochim. Acta, 1._77,475 (1961).
7. W. Kutzelnigg and R. Mecke, Spectrochim. Acta, 17, 530 (1961).
8. L. A. Ignatova, A. E. Gekhman, P. L. Ovechkin, and B. V. Unkovskii, Khim. Geterotsikl. Soedin.,
354 (1974).

312
NEW METHOD FOR THE SYNTHESIS OF cis-2,5-DISUBSTITUTED

SULFOLANE DERIVATIVES*

N . N. N o v i t s k a y a , G . K. S a m i r k h a n o v a , UDC 547.732.898.07 : 543.422.4

K. N. P e r v u s h i n a , R. V. K u n a k o v a ,
A. M. S h a k i r o v a , a n d G. A . T o l s t i k o v

A new method for the p r e p a r a t i o n of functional derivatives of sulfolane by ozonolysis of 13-

t h i a b i c y c l o [ 8 . 2 . 1 ] - c i s - 5 - t r i d e c e n e and its derivatives was developed.

Sufficiently effective general methods for the p r e p a r a t i o n of di- and polyfunctional sulfolane d e r i v a -
tives have not yet been described. The essential inadequacies in the known methods include the low yields
of the t a r g e t compounds, the m a n y steps involved in the syntheses, the difficulty in obtaining the starting
m a t e r i a l s , and the laborious separation of the s t e r e o i s o m e r s [1].
The possibility for the synthesis of 2 , 9 - d i c h l o r o - 1 3 - t h i a b i c y c l o [ 8 . 2 . 1 ] - c i s - 5 - t r i d e c e n e (I) by reaction
of sulfur dichloride with t r a n s , t r a n s , c i s - c y c l o d o d e c a - l , 5 , 9 - t r i e n e was r e c e n t l y d e m o n s t r a t e d [2]. We have
established that I is f o r m e d in a steady yield of no less than 9070 in the reaction of equimolar amounts of
r e a g e n t s in dilute dichloromethane solutions a t - 2 0 ~ 1 3 - T h i a b i c y c l o [ 8 . 2 . 1 ] - c i s - 5 - t r i d e c e n e (H) is ob-
tained in high yield by reduction of I by m e a n s of LiA1H4. Its ozonolysis as a function of the conditions and
solvents was studied. The ozonolysis was c a r r i e d out in dilute (1 : 20) solutions.
Acetoxyhydroperoxyaldehyde HI is f o r m e d in acetic acid at - 2 0 ~ The s t r u c t u r e of aldehyde III was
c o n f i r m e d by determination of the p e r c e n t a g e of active oxygen, positive reaction with 2,4-dinitrophenyl-
h y d r a z i n e , and IR s p e c t r a l data.
Absorption bands of equal intensity at 1760 and 1260 cm -1 a r e related, respectively, to the stretching
vibrations of the carbonyl group and the as~mametrical stretching vibrations of the C - O - C group of an e s -
t e r grouping, while the absorption band at 1015 crn - I is r e l a t e d to the s y m m e t r i c a l stretching vibrations of
this same grouping. The aldehyde group is c h a r a c t e r i z e d by the frequency of the stretching vibrations of
the carbonyl group at 1740 cm -1 and the s t r e t c h i n g vibrations of the CH group at 2730 c m -1. The a b s o r p -
tion at 930 c m -1 is due to the stretching vibrations of the - O - O - peroxide grouping.
F r e q u e n c i e s in the region of the vibrations of an SO 2 group are absent in the IR s p e c t r u m of aldehyde
III, but there are other frequencies in the region of the vibrations of the SO group (1050 cm-i); the SO vi-
brations t h e r e f o r e cannot be isolated. IIowever, inasmuch as m a c r o c y c l i e saturated sulfide VI is oxidized
only to sulfoxide VII under the ozonolysis conditions, it can be supposed that the degree of oxidation of the
sulfur atom is also the same in III. In addition, we showed by special experiments that under these same
conditions thiophan is oxidized to the sulfoxide, but thiophan sulfone is not f o r m e d even at 20 ~
Oxidation of III with hydrogen peroxide in the p r e s e n c e of sulfuric acid gives c i s - 2 , 5 - d i ( y - c a r b o x y -
propyl)sulfolane (IV) in 85-90% yield. The IR s p e c t r a of acid IV and its dimethyl and p - b r o m o p h e n a c y l e s -
t e r s contain bands at 1120, 1290, and 1310 c m "1, which are c h a r a c t e r i s t i c for the s y m m e t r i c a l and a s y m -
m e t r i c a l s t r e t c h i n g vibrations of the s o 2 group. As seen, the oxidation of SO to SO 2 p r o c e e d s during the

* Communication III of the s e r i e s "Reaction of Sulfur Halides with Unsaturated Compounds."

Institute of Chemistry, Bashkirskii Branch, A c a d e m y of Sciences of the USSR, Ufa. T r a n s l a t e d from

Khimiya Geterotsiklicheskilda Soedinenii, No. 3, pp, 360-364, March, 1974. Original a r t i c l e submitted
J a n u a r y 31, 1973.

9 1975 PlenumPublishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy of this article is available from the publisher for $15.00.

313
 decomposition of the ozonolysis product. The conformation of the substituents follows f r o m the fact that
the addition of SC12 to cyclic dienes always p r o c e e d s with the f o r m a t i o n of c i s - d i s u b s t i t u t e d h e t e r o c y c l e s [3].
Ozonation in f o r m i c acid p r o m o t e s the m o r e rapid oxidative decomposition of the hydroperoxide and
an i n c r e a s e in the yield of IV to p r a c t i c a l l y quantitative levels. The s t r u c t u r e of i n t e r m e d i a t e l y - f o r m e d
f o r m o x y h y d r o p e r o x y a l d e h y d e V follows f r o m the IR s p e c t r a , the r e s u l t s of i o d o m e t r i c titration of the a c -
tive oxygen, and a positive reaction with 2,4-dinitrophenylhydrazine.
The yield of acid IV falls on p a s s i n g f r o m acids to alcohols and then to i n e r t solvents (chloroform,
hexane). Judging f r o m the IR s p e c t r a of the products of ozonolysis of II, a m i x t u r e of m o n o m e r i e and p o l y -
m e r i c ozonides, the yields of which a r e N 60 and 40%, r e s p e c t i v e l y , is f o r m e d in i n e r t solvents. An in-
c r e a s e in the ozonolysis t e m p e r a t u r e in any of the solvents leads to a d e c r e a s e in the yield of IV.
The oxidation of the ozonolysis products is a c c e l e r a t e d c o n s i d e r a b l y by the use of seleniun dioxide.
Thus the oxidation of identical amounts of the i n t e r m e d i a t e with 30% hydrogen peroxide in acetic acid c o n -
raining sulfuric acid usually p r o c e e d s in 30-50 h, as c o m p a r e d with 20-30 h at 60 ~ in f o r m i c acid containing
sulfuric acid, while oxidation with hydrogen peroxide in the p r e s e n c e of a catalytic amount of selenium di-
oxide takes 12-15 h at r o o m t e m p e r a t u r e . The amount of hydrogen peroxide c o n s u m e d is reduced con-
siderably.
The a e e t o l y s i s of I gives 2 , 9 - d i a c e t o x y - 1 3 - t h i a b i e y c l c [ 8 . 2 . 1 ] - c i s - 5 - t r i d e c e n e (VIII), the s a p o n i f i c a -
tion of which gives diol IX. Ozonolysis of IX in acetic acid with subsequent oxidation in the p r e s e n c e of
sulfuric acid gives 2,5-di('/-butanolid-T-yl)sulfolane (XI) in high yield (91%), the IR s p e c t r u m of which con-
tains an absorption band at 1780 c m -1, which is c h a r a c t e r i s t i c for the s t r e t c h i n g v i b r a t i o n s of the carbonyl
group in a f i v e - m e m b e r e d laetene. The IR s p e c t r u m of i n t e r m e d i a t e X, in which absorption bands of an
aldehyde group a r e absent, the negative r e a c t i o n of X with 2,4-dinitrophenylhydrazine, and the c o n s i d e r a b l y
s m a l l e r amount of hydrogen p e r o x i d e r e q u i r e d for the f o r m a t i o n of XI as c o m p a r e d with the hydrogen p e r -
oxide consumption in the p r e p a r a t i o n of acid IV indicate that lactonization p r o c e e d s i m m e d i a t e l y after the
formation of the aldehyde through i n t e r m e d i a t e h e m i a c e t a l X, bypassing the step involving the formation of
the hydroxy acid.
Bislactone XI was also obtained in quantitative yield during m i l d e r oxidation by m e a n s of selenium
dioxide without heating.
Laetene XI is also f o r m e d in the ozonolysis of diaeetate VIII but in lower yield (50%7. Reaction of
the i n t e r m e d i a t e with 2,4-dinitrophenylhydrazine is also negative in this c a s e . H y d r o l y s i s of the i n t e r -
m e d i a t e at r o o m t e m p e r a t u r e in w a t e r also gives bislactone XI. Lactone XI r e a c t s v e r y r e a d i l y with a m -
monia in w a t e r to give 2 , 5 - d i ( a - h y d r o x y - T - a m i d o x y p r o p y l ) s u l f 0 l a n e (XID; its s t r u c t u r e was c o n f i r m e d by
i t s IR s p e c t r u m , which contains two bands at 1615 and 1680 e m -1, c h a r a c t e r i s t i c for a free CONH 2 group,
and a doublet at 3500, 3400 era -i.
The reduction of lactone XI by LiAlt{ 4 in ether at 20 ~ p r o c e e d s r e a d i l y and gives, in high yield, 2,5-
di(a,T-dihydroxypropyl)sulfolane (XIII), which was c h a r a c t e r i z e d as the t e t r a ( p - n i t r o b e n z o a t e ) (XIV).
The ozonation of dichloro sulfide I is c o m p l i c a t e d by side r e a c t i o n s as a consequence of the high l a -
bility of the chlorine a t o m s . Dichloro acid XVI t h e r e f o r e cannot be obtained in yields of m o r e than 10-20%,
but the yield can be r a i s e d to 30% in the ozonolysis of sulfexide XV.

EXPERIMENTAL
The IR s p e c t r a of m i n e r a l oil suspensions, hexaehlorobutadiene suspensions, liquid films, or CC14
solutions w e r e r e c o r d e d with a UR-20 s p e c t r o m e t e r . The PMR s p e c t r a w e r e obtained with a T e s l a BS487B
s p e c t r o m e t e r with an operating frequency of 80 MHz with hexamethyldisiloxane (HMDS) as the internal
standard. T h i n - l a y e r c h r o m a t o g r a p h y (TLC) was c a r r i e d out on activity III alttminum oxide.
2 , 9 - D i c h i o r o - 1 3 - t h i a b i c y c l o [ 8 . 2 . 1 ] - c i s - 5 - t r i d e e e n e (I). A solution of 35.8 g (0.34 mole) of SCI 2 in
200 nil of dry Ctt2CI 2 was added dropwise with s t i r r i n g in the c o u r s e of 5 h a t - 2 0 ~ to a solution of 64.8 g
(0.34 mole) of t r a n s , t r a n s , c i s - c y e l o d o d e c a - l , 5 , 9 - t r i e n e in 160 m l of d r y CH2C12. The solvent was then r e -
m o v e d by vacuum distillation, and the r e s i d u e was washed on the filter with d i m e t h y l f o r m a m i d e (DMF) and
ether. The solvents w e r e e v a p o r a t e d , and the r e s i d u e was worked up s i m i l a r l y to give 100 g (95%) of I
with mp 128-129~ Found: C 54.1; H 6.8; CI 27.0; S 12.0%. C12H18C12S. Calculated: C 54.3; H 6.8; CI
26.8; S 12.0%. IR spectrum, p, era-i: 686 (C-CI), 720 (cis-CH= CH). PMR spectrum, 6, ppm (in CDCI3):
3.12 (2H, m CI-C-II), 3.50 (2H, m S - C - H ) , 5.30 (2H, d, J=12 Hz, H-C), 1.87-2.07 (12H).

314
 + SCI 2

' I I1, VIII, IX

|1 R = H ; vIII R=OAc; IX R=Oft

,~ ~o3 o~ ~ /or
~c(cH93,-L..o/>--(ca2hc~ [o1
"o2c(c"2)3~(c.~.)~co~.
H-- -a
0 \02 H Oo
111, V IV
III

-20 ~

Vl VII
OH 0 0
I If II
/CH, /C\ . /C%
HO HO ~ 0 6H 2 H2C 0 ~ O Cfl~
o3,c.~co,, t \ Iol I -I / \ I I"
IX ( V I I I ) ~ - KfifiCH(CH2)zHCI- ~ S , . . ) _ CtH--CIH~ - ~2C--HC--(.s2--Cn_CU
; . . _
AcO
O 09
X XI
HO c----". OH HO ~ OH
HOH C I / \ ]
2C( H2)-HC~-nX.S.,,.-L'-CH(CH2)2CH2OH " " XI ~
LiAIH4 NH3
a2NOC(CH2)
~HC-\-/-x.St .)-CH(Ct~
I /
l )oCONl~
i
02 02
XIII XII

CI ~ CI CI ,~ CI
~ / ~ 01" I ~O~ '
HO~C(CHr)2HC I/S.._~/) --CH(CH2)2CO2H
I

O2
.o
XV XVI

1 3 - T h i a b i c y c l o [ 8 . 2 . 1 ] - c i s - 5 - t r i d e c e n e (II). This compound was obtained in 85% yield by reduction of

dichloride I with LiAIHr in ether and had bp 108-110 ~ (2 ram) and nD 2~ 1.5462. Found: C 73.7; H 10.5; S
15.5~0. C~2H20S. C a l c u l a t e d : C 73.4; tt 10.2; S 16.1%.- 9
2 , 9 - D i a c e t o x y - 1 3 - t h i a b i c y c l o [ 8 . 2 . 1 ] - c i s - 5 - t r i d e c e n e (VIII). This compound was obtained in 80% yield
by the action of sodium acetate on I in glacial acetic acid and had mp 143-144 ~ Found: C 61.4; H 7.8; S
10.5%. C16H2404S. Calculated: C 61.5; H 7.6; S 10.3%. IR spectrum, u, c m - l : 725 ( c i s - C H = CH), 1245,
1745 (OCOCH3). PMR s p e c t r u m , 6, ppm (in CC14): 5.5 ( ' C H = CH-), 1 . 8 7 (s OCOCH3);
2 , 9 - D i h y d r o x y - 1 3 - t h i a b i c y c l o [ 8 . 2 . 1 ] - c i s - 5 - t r i d e c e n e (IX). This compound w a s obtained in 90?0 yield
by saponification of VIII and had m p 176-178 ~ Found: C 63.1; H 9.0; S 14.07o. C12II2002S. "Calculated: C
63.1; H 8.8; S 14.1%. IR spectrum, v, Cm-l: 725 ( c i s - C H = CH-), 3300-3400 (OH).
c i s - 2 , 5 - D i ( T - c a r b o x y p r o p y l ) s u l f o l a n e (IV). A) O z o n i z e d oxygen w a s p a s s e d through a solution of 2 g
(0.01 mole) of II in 40 ml o f glacial acetic acid and 60 ml of CHCI 3 a t - 2 0 ~ until o z o n e began to appear in
the outlet f r o m the flask. The CHCI 3 w a s r e m o v e d by vacuum distillation at 20 ~ 10 m l o f 30?0 H202 and a
drop of sulfuric acid w e r e added, and the mixture w a s heated at 60 ~ until the peroxide d e c o m p o s e d . The
mixture was then vacuum evaporated to d r y n e s s at 40-506, after which the oxidation was repeated until a
c r y s t a l l i n e r e s i d u e had f o r m e d (30-50 h). This residue w a s c r y s t a l l i z e d f r o m acetone to give a product
with mp 164-165 ~ Found: C 52.9; H 7.7; S 9.9%. C14H24OGS. Calculated: C 52.6; H 7.6; S 10.0%. IR s p e c -
trum, u, c m - l : 1120 , 1290, 1310 (SO2); 1713 (COOH).
B) A 2 g (0.01 mole) s a m p l e of II in a solution of 40 ml of f o r m i c acid and 15 m l of ethyl acetate was
s i m i l a r l y o z o n i z e d . The o z o n o l y s i s product was oxidized as in method A (20-30 h, 10 m l of H202) to give
2.4 g (96%) of IV with mp 164-165 ~ ( f r o m acetone).
C) A 2 g (0.01 mole) s a m p l e of II w a s o z o n i z e d under the conditions of method B. The ethyl acetate
w a s r e m o v e d by vacuum distillation, 3.5 m l of 30% II202 and 0.001 g of SeO 2 w e r e added, and the mixture
w a s allowed to stand overnight. It was then heated at 60-80 ~ for 1-2 h to d e c o m p o s e the peroxide to give
2.5 g (98%) of IV with mp 165-165.5 ~

315
 Acetoxyhydroperoxyaldehyde IIL A 2 g (0.01 mole) sample of II was ozonizvd under the conditions of
method A. The solvents w e r e r e m o v e d by vacuum distillation at 0-20 ~ and the residue was dried thoroughly
in vacuo to give 3 g of a h y g r o s c o p i c oil. The m a t e r i a l contained 4.8% active oxygen (the calculated value
was 5.2%). The r e a c t i o n with 2,4-dinitrophenylhydrazine was positive. IR s p e c t r u m , v, c m - i : 930 ( - 0 - 0 - 7 ;
1260, 1760, 1015 (OCOCHa); 1740, 2730 (-CHO).
F o r m y l o x y h y d r o p e r o x y a l d e h y d e V. This compound was Similarly obtained under the conditions of
method B, It contained 5.3% active oxygen (calculated value 5.4%). The reaction with 2,4-dinitrophenyl-
h y d r a z i n e was positive. IR s p e c t r u m , u, c m - l : 930 ( - O - O - ) ; 1200, 1740 (OCOH); 1020 ( - C - O - C - ) ;
1780, 2730 (CHO).
2,5-Di(y-butanolid-7-yl)sulfolane (XI). A) A 2.3 g (0.01 mole) s a m p l e of IX was ozonized in 70 m l of
glacial acetic acid and 100 m l of c h l o r o f o r m a t - 2 0 ~ The c h l o r o f o r m was then r e m o v e d by v a c u u m d i s -
tillation, 3.5-4 ml of H202 and a drop of sulfuric acid w e r e added, and the m i x t u r e was heated at 60 ~ until
the peroxide had d e c o m p o s e d (10-15 h). When the oxidation was c a r r i e d out with selenium dioxide, a c a t -
alytic amount of selenium dioxide was added to the r e s i d u e a f t e r r e m o v a l of the c h l o r o f o r m by distillation,
and the m i x t u r e was allowed to stand at r o o m t e m p e r a t u r e overnight. The residual peroxide was d e c o m -
posed by heating at 60 ~ for 1-2 h, a f t e r which the solvent was r e m o v e d by evaporation, and the r e s i d u e was
c r y s t a l l i z e d f r o m acetone to give 2.5 g (91%) of XI with m p 176-177 ~ Found: C 50.6; H 5.5; S 10.9%.
ClzHlsO6S. Calculated: C 50.4; H 5.6; S 11.2%. PMR s p e c t r u m (pyridine), 6, ppm: 3.5 (2H, S - C - H ) ; 4.5
(2H, H - C - O - ) ; 2.06 (m), 2.37 (m, 12ti). IR s p e c t r u m , v, c m - l : 1100, 1300 (SO2); 1780 (CO).
B) A 0.23 g (0.001 mole) sample of IX was ozonized in a m i x t u r e of 7 ml of acetic acid and 10 m l of
c h l o r o f o r m . The solvents w e r e then r e m o v e d in vacuo, 10 m l of w a t e r was added to the r e s i d u e , ~nd the
m i x t u r e was heated at 40-50 ~ for 70 h. It was then cooled and filtered to give c r y s t a l s with rap 169-172 ~
The IR spectrttm was identical to the IR s p e c t r u m of sulfolane XI.
c i s - 2 , 5 - D i ( c ~ - h y d r o x y - T - a m i d o x y p r o p y l ) s u l f o l a n e (XII). Gaseous a m m o n i a was bubbled at 15-20 ~
through a s a t u r a t e d aqueous solution of 2 g (0.01 mole) of XI; a f t e r XI had d i s a p p e a r e d on the t h i n - l a y e r
c h r o m a t o g r a m [15-20 rain, R f 0.57, h e x a n e - a c e t o n e (1 : 1)], a m m o n i a was bubbled into the m i x t u r e for
another 2 h. The r e s u l t i n g p r e c i p i t a t e was r e m o v e d by filtration and c r y s t a l l i z e d f r o m alcohol to give XII
with m p 158-160 ~ Found: C 45.1; H 7.2; N 8.5; S 9.8%. Cl~H22N206S. Calculated: C 44.8; H 6.8; N 8.7;
S 9.9%. IR s p e c t r u m , u, c m - l : 1130, 1290 (SO2); 1615, 1680 (CONtt2); 3200, 3300, 3420 (OH, CONIt2).
2 , 5 - D i ( ~ , y - d i h y d r o x y p r o p y l ) s u l f o l a n e (XIII). A solution of 1 g (3.4 mmole) of XI in 100 ml of d r y
t e t r a h y d r o f u r a n (TttF) was added to a suspension of 0.34 g (0.009 mole) of LiAIH 4 in 20 m l of d r y THF,
a f t e r which the m i x t u r e was s t i r r e d for 15 rain. I t was then t r e a t e d with m o i s t THF and w a t e r , and the
p r e c i p i t a t e was r e m o v e d by filtration and washed on the f i l t e r with w a t e r . The combined f i l t r a t e s w e r e
e v a p o r a t e d , and the r e s u l t i n g orange oil was dried in vacuo. The salts w e r e s e p a r a t e d by dissolving the
oil in d r y acetone and filtering the solution. Workup gave 0.9 g of an oil. IR s p e c t r u m , u, c m - l : 1125,
1300 (SO2); 3200-3445 (OH).
9T r e a t m e n t of the oil with p - n i t r o b e n z o y l chloride gave t e t r a ( p - n i t r o b e n z o a t e ) XIV with m p 204-205 ~
Found: C 53.6; H 3.8; N 6.2; S 3.7%. C40H3~NlO18S. Calculated: C 54.1; H 3.6; N 6.3; S 3.6%. IR s p e c -
t r u m , v, c m - l : 1110, 1330 (SO2); 1355, 1535 (NO2); 1280, 1730 (OCOR); 1610 (Ph).
c i s - 2 , 5 - D i ( ~ - c h l o r o - T - c a r b o x y p r o p y l ) s u l f o l a n e (XVD. This compound was obtained in 10-20% yield
by ozonolysis of I by method B and in 30% yield Via method B by ozonolysis of sulfoxide XV; the product
had m p 147-150 ~ Found: C 39.9; H 4.9; C1 22.0; S 9.0%. C12H18C1206S. Calculated: C 39.9; H 5.0; C1
19.6; S 8.9%. IR s p e c t r u m , u, c m - l : 1130, 1320 (SO2); 1710 (COOH).
Dimethyl E s t e r of Acid IV. This compound was obtained by t r e a t m e n t of IV with diazomethane in
ether and had bp 225 ~ (2 ram) and nD 2~ 1.4920. Found: C 52.5; H 7.6; S 10.0%. C14H240~S. Calculated: C
52.8; H 7.7; S 9.9%. IR s p e c t r u m , u, c m - l : 1120, 1280, 1285 (SO2); 1210, 1740 (OCOCH3). PMR s p e c t r u m ,
6, ppm (CCI4): 3.55 (OCH3); 3.85 (2H, HC-SO2); 1.6-2.6 (16H).
Dimethyl E s t e r of Acid XVL This compound was s i m i l a r l y obtained f r o m XVI and had nD2~ 1.5075.
Found: C-3-~.0; H ~.-6; C1 18.3; S 8.2%. C12H22C1206S. Calculated: C 36.9; H 5.6; C1 17.3; S 8.3%. IR s p e c -
t r u m , u, c m - l : 1140, 1320 (SO2); 1210, 1740 (OCOCH3). PMR s p e c t r u m (CC14) , 6, ppm: 3.55 (OCH3) , 3.5-
4.0 (2H, HC-SO2); 2.5-1.2 (16H).
p - B r o m o p h e n a c y l E s t e r of Acid IV. This compound was obtained by the usual method and had mp
151-152 ~ Found: C 49.6; H 4.4; B r 22.2; S 4.7%. C28H39Br~OsS. Calculated: C 49.2; H 4.4; B r 23.4; S
4.7%. IR s p e c t r u m , v, c m - l : 1120, 1300 (SO2); 1710 (COPh); 1745 (OCOR).

316
 Sulfoxide XV was obtained by the method in [4] and had mp 138.5-140 ~ Found: C 51.2; H 6.5; C1
25.8; S 10.9%. C12H18C12OS. Calculated: C 51.2; H 6.4; C125.0; S 11.4~0. IR spectrum, v, cm-l: 680
(C-C1); 720 (cis-C=C); 1045 (SO).

LITERATURE CITED
io E. N. Karaulova, Chemistry of Petroleum Sulfides [in Russian], Nauka, Moscow (1970), p. 51.
2. F. Lautenschlaeger, J. Org. Chem., 3__33,2627 (1968).
3. W. N. Miiller, Angew. Chem., 8_~1,475 (1969).
4. G. A. Tolstikov, U. M. Dzhemilev, N. N. Novitskaya, V. P. Yur'ev, and R. G. Kantyukova, Zh. Obshch.
Khim., 41, 1833 (1971).

317
AMINOMETHYLATION OF SOME 4-THIAZOLIDINONES

Yu. V. Svetkin, S. A. Vasil'eva, UDC547.789.5:542.953.2:543.422.4

and V. M. Pronina

2 - A r y l a m i n o m e t h y l i m i n o - 3 - a r y l - 4 - o x o t h i a z o l i d i n e s w e r e o b t a i n e d by t h e M a n n i c h r e a c t i o n .
T h e s t r u c t u r e of the i s o l a t e d p r o d u c t s w a s c o n f i r m e d by a c i d h y d r o l y s i s , the f o r m a t i o n of
m o n o a c e t y l d e r i v a t i v e s , a n d the IR s p e c t r a .

T h e a m i n o m e t h y l a t i o n of 2 - i m i n o - 3 - a r y l - 4 - o x o t h i a z o l i d i n e s h a d not been s t u d i e d u n t i l w e b e g a n o u r
p r e s e n t r e s e a r c h . I t i s known t h a t r h o d a n i n e and i t s 5 - s u b s t i t u t e d d e r i v a t i v e s u n d e r g o the M a n n i c h r e a c -
tion in the 3 p o s i t i o n of the t h i a z o l i d i n e r i n g [1, 2]. 2 - I _ m i n o - 3 - a r y l - 4 - o x o t h i a z o l i d i n e s I r e a c t r e a d i l y w i t h
f o r m a l d e h y d e a n d p r i m a r y a r o m a t i c a m i n e s IIb to g i v e a m i n o m e t h y l d e r i v a t i v e s in h i g h y i e l d s . C o m p o u n d s
I, w h i c h h a v e two l a b i l e h y d r o g e n a t o m s , c a n u n d e r g o the M a n n i c h r e a c t i o n a t both the i m i n o a n d m e t h y l e n e
g r o u p s . On t h e b a s i s of a s t u d y of the IR s p e c t r a a n d the p r o d u c t s of the a c i d h y d r o l y s i s , i t w a s e s t a b l i s h e d
t h a t t h e c o n d e n s a t i o n of I p r o c e e d s a t t h e i m i n o g r o u p and t h a t t h e p r o d u c t s h a v e the I I I a - m s t r u c t u r e ( T a -
b t e 1).

O = C]- - N - -i C 6 H 4 R ' -~
CHgO
" ~
O ~ C !- - N--C6H4R'
I (CHaCO).
" O O=C--N--GH
I ] " R'
%,~f=x, ,,,c,.,N,~ c.~,,s~c=Nc" ~,~,c,,,,'~
~ o c,o\~,,c=xc,~c.,.
I ~ ' ~'
COCH 3
I I1 111 IV

An i n t e n s e a b s o r p t i o n band i s o b s e r v e d in t h e r e g i o n of the s t r e t c h i n g v i b r a t i o n s o f the c a r b o n y l

g r o u p of IN a t 1710-1720 e r a - t ; t h i s i s c h a r a c t e r i s t i c f o r the s t r e t c h i n g v i b r a t i o n s o f an u n c o n j u g a t e d c a r -
bonyl g r o u p [3]. T h e s t r u c t u r e of III i s c o n f i r m e d b y t h e p r e s e n c e in the I R s p e c t r u m of i n t e n s e a b s o r p -
tion b a n d s a t 1630 a n d 1470 c m -1 due to the s t r e t c h i n g v i b r a t i o n s of t h e C = N a n d CH 2 g r o u p s [4]. In c o n -
t r a s t to s t a r t i n g I, the a b s o r p t i o n a t 3300 c m -1 c o r r e s p o n d i n g to the s t r e t c h i n g v i b r a t i o n s of the NH g r o u p
i s a b s e n t in t h e IR s p e c t r a of p r o d u c t s III; t h i s i s in a g r e e m e n t w i t h the p r o p o s e d s t r u c t u r e of the c o m -
pounds.

T A B L E i. 2 - A r y l a m i n o m e t h y l i m i n o - 3 - a r y l - 4 - o x o t h i a z o l i d i n e s

Com- I i~ Empirical Found, % Calc., % !Yield.

;

pound i R' R" mp, ~ formula %

N.%iS, %t M 'N, %Is, %! M i
I ] ~ i '
IIIa ] H H 118--119 C16HIBN3OS ;14,3:1061290 14,1 10,8!297 92
IIlb ; p-CHz H 133--134 C17H17NaOS il36 9,913,06 13,5i 10,@311 90
Illc ]H~CHaO H 150--151 C~THIrNaOzS i 12,9[ 9,7~320 12,8 9,8 327 ', 88
IIId i p-CH3 143--144 CITHIrN~OS ~13.6! 10,2 303 13,5 !0,2 311 93
III e P-CH3 p-CH3 151--152 C~eH~N3OS i13.l', 9,9 316 19,9: 9,8 325 91
Illf ! p-CH30 p-CH3 130--131 C~sHIgN30~S i 19,5' 9,31337 12,3 9,4 341 90
III g ] P-C2HsO ', pCH3 151--152 CIgH2IN302S {11,9 8191350 11,8 9,0355 87
Illh I H p-Br i187--188 C16H~4BrNaOS 11,8i 8,5!371 11,2i 8,5 376 I 89
II1i ' P-CH3 ! p-Br 174--175 C7HIBBrN3OS !107i 82 379 1!0,8', 8,2 389 86
lllj p-CH30 P-Br i 152--153
162--163
C17H~sBrN302S [ 10 5, 7,8 396 10,3 7,9,405 85
C~8H sBrN302S [ 10,6! 7,6 413 [ 10,0 7,61 419 i 80
IIIk P-CzHsO i p-Br
l l I l m-NO2 'ill 204--205 (]16H14N403S 16,51 9,31335' 16,4~. 9,31342 84
IIIm! p-CHa ] m-NO~ 193--194 cl~a~N~O~S 15,9i 8,9[350 16,7i 9,0~I356 82

B a s h k i r s k i i S t a t e U n i v e r s i t y . T r a n s l a t e d f r o m K h i m i y a G e t e r o t s i k l i c h e s k i k h S o e d i n e n i i , No. 3, pp.
3 6 5 - 3 6 6 , M a r c h , 1974. O r i g i n a l a r t i c l e s u b m i t t e d M a r c h 20, 1973.

9 19 75 Plenum Publishing Corporation, 22 7 West 1 7th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

318
 TABLE 2. 2 - A c e t y l a r y l a m i n o r a e t h y l i r a i n o - 3 - a r y l - 4 - o x o t h i a z o l i d i n e s

CO1TI- I
pound f ~' R"
Imp, ~ (from i Empirical N,
,. %
. . . . . t Yield,
alc~176 i f~ found!calc.. 1 q~

IVa i H P-CHa 187--188 CI.~HI~N,~02,S 11,8 t 1,9 86

IVb P-CH3 m-NO~ 158--159 Cifl I::~N.~O~S 14,2 14.l 80
IVc p-OCHa H 167--168 CioH19N,~O3S 11.2 11,4 84
IVd ! p-OCHa p-CI-ta 119--120 C~H2~N.~OaS 10,8 10,9 89
lVe j p-CHa p-Br 164--I65 ClgHlsBrNaO~S 9,6 9,7 92
IVf it p-OC.-Hs p-Br 142---143 C=oH2oBrNaOsS 9,2 9,1 87

Mannich b a s e s III a r e stable in dilute acid solutions at 20~ but are r e a d i l y h y d r o l y z e d on brief h e a t -
ing to 3 - a r y l - 2 , 4 - t h i a z o l i d i n e d i o n e s and the starting amines. The acetylation of III with acetic anhydride
p r o c e e d s upon simple mixing of the components; the products a r e 2 - a c e t y l a r y l a m i n o m e t h y l i m i n o - 3 - a r y l -
4-oxothiazolidines I V a - f (Table 2).

EXPERIMENTAL
The IR s p e c t r a of KBr pellets at 600-3600 cm - i were r e c o r d e d with a UR-20 s p e c t r o m e t e r . The m o -
lecular weights were d e t e r m i n e d f r o m the m a s s s p e c t r a r e c o r d e d with an MKh-1303 m a s s s p e c t r o m e t e r at
an i n l e t - s y s t e m and i o n - s o u r c e t e m p e r a t u r e of 250 ~ an ionizing voltage of 50 V, emission c u r r e n t of 1.5
mA, and a c c e l e r a t i n g voltage of 2 kV. The 2 - i m i n o - 3 - a r y l - 4 - o x o t h i a z o l i d i n e s (I) were obtained by reaction
of acetochloroacetic anhydride with a r y l t h i o u r e a s [5].
2 - P h e n y l a m i n o m e t h y l i m i n o - 3 - p h e n y l - 4 - o x o t h i a z o l i d i n e (ILia). A 2.5 ml sample of 36% formalin and
0.6 g of aniline were added at 0~ to a solution of 1.5 g of 2 - i m i n o - 3 - p h e n y l - 4 - o x o t h i a z o l i d i n e in 40 ral of
ethanol. After 1 h, t h e precipitate was r e m o v e d by filtration, washed with water, and dried. The other HI
were synthesized under s i m i l a r conditions.
Acid Hydrolysis. A 1 g sample of IRa was refluxed for 5 rain in 25 ml of 10g0 HC1, after which the
m i x t u r e was cooled, and the precipitate was r e m o v e d by filtration to give a product with rap 143-144 ~
(from alcohol) in 43% yield. No melting-point d e p r e s s i o n was o b s e r v e d for a mixture of this product with
an authentic sample of 3-phenyl-2,4-thiazolidinedione [5]. The filtrate was neutralized with 10go Na2CO 3
solution, s a t u r a t e d with alkali, and e x t r a c t e d with ether. The amine contained in the e t h e r e x t r a c t was
t r e a t e d with a m i x t u r e of acetic anhydride and acetic acid. The resulting acetanilide (26%) had mp 114 ~
Acid H y d r o l y s i s of IVd. Water (0~ g), 0.5 g of CHaCOOH , and 1 g of acetic anhydride were added to
0.5 g of IVd. The c r y s t a l s that f o r m e d were r e m o v e d by filtration after 1 h.

LITERATURE CITED
1. M. A. Borisova, A. I. Ginak, and E. G. Sochilin, Zh, Organ. Khim., 6, 1738 (1970).
2. V. G. Zubenko and L. V. Bykova, Khimiya i Khim. Teklmol., 2, 9 (1969).
3. E. M. Peresleni, Yu. N. Sheinker, and I. P. Zosimova, Zh. Fiz. Khim., 39, 926 (1965).
4. K. Nakanishi, Infrared Spectra and Structure of Organic Compounds [Russian translation], Mir (1965),
p. 52.
5. Yu. V. Svetkin, A. N. :Minlibaeva, and S. A. VasiUeva, Zh. Obshch. Khim., 38, 116 (1968).

319
HETEROCYCLIC DIAZO COMPOUNDS
I. P R O P E R T I E S OF BENZOTHIAZOLE-2-DIAZONIUM SALTS

V. V. Shaburov, O. V . V a s i l ' e v a , UDC 547.789.6 : 543.422.4.6

and A. V. El'tsov

B e n z o t h i a z o l e - 2 - d i a z o n i u m t e t r a f l u o r o b o r a t e and its 6 - b r o m o , 6-methyl, and 6 - m e t h o x y

d e r i v a t i v e s a r e r e l a t i v e l y stable and have high e l e c t r o p h i l i c i t i e s . They a r e r a p i d l y con-
v e r t e d in weakly alkaline m e d i a to the c o r r e s p o n d i n g a n t i - d i a z o t a t e s , f r o m which p r i m a r y
n i t r o s o a m i n e s can be obtained by acidification.

H e t e r o c y c l i c diazo compounds that contain a pyridine nitrogen a t o m have high activity in diazo cou-
pling, and a n u m b e r of their p r o p e r t i e s approach those of diazo d e r i v a t i v e s of the benzene ring with e l e c -
t r o n - a c c e p t o r substituents.
It s e e m e d of i n t e r e s t to m a k e a m o r e detailed study of the p r o p e r t i e s of diazo compounds (I) b a s e d
on 2-aminobenzothiazole with v a r i o u s substituents in the benzene ring.

I a-d II a - d
I,II a R=H; b R=Br; C R=CH3; d ~,-CH30

The diazotization of the s t a r t i n g a m i n e s p r o c e e d e d in a c c o r d a n c e with the data in [1, 2]. The r e -

suiting diazo compounds w e r e isolated f r o m the solutions in the c r y s t a l l i n e state as the t e t r a f l u o r o b o r a t e s
(Ia-d), which w e r e r e l a t i v e l y stable s u b s t a n c e s .
The bands of the diazo group in the IR s p e c t r a o f the compounds a r e quite intense and lie at 2210-
2260 c m -1, the region c h a r a c t e r i s t i c for diazo compounds of the benzene ring with weak donor substituents.
The e l e c t r o n i c s p e c t r a of solutions of the diazo compounds in 50% sulfuric acid contain an intense band at
~ 400 rim, which is shifted m a r k e d l y to the long-wave portion of the s p e c t r u m in the c a s e of 6-methoxy d e -
r i v a t i v e Id (Table 1).
Judging f r o m qualitative e x p e r i m e n t s , the benzothiazolediazonium s a l t s r e a d i l y f o r m azo dyes with
v a r i o u s azo components in strongly acidic media. Thus s a l t Ib couples with an tt acid and anisole in 40%
sulfuric acid. Under s i m i l a r conditions, the p - n i t r o b e n z e n e d i a z o n i u m salt does not f o r m azo dyes. This
constiiutes evidence in favor of the high e l e c t r o p h i l i c i t y of diazo compounds b a s e d on benzothiazole [3].
The r a t e constant for t h e r m a l decomposition of 6 - m e t h o x y d e r i v a t i v e Id in 0.5~o sulfuric acid at 20~
which was found by a s p e c t r o p h o t o m e t r i c method, is 9.5 9 10 -5 sec -1. The p-toluenediazonium salt u n d e r -
goes decomposition at the s a m e r a t e under the s a m e conditions [4]. Thus the t h e r m a l stabilities of the
diazo d e r i v a t i v e s of 2 - a m i n o b e n z o - t h i a z o l e s in solution approach the t h e r m a l stabilities of the diazo c o m -
pounds of the benzene s e r i e s .
The absorption m a x i m a in the e l e c t r o n i c s p e c t r a a r e shifted to the s h o r t - w a v e region when dilute
solutions of s a l t s I a - d a r e m a d e alkaline t o pH 10 (Fig. 1); this is due to the f o r m a t i o n of the sodium salts
of the diazotates (IIa-d). The r e s u l t i n g solutions a r e incapable of entering into diazo coupling, and judging
f r o m the s p e c t r a , they r e g e n e r a t e the s t a r t i n g diazonium salt on acidification.

L e n s o v e t Leningrad Technological Institute. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Seed-

inenii, No. 3, pp. 367-371, March, 1974. Original a r t i c l e submitted May 5, 1973.

9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy o f this article is available from the publisher for $15.00.

320
 TABLE 1. Benzothiazote-2-diazonium Tetrafluoroborates (Ia-d)
N, % I
Corn - Empirical ~,..... ,rim I VN=*,b Yield,
R
pound formula found talc. (~g ~)'~ [ era-1 %

Ia
Ib
Ic
Id
~r
CHa
CHaO
CvH4BF4NaS
QHaBBrF4NaS
CsH6BF~NaS
CsH6BF4NaOS
16,5
12,2
16,1
14,9
16,9
12,8
16
15,1
365
i 386
385
425
(4,12)
(4,15)
(4 15)
(4,10)
i 2260
2259
2248
2217
78
12
31
62

Note: a l n 50% H2SO 4. b i n n i t r o m e t h a n e .

TABLE 2. Absorption Maxima of Benzothiazole-2-diazotates IIa-d

(in 0.i N NaOH) and 2-Benzothiazolylnitrosamines IIIa-d (in ethanol)
IIa-d IIIa-d
R
empirical formula xm~,, nm empirical formula }~=~, nm

H CrH4N3NaOS 322 C7HsNaOS 310a

Br QHaBrNaNaOS 332 CTH4BrN3OS 322
CHa C~HoNaNaOS 328 CsHrNaOS 320
CHaO CsH6N3NaO.~S 338 CaHTNsO~S 342

Note: aln chloroform, kmax 315 nm.

In preparative experiments the sodium salts of the diazotates (IIa-d) were formed readily even in the
cold on treatment with alkali and were isolated in pure form. An intense band at 330 nm (Table 2) is ob-
served in the electronic spectra of these compounds in 0.I N NaOH. The diazoiates are incapable of diazo
coupling, and this property makes it possible to assign the anti-diazotate structure to them. One's atten-
tion is drawn to the uriusual ease of formation of the anti-diazotates, which has previously been noted only
in the case of p-nitrobenzenediazonium salts. Rapid conversion of diazo compounds to anti-diazotates in
relatively weak media is apparently also characteristic for other diazo derivatives based on ~pyridine"
heterocycles. In this connection, the low yields of azo dyes obtained by several investigators [5, 6] become
understandable.
Compounds that are only slightly soluble in water and have elementary compositions that correspond
to primary nitrosamines were formed when an equivalent amount of acid was added to solutions of diazo-
tares IIa-d. In the presence of excess mineral acid these compounds are capable of being converted to
diazonium salts Ia-d; under the influence of alkali, they undergo reverse conversion to the diazotates. The
electronic spectra of alcohol solutions of these compounds have one band that is extremely close in posi-
tion to the band of the corresponding diazotates (Table 2).
At least three tautomeric forms - nitrosoamine A, nitrosoimine B, and diazo hydrate C - can be
presented for the nitrosoamines obtained:
H

A B C
Ill a-d
To solve the problem as to which form is actually realized, we synthesized two models with fixed struc-
tures; 2-(N-Methyl-N-nitrosoamino)benzothiazole (IV, form A) was obtained by nitrosation of the corre-
sponding 2-(methylamino)benzothiazole. 3-Methyl-2-nitrosoimino-benzothiazoline (V, form B) was syn-
thesized by nitrosation of 2-imino-3-methylbenzothiazoline. The electronic spectra of the compound ob-
tained by acidification of diazetates IIa and of IV in chloroform solution practically coincide, while the
long-wave band of V is shifted bathoehromically by 32 nm (Fig. 2).
The results provide evidence that the product of acidification of sodium benzothiazole-2-diazotate
(IIa) exists in nitrosoamine form A. Inasmuch as the changes in the electronic spectra for other benzo-
thiazole-2-diazotates and their corresponding acidification products are similar, we have also assigned
the primary nitrosoamine structure (IIIa-d) to the latter.
Thus diazo compounds based on benzothiazole and its derivatives are extremely electrophilic and
are very readily converted by alkalization to anti-diazotates, the conjugate acids of which are quite stable
and exist in the nitrosoamine form.

321
 Lg g

tg
4,1
l 3
,
t t ~&
~
. 4~!
, % " I t

3,9
\1\ // 3tg 9
^I I ,,,:/
/
l-x.:,,'0
I
3,7 / \\ ', / I ;/ I t
;'%1 I ; \\ 3~7-
" %% l

3,5:
3,5
3~3.
I

t
"'\ I
l %
'\ I
3,1.
I

2,g U I ,, 3,1 t , A,l'll'H

i i i i i t
240 280 320 360 400 440 ~,nm 26O 300 340 380 420
Fig. 1 Fig. 2
Fig. i. Electronic a b s o r p t i o n s p e c t r a : 1) benzothiazole-2-diazonium t e t r a -
fluoroborate (Ia) in 50% H2SO4; 2) 2-benzothiazolyldiazotate IIa in 0.1 N NaOH;
3) 2 , b e n z o t h i a z o l y l n i t r o s o a m i n e (Ilia) in alcohol.
Fig. 2 . Electronic a b s o r p t i o n Spectra of c h l o r o f o r m solutionsi 1) 3 - m e t h y l -
2 - n i t r o s o i m i n o b e n z o t h i a z o l i n e (V); 2) 2 - b e n z o t h i a z o l y l n i t r o s o a m i n e (IIIa); 3)
2 - ( N - m e t h y l - N - n i t r o s a m i n o ) benzothiazole (IV).

EXPERIMENTAL
Kinetic data on the t h e r m a l decomposition of diazonium salt Id and the UV s p e c t r a of the synthesized
compounds w e r e obtained with S F - 4 a and SF-8 s p e c t r o p h o t o m e t e r s with quartz cuvettes and l a y e r thick-
n e s s e s of 1 c m . The solution concentration was (0.6-1). 10 -4 M. The IR s p e c t r a of solutions of the di-
azonium s a l t s in n i t r o m e t h a n e w e r e r e c o r d e d with a UR-20 s p e c t r o m e t e r .
2-Aminobenzothiazole and its methyl d e r i v a t i v e w e r e obtained by the Gugerschoff method [7, 8], 2-
a m i n o - 6 - m e t h o x y b e n z o t h i a z o l e was obtained by the Kauffmann method [9], and 2 - a m i n o - 6 - b r o m o b e n z o -
thiazole was synthesized by bromination of 2-aminobenzothiazole in glacial acetic acid [7].
B e n z o t h i a z o l e - 2 - d i a z o n i u m T e t r a f l u o r o b o r a t e (Ia). A 1 g (6.6 m m o l e ) s a n ~ l e of 2 - a m i n o b e n z o t h i -
azole was m i x e d at 0~ with 13 ml of 42% t e t r a f l u o r o b o r i c acid and 1 ml of c o n c e n t r a t e d HzSO4, and 0.48 g
(6.8 m m o l e ) of 30% sodium nitrite solution was added gradually to the m i x t u r e . The m i x t u r e was then held
at 0~ for 1.5 h. T e t r a f l u o r o b o r a t e Ta was r e m o v e d by filtration, washed s u c c e s s i v e l y with a s m a l l amount
of t e t r a f l u o r o b o r i c acid, ice w a t e r , alcohol, and ether, and v a c u u m d r i e d o v e r c a l c i u m chloride.
6 - M e t h o x y b e n z o t h i a z o l e - 2 - d i a z o n i u m T e t r a f l u o r o b o r a t e (Id). A 1 g (5.5 m m o l e ) s a m p l e of 2 - a m i n o -
6-methoxybenzothiazole was m i x e d with 11 m l of 56% sulfuric acid, a f t e r which the m i x t u r e was cooled %o
0~ and 0.39 g (5.6 m m o l e ) of sodium nitrite (in the f o r m of a 30% solution) was added g r a d u a l l y at this t e m -
p e r a t u r e with s t i r r i n g under the liquid l a y e r . Stirring was continued at 0 ~ f o r 1.5 h, a f t e r which the m i x -
t a r e was cold filtered to r e m o v e a s m a l l amount of solid, and 0.75 g (6.8 m m o l e ) of sodium t e t r a f l u o r o -
b o r a t e was added to the filtrate. The p r e c i p i t a t e d Id was r e m o v e d by filtration and washed as indicated
above.
Compound Ic was s i m i l a r l y obtained. The diazotization of 2 - a m i n o - 6 - b r o m o b e n z o t h i a z o l e was c a r -
r i e d out in 70% sulfuric acid for 2 h.
Compounds I a - d (Table 1) w e r e purified by r e p r e c i p i t a t i o n f r o m n i t r o m e t h a n e solution by the addi-
tion of e t h e r .
Sodium B e n z o t h i a z o l e - 2 - d i a z o t a t e s (IIa-d). Ice and a diazonium s a l t solution, obtained by d i a z o t i -
zation of 1 g (5.5 m m o l e ) of 2 - a m i n o - 6 - m e t h o x y b e n z o t h i a z o l e under the conditions indicated above, w e r e
added gradually with external cooling to 40 m l of 20% sodium hydroxide solution. The r e s u l t i n g p r e c i p i t a t e

322
was r e m o v e d by filtration, and the f i l t r a t e was v a c u u m e v a p o r a t e d at 30-40 ~ The diazotate was r e m o v e d
by filtration and purified by r e p r e c i p i t a t i o n f r o m alcohol by the addition of e t h e r . Analytically p u r e IId
was obtained by r e p e a t e d r e p r e e i p i t a t i o n .
A s i m i l a r p r o c e d u r e was used to obtain I I a - c . The yields w e r e 5-18%. The composition of the di-
a z o t a t e s was c o n f i r m e d by e l e m e n t a r y a n a l y s i s for one to two e l e m e n t s .
2 - B e n z o t h i a z o l y l n i t r o s o a m i n e s (IIIa-d). An e q u i m o l e c u l a r amount of 50% acetic acid was added to a
cooled aqueous solution of purified sodium diazotate (1 : 50), and the r e s u l t i n g p r e c i p i t a t e was r e m o v e d by
filtration, washed on the filter with ice w a t e r , and v a c u u m dried over c a l c i u m chloride. P u r e p r i m a r y
n i t r o s o a m i n e s w e r e obtained in quantitative yields. The c o m p o s i t i o n of the n i t r o s o a m i n e s was c o n f i r m e d
by e l e m e n t a r y a n a l y s i s f o r one to two e l e m e n t s .
3 - M e t h y l - 2 - i m i n o b e n z o t h i a z o l e was obtained f r o m N - m e t h y l a n i l i n e by the method in [10]; nitrosation
was c a r r i e d out by the method in [10].
2 - { N - M e t h y l - N - n i t r o s o a m i n o ) b e n z o t h i a z o l e (IV). Sodium nitrite [0.324 g (4.7 , m o l e ) ] in the f o r m of
a 20% solution was added with s t i r r i n g at r o o m t e m p e r a t u r e to a solution of 0.5 g (3.0 , m o l e ) of 2 - m e t h y l -
a m i n o b e n z o t h i a z o l e in 3 ml of glacial acetic acid, a f t e r which the m i x t u r e was allowed to stand. The r e -
sulting light-yellow p r e c i p i t a t e was r e m o v e d by filtration, washed with water, and r e c r y s t a l l i z e d f r o m
benzene (1: 10). The yield was 85%. Xma x 315 nm (in alcohol), 320 nm (in c h l o r o f o r m ) . FOund: C 50.2;
H 4.0; N 21.7%. CsttTN3OS. Calculated: C 50.0; H 3.7; N 21.8%.

LITERATURE CITED
1. A. Spilliadis and M. H i l s e n r a t h , Rev. Chim., 1..~7, 271 (1966).
2. E a s t m a n Kodak Co., US P a t e n t No. 2,868,775 (1959); R e f e r a t i v n y Zh. Khim., 74,444 P (1960).
3. J. G o e r d e l e r and H. Haubrieh, B e r . , 9__33,397 (1960).
4. D. F. De T a r ancl A. R. Ballentine, J. Am. Chem. Soc., 7..~8,3916 (1956).
5. D. A. Drapkina, V. G. B r u d z ' , and Z. S. Sidenko, Zh. Obshch. Khim., 32, 1535 (1962).
6. L. P e n t i m a l l i , Chim. I n d u s t r i a , 39~ 11 (1957).
7. N. S. Drozdov, Zh. Obshch. Khim., 7, 1668 (1937).
8. C. Allen and J. Van Allan, in: Organic Syntheses, Vol. 3, Wiley.
9. C. G. Stuckwisch, J. A m . Chem. Soc., 71, 3417 (1949).
10. E. Besthorn, B e r . , 43, 1519 (1910).

323
SYNTHESIS IN T H E PHENOTHIAZINE SERIES
XXXVI.* QUATERNARY SALTS OF IMIDAZO[4,5,1-k,/]PHENOTHIAZINE
AND THEIR TRANSFORMATIONS

Z. I. E r m a k o v a , A . N. G r i t s e n k o , UDC 547.869.2.07
a n d S. V . Z h u r a v i e v

Q u a t e r n a r y salts of imidazo[4,5,1-k,l]phenothiazine were reduced with potassium b o r o h y -

dride to 1,2-dihydro-2-methylimidazo[4,5,1-k,/]phenothiazine, which was converted to 1,2-
d i h y d r o - 2 - m e t h y l i m i d a z c [ 4 , 5 , 1 - k , l ] p h e n o t h i a z i n e - l - t h i o n e and 1 - m e t h y l a m i n o - 1 0 - f o r m y l -
phenothiazine. The latter was hydrolyzed to 1-methylaminophenothiazine, which was also
obtained by reduction of methyl p h e n o t h i a z i n e - l - c a r b a m a t e . The PMR and IR s p e c t r a of
some of the derivatives are discussed.

A number of p r e p a r a t i o n s with c a r d i o v a s c u l a r and psychotropic action have been found in the pheno-
thiazine s e r i e s . Imidazophenothiazine derivatives m a y also have physiological activity.
An attempt to reduce imidazo[4,5,1-k,l]phenothiazine (I) with potassium borohydride or lithium alu-
minum hydride [2] did not give the d e s i r e d r e s u l t s . In this connection, the q u a t e r n a r y salts of I (IIa, b)
with methyl iodide and dimethyl sulfate were obtained and reduced with potassium borohydride to 1,2-
dihydro-2-methylimidazo[4,5,1-k,l]phenothiazine (III). The nature of the anion in the q u a t e r n a r y salt does
not affect the c o u r s e of the reduction. Singlets of the protons of the CH 2 group at 4.62 ppm and of the CH3
group at 2.66 ppm were observed in the PMR s p e c t r u m of a c h l o r o f o r m solution of III. These data confirm
the direction of the reduction. Just as in 1,2-dihydrobenzimidazole [3], the hydrogens of the methylene
group in III have hydride lability. The reaction of HI with sulfur gave 1 , 2 - d i h y d r o - 2 - m e t h y l i m i d a z o [ 4 , 5 , 1 -
k,/]phenothiazine-l-thione (IV). Heating III with carbon tetrachloride, which is a proton acceptor in t h i s
reaction, gives chloride IIc, and the carbon tetrachloride is reduced to c h l o r o f o r m . The formation of the
latter is c o n f i r m e d by the PMR s p e c t r u m of the filtrate obtained after separation of chloride IIc (proton
signal at 7.2 ppm). Like other q u a t e r n a r y salts, chloride IIe is reduced to III. When an attempt was made
to c o n v e r t III to imidazophenothiazone in analogy with [3], the imidazoline ring was cleaved to give 1,10-
disubstituted phenothiazine (V).
The IR s p e c t r a of a m i n e r a l oil suspension of V and a 0.1 M solution of V in c h l o r o f o r m contain c h a r -
a c t e r i s t i c bands for the NH group at 3374 and 3325 cm -1 (less intense) and for the CO group at 1674 cm-1;
dilution of the c h l o r o f o r m solution to a concentration of 1 . 1 0 -3 M leads to the disappearance of the bands
at 3374 and 3325 e m -1 and to the appearance of a band at 3430 cm-1; this indicates the p r e s e n c e of i n t e r -
m o l e c u l a r hydrogen bonds in the concentrated solutions. When V is deuterated (CH3OD+ D20) , the band of
the NH groups is shifted to 2453 c m -1.
The PMR s p e c t r u m of a c h l o r o f o r m solution of V contains singlets of protons for the N - C H 3 group
at 3.22p.pm, for the NH group at 6.5 ppm, and for the CHO group at 8.22 ppm. Compound V gives stable

* See [1] for communication XXXV.

Institute of P h a r m a c o l o g y , A c a d e m y of Medical Sciences of the USSR, Moscow. T r a n s l a t e d from

Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 372-374, March, 1974. Original a r t i c l e submitted
November 9, 1972.

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy of this article is available from the publisher for $15.00.

324
 L HC:--N 3Jx- H2C--N--CH~I s=Ci~N--CHa
I II ~ III IV
OH-

OHC NHCH3 NHCHs NHCOOCH3

V VI VII

lla X ~ | ; b x=CH3SO4; c X=CI

h y d r o c h l o r i d e s , Thus the data obtained made it p o s s i b l e to a s s i g n t h e 1 - m e t h y l a m i n o - 1 0 - f o r m y l p h e n o t h i a z i n e

s t r u c t u r e to V. Compound V was also obtained b y a l k a l i n e h y d r o l y s i s of the q u a t e r n a r y salts of imidazopheno-
thiazine at r o o m t e m p e r a t u r e . HeatingV in an alcohol solution of sodium hydroxide hydrolyzed it to 1 - m e t h y l -
aminophenothiazine (VI); the l a t t e r was also obtained by a l t e r n a t i v e synthesis by reduction of methyl pheno-
t h i a z i n e - l - c a r b a m a t e (VII) with lithium aluminum hydride.

EXPERIMENTAL
The PMR s p e c t r a w e r e r e c o r d e d with a V a r i a n T-60 s p e c t r o m e t e r . The IR s p e c t r a w e r e r e c o r d e d
with a UR-10 s p e c t r o m e t e r .
2-Methylimidazolio[4,5,1-k,l]phenothiazine Iodide (IIa). A 2.24 g (0.01 mole) s a m p l e of imidazo[4,5,1-
k,/]phenothiazine (I) was dissolved in a m i x t u r e of acetone and ether, 3 ml of methyl iodide was added, and
the m i x t u r e was allowed to stand for 3 days. A c r y s t a l l i n e p r e c i p i t a t e f o r m e d f r o m the solution; the yield
was 3.1 g. The c o l o r l e s s needles w e r e soluble in w a t e r and alcohol and had m p 248-250 ~ Found: I 34.2;
N 7.4%. C14HllIN2S. Calculated: I 34.7; N 7.6%.
2-Methylimidazolio[4,5,1-k,l]phenothiazine Methosulfonate (IIb). A 2.24 g (0.01 mole) s a m p l e of I
was m i x e d with 5 ml of distilled dimethyl sulfate, and the m i x t u r e was heated at 100-110 ~ for 1.5 h. It was
then cooled, and the r e s u l t i n g p r e c i p i t a t e was t r e a t e d with e t h e r to give 2.8 g (75%) of a substance with m p
247-248 ~ ( f r o m anhydrous ethanol). Found: N 8.1; S 18.2%. CtsH14N~O4S2. Calculated: N 8.1; S 18.2%.
2-iViethylimidazolio[4,5,1-k,/]phenothiazine Chloride (IIc). A 0.24 g (0.001 mole) s a m p l e of 1,2-di-
h y d r o - 2 - m e t h y l i m i d a z o l i n o [ 4 , 5 , 1 - k , / ] p h e n o t h i a z i n e was refluxed in 5 m l of carbon t e t r a c h l o r i d e , during
which a c o l o r l e s s c r y s t a l l i n e substance that was r e a d i l y soluble in w a t e r precipitated. The yield of p r o d -
uct with m p 243-244 o ( f r o m anhydrous i s o p r o p y l alcohol) was 0.3 g. Found: C1 12.5; N 9.9%. C14HllC1N2S.
Calculated: C1 12.8; N 10.2%.
1 , 2 - D i h y d r o - 2 - m e t h y l i m i d a z o [ 4 , 5 , 1 - k , / ] p h e n o t h i a z i n e (HI). A 3.5 g (0.01 mole) s a m p l e of IIb was
dissolved in 60 m l of 80% aqueous alcohol, and 1.5 g of p o t a s s i u m borohydride d i s s o l v e d in w a t e r was added
in portions. The r e a c t i o n m i x t u r e was s t i r r e d at 50 ~ for 1 h, a f t e r which it was cooled, and the r e s u l t i n g
g r e e n i s h p r e c i p i t a t e was r e m o v e d by filtration to give 1.8 g (75%) of III with m p 88-89 ~ ( f r o m aqueous eth-
anol). The l i g h t - g r e e n needles w e r e soluble in toluene and ethyl a c e t a t e but insoluble in w a t e r . Found: C
69.7; H 5.1; N 11.5; S 13.5%. C14H12N2S. Calculated: C 70.0; H 5.0; N 11.6; S 13.3%. UV s p e c t r u m (in a l -
cohol), k m a x , a m (log ~): 236 (4.40), 272-276 (4.20), 324-328 (3.67).
Compound IX was s i m i l a r l y obtained by reduction of Ia and IIc.
1 , 2 - D i h y d r o - 2 - m e t h y l i m i d a z o [ 4 , 5 , 1 - k , / ] p h e n o t h i a z i n e - l - t h i o n e (IV). A 0.48 g (0.002 mole) s a m p l e
of IX was fused with 0.1 g (0.003 mole) of sulfur at a bath t e m p e r a t u r e of 150 ~ f o r 30 rain. Hydrogen s u l -
fide was evolved, and the m a s s solidified. C r y s t a l l i z a t i o n f r o m toluene and then ethanol gave white needles
with m p 162-163 ~ Found: N 10.4; S 24.0%. CIr Calculated: N 10.4; S 23.7%.
1-1VIethylamino-10-formylphenothiazine (V). A) A 0.70 g (0.002 mole) s a m p l e of IIb was dissolved in
w a r m w a t e r , and a dilute solution of sodium hydroxide was added until the m i x t u r e was alkaline. A c r y s -
talline s u b s t a n c e [0.43 g (70%)] with mp 169-170 ~ ( f r o m ethanol) and R f 0.63 [activity II A1203, a l c o h o l -
c h l o r o f o r m (1:10)] p r e c i p i t a t e d . Found: N 11.3; S 12.7%. C14H12N2OS. Calculated: N 10.93; S 12.56%.
The h y d r o c h l o r i d e of V had m p 218 ~ (dec., f r o m aqueous ethanol). Found: C1 11.9%. CIcX12N2OS. HCL
Calculated: C1 12.2%.

325
 B) Oxygen was bubbled into a w a r m solution of 0.24 g (0.001 mole) of III in alcohol for 2 h, during
which the m i x t u r e darkened. It was t r e a t e d with c h a r c o a l and filtered, and 0.18 g (70%) of a c o l o r l e s s sub-
stance with rap 167'168 ~ p r e c i p i t a t e d f r o m the filtrate. No m e l t i n g - p o i n t d e p r e s s i o n was o b s e r v e d for a
m i x t u r e of this product with a s a m p l e of V obtained by method A.
1-Methylaminophenothiazine (VI). A) A solution of 0.54 g (0.002 mole) of methyl p h e n o t h i a z i n e - 1 -
c a r b a m a t e [4] in 3 m l of anhydrous t e t r a h y d r o f u r a n (THF) was added to an e t h e r solution of an e x c e s s of
lithium aluminum hydride. The m i x t u r e was then s t i r r e d and refluxed for 5 h. The e x c e s s lithium alu-
m i n u m hydride was d e c o m p o s e d with m o i s t THF. The aluminum hydroxide was r e m o v e d by filtration and
washed with e t h e r . The ether filtrate was evaporated, and the r e s i d u e was dissolved in dilute hydrochloric
acid. The acidic aqueous solution was t r e a t e d with activated c h a r c o a l and filtered, and the base was i s o -
lated by t r e a t m e n t with aqueous sodium hydroxide solution. The p r e c i p i t a t e was r e m o v e d by filtration to
give shiny plates with m p 84-85 ~ ( f r o m aqueous alcohol) that darkened on e x p o s u r e to a i r . The product had
R f 0.61 [activity II AI~O3, a l c o h o l - c h l o r o f o r m (1: 10)]. Found: N 12.3; S 13.9%. C13HI2N2S. Calculated: N
12.3; S 14.0%.
B) An aqueous solution of 0.1 g (2.5 m m o l e ) of sodium hydroxide was added to a solution of 0.51 g
(0.002 mole) of V in 5 ml of alcohol, and the m i x t u r e was refluxed for 2 h. It was then diluted with w a t e r
and t r e a t e d with a c t i v a t e d charcoal. The m i x t u r e was filtered, and 0.25 g of VI with m p 83-84 ~ p r e c i p i t a t e d
f r o m the f i l t r a t e .
C) Under the conditions of method B, 0.35 g (0.001 mole) of IIb gave 0.1 g of a substance with rap 83-
84 ~ which was identical to the product obtained above.

LITERATURE CITED
1. Z. I. E r m a k o v a , A. N. Gritsenko, a n d S. V. Zhuravlev, Khim. Geterotsikl. Soedin., 202 (1974).
2. A. N. Gritsenko, Z. I. E r m a k o v a , V. S. T r o i t s k a y a , and S. V. Zhuravlev, Khim. G e t e r o t s i k L Soedin.,
767 (1971).
3. A. V. E l ' t s o v , Zh. Organ. Khim., 3, 199 (1967).
4. S. V. Z h u r a v l e v , A. N. Gritsenko, and Z. I. E r m a k o v a , Khim. G e t e r o t s i k l . Soedin., No. 3, 235 (1971).

326
CHEMISTRY OF INDOLE
XL.* NITRATION OF THE BENZENE RING OF 5- AND 7-METHYLINDOLES

A. N. Kost, L. G . Y u d i n , UDC 547.754.756 : 542.958.1 : 543.544.25.51

E. Ya. zinchenko, A. B. Belikov,
and O. A. Solov'ev

Nitration of 5- and 7 - m e t h y l - 3 - e a r b e t h o x y i n d o l e s leads to a m i x t u r e of 4- and 6-nitroindoles

with p r e d o m i n a n c e of the 4 - n i t r o i s o m e r .

During the nitration of 5-hydroxyindole d e r i v a t i v e s it was noted that r e p l a c e m e n t of the hydrogen

atom of the hydroxyl g r o u p can change the orientation of the entering substituent a p p r e c i a b l y [1]. The
change in orientation m i g h t have been a s s o c i a t e d with the fact that the p r i m a r y p r o c e s s goes through a
step involving the f o r m a t i o n of the c o r r e s p o n d i n g oxoniu_m compound. In this connection, we r e p l a c e d the
RO group by a m e t h y l group, t h e r e b y s i m u l t a n e o u s l y excluding the p o s s i b l e contribution of the M effect to
the orienting effect of the substituent, and m a d e a c o m p a r a t i v e study of the nitration of a number of 5- and
7-methylindoles.
It was found that 4-nitroindole IIb containing s o m e 6 - n i t r o i s o m e r Ha is f o r m e d in the reaction of
nitric acid (sp. gr. 1.5).with 1 , 2 , 5 - t r i m e t h y l - 3 - c a r b e t h o x y i n d o l e (I) in acetic acid.
~o~
c.~~cooc~"~ c.~.{.~_~..cooc~.~+ c . ~ ~ c o o c ~ . ~
",,~_/~.. N/ "--CH 3 NO2/~N,./"C H3 " - . ~ / ' - . . Nj " x , C H3

CH 3 Clt 3 CH a

I II a 1113

~.~..]~coo~.~c.~..~~ooc~.~ NH 2

CH a CH a
III a !11 19

After reduction of II, the r e s u l t i n g a m i n e s , IIIa and HIb, could be r e a d i l y s e p a r a t e d and identified.
Thus r e p l a c e m e n t of the 5 - m e t h o x y group by a m e t h y l group does not change the orientation in nitration,
and the u n s h a r e d p a i r of e l e c t r o n s of the CH30 g r o u p consequently is not of substantial significance for the
orientation of the e n t e r i n g substituent, which is d e t e r m i n e d f i r s t of all by the o v e r a l l distribution of e l e c -
tron density in the 3 - c a r b e t h o x y i n d o l e s .
When t h e r e is a methyl group in the 7 position, i.e., in the nitration of 1 , 2 , 7 - t r i m e t h y l - 3 - c a r b e t h o x y -
indole (IV), substitution p r o c e e d s p r i m a r i l y in the 4 position (in the p a r a position r e l a t i v e to the methyl
group), and t h e r e is a s o m e w h a t l e s s e r d e g r e e of substitution in the 6 position ( i s o m e r r a t i o 4 : 3).
Thus in 7 - s u b s t i t u t e d indoles the effect of a substituent in the benzene ring is e x p r e s s e d m o r e strongly
than for 5 - s u b s t i t u t e d indoles. The PMR s p e c t r a of nitroindoles Va and Vb in the a r o m a t i c region each have

* See [1] for c o m m u n i c a t i o n XXXIX.

M. V. L o m o n o s o v Moscow State U n i v e r s i t y . T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedin-

enii, No. 3, pp. 375-379, March, 1974. Original a r t i c l e s u b m i t t e d F e b r u a r y 13, 1973.

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy of this article is available from the publisher for $15.00.

327
 NO 2
~..~COOC2 H5 ~-.~/CO0 C2Hs + ~COOC~H~

CH3 CH3 CHa CH3 CH3 CH3

IV Va vb

two d o u b l e t s of o r t h o - c o u p l i n g p r o t o n s with a s p i n - s p i n s p l i t t i n g c o n s t a n t of ~ 9 Hz. T h e 5 - H p r o t o n in

s t a r t i n g i n d o l e IV r e s o n a t e s at 6.73 p p m , w h i l e 5 - H in Vb r e s o n a t e s at 7.43 p p m . T h e s h i f t of the 5 - H p r o t o n
u n d e r t h e i n f l u e n c e of t h e a d j a c e n t n i t r o g r o u p i s 0.70 p p m (as c o m p a r e d with 0.21 p p m f o r the 4 - H p r o t o n ) ;
t h i s i s in c o n f o r m i t y with p r e v i o u s o b s e r v a t i o n s . A s i m i l a r e x a m i n a t i o n and c o m p a r i s o n with a l t e r n a t i v e
c a l c u l a t i o n s m a k e it p o s s i b l e t o a s s i g n s t r u c t u r e V a to t h e s e c o n d i s o m e r ,

M o r e d e f i n i t e d a t a on the s t r u c t u r e s of V a and Vb w e r e o b t a i n e d in a s t u d y of the m a s s s p e c t r a . U n -

d e r the i n f l u e n c e of e l e c t r o n i m p a c t , a r o m a t i c n i t r o c o m p o u n d s d i s i n t e g r a t e d i f f e r e n t l y d e p e n d i n g on the
p o s i t i o n of the n i t r o g r o u p w i t h r e s p e c t to the m e t h y l g r o u p [2]. The m a s s s p e c t r a of both V c o m p o u n d s
h a v e an i n t e n s e m o l e c u l a r p e a k , w h i c h c o r r e s p o n d s to the m o n o n i t r o c o m p o u n d , but t h e i r s u b s e q u e n t f r a g -
m e n t a t i o n d i f f e r s . The m o l e c u l a r ion of V a f o r m s e i t h e r a r e l a t i v e l y i n t e n s e i o n with m / e 230 ( M - 4 6 ) o r
an ion w i t h m / e 203 (M-73). B o t h of t h e s e p r o c e s s e s a r e c o n f i r m e d by the p e a k s of the c o r r e s p o n d i n g
m e t a s t a b l e i o n s . In a d d i t i o n , t h e r e i s a p e a k w i t h m / e 2 3 1 ( M - 4 5 ) i n the s p e c t r u m of V a . T h e ion with m / e
230 m a y be f o r m e d t h r o u g h the l o s s of a n i t r o g r o u p o r C2H5OH d u r i n g a M a e L a 2 f e r t y r e a r r a n g e m e n t . B o t h
p r o c e s s e s a p p a r e n t l y o c c u r in o u r c a s e , i n a s m u c h a s , on the one hand, a f u r t h e r l o s s by the 230 i o n of an
NO g r o u p to give an ion with m / e 200 (the l a t t e r l o s e s CO m o l e c u l e s t w i c e to give i o n s w i t h m / e 172 and
144) i s o b s e r v e d . On t h e o t h e r hand, the ion w i t h m / e 230 l o s e s an e t h o x y g r o u p , a n d t h i s l e a d s to an ion
+ NO2 ' +. NO~ ~+.

i" il }I -~ ~I} " ~ oco..o. LE JL

~L..~./.p.~N.,..~.CH3 - . ~ N ~p\CH3 *
CH3 CH 3 CH3 CH3 CH3 CH3
m/e 230 Va ,'~1+ 276 m/c 230

CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH~

,n/e [85 ,,I/e 231 m/c 203 m/e 200

'l -CO O I-CO

II

~,. I CH~ CH3 CH~.

~n:s CH:3 CH3 CH3 CH3 CH~,
~/. ,sT ,./. ,44 . . / . n2

with m / e 185,-which a l s o t h e n l o s e s CO to g i v e an ion with m / e 157. A l l of t h e i n d i c a t e d p r o c e s s e s a r e c o n -

f i r m e d by m e t a s t a b l e i o n s . T h u s f r a g m e n t a t i o n of t h e m o l e c u l a r ion of n i t r o i n d o l e V a i s t y p i c a l f o r a r o m a t i c

T A B L E 1. R e l a t i v e I n t e n s i t i e s and m / e V a l u e s of the P r i n c i p a l
F r a g m e n t I o n s in the M a s s S p e c t r a of N i t r o m e t h y l i n d o l e s
6-Nit~oindole IIa 4-Nitroindole Va. . . . . I - - - 6-Nitroindole v b
me I, % m/e I, % me 1, %

276 100 276 100 [ 276 109

259 54 231 50 I z59 87
231 45 230 21 ] 231 56
230 9 203 19 ~ 230 : 11
213 6 200 17 i 213 ] 12
203 11 185 12 ] 203 20
185 12 172 25 ! ls~ 28
157 24 157 72 ] 157 ! 22
144 25 !t

328
nitro compounds [2] and specifically it is s i m i l a r to the fragmentation of p-nitrotoluene, The splitting out
of an ethoxy o r carbethoxy group p r o c e e d s in the m a n n e r that is known for the ions of o-toluic acid e s t e r s [3].
At the same time, the m o l e c u l a r ion in the m a s s s p e c t r u m of 6-nitro i s o m e r Vb loses an OH group,
and this leads to the formation of an ion with m / e 2 5 9 (M-217),which is absent in the m a s s s p e c t r u m of 4 -
n i t r e i s o m e r Va. This ion then loses C2H5Ott molecules to give an ion with m / e 213, which is also c o m -
pletely absent in the s p e c t r u m of indole Va. This s o r t of path of disintegration is c h a r a c t e r i s t i c for a r o -
matic nitro compounds that contain a methyl group in the ortho position [2]. Peaks that a r e p r e s e n t in the
s p e c t r u m of 4 - n i t r o i s o m e r Va were also observed in addition to this (Table 1).
The m o l e c u l a r ion in the m a s s s p e c t r u m of 6-nitroindole IIa, r e g a r d i n g the s t r u c t u r e of which there
is no doubt, also loses an OH group to give

,[(~-~COOC2H5 .~__~COOC_H_-~ C H OH
O-- N~ . " ~ . . . . N / \ CH. NO ~/'-~...J"~ N/ x~CH~
[I/ "!.. 1 ~ " t I "
Ctl~ Cl-I~ o:~Cl'12 Ctt~ CH~ CH3
"CO

/ t-C2H50
~-~COOC2H51 ~ - - ~ C-~-OCO ~ + -NO2, ~ - - - - " ~ +
O-_~ ~ N .Y".CHa NO2A~'N"-~ N.-9~C H3 NO2~/~.">~.N f ' ~ C . 3 "~"~,,.-,t"x,,
N/'x. CU3
OH the CH 2 ~;H z CH. '~n3 CH 3 3 ~n3

t_OH m/e 231 . ,,:I e ~o3 ,,le ,s;

' CH2 CH3 CH2 CH3 CH3 CH3

m/e ~59 m/e 2i3 -l/e t85

an ion with m/e ( M - 1 7 ) . This ion then loses a C2HsOH molecule to give a c h a r a c t e r i s t i c ion with m / e 213.
In addition, other c h a r a c t e r i s t i c ions a r e p r e s e n t in the m a s s s p e c t r u m : m / e 231, 230, 213, 203, 185, and
157. This c o n f i r m s the c o r r e c t n e s s of the interpretation of the m a s s s p e c t r u m of 6-nitroindole Vb.
The UV s p e c t r a of 4 - (Va) and 6-nitroindoles (Vb) differ f r o m that of the starting 1 , 2 , 7 - t r i m e t h y l -
3-carbethoxyindole (IV) with r e s p e c t to the a p p e a r a n c e of a m a x i m u m in the long-wave region and the c h a r -
a c t e r i s t i c (for nitroindoles [4]) shift of the m a x i m u m to the s h o r t - w a v e region (see F i g . 1).

EXPERIMENTAL
The IR s p e c t r a of m i n e r a l oil suspensions were r e c o r d e d with an IKS-22 s p e c t r o m e t e r . The UV
s p e c t r a of c h l o r o f o r m solutions of IIa, Va, and Vb and of alcohol solutions of the remaining compounds
were r e c o r d e d with a Cary-15 s p e c t r o p h o t o m e t e r . The PMR s p e c t r a of t r i f l u o r o - a c e t i c acid solutions
were r e c o r d e d with a Varian S-60T s p e c t r o m e t e r with hexa:methyldisiloxane (ttMDS) as the external stan-
dard. The m a s s s p e c t r a of indoles IIa and Va were r e c o r d e d with an MKh-1303 s p e c t r o m e t e r with a s y s -
tem for introduction of the sample d i r e c t l y into the ion source (50 eV, 110-120~ The m a s s s p e c t r u m of
indole Vb was r e c o r d e d with a Varian MAT-111 Gnome s p e c t r o m e t e r (80 eV, 120~ The p r o c e s s was m o n -
itored by m e a n s of t h i n - l a y e r c h r o m a t o g r a p h y (TLC) on aluminum oxide (activity II, Brockmann c l a s s i f i c a -
tion) in b e n z e n e - e t h y l a c e t a t e - h e p t a n e (4 : 1 : 3).
1 , 2 , 7 - T r i m e t h y l - 3 - c a r b e t h o x y i n d o l e (IV). A m i x t u r e of 11.3 g (0.08 mole) of N - m e t h y l - o - t o l y l h y -
drazine and 12 ml (0.08 mole) of acetoacetic e s t e r was refluxed on a water bath for 1 h. The Water was
r e m o v e d by distillation, 20 ml of polyphosphoric acid was added to the residue, and the mixture was heated
to 95-100 ~ for 5-10 rain. It was then cooled, and the resulting precipitate was r e m o v e d by filtration and
r e c r y s t a l l i z e d f r o m methanol to give 2.4 g (15%) of indole IV With mp 97-98 ~ and R f 0.9. IR s p e c t r u m :
1675 c m -1 (CO). UV s p e c t r u m , hmax, rim (log ~): 220 (4.56), 290 (4.05); c h l o r o f o r m : 220 (4.40), 290 (4.13).
PMR s p e c t r u m * : ~ 6.63 (6-H, sd), 6.73 (5-H, d, J = 7 Hz), 7.57 (7-H, sd), 2.26, 2.21, 3.20 (N-CH3, 2-CH3,

* The following abbreviations were adopted h e r e and elsewhere: s is singlet, d is doublet, t is triplet, sd
is split doublet, and q is quartet.

329
 4,51 7-CH3, s), 4.23 (3-CH2, q), 1.30 ppm (CHa, t). Found: C 72.8; tI
7.5; N 6.2%. C14HtTNO2. Calculated: C 72.6; H 7.4; N 6.1~0.
1 , 2 , 7 - T r i m e t h y l - 3 - c a r b e t h o x y - 4 - n i t r o i n d o l e (Va) and 1,2,7-
T r i m e t h y l - 3 - c a r b e t h o x y - 6 - n i t r o i n d o l e (Vb). A 0.63 g (0.01 mole)
sample of nitric acid (sp. gr. 1.5) was added at room t e m p e r a -
ture to a solution of 2.31 g (0.01 mole) of trimethylindole IV in
3~5 ~ 80 ml of glacial acetic acid, and the m i x t u r e was s t i r r e d for 16 h.
The precipitate was then r e m o v e d by filtration, washed with 3 ml
of acetic acid and water, and air dried. R e c r y s t a l l i z a t i o n from
benzene gave 0.46 g of 4-nitroindole Va with rap 186-187 ~ and R f
I | I ! I I i~
200 ' 300 40C A.nm 0.35. IR spectrum: 1700 (CO), 1530, 1325 cm -I (NO2). UV s p e c -
t r u m : Xmax 365 am, log e 3.69. PMR spectrum: ~ 7.54, 6.88
Fig. i. U V s p e c t r a (in chloroform):
(5-H, 6-H, d, J = 9 Hz); 2.62, 2.43, 3.78 (N-CH3, 2-CH3, 7-Ctt3, s);
I) 1,2,7-trimethyl-3-carbethoxy-4-
4.30 (3-CH2, q); 1.25 ppm (CH~, t). Found: C 61.5; H 5.6; N 10.5%.
nitroindole (Va); 2) 1 , 2 , 7 - t r i m e t h y l -
CI4HI~N204. Calculated: C 61.0; H 5.8; N 10.1%. The acetic acid
3 , c a r b e t h o x y - 6 - n i t r o i n d o l e (Vb); 3)
filtrate was diluted with water, and the precipitate was r e m o v e d
1 , 2 , 7 - t r i m e t h y l - 3 - c a r bethoxyindole
by filtration, washed with water, and dried to give 1.4 g of a m i x -
(IV).
ture, which was separated with a column filled with aluminum
oxide. The column was eluted initially with petroleum ether and
then with b e n z e n e - p e t r o l e u m ether (2 9 1). The f i r s t yellow band contained 6-nitroindole Vb, the yield of
which was 0.5 g (18%) after r e c r y s t a l l i z a t i o n f r o m b e n z e n e - p e t r o l e u m ether (1 : 3); mp 138-141 ~ R f 0.53.
IR spectrum: 1670 (CO), 1505, 1310 cm -1 (NO2). UV s p e c t r u m , Xmax, nm (log c): 275 (4.35), 320 (3.75),
367 (3.82). PMR spectrum: ~ 7.43, 7.78 (4-H, 5-H, d, J = 9 Hz); 2.57, 2.57, 3.77 (N-CH3, 2-CH3, 7-CH3, s);
4.37 (3-CH2, q); 1.40 ppm (CH3, t). Found: C 61.1; H 6.1; N 10.7%. Ci4Hl~N204. Calculated: C 61.0; H 5.8;
N 10.1%. The second yellow band contained 0.2 g of 4-nitroindole Va. The overall yield of Va was 0.66 g
(24%).
1 , 2 , 5 - T r i m e t h y l - 3 - c a r b e t h o x y - 6 - n i t r o i n d o l e (IIa) and 1 , 2 , 5 - T r i m e t h y l - 3 - c a r b e t h o x y - 4 - a m i n o i n d o l e
(IIIb). As in the preparation of Va, 0.2 g (15%) of 6-nitroindole IIa with mp 167-168 ~ and R / 0 . 5 8 was ob-
tained from 1.1 g (0.0043 mole) of 1,2,5-trimethylindole I [5] in 40 ml of glacial acetic acid after r e c r y s -
tallization from b e n z e n e - h e p t a n e (1:2). IR spectrum: 1690 (CO), 1500, 1300 cm -1 (NO2). UV spectrum,
l m a x , nm (log c): 277 (4.43), 335(3.96). PMR spectrum: 6 7.67, 7.86 (4-H, 7-H, s); 2.55, 2.40, 3.48 (N-
CH3, 2-CH3, 5-CtIa, s); 4.28 (3-CH2, q); 1.33 ppm (CIt3, t). Found: C 61.1; H 6.0; N 10.6%. C14Hi6N204.
Calculated: C1 61.0; It 5.8; N 10.1%.
The acetic acid filtrate was diluted with water to give 0.9 g of a m i x t u r e of nitro i s o m e r s , which was
r e c r y s t a l l i z e d f r o m benzene and reduced with hydrazine hydrate (3 ml) with Raney nickel in methanol. The
methanol was removed, and the residue was s e p a r a t e d p r e p a r a t i v e l y on aluminum oxide in b e n z e n e - e t h y l
a c e t a t e - h e p t a n e (4 : 1 : 3). The edges of the plates were developed with iodine vapors: the upper substance
was 4-aminoindole IIIb (Rf 0.60), and the lower substance was 6-aminoindole IIIa (Rf 0.1). The aluminum
oxide was eluted with methanol to give 0.1 g (33%) of 4-aminoindole IIIb with rap 126-128 ~ IR spectrum:
1670 (CO), 3400 cm -1 (NH). UV spectrum, Amax, nm (log c): 223 (4.83), 249 (4.25), 306 (3.98). PMR s p e c -
trum: ~ 7.34; 7.13 (6-I-I, 7-H, d, J = 8 Hz); 2.73, 2.43, 3.70 (N-Ctts, 2-CHa, 5-CH3, s); 4.42 (3-Ctt2, q); 1.43
ppm (CH3, t). Found: C 68.3; tt 7.5; N 11.1%. C14H18N202. Calculated: C 68.2; H 7.4; N 11.4%.

LITERATURE CITED
1. E. Ya. Zinchenko, L. G. Yudin, and A. N. Kost, Khim. G e t e r o t s i k L Soedin., 1646 (1973).
2. S. Meyerson, I. Puskas, and E. K. Fields, J. Am. Chem. Soc., 88, 4974 (1966).
3. F. W. M c L a f f e r t y and R. S. Gohlke, Anal. Chem., 31, 2076 (1959).
4. W. Noland, L. R. Smith, and K. Rush, J. Org. Chem., 30, 3457 (1965).
5. A. N. Kost, L. G. Yudin, and E. Ya. Zinchenko, Khim. Geterotsikl. Soedin., 332 (1973).

330
CONDENSATION OF 2-(ACETAMIDO)CYCLOHEXANONE
WITH MALONONITRILE

V. I. Shvedov, M. V. Mezentseva, UDC 547.754'853.7 : 542.953

L. B. Altukhova, and A. N. Grinev

Depending on the conditions, condensation of 2 - ( a c e t a m i d o ) - c y c l o h e x a n o n e with m a l o n o n i t r i l e

gives 1 - a c e t y l - 2 - a m i n o - 3 - c y a n o - 4 , 5 , 6 , 7 - t e t r a h y d r o i n d o l e or 2 - a m i n o - 3 - c y a n o - 4 , 5 , 6 , 7 -
t e t r a h y d r o i n d o l e , f r o m which substituted t e t r a h y d r o p y r i m i d o [ 1 , 2 - a ] i n d o l e and t e t r a h y d r o -
pyrimido[4,5-b]indole w e r e synthesized.

In our r e s e a r c h (for e x a m p l e , see [1]) we have shown that N - a c y l d e r i v a t i v e s of ~ - a m i n o t h i o p h c n e

behave like unsubstituted a m i n e s . In this connection, we have i n v e s t i g a t e d the condensation of 2 - ( a c e t -
amido)cyclohexanone with m a l o n o n i t r i l e in the p r e s e n c e of piperidine and have feared that, depending on the
t e m p e r a t u r e , e i t h e r 1 - a c e t y l - 2 - a m i n o - 3 - c y a n o - 4 , 5 , 6 , 7 - t e t r a h y d r o i n d o l e (I) or 2 - a m i n o - 3 - c y a n o - 4 , 5 , 6 , 7 -
t e t r a h y d r o i n d o l e (rI), which is p r o b a b l y f o r m e d by t r a n s f e r of the acetyl group f r o m I to the piperidine, is
f o r m e d in high yield. When I is heated with acetic acid, 2 - a c e t a m i d o - 3 - c y a n o - 4 , 5 , 6 , 7 - t e t r a h y d r o i n d o l e (III)
is formed; this is a p p a r e n t l y a s s o c i a t e d with i n t r a m o l e c u l a r m i g r a t i o n of a COCH 3 group. A t r i a c y l d e -
r i v a t i v e (IV) is f o r m e d when I is refluxed with acetic anhydride. IIowever, acetylation of II with acetic an-
hydride in benzene gives a m i d e III, while acetylation in t r i e t h y l a m i n e gives a m i x t u r e of HI and IV.

~NHCOCtI~ I: 2-CN
/, t

/,,, N

NH2

It

VI V VII

The signals of the protons of t h r e e a c e t y l g r o u p s of IV a p p e a r in the PMR s p e c t r u m as two singlet s -

6H at 2.34 and 3H at 2.60 ppm. The s p e c t r u m of I contains a singlet signal at 2.53 ppm, which we a s s i g n e d
to the protons of the COCH 3 g r o u p attached to the r i n g nitrogen a t o m . The singlet lying at w e a k e r field
(2if, 7.10 ppm) is r e l a t e d to the protons of an unsubstituted amino group. The signal of the protons of the
COCII 3 g r o u p in the s p e c t r u m of HI is found at 2.10 ppm, while the signals of the protons of the NIl groups
a p p e a r as singlets at 10.70 and 11.16 ppm. A f o r m a m i d i n e d e r i v a t i v e (V) is f o r m e d when II is t r e a t e d with
ethyl o r t h o f o r m a t e mad then with a m m o n i a by the method in [2]. D e r i v a t i v e V is cyclized to 9-asnino-
5 , 6 , 7 , 8 - t e t r a h y d r o p y r i m i d o [ 4 , 5 - b ] i n d o l e (VI) under the influence of sodium methoxide. Condensation [3] of
II with a c e t y l a c e t o n e gives 2 , 4 - d i m e t h y l - 1 0 - c y a n o - 6 , 7 , 8 , 9 - t e t r a h y d r o p y r i m i d o [ 1 , 2 - a ] i n d o l e (VI).

S. Ordzhonikidze All-Union S c i e n t i f i c - R e s e a r c h P h a r m a c e u t i c a l - C h e m i s t r y Institute, Moscow. T r a n s -

lated f r o m K h i m i y a G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 3, pp. 380-382, March, 1974. Original a r t i c l e sub-
m i t t e d M a r c h 20, 1973.

9 19 75Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, withou; written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

331
 EXPERIMENTAL
The IR s p e c t r a of m i n e r a l oil suspensions of the compounds w e r e r e c o r d e d with a P e r k i n - E l m e r
s p e c t r o m e t e r . The UV s p e c t r a of ethanol solutions w e r e r e c o r d e d w i t h a Hitachi E P S - 3 T s p e c t r o p h o t o m -
e t e r . The PMR s p e c t r a w e r e r e c o r d e d with JNM-4H-100 and J E O L C-60ttL (Japan) s p e c t r o m e t e r s . The
i n t e r n a l s t a n d a r d s w e r e t e t r a m e t h y l s i l a n e and d e u t e r o d i m e t h y l f o r m a m i d e . The c o u r s e of the r e a c t i o n s
and the p u r i t i e s of the compounds obtained w e r e m o n i t o r e d by t h i n - l a y e r c h r o m a t o g r a p h y (TLC5 on Silufol
UV-254 plates in a c e t o n e - h e p t a n e (1: 1), b e n z e n e - m e t h a n o l (9: 15, and b e n z e n e - e t h y l acetate (1: 1) s y s -
tems.
1 - A c e t y l - 2 - a m i n o - 3 - c y a n o - 4 , 5 , 6 , 7 - t e t r a h y d r o i n d o l e (I5. A solution of 5.3 g (0.062 mole) of m a l o n o -
nitrile in 100 m l of absolute benzene was added to 9 g (0.062 mole) of 2-(acetamido)cyelochexanone [4] in
70 ml of absolute benzene* in such a way that the t e m p e r a t u r e of the r e a c t i o n m i x t u r e did not r i s e above
35 ~ The white p r e c i p i t a t e was r e m o v e d by filtration and washed with methanol and e t h e r to give 9.7 g
(77%5 of a product with m p 203-205 ~ ( f r o m ethanol). PMR s p e c t r u m , ppm: 1.70 (5,6-H), 2.25 (4-H5, 2.70
(7-H), 2.55 (COCH3), 7.10 (NH2). UV s p e c t r u m , ~max, nm (log e): 233 (4.42), 330 (3.245~ IR s p e c t r u m :
3435 and 3300 (VNH2), 2200 (vCN) , 1690 (Vc=o) cm -1. Found.. C 65.1; H 6.3; N 20.4%. CllH13N 3. Calcu-
latedi C 65.0; H 6.4; N 20.7%.
2 - A m i n o - 3 - c y a n o - 4 , 5 , 6 , 7 - t e t r a h y d r o i n d o l e (II). As above, but at 70-75 ~ II with mp 189-190 ~ ( f r o m
methanol) was obtained in 8470 yield. PMR s p e c t r u m , ppm: 1.62 (5,6-H), 2.27 (4,7-H), 5.43 (NH~), 9.86
(NHS. UV s p e c t r u m , Xmax, nm Clog e): 210 (4.37), 270 (3.66). IR s p e c t r u m : 3360 (VNH~), 3445 (VNH) , 218
(vCN) cm-1. Found: C 67.1; H 6.9; N 26.4%. C9HllN 3. Calculated: C 67.1; H 6.9; N 26.1%.
2 - A c e t a m i d o ~ 3 - c y a n o - 4 , 5 , 6 , 7 - t e t r a h y d r o i n d o l e (III). A) A m i x t u r e of 0.8 g (5 m m o l e ) of II, 75 m l of
absolute benzene, and 0.5 m l (5 m m o l e ) of acetic anhydride was refluxed for 1 h, a f t e r which it was cooled,
and the white p r e c i p i t a t e was r e m o v e d by filtration and washed with methanol and e t h e r to give 0.84 g (84%5
of a product with m p 283-284 ~ (dec., f r o m methanol). PMR s p e c t r u m , ppm: 1.70 (5,6-H), 2.10 (COCH3) ,
2.40 (4,7-II5, 10.70 and 11.16 (NH). IR s p e c t r u m : 3320 (VNH) , 2210 (vCN) , 1640 (VC=O) cm -1. UV s p e c -
t r u m , kmax, um Clog ~): 213 (4.19), 286 (3.985~ Found: C 64.6; H 6.4; N 20.4%. CllH13N30. Calculated:
C 65.0; H 6.4; N 20.770.
B) A m i x t u r e of 0.200 g (0.9 mmole) of I and 25 m I of glacial acetic acid was refluxed for 6 h, a f t e r
which it was cooled, and the p r e c i p i t a t e was r e m o v e d by filtration, washed with methanol and ether, and
r e c r y s t a l l i z e d f r o m m e t h a n o l to give 50% of a product with m p 283-284 ~
J - A c e t y l - 2 - d i a c e t a m i d o - 4 , 5 , 6 , 7 - t e t r a h y d r o i n d o l e (IV). A) A m i x t u r e of 0.5 g (0.002 mole) of I and
4 m l (0.04 mole) of acetic anhydride was refluxed for 1 h, a f t e r which the solution was cooled and poured
into w a t e r . The r e s u l t i n g oil began to c r y s t a l l i z e on cooling and t r i t u r a t i n g , and the solid was r e m o v e d by
filtration and washed with w a t e r to give 0.49 g (70%) of a product with m p 134-135 ~ (from ethanol). PMR
s p e c t r u m , ppm: 1.75 (5,6-H), 2.34 (1-COCH3) , 2.50 (4-H), 2.60 (2-COCH3) . 2.90 (7-H). UV s p e c t r u m , Xmax,
nm Clog ~): 216 (inflection) (4.17), 246 (3.91), 284 (3.44). IR s p e c t r u m : 2210 (vCN5 , 1760 (Vc= O) cm -1.
Found: C 62.5; H 6.0; N 15.0%. C15H17N~O3. Calculated: C 62.7; H 6.0; N 14.6%.
B) A m i x t u r e of 0.5 g (0.003 mole) of II, 3 m l (0.03 mole) of acetic anhydride, and 0.27 m l (0.003
mole) of t r i e t h y l a m i n e was refluxed for 2 h, cooled, and poured into water. The p r e c i p i t a t e was r e m o v e d
by filtration and washed with w a t e r and a s m a l l amount of methanol to give 42.5% of HI with m p 283-284 ~
(from methanol). The methanol m o t h e r liquor yielded IV (40.2%) with m p 134-135 ~ (from methanol).
2 - F o r m a m i d i n o - 3 - c y a a o - 4 , 5 , 6 , 7 - t e t r a h y d r o i n d o l e (V). A suspension of 2 g (0.012 mole) of II in 25
ml of ethyl o r t h o f o r m a t e was refluxed for 2 h, a f t e r which the m i x t u r e was e v a p o r a t e d to d r y n e s s in vacuo,
and 25 m l of ethanol, s a t u r a t e d at 0~ with a m m o n i a , was added to the r e s i d u e . The m i x t u r e was held at
r o o m t e m p e r a t u r e for 2 days, a f t e r which it was v a c u u m e v a p o r a t e d to d r y n e s s to give 2.34 g (100%) of a
product with m p 320 ~ (dec.). IR s p e c t r u m : 2200 c m -1 (vCN).
9 - A m i n o - 5 , 6 , 7 , 8 - t e t r a h y d r o p y r i m i d o [ 4 , 5 - b ] i n d o l e (VI). A m i x t u r e of 2 g of V in 30 m l of methanol
containing 0.7 g of sodium methoxide was refluxed for 1 h, a f t e r which it was vacuum e v a p o r a t e d to d r y -
n e s s to give 1.7 g (8570) of a product with m p > 360 ~ (dec., f r o m d i m e t h y l f o r m a m i d e ) . UV s p e c t r u m , Xmax,
um (log e): 224 (inflection) (4.145, 285 (3.88). Found: C 63.7; H 6.4; N 29.9%. CIoHI~Nr Calculated: C
63.8; H 6.4; N 29.8%.
* The r e a c t i o n can also be c a r r i e d out in alcohol and in e x c e s s piperidine.

332
 2 , 4 - D i m e t h y l - 1 0 - c y a n o - 6 , 7 , 8 , 9 - t e t r a h y d r o p y r i m i d o [ 1 , 2 - a ] i n d o l e (VH). A m i x t u r e of 0.4 g (2.4 re_mole)
of II, 2 ml of piperidine, and 0.25 ml (2.4 mmole) of acetylacetone was refluxed for 1 h, a f t e r which it was
cooled, and the precipitate was r e m o v e d by filtration and washed with methanol and e t h e r to give 0.22 g
(39.2%) of a product with m p 232-233 ~ (from methanol). Found: C 75.0; H 6.9; N 18.8%. C14H15Ns. Cal-
culated: C 75.6; H 6.7; N 18.6%.

LITERATURE CITED
1. V. I. Shvedov, I. A. Kharizomenova, and A. N. Grinev, USSR Author's Certificate No. 362,016 (1971);
Byul. Izobr., No. 2 (1973).
2. E. C. T a y l o r and R. W. Hendess, J. Am. Chem. Soc., 87, 1995 (1965).
3. V. I. Shvedov, I. A. Kharizomenova, L. B. Altukhova, and A. N. Grinev, Khim. Geterotsikl. Soedin.,
428 (1970).
4. V. I. Shvedov, L. B. Altukhova, and A. N. Grinev, Khim. Geterotsikl. Soedin., 131 (1972).

333
REACTION OF N-TRITYLAMINES WITH NITROGEN-CONTAINING
HETEROCYCLIC COMPOUNDS

P. F. Butskus, N. V. Raguotene, UDC 547.751T822.7t867.4

and A. I. Butskene

T r a n s t r i t y l a t i o n o c c u r s during the r e a c t i o n of N-trityl-N-(fl-cyanothethyl)amines with in-

dole, morpholine, and 2- and 4-aminopyridines. The detritylation and t r a n s t r i t y l a t i o n of the
synthesized compounds were studied.

T r a n s t r i t y l a t i o n to give, r e s p e c t i v e l y , 3-tritylindole (VI), N-tritylmorpholine (VII), and 2- (VIII) and

4-(tritylamino)pyridine (IX) o c c u r s during the reaction of N-trityl-N-(fl-cyanoethyl)amines (I) of the gen-
e r a l f o r m u l a RN[C(CGI-Is)3](CH2CH2CN) with indole (II), morpholine (III), and 2- (IV) and 4-aminopyridine (V).
The reagents used for the tritylation of II-V w e r e m e t h y l - (a), i s o p r o p y l - (b), butyl- (c), isobutyl- (d),
octyl- (e), allyl- (f), benzyl- (g), cyclohexyl- (h), phenyl- (i), and p - t e l y l - (j) I.
When VII-IX and N - t r i t y l p y r r o l i d i n e (X) and N-tritylpiperidine (XI) a r e heated with e x c e s s methanol,
allyl alcohol, ethylene glycol, glycerol, and phenol, transtritylation o c c u r s to give, r e s p e c t i v e l y , methyl
trityl ether (XII), allyl trityl ether (XIID, ethylene glycol monotrityl e t h e r (XIV), glycerol a - t r i t y l ether
(XV), and p-hydroxytetraphenylmethane. (XVI). When VII-XI are refluxed with acetic acid they give the de-
tritylation product - triphenylcarbinol. In c o n t r a s t to N - t r i t y l a t e d compounds VII-XI, C - t r i t y l a t e d d e r i v a -
tive VI does not f o r m t r a n s t r i t y l a t i o n and detritylation products with alcohols and acetic acid.

EXPERIMENTAL
3 - T r i t y l i n d o l e (VI). A mixture of 1.17 g (10 mmole) of II, 5 mmole of Ia-j, and 40 m m o l e of glacial
acetic acid in 10 ml of d r y benzene was refluxed for 10 h. The solvent was r e m o v e d by vacuum e v a p o r a -
tion, and the residue was t r e a t e d with a dilute solution of 40 mmole of sodium hydroxide. The precipitated
VI was washed with water and r e c r y s t a l l i z e d f r o m alcohol.* The yield of VI ranged f r o m 85 to 95%. The
product had mp 211-212~ which was in a g r e e m e n t with the l i t e r a t u r e data [1, 2].T
N - T r i t y l m o r p h o l i n e (VII). This compound was obtained as in the p r e c e d i n g experiment. A 0.87 g
(10 mmole) sample of HI was used to obtain VII with mp 175-176 ~ (mp 174-176 ~ [3]) in 87-96% y i e l d .

2-(Tritylamino)pyridine (VIII). This compound was obtained as in the preceding experiment. A 0.94 g
(10 mmole) sample of IV was used to obtain VIII with mp 151-152 ~ in 90-95% yield. The following melting
points a r e r e p o r t e d in the l i t e r a t u r e : 150-155 ~ [3], 150-151 ~ [4], and 152-153 ~ [5].
4-(Tritylamino)pyridine (IX). This compound (77-83%) was obtained as in the preceding e x p e r i m e n t s
f r o m 0.94 g (10 mmole) of V. It m e l t e d with the evolution of gas bubbles at 109-110 ~ solidified, and finally
melted at 140-142 ~ Found: N 8.2%. C24H20N2. Calculated N 8.3%.

* Here and e l s e w h e r e , in the case of N - t r i t y l a m i n e s Ii and Ij, detritylation products - N-(fl-cyanoethyl)-

aniline (rap 47-48 ~ in 75-80% yield) and N-(/3-cyanoethyl)-p-toluidine (rap 102-103 ~ in 87-90% yield) -
were isolated from the alcohol m o t h e r liquor by the addition of water.
t Here and e l s e w h e r e , the constants of the tritylation products obtained by means of t r i p h e n y l c h l o r o m e t h -
ane are p r e s e n t e d for comparison. No melting-point d e p r e s s i o n s were observed for m i x t u r e s of the t r a n s -
tritylation products with genuine samples of the corresponding tritylation products.

Vilnius State University. Vilnius State Teaching Institute. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i -

cheskikh Soedinenii, No. 3, pp. 383-384, March, 1974. Original article submitted F e b r u a r y 8, 1973.

9 19 75 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy of this article is available from the publisher for $15.00.

334
 Methyl T r i t y l E t h e r (XII). A m i x t u r e of 3 mm01e of VII-XI,* 10 m l of CH3OH, and 30 m m o l e of gla-
cial acetic acid was r e f l u x e d for 10 h. It was then diluted with ethanol, and w a t e r was added gradually to
p r e c i p i t a t e XII. The yield of XII r a n g e d f r o m 89 to 96%. The product had m p 80-83 ~ (rap 83-84 ~ [6]).
Allyl T r i t y l E t h e r (XIII). This compound was obtained as in the p r e c e d i n g e x p e r i m e n t . The yield of
XII with m p 74-76 ~ (rap 76 ~ [7]) was 88-97%.
Ethylene Glycol Monotrityl E t h e r (XIV). This compound was obtained as in the p r e c e d i n g e x p e r i m e n t .
The yield of XIV with m p 96-98 ~ (mp 98-100 ~ [7]) was 80-90%.
G l y c e r o l a - T r i t y l E t h e r (XV), This compound was obtained as in the p r e c e d i n g e x p e r i m e n t . The
yield of XV with m p 95-97 ~ {rap 92-94 ~ [7], 108-109 ~ [8], and 109-110 ~ [9]) was 60-80%.
p - H y d r o x y t e t r a p h e n y l m e t h a n e (XVD. A m i x t u r e of 3 m m o l e of VII-XI and 5 g of C6H5OH was r e -
fluxed for 5 h, a f t e r which it was t r e a t e d with aqueous sodium hydroxide solution, and the p r e c i p i t a t e d XVI
was r e m o v e d by filtration and t r e a t e d with dilute h y d r o c h l o r i c acid. The yield of XVI with m p 175-280 ~
(rap 280-282 ~ [10] and 284-285 ~ [11]) was 95-100%.
D e t r i t y l a t i o n of VII-XI. A m i x t u r e of 1 g of V I I - X I and 10 m l of 75% acetic acid was refluxed for 5-
7 rain. It was then cooled, and the p r e c i p i t a t e was r e m o v e d by filtration. The yield of t r i p h e n y l c a r b i n o l
with m p 161-162 ~ ranged f r o m 80 to 90%.

LITERATURE CITED
1. P. F. Butsk-us and N. V. Raguotene, Khim. G e t e r o t s i k L Soedin., 1056 (1970).
2. E. Funakubo and T. Hirotani, B e r . , 6_~9, 2123 (1936).
3. Belgian P a t e n t No. 625,441 (1963); Chem. A b s t r . , 61, 3121 (1964).
4. R. Dahlbom and T. E k s t r a n d , Svensk Kern. Tid., 56, 304 (1944); Chem. A b s t r . , 40, 3416 (1946).
5. R. A d a m s and J. Campbell, J. A m . Chem. Soc., 71, 3539 (1949).
6. G. L. Stadnikov, Zh. Russk. Fiz. Khim. Obshchestva, 47, 2040 (1915).
7. B. Helferich, P. Spewidel, and W. Toeldte, B e r . , 56, 766 (1923).
8. H. B r e d e r e c k , A. Wagner, and D. G e i s s e l , Ber~ 94, 812 (1961).
9. P. V e r k a d e , J. van d e r L e e , and W. M e e r b u r g , Rec. T r a y . Chim., 54, 716 (1935).
10. V. A. Z a g o r e v s k i i , Zh. Obshch. Khim., 27, 3055 (1957).
11. C. Mackenzie and G. Chuchani, J. Org. Chem., 20, 336 (1955).

* Compound X was s y n t h e s i z e d by the method in [4]. Compound XI was obtained by t r i t y l a t i o n of piperidine

by m e a n s of t r i p h e n y l c h l o r o m e t h a n e (the yield of product with m p 135-136 ~ was 78.8%).

335
 LACTAM ACETALS
VIII.* IONIZATION CONSTANTS OF SUBSTITUTED
1-ME T HYL-2-ME T HYLE NE P I P E RIDINES

V . G. G r a n i k , I. V. Persianova, UDC 541.121 : 547.743.1'822.3

a n d Y u . N. S h e i n k e r

The dependence of ApKa ( i n n i t r o m e t h a n e ) a n d Za I of m e t h y l e n e - g r o u p - s u b s t i t u t e d 1 - m e t h y l -

2-methylenepiperidines is e x p r e s s e d by the equation ApK a = - 0 . 4 1 + 11,8 Zo-I. The basieities
of t e r t i a r y enamines a r e m o r e than five o r d e r s of magnitude g r e a t e r than the basicities of
the c o r r e s p o n d i n g s e c o n d a r y enamines.

A n u m b e r of enamines - substituted 1 - m e t h y l - 2 - m e t h y l e n e p i p e r i d i n e s (In-i) and -hexahydroazepines

(IIa-i) - w e r e p r e v i o u s l y synthesized by the reaction of N - m e t h y l - 2 - p i p e r i d i n e diethyl acetals and N-
m e t h y l c a p r o l a c t a m [1-3] with compounds having active methylene (or methyl) groups.
( c H2~-~

CH 3

I n=2; I! n = 3

A c o m p a r i s o n of the basicitiesT of identically substituted r e p r e s e n t a t i v e s of both s e r i e s (see Table 1)

shows that the enamines of the piperidine s e r i e s (I) are 0.5 to one o r d e r of magnitude m o r e basic than the
c o r r e s p o n d i n g s e v e n - m e m b e r e d analogs (II). These data are e x t r e m e l y s i m i l a r to the r e s u l t s obtained in

* See [1] for communication VII.

9 ~ The ionization constants w e r e m e a s u r e d with an L P U - 0 1 potentiometer (with nitromethane as the solvent)
by the method in [4].

TABLE 1. ApKa (CHaNO2)* Values of Substituted 2-Methylene-

piperidines a n d - h e x a h y d r o a z e p i n e s (I, II)
A p K a (CHaNO2)
Compound R'
index I II

H NQ 6,85 7,91
CN CONH2 9,40 10,18
H CN 6,48 6,90
H COC6H5 3,02 4,02
H COC6H4NO2"p 4,76 5,06
H COC6H4OCH3-p 2,80 3,77
CN CsH5 7,01 8,75
COOC~H5 COOC~H5 4,05 5,53
H COC6H4NO2-m 4,57
CsH5 COOCH~ -- 2,77
C6H5 COOC2H5 -- 2,52
COCH3 COCH3 - - 3,00

* APKa (CH3NO 2) = (pKa of diphenylguanidine) - (pK a of the enamine)

[in nitromethane]. The e r r o r in the determination of ApKa does not
exceed 0.1 pK unit.

S. Ordzhonikidze All-Union S c i e n t i f i c - R e s e a r c h P h a r m a c e u t i c a l - C h e m i s t r y Institute, Moscow. T r a n s -

lated f r o m Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 385-388, March, 1974. Original article sub-
mitred M a r c h 30, 1973.

9 19 75Plenum Publishing Corporation, 227 West 17th Street, New York, N.Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.009

336
a m e a s u r e m e n t of the b a s i c i t i e s of l a c t a m s : in this c a s e also, 2 - p i p e r i d o n e is ~ 0.4 pK a unit m o r e b a s i c
than c a p r o l a c t a m [5]. T h e r e is evidently a definite analogy between these two c a s e s , i n a s m u c h as p r o -
tonation of both e n a m i n e s [6] and l a c t a m s [5] p r o c e e d s at the exocyclic carbon and oxygen a t o m s , r e s p e c -
tively.
( Ctl2)~l , H+ (CH~)~

R R

X=O, C/R"
x.l~. J' III n=2; IV n = $

The data available in the l i t e r a t u r e [5] m a k e it POSsible to a s s u m e that the b e s t conditions for amide
conjugation a r e r e a l i z e d in 2 - p i p e r i d o n e d e r i v a t i v e s . S i m i l a r r e l a t i o n s h i p s a p p a r e n t l y should also e x i s t
for the c o r r e s p o n d i n g e n a m i n e s .
The r e s u l t s obtained m a d e it p o s s i b l e to study the c h a r a c t e r of t r a n s m i s s i o ~ of the e l e c t r o n i c e f f e c t
of a substituent to the r e a c t i o n c e n t e r , which in this c a s e is t h e / 3 - c a r b o n atom of the e n a m i n e s .
It has been shown [6] that the A p K a values of e n a m i n e s I I a - / c a n n o t be s a t i s f a c t o r i l y c o r r e l a t e d with
the ~I and ~R constants. A m o r e detailed e x a m i n a ~ o n of the r e s u l t s obtained showed that I I / h a s an a n o m -
alously high basicity, which can be explained by substantial stabilization of the O - p r o t o n a t e d f o r m of V due
to hydrogen bonding*:
0 ~ CI4~

CH~
HI

A c o m p a r i s o n of the APKa (CH3NO 2) values of e n a m i n e s I a - k with the $a I constants showed that the
r e l a t i o n s h i p between these values is e x p r e s s e d by the equation
ApK~,= - 0 9 1 + 14,15~i; r=0.958, s=0.79.
C o r r e l a t i o n with r e s p e c t to the equation hpKa=ApK~,~ gives the following p a r a m e t e r s :
p[ = 14.12, PR = 0.581, APKa ~ = --0.99' r = 0.963, and s = 0.77. In o r d e r to a s c e r t a i n the significance of the
magnitude of PR, we c a l c u l a t e d the p a r t i a l coefficient of c o r r e l a t i o n r x z / y , w h e r e x=ffi, y = a R , and z =
A P K a , the value of which (0.34) m a k e s it p o s s i b l e to c o n s i d e r the A p K a and a R values to be mutually in-
dependent [8, 9]. It hence follows that PR is s t a t i s t i c a l l y r e l i a b l y indistinguishable f r o m z e r o .
S i m i l a r l y , for the ApK a (CH3NO 2) values of I a - i and khe Z~I c o n s t a n t s t the equation has the f o r m
ApKa-- -0.41 + i 1.8~(lr; r=0.986, s =0.38.
Calculation of the multiple c o r r e l a t i o n gives in this c a s e the equation ApK a - - - 0 . 7 9 9 + 1 2 . 5 8 ~ I -
0.27ZcrR, for which r x z / y = - 0 . 1 1 ; this m a k e s it p o s s i b l e to c o n s i d e r ApK a and ~R to be m u t u a l l y inde-
pendent.
In examining these equations o n e ' s attention is drawn to the e x t r e m e l y l a r g e values of the standard
deviations; this m a k e s it i m p o s s i b l e to c o n s i d e r the c o r r e l a t i o n s obtained to be c o m p l e t e l y s a t i s f a c t o r y . $
N e v e r t h e l e s s , i t can be a s s e r t e d that the inductive effect m a k e s the p r i m a r y contribution to the i n t e r a c -
tion of the substituent with the r e a c t i o n c e n t e r .
In the m e a s u r e m e n t of the ionization c o n s t a n t s of e n a m i n e s one should b e a r iu mind that the m e a -
s u r e d constant c o r r e s p o n d s to the sum of the contributions of C - and N-protonation (equilibrium between
A and B),* * although C-protonation, which is r e s p o n s i b l e for the high b a s i c i t y of e n a m i n e s as a c o n s e -

* A c e t y l a c e t o n e in nonaqueous solvents is a t a u t o m e r i c m i x t u r e with p r e d o m i n a n c e of the enol [7]. Con-

sequently it can be expected that in the c a s e of enamine IIl the O - p r o t o n a t e d f o r m r a t h e r than the C - p r o -
tonated f o r m (as is usually the ease) will be the m o r e s t a b l e f o r m t h e r m o d y n a m i c a l l y .
The constant for the m-O2NC6H4CO group c a l c u l a t e d by the method in [10] and the equations p r e s e n t e d in
[6] is 0.395. The ~R constant (0.136) was obtained by this s a m e method.
$ However, one should point out the i n a c c u r a c y of the ~ constants used for the a n a l y s i s , a portion of which
w e r e obtained by computation [6, 10].
* * In the c a s e of enamino ketones, one m u s t also take into account the p o s s i b i l i t y of O-protonation.

337
quence of the formation in this c a s e of the t h e r m o d y n a m i c a l l y m o r e stable cation [11, 12], is the p r e d o m -
inant p r o c e s s .
"*

I /X
R R RH
B

In this connection, it s e e m s of i n t e r e s t to c o m p a r e the r e s u l t s of m e a s u r e m e n t s of ApK a (CH3NO 2)

f o r t e r t i a r y (Ha, b) and s e c o n d a r y ( V i a , b) [1, 13] e n a m i n e s . It was found that the b a s i c i t i e s of e n a m i n e s
Via, b a r e lower by five o r d e r s of magnitude than the b a s i c i t i e s of e n a m i n e s IIa, b; of c o u r s e , this cannot
in any way be a s s o c i a t e d with the weak e l e c t r o n - d o n o r effect of the methyl group. This s t r a n g e , at f i r s t
glance, phenomenon can be explained by an examination of the equilibria that o c c u r during the protonation
of the indicated e n a m i n e s :

/R CH H+ CH
R' H \R' \R'

VI a, h Vi "H+ a,b VII a, b

V | , V I I a R = t t , R'=NO2; b R = C N , R'=CONH 2

As seen f r o m the s c h e m e s p r e s e n t e d above,* the p r i m a r y difference between e n a m i n e s Ha, b and

Via, b c o n s i s t s i n the fact that substantially m o r e stable i m m o n i u m cations IVa, b a r e f o r m e d in the p r o -
tonation of the f o r m e r (deprotonation r e q u i r e s cleavage of the C - H bond). In the second c a s e (Via, b),
the i m i n e ~ i m m o n i u m cation ( V I I ~ V I - H +) equilibrium m a k e s the p r i m a r y contribution to the effective
ionization c o n s t a n t . However, inasmuch as the ground s t a t e s of II and VI in both c a s e s a r e e n e r g i c a l l y ex-
t r e m e l y close, i t is c l e a r that the c o n s i d e r a b l y g r e a t e r stability of cation IV as c o m p a r e d with V I . H + leads
to substantially g r e a t e r basicity of t e r t i a r y a m i n e s II as c o m p a r e d with s e c o n d a r y a m i n e s VI. The f a c t
that p r i m a r i l y C-prot~nation takes place in the c a s e of s e c o n d a r y e n a m i n e s is c o n f i r m e d by the PMR s p e c -
t r a of IVa in c o n c e n t r a t e d H2SO4.
The above i n t e r p r e t a t i o n is in good a g r e e m e n t with the fact that when the b a s i c i t i e s of 3 - e t h y l - 3 -
c a r b e t h o x y - O - e t h y l v a l e r o l a c t i m (imine) (VIII) and 1 - e t h y l - 2 - e t h o x y - 3 - c a r b e t h o x y - l , 4 , 5 , 6 - t e t r a h y d r o -
pyridine (enamine) (IX) w e r e c o m p a r e d , the l a t t e r p r o v e d to be four to five o r d e r s of magnitude m o r e
basic [14, 15].

/~'-.~/C~Hs ~COOC2H s
i [~c~176
~.N//~,.OC2H5 ~-N/\OC2H5
C2H5
VIII IX
p.,k'~ 15.0%alcohol) 4.60 pK,, (50% alcohol) 9.65
ApK~ (CHINO2) 3,95 ApKo (CHzNO2) --0.03
VIII IX

It is c o m p l e t e l y c l e a r that the c o m p a r i s o n of the ionization constants of s e c o n d a r y and t e r t i a r y e n -

a m i n e s c o r r e s p o n d s a p p r o x i m a t e l y to a c o m p a r i s o n of t e r t i a r y e n a m i n e s with i m i n e s ( c o m p a r e the equi-
l i b r i a Ia, b~- IVa,b and VIIa,b ~ - V I - H+a,b).

LITERATURE CITED
1. G. Granik, A. M. Zhidkova, I. S. Kuryatov, V. P. Pakhomov, and R. G. Glushkov, Khim. G e t e r o t s i k l .
Soedin., 1532 (1973).
2. V. G. Granik and R. G. Glushkov, Zh. Organ. Khim., 7, 1146 (1971).
3. V. G. Granik, A. G. Sukhoruchkin, N. S. Kuryatov, V. P. Pakhomov, and R. G. Glushkov, Khim.
G e t e r o t s i k L Soedin., 954 (1973).
4. B. A. Korolev and B. I. Stepanov, Izv. Vuzov, Ser. Khim., 1_~1,1193 (1968).
5. R. ~Huisgen, H. B r a d e , H. Walz, and I. Glogger, B e r . , 9_.O0,1437 (1957).
6. V. G. Granik, I. V. P e r s i a n o v a , N. P. Kostyuchenko, R. G. Glushkov, and Yu. N. Sheinker, Zh. Organ.
Khim., 8, 181 (1972).

* F o r s i m p l i c i t y in both c a s e s , the equilibria a s s o c i a t e d with N-protonation w e r e d i s r e g a r d e d .

338
 7. J.MathieuandA.Allais,, Principles of Organic Synthesis [Russian translation], Inostr. Lit., Moscow
(1962), p. 551.
8. L.Z. Ru~shinskii, Mathematical Treatment of Experimental Results [in Russian], Nauka, Moscow
(1971), p. 125.
9. K. Doerfel, Statistics in Analytical Chemistry [Russian translation], Mir, Moscow (1969), p. 210.
10. M. Charton, J. Org. Chem., 28, 3121 (1963).
11. J. Elquero and B. Jacquer, Tetrahedron Left., 4719 (1965).
12. R.J. Hinman, Tetrahedron, 24, 185 (1968).
13. S. Petersen, West German Patent No. 863,056 (1953); Chem. Zentrallblat, 8416 (1953).
14. V.G. Granik, B. M. Pyatin, I. V. Persianova, E. M. Peresleni, R. G. Glushkov, and Y. N. Sheinker,
Tetrahedron, 26, 4367 (1970).
15. V.G. Granik, B. M. Pyatin, I. V. Persianova, R. G. Glushkov, and Yu. N. Sheinker, Zh. Organ. IChim.,
6, 1296 (1970).

339
STRUCTURE,~'TAUTOMERISM, AND TRANSFORMATIONS
OF f l - ( 3 - N I T R O - 2 - P Y R I D Y L ) -AND f l - ( 3 - N I T R O - 4 -
PYRIDYL)PYRUVIC ACID ESTERS

E. M. P e r e s l e n i , M. Ya. U r i t s k a y a , UDC 547.822.7 : 541.623 : 543.422

V. A. A z i m o v , V. A. Loginov~,
T. F. V l a s o v a , Yu. N. S h e i n k e r ,
and L. N. Yakhontov

It was shown by m e a n s of IR, UV, and PMR s p e c t r a that f l - ( 3 - n i t r o - 2 - p y r i d y l ) p y r u v i c acid

e s t e r s a r e p r a c t i c a l l y c o m p l e t e l y enolized in the c r y s t a l state and in solution; ethyl B-(3-
n i t r o - 4 - p y r i d y l ) p y r u v a t e has a n enol s t r u c t u r e in the c r y s t a l l i n e state and in pyridine s o l u -
tion: but e x i s t s as a m i x t u r e of keto and enol f o r m s in l o w - p o l a r i t y solvents.

P y r u v i c acid e s t e r s have a low capacity for transition to the enol f o r m [1]. However, the introduction
of e l e c t r o n - a e c e p t o r substituents of the n i t r o p y r i d y l or n i t r o a r y l type into the t - p o s i t i o n of these compounds
should p r o m o t e enolization [2, 3]. In fact, t h e r e a r e indications that e s t e r I [4] and 6 - m e t h o x y d e r i v a t i v e II
[5] exist p r i m a r i l y in the hydroxy f o r m . However, m o r e detailed investigations of the s t r u c t u r e of these
types of s u b s t a n c e s and of the position of the t a u t o m e r i c equilibrium in them have not been m a d e .

~ NO 2

RI'CN/'CH2--~-COOR' ~ R" ~ ' N > "--COOR'

O
A B

O OH
lJ I
CH 2 --C--COOC2H 5 CH~C--COOC2H s

No2 ~ No2 Ill

A B

! R=H. R'=C2Hs; [I R=OCH3,R'=CH3;

We have used the IR, UV, and PMR s p e c t r a to examine the s t r u c t u r e and t a u t o m e r i s m of e s t e r s I - I I I
in the c r y s t a l l i n e state and in solution; we also examined s o m e of the c h e m i c a l t r a n s f o r m a t i o n s of these
compounds.
A n a r r o w VCO band of an e s t e r group at 1725-1745 cln -1 and four bands of the s t r e t c h i n g v i b r a t i o n s
of double bonds a r e o b s e r v e d in the IR s p e c t r a of c r y s t a l s and solutions (in c h l o r o f o r m and dioxane) of e s -
t e r s I and II (Table 1). Two of the four bands p r a c t i c a l l y coincide with the bands in the s p e c t r u m of 6-
m e t h o x y - 3 - n i t r o - 2 - m e t h y l p y r i d i n e (IV) (1593 and 1508 e m -1) and thus a r e r e l a t e d to the v i b r a t i o n s of the
pyridine portion of the m o l e c u l e , while the h i g h e r - f r e q u e n c y band (1613-1643 c m -1) a p p a r e n t l y is a s s o c i -
ated with the p r e s e n c e in e s t e r s I and II of a double bond in the side chain of enol f o r m B.
A s i m i l a r p a t t e r n in this region of the IR s p e c t r u m is also o b s e r v e d for keto e s t e r III in the c r y s -
talline state and in pyridine solutions. In addition, a b r o a d split band at 1707-1735 c m - l , which is evidently

S. Ordzhonikidze All-Union S c i e n t i f i c - R e s e a r c h P h a r m a c e u t i c a l - C h e m i s t r y Institute, Moscow. T r a n s -

lated f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 3, pp. 389-393, March, 1974. Original a r t i c l e sub-
mitted F e b r u a r y 16, 1973.

9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy o f this article is available from the publisher for $15.00.

340
TABLE i. UV and IR Spectral Data

UV spectrum IR spectrum, u c m - *
Sub- solvent and
stance solvent am,,., nm (8) aggregate C=O C~G O-H
state
1 97% alcohol 248 (9100) Crystals 1725 s 1643s,1598m,1563s,1530 s
316 (15200) CHC13 1737 s 1625s,1605 s, 1562 vw,.1535s
100% alcohol 249 (8700) Dioxane 1744 s 1623s,1605s, 1560 vw, 1535s
316 (15300)
Dioxane 249 (9300) CCI4a 1735
32O (15900) 1745
97% alcohol 274 (8000) Crystals 1737 s 1613 s,br, 1584s. 1572 s, 1510 s
33O (13400) h
352 (10500)" CHCI3 1742 s 1628 vs,1595 s, 1578s,1520m
100% alcohol 272 (7700) Dioxane 1746 s 1625s,lg94s,1577m, 1522m
330 (14100)~
~350 (11400) ~ CCI4a 1735 s
Dioxane 244 (840o)c
272 (8200) c
330 (1380O) L
356 (10900) D
97% alcohol 267 (6200) Crystals 1708 s 1655m, 1590m, 1544 s, 1518 s 2600m, vbr
286 (5900)b Pyridine 1723 s 1640 w, 1525 s
340 (3650) CHCIa 1735 s 1666 w , 1 6 0 9 m , 1555 w,1525 s 3440 m
1710 mb
II1 100%alcohol 274 (8500) b
29O (9400) h Dioxane 1720 s 1648 w,1600 s,1553 w,1530s
330 (5000)- 1732 s
Dioxane 267 (93oo)b
283 (9ooo)~ cch ~ 1728,1707 3430m
330 (45o6)-
IV 97%alcohol 272 (5200) b Crystals 1593 ~s , 1 5 0 8 m
298 (9100)
V 97% alcohol 246 (6200) Liquid 1606 s. 1551 m, 1523 s

,Note; aBecause of low solubility, t h e vC= C b a n d s are not observed, bShoulder. CWeakly expressed indistinct
maxima.
 TABLE 2. Chemical Shifts of the P r o t o n s of E s t e r IH (6, ppm)
2-H 5-H 6-H CH2 =CH OCH2 CH3
Solvent
A B A B A AIB
1
i
CDCts 9,40 7,30 I 8,24 8,80 8,77
i 9,14 4,59 7,00 I 4,41 4,43 1,39 1 1,39
CD3COCDs 9,32 7,66] 8,86 8,90 8,79
I 9,14 4,82 6,91 1 4,41 4,36 1,41j 1,41
CD3OD 9,00 t 9,~
7,58 ] 8,44 8,68 8,63 -- 4,23 4,60 1,41 J 1,37
CD3COOD 9,40 9,18
7,63 i 8,49 8,92 8,81 7~1 4,41 4,46 1,40 1,37
CsDsN 8,71 6 4,17 1,05
CD~SOC~ 9;30 9,04 830 8,45 8,40 4,61 6,771 4,20 4,21 1,50 1,50

a s s o c i a t e d with the s t r e t c h i n g vibrations of the two carbonyl groups of f o r m A - the e s t e r and ketone c a r -
bonyl groups - a p p e a r s in the s p e c t r a of solutions of it in CHC13, CC14, and dioxane in the region of the
stretching vibrations of double bonds. It should be noted that the frequencies of the s t r e t c h i n g vibrations
of these groups in methyl pyruvate have v e r y close values [6].
Thus an examination of the IR s p e c t r a l data shows that I and II in the c r y s t a l l i n e state and in solu-
tions have enol s t r u c t u r e B, while III in c h l o r o f o r m , dioxane, and carbon t e t r a c h l o r i d e exists as a mixture
of the ketone and enol f o r m s but exists as the enol in pyridine.
The uOH bands in the high-frequency region of the s p e c t r a of e s t e r s I and ]I cannot be followed. This
is c h a r a c t e r i s t i c for compounds with a chelate hydrogen bond, for which one should observe a shift in the
uOH band to the low-frequency region and a d e c r e a s e in its intensity. The ring nitrogen atom and the hy-
droxyl group (C) can participate in the formation of this s o r t of hydrogen bond with closing of a s i x - m e m -
b e r e d ring for I and II. An i n t r a m o l e c u l a r hydrogen bond with the participation of the nitro group is un-
likely, inasmuch as in this case one m u s t a s s u m e the development of an e i g h t - m e m b e r e d ring. If the nitro
groups did participate in the f o r m a t i o n of i n t r a m o l e c u l a r hydrogen bonds, the c h a r a c t e r of the absorption
in the vOH region would be p r a c t i c a l l y identical for all of the investigated compounds (I-III). In fact, the
s p e c t r a in this region for e s t e r s I and lI, for which the VOH bands are p r a c t i c a l l y unobserved, differ f r o m
the s p e c t r u m of e s t e r III, in which a band at 2600 c m -1 appears for c r y s t a l s , while a distinct band at 3430-
3440 c m -1 appears for solutions. The possibility of an i n t r a m o l e c u l a r bond with the participation of the
hydroxyl group and ring nitrogen atom in e s t e r HI is excluded. The p r e s e n c e of a UOH band at 3430 em -1
in the s p e c t r u m of a solution of III can t h e r e f o r e be explained by i n t r a m o l e c u l a r interaction of the OH and
CO groups with the formation of a f i v e - m e m b e r e d ring (E). The retention of the low frequency when the
solution is diluted m a r k e d l y c o n f i r m s the i n t r a m o l e c u l a r c h a r a c t e r of this bond. The broad absorption
bands at 2600 em "1 in the s p e c t r a of c r y s t a l s of IH can be assigned with g r e a t probability to i n t e r m o l e c u l a r
interactions of compounds of the D type.

OH
I
.~ NO2 ROOC--C=~ -NO2 CtI=C~--C--ORo..H..O

i"--CO oR
~,O p
I E
C oI
CH=C--COOR

NT~No2

D
The UV s p e c t r a l data a r e in a g r e e m e n t with the a b o v e - d e s c r i b e d s t r u c t u r e of the compounds. Thus,
for example, the UV s p e c t r a of e s t e r s I - I I I differ appreciably f r o m the s p e c t r a of methoxy derivative IV
and 3 - n i t r o - 4 - m e t h y l p y r i d i n e (V), respectively, with r e s p e c t to the p r e s e n c e of l o n g e r - w a v e absorption
and the considerable i n c r e a s e in the intensity of the maxima. This indicates elongation of the conjugation
chain in the molecule and c o n f i r m s the enol s t r u c t u r e of the compounds under consideration. In c o n t r a s t
to e s t e r s I and II, the s p e c t r a of which in various solvents r e m a i n p r a c t i c a l l y unchanged, an appreciable
d e c r e a s e in the intensity of the absorption m a x i m u m at 267 nm with an i n c r e a s e in the polarity of the sol-
vent (Table 1) is o b s e r v e d in the s p e c t r a of e s t e r III. The absence of absorption above 250-270 nm in the
s p e c t r u m of nitro pyridine V - a model compound for ketone f o r m HIA -- indicates the p r e s e n c e of two tau-
t o m e r i c f o r m s in solutions of IH; the percentage of the hydroxy f o r m is reduced as the polarity of the sol-
vent i n c r e a s e s .

342
 A signal at 7.52 ppm, which c o r r e s p o n d s to the CH = proton in the CH=C(OH)COOR grouping, and the
signal of the proton of a hydroxyl group at 13.8 ppm a r e o b s e r v e d in the PMR s p e c t r u m of I {in CDCla).
Such a weak-field position of the signal of the OH group is an additional confirmation of a v e r y s t r o n g che-
late i n t r a m o l e c u l a r h y d r o g e n bond. Similar data were obtained for II.
A c c o r d i n g to the PMR s p e c t r a l data, III exists in two t a u t o m e r i c f o r m s . Thus in acetone, in addition
to the signal of the olefinic proton of the enol f o r m at 6.90 ppm, one o b s e r v e s a signal at 4.82 ppm of the
CH 2 group of the ketone f o r m (Table 2); the r a t i o of t a u t o m e r A to B is ~ 2 : 1. A m i x t u r e of two t a u t o m e r i c
f o r m s is also o b s e r v e d in CDC13, but in this ease the ratio of A to B is ~ 4 : 1. In CDaOD and CDaCOOD s o -
lutions the CH and CH z signals, as a r e s u l t of r a p i d deuterium exchange, do not appear. However, the dou-
bling of the other signals in the s p e c t r a attests to the p r e s e n c e of both t a u t o m e r i c f o r m s with ketone to
enol r a t i o s of 3 : 1 and 1.5 : 1, r e s p e c t i v e l y . The enol f o r m p r e d o m i n a t e s in CD3SO2CD3 (1 : 5), while the
keto f o r m is p r a c t i c a l l y absent in pyridine.
We have shown that, in c o n t r a s t to f l - ( 3 - n i t r o - 2 - p y r i d y l ) p y r u v i c acid e s t e r s , in which R e i s s e r t r e -
ductive eyelization is r e a d i l y r e a l i z e d by hydrogenation with palladium under n o r m a l conditions [7], in the
c a s e of ethyl f l - ( 3 - n i t r o - 4 - p y r i d y l ) p y r u v a t e the transition f r o m hydrogenation in an autoclave [8] to m i l d e r
conditions is a c c o m p a n i e d by the formation of uneyclized ethyl f l - ( 3 - a m i n o - 4 - p y r i d y l ) p y r u v a t e (VI).
The development, in addition to ethyl 6 - a z a i n d o l e - 2 - c a r b o x y l a t e (VII), of aminopyridine VI m a y be
a s s o c i a t e d with the existence of s t a r t i n g e s t e r III in solution as two t a u t o m e r i c f o r m s with c o m m e n s u r a b l e
CH2COCOO%H 5 CHr
~NH~, . __ill ~TN~NHOH
H

Yl VII VIII

amounts of both t a u t o m e r s .
Cyclization of amino e s t e r VI to azaindole derivative VII is a c c o m p l i s h e d with g r e a t difficulty on
prolonged refluxing in xylene. This m a k e s it possible to a s s e r t that e s t e r VI is not an intermediate in the
R e i s s e r t synthesis of azaindoles.
It is also i n t e r e s t i n g to note that the reduction of amino e s t e r HI on a nickel c a t a l y s t in pyridine does
not go to completion but is i n t e r r u p t e d at the step involving hydroxylamino derivative VIII.

EXPERIMENTAL
The IR s p e c t r a of m i n e r a l oil p a s t e s or solutions in c h l o r o f o r m , dioxane, and carbon t e t r a c h l o r i d e
w e r e r e c o r d e d with a P e r k i n - E l m e r 457 s p e c t r o m e t e r . The UV s p e c t r a Of solutions were obtained with an
E P S - 3 s p e c t r o p h o t o m e t e r . The PMR s p e c t r a were r e c o r d e d with JNIVI-4H-100 and C-60HL s p e c t r o m e t e r s
with tetramethylsilane as the internal standard.
Hydrogenation of Ethyl fl-(3-Nitro-4-pyridyl)pyruvate (III). A) A solution of 1.5 g of PdCl 2 in i0 ml
of 18% hydrochloric acid was added to a solution of 2 g (8 mmole) of III in 150 ml of alcohol, and hydroge-
nation was carried out at a pressure of 20-30 em (water gauge). After the calculated amount of hydrogen
had been absorbed, the catalyst was removed by filtration, and the solvent was vacuum evaporated to give
1.2 g of a substance, which, according to thin-layer chromatography (TLC), was a mixture of ethyl 6-aza-
indole-2-earboxylate (VII) and ethyl fl-(3-amino-4-pyridyl)pyruvate (VI) [AI203 with methanol as the mobile
phase and development with iodine vapors; Rf 0.8 for ester VII, and Rf 0 for ester VI]. The mixture was
crystallized from 60 ml of ethyl ~cetate to give 0.7 g (44%) of ester VII with nap 212-213 ~ The ethyl ace-
rate solution was evaporated to give 0.5 g (29%) of ester VI as yellow crystals with mp 147-149~ (from ben-
zene). The substance was quite soluble in alcohol and chloroform, was crystallized from benzene, acetone,
and ethyl acetate, and was only slightly soluble in water. Found: C 57.5; H 5.4; N 13.5%. CIoHI2N2Oa. Cal-
culated: C 57.6; H 5.7; N 13.5%.
]3) A 5 g sample of Raney nickel was added to a solution of 1 g (4 mrnole) of ester III in i00 ml of
pyridine, and the ester was hydrogenated at 20-30 cm (water gauge) until hydrogen absorption ceased. The
catalyst was removed by filtration, the solvent was vacuum evaporated, and the residue (0.75 g) was crys-
tallized from ethyl acetate and alcohol to give 0.23 g (24%) of ethyl fl-(3-hydroxylamino-4-pyridyl)pyruvate
(VIII) with nap 181 ~ (from alcohol). The white substance was quite soluble in acetone but only slightly sol-
uble in ether; benzene, chloroform, alcohol, and water. Found: C 53.6; H 5.5; N 12.2%. Ct0HI2N204. Cal-
culated: C 53.5; H 5.4; N 12.5~0.

343
 Ethyl 6-Azaindole-2-carboxylate (VII). A 0.15 g sample of calcined potassium carbonate was added
to a solution of 0.6 g (3 mmole) of ester VI in 30 ml of xylene, and the mixture was refluxed for 6 h. The
xylene solution was filtered, and the filtrate was vacuam evaporated to give 0.15 g (27%) of ester VII with
mp 212-214 ~ (from ethyl acetate) [8].

LITERATURE CITED
1o M. Becker, Ber. Bunsenges. Phys. Chem., 68, 669 (1964).
2. G. W. Wheland, in: Advances in Organic Chemistry, Wiley (1960).
3. M. Nishio and T. Ito, Agric. Biol. Chem., 29, 1119 (1965).
4. B. Frydman, S. J. Reil, J. Boned, and H. Rapoport, J. Org. Chem., 33, 3762 (1968).
5. B. Frydman, M. E. Despuy, and H. Rapoport, J. Am. Chem. Soc., 87, 3530 (1965).
6. L. Bellamy, Infrared Spectra of Complex Molecules, Methuen (1958).
7. L. N. Yakhontov and V. A. Azimov, Tetrahedron Lett., 1909 (1969).
8. M. If. Fischer and A. R. Matzuk, J. IIeterocycl. Chem., 6, 775 (1969).

344
SYNTHESIS AND STEREOISOMERISM OF N-OXIDES
OF THE DECAHYDROQUINOLINE SERIES
III.* E P I M E R I Z A T I O N OF THE C 2 CENTER IN I S O M E R I C
1, 2 - D I M E T H Y L - t r arts-DE CAHYDRO-4-Q UINO LONES DURING
THE P R E P A R A T I O N OF THE N-OXIDES

A. A. Akhrem, L. I. Ukhova, UDC 541.634+ 547.831.07

and N. F. Marchenko

The r e s u l t s of the oxidation of a n u m b e r of 4 - s u b s t i t u t e d 1 , 2 - d i m e t h y l d e c a h y d r o - 4 - q u i n o l o n e s

with hydrogen peroxide in m e t h a n o l a r e in c o n f o r m i t y with the r e s u l t s obtained by us e a r l i e r
and c o n f i r m that the s t e r e o c h e m i s t r y of the oxidation of nitrogen depends on the c o n f i g u r a -
tion of the m e t h y l substituent in the 2 position of the decahydroquinoline ring. Under these
conditions, the e p i m e r i e 1 , 2 - d i m e t h y l - t r a n s - d e c a h y d r o - 4 - q u i n o l o n e s undergo p a r t i a l i n t e r -
i s o m e r i z a t i o n at the 2 position to give a m i x t u r e of t h r e e N - o x i d e s that c o r r e s p o n d to both
amino k e t c h e s . The oxidation of the c o r r e s p o n d i n g ketals p r o c e e d s like the oxidation of
amino alcohols without e p i m e r i z a t i o n . It is t h e r e b y shown that the e p i m e r i z a t i o n of the C 2
c e n t e r during the f o r m a t i o n of the N - o x i d e s f r o m e p i m e r i e 1 , 2 - d i m e t h y l - t r a n s - d e c a h y d r o -
4-quinolones o c c u r s with the participation of the c a r b o n y l group.

In developing our r e s e a r c h on the s t e r e o c h e m i s t r y of the epoxidation of decahydroquinoline d e r i v a -

tives, in the p r e s e n t c o m m u n i c a t i o n we s e t forth the r e s u l t s of the oxidation of 1 , 2 - d i m e t h y l - 4 - e t h y n y l - (I)
a n d - 4 - v i n y l d e c a h y d r o - 4 - q u i n o l o n e s (VI) of the 2e4e configurational s e r i e s , l ' t h r e e s t e r e o i s o m e r i c 1,2-
d i m e t h y l - 4 - a c e t y l d e c a h y d r o - 4 - q u i n o l o n e s (2e4a, 2e4e, and 2 a 4 e - X I V , XIX, and XXIV, r e s p e c t i v e l y ) , and
two e p i m e r i c (with r e s p e c t to the 2 position) 1 , 2 - d i m e t h y l - t r a n s - d e c a h y d r o - 4 - q u i n o l o n e s (XXVII, XXXII)
with hydrogen p e r o x i d e in methanol.
A m i x t u r e of N - o x i d e s II and III, f r o m which individual p i c r a t e s IV and V w e r e isolated, was obtained
in the oxidation of a c e t y l e n i c alcohol I (2e4e) with hydrogen p e r o x i d e in methanol. Under the s a m e condi-
tions, two N - o x i d e s (VII and VIID, which w e r e identified through p i c r a t e s I X and X, a r e a l s o f o r m e d f r o m
vinyl alcohol VI. Oxidation of alcohol VI with 2 m o l e of p e r a c e t i c acid in c h l o r o f o r m gave epoxide N-oxide
XI, which was i s o l a t e d and identified through p i c r a t e XII, and the p r e s e n c e of N-oxide VIII was detected
qualitatively by t h i n - l a y e r c h r o m a t o g r a p h y (TLC). Oxidation of alcohol VI with p e r f o r m i c acid gave epoxide
XIII, and an epoxide N-oxide identical to XI was s y n t h e s i z e d f r o m the l a t t e r by oxidation with hydrogen p e r -
oxide. Compound XI was also obtained by oxidation of N-oxide VII with p e r a c e t i c acid.
Oxidation of keto alcohol XIV (2e4a) with hydrogen p e r o x i d e in methanol gave a m i x t u r e of i s o m e r i c
N-oxides XV and XVI, which could be s e p a r a t e d by f r a c t i o n a l c r y s t a l l i z a t i o n . Keto alcohol XIX (2e4e) un-
d e r s i m i l a r conditions a l s o f o r m s a m i x t u r e of two i s o m e r i c N - o x i d e s XX and XXI, which w e r e s e p a r a t e d
as p i c r a t e s XXII and XXIII.

* See [1, 2] for c o m m u n i c a t i o n s I and II.

The s y m b o l s 2a o r 2e indicate axial or e q u a t o r i a l o r i e n t a t i o n s of the m e t h y l group in the 2 position; 4 a
or 4e designate axial or e q u a t o r i a l o r i e n t a t i o n s of the 4 - R substituent.

Institute of P h y s i c a l Organic C h e m i s t r y , A c a d e m y of Sciences of the B e l o r u s s i a n SSR, Minsk. T r a n s -

lated f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 3, pp. 394-398, March, 1974. Original a r t i c l e sub-
m i t r e d F e b r u a r y 13, 1973.
]]

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
I stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,[
I recording or otherwise, without written permission o f the publisher. A copy o f this article is avaiZablefrom the publisher for $15.00.1
L_ !
345
 Kete alcohol XXIV (2a4e) behaves differently on oxidation with hydrogen peroxide in methanol and
gives only one N-oxide (XXV).
The above r e s u l t s are in c o n f o r m i t y with the r e s u l t s that we p r e v i o u s l y obtained and c o n f i r m the ef-
f e c t of the orientation of the methyl substituent in lhe 2 position of the decahydroquinoline r i n g on the
s t e r e o c h e m i s t r y of the oxidation of the nitrogen atom.
In c o n t r a s t to amino alcohols, which retain their configuration during oxidation, as attested to by the
reduction of the N-oxides obtained to the starting amino alcohols, e p i m e r i c amino ketones XXVII (2e) and
XXXII (2a) undergo partial i n t e r i s o m e r i z a t i o n at the 2 position on oxidation with hydrogen peroxide in
methanol to each give a mixture of three N-oxides that c o r r e s p o n d to both amino ketones. In both c a s e s ,
picrate x x x , which c o r r e s p o n d s to N-oxide XXVIII, and picrate XXXI, which c o r r e s p o n d s to N-oxide XXIX,
were isolated as a r e s u l t of separation of the mixture of N-oxides.
To relate the N-oxides to the starting amino ketches, the latter were r e g e n e r a t e d by catalytic h y -
drogenation of the N-oxides. Amino ketone XXVII was obtained from N-oxide XXVIII, while amino ketone
XXXII was obtained f r o m N-oxide XXIX, which was used in the hydrogenation as the picrate. On the basis
of the evident predominance of N-oxide XXVIII over N-oxide XXIX in the products of the oxidation of the
amino ketches, it can be concluded that amino ketone XXVII, which has an equatorial methyl group, and the
N-oxide formed f r o m it (XXVIII) are much m o r e stable under the oxidation conditions than ketone XXXII,
which has an axial methyl group, and its N-oxide (XXIX). In addition to N-oxides XXVIII and XXIX, a third
reaction product (XXXIII) was detected by TLC. On the basis of data on the s t e r e o c h e m i s t r y of the oxi-
dation of amino alcohols, it can be a s s u m e d that XXXIII was f o r m e d in the oxidation of ketone XXVII and is
an e p i m e r of N-oxide XXVIII with r e s p e c t to the nitrogen atom.

O O

i I
CH~ CH3

1.~/p. ~176 o o o
l.~/Pd
CH~ (el CH~(e) "CH~(a)

It might have been a s s u m e d that the carbonyl group participates in the epimerization of ketches
XXVII and XXXIL To verify this assumption, the c o r r e s p o n d i n g ethylene ketals (XXXIV and XXXV) were
oxidized under the conditions of the oxidation of the ketones. The oxidation of ketal XXXIV (2e) gave two
of its N-oxides, which, after r e m o v a l of the ketal grouping, were converted to a m i x t u r e of two N-oxides
of the ketone. N-Oxide XXVIII was isolated by c r y s t a l l i z a t i o n of the p i c r a t e s of the latter. The second
epimer of the mixture was identified as the N-oxide XXXIII by chromatography.
Only one N-oxide of the ketal, the h y d r o l y s i s of which gave N-oxide XXIX, is f o r m e d in the oxidation
of ketal XXXV (2a). It should be noted that individual N-oxide XXIX, in c o n t r a s t to its picrate (XXXI), is
e x t r e m e ! y unstable and r e a d i l y i s o m e r i z e s (in a column filled with A1203 under the conditions of its f o r -
marion and also simply on storage) to give a mixture of three N-oxides that c o r r e s p o n d to both ketones,
and the N-oxide oxygen is partially cleaved to give the starting ketone (XXXII).
The r e s u l t s provide evidence that the oxidation of ketals in which the carbonyl group is protected
proceeds like the oxidation of amino alcohols without epimerization at the C 2 center and c o n f i r m the a s -
sumption that the epimerization of this center during the formation of N-oxides f r o m e p i m e r i c 1,2-di-
m e t h y l - t r a n s - d e c a h y d r o - 4 - q u i n o l o n e s o c c u r s with the participation of the carbonyl group. The m e c h a n i s m
of the epimerization is under study.
r - - IO
O
[ - - ]O
0 + 0
I O
I

i~N ~ ~CH3-(e) CH3(e) " ~ / ! ~ ' H ' ~ ' c H $ (e) XXVIII XXXII!

I
CH~ CH3/\O O/ \ CH 3
XXXIV XXXVI X.XXVII

346
 f--I [--1
0 0 0 0

, H20~ ~ H20' H+
XXXII - , "CH3(a) = XXIX
-,-.~.~ ~'~N f ",CH3(a )
CH3 CH3 0

XXXV XXXVIII

EXPERIMENTAL
The course of the reaction was monitored by means of TLC on AI203. The reaction mixture was
chromatographed in the systems of solvents used both for the separation of the starting decahydroquinolones
[acetene-hexane-ether (i : 9 : i0)] and for the separation of their N-oxides [ethanol-acetone (I : 2)].
Oxidation of 1,2-Dimethyl-4-ethynyldecahydro-4-quinolone. A 1 g (5 mmole) sample of alcohol I
(2e4e, mp 114-115 ~ in 15 ml of methanol was oxidized with 4.92 g (15 mmole) of 10% hydrogen peroxide.
After the usual workup, the product was converted to the picrateo A total of 0.80 g of picrate IV with mp
211-212 ~ (from alcohol) and R/0.68 (the value corresponding to N-oxide ID precipitated on standing. Found:
C 50.7; H 5.2%~ CI~H21NO 2- C6H3N~O 7. Calculated: C 50.4; H 5.3%. The mother liquor yielded 0.8 g of
picrate V with mp 148-149 ~ and R/0.46 (the value corresponding to N-oxide III). Found: C 50.6; H 5.4%.
CI3H21NO 2. CsHsN307. Calculated: C 50.4; H 5.3%.
Oxidation of 1,2-Dimethyl-4-vinyldecahydro-4-quinolol. A) Oxidation of 0.75 g (4 mmole) of alcohol
VI (2e4e, mp 96 ~ in i0 ml of methanol by means of 4 g (12 nunole) of 10% H202 gave 0.73 g of reaction
product, which was converted to the picrate. Fractional crystallization of the mixture of picrates gave 0.6
g of picrate IX with mp 198-199 ~ (from alcohol) and R/0.63 (the value corresponding to N-oxide VII). Found:
C 50.3; H 5.8%. CI3H23NO ~" C6H3N3OT. Calculated: C 50.2; H 5.7%. The mother liquor yielded 0.55 g of
picrate X with mp 129-130 ~ and R/0.5 (the value corresponding to N-oxide VIII). Found: C 50.2; H 5.7%.
CI3H23NO2. C6H3N3OT. Calculated: C 50.2; H 5.7%.
B) A 1 g (5 mmole) sample of alcohol VI in 20 ml of chloroform was oxidized with i.I g (i0 mmole)
of 73% peracetic acid. The usual workup gave i.i g of a viscous substance. Fractional crystallization of
the mixture of picrates from ethanol gave 0.85 g of picrate XII with mp 185-186 ~ and Rf 0.60 [the value
corresponding to 1,2-dimethyl-4-(l,2-epoxy-ethyl)decahydro-4-quinolol N-oxide (XI)]. Found: C 48.4; H
5.6%. Ct~H23NO 3 9 C6H3N307. Calculated: C 48.5; H 5.6%. Two spots with R/0.60 and 0.50 (the latter was
identical to that of N-oxide VIII) were detected on chromatography of the mother liquor. N-Oxide XI was
also obtained by oxidation of N-oxide VII with 73% peracetic acid (i mole) in chloroform and by oxidation
of glycidic alcohol XIII with 10% hydrogen peroxide in methanol. Compound XIII (rap i12-i13 ~ R/0.84)
was obtained by oxidation of vinyl alcohol VI with performic acid. Found: C 69.4; H 10.2%. CI3H23NO ~.
Calculated: C 69.3; H 10.3%.
Oxidation of Isomeric 1,2-Dimethyl-4-acetyldecahydro-4-quinolols. A) Oxidation of 2 g (9 mmole)
of ketel XIV (2e4a, mp 139-140 ~ by means of 2.8 g (9 mmole) of 10% hydrogen peroxide in methanol gave
1.9 g of a mixture of isomeric 1,2-dimethyl-4-aeetyldecahydro-4-quinolol N-oxides. Fractional crystal-
lization of 1 g of a mixture of the N-oxide from alcohol-ether gave 0.4 g of N-oxide XV (rap 226-227 ~ R/
0.56. Found: C 64.8; H 10.0%. C13H23NO 3. Calculated: C 64.8; H 9.6%) and 0.2 g of N-oxide XVI (rap 195-
196 ~ R/0.65. Found: C 65.1; H 9.8%. CI3H23NO 3. Calculated: C 64.8; H 9.6%). Crystallization of the
mixture of picrates obtained from 0.9 g of the crude mixture of N-oxides from ethanol gave 0.7 g of pie-
rate XVII with mp 178-179 ~ and R/0.56. Found: C 48.4; H 5.9%. CI3H2~NO3- C6H3N30 ~. Calculated: C
48.5; H 5.6%. The mpther liquor yielded 0.4 g of picrate XVIII with mp 154-156 ~ and R/0.65. Found: C
48.4; H 5.7%. CI3H23NO 3. CsH3N30 ~. Calculated: C 48.5; H 5.6%.
B) Reaction of 0.8 g (3.5 mmole) of ketel XIX (2e4e, mp 61-62 ~ with 1.2 g (3.5 mmole) of 10% hy-
drogen peroxide in methanol gave 0.9 g of a mixture of isomeric N-oxides. Crystallization of the mixture
of picrates obtained from 0.7 g of the mixture of N-oxides from ethanol gave 0.8 g of picrate XXII with mp
162-163 ~ and R/0.75 (the value corresponding to N-oxide XX). Found: C 48.6; H 5.5; N 12.0%. CI3H23NO 3-
CGH3N307. Calculated: C 48.5; H 5.6; N Ii.9~o. The mother liquor yielded 0.i g of pierate XXIII with mp
161-162 ~ and R/0.57 (the value corresponding to N-oxide XXD. Found: C 48.4; H 5.8; N 11.8%. C13H23NO3.
C6H3N307. Calculated: C 48.5; H 5.6; N 11.9%. A mixture of picrates XXII and XXIII melted at 140-145 ~
C) A 0.8 g (3.5 mmole) sample of ketel XXIV (2a4e, mp 112-113 ~ gave 0.8 g of N-oxide XXV with
Rf 0.50; a 0.4 g sample of crude N-oxide XXV was converted to the picrate, and crystallization of the

347
l a t t e r f r o m ethanol gave 0.7 g of p i c r a t e XXVI with rap 187-188 ~ and R f 0.50. Found: C 48.6; H 5.4%.
C13H23NO3 9 C6H3N307. Calculated: C 48.5; H 5.6%. T h i n - l a y e r c h r o m a t o g r a p h y of the m o t h e r liquor gave
one spot ( R f 0.51).
Oxidation of I s o m e r i c 1 , 2 - D i r a e t h y l - t r a n s - d e c a h y d r o - 3 - q u i n o l o n e s (XXVII and XXXH). A) A solution
of 12.4 g (48 mmole) of 10% H202 in CH3OH was added to 3 g (16 mraole) of decahydroquinolone XXVH [2e,
bp 85-87 ~ (1.5 ram), nD 2~ 1.4956, R f 0.54]. T h r e e spots ( R f 0.54, 0.46, and 0) w e r e detected 2 h a f t e r the
s t a r t of the e x p e r i m e n t by TLC of the r e a c t i o n m i x t u r e in the s y s t e m of solvents for ketones; two spots
( R f 0.54 and 0) w e r e detected 72 h a f t e r the s t a r t of the e x p e r i m e n t . The s t a r t i n g ketone (XXVH) had been
oxidized a f t e r 2 weeks to give 3.2 g of a m i x t u r e of N - o x i d e s , TLC of which in the s y s t e m for ketones gave
one spot ( R f 0), while t h r e e spots ( R f 0.67, 0.57, and 0.35) w e r e detected in the s y s t e m of solvents for N -
oxides. The m i x t u r e of N-oxides was c o n v e r t e d to a m i x t u r e of p i e r a t e s . Crystallization of the l a t t e r f r o m
e t h a n o l - a c e t o n e (3 : 1) gave 3.8 g (59%) of p i c r a t e XXX with m p 175-176 ~ and R f 0.67 (the value c o r r e s p o n d -
ing to N-oxide XXVIII). Found: C 47.8; H 5.2%. CllH18NO 2. C6H3N307. Calculated: C 47.9; H 5.2%. The
m o t h e r liquor yielded 0.4 g (6%) of p i c r a t e XXXI with m p 137-138 ~ and R f 0.57 (the value c o r r e s p o n d i n g to
N-oxide XXIX). Found: C 48.0; H 5.4%. CllH18NO 2.C6H3N30?. CalCulated: C 47.9; H 5.2%.
B) A 7.8 g (21 mraole) s a m p l e of 10% H202 was added to a solution of 1.3 g (7 mraole) of d e c a h y d r o -
quinolone XXXII (2a, m p 51-52 ~ R f 0.46) in 10 m l of methanol. T h i n - l a y e r c h r o m a t o g r a p h y of the r e a c -
tion m i x t u r e 10, 20, 30, and 40 days a f t e r the s t a r t of the e x p e r i m e n t in the s y s t e m of solvents for the s e p -
aration of piperidones gave t h r e e spots ( R f 0.54, 0.46, 0). The oxidation was complete a f t e r 50 days to
give 1.3 g of a m i x t u r e of N-oxides as a v i s c o u s liquid, TLC of which in the s y s t e m of solvents for the s e p -
aration of piperidones gave one spot ( R f 0), while TLC in the s y s t e m for the s e p a r a t i o n of N-oxides gave
t h r e e spots ( R f 0 . 6 7 , 0.58, and 0.36). The m i x t u r e of N - o x i d e s was c o n v e r t e d to the p i c r a t e . F r a c t i o n a l
c r y s t a l l i z a t i o n of the l a t t e r f r o m ethanol gave 1.29 g (46%) of a p i c r a t e with rap 175-176 ~ and R f 0.67,
which did not d e p r e s s the melting point of p i c r a t e XXX. The m o t h e r liquor yielded 0.02 g of a p i c r a t e with
rap 136-137 ~ and R f 0.58, which did not d e p r e s s the melting point of p i c r a t e XXXI.
Catalytic Hydrogenation of N-Oxides XXVIII and XXIX. A) Hydrogenation of 0.1 g (0.4 mraole) of N-
oxide XXVHI o v e r a Lindlar c a t a l y s t (at 738 rata and 20 ~ r e s u l t e d in the consumption of 23 ral (1 ramole)
of hydrogen. Workup of the m i x t u r e gave 0.1 g of hydrogenation product, which gave one spot ( R f 0.55) on
TLC in the s y s t e m for piperidones. The r e a c t i o n product was t r e a t e d to give its h y d r o c h l o r i d e , m p 164-
165 ~ which did not d e p r e s s the m e l t i n g point of a genuine s a m p l e of the h y d r o c h l o r i d e of decahydroquino-
lone XXVII.
B) A total of 75 m l (10 ramole) of hydrogen was a b s o r b e d in the hydrogenation of 0.1 g of N-oxide
XXIX in the f o r m of p i c r a t e XXXI in the p r e s e n c e of P d / C a C O 3 (at 729 rata and 27~ Workup of the m i x -
t u r e gave 0.1 g of a substance, which gave one spot ( R f 0.46) on TLC in the s y s t e m for piperidones. The
substance was purified in a column filled with A120 ~ (1 : 15; CHC13) and c o n v e r t e d to the h y d r o c h l o r i d e with
rap 145-146 ~ No raelting-point d e p r e s s i o n was o b s e r v e d f o r a m i x t u r e of this h y d r o c h l o r i d e with the h y -
d r o e h l o r i d e of decahydroquinolone XXXII.
1 , 2 - D i r a e t h y l - t r a n s - d e c a h y d r o - 4 - q u i n o l o n e Ketals. A) A solution of 0.4 g (2 m m o l e ) of ketone XXVII,
0.5 g (6 raraole) of ethylene glycol, and 0.42 g (2 mraole) of p-toluenesulfonic acid in 30 ral of benzene was
heated with a D e a n - S t a r k t r a p until w a t e r liberation c e a s e d . The benzene was then r e m o v e d , and aqueous
KOH solution was added until the m i x t u r e was alkaline. The r e a c t i o n product was e x t r a c t e d with ether, the
ether was r e m o v e d f r o m the e x t r a c t by distillation, and the r e s i d u e was f r a c t i o n a t e d to give 0.4 g of 1,2-
dimethyldecahydro-4-quinolone ethylene ketal (XXXIV) as a v i s c o u s liquid. Found: C 69.5; H 10.5; N 6.1%.
CIaH23NO2. Calculated: C 69.3; H 10.2; N 6.2%.
B) A total of 0.38 g of 1,2-diraethyldecahydro-4-quinolone ethylene ketal (XXXV), which was obtained
as a viscous liquid, was similarly synthesized from 0.4 g (2 mmole) of ketone XXXII. Found: C 69.2; H
10.3; N 6.1%. CI3H23NO2. Calculated: C 69.3; H 10.2; N 6.2%.
Oxidation of Ketals XXXIV and XXXV with Hydrogen Peroxide. A) Oxidation of 0.4 g (1.7 mmole) of
ketal XXXIV with 10% H202 [1.8 g (5.1 ramole)] in chloroforra-methanol (1 : 1) gave 0.4 g of a mixture of
ketal N-oxides; Rf 0.73 and 0.34. The oxidation product (0.2 g) was converted to a mixture of picrates,
crystallization of which from alcohol gave 0.1 g of a picrate (corresponding to N-oxide XXXVD with rap
167-168 ~ and Rf 0.66. Found: C 48.3 H 5.5; N 12.0%. CI3H23NO3. C6H3N30~. Calculated: C 48.5; II 5.5;
N 11.9%. A mixture of this picrate with picrate XXX melted at 154-158~

348
 B) Similar oxidation of 0.3 g (1.3 mraole) of ketal XXXV with 10% H202 gave 0.3 g of N-oxide XXXVII
(Rf 0.56), which was converted to picrate XXXIX with rap 204-205 ~ (from alcohol). Found: C 48.4; H 5.6;
N 12.2%. C13H23NO3- C6H3N307. Calculated: C 48.5; H 5.5; N 11.9%.
Hydrolysis of Ketal N-Oxides XXXVI and XXXVIII. A mixture of N-oxides (Rf 0.67 and 0.36) was
obtained by heating 0.1 g of the crude mixture of N-oxides obtained from ketal XXXIV with 4~0 hydrochloric
acid at 80-90 ~ for 40 rain and subsequent workup of the reaction product (neutralization with potassium c a r -
bonate, extraction with chloroform, drying with MgSO4, and removal of the solvent). Crystallization of the
mixture of picrates gave 0.08 g of a pierate with rap 173-174 ~ and R f 0.67; it did not depress the melting
point of picrate XXX. Similarly, a substance with R f 0.56 (corresponding to N-oxide XXIX) was obtained
from 0.1 g of crude N-oxide XXXIII by heating with 4~0 HC1.

LITERATURE CITED
ii A. A. Akhrera, L. I. Ukhova, and N. F. Sakovich, Izv. Akad. Nauk SSSR, Otd. Khim. Nauk, 838 (1963).
2. A. A. Akhrem, L. I. Ukhova, N. F. Marchenko, and N. F. Uskova, Izv. Akad. Nauk SSSR, Ser. Khim.,
2776 (1968).

349
RESEARCH ON 6 - AND 7-SUBSTITUTED 2-
AND 4-THIOQUINOLONES. TRANSMISSION OF THE
ELECTRONIC EFFECTS OF SUBSTITUENTS IN T H E

BENZENE RING OF THIOQUINOLONES TO THE REACTION

CENTER

D. I. B i s k u p s k a y a UDC 547.831.88 : 541.132

The electronic effect of substituents on the a c i d - b a s e p r o p e r t i e s of 6- and 7-substituted 2-

thionolepidines and 4-thionoquinaldines were investigated. It is shown that the P K a ( - H +)
values for 6- and 7-substituted 2- and 4-thioquinolones and the PKa(+ H+) values for 7 - s u b -
stituted 2-thionolepidines and 6-substituted 4 - m e t h y l m e r c a p t o q u i n a l d i n e s c o r r e l a t e with the
a M substituent constants of Jaffe and Taft. The effect of a substituent is t r a n s m i t t e d p r i -
m a r i l y via an inductive m e c h a n i s m , r e g a r d l e s s of its position.

M e s o m e r i s m of the thione*--* zwitterion type is c h a r a c t e r i s t i c for 2- and 4-thioquinolones [1, 2]. In

view of the intimate relationship between the p r o t o t r o p i c p r o p e r t i e s and a c i d - b a s e c h a r a c t e r i s t i c s , the
ionization constants [3] were d e t e r m i n e d for I-XI (Table 1). Two s e r i e s of values - PKa(+ H+) during ti-
tration with a c i d (addition of a proton) and p K a ( - H +) during titration with alkali (loss of a proton) - were
obtained in the determination of the pK a values of the thioquinolones. The pKa(+ K+) value for the thione
s t r u c t u r e should pertain to the basic group, and the P K a ( - H +) value should pertain to the acid group. On
the other hand, for a zwitterion s t r u c t u r e the pK(+ H+) value c h a r a c t e r i z e s t h e acid group, and the p K ( - H +)
value c h a r a c t e r i z e s the basic group. The ionization constants of the investigated thioquinolones were a s -
signed by m e a n s of the UV and IR s p e c t r a [1, 2]. The ionization constants obtained w e r e c o m p a r e d with

TABLE 1. pK a Values of 6- and 7-Substituted 2-Thionolepidines

and 4-Thionoquinaldines*
CH3 S

CH~ R
H H C~

Series 1-3 Series 4 Series 5

substit- PKa substit- pK~
Uent uent
Iposinon +H~ _H position +H + -H +

OCHa 12,32] H lO,4q

CI !66
i
- 1148~.1 OCHa 10,08t,
NO_, 6 10,43| CI 9,26[ '~
H 12,42~ NO~ 8,261
OCH3 2,98(~ 12,20/ H 5,3o~
CI 7 3,40f~ 11,50}5 OCHa 5,0'6i
H.NCOCHa 7 3,16) 1220) CI 4,50
NO2 3,73 J

* In 70% ethanol at 20~

Leningrad P h a r m a c e u t i c a l - C h e m i s t r y Institute. T r a n s l a t e d f r o m Khimiya Geterotsiklicheskikh

Soedinenii, No. 3, pp. 399-402, March, 1974. Original article submitted M a r c h 15, 1973.

9 1975PlenumPublishing Corporation, 227 West 17th Street, New York, N. If. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy of this article is m,ailable from the publisher for $15.00.

350
 TABLE 2. Results of a Correlation Analysis of Series 1-5
pK~
i
Series' Ionization i Parameters* Jaffe o Taft o
constant !
E meta para meta para
{
i r 0,994 0,949 0,993 0,974
{ o --2,914 -- 1,996 --3,019 --2,117
Ig Ko ( c a l c . ) 12,53 12,04 12,57 12,16
pK.(-H-) 12,42 12,42 12,42 12,42
} lg KoS(exptl. )
0,122 0,357 0,129 0,258
I r 0,995 0,670 0,797
P --2,584 -- 1,345 - 1,826
lg Ko (talc.) 12,48 12,02 -- 12,10
pKo(-H-) lg Ko (r 12,42 12,42 12,42
i So 0,046 0,369 0.299
; r 0,998 0,640 0,762
0 1,623 0,810 1,10I
3 pK~(+H-) Ig I<o;~alc.~ 2,80 3,09 -- 3,04
lg Ko [expu.) 2,80 2,80 2,80
F & 0,014 0,241 0,203
i r 0,999 0,911 0,999 0,954
P -3,094 -ZOO0 -3,169 -2,467
4 pK. ( - H } Ig Ko (calc.) 10,44 9,88 10,46 10,06
Ig Ko (exptI.) 10,46 10,46, 10,46 10,46
So 0,026 0,490 0,031 0,356
r 0,999 0,930 0,998 0,960
-2,173 - 1,434 - 2,224 -- 1,530
5 pK~(-H-} lg Ko Ocale.) 5,28 4,90 5,30 4,99
lg Ko (exptl.) 5,26 5,26 5,26 5,26
J So " 0,031 0,306 0;048 0,233

* Calculated by the method of least squares [6]; n : 4 in alI s e r i e s .

D/(o L O C H 3
12~ ~ cOCH3

p&

OCH3
,o
CI

..r DCH3 ~ C
Ct
E
3 ~ NHCOCH3
i i i i ~.
o.'2 & %:ta Or2 O~4 O~6 0,8 6met a

Fig. 1 Fig. 2
Fig. 1. Correlation of the acidity constants of thioquinolones with the
(rM constants: A) s e r i e s 1; B) s e r i e s 2; D) s e r i e s 4.
Fig. 2. Correlation of the basicity constants of thioquinolones (C,
s e r i e s 3) and of S-methyl~_ioquinolines (E, s e r i e s 5) with the a M
constants.

the various substituent constants [4]. The results of the correlation analysis are presented in Table 2.
Investigations established a linear dependence of the acidity constants of the thioquinolones in s e r i e s 1, 2,
and 4 (Fig. 1, lines A, B, and D, respectively) and of the basicity constants for s e r i e s 3 and 5 (Fig. 2, lines
C and E) with the Jaffe and Taft a M substituent constants. The correlation of the ionization constants with
the Jaffe crlVI and induction constants (~O) indicates the p r i m a r y inductive character of the t r a n s m i s s i o n of
the electronic effect of a substituent. It is seen from the data in Table 2 that the p values for thioquino-
lones of s e r i e s 1 and 4 are higher than those in s e r i e s 2; this indicates the great effect of substituents in
the 6 position on the reaction center. The reaction constant of s e r i e s 3 of thioquinolones differs from the
p values of the other s e r i e s with r e s p e c t to sign; this probably attests to the occurrence of titration through
a transition state other thanthat in the other s e r i e s . The ionization constants [pKa(+H+)] in s e r i e s 3 and 4
were determined during titration with acid, but they characterize the basicities of the various functional

351
r
r
tO

TABLE 3. Characteristics of 7-Substituted 2- and 4-Thioquinolones and Their S-Methyl Derivatives

(:H~ S CH a t":. ~ Clla

R R \CHa
H
H
I--IV V -VI VII-IX X-XI

Found, % Calc., qo UV spectra Yield,

Empirical
R mp, *C IR spectra qo
formula n s N S "~mux 'nlT1 IIg 8
~o

OCH~ 244--246 CI1HIINOS 6,9 15,5 6,8 15,6 265:380 4.3C,; 4,32 14~Om 15,2~w, 1610--163(h~a. 83
2700~3140 m
II CI 264--266 CtoHsCINS a 6,6 15,2 6,7 15,3 270; 380 4,30; 4,20 140Ore, 1500 w, 1600--1630s. 83
'3800--3140 m
III NH2 225(dec.) CIoHIoN2S 4,5 16,9 4,7 16,8 380 3,17 1570--1660m, 2700--2900 w 7O
IV NHCOCHa 285(dec,) CI~HI2N2OS 2,1 13,7 2,0 13,8 235; 38,5--~390 4,48; ,3,90 141~w 1500--1700 m 72
V OCHa 215--216 CllHlrNOS 6,7 15,6 6,8 15,6 265; 375 3,93; 4.27 1415m 1570 1630s 2600-- 87
3100 s
VI CI 2~5~227 CloHsCI,NSb 6,6 15,2 6,7 15,3 265; 390 4.06; 4.2,4 1415m, 1585s. 1640m, 2600-- 86
3100s
VII OCHa 85--86 CI~.HIaNOS 6,3 14,6 6,4 14,6 245; 335 4,30; 4.1,5 87
VIII C1 41--42 CnHIoCI,NSc 6,2 14,3 6,3 14,,4 245; 33'5 4.32; 3,95 90
IX NHCOCH3 210~211 C12Ht~N2OS 1,3 13,1 1,4 13,0 245; 345 4,25; 3,76 72
X OCHa 97--97,5 Ct~.HIzNOS 6,2 14,5 6,4 14,6 2'35; 335 r 4,13 96
XI C1 139~140 CnHloCINS d 6,4 14,2 6.3 14,4 230:310 4.55:4,03 95

Note: aFound: C1 16.9%. Calculated: C1 16.9%. bFound: C1 16.8%. Calculated: C1 16.9%. CFound: C1
15.8%. Calculated: C1 15.9%. dFound: C1 15.9%. Calculated: C1 15.9%.
groups: in series 3 the pK(+H+) values characterize the basic properties of the sulfur atom, while they
characterize the basic properties of the nitrogen atom in series 5. Judging from the absolute value of re-
action constant p, it can be assumed that the degrees of polarity of the transition states in series 1 and 4
are close and higher than in series 2 and 5. Althoughthe substituents are in different positions in the thio-
quinolones in series 1 and 2, the (rM constants give the best correlation coefficient for both series. The
benzene ring of the thioquinolone molecules, regardless of the position of the substituent, can be regarded
as an overall substituent with respect to the reaction center. An induction mechanism, regardless of the
position of the substituent, apparently plays the decisive role in the transmission of the effect of a substit-
uent to the reaction center.

EXPERIMENTAL
The purity and authenticity of the products were monitored by thin-layer chromatography (TLC) on
AI203. The solvent was CHCI3, and the chromatograms were developed in UV light. The pK values were
determined by potentiornetric titration with an LPU-01 potentiometer.
The 7-substituted 2- and 4-thioquinolones were obtained by the method in [2]. The characteristics
of the 7-substituted thioquinolones and their S-methyl derivatives are presented in Table 3. The other sub-
stances were described in [I, 5].
7-Amino-2-hydroxylepidine (XII). A solution of 8.4 ml (0.1 mole) of diketene in 20 ml of dry ben-
zene was added in the course of 15 rain to 10.8 g (0.i mole) of rn-phenylenediamine in 50 ml of dry ben-
zene, after which the reaction mixture was refluxed for 1 h. The benzene was then removed by distillation
to dryness, and the residue was dissolved in absolute ethanol. The ethanol solution was filtered, and the
filtrate was diluted with water and cooled to precipitate a light-gray subsLance [93% (80% by the method in
[5])] with mp 270-272~ No melting-point depression was observed for a mixture of this product with a
genuine sample of XII [5].
7-Acetamido-2-chlorolepidine (XIID. A mixture of 0.96 g (5 mmole) of 7-amino-2-chlorolepidine
and 6 ml (6 mmole) of acetic anhydride was refluxed until the solid had dissolved completely, after which
the solution was poured into water. The yellow precipitate was washed repeatedly with water until it was
neutral to give a product (73%) with mp 178-180~ (dec., from alcohol). Found: CI 15.0; N 11.7%. CI2HIIN2OCI.
Calculated: Cl 15.1; N 11.9%.

LITERATURE CITED
io D. I. Biskupskaya and A. V. Voropaeva, Khim. Geterotsikl. Soedin., 521 (1973).
2. D. I. Biskupskaya and A. V. Voropaeva, Khim. Geterotsikl. Soedin., 1688 (1971).
3. A. A. Albert and E. Serjeant, Ionization Constants of Acids and Bases, Methuen (1962).
4. YUo A. Zhdanov and V. I. Minkin, Correlation Analysis in Organic Chemistry [in Russian], Izd. Ros-
tovsk. Univ., Rostov-on-Don(1966).
5. E. Besthorn and H. Byvanck, Ber., 3_1, 798 (1898).
6. A. Worthing and D. Heffner, Methods for the Treatment of Experimental Data [Russian translation],
Inostr. Lit., Moscow (1949).

353
RESEARCH IN P Y R A Z O L I D I N E CHEMISTRY
x x i I . * STABILITY OF THE N - N BOND OF 3,5-DIOXOPYRAZOLIDINE
ENOLATES WITH RESPECT TO HYDROGENOLYSIS IN THE PRESENCE
OF RANEY NICKEL

B. L. Moldaver, V. V. Zverev, UDC 547.772.2'775:542.941.7

M. P. Papirnik, M. E . A r o n z o n ,
and Yu. P. Kitaev

An i n c r e a s e in the r e s i s t a n c e of the N - N bond to hydrogenolysis on Raney nickel in alkaline

media is observed not only for 1,2,4-trisubstituted 3,5-dioxopyrazolidines but also for other
types of 3,5-dioxopyrazolidines that are capable of enolization. 3,5-Dioxopyrazolidines that
a r e capable of forming betaines also do not undergo hydrogenation in neutral ethanol. The
use of the potentiometrie method of Sokol'skii and D r u z ' made it possible to establish v e r y
slight adsorption of the enolates and betaines on the catalyst surface. The d e c r e a s e in ad-
sorbability is explained by a d e c r e a s e in the effective charges on the nitrogen atom of the
heteroring; this is in a g r e e m e n t with the r e s u l t s of calculations of the enolate and enol by
the P a r i s e r - P a r r - P o p l e method. An assumption r e g a r d i n g the g r e a t e r a r o m a t i c c h a r a c -
t e r of the eno[ate as c o m p a r e d With the enol is e x p r e s s e d on the basis of a c o m p a r i s o n of
the bond lengths.

1,2,4-Trisubstituted 3,5-dioxopyrazolidines, in c o n t r a s t to their behavior in neutral ethanol [2], do

not undergo hydrogenolysis at the N - N bond of the h e t e r o r i n g in ethanol with added alkali in the p r e s e n c e
of Raney nickel. It s e e m e d of i n t e r e s t to examine the behavior of other enolized 3,5-dioxopyrazolidines
during hydrogenolysis in alkaline media, to examine the possible r e a s o n s for the i n c r e a s e d stability of the
N - N bond, and to attempt to link them to the quantum-chemical c h a r a c t e r i s t i c s of the molecules.
It was found that not only 1,2,4-trisubstituted dioxopyrazoldienes, for example, 1,2-diphenyl-4-butyl-
3,5-dioxopyrazolidine (IV), but also compounds that are capable of simultaneous keto-enol and l a c t i m -
l a c t a m t a u t o m e r i s m - 1-phenyl- (I), 1,4-diphenyl- (II), and 5 - i s o a m y l - 3 , 5 - d i o x o p y r a z o l i d i n e s ( I I I ) - are
incapable of undergoing hydrogenation in ethanol containing two to three equivalents of potassium hydrox-
ide. The t r i s o d i u m salt of the enol of 4-butyl-l,2-di(p-sulfophenyl)-3,5-dioxopyrazolidine (V) does not un-
dergo hydrogenolysis in neutral ethanol, but 4-diethylaminoethyl-l,2-diphenyl-3,5-dioxopyrazolidine (VI),
which apparently exists in the betaine f o r m in neutral ethanol, is hydrogenated at a significantly lower rate
than its 4-alkyl analogs, for example, IV (Fig. 1). As already d e s c r i b e d in [3], 4-(p-aminobenzylidene)-
(VII) and 4 - ( p - n i t r o b e n z y l i d e n e ) - l , 2 - d i p h e n y l - 3 , 5 - d i o x o p y r a z o l i d i n e s (VIII) in neutral ethanol are h y d r o -
genated only to 4-(p-amin0benzyl)-l,2-diphenyl-3,5-dioxopyrazolidine (IX) (which is capable of forming a
betaine), in c o n t r a s t to 4 - b e n z y l i d e n e - l , 2 - d i p h e n y l derivative X, which is hydrogenated under these same
conditions with cleavage of the N - N bond to butylmalonie acid dianilide (XIa),
It is c h a r a c t e r i s t i c that 4 - ( p - a c e t a m i d o b e n z y l i d e n e ) - l , 2 - d i p h e n y l - 3 , 5 - d i o x o p y r a z o l i d i n e (XII), which
is unable to f o r m a betaine, is also hydrogenated to p-acetamidobenzylmalonie acid dianilide (XIc).

* See [1] for communication XXI.

Leningrad P h a r m a c e u t i c a l - C h e m i s t r y Institute. A. E. Arbuzov Institute of Physical and Organic

Chemistry, Academy of Sciences of the USSR, Kazan. T r a n s l a t e d f r o m Khimiya Geterotsiklicheskikh
Soedinenii, No. 3, pp. 403-407, March, 1974. Original article submitted March 23, 1973.

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, N.Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, miaiofilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

354
 W, ml/mhl
I0 The above data constitute an additional confirmation of the
8
fact of the decrease in the rate of hydrogenolysis of the N - N bond
of enolates of the 3,5-dioxopyrazolidineseries. The reasons for
S
this may be an increase in the strength of the Ni- 9.H bond in alka-
line media [4], a decrease in the adsorption of the enolate on the
2 catalyst, or an increase in the strength of the N - N bond of the het-
erocycleo
E%,ml
800 In considering the first of the possible reasons, one should
note that the hydrogenation of some compounds of other series oc-
700
curs even in very alkaline media [5]. We have also established that
600
substituted benzylidenemalonic acid dianilides are hydrogenatedonly
500 in neutral media and not in alkaline media [3]. 1,2-Diphenyl-4-
400 butyl-4-methyl-3,5-dioxopyrazolidine(XIII), which is incapable of
rnV enolization, is cleaved in alkaline media to methylbutylmalonic acid
mono(N,N'-diphenylhydrazide),which is then hydrogenated to methyl-
Fig. 1. Kinetic and potentiomet-
butylmalonie acid monoanilide [2]. It follows from the above data
ric c u r v e s of the hydrogenation
that the increase in the strength of the Ni- 9.H bond in alkaline media
of 3.25 m m o l e of IV and VI in
cannot be the only reason for the sharp decrease in the rate of hy-
ethanol at 30~
drogenation of the enolate of 3,5-dioxopyrazolidine.
In o r d e r to a s c e r t a i n whether the adsorption of 3,5-dioxopyrazolidine enolates on the c a t a l y s t changes,
we studied the reaction of IV-VI with the Raney nickel surface using the potentiometric method of Sokol'-
skii and D r u z ' [6]. It was found that IV in ethanol in the p r e s e n c e of two to three equivalents of alkali shifts
the catalyst potential (1090 mV) to the anode side by only 25 mV, while a shift of 200 mV is observed in
neutral ethanol (Fig. 1). Compounds V and VI in neutral ethanol do not shift the catalyst potential at all to
the anode side. These r e s u l t s are evidence in favor of the assumption that the p r i m a r y r e a s o n for the de-
c r e a s e in the rate of h y d r o g e n o l y s i s of the N - N bond of 3,5-dioxopyrazolidine chelates is the d e c r e a s e in
their adsorbability on the c a t a l y s t surface.
The l a t t e r m a y be caused by a change in the electronic charge of the molecules and the d e c r e a s e , as
a consequence of this, in the effective c h a r g e s on the nitrogen a t o m s of the hydrazine fragment. We r e -
cently e x p r e s s e d the a s s u m p t i o n that the magnitudes of the effective c h a r g e s on the nitrogen atoms in the
3 and 5 positions of the h e t e r o c y c l e , which depend on the nature of the substituents, affect the rate of hy-
drogenolysis of the N - N bond of v a r i o u s l y substituted 3,5-dioxopyrazolidines. The i n v e r s e dependence
between the magnitude of the rate of h y d r o g e n o l y s i s and the calculated (by the Htickel MO method) e f f e c -
tive c h a r g e s on the 3- and 5-C atoms of 4 - s u b s t i t u t e d 1,2-diphenyl-3,5-dioxopyrazolidines [7] was in a c -
cord with this assumption.
F r o m this point of view, it s e e m e d of i n t e r e s t to c o m p a r e the m o l e c u l a r d i a g r a m s of the enolate and
enol of 3,5-dioxopyrazolidine, which we calculated within the 7r-electron approximation by the P a r i s e r -
P a r r - : P o p l e method with the use of s e m i e m p i r i c a l p a r a m e t e r s [8, 9] (Table 1). The p a r a m e t e r s were s e -
lected in such a way as to s a t i s f y the principal p h y s i c o c h e m i c a l p r o p e r t i e s of simple molecules with N - N ,
N--C, and C =O bonds. The role of phenyl groups in stabilization of the anion was examined simultaneously.
The phenyl rings in s t r u c t u r e s A and B deviate from the conjugation plane by 30 ~ because of steric hin-
drance, while conjugation is artifically excluded in s t r u c t u r e C. As in [10, 11], the total e n e r g y of the
f r a g m e n t s was broken down into physical components. Conjugation with the phenyl substituents r a i s e s the
stability of the anionic s t r u c t u r e by 26 k c a l / m o l e , and the resonance component of the e n e r g y plays the
dominant role h e r e .
It follows f r o m the data p r e s e n t e d in Table I that the effective c h a r g e s of the nitrogen atoms in eno-
late A (0.196) a r e a p p r e c i a b l y lower than in enol C (0.318 and 0.357); this is in a g r e e m e n t with the above
assumption r e g a r d i n g the effect of the magnitude of the effective c h a r g e s of the nitrogen atoms and with
the experimental data on the d e c r e a s e in the rate of h y d r o g e n o l y s i s of dioxopyrazolidine enolates at the
N - N bond.
F r o m a c o m p a r i s o n of the calculated (as in [8, 9] f r o m the e x p r e s s i o n Rmn = a p m - n +b) bond lengths
of the enol and enolate of 1 , 2 - d i p h e n y l - 3 , 5 - d i o x o p y r a z o l i d i n e it follows also that the a r o m a t i c c h a r a c t e r of
the enolate is higher. The bond lengths in the enolate a r e c o n s i d e r a b l y m o r e equalized than in the enoh
the m a x i m u m difference in the calculated bond lengths in the enolate is 0.036 A, while that in the enol is
is 0.120 Ao Thus the i n c r e a s e in the a r o m a t i c c h a r a c t e l - i n the 1,2-diphenyl-3,5-dioxopyrazolidine enolate

355
 T A B L E I. R e s u l t s of Q u a n t u m - C h e m i c a l C a l c u l a t i o n s *
I
m -%qra m-n :1 Pro- n rtm-n m Aq m rn-n I Pm-n

16
7
0~x~._N~La17
15

14--0"6 a~lo
]2

2. 0,196 1--=2 0,120 1,431 1 0,318 1--2 0,225 1,412

3 0,175 2--3 0,349 1,395 2 0,357 I--5 0,494 1,369
4 -0,245 3--4 0,609 1,408 3 0,029 1--'14 0,229 1,417
6 - 0,650 3--6 0,632 t.251 4 --0.300 9 2--3 0,547 1,360
s o,o2~ 2--8 ~),275 1,408 5 0.185 2--8 0,222 1,418
9 - 0,039 8-9 olrr 1,402 6 0.035 3--4 0,746 1,,324
[0 -0,017 8--13 0,636 1,4(12 7 -0,573 3--6 0,188 1,331
I1 --0.042 9--10 0,671 1,396 8 0,003 4~5 0,427 1,440
12 --0,0~ 10--11 0,664 1,397 9 0~007 5--7 0,702 1,239
13 0,006 11--12 0,660 1,398 10 0,009 8--9 0,648 1,400
12--13 0,675 1,395 11 --0,003 8--13 0,649 1,400
12 0,003 9--10 0~671 1396
5 nt41"l 13 -0,027 lO--11 0,664 1,397
14 O,O[1 11--12 0,665 1,397
15 0,004 t2--13 0,669 1.397
16 0,004 14--16 0,647 1,401
C 17 0,012 14--19 0,647 1,401
18 0,005 15--16 0,670 1,396
2 0,137 ' 1--2 0,100 1,435 19 0~030 16--17 0,664 1,397
3 90,178 2--3 0,376 1,390 17--18 0,664 1,397
-4 -0~290 3--4 0,610 1,407 18--19 0,670 1,396
6 --0,670 3--6 0,618 1,254

* Symbols: m and n are the atom numbers, Aq m is the effective

atomic charge, m - n is the bond, P m - n is the v-bond order, and
R m - n is the calculated bond length in angstroms.

m a y a l s o be one of t h e r e a s o n s f o r t h e i n c r e a s e in the r e s i s t a n c e of the N - N b o n d to h y d r o g e n o l y s i s o v e r

Raney nickel.

H o w e v e r , we w e r e u n a b l e to d e l i m i t the e f f e c t of a r o m a t i z a t i o n and of the d e c r e a s e in a d s o r p t i o n of

the e n o l a t e on the c a t a l y s t by c o m p a r i s o n of the s t a b i l i t y of IV d u r i n g i t s h y d r o g e n a t i o n w i t h o u t a c a t a l y s t
by n a s c e n t h y d r o g e n i n a c i d i c a n d a l k a l i n e m e d i a (ethanol). U n d e r t h e s e c o n d i t i o n s , IV i s not h y d r o g e n a t e d
i n e i t h e r a l k a l i n e o r a c i d i c m e d i a ; t h i s c o n f i r m s the high s p e c i f i c i t y of R a n e y n i c k e l a s a c a t a l y s t for the
h y d r o g e n o l y s i s of the N - N bond of 3 , 5 - d i o x o p y r a z o l i d i n e s .

EXPERIMENTAL

S t a r t i n g c o m p o u n d s I, II, a n d IV-VI w e r e p r e v i o u s l y d e s c r i b e d i n [12]. C o m p o u n d III w a s o b t a i n e d by

the m e t h o d i n [13].

The h y d r o g e n o l y s i s o f I - V I a n d the m e a s u r e m e n t of the c a t a l y s t p o t e n t i a l w e r e a c c o m p l i s h e d with

the p r e v i o u s l y d e s c r i b e d v a r i a n t of the S o k o l ' s k i i - D r u z ' a p p a r a t u s [6].

A t t e m p t e d R e d a c t i o n of D i c x o p y r a z o l i d i n e IV i n H o m o g e n e o u s M e d i a . A) Z i n c d u s t w a s a d d e d i n
s m a l l p o r t i o n s i n the c o u r s e of 5 h with p e r i o d i c s h a k i n g a t r o o m t e m p e r a t u r e to 0.5 g of IV i n 50 m l of a
15% e t h a n o l s o l u t i o n of HCI. T h e f i l t r a t e w a s d i l u t e d with w a t e r to b r i n g a b o u t p r e c i p i t a t i o n . A t o t a l of
0.45 g of s t a r t i n g c o m p o u n d c o n t a i n i n g n o XI ( a c c o r d i n g to TLC) w a s o b t a i n e d . S i m i l a r r e s u l t s w e r e o b -
t a i n e d when the m i x t u r e was r e f l u x e d .
B) Z i n c d u s t w a s added in s m a l l p o r t i o n s in the c o u r s e of 2 h to a r e f l u x i n g m i x t u r e of 0.5 g of IV
a n d 50 m l of 50% NaOH s o l u t i o n . The f i l t r a t e w a s a c i d i f i e d a n d w o r k e d u p to give 0.45 g of the s t a r t i n g
c o m p o u n d c o n t a i n i n g no XI.

S i m i l a r r e s u l t s w e r e o b t a i n e d when the r e a c t i o n w a s c a r r i e d out in a l k a l i n e e t h a n o l s o l u t i o n .

( f l - D i e t h y l a m i n o e t h y l ) m a l o n i c A c i d D i a n i l i d e (XIb). A 7.0 g s a m p l e of VI a n d 3 g of R a n e y n i c k e l
w e r e r e f l u x e d i n 50 m l of e t h a n o l for 20 h with c h r o m a t o g r a p h i c m o n i t o r i n g on a c t i v i t y III a l u m i n u m oxide
i n e t h a n o l - a m m o n i a - e t h y l a c e t a t e (9.5 : 1 : 20) of the d e c r e a s e i n the c o n c e n t r a t i o n of the s t a r t i n g e c r u -

356
pound (the R f of VI is 0.61, and the R f of dianilide XIb is 0.83). After s e p a r a t i o n of the c a t a l y s t , the fil-
t r a t e was e v a p o r a t e d to d r y n e s s , and the r e s i d u e was t r e a t e d with 60 ml of 30% ethanol to r e m o v e the r e -
sidual s t a r t i n g compound. R e c r y s t a l l i z a t i o n f r o m ethanol gave 5.9 g (84%) of a c o l o r l e s s c r y s t a l l i n e s u b -
stance with m p 153 ~ IR s p e c t r u m : 1666, 1610, 1550, 1518, 1320, 1260 c m -1. UV s p e c t r u m (in neutral,
acidic, and alkaline ethanol): 246 nm (log ~ 4.4). Found: N 12.1%. C21H27N302. Calculated: N 11.9~. The
hydrochloride was obtained in benzene as a colorless crystalline substance with mp 206-207~ Found: N
i i . i ; Cl 9%; equiv, wt. 398. C21H27N302.HCl. Calculated: N 10.9; Cl 9.1%; equiv, wt. 390.
1,2-Diphenyl'4-(p-acetar idobenzylidene)-3,5-dioxopyrazolidine(XII). A solution of 0.6 g of amino-
benzylidenedioxopyrazolidineVII in 10 ml of acetic anhydride was heated at 130-140~ for 4 h. The cooled
reaction mixture was poured into water, and the aqueous mixture was worked up to give 0.67 g (90%) of a
red substance with mp 338-339~ (from acetic acid). IR spectrum: 3450, 3300, 1705, 1677, 1613, 1568, and
1500 cm-i. UV spectrum, kmax, nm (log a): acidic ethanol 243 (4.49), 384 (4.58); alkaline ethanol251 (4~176
Found: C 70.1; H 4.7; N 9.6%. C24HIgN303"0.5CH3COOH. Calculated: C 70.4; H 4.9; N 9.8~o.
p-AcetamidobenzyhnalonicAcid Dianilide (XIc). A 0.3 g sample of dioxopyrazolidineXII was hy-
drogenated in 30 ml of ethanol over 2 g of Raney nickel until hydrogen absorption had ceased. The catalyst
was separated, and the filtrate was evaporated to give 0.25 g of a colorless crystalline substance with mp
238-239~ (from aqueous dioxane)o IR spectrum: 1675, 1655, 1600, 1531, and 1500 cm-i. UV spectrum,
Xmax, nrn (log e): neutral and acidic ethanol 248 (4.62); alkaline ethanol 248 (4.69). Found: C 71.8; H 5.7;
N 10.7%. C24H23N303. Calculated: C 71.8; H 5.7; N 10.5%.

LITERATURE CITED
1. B.L. Moldaver and M. E. Aronzon, Khim. Geterotsikl. Soedin., 224 (1974).
2. B.L. Moldaver, M. E. Aronzon, and M~ P. Papirnik, Khim. Geterotsikl. Soedin., 407 (1970).
3. B.L. Moldaver and M. E~ Aronzon, Khim. Geterotsikl. Soedin., 804 (1970).
4. D.V. Sokol'skii, Hydrogenationin Solution [in Russian], Izd. Akad. Nauk KazakhSSR,Alma-Ata
(1962).
5. D.V. Sokol'skii, Trudy Instit. Khim. Nauk Akad. Nauk KazakhSSR, 5, 146 (1959).
6. D.V. Sokol'skii and V. A. Druz', Dokl~Akad. Naak SSSR, 7__3_3,5 (1949).
7. B.L. Moldaver, M. P~ Papirnik, V. V. Zverev, and Yu. P. Kitaev, Khim. Geterotsikl. Soedin., 781
(1973).
8. H. Jensen and P. N. Skaneke, Acta Chem. Scand., 2_~2,2899 (1968).
9. O. Gropen and P. N. Skancke, Acta Chem. Seand., 24, 1768 (1970).
10. V.V. Zverev, Teor. i ]~ksperim. Khim~ 5, 834 (1969---).
11. V.V. Zverev, Zh. Obsheh. Khim., 4_~i,379 (1971).
12. A.M. Khaletskii and B. L. Moldaver, Zh. Obsheh. Khim., 34, 216 (1964).
13. H. Briiumiger and R. Moede, Pharm. Zentralhalle, 108, 615 (1969).

357
 RESEARCH ON U N S A T U R A T E D AZOLE DERIVATIVES
I. SYNTHESIS AND TRANSFORMATIONS OF ~,fl-UNSATURATED
ACIDS IN THE AZOLE SERIES

I. I. Popov, A. M. Simonov, UDC 547.785.07 : 543.422.4.6

V. I. Mikhailov, a n d N. A . S i [ ' v a n o v i c h

A number of e s t e r s of some fl-(2-azolyDaerylic acids were synthesized by means of the

Wittig reaction and subjected to hydrolysis. The reaction of f l - ( 1 - m e t h y l - 2 - b e n z i m i d a z o l y D -
acrylic acid and its derivatives with bromine was studied. It is shown that 1 - m e t h y l - 2 -
ethynylbenzimidazole and 1,2-dimethylbenzimidazole a r e f o r m e d when methyl a - b r o m o - f l -
( 1 - m e t h y l - 2 - b e n z i m i d a z o l y l ) - a c r y l a t e is refluxed in sodium bicarbonate solution.

We have previously [1] d e s c r i b e d two methods for the synthesis of f l - ( 1 - m e t h y l - 2 - b e n z i m i d a z o l y l ) -

a c r y l i c acid (In) - by condensation of 1,2-dimethylbenzimidazole (Iia) with chloral and f r o m 1 - m e t h y l - 2 -
f o r m y l - b e n z i m i d a z o l e (IIIa) by m e a n s 9of the Wittig reaction. Continuing these investigations, we have sub-
jected 5 - m e t h o x y and 5 - n i t r o derivatives of 2-methylbenzimidazole (IIb and c) to condensation with chloral.
However, in c o n t r a s t to IIa [1], IIb and IIc do not r e a c t with chloral. On the other hand, the reaction of
9 f o r m y l b e n z i m i d a z o l e s with r e s o n a n c e - s t a b i l i z e d phosphoranes is apparently a general reaction [1, 2]. Thus
the reaction of aldehydes IIb, c,d with carbalkoxymethylenetriphenylphosphoranes IVa,b p r o c e e d s quite
smoothly on refluxing in benzene, and e s t e r s of fl-(2-benzimidazolyl)acrylic acids (Vb,c,d) are f o r m e d in
good yields (Table 1):

' r..~l~l..j..c~o(gnp~P=cucoor"
(,W,b, r ~ N L~L.c=.cncoor".--
1 I
R' R'
IIIb-d vb-f

I I
R' C~H5 vl vII
Ib-d
IO., l i l t , vc, f R=R'=CH3; Ib,111b. vb,o R=OCHs, R'=ctt3; Id, IIIC~vd R~R'=H: Ivz. v b - d
r,,=cH3: Ivb, ye,f R"=C2Hs; VIa R=CH3,b R~H; VII a R"=CHa,b R"=C2HS,C R"=H

1 - P h e n y l - 2 - f o r m y l i m i d a z o l e (IIIe) and 2-formylbenzothiazole (IIIg) r e a c t just as r e a d i l y with phos-

phoranes IV; the yields of e s t e r s Via and VIIa,b a r e quite high (Table 1).
Somewhat m o r e s e v e r e conditions a r e n e c e s s a r y for the preparation of e s t e r Vd: the reaction is
c a r r i e d out by prolonged refluxing of phosphorane IVa with aldehyde IIId in d i m e t h y l f o r m a m i d e ( D M F ) -
benzene (1: 1); this is due to the p o l y m e r i c s t r u c t u r e of IIId [3, 4].*
E s t e r s V, VI, and VII a r e quite smoothly hydrolyzed when they are refluxed in a l c o h o l i c p o t a s s i u m h y -
droxide solution to give the corresponding fl-azolylacrylic acids (I). The intense absorption band in the IR

,2-Formylbenzimidazol e is gradually depolymerized when it is refluxed in DMF and dimethyl sulfoxide

(DMSO) [41.

Rostov State University, Rostov-on-Don. T r a n s l a t e d f r o m Khimiya Geterotsiklicheskikh Soedinenii,

No. 3, pp. 408-412, March, 1974. Original article submitted D e c e m b e r 20, 1972.

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, N.Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

358
 T A B L E 1. ( 2 - A z o l y l ) a c r y l i c A c i d s and T h e i r E s t e r s
Found, ~ Calc., ~o I
Im [ Crystallization Empirical
~ ~ p,~ solvent formula C H I N j S !i
~3 i C iH N i s !"~
i"~

Vd 180 Aqueousalcohol
]d 240a IA l c o h o l C,0HsN~O2 ! i
Vb 185--186 Toluene CI3HI4N203 63,8 6,0Jl16 '63415,7~11,4! -- 68,0
Ve 132--133 !Dioxane Ct4HI6N203 64,9611 109 -- 64,6 6,2[10,8' 62,0
lb 250 '1Alcohol CI2HI2N203 619:54i 12,0' 162,0i5,2'12,1 -- 72.0
Vc 135-- 136i Aqueous alcohol CI3HI4N202 6 7 , 4 6,0112,2~ - - 67,8 6,1i 11,8! -- 65,0
vf 111--112 ~,Aqueous alcohol C14H[6N202 69,0,6,6i112 - - ~3,9 66i11,5: - - 81,0
lc 240 ':Alcohol C12Hl~N202 66,515,5112,9 -- '66,7 5 , 8 i 1 2 , ~ - - ' 75,0
Via 115 IPetroleum ether C~3H~2N202 68,85,3:12.4 ~ 68,4152112,3:-- 93,0
Vlb 219b iWater C,2I-I1oN202 ! 14,5 on,
,~,,~73[VI - - ' - - 87,0
\.'Ila 105 iAqueousatcohol CuHgNO2S 60,6:4,5 6,4 6,39114,6 77
VIIb 89 !Aqueous alcohol CI=HuNO=S]61414,9 6,~ 13,3 61.814,81 6,0!13,7 78
VIIc 219e !Alcohol C,oH~NO~Sr--I-- [ . . . . -[- ]- ~7~
I_
Note: a A c c o r d i n g to [13], m p 2390. b A c c o r d i n g to [14], m p 218-
219 ~ C A c c o r d i n g to [15], m p 219 ~

s p e c t r a of the a c i d s and e s t e r s at 968-970 c m -1 is e v i d e n c e in f a v o r of the p r e d o m i n a n t f o r m a t i o n of the

t r a n s i s o m e r s of t h e s e c o m p o u n d s .

The r e a c t i o n of a c i d Ia with b r o m i n e in c h l o r o f o r m or a c e t i c a c i d l e a d s to the f o r m a t i o n of an e x -

t r e m e l y s t a b l e p e r b r o m i d e . B r o m i n e adds to the C - C bond of a c i d Ia only upon the p r o l o n g e d a c t i o n of
e x c e s s b r o m i n e in the light. This s o r t of p h e n o m e n o n h a s been d e s c r i b e d f o r 4 - s t y r y t p y r i d i n e [5] and
5 ( 6 ) - m e t h y l - 2 - s t y r y l b e n z i m i d a z o l e [6].
The m e t h y l e s t e r of a c i d I a (Va) r e a c t s with b r o m i n e in c h l o r o f o r m to give a p e r b r o m i d e ; m e t h y l
f l - ( 1 - m e t h y l - 2 - b e n z i m i d a z o l y l ) - f l - b r o m o a c r y l a t e (VIII) is f o r m e d in a c e t i c acid with e x c e s s b r o m i n e .

Va CH3COOH I CBr=CHCOOCH3 CH=CHCON(C,: H5}2 CHCI~

I I
CH3 CH3
Vlll IX a

_ c6.s, p-cB,cooc. A A
CHBrCHBrCO I|1 a ":/ \N CH=EBrCOOCH3
I i
CH3 N(C2Hs)2 CH 3
IX X

The r e a c t i o n of the d i e t h y l a m i d e of a c i d Ia with b r o m i n e p r o c e e d s S o m e w h a t m o r e r e a d i l y ; it adds

two a t o m s of b r o m i n e to give d i b r o m o d e r i v a t i v e IX.
The s y n t h e s i s of m e t h y l ~ - b r o m o - f l - ( 1 - m e t h y l - 2 - b e n z i m i d a z o l y D a c r y l a t e (X) can be r e a l i z e d by
m e a n s of the Wittig r e a c t i o n - by r e a c t i o n of the p r e v i o u s l y d e s c r i b e d [7] c a r b o m e t h o x y b r o m o m e t h y l e n e -
t r i p h e n y l p h o s p h o r a n e (IVc) with a l d e h y d e IIIa [ i l ] .
The c o i n c i d e n c e of the a b s o r p t i o n bands in the UV s p e c t r a of e s t e r s VIII and X (Fig. 1) is e v i d e n c e
in f a v o r of the f a c t that the b r o m i n a t i o n of e s t e r V a p r o c e e d s in the side chain. A h y p s o c h r o m i c shift of
the m a x i m u m of the l o n g - w a v e a b s o r p t i o n as a c o n s e q u e n c e of d i s r u p t i o n of conjugation in the c a r b o n y l -
g r o u p - h e t e r o c y c l i e - r i n g s y s t e m (Fig. 2) is o b s e r v e d in the UV s p e c t r u m of d i e t h y l a m i d e IX.
An a t t e m p t to r e a l i z e the t r a n s i t i o n d i r e c t l y f r o m f l - ( 2 - b e n z i m i d a z o l y l ) a c r y l i e a c i d s to f l - ( 2 - b e n -
z i m i d a z o l y l ) p r o p i o l i c a c i d s by the usual m e t h o d ( b r o m i n a t i o n / d e h y d r o b r o m i n a t i o n ) , as in the c a s e of fl-
( 2 - b e n z o t h i a z o l y l ) a c r y l i c a c i d [8], w a s u n s u c c e s s f u l . Thus, f o r e x a m p l e , the action of a r e f l u x i n g alcohol
solution of p o t a s s i u m h y d r o x i d e on e s t e r VIII g i v e s r e s i n o u s r e a c t i o n p r o d u c t s of p o l y m e r i c s t r u c t u r e (see
[8]). Refiuxing e s t e r X in a l c o h o l i c p o t a s s i u m h y d r o x i d e solution g i v e s 1 , 2 - d i m e t h y l b e n z i m i d a z o l e (IIa), a p -
p a r e n t l y as a c o n s e q u e n c e of c l e a v a g e of the p r o d u c t s of d e h y d r o b r o m i n a t i o n of e s t e r X u n d e r the r e a c t i o n
conditions.* The use of a w e a k e r base e n a b l e d us to c h a n g e the d i r e c t i o n of the r e a c t i o n : The p r e v i o u s l y
d e s c r i b e d [11] 1 - m e t h y l - 2 - e t h y n y l b e n z i m i d a z o l e (XI) was i s o l a t e d a l o n g with IIa when e s t e r X w a s r e f l u x e d
in s o d i u m b i c a r b o n a t e solution.

* See [9, 10] f o r this s o r t o f c l e a v a g e of the C = C bond o f 2 - s u b s t i t u t e d b e n z i m i d a z o l e s to give 2 - m e t h y l

derivatives.

359
 o~x x

~atcoholic KOH r e f l u x ~ - - - - / ~

il a Xl

When XI is in turn refluxed in alcoholic p o t a s s i u m hydroxide solution, it is gradually c o n v e r t e d to Ha.

T h e s e o b s e r v a t i o n s provide a b a s i s for a s s u m i n g that 1 - m e t h y l - 2 - e t h y n y l b e n z i m i d a z o l e is an i n t e r -
m e d i a t e in the cleavage of the side chain of e s t e r X to a m e t h y l group.

EXPERIMENTAL
The [IV spectra of methanol solutions of the compounds were recorded with an SF-4A spectropho-
tometer. The IR spectra of mineral oil pastes of acids VIII and of chloroform solutions of the esters were
recorded with a UR-20 spectrometer.
General Method for the Preparation of/~-(2-AzolyDacrylic Acid Esters (V). A 0.01 mole sample of
IVa or IVb and 0.01 mole of the appropriate aldehyde were refluxed in a solution of 20 ml of benzene for
8-12 h; the course of the reaction was monitored by means of TLC on aluminum oxide in chloroform. At
the end of the reaction, the mixture was shaken with 40 ml of 5% hydrochloric acid. The hydrochloric acid
extract was made alkaline with saturated sodium bicarbonate solution, and the precipitated ester was re-
moved by filtration and washed with water. In the isolation of esters V, the solvent was first removed by
distillation, and the reaction product was separated from the triphenylphosphine oxide by chromatography
of the r e s i d u e in e t h e r on activity V aluminum oxide. The yields and m e l t i n g points a r e p r e s e n t e d in T a -
b l e 1.
E s t e r Vd was obtained by r e fluxing a solution of 2 - f o r m y l b e n z i m i d a z o l e with phosphorane IVa in a
m i x t u r e of 3 m l of DMF and 3 m l of benzene f o r 40 h on an oil bath. The product was e x t r a c t e d with dilute
h y d r o c h l o r i c acid.
H y d r o l y s i s of fl-(2-Azolyl)acrylic E s t e r s . A 0.01 m o l e s a m p l e of the a p p r o p r i a t e e s t e r was refluxed
f o r 4 h in 15% alcoholic p o t a s s i u m hydroxide solution. The alcohol was then r e m o v e d by distillation, and
the r e s i d u e was dissolved in w a t e r . The u n s a t u r a t e d acid was isolated f r o m the solution with dilute hy-
d r o c h l o r i c acid.
M e t h y l ~ - ( 1 - M e t h y l - 2 - b e n z i m i d a z o l y l ) - f l - b r o m o a c r y l a t e (VIII). A 1.2 g (60 mmole) s a m p l e of e s t e r
Va [1] was d i s s o l v e d in 5 m l of acetic acid, and 0.62 m l (12 m m o l e ) of b r o m i n e in 3 m l of acetic acid was
added dropwise with vigorous s t i r r i n g . As the color of the bromine d i s a p p e a r e d , a light-yellow p r e c i p i t a t e
(the p e r b r o m i d e ) f o r m e d . The m i x t u r e was s t i r r e d for another 4 h, and the p r e c i p i t a t e was r e m o v e d by
filtration, w a s h e d with acetic acid, shaken with sodium m e t a b i s u l f a t e solution (to d e c o m p o s e the p e r b r o -
mide) and a s a t u r a t e d sodium bicarbonate solution, a f t e r which it was e x t r a c t e d with c h l o r o f o r m . The e x -
t r a c t was d r i e d with sodium sulfate, and the solvent was r e m o v e d by distillation to give 1.1 g (73%) of c o l -
o r l e s s plates ( f r o m water) with m p 200-201 ~ (dec.). The product was soluble in alcohol, benzene, and di-
oxane. The R f value in CHC13 on a thin l a y e r of activity V a l u m i n u m oxide was 0.8 (the R f value of the
s t a r t i n g e s t e r was 0.6). The product d e c o l o r i z e d a p o t a s s i u m p e r m a n g a n a t e solution, did not contain tone-
genie halogen, and showed l i g h t - g r e e n f l u o r e s c e n c e in UV light (C = C conjugated with the ring). Found:
C 48.8; H 4.2; B r 26.3; N 9.7%. Cl~HIiBrN202. Calculated: C 48.9; H 4.1; Br 26.8; N 9.6%. UV s p e c t r u m ,
max, n m (log ~): 263 (3.57), 323 (4.37).
B - ( 1 - M e t h y l - 2 - b o n z i m i d a z o l y l ) - ~ , f l - d i b r o m o p r o p i o n i c Acid N,N-Diethylamide (IX). This compound
was obtained in 76% yield as c o l o r l e s s needles ( f r o m aqueous alcohol) with m p 140 ~ (dec.) by bromination
of IXa [1] in c h l o r o f o r m , as in the c a s e of e s t e r VIII. The product did not d e c o l o r i z e aqueous p o t a s s i u m
p e r m a n g a n a t e solution, did not contain ionogenic halogen, and did not f l u o r e s c e in UV light. Found: C
43.4; I-I 4.9; Br 38.1; N 10.3%. CisH19Br2N30. Calculated: C 43.2; H 4.6; B r 38.3; N 10.1%. UV s p e c t r u m ,
Xmax, nm (log ~): 262 (4.04), 290 (4.2).
Methyl ~-Bromo-fl-(1-methyl-2-benzimidazolyl)aerylate (X). A 2.1 g (5 mmole) samples of bromophos-
phorane IVc was dissolved in 15 ml of benzene, 0.8 g (5 mmole) of llla was added, and the mixture was
stirred to dissolve the solid completely. The mixture began to heat up, and light-yellow crystais of ester

360
 ~ge

4,0
9., 1: i ~
3,5 3,5

3,0
i i ~ I\ 310

\i ' J i I I , ~
250 3o0 3sO ~0 ~.~nm 250 300 350 400 ,t, nm

Fig. 1. UV s p e c t r a (in m e t h a - Fig. 2. UV s p e c t r a (in methanol)=

nol): i) Va; 2) VIII; 3) X. 1) Ia; 2) IXa; 3) IX.

X began to precipitate immediately. The mixture was heated on a water bath to dissolve the precipitate,
and the mixture was allowed to stand in w a r m water for a brief time. It was then cooled, and the p r e c i p i -
tated c r y s t a l s of the e s t e r were r e m o v e d by filtration. Prolonged heating often led to resinification of the
reaction products. The yield was 1.1 g (68%). The yellow p r i s m s with a p a l e - g r e e n tint had mp 186 ~ (dec.,
benzene) and were r e a d i l y soluble in c h l o r o f o r m and dioxane and only slightly soluble in alcohol [11].
Reaction of E s t e r X with Sodium Bicarbonate. A 0.6 g (20 mmole) sample of X was refluxed in a so-
lution of 1.4 g of sodium bicarbonate in 20 ml of water for 9 h, after which the dark oil (a mixture of IIa
and XI) was extracted with c h l o r o f o r m and c h r o m a t o g r a p h e d on aluminum oxide. The solvent was r e m o v e d
by distillation, and the mixture of IIa and XI was s e p a r a t e d on aluminum oxide in ether with collection of
XI in the f i r s t portions of the eluate. The yield of XI with mp 100 ~ (petroleum ether) (rap 100 ~ [11]) was
0.075 g (24%). The yield of IIa with mp 112 ~ [12] was 0.10 g (42%).

LITERATURE CITED
1. I. I. Popov, A. M. Simonov, and S. N. Kolodyazhnaya, Ehim. Geterotsikl. Soedin., 1566 (1970).
2. I. I. Popov and A. M. Simonov, Khim. Geterotsikl. Soedin., 122 (1971).
3. D. D. Dalgatov, B. A. Tertov, A. M. Simonov, V. I. Gaivoronskii, and O. A. Osipov, Zh. Vsesoyuzn.
I<him. Obshehestva, 8, 582 (1963).
4. H. R. Henkel, Chem. B e r . , 98, 1325 (1965).
5. J. M. Smith, H. W. Stewart, B. Roth, and E. H. Northey, J. A m e r . Chem. Soc., 70, 3997 (1948).
6. F. Fichter, J. Prakt. Chem., 74, 320 (1906).
7. G. Milrkl, Chem. Ber., 94, 2996 (1961).
8. O. Neunhoeffer and V. Georgi, Chem. Bet., 92, 791 (1959).
9. D.D. Dalgatov and A. M. Simonov, Khim. Geterotsikl. Soedin., 908 (1967).
10. M. T~ Ze Bris, Bull. Sec. Chim. France, 3411 (1967).
11. A.M. Simonovand I. I. Popov, Khim. Geterotsikl. Soedin., 140 (1971).
12. M.T. Le Bris, H. Wahl, and T. Jambu, Bull. Soe. Chim. France, 343 (1959).
13. K.H. Tars, Z. V. Presser, G. B. Wigton, and M. M. Joullie, J. Org. Chem., 26, 462 (1961).
14. L.M. Sitkina and A. M. Simonov, Khim. Geterotsikl. Soedin., 410 (1970).
15. W. Ried and W. Reitz, Chem. Ber., 89, 2429 (1956).

361
RESEARCH ON U N S A T U R A T E D AZOLE DERIVATIVES
H.* SYNTHESIS AND TRANSFORMATIONS OF SOME
fl-(2-AZ OLYL) PROPIOLIC ACIDS

A. M. S i m o n o v , I . I . P o p o v , UDC 547.785.5.07
V. I . M i k h a i l o v , N. A. S i l ' v a n o v i c h ,
a n d O. E . S h e l e p i n

a-Bromo-fl-(2-azolyl)acrylic acid est ers, the dehydrobromination of which with alcoholic

alkali gives fl-(2-azolyl)propiolic acids, were synthesized by means of the Wittig reaction.
Some 2-ethynylbenzimidazoles were synthesized by thermal decarboxylation of the fl-(2-
benzimidazolyl)propiolic acids. It is assumed that the ease of decarboxylation of these
acids is due to the possibility of the formation by them of dipolar ions.

We have previously [1] described the synthesis of ~-bromo-fl-(1-methy!-2-benzimidazolyl)acrylic

acid (IIa) by reaction of 1-methyl-2-formylbenzimidazole (Ia) with carbomethoxybromomethylenetriphenyl-
phosphorane (IH} [2]. Continuing these investigations in the azole series, we have introduced 5-substituted
2-formylbenzimida/oles (Ib,c) into the reaction with phosphorane IH.
?r N B,
]. [~ , ~ i...

[ [ I I
CI~I3 CH~ COOCH~ Call ~ COOCH,~ COOCH.4

I a-C II a-r VI VII

I. I I a R-H:b R=OCH~:c r~C".~

The reaction usually commences when solutions of I and III in benzene are mixed and proceeds with
'gentle warming of the reaction mixture. E s t e r s of fl-substituted a - b r o m o a c r y l i c acids (IIa-c) are obtained
in good yields. 1-Phenyl-2-formylimidazole (IV) [3] and 2-formylbenzothiazole (V) also r e a c t readily with
phosphorane III to give es t e r s VI and VII, respectively.
The only product in the reaction of es ter IIa with a solution of potassium hydroxide at room t e m p e r -
ature is the potassium salt of fl-(1-methyl-2-benzimidazolyl)propiolic acid, acidification of which gives
acid IXa in high yield.

,, -
oo. oo. C k - A oo,
I I
CH a C6Hs

IX XI XII
IX a R : H ; b R : O C H 3 ; C ~:=CH 3

This reaction also proceeds just as readily with a number of other a-bromo-2-azolyl-fl-acrylic acid
e s t e r s (Hb,c, VI, and VII) to give the corresponding 2-azolylpropiolic acids (IXb, c, XI, and XII).

* See [1] for communication I.

Rostev State University, Roster-on-Don. Translated from Khimiya Geterotsiklicheskik_h Soedinenii,

No. 3, pp. 413-417, March, 1974. Original article submitted December 20, 1972.

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, N.Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

362
 The ease of d e h y d r o b r o m i n a t i o n of e s t e r s I I a - c , VI,
and VII is a p p a r e n t l y explained by the lability of both the
halogen atom in the a - p o s i t i o n r e l a t i v e to the carboxyl
group and the hydrogen atom attached to the carbon a t o m
bonded d i r e c t l y to the h e t e r o c y c l e ring.
K Propiolic acids IXa, b and XI a r e stable for s e v e r a l
hours only as the h y d r a t e s . They undergo spontaneous
decarboxylation on a i r drying or o v e r phosphorus pent-
oxide. However, the yields of the 2-ethynyl d e r i v a t i v e s
O0
"tO
in this c a s e and when the propiolic acids a r e heated in
w a t e r a r e low (~ 20%). Decarboxylation of acids I X a - c
o and XI in vacuo m a k e s it p o s s i b l e to r a i s e the yields to
36-40% [3]. This p r o c e s s takes place m o r e smoothly
when alcohol s u s p e n s i o n s of the compounds a r e refluxed.
Acids IXa and XI a r e m o s t r e a d i l y d e c a r b o x y l a t e d in this
c a s e , acid IXb is d e c a r b o x y l a t e d with g r e a t e r difficulty,
and IXc is d e e a r b o x y l a t e d only on prolonged refluxing.
0
The e a s e of decarboxylation of acids IX is a p p a r -
i I I i I i I I |,, ! I t i , i ,

2 8 0 0 2 6 0 0 2400 2200 1r 1700 1500 1300 c m

ently due to weakening of the bond between the c a r b e x y l
group and the a - c a r b o n a t o m of the acids under the in-
Fig. 1. IR s p e c t r a : 1) acid XI; 2) acid IXa; fluence of the c o n c e r t e d - I effect of the C = C group [4]
3) p o t a s s i u m s a l t of IXa; 4) p o t a s s i u m salt and the 2 - b e n z i m i d a z o l y I grouping [5]. The higher the
of IXb. t h e r m a l stability of acids I X a - c , the higher the VCO wave
n u m b e r s in t h e i r IR s p e c t r a (Table 1).
TABLE 1. A b s o r p t i o n of the CO Inasmuch as the r e s i s t a n c e of acids I X a - c to de-
Group of fl-(2-Azolyl)propiolic Acids carboxylation is d e t e r m i n e d by the magnitude of the - I
and T h e i r H y d r o c h l o r i d e s effect of the benzimidazole ring, e l e c t r o n - d o n o r s u b s t i t -
P
f
vco,cm-I uents in the 5 position, by supplying e l e c t r o n s into the
Compound ' i hydro- r i n g of the h e t e r o c y c l e , p r o m o t e a d e c r e a s e in this effect
acid
chloride and an i n c r e a s e in the stability of the acids.
I

IXa 1600 1718 Considering the high dissociation constants of p r o -

IXb 1628, 1643 1705 pielic acids [6] and the quite high b a s i e i t i e s of benzimid-
IXC 1700, 1720 1725
XII 1710 1712_ azole d e r i v a t i v e s [7], one might a s s u m e that acids I X a - c ,
like 2 - i m i d a z o l y l c a r b o x y l i c acids [8], a r e d e c a r b o x y l a t e d
through the i n t e r m e d i a t e l y f o r m e d unstable dipolar ion A.

I
NH
o
~ I
. c,-

C---C--COOH
CH 3 CH3

Xlll

The betaine s t r u c t u r e of acids I X a - c is a p p a r e n t l y the r e a s o n for m a s k i n g of the absorption of the

C = C group in the IR s p e c t r a of these acids. In fact, the a b s o r p t i o n bands of the betaine s t r u c t u r e vanish
in the s p e c t r a of t h e i r p o t a s s i u m salts, and the C = C bond shows up usually quite distinctly at 2200 c m -1
(Fig. 1). The d i s a p p e a r a n c e of the betaine s t r u c t u r e when acids I X a - c a r e c o n v e r t e d to the h y d r o c h l o r i d e s
has a substantial effect on the stabilities of the compounds: h y d r o c h l o r i d e s XIII can exist for a long t i m e
without undergoing change. An i n c r e a s e in the f r e q u e n c i e s of the s t r e t c h i n g v i b r a t i o n s of the c a r b o x y l
group is o b s e r v e d in the IR s p e c t r a of the h y d r o e h l o r i d e s of acids I X a - c (Table 1).
2 - B e n z o t h i a z o l y l p r o p i o l i e acid (XII) is c r y s t a l l i z e d f r o m alcohol and does not undergo changes on
prolonged refluxing. As a consequence of the low basicity of benzothiazole, the f o r m a t i o n of a zwitterion
is a p p a r e n t l y hindered; this is r e s p o n s i b l e for the r e s i s t a n c e of this acid to decarboxylation, just as in the
c a s e of t h i a z o l e - 2 - c a r b o x y l i c acids [8]. The a b s e n c e of betainizatien of this acid is c o n f i r m e d by the IR
s p e c t r a l data: t h e r e is a l m o s t no shift in uCO on p a s s i n g f r o m the acid to its h y d r o c h l o r i d e (Table 1).
The d e c a r b o x y l a t i o n of acid XII at its m e l t i n g point gives a d a r k v i s c o u s p r o d u c t of p o l y m e r i c s t r u c -
ture; this is p r o b a b l y a s s o c i a t e d with the low t h e r m a l stability of the 2-ethynylbenzothiazole that is f o r m e d
in the p r o c e s s (see [9]).

363
 TABLE 2. a - B r o m o - f l - i 2 - a z o l y l ) a c r y l i c Acid E s t e r s

Corn imp i Solvont mpirical I Foundo I talc% i Yield,

Niq o
pound ! ~ iEfllylacetate ~ formula [~_ ~ ~ -B~
lib ]186 CmH13BrN2Oa 48,314A[24,~8,9 48.(],4.0 94,6 8,6 66,7
lIc I 175 i Alc~ ] C~aH~3BrN202 50,214,5t25,5j8,7 50,5]4,2 25,8 9,1 70
VII ! 76 Alcohol ] CI~HsBrNO~S* 46,913,0128,114,9 46,812,9 28,3 5,0 75

*Found: S 11.0%. Calculated: S 11.3%.

TABLE 3. fl-(2-Azolyl)propiolic Acids

Corn- imp, I Empirical i Found, % Calc., ~ !IR spec- Yield,

Solvent itra,cm-I qo
pound i~ i formula
i C [ H N C ]Hi N GmC*
i
J l i
IXb 142 -- CI~HmN203 i62,2 14,3 112,0 62,6i44' 122' 2290 85
IXc 218 Alcohol C12HIoN2Oe i670 4,4 i 12,8 67.3 4 7~ 13 1 2200 80
XII 203 Dioxane CloH~O~S~f 59,2 i2,8 i 7,2 59,1 2'51 ~'- -- 76

* The IR s p e c t r u m of the p o t a s s i u m s a l t in m i n e r a l oil.

~Found: S 15.5%. Calculated: S 15.8%.

EXPERIMENTAL
The IR s p e c t r a of c h l o r o f o r m solutions or m i n e r a l oil p a s t e s of the compounds w e r e r e c o r d e d with a
UR-20 s p e c t r o m e t e r .
Reaction of 2 - F o r m y l a z o l e s with C a r b o m e t h o x y b r o m o m e t h y l e n e t r i p h e n y l p h o s p h o r a n e (IID. A 0.01
m o l e s a m p l e of the a p p r o p r i a t e aldehyde I was added to a solution of 0.01 m o l e of III in 15-20 m l of ben-
zene, and the m i x t u r e was s t i r r e d until all of the solid had dissolved. The m i x t u r e heated up a p p r e c i a b l y ,
and yellowish Crystals of II began to f o r m i m m e d i a t e l y . To c o m p l e t e the reaction, the m i x t u r e was allowed
to stand on a w a t e r bath at 40-60 ~ for a c e r t a i n time, a f t e r which it was heated to the boiling point and
cooled. The c r y s t a l s of e s t e r s II w e r e r e m o v e d by filtration and washed with benzene. IIighly pure r e -
a6tion products w e r e obtained. This r e a c t i o n p r o c e e d s so smoothly that it can be used for the qualitative
determination of 2 - f o r m y l b e n z i m i d a z o l e s .
No p r e c i p i t a t e f o r m e d in the r e a c t i o n of aldehydes IV and V with phosphorane III, and e s t e r VI was
t h e r e f o r e e x t r a c t e d at the end of the r e a c t i o n with dilute h y d r o c h l o r i c acid and t r e a t e d with sodium b i c a r -
bonate. In o r d e r to isolate e s t e r VII, the solvent was r e m o v e d by distillation, and the reaction product
was c h r o m a t o g r a p h e d with a column filled with aluminum oxide in e t h e r to s e p a r a t e the triphenylphosphine
oxide; the f i r s t portions of the eluate w e r e collected.
fl-(2-Azolyl)propiolic Acids. A 0.01 m o l e s a m p l e of II was m i x e d with a solution of 4 g of p o t a s s i u m
hydroxide in 30 ml of alcohol, and the m i x t u r e was allowed to stand overnight at r o o m t e m p e r a t u r e . It
was then filtered to r e m o v e the p r e c i p i t a t e , which was a m i x t u r e of the p o t a s s i u m s a l t of the acid (only
slightly soluble in alcohol) and p o t a s s i u m b r o m i d e . The p r e c i p i t a t e was washed with alcohol and dissolved
in w a t e r , and the solution w a s acidified with dilute h y d r o c h l o r i c acid. The p r e c i p i t a t e d acid was r e m o v e d
by filtration and dried at 60 ~. The m e l t i n g points and the yields a r e p r e s e n t e d in Table 3.
Acids XI and XII w e r e obtained in the s a m e way as acids I X a - c , but, i n a s m u c h as their p o t a s s i u m
salts a r e quite soluble in alcohol, the reaction m i x t u r e was f i l t e r e d to r e m o v e the p o t a s s i u m bromide, the
solvent was e v a p o r a t e d without heating, and the r e s i d u e was dissolved in w a t e r . The aqueous solution was
then acidified with h y d r o c h l o r i c acid.
Acids I I a - c and XI gradually d e c a r b o x y l a t e d on s t o r a g e . T h e i r h y d r a t e s (in water), h y d r o c h l o r i d e s
(in IIC1 solution), or s a l t s (in alkaline solution) a r e m o r e stable. They w e r e purified by r e p r e c i p i t a t i o n
f r o m aqueous alkali solutions. Compound IXc can be r e c r y s t a l l i z e d f r o m alcohol by c a r e f u l heating. C o m -
pound XII can also be obtained by t r e a t m e n t of VII with boiling alcoholic p o t a s s i u m hydroxide solution (see
[2]) and, a f t e r isolation, can be r e c r y s t a l l i z e d f r o m alcohol or dioxane.
1 - M e t h y l - 2 - e t h y n y l - 5 - m e t h o x y b e n z i m i d a z o l e (Xb). A 2.3 g (0.01 mole) s a m p l e of IXb was heated in
20 ml of alcohol on a w a t e r bath until the solid had dissolved c o m p l e t e l y and v i g o r o u s c a r b o n dioxide e v o -
lution had ceased. The alcohol solution was e v a p o r a t e d without heating in a s t r e a m of a i r , and the r e s i d u e

364
was c h r o m a t o g r a p h e d on a l u m i n u m oxide, in c h l o r o f o r m . The solvent was e v a p o r a t e d to give 1.65 g (89%)
of shiny p a l e - r o s e plates with mp 162-163 ~ (ethyl acetate), which w e r e quite soluble in benzene, alcohol,
and c h l o r o f o r m . Found: C 70.6; H 5.5; N 15.2%. CllHIoN20. Calculated: C 70.9; H 5.4; N 15.0~0. IR s p e c -
t r u m (CHCI3): 3310 c m -1 (C-- CH).
1 , 5 - D i m e t h y l - 2 - e t h y n y l b e n z i m i d a z o l e (Xc). This compound was obtained by prolonged refluxing of
acid IXc in alcohol. It was isolated (in 52% yield) in the s a m e way as Xb. The light-yellow s h i n y plates
had mp 138 ~ ( f r o m a l c o h o l - e t h e r ) . Found: C 77.5; H 6.2; N 16.8%. CllHIoN2. Calculated: C 7%6; H 6.3;
N 16.5%. The IR s p e c t r u m (CHC13) contained an intense a b s o r p t i o n band at 3310 c m -I ( C - C - H ) .

LITERATURE CITED

1. I. I. Popov, A. M. Simonov, V. I. Mikhailov, and N. A. Sil'vanovich, Khim. G e t e r o t s i k l . Soedin., 408

(1974).
2o G. Miirkl, Chem. B e r . , ~ 2996 (1961).
3. A. M. Simonov and I. I. Popov, Khim. G e t e r o t s i k l . Soedin., 140 (1971).
4. G. Mansfield and M. C. Witting, J. Chem. Soe., 4781 (1956).
5. H. Walba, W. I. M u r r a y , G. Knitson, and A. Diaz, J. Am. Chem. Soc., 88, 1962 (1966).
6. R. A. Raphael, Acetylenic Compounds in Organic Synthesis, London (1955).
7. Outline of the C h e m i s t r y of Azoles [in Russian], Izd. Rostovsk. Univ., R o s t o v - o n - D o n (1965).
8. P. Haake, L. P. B a u s h e r , and J. P. McNeal, J. Am. Chem. Soc., 93, 7045 (1971).
9. I. I. Popov and A. M. Simonov, Khim. G e t e r o t s i k l . Soedin., 122 (1971).

365
HETEROCYCLIC ANALOGS OF PLEIADIENE
XI.* SYNTHESIS OF 1-(fl-DIALKYLAMINOALKYL)- AND
2-AMINOPERIMIDINES

A. F. Pozharskii, L. P. Pershina, UDC 547.856.7'822.3.07

I . S. K a s h p a r o v , a n d A. A . K o n s t a n t i n c h e n k o

The corresponding 1-fl-dialkylaminoethylperimidines were obtained by the action of fl-dial-

kylaminoethyl chloride hydrochlorides on perimidines in alkaline media. Some of the c o m -
pounds obtained f o r m substituted 2-aminoperimidines and 2-perimidone on r e a c t i o n with so-
dium amide or alkali. 2-Morpholino- and 2 - p i p e r i d i n o - l - m e t h y l p e r i m i d i n e s a r e obtained
f r o m 1 - m e t h y l - 2 - c h l o r o p e r i m i d i n e and morpholine or piperidine. The synthesized c o m -
pounds have weak b a c t e r i o s t a t i c , fungistatic, and tuberculostatic activity.

Almost all simple derivatives of perimidine have weak or m o d e r a t e bacteriostatic and fungistatic
activity [2]. In the p r e s e n t r e s e a r c h we have synthesized perimidine derivatives containing fl-diethyI-
amino, fi-piperidino, and fl-morpholinoethyl groups in the i position and morpholine and piperidine r e s i -
dues in the 2 position; the products w e r e also subjected to microbiological tests. The introduction of the
above groupings frequently intensifies the toxic effect of a preparation, apparently due to interaction of the
unshared e l e c t r o n pair of the amine nitrogen with the biological r e c e p t o r s [3].
1'Substituted perimidines H-IV w e r e obtained as a r e s u l t of the r e a c t i o n of perimidine with the ap-
propriate/~-dialkylaminoethyl chloride h y d r o c h l o r i d e s in alcoholic alkali in an i n e r t a t m o s p h e r e (because
of the high oxidizability of the N-anion of perimidine [4]). In connection with the appreciable resinification
of the reaction m i x t u r e , the isolation and purification of II-IV p r e s e n t definite difficulties (see the e x p e r i -
mental section of this paper). Caution should be e x c e r c i s e d in work with perimidines H-IV, inasmuch as
they cause pronounced i r r i t a t i o n of the skin and mucous m e m b r a n e s that lasts for 30-60 mino

/'/~' -- N

CICH~CH2NR2- HCI
KOH

Vl

* See [1] for communication X.

Rostov State University, Rostov-on-Don. T r a n s l a t e d f r o m Khimiya Geterotsiklicheskikh Soedinenii,

No. 3, pp. 418-421, March, 1974. Original article submitted M a r c h 7, 1973.

9 1975PlenumPublishing Corporation, 227 West 17th Street, New York, N.Y. I0011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, midrofilming,
recording or otherwise, without written permission of the publisher. A copy of this article is available from the publisher for $15.00.

366
 In the amination of I I - I V by m e a n s of sodium amide, we w e r e able to isolate a 2 - a m i n o d e r i v a t i v e (V)
in 52% yield only in the c a s e of p e r i m i d i n e IU. In the c a s e of II, the f o r m a t i o n of a c e r t a i n amount of amine
was p r o v e d by m e a n s of IR s p e c t r o s c o p y . Hydroxylation of 1-(fl-diethylaminoethyl)perimidine II with solid
alkali leads to p e r i m i d o n e VI (in 30~ yield).
We also obtained 2 - p i p e r i d i n o - and 2 - m o r p h o l i n o - l - m e t h y l p e r i m i d i n e s VII and VIII as a r e s u l t of the
facile r e a c t i o n of 2 - c h l o r o - l - m e t h y l p e r i m i d i n e with piperidine and m o r p h o l i n e .

--i, 3 ~-/ --
VII, VI|[

VII X~CH~; Ylll X = O

M i c r o b i o l o g i c a l tests* showed that U-IV and VII and VIU have weak t u b e r c u l o s t a t i c and fungistatic
activity. In addition, p r e p a r a t i o n III displays weak b a e t e r i o s t a t i c activity with r e s p e c t to staphylococcus,
the diphtheria bacillus, and a n t h r a n o i d s p o r e s .

EXPERIMENTAL
1-(fl-Diethylaminoethyl)perimidine (II). A solution of 6.6 g (0.12 mole) of p o t a s s i u m hydroxide [n 40
ml of alcohol was added dropwise, with continuous p a s s a g e of nitrogen through the s y s t e m , to a well s t i r r e d
and i c e - c o o l e d s u s p e n s i o n of 8.4 g (0.05 mole) of p e r i m i d i n e in 50 ml of ethanol. An alcohol solution of 9.4
g (0.055 mole) of diethylaminoethyl chloride h y d r o c h l o r i d e was then added dropwise. The r e a c t i o n m i x t u r e
was held in the cold for another 30 rain, a f t e r which it was refluxed under nitrogen f o r 3 h. The alcohol
was r e m o v e d by distillation, and the r e s i d u e was e x t r a c t e d with c h l o r o f o r m (250-300 ml) to obtain p e r i m i -
dine II. The e x t r a c t was d r i e d with sodium sulfate, e v a p o r a t e d to 50 ml, and p a s s e d through a column filled
with 300 g of a l u m i n u m oxide. The leading zone containing p e r i m i d i n e II was collected. The c h l o r o f o r m
was r e m o v e d by distillation, and the r e s u l t i n g oil was purified by one of two methods.
A) P c r i m i d i n e II was e x t r a c t e d with hot hexane until a new portion of hexane no longer b e c a m e c o l -
ored. The solution was e v a p o r a t e d with c h a r c o a l two to t h r e e t i m e s , and the solvent was r e m o v e d by d i s -
tillation to give 4.8 g (37%) of a l i g h t - y e l l o w oil.
B) The oil was d i s s o l v e d in ethanol, and a s a t u r a t e d alcohol solution of p i c r i c acid was added. The
yield of d i p i c r a t e was 17.7 g (86%); r e c r y s t a l l i z a t i o n gave 13.7 g (62%) of light-yellow c r y s t a l s with m p
216 ~ ( f r o m acetic acid). Found: C 48.1; H 3.7; N 17.8%. C17H21N3. 2C~H3N3OT. Calculated: C 48.0; H 3.7;
N 17.4%.
A solution of 13.7 g of the p i c r a t e in 200 m l of liquid a m m o n i a was e v a p o r a t e d at r o o m t e m p e r a t u r e
to 50-70 ml, i30-150 ml of anhydrous c h l o r o f o r m was added, and the r e s i d u a l a m m o n i a was e v a p o r a t e d .
The a m m o n i a t e d p i e r a t e was r e m o v e d by filtration, the filtrate was d e c o l o r i z e d with a c t i v a t e d c h a r c o a l ,
and the c h l o r o f o r m was r e m o v e d by distillation to give 4.5 g (35% b a s e d on the s t a r t i n g perimidine) of
c h r o m a t o g r a p h i c a l l y p u r e p e r i m i d i n e II. Found: C 75.5; H 7.8; N 15.2%. C17H21Na. Calculated: C 46.4;
H 7.8; N 15.7%. The h y d r o e h l o r i d e was obtained by p a s s i n g d r y HC1 into a benzene solution of a m i n e IL
Workup gave 4.3 g (78%) of l i g h t - y e l l o w c r y s t a l s with m p 260 ~ (dec., f r o m a l c o h o l - e t h e r ) . Found: C 58.3;
H 6.5; CI 19.8; N 12.3%. C17H2tN3. 2HC1.0.5tt20. Calculated: C 58.4; H 6.8; C1 20.3; N 12.0%.
1 - ( f l - P i p e r i d i n o e t h y l ) p e r i m i d i n e (HI). This compound was obtained in analogy with the s y n t h e s i s of II.
A f t e r column s e p a r a t i o n , the yield of c r u d e p e r i m i d i n e HI was 70%. It was m o r e conveniently purified by
method A. The light-yellow c r y s t a l s (44%) had m p 81.5-82 ~ ( f r o m hexane). Found: C 78.3; H 7.6; N 14.9%.
C18H2iN3. Calculated: C 77.4; H 7.5; N 15.0%. The h y d r o c h l o r i d e was obtained by bubbling d r y HCI into a
benzene solution of HI or into the hexane e x t r a c t of this compound obtained during purification by m e t h o d A .
The light-yellow c r y s t a l s (65% yield) had mp 277 ~ (dec., f r o m alcohol). Found: C 59.4; H 6.3; C1 19.5; N
11.0%. C18H2iN3- 2HC1.0.5H20. Calculated: C 59.9; H 6.6, CI 19.6; N 11.6%.
1-(B-Morpholinoethyl)perimidine (IV). This compound was obtained by the method u s e d to synthesize
a m i n e II. After purification by method A the yield Was 42%. The light-yellow c r y s t a l s had m p 117-118 ~

* The t e s t s w e r e p e r f o r m e d in the c h e m o t h e r a p y branch of the All-Union S c i e n t i f i c - R e s e a r c h P h a r m a c e u -

t i c a l - C h e m i s t r y Institute under the s u p e r v i s i o n of G. N. P e r s h i n '

367
( f r o m hexane). Found: C 72.2; H 6.8; N 15.1%. CI~H19N~O. Calculated: C 72.6; H 6.8; N 14.970. The h y -
d r o c h l o r i d e was obtained by p a s s i n g d r y HC1 into a benzene solution of IV or into a hexane e x t r a c t of this
compound, which was obtained during purification by method A. The light-yellow c r y s t a l s (70%) had m p
280 ~ ( f r o m a l c o h o l - e t h e r ) . Found: C 56.3; H 6.3; C1 19.2; N 11.670. Cl~H19N~O. 2HCI. 0.5H20. Calculated:
C 56.2; H 6.1; C1 19.5; N 11.5%.
2 - A m i n o - l - ( f l - p i p e r i d i n o e t h y l ) p e r i m i d i n e (V). A solution of 2.8 g (0.01 mole) of p e r i m i d i n e HI in 10
m l of absolute dimethylaniline was added with s t i r r i n g at 70-80 ~ in a s t r e a m of nitrogen to a finely ground
suspension of 1.9 g (0.05 mole) of sodium amide in 3 m l of absolute dimethylaniline. The m i x t u r e was held
at 150 ~ until hydrogen evolution c e a s e d (~ 2 h). The sodium d e r i v a t i v e was cooled and t r e a t e d with 20 m l
of w a t e r in an intense s t r e a m of nitrogen. The l i g h t - g r e e n c r y s t a l s had m p 206-207 ~ ( f r o m alcotlol). IR
s p e c t r u m ir~ CHC13: 3455, 3230-3280 c m -1 ( N - H ) . Found: C 73.3; H 7.7; N 19.07o. C18H22N4. Calculated:
C 73.5; H 7.5; N 19.07o.
i - ( ~ - D i e t h y l a m i n o e t h y l ) - 2 - p e r i m i d o n e (VD. A 2.67 g (0.01 mole) s a m p l e of II was fused with 2.24 g
(0.04 mole) of finely ground anhydrous p o t a s s i u m hydroxide [5] at 200-210 ~ for 1.5 h. The m a s s was then
cooled and t r e a t e d with 100 m l of 5% h y d r o c h l o r i c acid, a f t e r which it was n e u t r a l i z e d with c o n c e n t r a t e d
a m m o n i u m hydroxide. The d a r k - g r a y p r e c i p i t a t e was e x t r a c t e d with 120 m l of c h l o r o f o r m , and the e x t r a c t
was dried with sodium sulfate, c o n c e n t r a t e d to 20 ml, and p a s s e d through a column filled with aluminum
oxide (100 g). The column was eluted with c h l o r o f o r m , and the f i r s t fraction was collected. R e m o v a l of
the c h l o r o f o r m by distillation gave 0.85 g (30%) of a g r a y substance. The c o l o r l e s s needles ( f r o m aqueous
alcohol) had m p 137~. IR s p e c t r u m in CIICI~: 1685 c m -1 (C =O), 3440 c m -1 ( N - H ) . Found: C 71.9; H 7.4;
N 14.770. CITH2iN30. Calculated: C 72.0; H 7.4; N 14.8%.
l-Methyl-2-p}peridinoperimidine (VII). A solution of 2.1 g (0.01 mole) of l-methyl-2-chloroperimi-
dine in 2 ml (0.02 mole) of piperidine was refluxed for 3-5 rain until a precipitate began to form. The mix-
ture was then cooled, and the precipitated yellowish VII was removed by filtration and washed with water
to give a quantitative yield of product. After crystallization from petroleum ether it had mp 121-122 ~
Found: C 76.5; H 7.2; N 15.6%. CITHI9N 3. Calculated: 76.7; H 7.3; N 15.870. The hydrochloride was ob-
tained as colorless prisms with mp 236-237 ~ (from alcohol-ether). Found: C 67.3; H 6.6; Cl 11.5; N 13.7%.
CiTHIsN3.HCI. Calculated: C 67.6; H 6.7; C1 11.8; N 14.0%.
l-Methyl-2-morpholinoperimidine (VIII). This compound was obtained as in the preceding experi-
ment. The yield was quantitative. The colorless needles had mp 146-147 ~ (from petroleum ether). Found:
C 71.5; H 6.2; N 15.470. C161117N30. Calculated: C 71.8; H 6.4; N 15.7%. The hydrochloride was obtained
as colorless needles With mp 239-240 ~ (from alcohol-ether). Found: C 63.0; H 5.6; C1 11.3; N 13.5%.
CI6HiTN30.HCI. Calculated: C 63.3; II 6.0; Cl 11.6; N 13.87o.

LITERATURE CITED
1. V . I . Sokolov, B. A. A r d a s h e v , I. S. K a s h p a r o v , and A. F. P o z h a r s k i i , Khim. G e t e r o t s i k l . Soedin., 849
(1973).
2. G.N. Pershin, A. F. Pozharsldi, I. S. Kashparov, N. S. Bogdanova, N. A. Novitskaya, and A. L.
Mikerina, Khim.-Farmats. Zh., 2, 5 (1973).
3. A. Albert, Selective Toxicity and Related Topics, 4th ed., Methuen (1968).
4. A.F. Pozharskii and I. S. Kashparov, Khim. Geterotsikl. Soedin., 111 (1970).
5. A.F. Pozlmrskii and A. M. Simonov, Chichibabin Amination of Heterocycles [in Russian], Izd. RGU,
Rostov-on-Don (1971), p. 72.

368
SYNTHESIS OF AZO COMPOUNDS CONTAINING
TRIAZOLE AND TETRAZOLE RESIDUES

I. L. Shegal, K. V . S t a n o v k i n a , UDC 547.792'796.1

N. G . K o v a l e n k o , a n d L , M. S h e g a l

T r i a z o l e - and t e t r a z o l e d i a z o n i u m sulfates w e r e coupled with a r o m a t i c azo components. The

e f f e c t of the s t r u c t u r e and medium on the c h r o m a t i c i t y of the azo compounds was studied.

The ability of many h e t e r o c y c l i c diazonium salts to undergo coupling r e a c t i o n s is well known [1, 2].
H e t e r y l h y d r o x y a z o and h e t e r y l a m i n o a z o compounds have been obtained as a r e s u l t of coupling. T h e r e have
been studies devoted to the investigation of the t a u t o m e r i s m and e l e c t r o n i c s t r u c t u r e s of h e t e r y l a z o c o m -
pounds [3, 4], but the problem of the effect of the nature of the h e t e r o c y c l e on their s t r u c t u r e s , chromaticity,
and complexing ability has not yet r e c e i v e d adequate study.
It s e e m e d of i n t e r e s t to accomplish the synthesis of aminoazo and hydroxyazo compounds that con-
tain t r i a z o l e and t e t r a z o l e r e s i d u e s . F o r this, we c a r r i e d out the coupling of 1 , 2 , 4 - t r i a z o l c - 3 - d i a z o n i u m
and t e t r a z o l e d i a z o n i u m sulfates with various a r o m a t i c
azo components, as a r e s u l t of which we obtained a
s e r i e s of azo compounds in good yields (Table 1). These
compounds a r e slightly soluble in w a t e r but soluble in
organic solvents.
Compound IX was also obtained by alternative syn-
thesis by reaction of 5 - h y d r a z i n o t e t r a z o l e with p - b e n -
zoquinone. The compounds synthesized by the two m e t h -
ods proved to be identical with r e s p e c t to melting points
and absorption s p e c t r a .
The s p e c t r a of hydroxyazo compounds I, IV, V, VI,
XII, XIII, and XIV in the visible region contain two ab-
sorption maxima; this is apparently due to the presence
of a t a u t o m e r i c equilibrium between the oxoid (A) and
quinoid (B) f o r m s (Fig. 1).
It is i n t e r e s t i n g to note that in conformity with [4],
the p r e s e n c e of the g r e a t e r e l e c t r o n - a c c e p t e r t e t r a z o l e
ring g e n e r a l l y c a u s e s a bathochromic change in the
color as c o m p a r e d with the c o r r e s p o n d i n g t r i a z o l y l a z o
compounds. A bathochromic shift in the absorption
400 20 40 60 80.500 20 40 60 80 600 20 40 60 eO 700 maximum, which is a s s o c i a t e d with transition to the
A,l]m ionic state with a delocalized negative charge, is ob-
Fig. i. Absorption spectra in ethanol (1-3) s e r v e d during the action of alkali on the hydroxyazo
and alcoholic alkali (la-3a): 1 and la) t e t - compound.
razolylazophenol; 2 and 2a) 4 - t e t r a z o l y l a z o -
The color of 4 - ( 1 , 2 , 4 - t r i a z o l y l - 3 - a z o ) d i m e t h y l -
1-naphthol; ,3 and 3a) 9 - t e t r a z o l y l a z o - l O -
aniline (VIII) and 4 - t e t r a z o l y l a z o d i m e t h y l a n i l i n e (XVI)
hydroxyanthracene.

N. A. Ogarev Mordovskii State University, Saransk. T r a n s l a t e d f r o m Khimiya Geterotsiklieheskikh

Soedinenii, No. 3, pp. 422-424, March, 1974. Original article submitted May 21, 1973.

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from thepublisher for $15.00.

369
 T A B L E 1.
N--N
Z\N ~ - - N =N--k
H
N, ~'m~x'IIlTI
Empirical ill al-
~:z R . rap~, formula found tale. in coholic
ethanol alkali

p-HOC~H/ 205--206 CsHzN60"H20 33,4 33,8 402~8450456453 77

H CH 2,4-Dihydr0xy- 280--282 CsHTNsO~ 34.4 34,1 99
,ic. phenyl
III CH 4-Hydroxy-3-carboxy- 258-=259 CoHzNsOs
phenyl
29,5 30,0 402 430 48
IV [ CH 4-Hydroxy--a-naph- 253~255 C12HgN~O 28,7 29,3 446; 536 514 159
thyl
I 2-Hydroxy-a-naph-
thyl
237--2,38 CI~HgNsO 28,9 29,3 402; 450 490 19o
VI CH 10-1~ydroxyl-9-anthryl ~.~4--2~6 CI~H~,NsO 23,8 24,2
VII CH 2HyclroxY-S-methyl- 255~257 CgHgNsO 35,1 34,8 484 74
phenyl
VIII p-Dimethylamino- 205--208 CtoHI~N6~ 39,2 38,9 485 -- 13
phenyl
IX~N p-HOCeH~ - 134--135 CTH,N60 43,8 44,0 406 454 i54
2,4-Dihydroxy-
phenyl 178--179 CTH~NOOvH~O 37,9 37,5 412 488 199
4-Hydroxy-3-carboxy-
phenyI . . . . 266---268 CsH6N~Oz 28,6 28,1 406 422 189
i
XII
XllI N
4-Hydroxy-cx-naph-
thyl
2-Hydroxy-a-naph-
I thyl
XIV N I10-Mydroxyl-9-anthryl
(
242--243 C.H~N~O 35,5
~84"~4~00 CIIH~NoO
CIsH,0N00
35,3
28,4
35,0 410; 536 516
35,0 418; 4581 490 80
28,9 416; 535 565 45
98

XV N 2-Hydroxy-S-methyl-
! phenyl 112--143 CsHsN60 41,8 41,6 44
XVI N p-Dimethylamino- 146--146 CgHnNr 47,7 45,6 44
I pheny!

* The c o m p o u n d s w e r e p u r i f i e d for a n a l y s i s by c r y s t a l l i z a t i o n : I,
IV, V, VI, IX, XIII, XIV, XV, a n d XVI f r o m e t h a n o l , VII f r o m a q u e -
ous a c e t o n e , XII f r o m a q u e o u s p y r i d i n e , a n d II, III, VII!, X, a n d XI
from water.
t In a c i d i c m e d i a , Xmax 543 n m , c o m p a r e d with 462 n m i n c o n c e n -
t r a t e d acid.
$ In a c i d i c m e d i a , X m a x 5 15 ran, c o m p a r e d with 444 m n in c o n c e n -
t r a t e d acid.

u n d e r g o e s a b a t h o c h r o m i c change when a c i d i s added; this i s a s s o c i a t e d with the f o r m a t i o n of a c a t i o n

b e a r i n g a d e l o c a l i z e d p o s i t i v e c h a r g e (C). W h i l e XVI h a s a d e e p e r c o l o r t h a n t r i a z o l y l a z o c o m p o u n d VIII

N--N S N--NH O
I/ \\=N--N =o

H N
a B
Z=CH,N
d u e to the better delocalizationof the free pair of electrons of the dimethylamino group in the electron-
aceeptor tetrazole ring, in the case of cation form C the tetrazole ring hinders redistribution of the posi-
tive charge, and the cation of XVI is less deeply colored.
The addition of concentrated sulfuric acid to amines VIII and XVI, on the other hand, causes a hyp-
soohromic shift of the absorption m a x i m u m , which is associated with fileformation of a dication (D).

C D
Z=CH, ~.... 543nm. Z=N, Xm0x515 nm;Z=CH, ~..... 462 nm;Z=N, ~,~x 445 nmo

EXPERIMENTAL
1 , 2 , 4 L T r i a z o l y l - 3 - a z o s a l i c y l i c A c i d (HI). A t o t a l of 7 ml of a 1% s o d i u m n i t r i t e s o l u t i o n was added
a t 0 ~ to a s o l u t i o n of 0.84 g (0.01 m o l e ) of 3 - a m i n o - l , 2 , 4 - t r i a z o l e i n 25 m l of 30% s u l f u r i c a c i d , a f t e r w h i c h

370
 the mixture was allowed to stand for 15 rain. A solution of 1.38 g (0.01 mole) of salicylic acid in 40 ml of
9 ethanol was then added to the diazonium salt solution, and the mixture was neutralized to pH 3-4 by the ad-
dition of sodium acetate. The mixture was then allowed to stand in the cold for 24 h, and the precipitated
III was r e m o v e d by filtration and washed with water. A s i m i l a r method was used to obtain II, X, and XI.
Compounds I, IV, VII, and XV were obtained by the method d e s c r i b e d above, but without neutralization
of the reaction m i x t u r e with sodium acetate (Table 1).
1 , 2 , 4 - T r i a z o l y l - 3 - a z o d i m e t h y l a n i l i n e (VIII). A 0.84 g (0.01 mole) sample of 3 - a m i n o - l , 2 , 4 - t r i a z o l e
in 25 ml of 30% sulfuric acid was diazotized at 0~ with 7 ml of a 1% solution of sodium nitrite. The diazo-
nium salt solution was then added to a solution of 1.3 ml (0.01 mole) of dimethylaniline in 40 ml of ethanol
and 17 m I of pyridine a t 0~ and the mixture was allowed to stand at 0~ for 24 h. The d a r k - r e d precipitate
was then r e m o v e d by filtration and washed with water. Compounds VI, IX, XIV, and XVI were s i m i l a r l y
obtained.

Tetrazolylazophenol (IX). A 0.85 g (0.01 mole) sample of 5 - a m i n o t e t r a z o l e was diazotized in 25 ml

of 30% sulfuric acid at 0~ with 7 ml of 1% sodium nitrite solution, and the resulting diazonium salt was
reduced at 0-3 ~ with a solution of 3.8 g (0.02 mole) of SnCl 2 in 8 ml of c o n c e n t r a t e d HCI. A 1.1 g (0.01
mole) sample of benzoquinone was added to the solution, and the mixture was heated for 1 h on a water
bath. It was then cooled, and the precipitated IX was r e m o v e d by filtration and c r y s t a l l i z e d from aqueous
ethanol to give 1.47 g (77~0) of a product with mp 134-135 ~ No melting-point d e p r e s s i o n was observed for
a mixture of this product with a sample of IX obtained via the preceding method.

LITERATURE CITED
1. A . E . Chichibabin and M. D. R y a z a n t s e v , Zho Russk. Fiz. Khim. Obshchestva, 47, 1571 (1915).
2. A . M . Simonov and S. N. Kolodyazhnaya, Khim. Geterotsikl. Soedin., 1562 (1970).
3. Kawase Akira, Bunseki Kagaku, Japan. Analyst, 17, 56 (1968).
4. L . M . Yagupol'skii and L. Z. Gandel'sman, Zh. Obshch. Khim., 35, 1252 (1965).
5. S . B . Savvin, Zh. Analiticheskoi Khim., 28, 130 (1973).

371
CYCLIZATION OF ARYLHYDRAZONES OF
NITROFORMALDEHYDE AND ITS DERIVATIVES

A. I. Dychenko, L. S. P u p k o , UDC 547.873'775'794.3 : 543.422.4

a n d P . S. P e l ' k i s

2 , 3 , 4 , 5 - T e t r a h y d r o - i,2 , 4 - t r i a z i n e d e r i v a t i v e s a r e obtained when n i t r o f o r m a l d e h y d e a r y l h y -

d r a z o n e s a r e heated with formaldehyde and a r o m a t i c a m i n e s . B r o m o n i t r o f o r m a l d e h y d e
a r y l h y d r a z o n e s r e a c t with thiourea to give substituted 5 - i n i m o - 4 , 5 - d i h y d r o - l , 3 , 4 - t h i a d i -
azoles and r e a c t with sodioacetoacetic e s t e r to give 1 - a r y l - 3 - n i t r o - 4 - a c e t y l - 5 - p y r a z o l o n e s .
The action of chlerosulfonic acid on c y a n o n i t r o f o r m a i d e h y d e a r y l h y d r a z o n e s leads to ring
closing to the c o r r e s p o n d i n g 1 , 3 , 5 - t r i a z i n e s .

N - H y d r o x y m e t h y l a r y l h y d r a z o n e s of glycolaldehyde a r e f o r m e d in the r e a c t i o n of n i t r o f o r m a l d e h y d e
a r y l h y d r a z o n e s (I) with benzylamine in alcohol or d i m e t h y l f o r m a m i d e (DMF). It is known that closing to
a t r i a z i n e ring o c c u r s in the condensation of a r y l h y d r a z o n e s of glyoxal, p - n i t r o b e n z a l d e h y d e [1, 2], and
furfurai [3] with formaldehyde and benzylamine in DMF.
We have found that t r i a z i n e d e r i v a t i v e s (IVa-m, Table 1) a r e also f o r m e d on prolonged heating of
h y d r a z o n e s I with formaldehyde and benzylamine or a r o m a t i c a m i n e s . The IR s p e c t r a of IV contain an in-
tense C =N absorption band (1620 c m -1) but do not contain an NH absorption band (3220 cm-1).
Thiadiazole d e r i v a t i v e s (V) a r e f o r m e d when IT [4] a r e heated with t h i o u r e a . P y r a z o l o n e d e r i v a t i v e s
(VII) a r e obtained when II r e a c t with sodioacetoacetic e s t e r .
In analogy with [6], we obtained VI by r e a c t i o n of h y d r a z o n e s III [5] with chlorosulfonic acid. The
reaction a p p a r e n t l y p r o c e e d s through a step involving the formation of an i n t e r m e d i a t e that r e s u l t s
f r o m 2 m o l e of the nitrile and 1 m o l e of ehlorosulfonic acid [RC =NC(R) =NH]+SO3C1 - [7], which f o r m s the
c o r r e s p o n d i n g t r i a z i n e With a third m o l e c u l e of the nitrile. The IR s p e c t r a of VI contain an intense C = N
absorption band (1620 0m -1) but do not contain a C-= N absorption band (2250 cm-1).
R'
I
9. . . . . . CH20, R'NH. (Nx.~
~"3~\~-.--).}/"'2 RC6II4NH--N:CHNO 2 - - - - - RC6H4--N...N//J~.NO

I Re6, v
%.,R "-,,~,eOo IB~
.... KCN " ( N H ) CS RC H - - N - - N
RC6H4NH_N=C(CN)NO2 . RCBH4NH_N=C(Br)NO~ , ~2 6 4 ~ l ~...
9 III II HN ~ S ,/ NO2

' ~ S O aC) V

O2N--C=N--N
I HC6H4R

RC6H4N H-- N = C " ~ N C=N-- NHC6H4R i

i I v a R=p..COOH, b R=p,N%;
NO~ NO2 vl aa=p-ar, b R=p-NO2;
Yl V. a R=p-NOrb R=~)-NH~SO~

Institute of Organic' C h e m i s t r y , A c a d e m y of Sciences of the Ukrainian SSR, Kiev. T r a n s l a t e d f r o m

Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 3, pp. 425-427, March, 1974. Original a r t i c l e submitted
M a r c h 15, 1973.

9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, N.Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

372
 TABLE 1. T e t r a h y d r o t r i a z i n e s

i ! Empirical Found, Calc., i Yield,

Com -
% % %
pound Imp, ~ i formula
- iLT!-VI .~
IVa* ] p-Cl CHaCsH~ 125--126 ! C~6H~sC1N402 16,9 10,9 17,0 10,6 84
I'v~T p-Br CH2C~H~ 120--121 ~ CI6HIsBrN402 14,4 21,5 14,9 21,3 95
IVc I~NO~ CH~CsH~ 150--151 CIoHIsNsO4 20,8 20,5 -- 86
1Vd C~Hs 104--106 CIsHI4N402 t9,9 1L-,O 19,9 88
IVe
IVf
p-C1C~H4
p-BrCsH4
147--149 CIsHiaCI'N40~
164-166 C~sH~3BrN402
17,2
22,0
!17,7 1T0
89
22,2 83
,v7 p-Cl p-C1C~H4 135--137 CIsHI2CI~N402 16,1 16,0 46
p-C1 p-BrC6H~ 148--150 CfsHI2CIBrN402 29,1 9O
IVi p-Br p-BrC~H~ 130--132 CjsH~2,B~N402 36,3 36,4 92
IVj p-Br p-CHaC6H4 148--161 C~6H~sBrN402 21,4 2t,3 88
IV k* p-NOe p-C1C6H4 184--185 C~sHj2CINsO4 9,7 1974 9,7 7O
IVI p-NOe . p-BrC~H~ 190--192 C~sH~2BrNsO4 16,7 17,2 72
IVm 2,3-(CHa) p'CIC~H4 98--100 CaTH~TC1N402 16,3 16,3 75

* Found: C 57.7; H 4.4%. Calculated: C 58.2; H 4.5%.

]' Found: C 51.0; H 3.970. Calculated: C 51.2; H 3.770.
$ Found: C 49.9; H 3.470. Calculated: C 49.8; H 3.3%.

EXPERIMENTAL
2 - ( p - N i t r o p h e n y l ) - 4 - b e n z y l - 6 - n i t r o - 2 , 3 , 4 , 5 - t e t r a h y d r o - l , 2 , 4 - t r i a z i n e (IVc). A 1 g (4 mmole) s a m -
ple of nitroformaldehyde p - n i t r o p h e n y l h y d r a z o n e was dissolved in 10 ml of ethanol, and 1 g of 3670 formalin
(1 m m o l e of formaldehyde) and 0.6 g (6 remote) of benzylamine were added. The mixture was heated on a
boiling-water bath for 25 h, after which it was cooled, and the precipitate was r e m o v e d by filtration and
washed with alcohol. The yield of yellow c r y s t a l s (from alcohol) was 1.4 g (8670). Compounds IVa,b were
s i m i l a r l y obtained.
2 - ( p - N i t r o p h e n y l ) - 4 - ( p - c h l o r o p h e n y l ) - 6 - n i t r o - 2 , 3 , 4 , 5 - t e t r a h y d r o - l , 2 , 4 - t r i a z i n e (IVk). A 1.0 g (4
mmole) sample of n i t r o f o r m a l d e h y d e p - n i t r o p h e n y l h y d r a z o n e was dissolved in 20 ml of DMF, and 1.0 g of
36% formalin and 0.6 g (4 mmole) of p-chloroaniline were added. The mixture was heated on a water bath
for 3 h, after which it was allowed to stand at r o o m t e m p e r a t u r e for 14 h and then poured into ice water.
The precipitate was r e m o v e d by filtration and washed with water. The yield of orange c r y s t a l s (from di-
oxane) was 1.2 g (70%.)~ Compounds I V d - m were obtained under s i m i l a r conditions.
2 - N i t r o - 4 - ( p - c a r b o x y p h e n y l ) - 5 - i m i n o - 4 , 5 - d i h y d r o - l , 3 , 4 - t h i a d i a z o l e (Va). A 1.44 g (5 mmole) s a m -
ple of b r o m o n i t r o f o r m a l d e h y d e p - c a r b o x y p h e n y l h y d r a z o n e was dissolved in 20 ml of ethanol, and equimo-
lecular amounts of thiourea (0.38 g) and sodium hydroxide (0.2 g) in 3 ml of water were added. The m i x -
ture was heated on a w a t e r bath for 5-6 h. The product was isolated f r o m the alcohol solution by acidifi-
cation with 570 h y d r o c h l o r i c acid. Workup gave 0.26 g (2070) of d a r k - o r a n g e c r y s t a l s with mp 163-165 ~
(from alcohol). Found: N 17.770. CgHgN404S.C2tIsOH. Calculated: N 17.9%.
2 - N i t r o - 4 - ( p - n i t r o p h e n y l ) 7 5 - - i m i n o - 4 , 5 - d i h y d r o - l , 3 , 4 - t h i a d i a z o l e (Vb). This compound was s i m i l a r l y
obtained in 22% yield. The orange c r y s t a l s had mp 137-138 ~ (from alcohol). Found: S 11.870. C8HsN504S.
Calculated: S 12.070.
1 - ( p - N i t r o p h e n y l ) - 3 - n i t r o - 4 - a e e t y l - 5 - p y r a z o l o n e (VIIa). A 1 g (3.5 mmole) sample of b r o m o n i t r o -
formaldehyde p - n i t r o p h e n y l h y d r a z o n e was dissolved in absolute ethanol (20 ml), and 3.5 m m e l e of the so-
dium salt of acetoaeetic e s t e r in 7 ml of e t h e r was added to the alcohol solution. The mixture was then
heated on a w a t e r bath for 10 h. The solvent was partially evaporated, and the resulting precipitate was
r e m o v e d by filtration and washed with alcohol to give 0.26 g (26%) of brown c r y s t a l s with mp 202-203 ~
(dec., f r o m alcohol). Found: N 19.9%. CllHsN406. Calculated: N 19.270.
1 - ( p - A m i d o s u l f o n y l p h e n y l ) - 3 - n i t r o - 4 - a c e t y l - 5 - p y r a z o l o n e (VIIb). This compound was s i m i l a r l y ob-
tained. The brown c r y s t a l s had mp 250 ~ (dec., f r o m alcohol). The yield was 44%. Found: N 17.3%.
CllH10N406S. Calculated: N 17.270.
2 , 4 , 6 - T r i ( p - b r o m o p h e n y l h y d r a z o n o n i t r o f o r m y l ) - l , 3 , 5 - t r i a z i n e (Via). A 0.54 g (2 mmole) sample of
c y a n o n i t r o f o r m a l d e h y d e p - b r o m o p h e n y l h y d r a z i n e was dissolved in 40 ml of c h l o r o f o r m , after which the
solution was cooled with ice and 10 ml of chlorosulfonic acid was added slowly. The mixture was poured
into ice water after 3 h, and the resulting d a r k - o r a n g e precipitate was r e m o v e d by filtration and washed
with water until it was neutral. The yield of p r o d u c t with nap 145-147 ~ (from alcohol) was 0 . 4 2 g (80%).
Found: N 20.4%. C24H15Br3N1206. Calculated: N 20.8%.

373
 2,4,6-Tri(p-nitrophenylhydrazononitroformyl)-1,3, 5-triazine (VIb). This compound was similarly
obtained. The orange crystals had rap 152-153 ~ (from alcohol). The yield was 85%. Found: N 29.5%; tool.
wt. 739. C24Hl~N15OI2. Calculated: N 29.8%; reel. wt. 705.

LITERATURE CITED

1. W. Hahn, Roczn. Chem., 34, 329 (1960).

2. W. Hahn, Roczn. Chem., 36, 227 (1962).
3. N. Saldabol, L. Alekseeva, B. Brizga, L. Kruzmetra, A. Zile, and Yu. Popel, Khim.-Farmats. Zh.,
11, 38 (1968).
4. L . S . Pupko, A. I. Dychenko, and P. S. Pel,kis, USSR Author's Certificate No. 237,882; Byul. Izobr.,
9 (1969).
5. L . S . Pupko, A. I. Dychenko, and P. S. Pel'kis, Zh. Organ. Khim., 8, 39 (1972).
6. A. Cook and D. Jones, J. Chem. Soc., 278 (1941).
7. C. Grudmann, G. Weisse, and S. Seide, Ann., 577, 77 (1952).

374
LETTERS TO THE EDITOR

CATALYTIC SYNTHESIS OF PYRROLE FROM ETHANOLAMINES

K. M. Akhmerov, D. Yusupov, UDC 547.74 T435.1.07 : 543.544

A. B. Kuchkarov, and K. Akhmedov

The catalytic t r a n s f o r m a t i o n of monoethanolamine at high t e m p e r a t u r e s gives p y r r o l e . In addition to

p y r r o l e , the liquid r e a c t i o n p r o d u c t s contain a c e t o n i t r i l e , r e s i n , and water. The gaseous p r o d u c t s c o n s i s t
p r i n c i p a l l y of a m m o n i a and hydrogen. The a p p e a r a n c e of w a t e r and a c e t o n i t r i l e in the r e a c t i o n products is
evidence in f a v o r of the f a c t that the f o r m a t i o n of p y r r o l e p r o c e e d s through i n t e r m e d i a t e vinylamine.
The f o r m a t i o n of p y r r o l e f r o m diethanolamine p r o c e e d s m o r e r e a d i l y and gives b e t t e r yields than in
the f i r s t c a s e . T h i s is explained by the fact that the f o r m a t i o n of p y r r o l e h e r e p r o c e e d s through only one
i n t e r m e d i a t e - divinylamine - the dehydrogenation of which leads to the final t a r g e t product.
The e x p e r i m e n t s w e r e c a r r i e d out in a flow a p p a r a t u s . The r e a c t o r was c h a r g e d with 100 mI of
filled volume of an a l u m i n u m - z i n c - c h r o m i u m c a t a l y s t (9500 Wto% ~-A1203, 2.0 wt.% ZnO, and 3.0 wt.%
Cr203). Ethanolamine was p a s s e d through the c a t a l y s t l a y e r at 0.2 h -1.
The c a t a l y z a t e was analyzed by g a s - l i q u i d c h r o m a t o g r a p h y (GLC) [with an LKhM-7A c h r o m a t o g r a p h
with a t h e r m a l conductivity detector; the t h e r m o s t a t t e m p e r a t u r e was 175~ the column was 2 m long and
4 m m in d i a m e t e r , the phase was PEGA (polyethylene glycol a d i p a t e ) / C e l l i t e - 5 4 5 , and the c a r r i e r gas (he-
lium) flow r a t e was 60 m l / m i n ] .
In addition, the c a t a l y z a t e was rectified. The isolated~pyrrole fraction (bp 130-131 ~ nD 24 1.5042, and
d4 u 0.962) gave the c h a r a c t e r i s t i c coloration with a pine splinter m o i s t e n e d with h y d r o c h l o r i c acid.
The yield of p y r r o l e f r o m m o n o e t h a n o l a m i n e was ~ 10.0%; the yield f r o m diethanolamine was up to
18.5%.

T a s h k e n t l~olytechnical Institute. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 3,

p. 428, March, 1974. Original a r t i c l e s u b m i t t e d J u l y 3, 1973; r e v i s i o n submitted S e p t e m b e r 24, 1973.

9 1975Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy of this article is availablefrom the publisher for $15.00.

375
SYNTHESISAND PROPERTIES OF
4-CHLOROIMIDAZO[4,5-d]-I,2,3-TRIAZINE

V. I . O f i t s e r o v , Z. V. P u s h k a r e v a , UDC 547.785.5'872.3 : 543.422.4

V. S. M o k r u s h i n , a n d T. V. R a p a k o v a

When 4-chloroimidazo[4,5-d]-l,2,3-triazine (I) is heated in water the v-triazine ring opens to give
5-diazoimidazole-4-carbonitrile (II), which is stable only in solution. The formation of II was proved by
its diazo coupling with dimethylaniline and 2-naphthol and also by alternative synthesis of II and dyes III
+
and IV from 5(4)-aminoimidazole-4(5)-carbonitrile (absorption bands corresponding to VC - N and VN_ N
are observed in the IR spectra of II, III, and IV). The starting t was obtained by oxidative chlorination of

CI N(CH3) ~

N~N~:J----N/
H H H

H H
II III, IV

Ill Ar=4-(GH3)2NC6H4; IV Ar=2-hydroxynaphthyl

imidazo[4,5-d]-l,2,3-triazine-4-thione. Under mild conditions, I is converted to the known 4-N,N-dimethyI-

aminoimidazo[4-5-d]-l,2,3-triazine. Satisfactory analytical data were obtained for I, III, and IV, and the
individuality of the compounds was confirmed by means of descending paper chromatography in the n-butyl
a l c o h o l - a c e t i c a c i d - w a t e r (4:1 : 1} system.

S. M. Kirov Ural Pol .y.technical Institute, Sverdlovsk. Translated from Khimiya Geterotsiklicheskikh
Soedinenii, No. 3, pp. 428-429, March, 1974. Original article submitted July 17, 1973; revision submitted
September 17, 1973.

9 19 75Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

376
HIGH-TEMPERATURE SYNTHESIS OF THIOXANTHENE

M. G. Voronkov, l~. N . D e r y a g i n a , UDC 547.818.6

A . S. N a k h m a n o v i c h , L. G. Klochkova,
a n d G . M. I v a n o v a

It had a l r e a d y been shown in the l a s t c e n t u r y that thioxanthene is f o r m e d when phenyl o-tolyl sulfide
is p a s s e d through a "slightly i n c a n d e s c e n t " tube [1].
We have e s t a b l i s h e d that thiophenol r e a c t s with o - c h l o r o - or o - b r o m o - t o l u e n e at 650-660~ to give
thioxanthene and a s m a l l amount of phenyl o - t o l y l sulfide, which is evidently the i n t e r m e d i a t e :

S H + X/~-..~ "~v/"~.S/'~"~// S
I II Ill IV

By p a s s i n g an e q u i m o l a r m i x t u r e of I and H (X = C1) through a heated (to 600 ~ q u a r t z tube (30 m m in

d i a m e t e r ) we obtained HI and IV in 5.5 and 28.3% (based on the amount of s t a r t i n g H) or 7.7 and 38.5% yields
(based on the amount of II consumed). Compound I V h a s bp 160 ~ (4 ram) and nap 127" (rap 127 ~ [1]). Found:
C 78.85; H 5.00; S 16.00%. C13H10S. Calculated: C 78.90; H 5.05; S 16.15%.
Compounds III and IV w e r e obtained in 0.3 and 40.6% (based on the amount of s t a r t i n g II) or 0.37 and
49.5% yields (based on the amount of II consumed) at 650 ~ and a r a t e of p a s s a g e of a m i x t u r e of I and II (X =
Br) of 12 g / h .

LITERATURE CITED
1. C. G r a e b e and O. Schultefs, L i e b i g s Ann., 263, 14 (1891).

I r k u t s k Institute of Organic C h e m i s t r y , S i b e r i a n Branch, A c a d e m y of Sciences of the USSR. T r a n s -

lated f r o m K h i m i y a G e t e r o t s i k l i c h e s k i k h Seedinenii, No. 3, p. 429, March, 1974. Original a r t i c l e submitted
S e p t e m b e r 11, 1973.

9 1975Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced, ]
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy of this article is available from the publisher for $t5.00, ]

377
THERMOLYSIS OF 1-METHYL-2-ACETAMIDOBENZIMIDAZOLE

B. I. Khristieh and G. G. Yurchuk UDC547.785.5:542.954:543.422.25.4

In an a t t e m p t to bring about a F r i e s r e a r r a n g e m e n t , we heated 2 - a c e t a m i d o - l - m e t h y l b e n z i m i d a z o l e

(I) in an ampul at 240-245 ~ for 5 h, but we obtained a compound with m p 201 ~ ( f r o m alcohol) instead of the
expected b e n z o - s u b s t i t u t e d compound. Its s t r u c t u r e as b i s ( 1 - m e t h y l - 2 - b e n z i m i d a z o l y I ) a m i n e (II) was e s -

~ NHCOCH~ ~ ~H--
. NH 2 + Ill HE!

l I l
CH 3 CH s CH 3 I
CH~
I II III

tablished on the b a s i s of NMR and IR s p e c t r a l data and the r e s u l t s of e l e m e n t a r y a n a l y s i s . This s a m e s u b -

stance (II) is f o r m e d when 2 - a m i n o - l - m e t h y l b e n z i m i d a z o l e (III) is fused with its h y d r o c h l o r i d e at 250 ~ for
5 h. Under these conditions, 2 , b e n z a m i d o - l - m e t h y l b e n z i m i d a z 0 1 e r e m a i n s v i r t u a l l y unchanged.

Rostov State U n i v e r s i t y , Rostov-on-Don. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii,

No. 3, p. 429, M a r c h , 1974. Original a r t i c l e submitted October 15, 1973.

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 1001 I. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy of this article is available from the publisher for $15. 00.

378
GALA OCCASION FOR SOVIET SCIEINTISTS

In 1974 Soviet s c i e n t i s t s and all of the Soviet people will t r i u m p h a n t l y m a r k the 250th a n n i v e r s a r y
of the A c a d e m y of Sciences of the USSR. This date will include a review of the a c h i e v e m e n t s of Soviet
science and its r i c h t r a d i t i o n s in connection with which the p r o s p e c t s for future development will be d i s -
c u s s e d . In a d e c r e e of the C e n t r a l C o m m i t t e e of the C o m m u n i s t P a r t y of the Soviet Union (CC of the CPSU)
entitled ~The 250th Jubilee of the A c a d e m y of Sciences of the USSR ~ the quality of our s c i e n t i s t s ' a c h i e v e -
m e n t s was evaluated. M o r e o v e r , p r o b l e m s of the development of science and scientific - t e c h n i c a l p r o g r e s s
in o u r country that r e q u i r e urgent d i s c u s s i o n w e r e posed.
C r e a t e d b y t h e d e c r e e of P e t e r the F i r s t , the P e t e r s b u r g A c a d e m y of Sciences and its s u c c e s s o r -
A c a d e m y of Sciences of the USSR - have t r a v e r s e d a glorious path of d e v e l o p m e n t and have e n r i c h e d world
science with d i s c o v e r i e s of p a r a m o u n t significance. The m o s t outstanding Russian s c i e n t i s t s , including
such leading figures of organic c h e m i s t r y as IN. IN. Zinin, A. M. Butlerov, L. A. Chugaev, V. 1N. I p a t ' e v , P.
L Val'den, IN. D. Zelinskii, A. E. F a v o r s k i i , A. E. Arbuzov, V. M. Rodionov, I. IN, N a z a r o v , M . M . S h e m y a k i n ,
etco, h a v e b e e n m e m b e r s of the s t a f f of the A c a d e m y of Sciences. The d i s c o v e r i e s m a d e by them and t h e i r
scientific schools have had a s u b s t a n t i a l effect on the f o r m a t i o n and development of organic c h e m i s t r y , in-
cluding the c h e m i s t r y of h e t e r o c y c l i c compounds, and on the development of c h e m i c a l technology and the
c r e a t i o n of new dyes, m e d i c i n a l p r e p a r a t i o n s , and agents for the c h e m i z a t i o n of a g r i c u l t u r e .
The G r e a t O c t o b e r Socialist Revolution opened up broad p r o s p e c t s for development of the Academy
of Sciences. I m m e d i a t e l y a f t e r the revolution, the Soviet g o v e r n m e n t adopted m e a s u r e s for the financing
of the A c a d e m y and for the c r e a t i o n of a l a b o r a t o r y b a s e .
Excellent c h e m i c a l institutes p o s s e s s i n g s p e c i a l i z e d l a b o r a t o r y buildings equipped with m o d e r n in-
s t r u m e n t a t i o n are p r e s e n t l y functioning within the f r a m e w o r k of the A c a d e m y of Sciences. These c h e m i c a l
institutes have been c r e a t e d not only in Moscow and L e n i n g r a d but also in Siberia, Kazan, G o r ' k i i , S v e r d -
lovsk, and o t h e r cities in the country.
The A c a d e m y of Sicences of the USSR has been of g r e a t a s s i s t a n c e in the organization of o t h e r a c a d -
e m i e s of s c i e n c e s in the v a r i o u s republics of the Soviet Union. The training of p e r s o n n e l , the d i s c u s s i o n
of scientific t r e n d s , the holding of joint c o n f e r e n c e s and m e e t i n g s , and c o m p r e h e n s i v e aid f r o m the A c a d e m y
of Sciences of the USSR have enabled the a c a d e m i e s of the republics of the Soviet Union to rapidly achieve
t h e i r high scientific level.
INoteworthy in this r e s p e c t is the fact that one of the leading Soviet journals, in a t i m e l y field of o r -
ganic c h e m i s t r y - the c h e m i s t r y of h e t e r o c y c l i c compounds - is published by the A c a d e m y of Sciences of
the Lativian SSR and is issued in Riga. Our journal was o r g a n i z e d 9 y e a r s ago with the support of the P r e s -
idium of the A c a d e m y of Sciences of the USSR and since then has become the c e n t e r of publication of p a p e r s
on the c h e m i s t r y of h e t e r o c y c l e s , which constitutes about half the volume of organic c h e m i s t r y publications.
F r o m the m a t e r i a l published in the journal one m a y f o r m a judgment r e g a r d i n g the p r i n c i p a l t r e n d s
of the r e s e a r c h of Soviet c h e m i s t s s p e c i a l i z i n g in h e t e r o c y c l i c c h e m i s t r y , t h e i r i n t e r r e l a t i o n s h i p s , and the
chief c e n t e r s of r e s e a r c h in the field of h e t e r o c y c l e s . P a p e r s by A c a d e m i c i a n s I. L. Knunyant~, I. Ya.
Postovskii, B. A. Arbuzov, and A. S. Sadykov, and A s s o c i a t e M e m b e r s of the A c a d e m y of Sciences of the
USSR N. K. Kochetkov, M. G. Voronkov, Yu. A. Zhdanov, V. P. M a m a e v , A. V. B o g a t - s k i i , M. F. Shostakov-
skii, A. P. T e r e n t ' e v , P r o f e s s o r s Ya. L. G o l ' d f a r b , A. IN. Kost, K. Yu. INovitskii, IN. iN. Suvorov, Yu. P.
Shvachkin, and V. I. Minkin, and m a n y other p r o m i n e n t Soviet s c i e n t i s t s a r e published r e g u l a r l y in the journal.
In addition to p a p e r s by s c i e n t i s t s f r o m Moscow, Leningrad, Kiev, Riga, Sverdlovsk, Rostov-on-Don, p a p e r s
f r o m INovosibirsk, Saratov, I r k u t s k , A l m a Ata, Tashkent, Kazan, Odessa, Y e r e v a n , Tbilisi, Vilnius, Minsk,
and o t h e r cities in our country a r e published in the journal.

T r a n s l a t e d f r o m K h i m i y a G e t e r o t s i k l i c h e s k i k h Soedinenii, INo. 4, pp. 435-436, April, 1974.

9 1975Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

379
 The e v e r expanding significance of the c h e m i s t r y of h e t e r o c y c l i c compounds is explained by the fact
that this field of organic c h e m i s t r y is the basis of such important applied t r e n d s as synthetic m e d i c i n a l
substances (most of t h e m c r e a t e d on the b a s i s of h e t e r o c y e l i c compounds) and n a t u r a l biologically active
compounds (alkaloids, v i t a m i n s , e n z y m e s , etc.); the solution of the p r o b l e m of heredity and of the synthesis
of protein rings on the p r o b l e m of the investigation of the s t r u c t u r e and synthesis of the animate key f r a g -
ment of nucleic acid, which is a h e t e r o c y c l i c compound.
The c l a s s i c a l t r e n d s in the c h e m i s t r y of h e t e r o c y c l i c compounds that, as usual, require effort and
attentiveness are those dealing with natural and synthetic dyes. The inadequate volume of production of
a n u m b e r of cheap and p r a c t i c a l dyes in our country m a r k e d l y h a m p e r s the output of m o d e r n high-quality
textile a r t i c l e s .
In r e c e n t y e a r s compounds of the h e t e r o c y c l i c s e r i e s have played a m a j o r role in the c r e a t i o n of new
plant growth r e g u l a t o r s , h e r b i c i d e s , defoliants, fungicides, and a n u m b e r of o t h e r c h e m i c a l agents n e c e s s a r y
for a g r i c u l t u r e . The c h e m i c a l industry is doing intensive r e s e a r c h t o w a r d s the c r e a t i o n of new f o r m s of
fuels and e x p l o s i v e s , organic s c i n t i l l a t o r s and s e m i c o n d u c t o r s , motion picture m a t e r i a l s , and o t h e r e x -
t r e m e l y valuable c h e m i c a l products. This branch of c h e m i c a l science is of g r e a t value for the solution of
such p r o b l e m s as the protection of m e t a l s f r o m c o r r o s i o n , the c r e a t i o n of e o p o l y m e r s with new p r o p e r t i e s ,
et c.
All of this has been r e s p o n s i b l e for the grandiose scope of r e s e a r c h in the c h e m i s t r y of h e t e r o c y c l i c
compounds that is being done in the Soviet Union.
The c h e m i s t s specializing in h e t e r o c y e l i c c h e m i s t r y offer t h e i r m o s t c o r d i a l congratulations to the
Academy- of Sciences of the USSI~ on this i m p o r t a n t date of its 250th A n n i v e r s a r y and e x p r e s s t h e i r con-
fidence that Soviet s c i e n t i s t s will continue in the future to conquer new f r o n t i e r s on the path of scientific
and technical u r o g r e s s .

380
PHOTOCHEMISTRY OF QUATERNARY SALTS
OF AROMATIC HETEROCYCLES AND SOME
OF THEIR MESOIONIC DERIVATIVES (REVIEW)

A. V. El'tsov, V. M. Grebenkina, UDC 541.14:547.729'834

and V. S. Kuznetsov

The photochemical methods for the synthesis of q u a t e r n a r y salts of a r o m a t i c h e t e r o c y c l e s ,

t h e i r photochemical reduction r e a c t i o n s , photoreactions with water, some photochemical
t r a n s f o r m a t i o n s that p r o c e e d without a change in the charged h e t e r o c y c l e , and photoreactions
involving valence i s o m e r i z a t i o n and fragmentation of the mesoionic derivatives are examined.

The p h o t o c h e m i s t r y of q u a t e r n a r y salts of a r o m a t i c h e t e r o c y c l e s and some of t h e i r mesoionic d e r i v -

atives was not adequately r e f l e c t e d in a recent review on the photochemistry of h e t e r o e y e l e s [1]. Consid-
e r i n g the p e c u l i a r i t i e s of this class of compounds, we decided to fill this gap without, however, c o n s i d e r -
ing the f o r m a l l y r e l a t e d cyanine dyes and N-oxides~ The p r o p e r t i e s of the f o r m e r a r e associated to a con-
siderable extent with the polymethine chain (see, for example, [2]), which is absent in the o t h e r s y s t e m s , a n d
the p h o t o c h e m i s t r y of such dyes is t h e r e f o r e of independent i n t e r e s t . The principal directions of r e s e a r c h
on the p h o t o c h e m i s t r y of N-oxides were p r e s e n t e d in the review mentioned above [2], and the new r e s e a r c h
that has appeared since then (see [3]) has not fundamentally changed the situation.

Photochemical Methods for the Synthesis of Quaternary Salts of

Aromatic Heterocycles
Several types of photoreactions that lead to q u a t e r n a r y a r o m a t i c h e t e r o c y c l e s - construction of a
p r o p e r l y charged h e t e r o r i n g , closing of new c a r b o c y c l e s o r h e t e r o c y c l e s to q u a t e r n a r y a r o m a t i c h e t e r o -
cyclic compounds, and alkylation (arylation) of h e t e r o c y c l e s - have been described.
The r e a c t i o n s of the first type include the well-known (in the alkaloid s e r i e s ) photochemical closing
of a q u a t e r n a r y h e t e r o c y c l e as a result of t r a n s a n n u l a r interaction of the carbonyl and amino groups [4].
It leads to b e r b e r i n e (I) and its derivatives:

< .*
O "~ OCH3
~ ~ OCH3

~OCH3 ~'~j"~,~,OCH3

The p h o t o c h e m i c a l i n t r a m o l e c u l a r acylation of the benzene ring in II gives p r o t o b e r b e r i n e derivatives III

in good yield [5].
The photocyclization of the benzoyl analog of H p r o c e e d s differently under s i m i l a r conditions to give
IV [6]. (See equation on following page.)
Many q u a t e r n a r y and mesoionic a r o m a t i c h e t e r o c y c l e s have been synthesized by photocyclodehydro-
genation. Thus, irradiation of alcohol solutions of 1 - s t y r y l p y r i d i n i u m salts and substituted 1 - s t y r y l p y r i d -

Lensovet Leningrad Technological Institute. T r a n s l a t e d from Khimiya Geterotsiklicheskikh Soedinenii,

No. 4, pp. 437-452, April, 1974. Original article submitted July 31, 1973.

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 1001I. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

381
 R/ ~~~-
I ~ I R Z- R
R N. 3~,.2 R~I N~CH3 R ~ N ~ 0

R ~ R ~ R

inium salts in the p r e s e n c e of iodine makes it possible to obtain phenanthridizinium derivatives V in good
yields CuP to 60%) [7, 8]. Selective cyelization was not observed when the starting 3-methylpyridinium ring
was u n s y m m e t r i c a l l y substituted [8] (both possible i s o m e r s are formed).
R R

R'~ I2 Rl I-

The photodehydroeyclization of 2 , 3 - d i a r y l t e t r a z o l i u m salts (VI) has been studied for numerous ex-
amples [9-13]. As in the carbocyclic s e r i e s , nitro compounds were not cyclized. In contrast to the A?and
i s o m e r s [13], cyclization did not o c c u r if one of the a r y l groups was a - p y r i d y l . Photocyclization o f t e n
gives high yields (35-85%) and may be of preparative interest.

-- h~ /~N--N

-- ~ R R"

Similar photocyclization was o b s e r v e d on irradiation o f m e s o i o n i c d i a r y l - l , 3 , 4 - t h i a d i a z o l e s VII (30%

yield) [14, 15] and condensed pyridinium derivatives VII [16] and VIII [17].
R R
S ,..S S ....S

I I
C6H
5 C6H
S
Although photodehydroeyclization of salts of aromatic h e t e r o c y c l e s is, on the whole, e x t r e m e l y s i m -
ilar to the analogous reactions of c a r b o c y c l e s and h e t e r o e y c l i c bases, the differences in the r e a c t i v i t i e s
of the s a l t s and bases a r e s o m e t i m e s e x t r e m e l y substantial. Thus, in contrast to q u a t e r n a r y salt VIII,
the corresponding phenylbenzoquinoline is not cyclized under the same conditions but is capable of u n d e r -
going this sort of t r a n s f o r m a t i o n in strongly acidic media [16]. 1,3-Diphenylbenzo[f]quinoline behaves
s i m i l a r l y [18]. The reduced reactivity of the h e t e r o e y c l i e bases as c o m p a r e d with the salts is probably
caused by the possibility of v * * - n transitions in the f o r m e r . This same r e a s o n leads to loss of the ability
to undergo cyclization in the case of some substituted stilbenes, which have low-lying njr* levels, inas-
much as the p r e s e n c e of the l a t t e r r e i n f o r c e s p r o c e s s e s involving the deactivation of the excited Sl(~**-r)
state of the c i s - s t i l b e n e s [19] that is responsible for the cyclization [20].
The photochemical dehydrocyclization of the 1-phenacylpyridinium ion iX) could not be realized, but
the corresponding phenanthridizinium ion (XI) can be obtained by photocyclization of the 2 - b r o m o - l - p h e n -
acylpyridinium ion (XII) [21].

382
 0 OH 0

A r e l a t e d r e a c t i o n , although it leads to closing of a n o n a r o m a t i c ring, is photocyclization of 2 - h a l o - 1 -

b e n z y l p y r i d i n i u m ions (XIII, R=C1, Br; R ' = H ) , which m a k e s it p o s s i b l e to obtain the p r e v i o u s l y unknown
p y r i d o [ 2 , 1 - a ] i s o i n d o l i u m d e r i v a t i v e s (XIV) in good yields [21, 22].

R C0H5CH2._N_j ~ - ~ " ~ O

x .__J x._lv x_v

The i s o m e r containing a halogen in the ortho position of the benzyl residue (XIII, R =H, R' =Hal) c y c l i z e s
much m o r e slowly and gives a p o o r e r yield; this indicates the lower r e a c t i v i t y of the halogen in the benzene
ring. This is also indicated by the fact that the dibromo d e r i v a t i v e (XIII, R = R ' =Br) is cyclized only in
one direction, c o r r e s p o n d i n g to splitting out of a bromine atom f r o m the pyridinium ring [22]. The fluoro
d e r i v a t i v e (XIII, R = F, R' =H) does not undergo p h o t o c h e m i c a l cyclization but is c o n v e r t e d to a 1 - b e n y z l - 2 -
pyridone d i m e r (XV). The p r i m a r y r e a c t i o n is a p p a r e n t l y r e a c t i o n with the solvent - w a t e r . The compound
that does not contain a halogen atom (XIII, R = R ' =H) p h o t o c y c l i z e s v e r y slowly [22].
E x a m p l e s of the p h o t o c h e m i c a l quaternization of a r o m a t i c h e t e r o c y c l e s a r e well known. Thus, UV
i r r a d i a t i o n of solutions of acridine [23, 24] and b e n z a c r i d i n e s [24] in CC14 and CBrC1 a leads to N - t r i c h l o r o -
methyl derivatives,

..{.. CCt4 h~,,

I
CC!. 3 C~-
XVI

f o r e x a m p l e , to XVI. On the b a s i s of a c o m p a r i s o n of the quantum yields of the r e a c t i o n with the calculated

w - e l e c t r o n c h a r g e s on the nitrogen a t o m s in the rr*~rrand ~r*--n excited s t a t e s , Kellmann [24] p r o p o s e s an
ionic m e c h a n i s m f o r the quaternization, but his conclusion s e e m s inadequately substantiated.
The p h o t o c h e m i c a l N - a r y l a t i o n of pyridine and 4-picoline o c c u r s during nucleophilic substitution of
the nitro group in the excited s t a t e s of e t h e r s and e s t e r s of p - n i t r o p h e n o l [25-27]. p - N i t r o p h e n o l itself
and m - n i t r o a n i s o l e , nitrobenzene, and p - d i n i t r o b e n z e n e do not r e a c t u n d e r t h e s e conditions [26]. On the
o t h e r hand, the nitrile group in the o t h e r ring can be r e p l a c e d s i m u l t a n e o u s l y with r e p l a c e m e n t of the nitro
group in diphenyl e t h e r d e r i v a t i v e Xu [27].

NC~O-~ -No2 Pyr~dlne, C N ~ O- ~ - N~

XV!I water
The N - a r y l a t i o n of pyridine gives good yields and is of p r e p a r a t i v e i n t e r e s t ; this type of r e a c t i o n has
not been studied f o r o t h e r h e t e r o c y c l e s .

Photochemical Reduction of Quaternary Aromatic Heterocycles

The a p p e a r a n c e of anomalous long-wave a b s o r p t i o n bands in the e l e c t r o n i c s p e c t r a of the iodides or
b r o m i d e s of q u a t e r n a r y a r o m a t i c h e t e r o c y c l e s has been explained as being the r e s u l t of photoreduction of
the cations to the c o r r e s p o n d i n g r a d i c a l s as a consequence of e l e c t r o n t r a n s f e r f r o m the halide ion to the
p o s i t i v e l y c h a r g e d h e t e r o r i n g in a solvated ion p a i r [28]. The I~ and I F ions w e r e identified during flash
photolysis of solutions of iodides of substituted N - a l k y l p y r i d i n i u m and -quinolinium ions [29, 30]; this made
it p o s s i b l e to c o n s i d e r the f o r m a t i o n of I" to be proved [30].
R+I-~-- (RI).~-R+ I
I + I-~--I2-
2I~--I2
I - + I2~-~-Ia-

383
 The s a m e authors also o b s e r v e d absorption that was apparently r e l a t e d to the quinoline radical. The
f o r m a t i o n of CI" was s i m i l a r l y o b s e r v e d in the case of dichloride XVIII [31], i.e., the chloride ion also m a y
act as a reducing agent of the m o s t electrophilic q u a t e r n a r y salts of h e t e r o c y c l e s during i r r a d i a t i o n . Hop-
kins and c o - w o r k e r s [32] investigated the photoreduction of salts XVIII to cation r a d i c a l XIX by p r i m a r y
and s e c o n d a r y alcohols. They a s s u m e that the r a t e - d e t e r m i n i n g step is e l e c t r o n t r a n s f e r f r o m the alcohol
molecule to the singlet excited state of dication XVIII. The alcohol r a d i c a l s f o r m e d w e r e detected by m e a n s
of spin labeling.

('; H3-- N ~ N --CH3 +h~

e * CH~ N~N -'\ --CH3

2 CL- C~-
XVi IJ XIX

The photoreduction of acridinium s a l t s XX by alcohols p r o c e e d s via a different s c h e m e . The p r i n -

ciple products a r e 1 , 1 ' - d i a l k y l - 9 , 9 ' - d i a c r i d a n y l s XXII [33, 34]. It is p r o p o s e d [34] that the f i r s t t r i p l e t
state of the a c r i d i n i u m ion s t r i p s a proton f r o m the alcohol to give r a d i c a l cation XXI, which d i m e r i z e s .
D i m e r XX-II, although it can be isolated, is photochemically unstable and d e c o m p o s e s to 1 - a l k y l a c r i d i n i u m
ion and 1 - a l k y l a c r i d a n [34]. G6th and c o - w o r k e r s [35] u n d e r s i m i l a r conditions o b s e r v e d the f o r m a t i o n of
not only d i m e r s XXII but also hydroxyalkyl d e r i v a t i v e s XXIV, which c o r r e s p o n d to the reaction of r a d i c a l
cations XXI with alcohol r a d i c a l s . In the case of 9-substituted XXIII, in which d i m e r i z a t i o n is difficult,
the yield of the product of reductive hydroxyalkylation i n c r e a s e s to 40%.
H A~k
N
hv

RCH2OH
Ark
X xx._!
RdHOH l
ALR

CH3 R CHOH XX
I..,~1

I
CH 3 AIK
xxl_.~

Although t h e r e are no available data on s i m i l a r photoreactions of q u a t e r n a r y pyridinium and quinolin-

ium salts, the r e a c t i o n of protonated pyridines [36] and quinolines [37] with alcohols, which o c c u r s during
i r r a d i a t i o n , is well known.

2R
H R CHOH C

RCH20H /.~
H

xxv__j
XXV

Its principle products a r e 1,2- and 1,4-dihydro d e r i v a t i v e s (for e x a m p l e , XXV), which a r e readily dehydrated
in acidic m e d i a to give 2- and 4-alkylquinolines and - p y r i d i n e s (for e x a m p l e , XXVI).
B i o c h e m i c a l investigations of photosynthesis p r o c e s s e s in plants indicate that the photoreduction of
a substituted pyridinium ion - nicotinamide adenine dinueleotide - p o s s i b l y plays an important role in them
(see, f o r e x a m p l e , [38]). However, an attempt to a c c o m p l i s h this t r a n s f o r m a t i o n in v i t r o was u n s u c c e s s -
ful [39].

Some Photoreactions of Quaternary Aromatic Heterocycles with Water

A n u m b e r of pyridinium s a l t s undergo complex t r a n s f o r m a t i o n s on i r r a d i a t i o n in water. F o r e x a m p l e ,
the photodegradation of the herbicide p a r a q u a t (XVIII) leads to cleavage of the pyridinium ring to u l t i m a t e l y

384
give an isonicotinic acid d e r i v a t i v e (XXVIII) [31, 40]. Amino aldehyde XXVII is p r o p o s e d [34-40] as the
i n t e r m e d i a t e in the f o r m a t i o n of the l a t t e r , but it r e m a i n s u n c l e a r what r e l a t i o n s h i p the p a r a q u a t r a d i c a l
cation, which is r e a d i l y f o r m e d on i r r a d i a t i o n , has to this p r o c e s s .
H

COO-

t I l
":H 3 CH 3 CH3
<VIII XXVll XXVlll

A q u a t e r n a r y d e r i v a t i v e of nicotinamide (XXIX) undergoes photooxidation to a substituted ~ - p y r i d o n e

(XXXI) on photolysis in aqueous solution [41]. I t is supposed that the l a t t e r is f o r m e d f r o m the product of
the d a r k h y d r o l y s i s of the pyridinium ion - 1 - m e t h y l - 2 - h y d r o x y - l , 2 - d i h y d r o d e r i v a t i v e XXX - but this
a s s e r t i o n has not been p r o v e d .

CONH 2 CONH 2 ,,,CO NH 2

[o]
I H ~ 0
CH 3 CH 3 CH 3

x.xlx xx__.~x xxx.._~l

In addition, the photohydrolysis of p y r i d i n i u m ions which includes a s k e l e t a l t r a n s f o r m a t i o n is known [42].
In alkaline m e d i a , this r e a c t i o n p r o c e e d s p r a c t i c a l l y to c o m p l e t i o n and gives 6 - a z a b i c y c l o [ 3 . 1 . 0 ] h e x - 3 - e n -
2-ol d e r i v a t i v e s XXXIII and XXXIV in good quantum yields (~0.1). To explain the 1,2-shift of substituents
that is s o m e t i m e s o b s e r v e d in the c a s e of picolines and lutidines, it has been a s s u m e d that 1-(methylazonio}
benzovalene (XXXII) is initially f o r m e d .
Thus, t h e r e is a s i m i l a r i t y to the photohydration of benzene, which p r o c e e d s through benzovalene [43].
This s i m i l a r i t y is a p p a r e n t l y due to the 7r**--~r nature of the excitation of the q u a t e r n a r y h e t e r o r i n g . (Py-
ridine, in which ~r*~ n excitation is p o s s i b l e , is photohydrated differently to " D e w a r p y r i d i n e " [44, 45].) In
n e u t r a l o r acidic m e d i a , b i c y c l i c compounds (XXXIII) r e a d i l y undergo r e v e r s e d a r k r e a r r a n g e m e n t to give
pyridinium ions, and the i n t e r m e d i a t e l y o b s e r v e d UV absorption m a y be r e l a t e d in one case to chain amino
aldehyde XXXV and in the o t h e r c a s e to 1 - m e t h y l - 2 - h y d r o x y - l , 2 - d i h y d r o p y r i d i n e (XXXVI) [42].
In this connection, it can be a s s u m e d that bicyclic products of the XXXIII type a r e also initially f o r m e d
in the a b o v e - d e s c r i b e d , m o r e c o m p l e x t r a n s f o r m a t i o n s of pyridinium ions [34, 40, 41], and the XXXIII then
undergo t r a n s f o r m a t i o n s in analogy with XXXV o r XXXVI.
R ~N/CH3 _ / - Nt"CH3 j N , . J CH3

CH 3 OH
XXXI] XXXIIt
/CH3 /CH 3

H3C
/NNo
NXXV
H
G<
I
CH 3
XXXV___.~
OH
R
-
R
XXXlV

In o r d e r to explain the origin of XLI-X'LIII - p r o d u c t s of the photolysis o f p y r i l l i u m salt XXXVII in

w a t e r - B a r l t r o p and c o - w o r k e r s [46] s u c c e s s f u l l y used the concept of the i n t e r m e d i a t e f o r m a t i o n of
oxoniobenzovalene XXXIX, (see equation on following page), the p r e c u r s o r of which is a s s u m e d to be cation
d i r a d i c a l X X X ~ I I r a t h e r than cation XL, i n a s m u c h as the t r a n s f o r m a t i o n s of the l a t t e r do not explain the
development of diketone XLII.
The s a m e authors p r o p o s e a s c h e m e with an oxoniobenzovalene i n t e r m e d i a t e to explain the data in
[47] on the phototysis of a - p y r o n e s . The p r e r e q u i s i t e f o r the s i m i l a r i t y between the l a t t e r and p y r i U i u m
s a l t s is a sufficiently l a r g e contribution to t h e i r e l e c t r o n i c s t r u c t u r e s of limiting s t r u c t u r e XLIV.

385
 ~ , C H3)3 ~(CH3)3 " C(CH3)3 C{CH3}3

H3CA+O.~CH 3 h~ I , . H 3 C ~ + ~CH3 ~3C~CH 3. L ~ O

H3C CH3
XXXVII XXXVIII XXX,IX I

1
( H3C)2~ C-- CH2
1
C(CH3)3
,'
C (CH3)3

H3C CH3
H3C CH 3 H3C CH QH OH
O
x-~ i~o~ I XL~

0-
OH

0 H3C~ II
O
f:
H3
II ~CH 3
O
H2C <S OH
CH3

XLIV XLl"~-i XLIII

Photochemistry of Mesoionic Compounds

Misoionic compounds can be c o n s i d e r e d to be a r o m a t i c q u a t e r n a r y h e t e r o c y c l e s that have substituents
with an integral negative charge in which the o b s e r v e d i n t r a m o l e c u l a r c o m p e n s a t i o n of c h a r g e s can be t r a n s -
mitted only by valence s t r u c t u r e s of d i r a d i c a l c h a r a c t e r . The effective c h a r g e s in m e s o i o n i c h e t e r o c y c l e s
a r e c o n s i d e r a b l e , and this m a k e s t h e m c l o s e l y r e s e m b l e q u a t e r n a r y h e t e r o c y c l e s .
The data p r e s e n t e d below on the photochemical r e a c t i o n s of m e s o i o n i c compounds show that f r a g -
mentation and i s o m e r i z a t i o n r e a c t i o n s a r e f i r s t and f o r e m o s t c h a r a c t e r i s t i c for t h e m , i.e., the excited
s t a t e s of the m e s o i o n i c h e t e r o c y c l e s and q u a t e r n a r y h e t e r o c y c l e s that are r e s p o n s i b l e for the p h o t o c h e m -
ical t r a n s f o r m a t i o n s differ in t h e i r r e a c t i v i t i e s .
Several t y p e s of t r a n s f o r m a t i o n s during which, as it is a s s u m e d , i n t e r m e d i a t e [2.1.0] bicyclic c o m -
pounds a r e f o r m e d , are known f o r f i v e - m e m b e r e d m e s o i o n i c h e t e r o c y c l e s . Thus, it has been found [48]
that the photolysis of N-phenylsydnone (XLV) gives i s o m e r i c 4 - p h e n y l - A 2 - 1 , 3 , 4 - o x a d i a z o l i n - 5 - o n e (XLIX);
e x p e r i m e n t s with 14CO2 and a study of the dependence of the f o r m a t i o n of oxadiazoline XLIX on the c a r b o n
dixoide p r e s s u r e have shown that splitting out and subsequent addition of CO 2 in a different orientation a p -
p a r e n t l y occur. It is a s s u m e d that e i t h e r diazirine XLVII or nitrilimine XLVIII p a r t i c i p a t e in the addition
reaction. It should be noted that only the indicated p h o t o i s o m e r i z a t i o n was o b s e r v e d during an attempt to
introduce sydnone XLV into photochemical cycloaddition with r e a g e n t s containing multiple bonds.

x-C? X...Lyl X'LV.t~ XLW, X~

This s o r t of i s o m e r i z a t i o n was not noted in the photolysis of 3,4-diphenylsydnones. The f o r m a t i o n

of the chief photolysis products - 2 , 4 , 5 - t r i p h e n y l - l , 2 , 3 - t r i a z o l e s and some o t h e r s u b s t a n c e s - is explained
[49-51] by a complex chain of t r a n s f o r m a t i o n s of C , N - d i p h e n y l n i t r i l i m i n e s o r diphenyldiazirines that a r i s e
f r o m the bicyclic compound, as in the c a s e of XLVI. The s t r u c t u r e s of the adducts of the photochemical
1,3-dipolar cycloaddition of olefins and a c e t y l e n e s , which gives yields up to 50-80% [50-52], also indicate
that n i t r i l i m i n e s are f o r m e d i n t e r m e d i a t e l y during the photolysis [51].
However, the r e s u l t s of r e s e a r c h on m e s o i o n i c 1,3-dithiolium [53] and 1 , 2 , 4 - t r i a z o l i u m [54] d e r i v -
atives provide evidence that valence i s o m e r i z a t i o n to a new f i v e - m e m b e r e d h e t e r o c y c l e that does not have
f o r m a l c h a r g e s m a y p r e c e d e cleavage of the bicyclic i n t e r m e d i a t e s . Thus, 1,3-dithiolium compound L is
c o n v e r t e d (in 80%yield) to 1,2-dithiol LII as a result, as a s s u m e d in [53], of s i g m a t r o p i c r e a r r a n g e m e n t
of bicycle LI,

386
 S C6H5 l 5
C671

C6H5~ =N C6HsCON C6H5CON

-)

The principle products in the photolysis of LIII are ~rylazobenzene LVI, a r y l i s o c y a n a t e LVII, and
benzimidazole (LIX). The formation of benzimidazole in this case and its absence in the photolysis of N-
phenylsydnone made it possible to conclude that these two p h o t o t r a n s f o r m a t i o n s p r o c e e d without the f o r m a -
tion of a c o m m o n intermediate (diazirine XLVII might have been assumed to be such an intermediate). The
i s o m e r i z a t i o n of bicycle LIV to t r i a z o l e LV with subsequent t r a n s f o r m a t i o n s of the l a t t e r explains the s t r u c -
t u r e s of the final products obtained.

~6H5 6H5
N\ C6HSXXN/~N
~/-I-
k',--,',N h'q

LIII LI._.VV LV LV__~I

:J~ -- R NCO

/~N C6 H5N~ CH--N: . . . .

N
XLVII LVlll LIX

The assumption of initial valence i s o m e r i z a t i o n thus eliminates the n e c e s s i t y for r e s o r t i n g to an ex-

amination of the formation of unstable 4~-eleetron 1H-diazirines in the photofragmentation of mesoionic
five-membered heterocycles.

The two indicated s c h e m e s of the t r a n s f o r m a t i o n s (with the intermediate formation of a 4~-electron

h e t e r o c y c l e and with valence isomerization) cannot be distinguished on the basis of other investigations,
in which the individual photofragTnentation products were identified. These investigations included, for e x -
ample, the isolation of diphenylacetylene and sulfur during the photofragmentation of 2 , 4 - d i p h e n y l - l , 3 -
dithiolium-5-olate [55] and the tying up of the benzonitrile sulfide formed during the photolysis of 4-phenyl-
1 , 3 , 2 - o x a t h i a z o l i u m - 5 - o l a t e and its derivatives [56] as a result of reactions with acetylenedicarboxylic
acid e s t e r . It was apparently expedient to specially synthesize the proposed intermediate f i v e - m e m b e r e d
h e t e r o c y e l e s and investigate t h e i r t r a n s f o r m a t i o n s in o r d e r to verify the assumption regarding the valence
i s o m e r i z a t i o n of the p r i m a r y intermediate - a [2.1.0]bicycleo
The s t r u c t u r e s ofthe products of photolysis of 2,3-disubstituted 4-aminothiazolium salts in w a t e r e n -
abled Chinone and c o - w o r k e r s [57] to also assume the formation of bicyclic compounds LX as intermediates.
Although the scheme for the formation of the two chief final products of the reaction of LXII and LXIII is
not completely clear, it s e e m s probable that LXII a r i s e s as a result of valence i s o m e r i z a t i o n of bicycle LX
to isothiazole LXI and its subsequent cleavage.
R
R I
R S A O~-C
# ~/H + c=c
HJC%NH R'N'~H \CN "
~H \H I,
m
LX LXI LXII LXlII
Photolysis of sydnonimine salts in w a t e r gives ~ - k e t o acids [57]. The difference between these r e -
sults and the above-indicated data on sydnones is apparently a s s o c i a t e d to a considerable extent with the
pronounced change in the nature of the solvent.

1 , 3 , 4 - T h i a d i a z o l i u m - 2 - t h i o l a t e s (LXIV) undergo photofragmentation with the intermediate formation

of unstable heteroeumulenes LXV, which are detected from the IR s p e c t r a [58]. The formation of h e t e r o -
cumulenes LX-v- is not, however, a purely photochemical t r a n s f o r m a t i o n , inasmuch as t h e i r bands are not
o b s e r v e d in the IR s p e c t r u m during l o w - t e m p e r a t u r e photolysis.

387
 R' -S .-S RSr -
I
N_~N R--N--N=C:S
R/
xJ---9
9 LXV

In a recent study [59] it was found that the photolysis of 4-pheny1-1,3,2-oxathiazolium-5-olate ap-
parently prooedes simultaneously via two paths, one of which commences with the formation of a [2.1.0]
bicycle, while the other begins with the formation of a heterooumulene.
S u m m a r i z i n g the above-indicated e x p e r i m e n t a l data, which provide evidence for the r e a d y f o r m a t i o n
of [2.1.0]bicyelic compounds f r o m f i v e - m e m b e r e d m e s o i o n i c h e t e r o c y c l e s , it can be a s s u m e d that the
bicyclic compounds a r i s e d i r e c t l y f r o m the excited states of the s u b s t r a t e m o l e c u l e s that have d i r a d i c a l
c h a r a c t e r : the t r i p l e t states a r e m o r e likely to have diradical c h a r a c t e r [60]. A calculation of sydnone,
sydnonimine, and the sydnonimine cation by the MO method (within the P o p l e - P a r i s e r - P a r r approximation)
[61] indicates the low e n e r g y of the f i r s t t r i p l e t state. Considerable charge t r a n s f e r , which should o c c u r
during the T 1 - SOt r a n s i t i o n (it can be thoroughly illustrated, with the well-known r e s t r i c t i o n [60], by v a l -
ence s t r u c t u r e s LXVI and LXVII),
R~ R|

N--O N~-O

LXVI, LXVII
can Encrease the probability of this transition.
It should be added that in the f i r s t t r i p l e t state of sydnone and its d e r i v a t i v e s , the highest spin density
values are p r e c i s e l y in the 2 and 4 positions, due to which a new cr bond should be f o r m e d (this is i l l u s t r a t e d
by s t r u c t u r e LXVI). This allows us to a s s u m e that it is probable that the f i r s t t r i p l e t states p a r t i c i p a t e in
the examined photochemical t r a n s f o r m a t i o n s of sydnones and r e l a t e d compounds, but t h e r e is no direct e x -
p e r i m e n t a l evidence for this, and t h e r e a r e no q u a n t u m - c h e m i c a l calculations for d e r i v a t i v e s o t h e r than
those of sydnones.
Of the s i x - m e m b e r e d m e s o t o n i e a r o m a t i c h e t e r o c y e l e s , p y r i d i n i o - l - a c y l i m i d e s LXVIII, p a r t i c u l a r l y
1 - a l k o x y c a r b o n y l i m i d e s [62-69] (in addition, 1 - a c e t y l i m i d e [66], 1 - b e n z o y l i m i d e , and, 1 - t o s y l i m i d e [63,
66, 67, 69]) have been investigated a l m o s t e x c l u s i v e l y . The chief photochemical r e a c t i o n of these compounds
is i s o m e r i z a t i o n to 1 - a c y l - l H - 1 , 2 - d i a z e p i n e s (LXX). This photochemical synthesis s e e m s of p r e p a r a t i v e
i n t e r e s t , inasmuch as the yields r e a c h 90-95% [62, 64, 67, 68]. The effect of substituents on this t r a n s -
f o r m a t i o n has been investigated, although on a limited scale. Thus, it has been found that substitution of
both of the ~ positions with methyl groups does not block the reaction, but incorporation of an e t h o x y c a r -
bonylimino group in the mono-o~-substituted compound o c c u r s on the side of the unsubstituted ~ position
[68]. A 4 - e t h o x y c a r b o n y l group p r e v e n t s p h o t o i s o m e r i z a t i o n (the substance is r e s i s t a n t to irradiation)
[69]. It has been a s s u m e d [67-69] that the t r a n s f o r m a t i o n p r o c e e d s through i n t e r m e d i a t e pyridodiazirine
LXIX. The isolation of side products - 2 - a c y l a m i n o p y r i d i n e s (LXXD [69] a n d 2 - a m i n o p y r i d i n e s [67] - is
c o n s i d e r e d to be a c o n f i r m a t i o n of this s c h e m e .
R
R

~N NHCORL
R .LXXI
-N~COR I --COR' ~

""COP'
LXVIII I"XlX X'
L~-X

Q u i n o l i u n i o - l - a c e t y l i m i d e undergoes photolysis s i m i l a r l y to give, in low yields, 2 - a c e t y l a m i n o -

quinoline and benzodiazepine d e r i v a t i v e LXXII, the methoxy group of which a r i s e s f r o m the solvent
(methanol) [70]. (See equation on following page.)
I n a s m u c h as the p h o t o i s o m e r i z a t i o n of p y r i d i n i o - l - a l k o x y c a r b o n y l i m i d e p r o c e e d s to give good yields
in acetone, it has been a s s u m e d [68], that it o c c u r s through a betaine t r i p l e t state, which is populated due
to sensitization by acetone. However, it was l a t e r found [71] that the effect of the t r i p l e t s e n s i t i z e r eosin

388
 [ H I
OCH3
1
~ ~ ~-~CH_~_~C(CN) 2
H
COCH 3 / C-
NC \ C N
LXXll LXXIII LXXlV

r e d u c e s only to r e i n f o r c e m e n t of a side p r o c e s s (with r e s p e c t to [ s o m e r i z a t i o n ) - splitting out of a nitrene.

When the i r r a d i a t i o n was effeoted through a GWV f i l t e r in the p r e s e n c e of eosin, in which case the p y r i d i n -
iumimide was not d i r e c t l y excited, cleavage p r e d o m i n a t e d . In this connection, it has been concluded [71]
a betaine t r i p l e t state p a r t i c i p a t e s in the cleavage of the nitrene. A q u a n t u m - c h e m i c a l calculation [72] by
the P o p l e - P a r i s e r - P a r r method indicates, on the o t h e r hand, an i n c r e a s e in the o r d e r of the bond between
the exocyclic atom and the o~-carbon a t o m of the h e t e r o r i n g of LXVIII in the Sl state; this m a k e s it p o s -
sible to c o n s i d e r the p a r t i c i p a t i o n of the l a t e r probable* in the f o r m a t i o n of bicycle LXIX.
When the nature of the anionoid c e n t e r of 1 - p y r i d i n i u m ylids t h e r e m a y be a pronounced change in the
r e a c t i v i t i e s , which is d e m o n s t r a t e d by the p h o t o c h e m i c a l i s o m e r i z a t i o n of 1 - p y r i d i n i u m dicyanomethylide
(LXXIII) to 2 - ( 2 , 2 - d i c y a n o v i n y l ) p y r r o l e (LXXIV) (the l o w e r yield is a s s o c i a t e d with the simultaneous s p l i t -
ting out of a d i c y a n o c a r b e n e , which p r o c e e d s to a c o n s i d e r a b l e degree) [64].
Side r e a c t i o n s (with r e s p e c t to p h o t o i s o m e r i z a t i o n ) of photocleavage of substituted n i t r e n e s o r c a r -
benes were also o b s e r v e d in o t h e r c a s e s [68, 70, 73, 74].
T r i a z o l i u m imides LXXV have undergone only side cleavage, and the final product of the nitrene t r a n s -
f o r m a t i o n s was azo compound LX-XVI [75]. T r i a z o l i u m a c e t y l i m i d e LXXVH, in addition to s i m i l a r cleavage,
was s i m u l t a n e o u s l y i s o m e r i z e d to t r i a z o l e c a r b o x y l i c acid m e t h y l a m i d e L X X V I I I [76], but the m e c h a n i s m of
this r e a c t i o n is not c l e a r .

N-cN/C6H5 N__N/C6H5

t;
N-- C6H4NO2 - p
L XXV LXXVI

.CH.C.H. N N/CH2C6H5
N----"N/ ,: o
h'V
' N - ~ C O NHCl'l 3

N~COCH 3
LXXVll LXXVIII

The r e v e r s e p h o t o c h e m i c a l t r a n s f o r m a t i o n of p y r y l i u m 3-oxides, for e x a m p l e , L X X I X and its benzo

d e r i v a t i v e (LXXXI) [78, 79], to the c o r r e s p o n d i n g oxides LXXX and LXXXII is well known [77]. In connec-
tion with the isolation of side p r o d u c t s of the t r a n s f o r m a t i o n LX-XXI ~LX-XXII in alcohol ( c i s - and t r a n s - 3 -
e t h o x y - 2 - h y d r o x y - 2 , 3 - d i p h e n y l i n d a n o n e s ) , Ullmann and H e n d e r s o n [79] a s s u m e that t h e s e photochromic
t r a n s f o r m a t i o n s (forward and r e v e r s e ) a p p a r e n t l y p r o c e e d through v i b r a t i o n a l l y excited ground s t a t e s of
the t a u t o m e r s , although the p a r t i c i p a t i o n of the c o r r e s p o n d i n g t r i p l e t s is not" excluded. To the l a t t e r one
m a y add that the t r a n s f o r m a t i o n of m e s o i o n i c p y r y l i u m d e r i v a t i v e s to bicyclic oxides could also o c c u r via
yet a n o t h e r m e c h a n i s m - through oxoniobenzovalene d e r i v a t i v e s L ~ I I o (See s c h e m e onthe followingpage.)

Photoreactions without Changes in t h e Quaternary

Aromatic Heterocycle
The effect of a q u a t e r n a r y a r o m a t i c h e t e r o c y c l e is weakly m a n i f e s t e d in a n u m b e r of photochemical
r e a c t i o n s of the side chain o r adjacent ring. The c i s - t r a n s i s o m e r i z a t i o n of q u a t e r n a r y s a l t s of 1 - a r y l - 2 -
h e t a r y l e t h y l e n e s [80-82], the d i m e r i z a t i o n of the s a m e compounds to cyclobutane d e r i v a t i v e s [80, 83, 84],
and the d i m e r i z a t i o n of a c r i d i z i n i u m salt LXXXIV [85] and its benzo d e r i v a t i v e s [86] a r e among such t r a n s -
*A l a t e r study [92] showed that c o n s i d e r a t i o n of the o r d e r s of the bonds of the exocyclic nitrogen with the
C 2 and C 6 a t o m s of the pyridine ring in the S 1 state is useful for the i n t e r p r e t a t i o n of the p r i m a r y path of
i s o m e r i z a t i o n of substituted pyridinium i m i d e s . This path c o r r e s p o n d s to a higher bond o r d e r , which is
p r o m o t e d by e l e c t r o n - d o n o r substituents attached to the o~-carbon atom and e l e c t r o n - a c c e p t o r substituents
attached to the c o r r e s p o n d i n g f l - c a r b o n atom.

389
 C6H5 C6H5 C6H5 C61"15

It+;/ " II "~"cG% I II ~II ~ C6H5

C6H5 :[ C6H5 C6H5 II !! C6H5
0 0 0 0

LXXIX LXXX LXXXl LXXXII

LXXIX Lxxx
c,H , c,Hs c,H.]
LXXXIH

f o r m a t i o n s , in which the p r i n c i p l e s e s t a b l i s h e d for c a r b o c y c l e s and uncharged h e t e r o c y c l e s a r e b a s i c -

ally retained.

N h'~

LXXXIV

E x a m p l e s of the few r e a c t i o n s in which the e l e c t r o n - a c c e p t o r effect of q u a t e r n a r y pyridinium rings

is e x e r t e d a r e the photoreactions with nucleophiles of 1,2-bis(pyridinio)ethylene, for e x a m p l e , LXXXV
[87]. The l a t t e r , like other olefins with e l e c t r o n - a c c e p t o r substituents [88], readily add w a t e r and alcohols
on i r r a d i a t i o n to give LXXXVI.

CH3--N~ ~- CH=CH---~N--CH 3'

R
LXXXV LXXXVt R : OH , ORI

The quantum yields in the r e a c t i o n of 3-pyridinio d e r i v a t i v e s are c o n s i d e r a b l y l o w e r than in the r e -

actions of the 2- and 4 - i s o m e r s ; this is explained by the weak a c c e p t o r p r o p e r t i e s of the 3 - p y r i d i n i u m r e s i -
due.
It has been a s s u m e d [87] that the exiplexes of the LXXXV cation with w a t e r o r alcohols a r e c o n v e r t e d
to adducts LXXXVI in the ground state (possibly with intermediate splitting out of a proton). Decomposition
of the exiplex due to e l e c t r o n t r a n s f e r to the olefin with subsequent proton t r a n s f e r and addition of an e t h e r
r a d i c a l is c o n s i d e r e d probable for the r e a c t i o n with e t h e r s :

CH3-CH}"-O--CH2"-CH3 ] L ]

L C H~,.C H~_O__~H__ CH 3 H3c / OCH2CH 3

The photolysis of ( 1 - m e t h y l - 2 - p y r i d i n i o ) f e r r o e e n e does not involve the h e t e r o e y c l e and m a y s e r v e

as a method f o r the p r e p a r a t i o n of pyridinium cyclopentadienylides [89].
T h e r e are data available [90, 91] r e g a r d i n g the photooxidative hydroxylation of q u a t e r n a r y p h e n a -
zinc d e r i v a t i v e s in the 6- and 9-positions.

390
 R i R
N..,. N

I CH 3 OH
CH 3

LXXXVII LXXXVIII

R OOH R OH

1 t
CH 3 CH 3

LXXXIX

McIlwain [90] proposes 6,9-endo-peroxide LXXXVII and the corresponding 6- and 9-hydroperoxides
(LXXXVIII and LXX~XIX) as intermediates.

LITERATURE CITED
1. S . T . Reid, Advances in Heterocyclic Chemistry, Vol. 11, New York (1970), p. 1.
2. R . A . Pierce and R. A. Berg, J. Chem. Phys., 5 ! , 1267 (1969).
3. D. Bryce-Smith, Photochemistry, Vol. 2, The Chemical Society, London (1971), p. 634.
4. X.A. Dominguez and J. G. Delgado, Tetrahedron Lett., 2493 (1967).
51 G. R. Lenz and N. C. Yang, Chem. Commun., 1136 (1967).
6. M. P. Cava and S. C. Havlicek, Tetrahedron Lett., 2625 (1967).
7. R. E. Doolittle and C. K. Bradsher, Chem. Ind., 1631 (1965).
8. R. Eo Doolittle and C. K. Bradsher, J. Org. Chem., 3_~.1,2616 (1966).
9. F. Weygand and J. Frank, Z. Naturf., 3._B, 347 (1948).
10. J. Hausser, D. J er c he l , and R. Kuhn, Bet . , 82, 195 (1949).
11. D. J e r c h e l and H. Fischer, Ann~ 59(}, 216 (1954).
12~ D. J e r c h e l and H. Fischer, Ber~ 8.88, 1595 (1955).
13. D. J e r c h e t and H. Fischer, Ber., 89, 563 (1956).
14. R . M . Moriarty, J. M. Kliegman, and R. B. Desai, Chem. Commun., 1255 (1967).
15. R . M . Moriarty and R. Mukherjee, Tetrahedron Lett., 4627 (1969).
16. F. Andriani, R. Andrisano, J. Salvador,, and M. Tramontini, J. Chem. Soc., C, 1007 (1971}.
17. O . L . Chapman, OrganicPhotochemistry, Vol. 1, Marcel Dekker, New York (1967), p. 25.
18. R. Huisgen, Ann., 564, 16 (1949).
19. E . V . Blackburn and C. J. Timmons, J. Chem. Soe., C,172 (1970).
20. Vo A. Krongauz, Usp. Khim., 4.~.1, 852 (1972).
21. A. Fozard and C. K. Bradsher, Tetrahedron Lett., 3341 (1966).
22. A. Fozard and C. K. Bradsher, J. Org. Chem., 32, 2966 (1967).
23. N. Ivanoff and F. Walch, J. Chim. Phys., 54, 473 (1957).
24~ A. Kellmann, J. Chim. Phys., 63, 949 (1966).
25. L. Letsinger and O. B. Ramsay, J. Amer. Chem. Soc., 86, 1447 (1964).
26. L. Letsinger, O. B. Ramsay, and J. H. McCain, J. Amer. Chem. Soc., 87, 2945 (1965).
27. K . E . Steller and R. L. Letsinger, J. Org. Chem., 35, 308 (1970).
28. E . M . Kosower, in: Problems in Physical Organic Chemistry, Wiley (1972).
29. E . M . Kosower and L. Lindquist, Tetrahedron Lett., 4481 (1965).
30. R . F . Cozzens and T. A. Gover, J. Phys. Chem., 74, 3003 (1970).
31. J . F . Mckellar and P. N. Turner, Photochem. Photobiol., 13, 437 (1971).
32. A . S . Hopkins, A. Ledwith, and M. F. Stam, Chem. Commun., 494 (1970).
33. Fo Mader and V. Zanker, Ber., 9_~7,2419 (1964).
34. V. Zanker, E. Erhardt, F. Mader, and J. Thies, Z. Naturf., 21B, 102 (1966).
35. H. G~th, P. Cerutti, and H. Schmid, Helv. Chim. Acta, 4._88,1395 (1965).
36. D. Bryce-Smith, Photochemistry, Vol. 2, New York (1971), p. 524.
37. D. Bryce-Smith, Photochemistry, Vol. 1, New York (1970), p. 288.
38. E. No Mukhin, V. A. Protashchik, and V. L. Shmeleva, ~n- Problems in Biophotochemistry [in Rus-
sian], Nauka, Moscow (1973), p. 204.

391
39. B. Ekert and R. Monier, Bull, Soc. Chim. Biol., 40, 793 (1958).
40. P. Slade, Nature, 207, 515 (1965).
41. S . J . Wang, Biochemistry, 7, 3740 (1968).
42. L. Kaplan, J. W. Pawlik, and K. E. Wilzbach, J. Amer. Chem. Sot., 9_~4,3283 (1972).
43. E. Farenhorst and A. F. Bickel, Tetrahedron Lett., 5911 (1966).
44. J. Joussot-Dubien and J. Houdard-Porevre, Bull. Soc. Chim. France, 2619 (1969).
45. K . E . Wilzbach and D. J. Rausch, J. Amer. Chem. Soc., 92, 2178 (1970).
46. J . A . Barltrop, K. Dawes, A. C. Day, and A. J. Summers, J. Amer. Chem. Soc., 9_.55,2406 (1973).
47. M. Shiozaki and M. Hiraoka, Tetrahedron Lett., 4655 (1972).
48. C.H. Krauch, J. Kuhls, and H. J. Pick, Tetrahedron Lett., 4043 (1966).
49. Y. Huseya, A. Chinone, and M. Ohta, Bull. Chem. Soc. Japan, 4_~4,1667 (1971).
50. M. M~frky, H. J. Hansen, and H. Schmid, Helv. Chim. Acta, 5_.~4,1275 (1971).
51. C.S. Angadiyavar and M. V. George, J. Org. Chem., 3__6.6, 1589 (1971).
52. H. Gotthardt and F. Reiter, Tetrahedron Lett., 2749 (1971).
53. H. Kato, F. Shiba, and H. Joshida, Chem. Commun., 1591 (1970).
54. H. Kato, T. Shiba, and J. Miki, Chem. Commun., 498 (1972).
55. H. Kato, M. Kawamura, and T. Shiba, Chem. Commun., 959 (1970).
56. H. Gotthardt, Ber., 105, 188 (1972).
57. A. Chinone, J. Husseya, and M. Ohta, Bull. Chem. Soc. Japan, 4..~3,2650 (1970).
58. R . M . Moriarty, R. Mukherjee, O. L. Chapman, and D. R. Eckroth, Tetrahedron Left., 397 (1971).
59. A.Hohn, N. Harrit, H. Bechgardt, O. Buchardt, and S. E. Harnung, Chem. Commun., 1125 (1972).
60. S. MacGlynn, T. Adzumi, and M. Kinosita, Molecular Spectroscopy of the Triplet State, P r e n t i c e - H a l l
(1969).
61. D.A. Bochvar and A. A. Bagatur'yants, Teor. i ]~ksperim. Khim., 5, 19 (1969).
62. J. Streith and J. M. Cassal, Angew. Chem., Intern. Ed., 7, 129 (1968).
63. J. Streith and J. M. Cassal, Tetrahedron Lett., 4541 (1968).
64. J. Streith, A. Blind, J. M. Cassal, and C. Sigwalt, Bull. Soc. Chim. France, 949 (1969).
65. T. Sasaki, K. Kanematsu, and A. Kakehi, Chem. Commun., 432 (1969).
66. B. Snieckus, Chem. Commun., 831 (1969).
67. J. Streith and J. M. Cassal, Bull. Soc. Chim. France, 2175 (1969).
68. T. Sasaki, K. Kanematsu, A. Kakehi, J. Ichikawa, and K. Hayakawa, J. Org. Chem., 3_~5,426 (1970).
69. A. Balasubramanian, J. M. McIntosh, and V. Snieckus, J. Org. Chem., 3__55,433 (1970).
70. T. Shiba, K. Yamane, and H. Kato, Chem. Commun., 1592 (1970).
71. J. Streith, J. P. Luttringer, and M. Nastasi, J. Org. Chem., 3_~6,2962 (1971).
72. R. Gleiter, D. Schmidt, and J. Streith, Helv. Chim. Acta, 54, 1645 (1971).
73. V. Snieckus andG. Kan, Chem. Commun., 172 (1970).
74. K . T . Potts and R. Dugas, Chem. Commun., 732 (1970).
75. C.W. Bird and D. J. Wong, Tetrahedron Lett., 3187 (1971).
76: H . J . Timpe and H. G. O. Becker~ J. Prakt. Chem., 314, 325 (1972).
77. J . M . Dunstan and P. Yates, Tetrahedron Lett., 505 (1964).
78. E . F . Ullmann and J. E. Mills, J. Amer. Chem. Soc., 86, 3814 (1964).
79. E . F . Ullmann and W. A. Henderson, J. Amer. Chem. Soc., 8_~8,4942 (1966).
80. J . L . R . Williams, S. K. Webster, and J. A. Van Allan, J. Org. Chem., 2.~6,4893 (1961).
81. D.G. Whitten and M. T. McCall, J. Amer. Chem. Soc., 9_~1,5097 (1969).
82. H. Gffsten and D. Schulte-Frohlinde, Ber., 104, 402 (1971).
83. F. Andreani, R. Andrisano, and M. Tramontini, J. Heterocycl. Chem., 4, 171 (1967).
84. J . L . R . Williams; J. M. Carlson, J. A. Reynold, and R. E. Adel, J. Org. Chem., 21.8, 1317 (1963).
85. C . K . Bradsher, L. E. Beavers, and J. H. Jones, J Org. Chem., 22, 1740 (1957).
86. W . J . Tomlinson, E. A. Chandross, R. L. Fork, C. A. Pryde, and A. A. Lamola, Appl. Optics, 1_!1,533
(1972).
87. J . W . Happ, M. T. McCall, and D. G. Whitten, J. Amer. Chem. Soc., 93, 5496 (1971).
88. S . F . I~elson and P. J. Hintz, J. Amer. Chem. Soc., 91, 6190 (1969).
89. A.N. Nesmeyanov, V. A. Sazonova, V. E. Fedorov, and S. A. Busev, Dokl. Akad. Nauk SSSR, 204,
616 (1972).
90. H. McIlwain, J. Chem. Soc., 1704 (1937).
91. M . E . Flood, R. B. Herbert, and F. G. Hoolliman, Tetrahedron Lett., 4101 (1970).
92. M. Nastas[ and I. Streith, Bull. Soc. Chim. France, 630 (1973).

392
EFFECT OF STRUCTURAL FACTORS ON THE
DISINTEGRATION OF THE MOLECULAR IONS OF
NITROPHENYLISOXAZOLES DURING ELECTRON
IMPACT

K. K. Zhigulev, R. A. Khmel'nitskii UDC 547.786.2 : 543.51

S. D. Sokolov, and N. M. Przheval'skii

The dissociative ionization of some nitrophenylisoxazoles was investigated. The effect of the
e n e r g y of the ionizing e l e c t r o n s and the t e m p e r a t u r e of the inlet s y s t e m on the elimination of
NO by the m o l e c u l a r ion is examined. On the basis of a c o m p a r i s o n of the intensities of the
peaks of the (M-NO) + ions, the p r e s e n c e of a c o r r e l a t i o n between the probability of detach-
ment of NO from the m o l e c u l a r ion and the stability of the cyclic conjugated s t r u c t u r e s with
localization of the c h a r g e on the oxygen atom is d e m o n s t r a t e d .

A r o m a t i c nitro compounds have quite frequently been c o n s i d e r e d as subjects for an investigation of

the effect of e l e c t r o n i c and s t e r i c factors on the i s o m e r i z a t i o n of the m o l e c u l a r ion and its behavior in the
f i r s t steps of dissociative ionization [1-6]. The p r e s e n c e of a nitro group in the molecule leads to the ap-
p e a r a n c e of a n u m b e r of specific ions - ( M - N O 2 ) + , ( M - N O ) + ( M - O ) + , (M-NO2H) + (M-OH) + and (M-H20) + -
among which the (M-NO) + f r a g m e n t s a s s o c i a t e d with the formation of a r e a r r a n g e d m o l e c u l a r ion [2] are
of p a r t i c u l a r interest.
In the p r e s e n t r e s e a r c h we continued our investigation of the effect of s t r u c t u r a l factors on the dis-
sociative ionization of isoxazoles [7-11]. The m a s s s p e c t r a of p - n i t r o p h e n y l i s o x a z o l e s I - I I I were studied.

I II III

The m a s s s p e c t r a of these compounds were obtained with a modified MKh-1303 s p e c t r o m e t e r at ion-

i z i n g - e l e c t r o n e n e r g i e s of 50 (Table 1), 30, 20, 15, and 12 eV, an e m i s s i o n c u r r e n t of 1.5 mA, and a c c e l e r -
ating voltage of 2 kV, and an i n l e t - s y s t e m and i o n - s o u r c e t e m p e r a t u r e of 250~
In the elimination of NO f r o m the m o l e c u l a r ions of I-III, one may expect the formation of cyclic con-
jugated s t r u c t u r e s , A, B, and C with localization of the charge on the oxygen atom.

+ +
A B C

.E~=6~~ ~ e~3=6C~~ , ,E~=6CC~247 I~~

S t r u c t u r e s A, B, and C are nonequivalent with r e s p e c t to t h e i r e n e r g i e s . The probability of t h e i r

f o r m a t i o n and, consequently, the intensity of the peaks of the (M-NO) + ions should t h e r e f o r e differ for
I-IlI. An idea r e g a r d i n g the relative stabilities of s t r u c t u r e s A, B, and C can be obtained by comparing
the intensities of the peaks of the (M-NO) + ions that a r i s e at low i o n i z i n g - e l e c t r o n e n e r g i e s , where the

K. A. T i m i r y a z e v Moscow A g r i c u l t u r a l Academy. T r a n s l a t e d from Khimiya Geterotsiklicheskikh

Soedinenii, No. 4, pp. 453-456, April, 1974. Original article submitted N o v e m b e r 28, 1972.

9 19 75 Plenum Publishing Corporation, 22 7 West 1 7th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

393
 T A B L E 1. M a s s S p e c t r a of N i t r o p h e n y l i s o x a z o l e s I - I l l O b t a i n e d at
E l e c t r o n E n e r g i e s of 50 e V
I 39 (t3,2), 42 (6,1), 50 (34,2), 51 (14,8), 62 (14,0), 63 (27,7), 64 (6,1), 74 (ll,b),
75 (30,31, 76 (29,5), 77 (11,6), 87 (5,4), 88 (lO,1), 89 (68,0), 90 (13,2), 102 (15,5),
ll5 (7,1), 116 (16,0), 132 (lO,1), 143 (31,0), 144 (9,5), 148 (5,9), 162 (11,6), 174
(5,4), 189 (96,7), 190 (100,0), 191 (11,8)
II 39 (18,71, 40 (9,3), 41 (5,51, 43 (8,8), 45 (9,5), 50 (43,71, 51 (20,2), 52 (11,8),
62 (14,0), 63 (34A), 64 (9,7), 65 (8,91, 68 (11,2), 74 (15,61, 75 (28,01, 76 (48,31,
77 (25,0), 73 (5,3), 88 (6,7), 89 (84,5), 90 (9,5), 90 (9,5), 92 (23,2), 102_ (5,7),
104 (35,81, 116 (10,3), 117 (7,41, 120 (22,0), 132 (26,6), 144 (7,61, 150 (41,01,
160 (38,1), 189 (13,3), 190 (100,0), 191 (11,2)
III 39 (26,4), 40 (19,51, 41 (19,51, 42 (11,71, 43 (t00,01, 50 (t4,7), 51 (25,4), 52 (11,7),
53 (7,8), 55 (10,7), 62 (19,51, 63 (27,4), 64 (13,7), 65 (14,6), 74 (7,8), 75 (16,61,
77 (58,5), 78 (15,6), 87 (11,71, 88 (22,4), 89 (21,51, 90 (7,8), 91 (42,01, 92 (7,81,
101 (9,8), 102 (23A), 103 (53,7), 104 (26,4), 105 (10,71, 114 (9,81, 115 (9,81,
117 (11,7), 118 (29,3), 119 (75,5), 120 (9,8), 128 (7,8), 129 (17,5), 130 (25,4),
131 (11,7), 134 (9,8), 144 (7:8), 145 (14,6), 146 (14,6), 157 (9,8), 172 (14,6),
175 (17,6), 188 (58,5), 189 (10,7), 203 (18,0), 218 (100,0), 219 (14,6)

T A B L E 2. I n t e n s i t i e s of t h e Ion P e a k s in the M a s s S p e c t r a of
p-Nitrophenylisoxazole s

Energy, Compound
eV Ill

I (M- NO) +liar,- 100% 50 4,4 38,1 43,0

12 5,5 22,1 117,2
E'l i/Eli" 100% 50 1t,4 15.7 19,5
Mass numbers of the ions whose 160 160 188, 146
intensities enter into Z'Ii 132 132 119, 118
89 89 104, 103
102

r o l e o f s e c o n d a r y d i s i n t e g r a t i o n p r o c e s s e s i s s m a l l . In t h e c o m p a r i s o n of the m a s s s p e c t r a o b t a i n e d at
r e l a t i v e l y low e l e c t r o n e n e r g i e s one m u s t t a k e into a c c o u n t the i n t e n s i t i e s of the p e a k s of t h e f r a g m e n t s
f o r m e d in the e n s u i n g s t e p s of t h e d i s i n t e g r a t i o n of t h e ( M - N O } + i o n s . The i n t e n s i t i e s of t h e p e a k s of the
( M - N O ) + ions at i o n i z i n g e l e c t r o n e n e r g i e s of 50 and 12 eV, t h e s u m s of the i n t e n s i t i e s of t h e ( M - N O ) +
i o n p e a k s , and t h e m o s t i m p o r t a n t f r a g m e n t s f o r m e d d u r i n g t h e i r d i s i n t e g r a t i o n a r e p r e s e n t e d in T a b l e 2.
T h e m a s s n u m b e r s of the ions w h o s e p e a k i n t e n s i t i e s a r e s u m m a r i z e d a r e p r e s e n t e d in the l a s t line of
T a b l e 2.

It f o l l o w s f r o m the r e s u l t s o b t a i n e d t h a t t h e p r o b a b i l i t y of t h e d i s i n t e g r a t i o n M + ~ ( M - N O ) + i n c r e a s e s
in t h e o r d e r I <II < I I I . W h e n t h e r e is a c o r r e l a t i o n b e t w e e n the s t a b i l i t y of t h e ( M - N O ) + i o n s and t h e p r o b -
a b i l i t y of t h e i r f o r m a t i o n , t h e a b o v e s i g n i f i e s t h a t E A < E B < EC, w h e r e E i s t h e e l e c t r o n e n e r g y of t h e s t r u c -
ture.

T h e h i g h e r s t a b i l i t y of s t r u c t u r e C a s c o m p a r e d w i t h A and B a l s o f o l l o w s f r o m an e x a m i n a t i o n of
the e f f e c t of t h e i o n i z i n g - e l e c t r o n e n e r g y on t h e I ( M - N O ) + / I M + r a t i o .
A v e r y p r o n o u n c e d i n c r e a s e in t h i s r a t i o a s t h e i o n i z i n g - e l e c t r o n e n e r g y is r e d u c e d f r o m 50 to 12 eV
is o b s e r v e d o n l y in the c a s e of III. It t h e r e f o r e f o l l o w s t h a t the e n e r g y of a c t i v a t i o n of t h e p r o c e s s u n d e r
c o n s i d e r a t i o n i s low in the c a s e o f III a s c o m p a r e d w i t h t h a t f o r I and II.

We i n v e s t i g a t e d t h e e f f e c t of the i o n i z i n g e l e c t r o n e n e r g y and t h e i n l e t - s y s t e m t e m p e r a t u r e on t h e
p r o b a b i l i t y o f e l i m i n a t i o n of NO by the m o l e c u l a r ion of HI o v e r a r e l a t i v e l y wide r a n g e of v a l u e s o f the
i n d i c a t e d p a r a m e t e r s ( F i g s . 1 and 2). It c a n be s e e n t h a t t h e I ( M - N O ) + / I M + r a t i o r e m a i n s v i r t u a l l y u n -
c h a n g e d up t o i o n i z i n g - e l e c t r o n e n e r g i e s o f 3 0 - 2 5 eV. T h e e f f e c t of t e m p e r a t u r e in t h i s i n t e r v a l i s a l s o
o n l y s l i g h t . A v e r y p r o n o u n c e d i n c r e a s e in t h e I ( M - N O ) + / I M + r a t i o is o b s e r v e d at 1 5 - 9 e V . M o r e o v e r ,
t h e e f f e c t o f t e m p e r a t u r e on t h e y i e l d of ( M - N O ) + i o n s a l s o i n c r e a s e s s h a r p l y .
On t h e b a s i s of the d a t a o b t a i n e d , it c a n be a s s u m e d t h a t t h e d i s i n t e g r a t i o n of the m o l e c u l a r ion M + ~
( M - N O ) + in t h e c a s e of III a p p a r e n t l y p r o c e e d s in t h e g r o u n d e l e c t r o n s t a t e , d u r i n g w h i c h r e t e n t i o n o f t h e
i s o x a z o l e r i n g i s an i m p o r t a n t f a c t o r t h a t d e t e r m i n e s t h e e f f e c t i v e n e s s of t h e e l i m i n a t i o n of NO. T h e p r o -
n o u n c e d d e p e n d e n c e o f t h e p r o b a b i l i t y o f the r e a l i z a t i o n o f t h i s p a t h o f d i s i n t e g r a t i o n on the t e m p e r a t u r e
i n d i c a t e s t h e i m p o r t a n c e of t h e v i b r a t i o n a l e x c i t a t i o n of t h e m o l e c u l e f o r t h e f o r m a t i o n of ( M - N O ) + i o n s .
I t s e e m e d of i n t e r e s t to c o m p a r e t h e i n t e n s i t i e s of t h e ( M - N O ) + ion p e a k s w i t h t h e v - e l e c t r o n e n -
e r g i e s (E 7r) of s t r u c t u r e s A, B, and C. F o r t h i s , we c a l c u l a t e d t h e EA 7r, EBrr , and EC 7r v a l u e s by m e a n s of
t h e MO LCAO m e t h o d w i t h i n the Hffckel a p p r o x i m a t i o n [12-14].

394
 300 I (w--~'~ 100%
qSO I (_.M-uo~)+ 100%
IM+ 250
200 t=245~ I
I 200.
150
150
100 :235+

50 S 100

50

Fig, 1 Fig. 2
Fig. 1. Dependence of the ratio of the intensities of the (M-NO) + and
M + ion peaks on the ionizing e l e c t r o n e n e r g y for two i n l e t - s y s t e m t e m -
peratures.
Fig. 2. Dependence of the ratio of the intensities of the (M-NO) + and
M + ion peaks on the i n l e t - s y s t e m t e m p e r a t u r e of the m a s s s p e c t r o m e t e r
at an i o n i z i n g - e l e c t r o n e n e r g y of 12 eV.

The r e s u l t s of the calculation show that the stability of the examined s t r u c t u r e s i n c r e a s e s in the o r d e r
A <B << C. Thus, a c o r r e l a t i o n between the intensity of the peaks and the ~r-electron e n e r g y of the fragments
of the s t r u c t u r e s of the (M-NO) + ions is observed.
This r e s u l t makes it possible to explain the interesting fact that the formation of (M-H) + ions in the
m a s s s p e c t r a of m e t h y l i s o x a z o l e s (in the absence of interaction of the adjacent groups) is o b s e r v e d only
when the methyl group is attached to the C 4 atom [15], in which case the formation of s t r u c t u r e s of the C
type is possible.
The disintegration of the m o l e c u l a r ions of I and II includes the most important features of the d i s -
sociative ionization of unsubstituted 3- and 5-phenylisoxazoles [15]. Thus, intense (M-H) + ion peaks are
p r e s e n t in the m a s s s p e c t r a of 3-phenylisoxazole and its nitro derivative (I). The formation of acyl I)hCO +
o r p-NO2C~H4CO + ions is c h a r a c t e r i s t i c for the dissociative ionization of 5-phenylisoxazole and 5 - ( p - n i t r o -
phenyl)isoxazole. M o r e o v e r , the introduction of a nitro group into the benzene ring leads to considerable
complication of the m a s s s p e c t r a . Thus, the formation of ( M - O ) +, (M-NO) +, and (M-1~O2)+ ions is ob-
s e r v e d in the dissociative ionization of I-HI.
Despite the considerable difference in the s t r u c t u r e s of i s o m e r s I and 17 a s e r i e s of peaks that c o r -
respond to the same m a s s n u m b e r s (160, 132, and 89) is p r e s e n t in t h e i r m a s s s p e c t r a . In all likelihood,
these ions are f o r m e d as a r e s u l t of the s u c c e s s i v e disintegration of the m o l e c u l a r ion:

M+-+ (M--NO) +-+ (M--NO--CO) +-+(M--NO--CO--HCNO) +.

Ions with m a s s 89, the peaks of which are distinguished by p a r t i c u l a r l y high i n t e n s i t i e s , are of con-
siderable interest. It is reasonable to a s s u m e that the conditions for the realization of the reaction M +-*
( M - N O - C O - H C N O ) + should e n s u r e the effective formation of ions with m a s s 89 in the case of both i s o m e r s

~N02 ~0//~?

mfe 132
m/e 190 [M__N OI+
"~'~r ,,,/e 160 m,/z 89

NO2 mile 132

m/e 190

395
 II and III. It is seen from the disintegration schemes presented above that the probable structures of ions with
mass 132 are favorable from the point of view of the possibility of their disintegration andthe formation of ions
with mass 89.
Taking into account the high intensities of the peaks of these ions, one should note the possibility of
their additional stabilization due to rearrangement to the dehydrotropylium structure.

LITERATURE CITED
1. J . H . Beynon, R. A. Saunders, and A. E. Williams, Ins. Chim. Belge, 311 (1964}.
2. M . M . Bursey and F. W. McLafferty, J. Amer. Chem. Soc., 88, 5023 (1966).
3. M . M . Bursey, Org. Mass Spectrometry, 1, 31 (1968).
4. G.H. Lord and B. J. Millard, Org. Mass Spectrometry, 2, 547 (1969).
5. R . H . Shapiro and J. W. Serum, Org. Mass Spectrometry, 2, 533 (1969).
6. R . T . Aplin, M. Fischer, D. Becher, H. Budzikiewicz, and C. Djerassi, J. Amer. Chem. Soc., 87, 4888
(1965).
7. R.A. Khmel'nitskii, K, K. Zhigqlev, S. D. Sokolov, and L. P. Tsurkanova, Zh. Organ. Khim., 6, 2162
(1970).
8. R.A. Khmel'nitskii, K. K. Zhigulev, and S. D. Sokolov,Izv. Timiryazev. Sel'skokhoz. Akad., 197 (1971).
9. K.K. Zhigulev, R. A. Khmel'nitskii, and S. D. Sokolov, Khim. Geterotsikl. Soedin , 737 (1971).
10. K.K. Zhigulev, R. A. Khmel'nitskii, M. A. Panina, I. I. Gradberg, and B. M. Zolotarev, Khim. Get-
erotsikl. Soedin., 889 (1972).
11. K.K. Zhigulev, S. D. Sokolov, and R. A. Khmel'nitskii, Khim. Geterotsikl. Soedin., 1336 (1972).
12. A. Streitwieser, Molecular Orbital Theory for Organic Chemists, Wiley (1961).
13. B. Pullman and A. Pullman, Rev. Mod. Phys., 32, 428 (1960).
14. D.A. Bochvar, A. A. Bagatur'yants, and A. V. Turkevich, Izv. Akad. Nauk SSSR, 353 (1966).
15. J. Bowie, R. K. KaUury, and R. C. Cooks, Austral. J. Chem., 22, 3 (1969).

396
THERMAL ISOMERIZATION OF THE ISOXAZOLE
RING AND REARRANGEMENT PROCESSES IN THE MASS
SPECTRA OF 3-ARYL-5-METHYLISOXAZOLE-4-CARBOXYLIC
ACIDS

K. K. Zhigulev, R. A. Khmel'nitskii, UDC 547.786.2: 542.952:543.5

and M. A. Panina

The m a s s s p e c t r a of 15 compounds of 3 - a r y l - 5 - m e t h y l i s o x a z o l e - 4 - o a r b o x y l i c acid and t h e i r

derivatives were investigated. T h e r m a l i s o m e r i z a t i o n of the isoxazole ring was observed for
s e v e r a l derivatives of this s e r i e s . The formation of r e a r r a n g e d pseudomolecular ions of the
a r y l a m i n e s during the dissociative ionization of 3 - a r y l - 5 - m e t h y l i s o x a z o l e - 4 - c a r b o x y l i e acids
was examined on the b a s i s of a study of the m a s s s p e c t r a of labeled compounds. It is a s s u m e d
that t h e r e is a high probability of c o n c e r t e d elimination of s e v e r a l groups in the first step of
the disintegration of the m o l e c u l a r ion.

We have p r e v i o u s l y examined ill the m a s s s p e c t r o m e t r y of some 3 - a r y l - 5 - m e t h y l i s o x a z o l e - 4 - c a r -

boxylic acids. The p r e s e n t p a p e r is devoted to a study of the effect of s t r u c t u r a l factors on the c h a r a c t e r
of the disintegration of the m o l e c u l a r ion in this s e r i e s of compounds. The m a s s s p e c t r a of 15 compounds
of 3 - a r y l - 5 - m e t h y l i s o x a z o l e - 4 - c a r b o x y l i c acid and t h e i r derivatives (I-XV) were investigated. The m a s s
s p e c t r a were obtained with a Varian MAT-CH-6 s p e c t r o m e t e r at an i o n i z i n g - e l e c t r o n e n e r g y of 70 eV and
an i o n i z a t i o n - c h a m b e r t e m p e r a t u r e of 180~

I-XY

R' R2 R3 R' R: R3

] OIl H H IX Nt~2 2-C1 H

II OH 3-NOz H X OCHs 2-Ct 6-CI
III OH 3-XH2 bI XI OD H H
IV OH 4-N=CHC6H4=2-OH H XII OD 3-NO~ H
V OH 2-C1 H XIII OD 3-ND2 H
VI OH 2-C1 6-C1 XIV OD 2-C1 H
VII OC2Hs H H XV OD 2-C1 6-C1
VIII OCH3 2-CI H

The dissociative ionization of I-XV p r o c e e d s s i m i l a r l y in many r e s p e c t s . The principal paths of

disintegration are a s s o c i a t e d with the formation of acetyl ions with m a s s 43 and [0ns with m a s s 143 + m
(R2, R3). * Peaks of (M-CH3) + ions are also observed in all of the m a s s spectra, but t h e i r intensity is v e r y
low. An important p e c u l i a r i t y of the disintegration of the m o l e c u l a r ions of the acids is the formation of
(M-CO2)+ ions.
The e x p r e s s i o n m(R 2, R 3) is the sum of the m a s s e s of the c o r r e s p o n d i n g R 2 and R 3 r a d i c a l s .

K. A. T i m i r y a z e v Moscow A g r i c u l t u r a l Academy. T r a n s l a t e d from Khimiya Geterotsiklieheskikh

Soedinenii, No. 4, pp. 457-460, April, t974. Original article submitted N o v e m b e r 28, 1972.

9 19 75Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

397
TABLE 1. Effect of Substitution in the The elimination of CO 2 m a y p r o c e e d with both the
Benzene Ring on+the Relative Intensity of participation of the oxygen atom of the c a r b o n y l group
R 2, R3-C6H3-1~H2 Ions through a s i x - m e m b e r e d t r a n s i t i o n state and with the p a r -
.+
ticipation of a nitrogen atom through a f i v e - m e m b e r e d
R2,R3-C6H3-NH., li,'Xli 9 1(30% lid~3. 100% t r a n s i t i o n state. Ohashi and c o - w o r k e r s [2] have p r o p o s e d
a s c h e m e including a s i x - m e m b e r e d t r a n s i t i o n state.

6,3 52,2
lA,_c.~l+-c,, r,/C~~
CI cH3.]~.o.~} r~ ~ ca3co
4,2 43,2

+' -Crla II--~c -cli2c~

c~nh~ 4,9 39,0
H--O--ilij N " CH3

However, our investigation of the m a s s s p e c t r a of labeled

nn~ ~h~ 1,5 23,4 compounds showed that the hydrogen atom can also m i -
grate to the nitrogen a t o m .
0,6 2,4 This conclusion follows f r o m the detection in the
m a s s s p e c t r a of 3 - a r y l - 5 - m e t h y l i s o x a z o l e - 4 - e a r b o x y l i c
acids of peaks with m a s s 91 +m(R2,+R3). Two s t r u c t u r e s -
R 2, R 3 - C 6 H 3 - O + and R 2, R 3 - C 6 H 3 - N H 2 - a r e probable
for these ions. An examination of the m a s s s p e c t r a of the deutero analogs of the acids shows that ions with
m a s s 91 + m(R 2, R 3) in the m a s s s p e c t r a of the nondeuterated compounds fully contain the hydrogen of a
c a r b o x y l group. Thus, the s t r u c t u r e of ions with m a s s 91 +m(R 2, R 3) should c o r r e s p o n d to the s t r u c t u r e of
the p s e u d o m o l e c u l a r ions of aniline o r the c o r r e s p o n d i n g a r o m a t i c a m i n e s . It is i n t e r e s t i n g to note that the
f o r m a t i o n of R 2, R 3 - C 6 H 3 - N ~ 2 ions should o c c u r as a r e s u l t of t h r e e s u c c e s s i v e m i g r a t i o n s of two h y d r o -
gen a t o m s and of an r._--yl radical.
The f o r m a t i o n of R2,R3-C~H3-1~2 ions is not o b s e r v e d for the acid d e r i v a t i v e s . The intensities of
the peaks of the R2,R3-C6H3-1~H 2 ions with r e s p e c t to the total ion c u r r e n t and the intensities of the CH3CO +
ion peak a r e p r e s e n t e d in Table 1. It follows f r o m t h e s e data that substitution of the hydrogen a t o m in the
ortho position of the benzene ring by a chlorine atom l o w e r s the p r o b a b i l i t y of m i g r a t i o n as c o m p a r e d with
a phenyl substituent only to a slight d e g r e e . The halogen atom in the t r a n s i t i o n state probably p a r t i a l l y
c o m p e n s a t e s for the n e g a t i v e - I effect through the +M effect. The f o r m a t i o n of ions with m a s s 91 +m(R2,R 3)
in the m a s s s p e c t r u m of X shows that the C 1 atom of the benzene ring u n d e r g o e s attack on the nitrogen atom
side.
The M - N O 2 and M - N H 2 groups can only f o r m a l l y m a n i f e s t a - I effect. As one should have expected,
p a r t i c u l a r l y pronounced inhibition of the r e a c t i o n is o b s e r v e d when R = N O 2.

t:d3 O / ~R3 It
C +./ft
-CO2~ ~C~I - ~C=C{Y \D -C'H20 "\/N-~//+'/7-r
o~C~ , c/ \~+. 2 I/-:-~ ~ - ~ D ~'r~

As shown by Nishiwaki [3, 4], isoxazole d e r i v a t i v e s containing RO, RS, and NH 2 groups attached to the
C a atom a r e capable of undergoing t h e r m a l valence i s o m e r i z a t i o n to 1 - a z i r i n e d e r i v a t i v e s . In the r e c o r d -
ing of the m a s s s p e c t r a of m e t h y l e s t e r VIE and amide IX of 5 - m e t h y l - 3 - ( 2 , - c h l o r o p h e n y l ) i s o x a z o l e - 4 - c a r -
boxylic acid with an MKh-1303 s p e c t r o m e t e r at an i n p u t - s y s t e m t e m p e r a t u r e of 250 ~ we o b s e r v e d a change
in the intensities of the p e a k s with t i m e ; this indicated some s o r t of t r a n s f o r m a t i o n of the substance in-
t r o d u c e d into the s p e c t r o m e t e r .
A s t e a d y - s t a t e distribution of the intensities of the peaks, which c o r r e s p o n d s to t r a n s f o r m a t i o n p r o -
duct VIIIa or IXa, was e s t a b l i s h e d 40 m i n a f t e r introduction of the s a m p l e . The intensities of the p e a k s of
some of the ions in the m a s s s p e c t r a of VIII, VIIIa, IX, and IXa a r e p r e s e n t e d in Table 2. All of the values
w e r e taken in p e r c e n t with r e s p e c t to the intensity of the ( M - C I ) + ion p e a k in the m a s s s p e c t r a of VIII o r
IX, r e s p e c t i v e l y . It follows f r o m an e x a m i n a t i o n of the data in Table 2 that the (M-C1) + ion peak is a l m o s t
c o m p l e t e l y absent in the s p e c t r a of VIIIa and IXa, while the intensity of the m o l e c u l a r ion peak i n c r e a s e s
on the a v e r a g e by a f a c t o r of two. Consequently, the change in the m a s s s p e c t r a with t i m e is due to i s o m e r -

398
 TABLE 2. Relative I n t e n s i t i e s of the Peaks of Some Ions in the M a s s
S p e c t r a of Methyl E s t e r VIII and Amide IX of 3 - ( 2 ' - c h l o r o p h e n y l ) - 5 -
m e t h y l i s o x a z o l e - 4 - c a r b o x y l i c Acid and T h e i r I s o m e r i z a t i o n P r o d u c t s
(VIIIa and IXa)
Compound
Ions
VIII VIIIa [ IX IXa

M+ 7,0 11,3 7,4 17,1

(M--R') + 5,3 5,7 10,4 23,2
(M--CI) + 100,0 o lOO,O 0
(M--RI-A2H~CO) + 27,0 3,6 19,7 4,0
CHACO+ 51,0 44,3 42,4 31,8

ization of s t a r t i n g m a t e r i a l s VIII o r IX, which leads to d i s r u p -

100 ;>,,, tion of the a r o m a t i c s t r u c t u r e of the isoxazole ring. The in-
.? c r e a s e in the intensity of the m o l e c u l a r peak is a r e s u l t of the
80, a b s e n c e of the disintegration M + ~ (M-C1)+; this is due to the
(P'4-c[ )4- i~ O i m p o s s i b i l i t y of the f o r m a t i o n of the a r o m a t i c s t r u c t u r e of the
60
p y r y l i u m cation.
40
12
20 _c~o _c//~

9 9 -//- /I ,o~.,,~
,b zb s'o t,min
[~;-cz]+ (~00.o) ~, [M-c,] + (o.o)
Fig. 1. Dependence of the intensity
The t i m e r e q u i r e d f o r the c o n v e r s i o n I X - * I X a at an inlet
of the M + and (M-C1) + ion p e a k s on
t e m p e r a t u r e of 250 ~ is 35-40 m i n (Fig. 1).
t i m e in the m a s s s p e c t r u m of 3 - ( 2 ' -
chlorophenyl)- 5-methylisoxazole-4- As s e e n f r o m the data in Table 2, the absence of the p r o -
carboxamide. c e s s M +-* (M--C1) +, which is linked to the d i s s o c i a t i o n of a con=
s i d e r a b l e f r a c t i o n of the m o l e c u l a r ions, leads to an a p p r e c i -
able i n c r e a s e in the p r o b a b i l i t y of d i s i n t e g r a t i o n v i a the path M +-* ( M - R I ) +. In addition, the probability of
the p r o c e s s M + ~ ( M - R I - C H 2 C O ) + d e c r e a s e s with unexpected s h a r p n e s s . This fact can be explained by
taking into account the possible t r a n s i t i o n states of the r e a c t i o n to f o r m the ( M - R i - C H 2 C O ) + ions for VIII,
IX, and VIIIa, IXa.
In the c a s e of isexazole d e r i v a t i v e s , the p r o b a b i l i t y of c o n c e r t e d detachment of R 1 and CH2CO is c o n -
s i d e r a b l y higher than the p r o b a b i l i t y of this p r o c e s s for the i s o m e r i c a z i r i n e owing to the q u a s i p l a n a r
configuration of the s t a r t i n g state. In o t h e r words, the c o n c e r t e d p r o c e s s

/
~__ o / c + /i(-R',-CH~CO +.o~C'-~---~
" " - " H--O=C'==Q..]I ,/~ i[ II
~N L'r"C tt2""~O-N
O//'~H 3 CH3J\~.) [M__RI__CH2CO]+ ,

M + ~ ( M - R i - C H 2 C O ) + should be c h a r a c t e r i z e d by a l o w e r (in absolute value) value of the activation e n t r o p y

(ASS< 0) f o r d i s i n t e g r a t i o n of the m o l e c u l a r ions of isoxazole d e r i v a t i v e s . Thus, it can be a s s u m e d that the
m e c h a n i s m of c o n c e r t e d d e t a c h m e n t of R i and CH2CO groups p l a y s a significant role in the f o r m a t i o n of
( M - R 1 - C H 2 C O ) ions.

LITERATURE CITED
It K. K. Zhigulev, R. A. K h m e l ' n i t s k i i , M. A. Panina, I. I. G r a n d b e r g , and B. M. Z o l o t a r e v , Khim. G e t -
e r o t s i k l . Soedin., 889 (1972).
2. M. Ohashi, H. K a m a c h i , H. Kakisawa, A. T a t e m a t s u , H. Y o s h i r i m i , H. Kano, and H. Nakata, Org.
M a s s S p e c t r o m e t r y , 2, 195 (1969).
3. T. Nishiwaki, T e t r a h e d r o n Lett., 2049 (1969).
4. T. Nishiwaki, C h e m . Commun., 945 (1970).

399
 S Y N T H E S I S AND S T U D Y O F T H E L U M I N E S C E N C E
PROPERTIES OF ANHYDRIDES AND N - P H E N Y L I M I D E S
OF 4- (2-ARYL-1,3,4-OXADIA ZOL- 5-YL)NA PHTHALIC
ACIDS

S. E. K o v a l e v , B . M. K r a s o v i t s k i i , UDC 547.793.4'816.836.3.07:542.953
a n d N. A. P o p o v a

4-(2-Aryl-l,3,4-oxadiazol-5-yl)naphthalic anhydrides were obtained by condensation of 4-

chlorocarbonylnaphthalie anhydride with monohydrazides of substituted benzoic acids and
subsequent cyclodehydration; the corresponding N-phenylimides were obtained from the
4-(2-aryl-l,3,4-oxadiazol-5-yl)naphthalic anhydrides. The UV and luminescence spectra are
presented.

We recently [1] described 4-(2-phenyl-l,3,4-oxadiazol-5-yl)naphthalic anhydride (Ia), which lumin-

esces in toluene in the violet region of the spectrum. The subject of the present communication is the syn-
thesis and investigation of the optical properties of phenyl-substituted anhydrides (I) and the correspond-
ing N-phenylimides (II).
Anhydrides I were synthesized by condensation of monohydrazides of substituted benzoic acids with
4-chlorocarbonylnaphthalic anhydride and subsequent cyclodehydration of the unsymmetrical N,N'-diaroyl-
hydrazines by heating them with phosphorus oxychloride:

P"RC6H~CONHNH~+ C I o c ~ C ~ : ~ p. RC6H4CONtiNHOC--~/ - - ~ C~oZO

~"
cJ
%

POC|3
~ . ~ ~ ~o / \ / \ -%
~ - ~o
! t!

I, ll a R=H; b R=Cl; c R=NO2; d R=C.a; e R=OCHa; f R=N(CH3) 2

The corresponding N-phenylimides (IIa-f) were obtained by condensation of I with aniline.
The absorption spectra of naphthalic anhydride and Ia at 300-500 nm consist of broad bands with vi-
brational structures in the vicinity of the absorption maxima. The introduction of a phenyloxadiazolyl r e s i -
due into the 4-position of the naphthalic anhydride causes a c o n s i d e r a b l e shift in the absorption maximum
(~35 nm) to the long-wave region of the spectrum and i n c r e a s e s the absorption intensity.
It is known that the oxadiazole ring in diaryloxadiazole molecules in both the ground state and the
excited states has an electron-acceptor effect, which is intensified in the excited state [2, 3]. This effect
leads to a decrease in the electronic interaction of the phenyl and naphthalic anhydride portions of the mole-
cule and is reflected in the shift of the absorption spectrum of phenyl0xadiazolylnaphthalic anhydride to the
short-wave region (~20 rim) as compared with its phenyloxazolyl analog [1], for which the el eet ron-a e e e p to r
properties of the heterocyclic grouping in the excited state show up to a l e s s e r extent [3].
All-Union Scientific-Research Institute of Single Crystals, Scintillation Materials, and E x t r e m e l y P u r e
Chemical Substances, Kharkov. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 461-
463, April, 1974. Original article submitted January 2, 1973.

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy of this article is available from the publisher for $15.00.

400
 TABLE 1. Anhydrides and Phenylimides of Aryloxadiazolylnaph-
thalic Acids

} rap, *C
Empirical
formula
N, %

s
Absorption

calc.[~. . . . nm[ lg~

Luminescence

nine'max' 11 ~.~
P
la i365, 385e 4,30 425 0,14
Ib H1 200(dec.)a C2oHgN204CI 7,8 7,4 365, 385e' -- 425 Weak
][um.
Ic NO2 350b C2oHgN306 0,7 10,8 865, 385e !2L
Id CH3 259a C~IHI2N204 7,9 7,9 365 ] 4,3-~ OE4 5 8
Ie OCH3 254 a C21HI~N205 7,3 7,5 3?5 4,35 453 0,29 67
If N(CHJ2 l~0(dee. )( C2~HIsN304 ,1,2 10,9/320, 425 4,44; 4J5 4i0 0,31 48
IIa 288a C26HIsN3Oa 0,4 10,11365, 385 4,43 434i 590 Weak 70
lure.
IIc NO2 265a C26H14N4Os 2,0 19i13%385 4,32; 4,24 50
IId CH3 254a C27HIvN3Os 9,8 9,71 4,4,11 43'0 Wea-k 67
lurn.
IIe OCH3 252d C27HITN304 9,0 455 0,12 5o
IIf N (CH3)2 I00(dec.)c C28H2oN40~ ~2,2 320, 415 4,38; 4,221 565 0,23 171

a)From acetic anhydride, b) F r o m aqueous d i m e t h y l f o r m a m i d e .

c) F r o m ethanol, d) F r o m xylene, e) Inflection.

O n e ' s attention is drawn to the inflection in the long-wave portion of the curve for I, which gradually
vanishes as e l e c t r o n - d o n o r substituents with i n c r e a s i n g e l e c t r o n - d o n o r p r o p e r t i e s are introduced but which,
on the other hand, is displayed m o r e distinctly when e l e c t r o n - a c e e p t o r substituents are introduced.* The
s p e c t r a of m e t h y l - (Id), c h l o r o - fib), and n i t r o - s u b s t i t u t e d (Ic) compounds do not differ f r o m the s p e c t r u m
of Ia with r e s p e c t to the position of the chief m a x i m u m ; a s m a l l bathochromic effect ('-q0 nm) is observed
when a methoxy group is introduced. The s p e c t r u m of If is c o n s i d e r a b l y complicated. In addition to the
band this is also p r e s e n t in the s p e c t r a of the o t h e r derivatives but shifted to the s h o r t - w a v e region (Xmax
320 nm); t h e r e is a long-wave band (kmax 425 nm), which is apparently a c h a r g e - t r a n s f e r band and is due
to the e l e c t r o n i c interaction of the dimethylamino and carbonyl groups at the ends of the conjugation chain.
The luminescence s p e c t r a of I which are r e p r e s e n t e d by a s t r u c t u r e l e s s band differ little in c h a r -
a c t e r from one another. The e l e c t r o n i c nature of the substituents introduced into the phenyl ring of the
luminescing compounds affects the magnitude of the long-wave shift of the luminescence m a x i m u m , and
the Stokesian shift i n c r e a s e s c o n s i d e r a b l y as the e l e c t r o n - d o n o r p r o p e r t i e s of the substituents i n c r e a s e .
The introduction of e l e c t r o n - d o n o r substituents doubles the luminescence quantum yield. The nitro d e r i v -
ative (Ic) has p r a c t i c a l l y no luminescence in e i t h e r toluene or in the c r y s t a l l i n e state; the chloro derivative
fib) also has v e r y weak luminescence.
The absorption s p e c t r a of toluene solutions of N-phenylimides of aryloxadiazolylnaphthalic acids are
p r a c t i c a l l y the same as the s p e c t r a of the anhydrides f r o m which they were obtained. However, the phenyl-
imides have less intense luminescence than the anhydrides.

EXPERIMENTAL
The absorption spectra were recorded with an SF-4 spectrophotometer. The luminescence spectra
were recorded with an apparatus consisting of a ZMR-3 mirror monochromator, an F]~U-18 optical emis-
sion detector, and an M-95 microammeter; the photoluminescence was excited with an SVDSh-500 lamp,
from the spectrum of which light of wavelength 365 nm was isolated by means of a DMR-4 quartz mono-
chromator. The absolute luminescence quantum yields of toluene solutions were determined by the equal
absorption method [4].
4-[2-(4-Methoxyphenyl)-l,3,4-oxadiazol-5-yl]naphthalic Anhydride (Ie). A saturated sodium carbon-
ate solution was added with vigorous stirring to a mixture of solutions of 1.66 g (0.01 mole) of 4-methoxy-
benzhydrazide in I00 ml of 10%hydrochloric acid and 2.6 g (0.01 mole) of 4-chlorocarbonyl-l,8-naphthalic
anhydride in 50 ml of benzene until the mixture was alkaline. Stirring was then continued at room tem-
perature for 2.5 h, after which the mixture was acidified with concentrated hydrochloric acid. The result-

* Because of the low solubilities of Ib and Ic, the absorption s p e c t r a of toluene solutions of these compounds
were m e a s u r e d qualitatively.

401
 ing precipitate was r e m o v e d by filtration and washed successively with 10% sodium carbonate solution,
water, and a small amount of ethanol. The product was refluxed in 40 ml of phosphorus oxychloride for
40 min, a f t e r which the mixture was poured o v e r ice, and the precipitate was r e m o v e d by filtration and
washed with w a t e r until it gave a neutral reaction (Table 1).
A s i m i l a r p r o c e d u r e was used to obtain 4 - [ 2 - ( 4 - t o l y l ) - l , 3 , 4 - o x a d i a z o l - 5 - y l ] - and 4- [2- (4-dimethyl-
aminophenyl)-l,3,4-oxadiazol-5-yl]naphthalic anhydrides (Id and If, Table 1).
4-[2-(4-Chlorophenyl)-l,3,4-oxadiazol-5-yl]naphthalic Anhydride fib). A mixture of solutions of
equimolar amounts (0.01 mole) of 4-chlorobenzhydrazide and 4 - c h l o r o c a r b o n y l - l , 8 - n a p h t h a l i c anhydride
in pyridine was heated with s t i r r i n g for 3 h up to the boiling point, a f t e r which it was refluxed for another
hour. The reaction mixture was cooled to room t e m p e r a t u r e and poured into water. The precipitate was
removed by filtration and washed with w a t e r and ethanol. The product was refluxed for 6 h in 50 ml of
phosphorus oxychloride, a f t e r which the mixture was poured over ice, and the precipitate was removed by
filtration and washed with water until it was neutral. It was then dried and chromatographed on activity II
aluminum oxide with elution by acetone (Table 1).
A s i m i l a r p r o c e d u r e was used to obtain 4- [2- (4-nitrophenyl)-l,3,4-oxadiazol-5-yl]naphthalic anhydride
(Ic) (Table 1).
Aryloxadiazolylnaphthalic Acid Phenylimides ffla-f). A mixture of solutions of 0.01 mole of a r y l -
oxadiazolylnaphthalic anhydride and 0.1 mole of aniline in 100 ml of acetic acid was refluxed for 6 h. The
c o u r s e of the reaction was monitored by t h i n - l a y e r e d chromatography on aluminum oxide. The solvent
was evaporated to one tenth of the starting volume, and the residue was cooled. The precipitate was r e -
moved by filtration, washed s u c c e s s i v e l y with 10%hydrochloric acid, water, and a small amount of ethanol,
dried, chromatographed on activity II aluminum oxide (elution with acetone), and c r y s t a l l i z e d (Table 1).

LITERATURE CITED
I. B. iV[.Krasovitskii, S. E. Kovalev, and E. A. Shevchenko, USSR Author,s Certificate No. 327,226; Byul.
Izobr., No. 5 (1972).
2. A . E . Lutskii, A. V. Shepel', O. P. Shvaika, and G. P. Klimisha, Khim. Geterotsikl. Soedin., 461 (1969).
3. L . M . Kutsyna, N. Ya. Makovetskii, and A. V. Shepel', in: Single C r y s t a l s , Scintillators, and Organic
Luminophores [in Russian], No. 4, Kharkov (1968), p. 94.
4. A . S . Cherkasov, Zh. Fiz. Khim., 29, 2209 (1955).

402
 RESEARCH ON THE CHEMISTRY OF PHENOXAZINES
VIII.* SYNTHESIS OF AMINO DERIVATIVES OF PHENOXAZINONES

I. Ya. Postovskii, K. I. Pashkevich, UDC 547.867.7.07

and G. B. Afanas'eva

The r e a c t i o n of 3-phenoxazinone, b e n z o [ c ] p h e n o x a z i n - 3 - o n e , and benzo[a]phenoxazin-9-one

with piperidine and o t h e r s i m i l a r a m i n e s leads to r e p l a c e m e n t of a hydrogen atom in the
quinoid ring in the m e t a - p o s i t i o n r e l a t i v e to the bridge nitrogen a t o m . Benzo[a]phenoxazin-
9-one also f o r m s 5,10-diamino d e r i v a t i v e s . In all c a s e s , the amine residue is displaced by
thiophenol~

2 - A m i n o - 3 - p h e n o x a z i n o n e has b a c t e r i o s t a t i e action [2] and is the b a s i s of antibiotics of the aetino-

m y c i n c l a s s [3, 4]. No study of the physiological activity of aminophenoxazinones with a substituted amino
group in the quinoid ring has b e e n m a d e up to now because of the lack of an acceptable method f o r the s y n -
t h e s i s of these compounds.

The known method f o r the p r e p a r a t i o n of 2 - a m i n o - 3 - p h e n o x a z i n o n e is based on the oxidative c o n -

densation of o - a m i n o p h e n o l [5]. This method is not suitable f o r the p r e p a r a t i o n of X - s u b s t i t u t e d 2 - a m i n o
d e r i v a t i v e s of phenoxazinones. The p o s s i b i l i t y of the d i r e c t introduction of a thiophenol residue into the
quinoid ring of phenoxazinones in the m e t a - p o s i t i o n r e l a t i v e to the nitrogen a t o m (the 2 - p o s i t i o n in the case
of 3-phenoxazinone) was shown in p r e c e d i n g p a p e r s [6, 7]. In the p r e s e n t r e s e a r c h we have investigated

I IV-VII XIV

- -

%__/
II| X-XI ~ XII, Xlll

0 ~
~-~
%!=: ~XVI
r

!1 VIII, IX N SAt

IV, VIII, X, Xll X = O; V, IX, XI, XHI X= CH2; ~ ~'0/~'~'<0

Vl X~CH2CH~; VII X=NCH3; XIV-XVI Ar=p-C6H4CH3 " ~ J - J ~ XY

* See [1] c o m m u n i c a t i o n VII.

S. M. K i r o v U r a l Polytechnic Institute, Sverdlovsk. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h

Soedinenii, No. 4, pp. 464-467, April, 1974. Original a r t i c l e submitted May 17, 1973.

9 1975Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

403
 T A B L E 1. Amino D e r i v a t i v e s of Phenoxazinones

~o mp, ~ (crystalliza- Empirical Found, % [ Calc., % kmax, nm

tion solvent) formula (log ~ )
CHIN C IH [ N

IV 210-~11 CmH14N203 426* (4,24) 43

(butanol - benzene) 68,0 5,1 i 440 (4,22)
4,: 1)
V (ethanol~4--186 C17H16N2Oz 72,9 5,8 427* (4,19) 53
443 (4,23)
VI 157--158 CIsH18N202 Z3,6 6,2 45
(isopropyl
alcohol)
VII 186--187 C~THtzNsOz 69,2 6,0 42
(isopropyl
alcohol)
VIII 235--236 C2oHI6N20~ 72,6 4,9 479 (4,47) 30
(butanol) 493* (4,45)
IX 238--'239 C2xH~sN20~ 76,2 5,5 482* (4.47) 28
(dimethylformamide) _498r (4,49)
X 235--T.37 C2oHI6N20~ 71,9 5,1 491 (i38) ~ 40
(isoamyl alcohol)
XI 216--218 I C21HjsN202 76,4 5,7 45
(isopropyl alcohol- I
t benzene) (1:1) I
XII 271--273 ] C24H2~N304 69,0 5,5 525 (4,44) 25
I(dimethylformamide)]
XII 1 260--~262 C26H27N30= 75,7 5,9 40
(dimethylformamide)

* Shoulder.

the d i r e c t introduction of an amino group into the quinoid ring of 3-phenoxazinone if), benzo[c]phenoxazin-3-
one (II), and benzo[a]phenoxazin-9-one ffII).
When s e c o n d a r y a m i n e s of the piperidine type are refluxed with I - I I I in benzene or alcohol, the amine
residue e n t e r s the quinoid ring of the phenoxazinone molecule in the m e t a - p o s i t i o n relative to the nitrogen
atom to give monoamino d e r i v a t i v e s IV-XI. In the c a s e of III, diamino d e r i v a t i v e s XII and XIII w e r e also
isolated (Table 1).
The introduction of an e l e c t r o n - d o n o r substituent into the m e t a - p o s i t i o n relative to the bridge n i t r o -
gen atom in the quinoid ring of phenoxazinones leads to a h y p s o c h r o m i e shift of the m a x i m u m of the long-
wave band, while the introduction of the s a m e substituent into the p a r a - p o s i t i o n r e l a t i v e to the nitrogen
atom in the benzoid ring leads to a b a t h o c h r o m i c shift of the m a x i m u m of this band [6, 7]. The m a x i m a of
the long-wave bands of the monoamino d e r i v a t i v e s obtained in this study a r e shifted h y p s o c h r o m i c a l l y as
c o m p a r e d with the m a x i m a in the e l e c t r o n i c s p e c t r a of the s t a r t i n g phenoxazinones ff-III); this a t t e s t s to
e n t r y of the amine r e s i d u e s into the quinoid portion of the molecule.
To c o n f i r m the site of e n t r y of the substituent we investigated the r e a c t i o n of 3-phenoxazinone with
a m m o n i a . It was found that the known 2 - a m i n o - 3 - p h e n o x a z i n o n e [5] is f o r m e d when the r e a c t a n t s a r e heated
in sealed tubes f o r a long time, i.e., the attack of the amine is actually directed to the quinoid ring in the
r e c t a - p o s i t i o n relative to the nitrogen atom.
The amino group in the amino d e r i v a t i v e s (IV-XII) of phenoxazinones is readily displaced by a t h i o -
c r e s o l r e s i d u e . M o r e o v e r , in the case of monoamino d e r i v a t i v e s of 3-phenoxazinone and benzo[a]phenox-
a z i n o - 9 - o n e , in addition to d i s p l a c e m e n t one o b s e r v e s e n t r y of a second thiophenol molecule into the b e n -
zoid ring of I and 11-Ito give di(arylthio) d e r i v a t i v e s XIV and XVI, which a r e identical to the compounds
obtained in [6, 7]. Only d i s p l a c e m e n t of the amine residue by thiophenol to give XV is o b s e r v e d f o r amino
d e r i v a t i v e s of benzo[c]phenoxazin-3-one, in which t h e r e is no e l e c t r o p h i l i e c e n t e r in the benzoid ring (VIII
and IX). The d e s c r i b e d r e a c t i o n s also c o n f i r m the e n t r y of a m i n e s into the quinoid ring of I - H I .

EXPERIMENTAL
The absorption spectra of 5 - 10 -4 M solutions of the compounds in chloroform were recorded with
an SF-10 spectrometer. C o l u m n chromatography was carried out with activity IT neutral aluminum oxide
with elution with anhydrous chloroform.

404
 2 - M o r p h o l i n o - 3 - p h e n o x a z i n o n e (IV). A 2 - m l (20 m m o l e ) s a m p l e of m o r p h o l i n e was added to 0.5 g
(2.5 m m o l e ) of 3-phenoxazinone in 10 m l of benzene, and the m i x t u r e was refluxed on a w a t e r bath f o r 4 h.
It was then cooled, and the p r e c i p i t a t e d c r y s t a l s w e r e r e m o v e d by filtration, washed with alcohol, and dried.
The d r y p r e c i p i t a t e was d i s s o l v e d in c h l o r o f o r m and c h r o m a t o g r a p h e d with a column. The f i r s t (red) frac-
tion was collected, the solvent was r e m o v e d by distillation, and the residue was r e c r y s t a l l i z e d to give 0.5 g
of amine IV (Table 1).
2 - P i p e r i d i n o - (V), 2 - H e x a m e t h y l e n e i m i n o - (VI), and 2 - ( N - M e t h y l - p i p e r a z i n o ) p h e n o x a z i n - 3 - o n e s (VII)
and 2 - M o r p h o l i n o - (VIII) and 2 - P i p e r i d i n o - b e n z o [ e ] p h e n o x a z i n - 3 - o n e s (IX). These compounds were s i m -
i l a r l y obtained.

2 - A m i n o - 3 - p h e n o x a z i n o n e . A 0.5-g (2.5 m m o l e ) s a m p l e of 3-phenoxazinone was heated in 10 m l of

alcohol s a t u r a t e d with a m m o n i a in a s e a l e d tube at 95-100 ~ for 10 h. The solvent was then r e m o v e d , and
the residue was d i s s o l v e d in c h l o r o f o r m and c h r o m a t o g r a p h e d . The y e l l o w - o r a n g e fraction was collected,
the solvent was r e m o v e d by distillation, and the residue was r e c r y s t a l l i z e d to give 0.1 g (18%) of 2 - a m i n o -
3-phenoxazinone, which was identical to the compound obtained by independent s y n t h e s i s via the method in
[5]. The product had m p 249-250 ~ (from alcohol).
10-Morpholinobenzo[a]phenoxazin-9-one (X). A 2 - m l (20 m m o l e ) s a m p l e of morpholine was added
to a m i x t u r e of 25 m l of benzene and 0.8 g (3 m m o l e ) of benzo[a]phenoxazin-9-one, and the m i x t u r e was r e -
fluxed on a w a t e r bath for 4 h. It was then cooled, and the p r e c i p i t a t e was r e m o v e d by filtration, washed,
dried, and c h r o m a t o g r a p h e d with a column. The red f r a c t i o n was collected, the solvent was r e m o v e d by
distillation, and the residue was r e c r y s t a l l i z e d to give 0.3 g of amine X (Table 1).
5,10-Dimorpholinobenzo[a]phenoxazin-9-one (XII). A m i x t u r e of 0.8 g (3 m m o l e ) o f b e n z o [ a ] p h e n o x a z i n -
9-one, 6 m l (60 m m o l e ) of m o r p h o l i n e , and 10 m l of benzene was refluxed f o r 8 h. It was then cooled, and
the r e s u l t i n g p r e c i p i t a t e was r e m o v e d by filtration, dried, and c h r o m a t o g r a p h e d with a column. The violet
f r a c t i o n was collected, the solvent was e v a p o r a t e d , with a column. The violet fraction was collected, the
solvent was e v a p o r a t e d , and the r e s i d u e was r e c r y s t a l l i z e d to give 0.3 g of amine XII.
10- Pipe ridinobenzo [a]phenoxazin- 9-one (XI) and 5,10- Dipipe ridinobenzo [a]phenoxaz in- 9-one (XIII).
T h e s e compounds w e r e s i m i l a r l y obtained (see Table 1).
2,7-Di(tolylthio)phenoxazin-3-one (XIV). A 0 . 5 - g (1.8 m m o l e ) s a m p l e of 2 - m o r p h o l i n o - 3 - p h e n o x a z i n -
one and 0.3 g (2.4 mole) of p - t h i o c r e s o l was heated in 10 m l of alcohol with two drops of h y d r o c h l o r i c acid
f o r 4 h on a w a t e r bath, a f t e r which a n o t h e r 0.1 g (0.8 m m o l e ) of p - t h i o c r e s o l was added, and the m i x t u r e
was refluxed for 2 h. A f t e r this, 5 m l of 10%alcohol solution of f e r r i c chloride was added, and the solvent
was r e m o v e d by distillation. The d r y residue was dissolved in c h l o r o f o r m and e h r o m a t o g r a p h e d with a
column. The f i r s t (red) f r a c t i o n was collected, the solvent was e v a p o r a t e d , and the residue was r e c r y s t a l -
lized to give 0.3 g of dithio d e r i v a t i v e _'k'IVwith mp 232-233 ~ (from butanol). The product was identical to
the 2 , 7 - d i ( t o l y l t h i o ) - 3 - p h e n o x a z i n - 3 - o n e obtained by d i r e c t r e a c t i o n of p - t h i o c r e s o l with 3-phenoxazinone.
The amine residue was s i m i l a r l y displaced by t h i o c r e s o l f r o m the o t h e r amino d e r i v a t i v e s of 3 - p h e n o -
xazinone, b e n z o [ c ] p h e n o x a z i n - 3 - o n e , and benzo[a]phenoxazin-9-one.

LITERATURE CITED
1. G. B. A f a n a s ' e v a , T. S. Viktorova, K. I. Pashkevich, and L Ya. Postovskii, Khim. G e t e r o t s i k l . Soedin.,
348 (1974).
2 N. G e r b e r and M. L e c h e v a l u r , Biochem., 3, 398 (1964).
3. W. Sch~ffer, P r o g r . O r g . Chem., 6, 135 (19"64).
4. M. I o n e s c u and H. Mantsch, Adv. H e t e r o c y c l . Chem., 8, 83 (1967).
5. A. O s m a n and I. Bassiouni, J . A m e r . Chem. Soc., 82, 1607 (1960).
6. K. I. Pashkevich, G. B. A f a n a s ' e v a , and L Ya. Postovskii, Khim. G e t e r o t s i k l . Soedin., 746 (1971).
7. G. B. A f a n a s ' e v a , K. I. Pashkevich, I. Ya. Postovskii, V. G. Vykhristyuk, N. P. Shimanskaya, and
V. D. Bezuglyi, Khim. G e t e r o t s i k l . Soedin., 1345 (1972).

405
REACTION OF SULFOLENES AND THEIR DERIVATIVES
WITH SOME SULFUR-CONTAINING NUCLEOPHILES

T . t~. B e z m e n o v a , T. N. Varshavets, UDC 547.733.07

and A. Ya. Bezmenov

Reaction of 2-sulfolene, 4 - h y d r o x y - 2 - s u l f o l e n e , 4 - b r o m o - and 3 - c h l o r o - 2 - s u l f o l e n e s , 3-

c h l o r o - 4 - h y d r o x y s u l f o l a n e , and 3,4-dibromo(dichloro)sulfolanes with sodium m e t h a n e - ,
h e x a n e - , a l l e n e - , benzene-, and p - t o l u e n e s u l f i n a t e s and m a g n e s i u m gave 3 - m e t h y l - , 3-
hexyl-, 3 - a l l y l - , 3 - p h e n y l - , and 3-(p-tolylsulfonyl)sulfolanes, 3 - m e t h y l - , 3 - p h e n y l - , and
3- (p-tolylsulfonyl)-4-hydroxysulfolanes, and 3 - p h e n y l - and 4-phenylsulfonyl-2-sulfolene s.

The b a s e - c a t a l y z e d addition of m e r c a p t a n s to 2-sulfolenes and 3-sulfolenes, which gives sulfolanyl

sulfides, is well known [1]. Sulfolanyl sulfones were synthesized by oxidation of the l a t t e r [2]. The method
does not extend to sulfides that contain r e a d i l y oxidized groups. It has been p r o p o s e d [2] that such sulfones
be synthesized by r e a c t i o n of the s a l t s of sulfinic acids with halogen d e r i v a t i v e s of sulfolane. Considering
the limited a c c e s s i b i l i t y o f / 3 - h a l o s u l f o l a n e s [3-5], we worked out a o n e - s t e p method for the p r e p a r a t i o n
of sulfolanyl sulfones by r e a c t i o n of sulfinic acid salts with 2-sulfolene [6].
A study of the p r o p e r t i e s of f l - d e r i v a t i v e s of sulfolane that contain h e t e r o a t o m s [7] showed that in
the p r e s e n c e of b a s e s sulfolanyl sulfones are a l m o s t completely c o n v e r t e d to 2-sulfolene and sulfinic acid
salts, so that t h e i r addition cannot be r e a l i z e d in aqueous media.
: ~ /--S0,R
+ RSOzNa [..SO~ j " + NaOH
2

If the alkali f o r m e d is r e m o v e d f r o m the r e a c t i o n by m e a n s of an acetate o r phosphate buffer, the sulfol-

anyl sulfones a r e f o r m e d in good yields (see Table 1). 4 - H y d r o x y - 2 - s u l f o l e n e r e a c t s s i m i l a r l y to give
3 - a l k y l ( a r y l ) s u l f o n y l - 4 - h y d r o x y s u l f o l a n e s . T h e s e s a m e products a r e obtained by reaction of sulfinic acid
s a l t s with 3 - e h l o r o - 4 - h y d r o x y s u l f o l a n e .
A product identified as 4 - p h e n y l s u l f o n y l - 2 - s u l f o l e n e (3;) was isolated in the reaction of 3 , 4 - d i b r o m o
(chloro)sulfolanes and 4 - b r o m o - 2 - s u l f o l e n e with sodium benzenesulfinate in aqueous m e d i a and in acetic
acid. In acetic acid 3,4-diphenylsulfonylsulfolane (XI) was also obtained in 25%yield. The products were
identified by c h e m i c a l and s p e c t r a l methods - by IR s p e c t r o s c o p y f r o m the p r e s e n c e in the s p e c t r u m of X
of the c h a r a c t e r i s t i c C - H absorption band for a c i s - d i s u b s t i t u t e d double bond at 645 cm -1, which is absent
in the case of XI, and by UV s p e c t r o s c o p y for X and PMR s p e c t r o s c o p y (Fig. 2). The ratio of the integral
intensities of the signals of the protons in the 4- and 5-positions (r 6.25 ppm and 5.87 ppm, r e s p e c t i v e l y )
x x = ~SO2%H ~ ~ ~--~ x

~y-2 SOsC6Hs~ . sO~%H~

--/~ o,,o " ~ ~s~ x

of the proton in the 3-position (~ 5.66 ppm, M), and of the protons in the 2-position (~ 2.73 ppm, M) is
1 : 1 : 1 : 2 for sulfolene X.

Institute of the C h e m i s t r y of H i g h - M o l e c u l a r - W e i g h t Compounds, A c a d e m y of Sciences of the U k r a i n -

ian SSR, Kiev. T r a n s l a t e d f r o m Khimtya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 4, pp. 468-471, April, 1974.
Original a r t i c l e submitted July 28, 1972; r e v i s i o n submitted O c t o b e r 25, 1973.

9 1975PlenumPublishing Corporation, 227 West 17th Street, New York, N.Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy o f this article is available from the publisher for $15.00.

406
 TABLE I. SulfolanylSulfones R-SO2-R'
R (in the Empirical Found,% Calc., %
3-position) R' mp, Z: formula
u~ CFH s c.ls
]

I CHa ISulfolanyl 133---134 CsHIoO4S2 30,3 5,0 32,2 ,30,5~5,1 32,3 50

II CH~=CH--CH.,I 71--72 C7H~204S2 37,215,4 28,8 37,515,4 28,6 5,0
III C~HI3 "I 86,56:7 CIOH2oO4S2 45,218,0 23,7 45,1 7,5128,970
IV C~Hs C,oH,204S2 46,0 4,5 24,6 46,2 4,6]24,6 70
V C7H7 117 CHH,404S2 48,7/ 5,3 23,2 48,2 5,1 23,4 70
VI CH~ 4=Hydroxy.- 192--19: C5H1oO5S2 29,2/ 4,7 29,9 26,0 4,7 29,9 30
sulfolanyl
VIE C~Hs 153 C,oHIsOsS2 43.5/4,7 23,2 43,5 4,4 23,2 90
VIII C 7 H 7 142--14~ C11H140~$2 44,6/ 5,0 22,5_ 45,5 4,9122,1. 80
IX C6Hs 2 -Sulfolenyl 153--15~ CioH,oO4S2 46,4/ 3,7 /

N,9t 4t3,5 3,9t24,8 70

C6H~ 2-Snlfol- 138 CioHlo04S2 46,714,1 25,0 46,5 3,9 24,8 85
enyl *
XI C~H~ 284.-.-,285 C~6H~oO8S~ 47,5i4'1i .)3,9147,9 4,0/24,0t55

* Substituent R in the 4-position.

tSubstituent R in the 3- and 4-positions.

o,8 i ".
d I /~" ~" t2.< lu/
I i

% \ . .

250 300 .~, nm

J'2,o 3,0 6,0 {, ppm

Fig. 1 Fig. 2
Fig. 1. UV s p e c t r a in 10%aqueous dioxane of 4 - p h e n y l s u l f o n y l - 2 - s u l -
folane (a); 3-phenylsulfonyl-2-sulfolene (b); and 4-phenylsulfonyl-2-
sulfolene containing }{OH (c).
Fig. 2. PMR spectrum of a 10% solution of 4-phenylsulfonyl-2-sulfolene.

The i s o m e r i c 3-substituted sulfonyl-3-sulfolenes and sulfonyl-2-sulfolenes were not detected. 3-

Phenylsulfonyl-2-sulfolene was isolated in the reaction of sodium benzenesulfinate with 3 - c h l o r o - 2 - s u l f o l e n e
and was identified by t h i n - l a y e r c h r o m a t o g r a p h y (Rf 0.43),IR and UV spectroscopy, and a mixed m e l t -
ing point determination with previously d e s c r i b e d pr6duets [8]. It was established by means of UV s p e c t r o -
scopy (Fig. 1) that 4-phenylsulfonyl-2-sulfolene is not i s o m e r i z e d in alkaline media. A smooth reaction
between o - n i t r o p h e n y l - 2 , 3 - d i b r o m o ( d i c h l o r o ) p r o p y l sulfone and sodium p-toluenesulfinate, which leads to
the trisulfone ArSO2CH2CH(SO2Ar)CH2SO2Ar, has been r e p o r t e d [9]. On the other hand, o~,fl-unsaturated
sulfones ArSO2CH =CHCH2SO2Ar are f o r m e d in good yields with p - c h l o r o - , p - b r o m o - , and p-iodophenyl
2 , 3 - d i b r o m o p r o p y l sulfones. The reaction with 3,4-dibromosulfolane p r o c e e d s s i m i l a r l y .
The data obtained in this study can be explained if one a s s u m e s that the substitution reaction p r o -
ceeds via an e l i m i n a t i o n - a d d i t i o n s c h e m e leading to the formation of 4-phenylsulfonyl-2-sulfolene, which
does not add a second sulfinate molecule in alkaline media but f o r m s a trisulfone (XI) in acetic acid.

EXPERIMENTAL
The UV s p e c t r a of ethanol and 10%aqueous dioxane solutions of the compounds were r e c o r d e d with an
SF-16 s p e c t r o p h o t o m e t e r . The IR s p e c t r a were r e c o r d e d with a UR-20 s p e c t r o m e t e r . The PMR s p e c t r a

407
 of CDC13 and dimethyl sulfoxide (DMSO) solutions were recorded with a Varian-60A s p e c t r o m e t e r with an
operating frequency of 60 MHz and cyclohexane as the internal standard.
2-Sulfolene, 3-chloro-2-sulfolene, and 4-hydroxy-2-sulfolene were obtained by isomerization of 3-
sulfolene, 3-chloro-3-sulfolene [10], and 3,4-epoxysulfolane [11], respectively. The 3,4-dihalosulfolanes
and 3-chloro-4-hydroxysulfolane [12] were synthesized by bromination and chlorination of 3-sulfolene, while
4-bromo-2-sulfolene [13] was synthesized by reaction of 3,4-dibromosulfolane with pyridine. The products
were ehromatographed in a loose thin l a y e r of activity II A1203; the eluent was diethyl ether, and the chroma-
tograms were developed with iodine vapors.
3-Aryl(alkyl)sulfonylsulfolanes. An equimolar mixture of 2-sulfolene and the sulfinic acid salt was
heated at 100 ~ in an aqueous solution of phosphate (acetate) buffer or in acetic acid for 5-6 h. Sulfones III-
V were isolated from the cooled (to 0~ solutions by filtration. An additional amount of the product was
isolated by evaporation of the filtrate and recooling. Sulfones I and II were isolated by evaporation of the
solvent and crystallization of the residue from methanol.
3-Aryl(methyl)sulfonyl-4-hydroxysulfolanes (VI-VIII). These compounds were obtained by a procedure
similar to that used in the preceding experiment by reaction of sulfinic acid salts with 4-hydroxy-2-sul-
folene and 3-chloro-4-hydroxysulfolane. They were isolated as sulfones I and II.
3-Phenylsulfonyl-2~sulfolene (IX). A 3.8-g (0.025 mole) sample of 3-chloro-2-sulfolene and 4.1 g
(0.025 mole) of sodium benzenesulfinate were refluxed in a solution of 15 ml of CH3COOH in 40 ml of water
for 5-6 h. The products isolated were sulfones III-V.
4-Phenylsulfonyl-2-sulfolene IX). This compound was obtained in 80-85%yield by reaction of sodium
benzenesulfinate with 3,4-dibromo(dichloro)sulfolanes and 4-bromo-2-sulfolene in molar ratios of 2:1 and
1 : 1, respectively. The product depressed the melting point of IX, and its IR, UV (Fig. 1), and PMR (Fig. 2)
spectra differed from those of IX. Its spectrum (Fig. 1) did not change in 0.1 N KOH at 50 ~
3,4-Oiphenylsulfonylsulfolane (XI). This compound was obtained: a) in 55%yield imp 284-285 ~ by
reaction of sodium benzenesulfinate with X in acetic acid in a m ol ar ratio of 1 : 1 and (b) in 25%yield in a
mixture containing X by reaction of sodium benzenesulfinate with 3,4-dibromo(dichloro)sulfolanes and 4-
bromo-2-sulfolene in a molar ratio of 2: 1.

LITERATURE CITED
1. D. Delfs, US Patent No. 2,219,006 (1940); Chem. Abstr., 35, No. 19027 (1941i.
2. R . C . Morris and E. C. Shokal, US Patent No. 2,452,949 (1948); Chem. Abstr., 4.5, 2237 (1949).
3. H . E . Faith, M. P. Kautsky, and B. E. Abren, J. Org. Chem., 2~7, 2889 (1962).
4. V . I . Dronov and V. A. Snegotskaya, Khim. Geterotsikl. Soedin., No. 3, 5 (1971).
5. T. Ywao, T. Yoshinoa, and Y. Zen-uh, Tetrahedron Lett., 3893 (1971).
6. T. ]~. Bezmenova, A. A. Dolgalev, and A. P. Soboleva, USSR Author's Certificate No. 311,909 (1971);
Byul. Izobr., No. 25, 98 (1971).
7. T. t~. Bezmenova, Summaries of Papers Presented at the 12th Scientific Session on the Chemistry
and Technology of Organic Compounds of Sulfur and Sulfurous Oils [in Russian], Zinatne, Riga (1971),
p. 162.
8. T. t~. Bezmenova, A. F. Rekasheva, A. A. Dolgalev, and T. N. Varshavets, Khim. Geterotsikl. Soedin.,
1617 (1970).
9. V . N . Mikhailova, V. P. Yur'evich, and A. D. Bulat, Zh. Organ. Khim., 7, 562 (1971).
10. I . G . Turyanchik and T. ~. Bezmenova, USSR Author,s Certificate No. 215,232 (1968); Byul. Izobr.,
No. 13, 22 (1968).
11. Chem. Werke Huels. A.-G., Dutch Patent No. 6,614,511 (1967); Chem. Abstr., 8_~8,78, 127 (1968).
12. M. Prochazka and V. Horac, Chem. Listy, 52, 1768 (1958).
13. W . G . Bailey and E. W. Cummins, J. Amer. Chem. Soc., 76, 1932 (1954).

408
F L U O RO S U L F O N Y L - C O N T A I N I N G HETEROCYCLIC
COMPOUNDS
VIII.* TRANSFORMATIONS OF ttEXAFLUORODIMETHYL SULFONENE
TRIMER UNDER BASE SOLVOLYSIS CONDITIONS

G. A. Sokol'skii, V. M. Pavlov, UDC 547.221T876 ' : 543.422.25

V. M. Golovkin, and I. L. Knunyants

Salts of hexafluorodimethylmethionic and o t - h y d r o h e x a f l u o r o - 2 - p r o p a n e - 2 - s u l f o n i c acids, the

amide of the l a t t e r , and a n u m b e r of sulfones containing a - h y d r o h e x a f l u o r o i s o p r o p y l , p e n t a -
f l u o r o i s o p r o p e n y l , /~,fl,fl-trifluoroethyl, and methyl groups w e r e obtained by alkaline h y d r o -
l y s i s , aleoholysis, and a m m o n o l y s i s of hexafluorodimethyl sulfonene t r i m e r .

In a p r e c e d i n g c o m m u n i c a t i o n it was shown that cyclic trisulfone I, which is a t r i m e r of h e x a f l u o r o -

dimethyl sulfonene, r e a c t s with nueleophilic r e a g e n t s to give d o n o r - a c c e p t o r c o m p l e x e s ; c o m p l e x e s based
on s e c o n d a r y a m i n e s a r e unstable - they d e c o m p o s e to give a m i d e s of ~ - h y d r o h e x a f l u o r o p r o p a n e - 2 - s u l -
fonic acid [1]. In the p r e s e n t communication,
(CF3) 2
/S02--C~ R2NH / S 0 2 - - C ~ F3)2 +
{CF3)2--C SO~ - (CF3)2-- C - SO2 R2NH ~ r ~
\SO2__C / " \SO2_._C / "
(CF3)2 (CF3) 2
I
we examine the t r a n s f o r m a t i o n s of trisulfone I during a l e o h o l y s i s , alkaline h y d r o l y s i s , and a m m o n o l y s i s .
It was found that solutions of trisulfone I in methanol, ethanol, and benzyl and o t h e r alcohols a r e
stable at 20~ for m a n y weeks (according to m o n i t o r i n g by UV and 19F NMR s p e c t r o s c o p y ) . Reaction b e -
tween t r i s u l f o n e I and aliphatie aloehols o c c u r s only when the m i x t u r e is heated above 60-70~ in this e a s e ,
different p r o d u c t s a r e f o r m e d , depending on the r e a g e n t ratio. Thus, when a limited amount (the optimum
is 2-3 equivalents) of alcohol is used, o~-hydrohexafluoroisopropyl p e n t a f l u o r o i s o p r o p e n y l sulfone (II) can
be isolated; f i , f l , f l - t r i f l u o r o e t h y l ~ - h y d r o h e x a f l u o r o i s o p r o p y l sulfone (III) is isolated in the e a s e of e x c e s s
aleohol (6 o r m o r e equivalents). Sulfone II can be c o n v e r t e d to sulfone III by t r e a t m e n t with alcohol o r
w a t e r . Both sulfones a r e stable on s t o r a g e in sealed quartz ampoules but are unstable when they a r e s t o r e d
in o r d i n a r y l a b o r a t o r y (alkali) g l a s s ; when they a r e s t o r e d in o r d i n a r y l a b o r a t o r y glass, e a c h of these
sulfones is
! ROH CF3\
9 ~ CF2//CSO~CH
(CF3)~" ~ " CF'3CH2SO2CH (C F3~2

[I III
\ /
/CF3
CF:~CHzSOzC%cF3 ~ CF~CH2SOzCH2CF:,

IV V

c o n v e r t e d to f l , f l , f i - t r i f l u o r o e t h y l p e n t a f l u o r o i s o p r o p e n y l sulfone (IV) (after 2-2.5 weeks and 8-10 months,

r e s p e c t i v e l y ) . T r e a t m e n t of IV with alcohol o r w a t e r gives the e x t r e m e l y stable bis (fl, g,n - t r i f l u o r o e t h y l )
sulfone (V).
* See [1] for c o m m u n i c a t i o n VII.
Institute of H e t e r o o r g a n i e Compounds, A c a d e m y of Sciences of the USSR, Moscow. T r a n s l a t e d f r o m
Khimiya G e t e r o t s i k l i e h e s k i k h Soedinenii, No. 4, pp. 472-476, April, 1974. Original a r t i c l e submitted M a r c h
9, 1973.

9 1975PlenumPublishing Corporation, 227 West 17th Street, New York, N.Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
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409
 The s t r u c t u r e s of all of these fluorine-containing sulfones w e r e p r o v e d by igF NMR s p e c t r o s c o p y
and f r o m the r e s u l t s of a l k a l i m e t r y and t h o r i o m e t r y , for example:
CFa
~CSO2 CH(CFa)2+110H---~CH3SO2CH~+4CO2+11F-
CF2
CFa CH2SO2CH2CF~ + 6OH----~CHa$O~CH3+ 2CO2+ 6F'-]- 2H20

A s t r i c t sequence of f o r m a t i o n of the r e a c t i o n products is also o b s e r v e d during the alkaline h y d r o l y -

sis of trisulfone I. In this c a s e , a rapid r e a c t i o n is r e a l i z e d at 20~ the r e s u l t of the r e a c t i o n depends on
the amount of alkali used. Thus, if two equivalents of p o t a s s i u m hydroxide in alcohol a r e u s e d in the t r e a t -
ment of solutions of trisulfone I (in dioxane o r alcohol), a hexafluorodimethylmethionic acid salt (VI) is
f o r m e d , while t h r e e equivalents of alkali give an ~ - h y d r o h e x a f l u o r o p r e p a n e - 2 - s u l f o n i c acid salt (VII), which
can also be obtained d i r e c t l y f r o m salt VI. If trisulfone I is t r e a t e d with aqueous alkalis, one can isolate
fluorine-containing sulfones that a r e identical to those d e s c r i b e d above - I I I (optimally six equivalents of
alkali) and V (optimally 9-12 equivalent of KOH). Dimethyl sulfone (18 o r m o r e equivalents of KOH) and a
sulfoacetic acid salt (22 o r m o r e equivalents of KOH) a r e f o r m e d when e x c e s s alkali is used. It was e s -
tablished by analytical e x p e r i m e n t s that t h e s e l a t t e r compounds along with c a r b o n - d i o x i d e gas and s a l t s of
sulfuric and hydrofluoric acids, a r e the final products of the alkaline h y d r o l y s i s of trisulfone I; the o v e r a l l
consumption of alkali is 22 equivalents with r e s p e c t to methyl orange or 27 equivalents with r e s p e c t to
phenolphthalein.
On the b a s i s of the e x p e r i m e n t a l facts p r e s e n t e d above, it can be a s s e r t e d that the alkaline h y d r o l y s i s
of trisulfone I is a m u l t i s t e p p r o c e s s and is c h a r a c t e r i z e d by a s t r i c t l y d e t e r m i n e d sequence of steps that
is d e t e r m i n e d by the stabilities of the p r o d u c t s f o r m e d .
! + 2KOH---~I I + KOSO2C(CF~)2SO2OK+ HF
vI
I + 3KOH---MI + (CFa)2CHSO~OK+ 2SO4 ~J-HF
I+ 6KOH--~II I + VII + K2SO4+3KF+ CO~+ H20
I+ 9KOH--~V+VI1+ K2SO4+6KF+2CO2+2H~O
1+ 12KOH---~V-~CFaCH2SO2OK+K2SO4+9KF+3CO2+3H~O
I-t-18KOH---~CH3SO2CH~-]-CF3CH2SO2OK+K2SO4+ 15KF+5CO2+ 5H20
I +22KOH---~CHaSO2CHa+ KOOCCH2SO2OK-]-K2SO4-t-18KF+5CO2+ 7H20
The alcoholysis of trisulfone I is r e a l i z e d via a s i m i l a r s c h e m e . It might be a s s u m e d that the a m i d e s
of ~ - h y d r o h e x a f l u o r o p r o p a n e - 2 - s u l f o n i c acid, which w e r e p r e v i o u s l y obtained in the r e a c t i o n of trisulfone
I with s e c o n d a r y a m i n e s [1], are f o r m e d via a s i m i l a r s c h e m e . The r e s u l t of the a m m o n o l y s i s of trisulfone
I is an additional c o n f i r m a t i o n of this. Thus, its r e a c t i o n with a m m o n i a in benzene solution is a c c o m p l i s h e d
at 20 ~ during which the a m m o n i a consumption is ~11 equivalents; sulfamide and ~ - h y d r o h e x a f l u o r o p r o p a n e -
2-sulfamide (VIII) w e r e isolated f r o m the r e a c t i o n products; a m m o n i u m fluoride (six equivalents) is f o r m e d
simultaneously.
| CF~\ /CF 3 |
! !1 NHa ~ [ NC/)CHSO2CH(xcN ] + H2NSO2NH2 {CFa)2CHSO2NH2 6 NH4F
VIII

The a - h y d r o h e x a f l u o r o p r o p a n e - 2 - s u l f a m i d e s t r u c t u r e was p r o v e d by tgF NMI~ s p e c t r o s c o p y and also

f r o m the r e s u l t s of a l k a l i m e t r y and t h o r i o m e t r y . B i s ( ~ - c y a n o - f l , fl, fl-trifluoroethyl)sulfone could not be
isolated; its f o r m a t i o n can only be postulated on the b a s i s of the s t o i c h i o m e t r y of the reaction u n d e r c o n -
s i d e r a t i o n and in analogy with the r e s u l t s of the a m m o n o l y s i s of hexafluoropropylene [2].

CFaCFfCF 2 NHa. [CFaCHFCF2NH2] ~ CFaCltFCN

O n e ' s attention is drawn to the fact that sulfonyl-eontaining compounds of t h r e e t y p e s - sulfones,

sulfuric acid, and sulfonic acid d e r i v a t i v e s - a r e always f o r m e d in the exhaustive alcoholysis, h y d r o l y s i s ,
o r a m m o n o l y s i s of trisulfone I. When the p r o c e s s was controlled (2 equivalents of KOH), in plaoe of the
l a t t e r acid d e r i v a t i v e s , we w e r e able to r e c o r d a hexafluorodimethylmethionic acid d e r i v a t i v e (VI). The
p r e c u r s o r of all of t h e s e s u b s t a n c e s is a p p a r e n t l y a t r i s u l f o n y l compound that is f o r m e d in the f i r s t steps
of the p r o c e s s - coordination of the nueleophile (of the H - B ) type with trisulfone I, decyclization of the
l a t t e r u n d e r the s o l v o l y s i s conditions to a dipolar ion of the linear type, and stabilization of this i o n b y s p l i t -
ting out of a fluoride ion.

HB ~ / SO2--c~ Fs)2 - + CFa\

I ~ (CF2)~- % -- ? 0 2 B + H~ (CF3)2CSO2C(CF3)2SO2C{CF3)2SO2BH-~F ~ ClV2;~
.~CS02C(C Fa)2SO~C(CFa)2SO2--B
SO2--C(CFa)2

410
 This i n t e r p r e t a t i o n of the f i r s t steps of the above-examined t r a n s f o r m a t i o n s of trisulfone I c l e a r l y
explains the r e s u l t s of alcoholysis, alkaline h y d r o l y s i s , a m m o n o l y s i s , and a m i n o l y s i s . This m a k e s it p o s -
sible to predict that the reaction of cyclic trisulfone I with all nucleophilic reagents will be realized via
the same scheme p r e s e n t e d above.

EXPERIMENTAL
The 19F NMR s p e c t r a were r e c o r d e d by I. V, Galakhov and L. I. Ragulin with a H i t a c h i - P e r k i n E l m e r
model R-20 s p e c t r o m e t e r at 34.5~ the field intensity was 14,092 G, the frequency was 56.456 MHz, the
resolution was 3 910 -8, and the e x t e r n a l standard was t r i f l u o r o a c e t i c acid. The s p e c t r a l data are p r e s e n t e d
in Table 1o

Hexafluorodimethyl Sulfonene T r i m e r (I). This compound was obtained by p y r o l y s i s of hexafluoro-

isobutenylidene sulfate [3] and was purified by sublimation.

~ - H y d r o h e x a f l u o r o i s o p r o p y l P e n t a f l u o r o i s o p r o p e n y l Sulfone (II). A 3,24-g (0.03 mole) sample of

benzyl alcohol was added to a solution of 6.42 g (0.01 mole) of I in 50 ml of dioxane, and the mixture was
heated
9 on a b o i l i n g - w a t e r bath f o r 3 h. The solvent was then r e m o v e d by vacuum distillation, and the r e s -
idue was mixed with anhydrous m a g n e s i u m sulfate; the mixture w a s p l a c e d in a sublimation apparatus (of
the finger type), and the sublimate was collected by heating on a w a t e r bath (at 50-80 mm), This p r o c e d u r e
gave 2.4 g (69%) of sulfone II as white plates with mp 33 ~ Found: C 21.0; H0.5; F 60~ S 9,5%0 C~HO2FIIS,
Calculated: C 20.8; H 0~ F 60.4; S 9.3%~

Similarly, 2,1 g (60%) of II was obtained from 6.42 g of I and 1.84 g of ethanol.
f l , f l , f i - T r i f l u o r o e t h y l ol-hydrohexafluoroisopropyl Sulfone (III). A solution of 6.42 g (0.01 mole) of
I in 30 m l of methanol was heated at 70 ~ for 1 h, during which a c r y s t a l l i n e precipitate formed. The m i x -
ture was cooled, and the precipitate was r e m o v e d by filtration and sublimed from a mixture with magnesium
sulfate to give 2,5 g (84%) of sulfone III as white needles with mp 55 ~ Found: C 20.0; H 1.1; F 57.1; S 11.1%
CsH302FgS. Calculated: C 20.1; H 1.0; F 57.4; S 11.7%.
Similarly, III was obtained in 78%yield by heating a solution of I in benzyl alcohol at 100%
A methanol solution of 3.66 g (~0.05 mole) of p o t a s s i u m hydroxide was added slowly to a solution of
6.42 g (0.01 mole) of I in 150 m l of methanol, during which a precipitate formed. The solvent was r e m o v e d
by vacuum distillation, and the residue was e x t r a c t e d twice with hot dibutyl e t h e r in 1 0 - m l portions. Cool-
ing of the e x t r a c t to 0 ~ gave 2.7 g (90%) of HI.

A 0 . 5 - m l sample of w a t e r o r ethanol was added to a solution of 1.7 g (0.005 mole) of sulfone II in hot
dibutyl ether, and the m i x t u r e was cooled to 0 ~ to give 1.4 g (94%) of sulfone III.
f l , f l , f i - T r i f l u o r o e t h y l P e n t a f l u o r o i s o p r e p e n y l Sulfone (IV). Crystalline sulfone II was s t o r e d in a
sealed glass ampoule at 20 ~=3~ for 18 days. The c r y s t a l l i n e m a s s was then mixed with m a g n e s i u m sulfate
and sublimed to give sulfone IV (76%) as white p r i s m s with mp 129 ~ Found: C 21.2; H 1.0; F 54.5; S 12.0%.
CsH202FsS. Calculated: C 21.6; H 0.7; F 54.7; S 11.5%.
Crystalline sulfone III was s t o r e d in a sealed glass ampoule at 20 J= 5~ 'for 280 days. Sublimation of a
mixture of this m a t e r i a l with m a g n e s i u m sulfate gave sulfone IV in 64%yield,
Bis(fl,fi,fl'-trifluoroethyl)sulfone~ (V). An alcohol solution of 4.94 g (0.09 mole) of p o t a s s i u m hydroxide
was added slowly to a solution of 6.42 g (0.01 mole) of I in 150 ml of ethanol, during which a precipitate
f o r m e d . The solvent was r e m o v e d by vacuum distillation, and the residue was e x t r a c t e d twice with 10-ml
portions of hot dioxane. Cooling of the e x t r a c t to 20 ~ gave 2.0 g (87%) of sulfone V as white scales with mp
127 ~ Found: C 21.1; H 2.1; F 49.3; S 14.3%. C4H402F~S. Calculated: C 20.8; H 1.7; F 49.6; S 13.9%.
A 0 , 5 - m l sample of w a t e r o r ethanol was added to a solution of 1.4 g (0.005 mole) of sulfone IV in
hot dioxane, and the mixture was cooled to 20 ~ to give 1.1 g (95%) of sulfone V.
P o t a s s i u m Hexafluorodimethylmethionate (VI). A solution of 1.12 g (0.02 mole of potassium hydroxide
in 10 ml of methanol was added to a solution of 6.42 g (0.01 mole) of I in 100 ml of methanol, during which
a precipitate f o r m e d . The solvent was r e m o v e d by vacuum distillation at room t e m p e r a t u r e , and the r e s i -
due was washed with 10 ml of hot dioxane to give 3.5 (90%) of salt VI as white scales with mp 189 ~ (decomp.
~
pt.). Found: C 8.9; F 28~ S 16.1~. C306F6S2K2. Calculated: C 9~ F 29.4; S 16.5%~ Salt VI was soluble
in w a t e r (with decomposition) and insoluble in most organic solvents.

411
 TABLE 1
Alkalimetry 19FNMRspectra
KOHconsump., Ifluoride
clmmiea spin--spin
Com-
/ equiv, ion signal
pound solvent shift, coupling
fphenolph:Me.y, !fou .d, character
ppm constant
~halein i Orange Ieqmv"
t 26,91 22,12 18,01 Dioxane Singlet -- 18,3
II 15,10 11,15 11,05 Dioxane Multiplet,. -2&0 u
doublet, -- t 6 , 3 8,l
multiplet --4,0
III 11,93 8,94 9,10 Dioxane Doublet, --16,2
triplet - - 17,0 9,0
IV 10,93 8,03 7,98 Dioxane Multi.plet, --23,0
triplet, -- 18,7 9,0
multtplet' --4,0
V 8J5 5.99 5,94 Dioxane Triplet -- 16,0 9,0
VI 8,97 7,95 5,91
VII 7,94 6,98 5,93 Water Doublet -15,8 8,0
VIII 7,95 6,93 5,91 Alcohol Doublet - 16,2 9,0

Potassium ~ - H y d r o h e x a f l u o r o p r o p a n e - 2 - s u l f o n a t e (VII). A solution of 1.68 h (0.03 mole) of p o t a s -

sium hydroxide in 10 ml of methanol was added dropwise to a solution of 6.42 g (0.01 mole) of I in 25 ml
of dioxane, during which a precipitate formed. The precipitate was removed by filtration and r e c r y s t a l -
lized from 50%aqueous ethanol to give 2.0 g (74%) of salt VII as white p r i s m s with mp 254 ~ (decomp. pt.).
Found: C 13.0; H 0.6; F 42%0; S 12.3%. C3HO3F6SK. Calculated: C 13.3; H 0.4; F 42.4; S 11.8%.
R e c r y s t a l l i z a t i o n of salt VI from w a t e r - e t h a n o l (1 : 1) gave salt VII in 94%yield.
Alkaline Hydrolysis of Trisulfone I. A suspension of 32.8 g ("0.1 mole) of barium oxide octahydrate
in 100 ml of water was added to a solution of 6.42 g (0.01 mole) of I in 100 ml of ethanol, and the mixture
was shaken vigorously for 2 h. The precipitate was centrifuged, r e m o v e d by filtration, and washed with
10 ml of hydrochloric acid (1 : 5) and 10 ml of water. It was then t r a n s f e r r e d to a 100-ml volumetric flask,
and sulfuric acid (1 : 10) was added up to the m a r k . The fluoride ion content (17.6 equivalents) in analiquot
of this solution was determined.
The m o t h e r liquor was evaporated, and the residue was washed twice with 1 0 - m l portions of e t h e r and
r e e r y s t a l l i z e d from aqueous alcohol (1 : 1) to give 2.5 g (91%) of b a r i u m sulfoacetate. Found: C 8.7; H 0.8;
S 11.6%. C2I-I2OsSBa. Calculated: C 8.9; H 0.7; S 11.8%.
The e t h e r e x t r a c t was evaporated, and the residue was r e c r y s t a l l i z e d f r o m toluene to give 0.8 g (85%)
of dimethyl sulfone, which was identical to a genuine sample.
ce-Hydrohexafluoropropane-2-sulfamide (VIII). Dry ammonia was bubbled slowly into a solution of
4.6 g (0.007 mole) of I in 150 ml of dry benzene until the signs of a reaction - heat evolution and formation
of a white precipitate - ceased. The a m m o n i a consumption was 1.8-1.9 liter. The benzene was r e m o v e d
from the reaction mixture by vacuum distillation, and the residue was e x t r a c t e d twice with 1 5 - m l portions
of hot c h l o r o f o r m . The e x t r a c t was cooled to 0 ~ to give 1.6 g (97%) of sulfamide VIII as white s c a l e s with
mp 103.5 ~ Found: C 15.2; H 1.2; N 5.8; F 49.2; S 13.7%. C3H~:)21NF6S. Calculated: C 15.6; H 1.3; N 6.1;
F 49.4; S 13.8%.
The residue from the reaction mixture was t r e a t e d with water, and the fluoride ion content (6.08
equivalents) i n an aliquot was determined.
Alkalimetry. A weighed sample (0.01-0.03 g) of the test p r e p a r a t i o n was dissolved in 10 ml of ethanol,
and the solution was diluted with 50 ml of 0.1 N potassium hydroxide. After 24 h, the e x c e s s alkali was
titrated with 0.1 N hydrochloride, first with r e s p e c t to phenolphthalein and then with r e s p e c t to Methyl
Orange. I n o t h e r e x p e r i m e n t s the fluoride ion content in the alkaline hydrolyzate was determined by t h o r i o -
m e t r y . The results of the analyses are p r e s e n t e d in Table 1.

LITERATURE CITED

le G. A. Sokol'skii, V. M. Pavlov, V. V. Ezhov, and I. L. Knunyants, Khim. Geterotsikl. Soedin., 45

(1974).
2. I. L. Knunyants, L. S. German, and B. L. Dyatkin, Izv. Akad. Nauk SSSR, Otd. Khim. Nauk, 1353 (1956)o
3. G. A. Soko~'skii, V. M. Pavlov, V. M. Golovkin, V. F. Gorelov, and I. L. Knunyants, Khim. Geterot-
sikl. Soedin., 42 (1974).

412
SPECTROSCOPIC STUDY OF ORGANOSILICON

DERIVATIVES OF THIOPHENE
V.* IR SPECTRA OF MONO- AND DISUBSTITUTED THIOPHENES

S. Y a . K h o r s h e v , N . S. V y a z a n k i n , UDC 543.422.4 : 547.245 : 547.732

A. N. E g o r o c h k i n , E. A. Chernyshev,
V. I. Savushkina, O. V. Kuz'min,
and V. Z. Anisimova

The IR s p e c t r a of o r g a n o s i l i c o n derivatives of thiophene were investigated. A c o m p a r i s o n

of the r e s u l t s with the l i t e r a t u r e data made it possible to isolate the c h a r a c t e r i s t i c a b s o r p -
tion bands of the substituted thiophene ring and to r e v e a l some r e g u l a r i t i e s in the IR s p e c t r a
of thienylsilanes. The ~* inductive constants of substituted thienyl groups x-- -- were
s

calculated f r o m the e x p e r i m e n t a l v ( S i - C l ) values. An analysis of the or* values shows that

e l e c t r o n - d o n o r substituents X lower the a c c e p t o r capacity of the thienyl substituent as a
whole, while e l e o t r o n - a c o e p t o r substituents i n c r e a s e it.

In the p r e s e n t r e s e a r c h we have investigated the IR s p e c t r a of thienylsilanes with the following s t r u c -

ture:

R ~s~SIR, R"R"'

I R=H, R'=R"=R'"=CHa; II R=H, R'=R"=R'"=CzH~; III R=H, R'=R"=R"=CI;

IV R=H, R'=R"=CI, R'"=CH~; V R=R'=H, R"=R'"=CHa; VI R=R'=H, R"=CHa,
R"=CI; VII R=R'=H, R"=CHa, R'"=Br; VIII R=R'=R"=H, R'"=CHa; IX R=R'=
R"=H, R"=Cl; X R=R'=R"=H, R'"=Br; XI R=R'=R"=R'"=H; XII R=H.
R'=R"=CHa, R"=2-thienyl XIII R=R'=H, R"=C~Hs, R'"=2-thienyl XIV R=R'=H,
R"=C6Hs, R'"=2-thienyl XV R=R'=H, R"=R"=2-thienyl XVI R=5-CHa, R'=R"=H,
R'"=CI; XVII R=5-CI, R'=C1, R"=R"'=H; XVIII R=5-SiH2CHa, R':CH3, R"=R'"=H;
XIX R=5-SiH2CI, R'=CI, R"=R'"=H; XX R=5-SiH2Br, R'=Br, R"=R"r=H; XXI
R=5-CHa, R'=R"=R"=H; XXII R=5-SiHa, R'=R"=R'"=H: XXIII R=5-Cl, R'=R"=
R"=H; XXIV R=5-SiH2C1, R'=R"=R"=H; XXV R=5-SiH~Br, R'=R"=R'"=H; XXVI
R=5-CI, R'=H, R"=R"~=Cl; XXVII R=5-Si(CHa)2H, R'=H. R"=R'"=CHa; XXVIII
R=5-Cl, R'=C1, R"=R'"=CHa; XXIX R=5-CI. R'=R"=R'"=CH3; XXX R=5-CHa,
R'=R"=R'"=C1; XXXI R=5-CI, R'=R"=R"=CI; XXXlI R=3-CHa, R'=C1, R"=R'"=
CHa; XXXIIIR=3-CHa, R'=CH3, R"=R'"=C1; XXXIVR=3-CHa, R'=C2Hs, R'~=R"=CI;
XXXVR=a-CHa, R'=R'=R'"=Cl.
A c o m p a r i s o n of the r e s u l t s with the l i t e r a t u r e data makes i t p o s s i b l e t o determine the c h a r a c t e r i s t i c
absorption frequencies of o r g a n o s i l i c o n derivatives of thiophene (Table 1) a~d to r e v e a l some r e g u l a r i t i e s
in the IR s p e c t r a of these d e r i v a t i v e s .

Stretching Vibrations of the Thiophene Ring C - H Bonds

T h r e e absorption bands at 3065, 3080, and 3110 cm -1, which c o r r e s p o n d to u ( C - H ) of the thiophene
ring, are p r e s e n t in the IR s p e c t r a of thienylsilanes I-XV. When substituents with l a r g e - I effects (halogens)
are bonded to the silicon atom, the frequencies of these bands i n c r e a s e by " 5 - 1 0 cm -1. In addition, r e d i s -
* See [1] for communication IV.

Institute of C h e m i s t r y , A c a d e m y of Sciences of the USSR, G o r ' k i i . T r a n s l a t e d f r o m Khimiya G e t e r o -

tsiklicheskikhSoedinenii, No. 4, pp. 477-481, April, 1974. Original article submitted D e c e m b e r 22, 1972;
r e v i s i o n submitted September 10, 1973.

9 19 75Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy of this article is availablefrom the publisher for $15.00.

413
 TABLE 1. Absorption Bands of the Thienyl Grouping in the IR
Spectra of Organosilicon Derivatives of Thiophene
Stzetching vibra- Stretching vibra- Deformation vibrations of the
Com- tioni of the tRons of the C - H bond, cm -I
pound thiophene ring 1 thiophene ring,
C - H bonch cm" cm'l in-plane l out-of-plane

I 3110 3080 3067 1503 14101 1330 865 765 710

11 3110 5980 3065 1505 1415 1330 858 732 710
Ill 3115 3090 3070 1500 1408[ 1332 865 760 725
IV 3112 3090 3075 1500 14101 1333 860T 760 720
V 3110 3082 3065 1503 1410 1330 870 770 710
VI 3112 3087 3068 1502 1410 1330 860 755 715
VII 3115 3087 3063 1503 1410 1330 860 750 720
VIII 3112 3085 3067 1502 1410 1330 860 750 715
IX 3115 3090 3070 1503 1408 1332 870 750 720
X 3115 3090 3070 1502 1410 1332 870 760 720
XI 3110 3085 3070 1500 1410 1330 870 770 715
XII 3110 3080 3065 15OO 1410 1330 860 783 710
XIII 3110 3080 3065 1500 1410 1330 860 77600 715
XIV* [500 140'5 1330 860 715
XV 3110 3080 3070 [500 1408 1330 860 750 715
XVI 3080 [495 1420 1315 810 700
XVII 3090 [515 1415 1300 805 670
XVIII 3070 [495 1420 1277 760 710
XIX 3080 t490 1415 1280 820 680
XX 3075 [495 1410 1280 760 715
XXI 3087 3067 [495 1420 1315 805 68o
XXII 3075 1495 1415 1280 815 68o
XXIII 3090 3070 k510 1420 1300 800 68o
XXIV~f (<--~) [493 1415 1280 815 680
XXV 3080 3065 495 1410 1280 815 68o
XXVI 3100 3070 515 1415 1300 805 670
XXVII 3070 3057 495 1415 1273 670
XXVIII 3070 1518 1418 1300 685
XXIX 3095 3070 1517 1420 130o 800 7oo
XXX 3080 1530 -- 1315 810 680
XXXI <(-->> -- 1412 130o 80,5 67o
XXXII$ 3110 3073 1520 1395
XXXIII 3110 3075 1520 1390
XXXIV 3110 3075 1520 1388 1~2
XXXV 31121 3078 1520 1390 1318

* T h e t h i o p h e n e r i n g v ( C - H ) b a n d s a r e o v e r l a p p e d by the C - H
s t r e t c h i n g v i b r a t i o n s of the CsH 5 g r o u p .
~The d a s h d e n o t e s that the s p e c t r u m was not r e c o r d e d in t h i s
r e gion.
SThe a b s o r p t i o n b a n d s r e l a t e d to the o u t - o f - p l a n e d e f o r m a t i o n
b a n d s of the C - H bond w e r e not i s o l a t e d f o r XXXII-XXXV.

t r i b u t i o n of the i n t e n s i t i e s of t h e s e a b s o r p t i o n b a n d s i s o b s e r v e d . T h i s shows up quite g r a p h i c a l l y in the

s p e c t r a of t h i o p h e n e s t h a t have s u c h s u b s t i t u e n t s a s (CH3)Si (I), (CH~2HSi (V), (CH3)H2Si (VIII), H3Si (XI),
and C13Si (III). O n p a s s i n g f r o m I to V and t h e n to VIII, XI, and I l l , the i n t e n s i t y of the m a x i m u m of the
l o w - f r e q u e n c y b a n d d e c r e a s e s , while the i n t e n s i t y of the h i g h - f r e q u e n c y band i n c r e a s e s . While the l o w -
f r e q u e n c y band has the m a x i m u m i n t e n s i t y and the h i g h - f r e q u e n c y band has the m i n i m u m i n t e n s i t y for I,
the r e v e r s e d i s t r i b u t i o n of i n t e n s i t i e s of t h e s e b a n d s is o b s e r v e d f o r III.

I n [2] it was shown that the line at 3110 c m -1 b e l o n g s to v i b r a t i o n s with p r i m a r y p a r t i c i p a t i o n of the

a - C - H b o n d s of the t h i o p h e n e r i n g , while the l i n e s at 3073 and 3086 c m - I a r e a f f i l i a t e d p r i m a r i l y with the
f l - C - t I b o n d s . O u r data c o n f i r m t h i s . I n fact, the band at 3110 c m "l, which is a b s e n t in the IR s p e c t r a of
2 , 5 - d i s u b s t i t u t e d t h i o p h e n e s (XV -XXXI), shows up d i s t i n c t l y in the s p e c t r a of 2 , 3 - d i s u b s t i t u t e d t h i o p h e n e s
(XXXII-XXXV). One b r o a d l o w - i n t e n s i t y band is u s u a l l y o b s e r v e d in the s p e c t r a of XVI-XXX i n the r e g i o n
of the C - H s t r e t c h i n g v i b r a t i o n s . On the whole, the v ( C - H ) b a n d s of the t h i o p h e n e r i n g a r e of low i n t e n -
s i t y . The e x a m i n e d r e g u l a r i t i e s m a y t h e r e f o r e have only l i m i t e d a p p l i c a t i o n f o r the i d e n t i f i c a t i o n of the
t h i e n y l g r o u p in o r g a n o s i l i c o n d e r i v a t i v e s of t h i o p h e n e f r o m the IR s p e c t r a .

Skeletal Vibrations of the Thiophene Ring

The a b s o r p t i o n b a n d s at ~ 1 5 0 0 - 1 5 4 0 , 1400-1445, and 1335-1365 c m -1 [3, 4] c o r r e s p o n d to the s t r e t c h -

i n g v i b r a t i o n s of the t h i o p h e n e r i n g i n 2 - s u b s t i t u t e d t h i o p h e n e s . A b s o r p t i o n b a n d s at 1503 ~ 3 , 1410 ~- 2, and
1332 * 2 c m -1 a r e o b s e r v e d f o r 2 - t h i e n y l s i l a n e s I - X V . The m o s t i n t e n s e band is at 1410 c m -1. T h e i n -
t e n s i t i e s of the m a x i m a of the o t h e r two b a n d s a r e c o m p a r a b l e and have about h a l f the i n t e n s i t y of the band

414
at 1410 cm -1. T h e s e t h r e e a b s o r p t i o n bands can be u s e d as analytical bands for the identification of 2-
thienylsilane s.
2,5-Disubstituted thiophenes XVI-XXXI have a b s o r p t i o n bands at 1490-1520, 1390-1420, and 1275-
1318 c m -1. The intensities of t h e s e a b s o r p t i o n bands a r e p r i m a r i l y d e t e r m i n e d by the nature of the sub-
stituents in the thiophene ring. Thus, if two silyl substituents are attached to the thiophene ring in the 2-
and 5-positions, the r a t i o of the intensities of the m a x i m a of the bands at 1495, 1410, and 1280 cm - I is
3 : 1 : 2 (XIX, XX, and XXV) o r 2 : 1 : 2 (XXII and XXIV), i.e., the 1410 cm -1 band is the l e a s t intense band.
R e p l a c e m e n t of one of the o r g a n o s i l i c o n s u b s t i t u e n t s by a chlorine a t o m leads to a c e r t a i n shift in the band
at 1410 c m -1 to the h i g h - f r e q u e n c y side and a s h a r p i n c r e a s e in its intensity with a s i m u l t a n e o u s d e c r e a s e
in the intensities of the m a x i m a of the bands at 1280 and 1495 c m -1 (XVH, XXIX, and XXIII). The i n t r o d u c -
tion of m e t h y l and silyl substituents into the 2 - and 5 - p o s i t i o n s o f t h e t h i o p h e n e ring leads to a d e c r e a s e in
the intensity of the m a x i m a of all t h r e e of the e x a m i n e d a b s o r p t i o n bands to e x t r e m e l y low values (XVI,
XXI, and XXX).
The a b s o r p t i o n bands at 840-870, 740-770, 545-570, and 440-470 c m -i a r e r e l a t e d to the d e f o r m a t i o n
v i b r a t i o n s of the thiophene ring [4, 5]. However, these bands a r e of low intensity and a r e frequently o v e r -
lapped by the bands that c o r r e s p o n d to the v i b r a t i o n s of the substituents in the thiophene ring. We m a d e
a c o m p l e t e l y unambiguous identification of the d e f o r m a t i o n v i b r a t i o n s only for I-XV, in the IR s p e c t r a Of
which weak bands at 570 4-5 and 480 :~ 5 c m -1 a r e o b s e r v e d .
We did not isolate the a b s o r p t i o n band r e l a t e d to the ring pulsation v i b r a t i o n [3, 5], i n a s m u c h as it
is o v e r l a p p e d by one of the d e f o r m a t i o n v i b r a t i o n s of the C - H bonds [6].

Deformation Vibrations of the Thiophene Ring C- H Bonds

The a b s o r p t i o n bands at 1215-1240, 1075-1085, and 1030-1050 c m -I a r e r e l a t e d to the in-plane v i b r a -
tions of the C - H bonds of the 2 - s u b s t i t u t e d thiophene ring [3, 4]. N a r r o w intense bands at ,..1220, 1090,
and 1 0 1 0 " 1 0 c m - I a r e o b s e r v e d in the s p e c t r a of monosubstituted thiophenes I-XV. F o r 2,5-disubstituted
thiophenes the a b s o r p t i o n m a x i m a at 1210-1225 and 975-1030 c m -1 c o r r e s p o n d to this vibration, while the
two a b s o r p t i o n bands at 1222 ~-3 and 1110 ~-2 cm -1 c o r r e s p o n d to this v i b r a t i o n for 2,3-disubstituted t h i o -
phenes (XXXII-XXXV).
The a b s o r p t i o n bands at 890-915, 780-855, and 670-725 c m -1 c o r r e s p o n d to the o u t - o f - p l a n e d e f o r m a -
tion v i b r a t i o n s of the C - H bonds of the 2 - s u b s t i t u t e d thiophene ring [3, 4]. In the s p e c t r a of I-XV, the t h r e e bands
at 865 =~5, 760 ~ 10, and 715 ~-5 cm - I c o r r e s p o n d to this vibration. Absorption is o b s e r v e d at w i d e r r a n g e s
(750-820 and 670-715 c m -l) in the s p e c t r a of 2,5-disubstituted thiophenes XVI-XXXI. The s m a l l n u m b e r
of i n v e s t i g a t e d compounds, which have m a n y a b s o r p t i o n bands o v e r the e x a m i n e d range, made it i m p o s s i b l e
f o r us to isolate the a b s o r p t i o n bands r e l a t e d to the o u t - o f - p l a n e v i b r a t i o n s of the C - H bonds in 2 , 3 - d i s u b -
stituted thiophenes (XXXII-XXXV). It has been noted [7] that the o u t - o f - p l a n e d e f o r m a t i o n v i b r a t i o n s of
the C - H bonds in thiophene d e r i v a t i v e s a r e l e s s s e n s i t i v e to the effect of substituents than the analogous
v i b r a t i o n s in substituted b e n z e n e s .

Vibrations of Silyl Groups Attached to the Thiophene Riog

It is known that the v i b r a t i o n a l s p e c t r a of o r g a n o s i l a n e s display a c h a r a c t e r i s t i c p e c u l i a r i t y called
[8] the " b a r r i e r effect of the silicon a t o m . " A t h e o r e t i c a l calculation of the v i b r a t i o n a l s p e c t r a of e t h y l -
c h l o r o s i l a n e s [9, 10] shows that f o r s u b s t a n c e s of the RSi(Ri) 3 type, where R is a fixed organic grouping,
but R i is a v a r i a b l e substituent, the set of f r e q u e n c i e s and the f o r m s of the n o r m a l v i b r a t i o n s of R is a l -
m o s t c o m p l e t e l y independent of the nature of R i. Any silyl grouping can t h e r e f o r e be c h a r a c t e r i z e d by
the a p p r o p r i a t e set of a b s o r p t i o n bands. No difficulties a r e e n c o u n t e r e d in the a s s i g n m e n t of the bands
c h a r a c t e r i s t i c f o r the S i - C H 3 , Si-C2H~, S i - H a l , and S i - H bonds [11].
Let us e x a m i n e t h i e n y l s i l a n e s that contain an S i - C 1 bond in s o m e w h a t g r e a t e r detail (Table 2). It
is known that the s t r e t c h i n g v i b r a t i o n u s u a l l y a s s o c i a t e d with the p r e s e n c e of an S i - C 1 bond in a m o l e c u l e
has a c o m p l e x f o r m [11, 12]. In view of this, it might have been e x p e c t e d that the f r e q u e n c y of this v i b r a -
tion, v(Si-C1), depends on a l a r g e n u m b e r of i n t r a m o l e c u l a r f a c t o r s . However, it has b e e n shown e x p e r i -
m e n t a l l y [13] that v(Si-C1) f o r (Ri)3SiC1 compounds is l i n e a r l y r e l a t e d to ~ * o f substituents R i, i.e., at
l e a s t f o r this type of compound the chief r e a s o n f o r the change in the position of v(Si-C1) is the inductive
effect of substituents R i. On the b a s i s of this, the i n c r e a s e in v (Si-C1) on p a s s i n g f r o m XVI and then to (IX,
XIX, XXIV) can be explained p r i n c i p a l l y by an i n c r e a s e in the e l e c t r o n - a c c e p t o r p r o p e r t i e s of the thienyl g r o u p -

415
TABLE 2. Frequencies of the ing. The increase in ~s(Si-C1)from 510 to 562 cm -1 (XXX, II, and
S y m m e t r i c a l (vs) and A s y m - XXXI) also attests to an i n c r e a s e in t h e - I effect of the thienyl group.
m e t r i c a l (Vas) S t r e t c h i n g Taking into account the data in [13] and the fact that the ~* constant
Vibrations of the S i - C 1 Bond of the 2-thienyl group is 0.93 [14], one can approximately evaluate
in the IR S p e c t r a of the
Investigated Compounds the r constants of substituted thienyl groups X-- x - ~

Compound u s, c m "I Uas, c m "I Calculations have shown that the ~* values a r e 0.63, 0.95, 0.95, and
1.13, r e s p e c t i v e l y , for X=CH3, SiH2C1 , Sill3, and C1. Thus, the
Ill 53o 590 same tendency is followed in thiophene derivatives as in phenyl de-
IV 512 552 rivatives: e l e c t r o n - d o n o r groupings lower the acceptor capacity
VI 516
IX ,535 of the thienyl substituent as a whole, while e l e c t r o n - a c c e p t o r group-
XVI 530 ings r a i s e it.
XVII 545
XIX 540
XXIV 54o The v(Si-C1) frequencies are d e p r e s s e d in thienylchlorosilanes
XXVI 545 580 VI, XXXII, and XXXIII, which contain one o r two methyl groups at-
XXVIII 517
XXX 510 585 tached to the silicon atom. Replacement of the ethyl group by a
XXXI 562 59o
XXXII 495 m e t h y l group in s i m i l a r l y constructed XXXIV and XXXIII leads to
XXXIII 5o5 550 a d e c r e a s e in v as(Si-C1)by 25 c m - l . The r e a s o n for the d e c r e a s e
XXXIV 510 575
XXXV 512 585 in the frequencies of the stretching vibrations of the S i - C 1 bond is
the effect of ~, ~ conjugation - , ~c-' s~ - - o We examined this ef-
fect in detail in a study of methyl(ethyl)chlorosilanes by IR and NMR
s p e c t r o s c o p y [15].
We examined the effect of d v - p ~ interaction in the Si-thienyl fragment and the dependence of this
effect on the nature of t h r e e other substituents attached to the silicon atom in [1, 16-19]. We note h e r e
only that the capacities of the thienyl and phenyl groups for dlr-plr interaction with the silicon atom are
approximately identical.

EXPERIMENT AL
The IR spectra of pure liquid samples of the organosilicon derivatives of thiophene were obtained
with a UR-20 spectrometer.

LITERATURE CITED
1. A . N . Egorochkin, N. S. Vyazankin, A. I. Burov, E. A. Chernyshev, V. I. Savushkina, and O. V. Kuz'
min, Khim. Geterotsikl. Soedin., 1483 (1972).
2. Ya. M. Kimel'fel'd, V. T. Aleksanyan, N. N. Magdesieva, and Yu. K. Yur'ev, Zh. Strukt. Khim., 7,
42 (1966).
3. M. Horak, I. J. Hyams, and E. R. Lippingott, Spectrochim. Acta, 22, 1355 (1966).
4. J . J . P e r o n , P. Saumagne, and J. M. L e b a r s , Spectrochim. Acta, 26A, 1651 (1970).
5. M. Rico, J. M. Orza, and J . Morcillo, Spectrochim. Acta, 2.~.1,689 (1965).
6. V . T . Aleksanyan, Ya. M. Kimel'fel'd, N. N. Magdesieva, and Yu. K. Yur'ev, in: Optics and Spectro-
scopy [in Russian], Vol. 3, Nauka, Leningrad (1967), p. 168.
7. A. Minori and K. Yuzo, J. Mol. Spectr., 3__4.,4 288 (1970).
8. A . D . Petrov, Yu. P. Egorov, V. F. Mironov, G. I. Nikishin, and A. A. Bugorkova, Izv. Akad. Nauk
SSSR, Otd. Khim. Nauk, 50 (1956).
9. N . N . Vyshinskii, M a s t e r ' s Dissertation [in Russian], Gor'kii (1963).
10. S . E . Rudakova, M a s t e r ' s Dissertation [in Russian], Moscow (1965).
11. N . A . Chumaevskii, Vibrational Spectra of Heteroorganic Compounds of Group IVB and VB Elements
[in Russian], Nauka, Moscow (1971).
12. L . A . Leites, I. D. Pavlova, and Yu. P. Egorov, T e o r . i ]~ksperim. Khim., 1, 311 (1965).
13. H. Kriegsmann, Allg. Prakt. Chem., 19,.5 (1968L
14. P . A . Ten, Thije, and M. A. Janssen, Rec. T r a v . Chim., 84, 1169 (1965).
15. A . N . Egorochkin, N. S. Vyazankin, A. I. Burov, and S. Ya. Khorshev, Izv. Akad. Nauk SSSR, Set.
Khim., 1272 (1970).
16. A . N . Egorochkin, S. Ya. Khorshev, N. S. Vyazankin, T. I. Chernyshev, and O. V. Kuz'min, Izv. Akad.
Nauk SSSR, Set. Khim., 544 (1971).

416
17. A . N . Egorochkin, S. Ya. Khorshev, N. S. Vyazankin, T. I. Chernysheva, and O. V. Kuz'm[n, Izv. Akad.
Nauk SSSI~, Ser. Khim., 776 (1971).
18. A . N . Egorochkin, N. S. Vyazankin, A. I. Burov, E. A. Chernyshev, V. I. Savushkina, and B. M. Tabenko,
Khim. Geterotsikl. Soedin., 911 (1972).
19. A . N . Egorochkin, N. S. Vyazankin, S. E. Skobeleva, S. Ya. Khorshev, E. A. Chernyshev, V. I. Savush-
kina, and O. V. Kuz'min, Khim. Geterotsikl. Soedin., 1057 (1972).

417
 INVESTIGATION OF H COMPLEXES OF 2-THIENYL
PHENYL KETONES BY I R S P E C T R O S C O P Y

N. F. Pedchenko, N. D. T r u s e v i c h , UDC 541.571.9:547.73 : 543.422.4

and V. F. Lavrushin

The shifts of the s t r e t c h i n g v i b r a t i o n s of the hydroxyl groups of phenol and pentachlorophenol

during the f o r m a t i o n of i n t e r m o l e c u l a r hydrogen bonds with 2-thienyl phenyl ketones contain-
ing substituents in the benzene ring w e r e m e a s u r e d . A c o r r e l a t i o n dependence between the
AAPOt-I values and o~- substituent constants was established.

In a p r e c e d i n g communication [1] we d e s c r i b e d the r e s u l t s of an investigation of the p r o t o n - a c c e p t o r

capacity of 2-thienyl phenyl ketones by UV, PMR, and IR s p e c t r o s c o p y . The magnitude of the shift of the
frequency of the s t r e t c h i n g v i b r a t i o n s of the OH group of phenol in the IR s p e c t r a , which a r i s e s during the
f o r m a t i o n of a ) C ~ O - . . H - O - h y d r o g e n b o n d , can be used as a m e a s u r e of the s t r e n g t h of the b a s e s
in a s e r i e s of monotypic compounds [2].
Continuing our study of the basic p r o p e r t i e s of thienyl phenyl ketones, we have m e a s u r e d the shift
in the f r e q u e n c i e s of the s t r e t c h i n g v i b r a t i o n s of the hydroxyl groups (VOH) of phenol and pentachlorophenol
in c a r b o n t e t r a c h l o r i d e solutions that a r i s e s as a consequence of the f o r m a t i o n of an i n t e r m o l e c u l a r h y d r o -
gen bond with monosubstituted 2-thienyl phenyl ketones.
The a b s o r p t i o n s p e c t r a of solutions of phenol and pentachlorophenol at v a r i o u s 2-thienyl phenyl ketone
concentrations a r e p r e s e n t e d in Fig. 1. The s p e c t r a contain, in addition to the absorption band of a free
hydroxyl group for phenol o r the a s s o c i a t e d i n t r a m o l e c u l a r hydrogen bond for pentachlorophenol as ketone
is added to a solution of the p r o t o n - d o n o r , a wider band that is shifted to lower f r e q u e n c i e s . The half-width
of this band is m u c h g r e a t e r than the half-width of the absorption band of a f r e e hydroxyl group. When the
ketone concentration in the s y s t e m is i n c r e a s e d , the intensity of the high-frequency band falls, while the
intensity of the l o w - f r e q u e n c y band i n c r e a s e s . This s o r t of the change i n t h e s p e c t r u m a t t e s t s to the develop-
ment of a hydrogen bond between the components of the solution (the complex composition is 1 : 1 [3, 4]).
The b r o a d band is affiliated with a hydroxyl group that p a r t i c i p a t e s in the f o r m a t i o n of an H complex.
O n e ' s attention is drawn to the inflection at ~3300 cm -~ on the contours of the POH o b a n d of the H
complex of pentachlorophenol with 2-thienyl phenyl ketone (Fig. 1, c u r v e b). T h e r e a r e ~ A ~ r a d i c t o r y opin-
ions in this connection in the l i t e r a t u r e . F r i t z s c h e , who o b s e r v e d the a s y m m e t r y of these bands [5], c o n -
s i d e r e d them to be doubled and explained this fact by the p r e s e n c e of two t y p e s of H c o m p l e x e s of phenol
with c a r b o n y l b a s e s . However, Iogansen and c o - w o r k e r s [6] supposed that t h e r e is only local distortion
of the usual contour of the b r o a d band that is caused by disruption of the c o m p e n s a t i o n of the a b s o r p t i o n
in the region of the f i r s t overtone of the c a r b o n y l band and also possibly due to the r e s o n a n c e interaction
of the contiguous POH...O and 2 PC = O v i b r a t i o n a l levels.
We studied the position of the f i r s t overtone of the c a r b o n y l group of the investigated ketone in c a r -
bon t e t r a c h l o r i d e solution (2vC =O for 2-thienyl phenyl ketone, for e x a m p l e , is 3260 c m - i ) . In the f o r m a -
tion of the H c o m p l e x of the ketone with pentachlorophenol (which is a m o r e acidic proton donor than phenol),
the 2p C =O band u n d e r g o e s a c o n s i d e r a b l e shift and, c o r r e s p o n d i n g l y , the c o m p e n s a t i o n of the absorption
at 3300-3350 c m -1 is disrupted (when the s p e c t r u m is r e c o r d e d with a d o u b l e - b e a m s p e c t r o m e t e r with iden-

M. G o r ' k i i Kharkov State University. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No.

4, pp. 482-485, April, 1974. Original a r t i c l e s u b m i t t e d O c t o b e r 10, 1972; r e v i s i o n submitted July 13, 1973.

9 1975 Plenum Publishing Corporation, 227 West l 7th Street, New York, N.Y. 10011. No part o f this publication may be reproduced,
stored in a retn'eval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy o f this article is available from the publisher for $15.00.

418
 T A B L E 1. IR S p e c t r a of H C o m p l e x e s of ~-C4H3SCOR with Phenol
(1) and Pentachlorophenol (2)

Ihydrogen hydrogen
I bond bond
VOH...O, A V O K , i strength, vorL..o. AV0 ~, strength,
en2-1 kcal/mole cm-i CrTl-1 keaI/mole
~cc~topcc~to{ acc,~olacc~ to

343O 181+-1 3,1 3,9 3350 242+_2 4,2 4,7

II 4-Anisyl 3421 190+_2 3,3 4,1 264 1 4.6 4,9
III
IV
4-Tolyt
Phenyl
3433
3439
1~s722 3,1
3,0
3,9
3,8
73~ 4,2
4,2
4,7
4,7
V 4-Diphenylyl 3442 169_+2 2,9 3,8 233_+1 4,0 4,6
VI 4-Chlorophenyt 3451 160+3 2,8 3,6 227 4,0 4,5
VII
VIII
4-Bromophenyl
4-Nitrophenyl
3453 i~8~2 2,7
2,5
3,.6
3,3
3373 219~82 3,8
3,4
4,4
4,1
IX 2-Thienyl 3~3 168 2,9 3,8 3350 235+2 4,1 4,6

* Benzophenone.

avoM,cn3 "I &va~,ciE -I

?00,
co c0c,,oH

- _ ~

150.

0
.
3400
. .
3200
. .
3600
. . .
3400 3200 c m -1
100.

4,5 5~0 5,5

~ 6,0 6,5
b
pKsH*
1 200

Fig. 1 Fig. 2
Fig. 1. IR s p e c t r a of solutions of phenol (a, c =0.01 M) and pentachlorophenol (b, c =0.03
M) containing 2-thienyl phenyl ketone. Ketone concentration: 1) 0.00; 27 0.01; 3) 0,05; 4)
0.10 M (a); 1) 0.00; 27 0.05; 3) 0.10; 4) 0.15 M (b).
Fig. 2, Dependence of the pK of protolytic equilibrium and the AvOH values of phenol (a)
and pentachlorophenol (b) (the Roman n u m e r a l s in the figure c o r r e s p o n d to the n u m b e r s
of the compounds in Table 17,

t i c a l amounts of c a r b o n y l compound in the paths of both b e a m s ) . We t h e r e f o r e obtain a b r o a d s o l i t a r y a b -

sorption band of an a s s o c i a t e d hydroxyl group of the p r o t o n donor with a s u p e r i m p o s e d overtone of the c a r -
bonyl group on the b a s e of the s p e c t r o g r a m (as noted by Iogansen [6]7.
The shifts of the f r e q u e n c i e s of the s t r e t c h i n g v i b r a t i o n s of the hydroxyl groups of phenol and p e n t a -
chlorophenol that we obtained a r e p r e s e n t e d in Table 1. F o r c o m p a r i s o n , the AvOH values for H c o m p l e x e s
with benzophenone a r e also p r e s e n t e d in Table 1. R e p l a c e m e n t of the phenyl ring in the benzophenone m o l e -
cule by a thienyl ring is a c c o m p a n i e d by a d e c r e a s e in AvOH (I and V), i.e., by a d e c r e a s e in the basic
p r o p e r t i e s of 2-thienyl phenyl ketone.

A similar fact was noted in the case of replacement of the benzene ring in the chalcone molecule by
a thiophene ring next to the carbonyl group and was explained by the dominating effect of the negative in-
ductive effect of the thienyl ring as compared with its positive conjugation effect [4]. In addition, the thienyl
grouping creates additional steric hindrance to the approach of the phenol and pentachlorophenol molecules
to the C =O group.

It is also a p p a r e n t f r o m the data in Table 1 that the AVot t value is sensitive to the effect of s u b s t i t -
uents in the 4 - p o s i t i o n of the benzene ring. The introduction into the 2-thienyl phenyl ketone molecule of

419
 electron-donor substituents (II and l/I) leads to an increase in the AvOH value, i.e., to an increase in the
basicity of the compounds, while electron-acceptor substituents bring about a decrease in the electron
density on the oxygen of the carbonyl group and thereby cause a decrease in the AvOH values (VI and VII).
Thus, the strength of the hydrogen bonds formed increases in the following o r d e r of substituents: Br < C1 <
H < C~H~< CHs <OCH 3. The calculated values of the hydrogen bond energy [7, 8] are presented in Table 1
and are within the limits of the values usually observed for these sorts of H complexes.
The strength of the hydrogen bonds increases in the above o r d e r of substituents when phenol is r e -
placed by the more acidic proton-donor pentachlorophenol.
The shifts of the frequencies of the stretching vibrations of the hydroxyl groups of phenol and penta-
chlorophenol correlate satisfactorily (r is 0.95 for phenol and 0.97 for pentachlorophenol) with the p a r a m -
eters of substituents in the benzene ring in accordance with the equation ( ~ O H R - AvOH H) Nhc/2.303RT =
po-+, where AVoHR and AvOHH are the shifts in the frequencies of the stretching vibrations of the hydroxyl
groups of phenol and pentachlorophenol with substituted and unsubstituted 2-thtenyl phenyl ketones, and N,
h, c, T, and R are known physical constants. The p values of-0. 068 for phenol a n d - 0 . 0 9 3 for pentachloro-
phenol confirm the gr eat er polarization of the carbonyl group of ketones during the formation of a hydro-
gen bond with pentachlorophenol than during association with phenol. Using the linear dependence between
the AAvOH values and ~+ substituent constants that we obtained, we calculated the AvOH values for 2-thienyl
4-nitrophenyl ketone and for 2-thienyl 4-diphenylyl ketone, which we were unable to determine because of
the insolubility of these ketones in carbon tetrachloride.
It is interesting to note the observed approximately linear dependence between the previously obtained
[1] protolytic equilibrium constants and the shifts of the frequencies of the stretching vibrations of the
hydroxyl groups of the proton-donor as a result of the formation of a hydrogen bond with substituted 2-
thienyl phenyl ketones (Fig. 2).

EXPERIMENTAL
The 2-thienyl phenyl ketones were synthesized from thiophene and the appropriate acid chlorides
via known methods [9].
The carbon tetrachtoride, phenol, and pentachlorophenol were purified in accordance with known methods.
The frequencies of the stretching vibrations of the hydroxyl groups of the phenols were measured
with a UR-20 spectrometer (with an LiF prism and a cuvette thickness of 4 mm for phenol and 1 mm for
pentachlorophenol) in CC14 solutions. The phenol concentration was 0.01 M, the pentachlorophenol concen-
tration was 0.03 M, and the ketene concentrations were 0.05 and 0.15 M, respectively. A solution of the
ketone in carbon tetrachloride of the same concentration was placed in the comparison cuvette. The f r e -
quency of the stretching vibrations of the hydroxyl group of unassociated phenol was taken to be 3610 ~-1
cm -1. In connection with the fact that the experimentally determined v OH...CI band of pentachlorophenol
is the band of the intramolecular hydrogen bond, the frequency of the stretching vibrations of the hydroxyl
group of pentachlorophenol was taken as 3592 cm -i in accordance with [10]. The position of the maximum
of the band of the H complex was found by the kanod method [11]. The measurements were repeated three
to five times in two independent experiments and were processed statistically with a reliability (~) of 0.95.

LITERATURE CITED
1. N . F . Pedchenko, N. D. Trusevich, N. S. Pivnenko, and V. F. Lavrushin, Zh. Organ. Khim., 8, 1882
(1972).
2. M . I . Vol'pin (editor), Modern Problems of Physical Organic Chemistry, Wiley (1972).
3. T. Gramstad, Speetr. Acta, 1..~9,497 (1963).
4. L . A . Kutulya, S. V. Tsukerman, Yu. N. Surov, N. S. Pivnenko, and V. F. Lavrushin, Zh. Obshch.
Khim., 40, 1337 (1970).
5. H. Fritzsche, Spectr. Acta, 21, 789 (1965).
6. A . V . Iogansen and B. V. Rassadin, Zh. Prirodnykh Soedin., 11,182 (1969).
7. N . D . Sokolov, in: Hydrogen Bonding [in Russian], Nauka, Moscow (1964), p. 7.
8. A.V. Iogansen and B. V. Rassadin, Zh. Prirodnykh Soedin., 11, 834 (1969).
9. H . D . Hartough, Thiophene and Its Derivatives, InteVseienee Publishers, New Y o r k - L o n d o n (1952).
10. S.M. Petrov and V. S. Pilyugin, Zh. Prirodnykh Soedin., 15, 555 (1971).
11. S.V. Tsukerman, Yu. N. Surov, V. F. Lavrushin, and Yu. K. Yur'ev, Khim. Geterotsikl. Soedin.,
868 (1966).

420
CYCLIZATIOI~ OF SOME SUBSTITUTED 2- (N-ACYLTHIOUREIDO)-
3-CARBETHOXYTHIO PHENES

A. A. Dobosh, S. M. K h r i p a k , UDC 547.73.85

and I. V. Smolanka

The i n t r a m o l e c u l a r cyclization of 2-(N-aeylthioureido)-3-carbethoxy-4,5-R,l~'-thiophenes

with the formation of potassium salts of 2-thio-4-oxo-5,6-R,RV-3,4-dihydrcthieno[2,3-d]
pyrimidine was studied, and some of t h e i r S - d e r i v a t i v e s were obtained.

The i n t r a m o l e c u l a r cyclization of thiophenes containing a 2 - N - R - t h i o u r e i d o group, namely, 2-fN-

a c y l t h i o u r e i d o ) - 3 - c a r b e t h o x y - 4 , 5 - R , R ' - t h i o p h e n e s (AT), leads to pyrimidinothicphenes. The AT were ob-
tained by reaction of 2 - a m i n o - 3 - c a r b e t h o x y - 4 , 5 - d i m e t h y l t h i c p h e n e [1] (I) and 2 - a m i n c - 3 - c a r b e t h o x y - 4 , 5 ,
6,7-tetrahydrobenzo[d]thiophene [1] (VII) with benzoyl and cinnamoyl isothioeyanates (II, IV, VIII, and IX).
CHa~COOC2H5 CHa'-.~--~I COOC~H5 CH3~COOC2H5
C H : ~ S / J ~ N HCSNHCOC6H5 CH3/I'~S I.fiJ"-NH2 ~CH3/q-~S/~" NHCgNHC0 CH= CHC6H5
II I IV

V !11 YI

Heating II and IV in alkali solution gives potassium salt III, which r e a c t s readily with some halo de-
rivatives to give S - d e r i v a t i v e s V and VI.
Similarly, potassium salt XI was obtained f r o m VIII, IX, and X [21.
..~COOC2H 5 "

~ ~-Sj "-NH2
VII -~...~ 0
" ~ COOC2fls COOC2 NH

~-Sf "NHCSNHCO%H5 ~ "-S/ "NHCSN OCH=CHC6H5 SH

.,, ,x ? J
SK
XI

The cyclization of AT under the influence of alkali takes place with splitting out of acyl groups and
f o r m a t i o n of condensed pyrimidinothiophenes that do not contain a substituent in the 3-position of the p y r i -
midine ring.
It might have been a s s u m e d that the cyclization of AT would give 3 - N - a c y l derivatives of the p y r i m i d -
ine ring, which are hydrolyzed with splitting out of acyl groups by the action of e x c e s s alkali. To v e r i f y
this assumption, we c a r r i e d out the cyclization of AT with a two-fold amount and e q u i m o l e c u l a r amounts
of alkali. In the first case, III and XI were formed, while in the second case a mixture from which ~38%

Uzhgorod State University. T r a n s l a t e d from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 486-
488, April, 1974. Original a r t i c l e submitted D e c e m b e r 19, 1972.

9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy o f this article is available from the publisher for $15.00.

421
 tgE
4.% -~ of cyclic products III and XI and N42%of s t a r t i n g AT w e r e isolated
.. :." ~,
4,~. " \
is f o r m e d . Thus, the cyclization of AT with alkali is a c c o m p a n i e d
by simultaneous splitting out of acyl groups and is not a c c o m p a n -
ied by h y d r o l y s i s of 3 - N - a c y l d e r i v a t i v e s of the p y r i m i d i n e ring.
4,2 ~ ~ F o u r absorption m a x i m a a r e o b s e r v e d in the UV s p e c t r a of
4,, :'~L ~ r. .'.. lI and VIII, while t h r e e a b s o r p t i o n m a x i m a a r e o b s e r v e d in the UV
~\, !i;\ ~'~ s p e c t r a of IV and IX. The intense a b s o r p t i o n band at 230-240 nm
~.i~i (log a 4.0-4.3) is a s s o c i a t e d with the fact that these compounds
e x i s t in the thione form in alcohol solution (Fig. 1).

3,a2 i \ The UV s p e c t r a of S - d e r i v a t i v e s V and VI a r e s i m i l a r , and

3,7- JJ ~4 "\ ~ 3 i n a s m u c h as t h e s e compounds e x i s t in the thiol f o r m , the a b s o r p -
!
V tion band at 230-240 nm is absent in t h e i r s p e c t r a ; this is in a g r e e -
240 280 320 360 400 A ~ nl'~/1
m e n t with the data in [3, 4]. P o t a s s i u m salt XI has two absorption
Fig. i . UV spectra: i) 2- m a x i m a at 285 and 335 (log e 4.20, 4.36).
(N-cinnamoylthioure ido) -3 -
The a b s o r p t i o n band at 355-370 nm of II, IV, VIII, and IX
c a r b e t h o x y - 4 , 5-dimethylthloph-
c o r r e s p o n d s to the absorption of the acylthioureido c h r o m o p h o r e .
ene (IV); 2i 2-(N-benzoylthioureido)-
The intense absorption bands at 260-340 nm a r e due to a b s o r p -
3-carbethoxy-4,5-dimethylthiophene
tion of the a r o m a t i c s y s t e m s .
(If); 3) p o t a s s i u m salt of 2 - t h i o - 4 -
oxo-5, 6 - d i m e t h y l - 3 , 4 - d i h y d r o t h i - The UV s p e c t r o s c o p i c data, a n u m b e r of a l t e r n a t i v e s y n t h e s e s ,
eno[2,3-d]pyrimidine (Ill); 4) 2 - e t h - and the r e s u l t s of e l e m e n t a r y a n a l y s i s c o n f i r m the c o r r e c t n e s s
ylthio-4-oxo-5,6-dimethyl-3,4-di- of the s c h e m e s p r e s e n t e d above.
hyd rothieno [2,3-d]pyrimidine (V).

EXPERIMENTAL
The UV s p e c t r a of alcohol solutions (c 1 9 10 -5 to 1 9 10 -2 M) w e r e r e c o r d e d with an S F - 4 A s p e c t r o -
photometer.
2 - ( N - B e n z o y l t h i o u r e i d o ) - 3 - c a r b e t h o x y - 4 , 5 - d i m e t h y l t h i o p h e n e (II). A 2-g (0.01 mole) s a m p l e of I
and 1.6 g (0.01 mole) of benzoyl isothiocyanate w e r e heated in ethanol f o r 30 m i n on a b o i l i n g - w a t e r bath.
Workup of the m i x t u r e gave 3.4 g (94%) of a product with mp 195-197 ~ (from benzene). Found: C 56.3; N
7.8; S 17.8%. CI?HIsN203S2. Calculated: C 56.3; N 7.7; S 17.7%.
2-(N-Cinnamoylthioureido)-3-carbethoxy-4,5-dimethylthiophene (IV). A 2-g (0.01 mole) sample of
I and 1.9 g (0.01 mole) of cinnamoyl isothiocyanate were heated in benzene on a boiling-water bath for 1 h.
Workup of the mixture gave 3.4 g (87%) of a product with mp 191-193~ [from dimethyl sulfoxide (DMSO)].
Found: N 7.3%. C19H2~T203S2. Calculated: N 7.2%.
P o t a s s i u m Salt of 2 - T h i o - 4 - o x o - 5 , 6 - d i m e t h y l - 3 , 4 - d i h y d r o t h i e n o [ 2 , 3 - d ] p y r i m i d i n e (III). A m i x t u r e
of 3.6 g (0.01 mole) of II o r 3.9 g (0.01 mole) of IV and 1.1 g (0.02 mole) of p o t a s s i u m hydroxide in aqueous
alcohol solution was heated on a b o i l i n g - w a t e r bath f o r 2 h. Workup of the m i x t u r e gave 1.9 and 1.8 g (75
and 72%, r e s p e c t i v e l y ) of products with mp > 350 ~ (from aqueous ethanol). Found: C 38.6; N 11.2%.
C8HTKN2OS2. Calculated: C 38.6; N 11.2%. No melting-point d e p r e s s i o n was o b s e r v e d for m i x t u r e s of the
products.
2 - E t h y l t h i o - 4 " o x o - 5 , 6 - d i m e t h y l - 3 , 4 - d i h y d r o t h i e n o [ 2 , 3 - d ] p y r i m i d i n e (V). A m i x t u r e of 2.5 g (0.01
mole) of HI and 1.1 g (0.01 mole) of ethyl b r o m i d e in ethanol was heated for 1 h at 50-60 ~ Workup gave
1.8 g (76%) of a product with mp 230-231 ~ (from methanol). Found: N 11.8%. CIoHI2N2OS 2. Calculated
N II.7%.
2-Acetylthio-4-oxo-5,6-dimethyl-3,4-dihydrothieno[2,3-d]pyrimidine(VI). A mixture of 2.5 g (0.01
mole) of IT[ and 0.8 g (0.01 mole) of acetyl chloride was heated in benzene at 50-60~ for 30 min. Workup
gave 2.2 g (87%) of a product with mp 272~ (decompo, fromDMSO)o Found: N 11.0%. CIoHIoN202S2. Cal-
culated: N 11.0%.
2-(N-Benzoylthioureido)-3-carbethoxy-4,5,6,7-tetrahydrobenzo[d]thiophene (VIII). A 1.65-g (0.01
mole) sample of benzoyl isothioeyanate was added to 2.25 g (0.01 mole) of VII, which dissolved with the
evolution of a c o n s i d e r a b e l amount of heat. The m e l t began to c r y s t a l l i z e on cooling. Workup gave 3.7 g
(95%) of a product with m p 163-164 ~ (from methanol). Found: N 7.3%. C19H20N203S2. Calculated: N 7.2%.

422
 2-(N-Cinnamoylthioureido)-3-carbethoxy-4,5,6,7-tetrahydrobenzo[b]thiophene (IX). This compound
was obtained from VII by the method used to obtain IV. Workup gave 78%of a product with mp 202-20~ ~
(from benzene). Found: N 6.8%. C21H22N203S2. Calculated: N 6.8%.
Potassium Salt of 2-Thio-4-oxo-3,4,5,6,7,8-hexahydrobenzo[b]thieno[2,3-d]pyrimidine (XI). This
compound was similarly obtained from VIII and IX by the method used to obtain III. An equimolecular
amount of potassium hydroxide was used in the preparation of XI from X [2]. The yields were 80, 74, and
69% f r o m VIII, IX, and X, respectively; mp 345~ (decomp., from aqueous ethanol). Found: N 10~
Ci0HgKN2OS2. Calculated: N 10.1%. No melting-point depression was observed for mixtures oftheproducts.

LITERATURE CITED
11 K. Gewald, E. Sehinke, and H. B6ttcher, Chem. Ber., 9__99,94 (1966).
2o S. M. Khripak, A. A. Dobosh, and I. V. Smolanka, Khim. Geterotsikl. Soedin., 567 (1973).
3. G. F. Bol'shakov, V. S. Vatago, and F. B. Agrest, Ultraviolet Spectra of Heterocyclic Compounds [in
Russian], Khimiya, Leningrad (1969), p. 17.
4. I. V. Smolanka, A. A. Dobosh, and S. M. Khripak, Ukr. Khim. Zh:, 3._99,402 (1973).

423
5,6-TRIMETHYLENE T H I A PY R Y L I U M AND
5,6,7,8-TE T R A IIY D R O T H I O C H R O MYLIUM SALTS

V. G. Kharchenko, S. K . K l i m e n k o , UDC .~47.818.222 : 543.422.4

and M. N. Berezhnaya

5 , 6 - T r i m e t h y l e n e t h i a p y r y l i u m s a l t s have been obtained for the f i r s t t i m e . 5 , 6 - T r i m e t h y l e n e -

y - t h i o p y r a n s (or 5 , 6 , 7 , 8 - t e t r a h y d r o - y - t h i o c h r o m e n e s ) , which belong to a p r e v i o u s l y unknown
s e r i e s of t w o - r i n g sulfides, a r e f o r m e d by r e a c t i o n of the ~ , 6 - t r i m e t h y l e n e t h i a p y r y l i u m salts
(or 5 , 6 , 7 , 8 - t e t r a h y d r o t h i o c h r o m y l i u m salts) with G r i g n a r d r e a g e n t s and lithium aluminum hy-
dride.

1,5-Diketones r e a c t with hydrogen sulfide and hydrogen chloride to give t h i a p y r y l i u m , t e t r a h y d r o -

t h i o c h r o m y l i u m , o r s y m - o c t a h y d r o t h i o x a n t h y l i u m chlorides [1]. We have e s t a b l i s h e d that " s e m i e y e l i c "
1,5-diketones I - H I a r e oyelized to 5 , 6 - t r i m e t h y l e n e t h i a p y r y l i u m (IV, V, VII, and VIII) o r 5 , 6 , 7 , 8 - t e t r a h y -
d r o t h i o c h r o m y l i u m (VI and IX) salts in 40-65% yields on reaction with hydrogen sulfide and acids (hydro-
gen chloride and p e r c h l o r i c acid} i n g l a c i a l acetic acid o r e t h e r at 20-40~
R

(C ~ H2S/H X (C
CsH 5 C6H5
X-
I-Ill IV-IX 9

IV X=C1, n=l, R=H; V X=C1, n=l, R=C6Hs; VI X=CI, n=2, R=H; VII X=C[O4,
n=l, R=H; VIII X=C|O4, n=l, R=CeHs; IX X=C104, n='~, R=H
The f o r m a t i o n of s a l t s f r o m 1,5-diketones I - I I I and p e r e h l o r i e acid is c o m p l e t e a f t e r 6-7 h, while
up to 3 days are r e q u i r e d for the f o r m a t i o n of s a l t s with hydrogen chloride at 20-25 ~ The completion of
the r e a c t i o n can be judged f r o m the d i s a p p e a r a n c e of the starting 1,5-diketone and the c o r r e s p o n d i n g s u l -
fide with a thiopyran ring in the r e a c t i o n m i x t u r e .
Chlorides IV-VI exchange an anion with p e r c h l o r i e acid, p o t a s s i u m iodide, o r f e r r i c chloride at 20 ~
and undergo c o n v e r s i o n to, r e s p e c t i v e l y , p e r c h l o r a t e s VII-IX, iodides X-XII, o r t e t r a e h l o r o f e r r a t e s XIII
and XIV. Iodides X-XII and t e t r a o h l o r o f e r r a t e s XIII and XIV, r e s p e c t i v e l y , are s i m i l a r l y obtained f r o m the
reaction of p e r e h l o r a t e s V I I - I X with p o t a s s i u m iodide and a hydrochloric acid solution of f e r r i c ehloride
(Table 1). P e r e h l o r a t e s VII and IX add m e t h y l - , benzyl-, and phenylmagnesium halides to give 2,4--disub-
stituted 5 , 6 - t r i m e t h y l e n e - y - t h i o p y r a n s (XV and XVI) o r 5 , 6 , 7 , 8 - t e t r a h y d r o - y - t h i o e h r o m e n e s (XVII-XIX).
They are oxidized to the c o r r e s p o n d i n g 2,4-disubstituted salts X : ~ - ~ I (Table 1) by the action of 7 0 % p e r -
ehloric acid.
R R

R/~gHIg
Vii, iX
CIO~"
XV- XIX Vlll, XX-XXIII
XV, XX R=CHn, n=l; XVI, XXI R=CHzC6Hs, n=l; XVII, XXII R=CH3, n=2; XVIII,
XXIII R=CHzCd-15,n=~2; XIX R=C6Hs, n=~2

N. G. C h e r n y s h e v s k i i Saratov State U n i v e r s i t y . T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i e h e s k i k h Soed-

inenii, No. 4, pp. 489-492, April, 1974. Original article submitted N o v e m b e r 15, 1972.

9 1975 Plenum Publishing Corporation, 227 Nest 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

424
 TABLE 1. 5 , 6 - T r i m e t h y l e n e t h i a p y r y l i u m and 5,6,7,8-
Tet r a h y d r o t h i o c h r o m y l i u m Salts
{
Empirical Fs ,% Calc., % Yield,
Com-
pound rap, "Ca formula 9
El S CI S

IV H Cl 49--50 CI4HI3CtS 14,5 12,9 14,3 12,9 51

VII H [04 154--156 Ct4HI3CIO4S 11,3 10.4 11,3 10,2 65
X H f 164--165 CI4HI3ISb -- 9,4 -- 9,4 74
XIII
V
H
C6H5
gF' 106--107
142--144
CI4HI~CI4FeS
C2oH~rCIS
34,6
I 1,2
8.0
9,7
34.5
10.9
7,8
9,9
85
51
VIII C6H5 ICI04 213----215 C20H17C104S 9,2 8,1 9,2 8,3 59
XI C6H5 209--210 C2oH,vlS 1--3,6 7,4 -- 7,7 94
VI H CI 101--I03 CI~H,sC1S 12,3 13,5 12.2 60
IX H C104 162--163 C~sH,sCIO4S 10,8 9,7 tO,9 9,8 64
XIV H IFeCI4 113---i14 C15HIsCI4FeS 33,4 7,7 33,4 7,5 71
XII H 159--160 C~HLgSc t~-,8 8,9 9,1 95
XX CH~ CIO~ 186--1,87 C~sHIsCIO4S 9,9 10,,9 9,8 60
XXI CH~C6Hs[ CIO4 160--161 C21H19CIO4S 8,9 7,8 8,8 8,0 54
XXII CH3 CIO, 203--205 C,6H~vC104S 10,I 9,5 10,5 9,4 56
XXIII CHeC6Hs C104 155--158 C2~HmCIO4S 8,5 7,8 8,4 7,6 52

a) The p e r c h l o r a t e s and t e t r a c h l o r o f e r r a t e s were r e c r y s t a l l i z e d

from glacial acetic acid, the iodides were r e p r e c i p i t a t e d from
c h l o r o f o r m o r nitromethane solution by the addition of e t h e r , and
the chlorides were r e p r e c i p i t a t e d from c h l o r o f o r m o r acetic anhy-
dride solutions by the addition of absolute e t h e r , b) Found: I37.1%.
Calculated: I 37.3%. c ) F o u n d : I 35.8%. Calculated: I 35.8%.

TABLE 2. 5 , 6 - T r i m e t h y l e n e - y - t h i o p y r a n s and .5,6,7,8-Tetrahydro-

y -thiochromenes

Com- Emp~xical Found, % Calco, % Yield

rap, 2:
pound -formula
c!.j s c i H I s

XVI 52--53 C21H2oS 83,4 6.8 10,3 82,8 6,6 lO,5 81

XVII 49--51 C16H18S 79,5 7,1 13,4 79,2 7,5 13,2 73
XVIII 58--60 C22H22S 83,3 7.2 102 83,0 7,0 lO,1 90
XXIV 53---54 C14HI4S 78,2 614 15,0 78,5 6,6 t5,0 88
XXV 49--5l CIsHI6S 78,8 7,0 14,0 78,9 7,1 14,1 90

T A B L E 3. E l e c t r o n i c A b s o r p t i o n The C - 4 u n s u b s t i t u t e d s a l t s (VII and IX) s e e m of p a r -

S p e c t r a of Sulfides XVI and XVIII t i c u l a r p r e p a r a t i v e i n t e r e s t , i n a s m u c h as the s y n t h e s i s of
2 , 4 - d i s u b s t i t u t e d t w o - r i n g s u l f i d e s XV-XVIII and s a l t s XX-
Compound kmax, nm (hexane) ! logs XXIII, which c a n n o t be o b t a i n e d by o t h e r m e t h o d s , is p o s -
sible from them.
XVI 237, 299 4,43; 3,32
XVIII 238, 289 4,50; 3,45 L i t h i u m a l u m i n u m h y d r i d e r e d u c e s s a l t s VII and IX to
t h i o p y r a n s XXIV o r X-'XV. Sulfides XV, XVI, and X~XIV (Table
2) a r e m e m b e r s of the p r e v i o u s l y u n k n o w n h o m o l o g o u s s e r i e s
of t w o - r i n g s u l f i d e s with the 5 f i - t r i m e t h y l e n e - y - t h i o p y r a n
s t r u c t u r e . The s t r u c t u r e of s u l f i d e s XV-XVIII, XXIV, and XXV was c o n f i r m e d by c o n v e r s i o n to p e r c h l o r -
a t e s XX-XXIII, VII, and IX and by a l t e r n a t i v e s y n t h e s i s of the k n o w n [2] 2 , 4 - d i p h e n y l - % ~ , 7 , 8 - t e t r a h y d r o - y -
t h i o c h r o m e n e (XXIX). The UV s p e c t r a of s u l f i d e s XVI and XVIII (Table 3) a r e s i m i l a r to the s p e c t r u m of
u n s u b s t i t u t e d y - t h i o p y r a n [3].

The t h i a p y r y l i u m ion is c h a r a c t e r i z e d f r o m the IR s p e c t r a l d a t a i n the l i t e r a t u r e by t h r e e b a n d s at

1390-1410, 1470-1500, and 1560-1590 c m -1 [1, 4]. The p r e s e n c e of a r o m a t i c s u b s t i t u e n t s in the i n v e s t i g a t e d
s a l t s h i n d e r s a s s i g n m e n t of the b a n d s at 1470-1500 c m -1. T h i s band does not change its p o s i t i o n and i n -
t e n s i t y on p a s s i n g f r o m t h i o p y r a n s XV-XIX, XXIV, and XXV to the c o r r e s p o n d i n g t h i a p y r y l i u m s a l t s , V,
VII-XI, XIII, a n d XX-XXIII and a p p e a r s at 1495 =~5 c m - l , so t h a t one should a p p a r e n t l y a s s i g n it to a r o m a t i c
a b s o r p t i o n . The t h i a p y r y l i u m s a l t s a r e r e a d i l y d i s t i n g u i s h e d f r o m the c o r r e s p o n d i n g t h i o p y r a n s by the
v e r y i n t e n s e a b s o r p t i o n at 1390-1405 a n d 1560-1570 c m - l . The band at 1.560-1570 c m -1 is u s u a l l y s p l i t ,
and a s h o u l d e r at 1.540 c m - i a p p e a r s on the p r i n c i p a l band. The s p e c t r a of p e r c h l o r a t e s V I I - I X and XX-
XXIII a r e c h a r a c t e r i z e d by the p r e s e n c e of i n t e n s e b a n d s at 6 2 0 - 6 2 z and 1085-1090 c m - l , which s h o u l d be
a s s i g n e d to the a b s o r p t i o n of CIO C i o n s .

425
 TABLE 4. Action of Protic Acids on Saturated Solutions of 1,5-
Oiketones - I I I
Starting Reaction time,* h, Reactionproduct
compound Solvent Acid at 20"C . (yield, ~

I CH,COOH HC1 6,5 (4S) IV (52)

II CH~COOH H,CI 6,5 (72) v (51)
III CHsCOOH 14C1 ~,0 (i8) vi (6o)
I CH,COOH HCI04 ~S VII 165)
II CHaCOOH HCI04 7,O VIII (59)
III CH3COOH BCI04 6~ IX {64)
I (c~u0,o I-ICl 6,O(4O) IV (64)
II (C~Hs)~D HCI 2o,o (4s) V (5~)
Itl (C~5) ~O HC1 6.0 (24) VI (53)

* The time required for H2s/Hc1 cosaturation is indicated in the

e x p e r i m e n t s with hydrogen chloride, and the length of time the
mixture was held at 20* is given in parentheses.

EXPERIMENTAL
The IR s p e c t r a were r e c o r d e d with a U13-20 s p e c t r o m e t e r , while the electronic s p e c t r a were r e c o r d e d
with an SF-4A s p e c t r o p h o t o m e t e r .
The 2 - m o n o - and 2,4-disubstituted 5,6-trimethylenethiapyrylium and 5 , 6 , 7 , 8 - t e t r a h y d r o t h i o c h r o m y l -
ium chlorides and p e r c h l o r a t e s (IV-IX) (Table 1) were obtained as described in [1] in acetic acid with the
appropriate m i n e r a l acids. The experiments in e t h e r were c a r r i e d out s i m i l a r l y . The 1,~-diketones were
introduced in 0.05-mole amounts into 70-100 ml of the solvent (Table 4). When acetic acid was used as
the solvent, salts IV-IX were c r y s t a l l i z e d by the addition of ether; p e r c h l o r a t e s VII-IX c r y s t a l l i z e d in bet-
t e r fashion than chlorides IV-VI. The h y g r o s c o p i c chlorides were precipitated by the addition of absolute
ether. The use of e t h e r as the solvent considerably facilitated isolation of salts IV-IX. The reaction was
followed by m e a n s of t h i n - l a y e r c h r o m a t o g r a p h y (TLC) on aluminum oxide [ c y c l o h e x a n e - c h l o r o f o r m - e t h e r
(2: 2: i)].
5,6-Trimethylenethiapyrylium and 5,6,7,8-tetrahydrothiochromylium iodides and tetrachloroferrates
(X-XIV, Table 1)were obtained by exchange reactions by the method in [5].
Action of Grignard Reagents on Perchlorates VII and IX. The 2,4-disubstituted 5,6-trimethylene-T-
thiopyrans and 5,6,7,8-tetrahydro-y-thiochromenes (XV-XIX) (Table 2) were obtained from perchlorates
Vll or IX and the appropriate organomagnesinm compounds as described in [6]. Sulfides XVI-XVIII were
crystallized by cooling solutions of them in ether-alcohol (4 : 1). Sulfide XV was isolated as an oil and
characterized as perehlorate XX. Sulfide XIX was identified by a mixed-melting point determination with
a genuine sample of 2,4-diphenyl-5,6,7,8-tetrahydro-T-thiochromene [2].
Reaction of Lithium Aluminum Hydride with Perchlorates VII and IX. 2-Phenyl-5,6-trimethylene-y-
thiopyran (XXIV) (Table III). A 0.01-mole sample of p e r c h l o r a t e VII was added in portions in the c o u r s e
of an hour to 0.02 mole of lithium aluminum hydride in 150 ml of absolute ether, after which the mixture
was s t i r r e d at 20 ~ for ~1 h and then refluxed for 3 h. The e t h e r l a y e r was decanted, and the residue was
washed with ether. The e t h e r e x t r a c t s were combined, washed with water, and dried with anhydrous m a g -
nesium sulfate. The e t h e r was evaporated, and the residue was c r y s t a l l i z e d by cooling below 0 ~ Workup
gave 2 g (88%) of XXIV.
2-Phenyl-5,6,7,8-tetrahydro-y-thiochromene (XXV) was similarly obtained from perchlorate IX
(Table 3).
Reaction of P e r c h l o r i o Acid with Sulfides XV-XVIII, XXIV, and XXV. P e r c h l o r a t e s XX-X'XIII, VII, and
IX (Table 1) were obtained by reaction of sulfides XV-XVIII, XXIV, and XXV with a fivefold to sixfold e x -
cess of 70%perchloric acid in acetic acid solution as described in [6].
Chromatography on A120 3 with isooctane established that saturated sulfides are f o r m e d along with
salts XX-XXIII, VII, and IX; we will r e p o r t this separately.

LITERATURE CITED
1. V. G. Kharchenko, M. E. Stankevioh, N. M. Kupranets, V. I. Kleimenova, and S. K. Klimenko, Zh.
Organ. Khim., 8, 193 (1972).

426
2o V. G. Kharchenko, S. K. Klimenko, V. I. Kleimenova, N. M. Kupranets, and A. R. Yakoreva, Khim.
Geterotsikl. Soedin., No. 3, 73 (1971).
3. J. Strating, J. H. Keiyer, E. Molenaar, and J. Brandsma, Angew. Chem., 74, 469 (1962).
4. V. G. Kharchenko, M. E. Stankevich, A. R. Yakoreva, A. A. Rassudova, and N. M. Yartseva, Khim.
Geterotsikl. Soedin., 916 (1972).
5. S. K. Klimenko and V. G. Kharchenko, Khim. Geterotsikl. Soedin., No. 3, 85 (1971).
6. V. G. Kharchenko, A. A. Rassudova, T. I. Krupina, S. K. Klimenko, and T. P. Chepurnenkova, Khim.
Geterotsikl. Soedin., 338 (1970).

427
BENZAZOLES AND NAPHTHAZOLES
XXXVII.* STRUCTURE AND THERMOCHROMIC PROPERTIES
OF I- BENZOTHIAZOLYL-5-(p-NITROPHENYL)FORMA ZANS

G. N.Lipunova, N. N. Gulemina, UDC 547.556.9'789.6 : 539.193 9

A. P. Zeif, and N. P. Bednyagina 541.623 : 543.422.4.6

1 - B e n z o t h i a z o l y l - 5 - ( p - n i t r o p h e n y l ) f o r m a z a n s , which have t h e r m o c h r o m i c p r o p e r t i e s , were

synthesized. The s t r u c t u r e of the compounds was studied by means of IR and UV s p e c -
t r o s c o p y and quantum-mechanical calculations, the state of the t a u t o m e r i c equilibrium was
established, and the most probable planar conformations of the f o r m a z a n s as a function of
the c h a r a c t e r of the substituent in the 3-position of the f o r m a z a n chain were found. It is
shown that the t h e r m o c h r o m i s m of these compounds in solution is related to dissociation
of the hydrogen of the NH bond of the f o r m a z a n grouping and that the d e e p l y - c o l o r e d t h e r -
mally induced f o r m is the anionic aci f o r m .

More and m o r e attention has been directed to the problem of the p h o t o c h r o m i s m and t h e r m o c h r o m i s m
of compounds in recent y e a r s [2]. The p h o t o c h r o m i s m of f o r m a z a n s was f i r s t studied in the t r i a r y l f o r m -
azan s e r i e s [3]. Both photochromic [4] and t h e r m o c h r o m i c [5] compounds were found among the f o r m a z a n s
of the benzazole s e r i e s . 1 - B e n z o t h i a z o l y l - 3 - m e t h y l ( p h e n y l ) - 5 - ( p - n i t r o p h e n y l ) f o r m a z a n s had positive t h e r -
m o c h r o m i s m , but the nature of the phenomenon and the effect of the substituent in the 3-position r e m a i n e d
unstudied.

This communication is devoted to a study of the interrelationship between the s t r u c t u r e and t h e r m o -

chromic p r o p e r t i e s in f o r m a z a n s of the general f o r m u l a

" ~ S ~ N HN NO 2

\c//
J
R
I-V

I R~CHa; II R=C6Hs; III R=CH(CHa)2; IV R=H; V R=CH3;

I-IV R'~H; V R'=NO 2

Two VNH bands, which can be assigned to the absorption of the amine (VNH 3350-3360 cm -1) andimine
(VNH 3450-3460 cm -~) t a u t o m e r i c f o r m s on the basis of previous investigations [6-8], are o b s e r v e d in the
IR s p e c t r u m of f o r m a z a n I in CC14 at 3100-3500 cm -1 (Table 1). One should note the low intensity of the
bands as c o m p a r e d with the s p e c t r u m of 1 - b e n z o t h i a z o l y l - 3 - m e t h y l - 5 - p h e n y l f o r m a z a n . The d e c r e a s e in
intensity is not a s s o c i a t e d with the formation of an i n t r a m o l e c u l a r hydrogen bond, inasmuch as the e l e c -
tronic s p e c t r u m in the visible region of f o r m a z a n I in CC14 (Table 1) is identical to the s p e c t r u m of its
methylation product ( k m a x 456 nm).

* See [1] for communication XXXVI.

S. M. Kirov Ural Polytechnic Institute, Sverdlovsk. T r a n s l a t e d f r o m Khimiya Geterotsiklicheskikh

Soedinenii, No. 4, pp. 492-499, April, 1974. Original article submitted D e c e m b e r 26, 1972.

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

428
 T A B L E 1. P h y s i c o c h e m i c a l C h a r a c t e r i s t i c s of 1 - B e n z o t h i a z o l y l - 5 -
(p-nitrophenyl) formazans
{IR I Electronic spectrum, )'max, nm
Corn-. spectrum, I alcohoiiciabsolute 60%
pound UNH, crn-I 1 ccl~ benzene alcohol N a O H acetone acetone

I 3435,3354 458 480 475 :I: 600 468 60O

II None 540---600 540--600 510---590 610 486, 580J" 500, 598~r
III 3&50 522, 570 ~" 520, 570 "f 504, 570"t" 616 504~0 ~f 510, 600~
IV 3485 484 468 484, 600 608 6OO
in CHC13
V 3343 474 425 600 590 630
in CHC13

* C o m p o u n d s I-lll in CC14; IV a n d V in CHC13.

$ T h e l o n g - w a v e b a n d i s an i n f l e c t i o n .
A d i f f e r e n t v a l u e w a s e r r o n e o u s l y p r e s e n t e d in [8].

TABLE 2

Group Element ~, eV -~'v ,eV -~'~ , eV

N 15,43 . ~ - 6 2,37 8,21

Nd
/ - " . q' "/xdG, Oh O2 18,89 19,8
C 11.13 ~-d 2,02 9,94
N 15,43 14,56
\ d --". ~\/G5 , ,
/ O1 18,89 9N-:-O 2,37 20,9
02 18,89 N--O 2,37 19,8
C 11,13 N--C 2,816 9,94
*One 7r e l e c t r o n w a s a s s u m e d to b e d e l o c a l i z e d o v e r the e n t i r e
;r s y s t e m .

with H ~vith H with H with H T h e a b s e n c e of a VNH b a n d f o r II in CC14 a n d t h e a p -

a 9 onNs(2) onNl(2 ) onNl(l ) onNs(I)
p e a r a n c e of a l o w - i n t e n s i t y VNH b a n d at 3308 c m -1 in CHCI 3
[8] m a k e s it p o s s i b l e to a s s u m e a c h e l a t e s t r u c t u r e with a
~5,", ,i 3 ,,, ,, 2o ,
w e a k i n t r a m o l e c u l a r h y d r o g e n bond f o r t h i s c o m p o u n d . When
t h e e l e c t r o n i c s p e c t r u m of II in CC14 w a s b r o k e n down into
oL "v:', Ill , o 131 G a u s s i a n c o m p o n e n t s b y t h e m e t h o d in [9], we w e r e a b l e to
.5 20 20 -~0 30 20 ~ 30 20 40 30 20 z~O 20
i s o l a t e two a b s o r p t i o n b a n d s i n t h e v i s i b l e r e g i o n at 18,750
r" 103 , em'~
c m -1 (533 nm) and 21,250 c m -1 (470 r i m ) ( F i g . 1). T h e m o s t
b With 1HB Without 1HB
C.!O~ 3 I i n t e n s e l o n g - w a v e b a n d at 18,750 c m -1 c a n be l i n k e d t o t h e
a b s o r p t i o n of t h e d e e p l y - c o l o r e d c h e l a t e f o r m , w h i l e t h e l o w -
,5 ~ f' '16 ~, 5 / ', 2
i n t e n s i t y b a n d at 21,250 c m -1 c h a r a c t e r i z e s t h e a m i n o f o r m .
T h e i n t e n s i t y o f the a b s o r p t i o n at 21,250 c m -1 i n c r e a s e s in
,~0 30 20 ,:,0 30 20 40 30 20 t h e e l e c t r o n i c s p e c t r a of f o r m a z a n II in p o l a r s o l v e n t s ( a l -
AE,lOa. cm-I
c o h o l and a c e t o n e ) ; t h i s c a n be e x p l a i n e d b y o p e n i n g of t h e
F i g . 1. E l e c t r o n i c a b s o r p t i o n s p e c t r a chelate ring.
of I (a) a n d II (b) in CC14 a n d t h e i r c a l -
An i s o p r o p y l g r o u p a t t a c h e d to t h e m e s o c a r b o n , l i k e
c u l a t e d s p e c t r a in t h e a n t i , t r a n s (1) a n d
a p h e n y l g r o u p , p r o m o t e s c h e l a t i o n of t h e f o r m a z a n chain;
s y n , t r a n s (2) c o n f i g u r a t i o n s (H a t t a c h e d
t h i s w a s p r e v i o u s l y n o t e d in the a r y l f o r m a z a n s e r i e s [10].
to N 1 and H a t t a c h e d to N 5 i n d i c a t e t h e
amino form with the hydrogen atom at- T h e e l e c t r o n i c s p e c t r a of f o r m a z a n III in v a r i o u s s o l v e n t s
t a c h e d to N1 o r to Ns; " w i t h IHB" i n d i - h a v e t h e s a m e c h a r a c t e r a s t h o s e of f o r m a z a n II ( T a b l e 1).
cates with allowance for the intramolec- H o w e v e r , in c o n t r a s t to II, a l o w - i n t e n s i t y VNH band, which
u l a r h y d r o g e n bond, w h i l e " w i t h o u t IHB" a t t e s t s to t h e p r e s e n c e in s o l u t i o n of a n o p e n a m i n o f o r m in
a d d i t i o n to a c h e l a t e f o r m , a p p e a r s in t h e IR s p e c t r u m of
i n d i c a t e s d i s r e g a r d i n g t h e IHB. T h e Xth
f o r m a z a n III in CC14.
v a l u e f o r (2) w i t h H a t t a c h e d to N 1 is
0.964). F o r m a z a n IV b e h a v e s u n u s u a l l y . T h e r e i s o n l y t h e
VNH b a n d of t h e i m i n o f o r m at 3485 c m -1 in t h e IR s p e c -
t r u m , and t h i s b a n d is d i f f u s e in c h a r a c t e r ; t h i s m a y b e a s -

429
 TABLE 3

fexp/fth raio for the calculated configurations

Transition syn-trans anti-trans
H i ON1 I*I tO N~ H tON, H ~0 N~

(1) ~--nl* 1,48 0,446 0,784 0,312

(2) nrn,* 1,18 0,424 0,14 0,628
(3) r 0,51 3,13 2,23 3,2
(5) ~:--NO2* 0,558 1,86 tl,1 1,72

l
~. 10-3

lo

0
25 2'O ~ I; 35 30 25 20 ;s
AE. 1 0 " c m - 1

Fig. 2. T e m p e r a t u r e variations of the electronic s p e c t r a

of I in aqueous alcohol solution (the t e m p e r a t u r e of the r e -
v e r s e transition is indicated in parentheses); experimental
spectrum for aqueous alcohol solution at 60 ~ and calculated
spetrum for aci f o r m T.

sociated with the p r e s e n c e of i n t e r m o l e e u l a r hydrogen bonds between the n i t r o and NH groups. Two a b s o r p -
tion maxima (Table 1), of which the long-wave band that coincides in position with the absorption maximum
of the Na salt of IV is probably affiliated with the aci f o r m that a r i s e s due to intermolecular proton t r a n s -
fer, a r e observed in the electronic s p e c t r a of an alcohol solution of f o r m a z a n IV.
The introduction of an NO 2 group into the 6-position of the benzothiazole ring causes a shift in the
a m i n e - i m i n e equilibrium to f a v o r the amine f o r m . The position of the long-wave absorption band in the
electronic s p e c t r a of V depends m a r k e d l y on the nature of the solvent. In nonpolar solvents, V absorbs at
435 or 475 nm as c o m p a r e d with 600 nm in polar solvents.
To p r e c i s e l y determine the s t r u c t u r e of the f o r m a z a n s we p e r f o r m e d q u a n t u m - m e c h a n i c a l calcula-
tions of t h e i r v - e l e c t r o n s y s t e m s by the p a r i s e r - p a r r - P o p l e method with the use of p a r a m e t e r s p r e -
viously employed for compounds of this c l a s s [11]. The p a r a m e t e r s of the nitro and a c t - n i t r o groups, which
were found by the method in [12, 13], a r e p r e s e n t e d in Table 2. The angles and i n t e r a t o m i c distances were
a s s u m e d to be the same as those in nitrobenzene [14]. Because of the absence of x - r a y diffraction data for
the a c i - n i t r o group, we used the bond lengths and valence angles of s i m i l a r compounds [14]. All of the c o m -
pounds were a s s u m e d to be coplanar.
The site of localization of the acid hydrogen of the f o r m a z a n grouping had to be p r e c i s e l y determined.
In [15] it was shown that the hydrogen in 1 - p h e n y l - 5 - ( p - n i t r o p h e n y l ) f o r m a z a n is attached to the nitrogen
atom linked to the p-nitrophenyl grouping. The amino f o r m s of f o r m a z a n s I and II were t h e r e f o r e calculated
for a model with a hydrogen atom attached to the N 1 and N 5 atoms.
P r o c e e d i n g f r o m the IR and electronic s p e c t r a l data, we calculated I for the amine t a u t o m e r i c f o r m
of the a n t i - t r a n s and s y n - t r a n s configurations relative to the C =N bond of the f o r m a z a n ring, which differ
most f r o m one another with r e s p e c t to calculations of the electronic s p e c t r a [11]. Inasmuch as the anti-
t r a n s f o r m excludes the chelate s t r u c t u r e , the calculation of II was made for the s y n - t r a n s configuration of
the amino f o r m with i n t r a m o l e c u l a r hydrogen bonding and without it.
The experimental s p e c t r u m of f o r m a z a n I in CC14 was broken down into its Gaussian components, as
in the case of II (Fig. 1).~

Long-wave absorption bands at 16,80() and 16,750 cm -1, respectively, the assignment of which is not dis-
cussed in this paper, were isolated during the analysis of the s p e c t r a of I and II in CC14.

430
 TABLE 4
Cornpound I II III Iv V

820 8,94 9,53 7,38 6,73

-+0,02 ---+0,04 -+0,02 --+0,04

A comparison of the experimental and calculated spectra of I and II, which are presented in Fig. i,
shows that I exists in CCI 4 as an equilibrium mixture of tautomeric forms of syn-trans configurations with
the hydrogen atom attached to N I or Ns, while predominance of the chelate form is characteristic for If.
Moreover, as in [11], the long-wave band is affiliated with the (I) ~ i-~ 2" transition from the upper filled
~i level, localized on 51, to the lower vacant ~ 2" level, localized on the formazan grouping. The following
bands are affiliated with the transitions: (2) ~ 2-~i*; (3) 52-~ 1"; (4)5 i-~i*; (5) ~ i-NO 2.; (6) (52 + 53) -
~I*; (7) P-~I*; (8) NO2-~I*. Here, 52 and 52 are the states localized in the p-nitrophenyl and benzo-
thiazole residues, respectively. The symbols and localization of the remaining states are the same as in
[11]. The correctness of the selection of the configurations for formazan I (syn-trans rather than anti-
trans) is confirmed by the ftheor ratio (Table 3).
Formazans I-IV display positive thermochromism, and the ease of the thermochromic transitions de-
pends on the structure. The most distinct thermochromic transitions in the change in color from red
()~max 475 nm) to blue (kma x 600 nm) were obtained for I in 75% alcohol for formazan I concentrations of
5 9 10 -5 to 5 ~ 10 -4 mole/liter (Fig. 2). In contrast to I, the thermochromic transitions of formazans II and
III under the same conditions are not so distinct. There is no isopiestic point in the electronic spectra, and
the thermochromic transition is characterized only by an increase in the absorption intensity at 600 nm.
Heating of an alcohol solution of IV is accompanied by an increase in the absorption intensity at 480 nm and
a decrease in the absorption at 600 nm (Fig. 3), i.e., in this case there is an irreversible transition of the
blue form to the red form. However, after water is added, subsequent heating of the dilute solution leads
to thcrmochromic transitions that are similar to the transitions for formazan I. Formazan V does not have
thermochromic properties, inasmuch as it has an absorption maximum at 600 nm (blue form) in aqueous
alcohol solution.
The nature of the thermochromic transitions was investigated in greater detail in the case of formazan
I. Its light-absorption curves have a distinct isopiestic point at 524 nm, which is evidence for equilibrium
of two forms in solution (Fig. 2). As established above, I exists in the amino form (kma x 475 nm) in al-
cohol solution, and the color is shifted bathochromically in alcoholic alkali; the electronic spectrum of the
anion coincides with the spectrum of the thermally induced form with respect to the position of the max-
imum and the intensity. The introduction of a nitro group into the phenyl ring in the para-position relative
to the N 5 atom increases the acidity of the N-H bond (pK a 8.2) as compared with unsubsitituted l-benzo-
thiazolyl-3-methyl-5-phenylformazan (pK a 9.1). Thermochromic transitions appear for I only in aqueous
alcohol solutions, the pH of which is 8.3, i.e., a value close to the pK a of I, and are absent in alcohol solu-
tion (pH 7.1).
All of this provides a basis for assuming that both the Na salt and the blue tautomeric form have close
electronic structures told that the thermochromism is related to dissociatiop of the formazan at the N-H
bond and transition of the starting amino form (1) to the aci form (2) [sic]. A similar sort of mechanism
was presented in [16] for the explanation of the photochromism of dinitrobenzylpyridine.

~ S~
%~ :N" H-
N N N N
\ c -"" \ c -//
CH 3 CH 3

To p r e c i s e l y d e t e r m i n e t h e s t r u c t u r e of t h e b l u e t a u t o m e r i c f o r m we m a d e q u a n t u m - m e c l m n i c a l c a l -
c u l a t i o n s of t h e ~ r - e l e c t r o n s y s t e m of I in the a c i f o r m (the p a r a m e t e r s a r e p r e s e n t e d in T a b l e 2).
A c o m p a r i s o n o f t h e e x p e r i m e n t a l and c a l c u l a t e d s p e c t r a of I ( F i g . 2) c o n f i r m s t h a t the l o n g - w a v e
a b s o r p t i o n b a n d at 600 n m (the b l u e f o r m ) i s a f f i l i a t e d w i t h t h e 7r 1-7r 2* t r a n s i t i o n of t h e a c i f o r m .
P r o c e e d i n g f r o m t h e a b o v e a s s u m p t i o n r e g a r d i n g t h e m e c h a n i s m of t h e t h e r m o c h r o m i c t r a n s i t i o n s ,
it w a s of i n t e r e s t to e x a m i n e t h e t h e r m o c h r o m i e p r o p e r t i e s of the r e m a i n i n g f o r m a z a n s at pH v a l u e s of
a q u e o u s a l c o h o l s o l u t i o n s t h a t a r e c l o s e to t h e p K a v a l u e s . F o r t h i s , we m e a s u r e d t h e a p p a r e n t i o n i z a t i o n
c o n s t a n t s of I - V , t h e p K a v a l u e s of w h i c h a r e p r e s e n t e d in T a b l e 4.

431
 ~1o_~ a , E.lo- 3 b ~, ~.1o-~ c The ionization constants obtained a r e in good
1- ~i ~ 2[ loo.,. / ~ a g r e e m e n t with the data on the s t r u c t u r e of I-V.
The acid p r o p e r t i e s of II and III are weakened, while
,c /~,o ~ } I /Jo~ t~ t h e r e is a general tendency for an i n c r e a s e in the
acid p r o p e r t i e s in the 5-(p-nitrophenyl)-substituted
formazans.

2~ 20 15 25 20 15 25 20 15 The t e m p e r a t u r e dependence of the electronic

~E , 1 0 " a m " l s p e c t r u m of II in an alcohol buffer solution with pH
Fig. 3. Temperature variations of the electronic 8.8, which is close to the pK a value, is p r e s e n t e d in
s p e c t r a of f o r m a z a n s IV (a) and II (b); electronic Fig. 3 and shows that the pattern of the t h e r m o c h r o m i c
s p e c t r u m of I in acetone as a function of the p e r - transitions is m o r e distinct than in an aqueous al-
centage of water (c). cohol solution with pH 8.15. A s i m i l a r dependence
is also c h a r a c t e r i s t i c for III.
A c o m p a r i s o n of the long-wave absorption band in the experimental s p e c t r u m of the t h e r m a l l y in-
duced II and III f o r m s ~vith the Xmax values of the Na salts of the f o r m a z a n s shows that the t h e r m o c h r o m -
i s m is due to dissociation and a shift of the t a u t o m e r i c equilibrium of the amino and aci f o r m s in these
cases also. The appearance of the aci form when aqueous alcohol solutions of II and HI with pH values far
f r o m the'pK~ values a r e heated is h a m p e r e d because of the p r e s e n c e in the solutions of the t a u t o m e r i c
chelate form, and this also explains the indistinct s p e c t r a l c h a r a c t e r i s t i c s of the t h e r m o c h r o m i c t r a n s i -
tions.
The pKa values of f o r m a z a n s IV and V a r e lower than the pH values of t h e i r alcohol solutions, and the
aci f o r m is o b s e r v e d (IV) or predominates (V} for them even in cold solutions.
An investigation of the effect of the solvent on the t h e r m o c h r o m i c behavior of I - V showed that the
shift in the equilibrium to favor the aci f o r m in aqueous acetone solutions depends to a m a r k e d degree on
the a c e t o n e - w a t e r ratio, even without heating (Fig. 3 and Table 1). In this case, f i r s t of all, the increase
in the pH of the aqueous acetone solution as a function of the percentage of water and, secondly, the i n c r e a s e
in the lability of the proton of the NH bond due to the a c c e p t o r c h a r a c t e r of acetone probably affect the shift
of the equilibrium. Heating of 70-80% acetone solutions is c h a r a c t e r i z e d by distinct t h e r m o c h r o m i e t r a n s i -
tions for f o r m a z a n s I, II, and IV.

EXPERIMENTAL

The electronic s p e c t r a of solutions of I-V (5 9 1 0 - 4 to 5 " 1 0 - 5 M) were r e c o r d e d with VSU-2P*, SF-4,

and SF-2M s p e c t r o p h o t o m e t e r s . The IR s p e c t r a of saturated solutions of the f o r m a z a n s in CC14 in the LiF
region were obtained with a UR-20 s p e c t r o m e t e r . The ~r-electron s y s t e m s were calculated with a Minsk-2
computer. The apparent ionization constants of the f o r m a z a n s were m e a s u r e d s p e c t r o p h o t o m e t r i e a l l y [17]
in 50% alcohol buffer solutions ( a m m o n i a - a c e t a t e buffer); the working concentration of the f o r m a z a n s was
5 910 -5 M, the t e m p e r a t u r e was 22 ~ and the analytical wavelength was 600 nm.
The synthesis of I and II is described in [8].
Isobutyraldehyde 2-Benzothiazolylhydrazone. A 0.025-mole sample of isobutyraldehyde was added to
a suspension of 0.02 mole of 2-hydrazinobenzothiazole VII in 40 ml of alcohol, after which the reaction mix-
ture was heated f o r 10 rain, during which all of the solids dissolved. The mixture was cooled to precipitate
the hydrazone. Workup gave 65% of VI with mp 165 ~ (alcohol). Found: C 60.5; H 6.0; N 18.8%. C I 1 H 1 3 N 3 S .
Calculated: C 60.3; H 5.9; N 19.2%.
1 - B e n z o t h i a z o l y l - 3 - i s o p r o p y l - 5 - ( p - n i t r o p h e n y l ) f o r m a z a n (IID. A diazonium salt solution, p r e p a r e d
f r o m 0.05 mole of p-nitroanaline, was added gradually with cooling to a solution of 0.05 mole of IV in al-
c o h o l - p y r i d i n e (2 : 1) containing 0.01 mole of CH3COONa. Compound III was precipitated by bringing the
pH of the solution up to 7 by t r e a t m e n t with 2 N NaOH. Workup gave 45% of III with mp 172 ~ (nitromethane).
Found: C 55.8; H 4.5; N 22.8%. C17H16N6OaS. Calculated: C 55.6; H 4.6; N 22.7%.
Acetaldehyde 6 - N i t r o - 2 - b e n z o t h i a z o l y l h y d r a z o n e . This compound was obtained by the method used to
p r e p a r e VI. The yield of product with mp 288-290 ~ (alcohol) was 60%. Found: "C 45.9; H 3.6; N 23.8%.
CgHIsN402S. Calculated: C 45.8; H 3.4; N 23.7%.
9 The authors thank V. I. Minkin for allowing us to use this s p e c t r o p h o t o m e t e r .

432
 1 - ( 6 - N i t r o b e n z o t h i a z o l y l ) - 3 - m e t h y l - 5 - ( p - n i t r o p h e n y t ) f o r m a z a n (V). This compound was obtained by
the method used to p r e p a r e III, but the isolation was c a r r i e d out at pH 5-6. Workup gave 56% of V with mp
237 ~ (nitromethane). Found: C 45.7; H 3~176 C15H~N?O4S'H20. Calculated: C 46.0; H 3.3%.
Nitroformaldehyde p-Nitrophenylhydrazone (VIII}. This compound was obtained by the method in [18].
1 - B e n z o t h i a z o l y l - 5 - ( p - n i t r o p h e n y l ) f o r m a z a n (IV). Saturated solutions~ each containing 0.05 mole of
VII and VIII in pyridine, w e r e mixed, and the m i x t u r e was heated for 15 rain and allowed to stand for 15 days.
The resulting p r e c i p i t a t e was r e m o v e d by filtration and washed with a small amount of alcohol. Workup
gave 75% of V with mp 250 ~ (dimethylformamide). Found: C 51.4; H 3.3; N 26.0%. C14H10N~O2S. Calculated:
C 51.5; H 3.0; N 25.8%.

LITERATURE CITED

1. L . P . Sidorova and N. P. Bednyagina, Khim. Geterotsikl. Soedin., 1138 (1972).

2. G. Hayasi and K. Maeda, Kagaku-no Reiki, 2_22,No. 1, 1 (1968).
3. I. Hausser, D. J e r h e l , and K. Kuhn, B e t . , 8__44,651 (1951).
4. N . P . Bednyagina, G. N. Lipunova, and G.A. Mokrushina, USSR Author's Certificate No. 241,442 (1969);
Byul. Izobr,, No. 14, 23 (1969).
5. Yu. A. Rybakova, G.N. Lipunova, and N. P. Bednyagina, USSR Author's Certificate No. 296,791 (1971);
Byul. Izobr., No. 9, 86 (1971).
6. N . P . Bednyagina and G. N. Lipunova, Khim. Geterotsikl. Soedin., 877 (1969).
7. A . P . Zeif, L. N. Shchegoleva, G.N. Lipunova, A . P . Novikova, and N. P. Bednyagina, Zh. Organ. Khim.,
6, 1332 (1970}.
8. N . P . Bednyagina, N. V. Serebryakova, and G.N. Lipunova, Khim. Geterotsikl. Soedin., 342 (1967).
9. V . D . Vdovenko (editor}, Spectroscopic Methods in the C h e m i s t r y of Complexes [in Russian], Khimiya,
M o s c o w - L e n i n g r a d (1964), p. 102.
10. F. Neugebauer and H. Frischmann, Ann., 706, 107 (1967).
11. A . P . Zeif, G. N. Lipunova; N. P. Bednyagina, L. N. Shchegoleva, and L. I. Chernyavskii, Zh. Organ.
Khim., 6, 2590 (1970).
12. J. F i s c h e r , H. O l m e r s , and M. Sundbom, Acta, Chem. Scand., 2_~2, 607 (1968).
13. O. Gropek and P. N. Scancke, Acta Chem. Scand., 23, 2695 (1969).
14. Tables of Interatomic Distances, Spec. Pull., London, No. 11 (1958).
15. F . A . Neugebauer and M. Jenne, T e t r a h e d r o n Lett., 1._00,771 (1969).
16. J . D . Magarum, L. J. Miller, E. Saito, M. Brown, and R. Hardwick, J. Phys. Chem., 6_~6,2434 (1962).
17. A. Albert and E. Serjeant, Ionization Constants of Acids and Bases, Barnes and Noble, Inc. (1962).
18. R . I . Ogloblina, N. P. Bednyagina, and N. N. Gulemina, Khim. Geterotsikl. Soedin., 393 (1972).

433
CYCLIZATION OF BENZOYLCYANOTHIOACETIC

ACID ARYLAMIDES

R. G. Dubenko and E. F. Gorbenko UDC 547.789.1.3.6' 773 : 542.953

3 - A r y l a m i n o - 4 - c y a n o - 5 - p h e n y l p y r a z o l e s and 3 - a r y l - 4 - p h e n y l - 2 - [ ( b e n z o y l ) c y a n o m e t h y l -
e n e ] - 4 , 5 - t h i a z o l i n e s , r e s p e c t i v e l y , w e r e obtained by condensation of benzoylcyanothio-
acetic acid a r y l a m i d e s with hydrazine h y d r a t e or with o~-bromoacetophenone. 2-[(Benzoyl)-
cyanomethyl]benzothiazole d e r i v a t i v e s w e r e synthesized by oxidative cyelization of benzoyl-
cyanothioacetic acid a r y l a m i d e s .

In o r d e r to obtain compounds with p o s s i b l e physiological activity, we investigated the cyclization of

benzoylcyanothioacetic acid a r y l a m i d e s [1, 2].
Condensation of f i - k e t o n i t r i l e s with hydrazine hydrate [3, 4] leads to a m i n o - and i m i n o p y r a z o l e s . It
might have been a s s u m e d that 3 - a m i n o - 4 - b e n z o y l - 5 - a r y l a m i n o p y r a z o l e s or 3 - p h e n y l - 4 - a r y l t h i o c a r b a m o y l -
5 - a m i n o p y r a z o l e s would have been synthesized in the condensation of benzoylcyanothioacetic acid a r y l -
a m i d e s (I) with hydrazine hydrate. However, the p r e v i o u s l y undescribed 3 - a r y l a m i n o - 4 - c y a n o - 5 - p h e n y l -
p y r a z o l e s (H-V, Table 1) w e r e isolated as a r e s u l t of this reaction.
The p r e s e n c e of a nitrile group is c o n f i r m e d by saponification of 3 - ( p - c h l o r o p h e n y l a m i n o ) - 4 - c y a n o -
5-phenylpyrazole (V) to 3 - ( p - c h l o r o p h e n y l a m i n o ) - 4 - c a r b a m o y l - 5 - p h e n y l p y r a z o l e (XII).
CN
CN
I K~[F~(CN)6] R....~S~ / HCOC6H~

I ~ VI-IX
N2H 4
1 9

C6H4R'P
II-y

II. V I , X R=H; Ill. VII R=CH3; IV R=NH2; IX, X| R=NO2; v. vlll R=CI

The IR s p e c t r a of I I - V contain a c h a r a c t e r i s t i c absorption band at 2220 cm -1 (VC_=N) [5] and bands at

1610, 1575, and 1495 cm -1 (vibrations of the p y r a z o l e ring [6, 7]). Absorption bands at 1650 cm -1 (v C=O )
and at 1500-1510 c m "I which a r e c h a r a c t e r i s t i c for vibrations of the C - N bond in the thioamide group [5]
a r e absent. In addition to absorption bands of the p y r a z o l e ring, the IR s p e c t r u m of XII contains absorption
bands at 1670 c m -1 (v C=O) and at 3370 cm -1 (v NH) [5], which c o r r e s p o n d to the s t r e t c h i n g vibrations of a
p r i m a r y amide group; the c h a r a c t e r i s t i c absorption band for the nitrile group [5] is absent. It t h e r e f o r e
follows that the p r o d u c t s have s t r u c t u r e s II-V.
The r e a c t i o n of benzoylcyanothioacetic acid a r y l a m i d e s with hydrazine h y d r a t e s p r o b a b l y c o m m e n c e s
with attack at the carbonyl group, as in the c a s e of benzoylthioacetic [8] and monoacetylthioacetic acid [9]
a m i d e s . However, we w e r e unable to isolate the i n t e r m e d i a t e hydrazone. Simultaneous reduction of the
nitro group to an amino group (IV, T a b l e 1) o c c u r s in the c a s e of benzoylcyanothioacetic acid p - n i t r o p h e n y l -
amide.

Institute of Organic C h e m i s t r y , A c a d e m y of Sciences of the Ukrainian SSR, Kiev. T r a n s l a t e d f r o m

Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 500-502, April, 1974. Original a r t i c l e submitted Octo-
b e r 31, 1972.

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, N.Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

434
 TABLE 1. 3 - A r y l a m i n o - 4 - c y a n o - 5 - p h e n y l p y r a z o l e s (II-V) and
2- [(Benzoyl)cyanomethyl]benzothiazoles (VI-IX)
Empirical N, % Yield,~o
Compound mp,
formula found calc.

1I 257--258 C16HIzN4 21,1 21,5 56

llI 193--194 C~:Ht4N4 20,4 20,4 57
IV 160--i61 C16H13N5 25,1 25,4 58
V 2'36--237 C,6HHC1N4* t8,9 19,0 60
VI 234--235 C16HloN2OS 10,0 10.1 57
VII 241--242 C,vH~N20S 9,8 9.6 56
VIII 264--265 C~GHgCIN2OS 9,3 9,0 53
IX 25,4--255 C,6HgN3QS 12,8 13:0 51

*Found: C 65.1; H 3.8~. Calculated: C 65.4; H 3.7%.

Found: C 59.0; H 2.8%. Calculated: C 59.5; H 2.8%.

The benzoylcyanothioacetic acid a r y l a m i d e s undergo oxidative cYClization with potassium f e r r i c y a n i d e

in aqueous alkali to give 2-[(benzoyl)cyanomethyl]-6-benzothiazole derivatives (VI-IX). Compound I is not
b r o m i n a t e d at the methylidyne group by the action of b r o m i n e in acetic acid [10], but oxidative cyclization
products identical to the compounds obtained in the oxidation with potassium f e r r i c y a n i d e (VI-IX) a r e f o r m e d .
3 - A r y l - 4 - p h e n y l - 2 - [ ( b e n z o y l ) c y a n o m e t h y l e n e ] - 4 , 5 - t h t a z o l i n e s (X, XI) were isolated when benzoyl-
eyanothioacetic acid a r y l a m i d e s (I) were heated with w-bromoacetophenone in alcohol.
We thank P. S. P e l ' k i s for his advice and interest in this r e s e a r c h .

EXPERIMENTAL
The IR s p e c t r a of KBr pellets of the compounds were r e c o r d e d with a UR-10 s p e c t r o p h o t o m e t e r .
3 - ( p - C h l o r o p h e n y l a m i n o ) - 4 - c y a n o - 5 - p h e n y l p y r a z o l e (V). A 1.2-ml sample of hydrazine hydrate was
added dropwise to 0.6 g (2 mmole) of benzoytcyanothioaeetic acid p-chlorophenylamtde, and the mixture was
refluxed until hydrogen sulfide evolution c e a s e d (~ 10-12 h). The mixture was cooled, and the resulting
y e l l o w - o r a n g e c r y s t a l l i n e precipitate was r e m o v e d by filtration, washed with alcohol, and c r y s t a l l i z e d from
alcohol to give 0.34 g of product.
Compounds II, III, and IV were synthesized s i m i l a r l y (Table 1).
2 - [ ( B e n z o y l ) c y a n o m e t h y l ] - 6 - n i t r o b e n z o t h i a z o l e (IX). A solution of 0.32 g (1 mmole) of benzoylcyano-
thioacetic acid p - n i t r o p h e n y l a m i d e and 2.2 g of sodium hydroxide in a mixture of 10 ml of water and 5 ml
of alcohol was added with s t i r r i n g to a solution of 0.8 g of potassium f e r r i c y a n i d e in 20 ml of water con-
taining 30 g of ice. The mixture was s t i r r e d for 6 h and then allowed to stand overnight at r o o m t e m p e r a -
t u r e . The resulting precipitate was r e m o v e d by filtration and washed with water to give 0,32 g of product.
The product was c r y s t a l l i z e d f r o m acetic acid.

Compounds VI-VIII were s i m i l a r l y obtained (Table 1), but the products precipitated only after acidifi-
cation to pH 1-2 with concentrated h y d r o c h l o r i c acid.
3,4-Diphenyl-2-[(benzoyl)cyanomethylene]-4,5-thiazoline (X). A 0.8-g (2.8 mmole) sample of benzoyl-
cyanothioacetic acid phenylamide and 0.5 g (2.8 mmole) of cc-bromoacetophenone were dissolved in 5 ml of
alcohol, and the solution was refluxed f o r 5 h. It was then cooled, and the resulting light-yellow c r y s t a l s
were r e m o v e d by filtration, washed with cold alcohol, and dried to give 0.45 g (45%) of a product with mp
184-185 ~ (from alcohol). Found: N 7.7%. C24H16N2OS. Calculated: N 7.4%.
3-(p--Nitrophenyl)-4-phenyl-2-[(benzoyl)cyanomethylene]-4,5-thiazoline (XI), This compound was
s i m i l a r l y obtained in 47% yield and had mp 247-248 ~ (from alcohol). Found: N 7.4%. C24HisN303S. Cal-
culated: N 7.5%.
3 - ( p - C h l o r o p h e n y l a m i n o ) - 4 - c a r b a m o y l - 5 - p h e n y l p y r a z o l e (XII). This compound was obtained by s a -
ponification of 3 - ( p - c h l o r o p h e n y l a m i n o ) - 4 - c y a n o - 5 - p h e n y l p y r a z o l e (V) with concentrated sulfuric acid; the
m i x t u r e of reagents (1 : 10) was allowed to stand in the cold for 36 h. Workup gave 60% of a product with
mp 227-228 ~ (from alcohol). Found: N 17.86%. C16H13C1N40. Calculated: N 17.98%.

435
 LITERATURE CITFD
1. R . G . Dubenko, E. F. Gorbenko, and P. S. Pel, kis, Zh. Organ. Khim., 5, 1832 (1969).
2. R . G . Dubenko, E. F. Gorbenko, and P. S. Pel'kis, Zh. Organ. Khim., 6, 1749 (1970).
3. F. Bell, J. Chem. Soc., 285 (1941).
4. S. Cusmano, Gazz. Chim. Ital., 8.1, 380 (1951); Chem. Zentrallblat, 7166 (1952).
5. L. Bellamy, Infrared Spectra of Complex Molecules, Methuen (1958).
6. C.R. Hauser and C. E. Cain, J. Org. Chem., 2_3, 1142 (1958).
7. C.S. Rondestvedt and P. K. Chang, J. Amer. Chem. Soc., 77, 6532 (1955).
8. T. Benedetto, Gazz. Chim. Ital., 9._22,1651 (1962).
9. A.N. Borisevieh and P. S. Pel'kis, Khim. Geterotsikl. Soedin., 312 (1969).
10. A. Hugershoff, Ber., 3__66,3121 (1903).

436
SEMICARBAZONES AND THIOSEMICARBAZONES
OF THE HETEROCYCLIC SERIES
XXVIIo* SPECTRA AND STRUCTURE OF ISATTN/3-THIOSEMICARBAZONES

A. B. Tomehin, I. S. Ioffe~, UDC 547.754.756:543.422.6:541.621

A. I. Kol'tsov, and Yu. V. Lepp

Isatin/3 - t h i o s e m i c a r b a z o n e and its alkyl d e r i v a t i v e s containing a hydrogen a t o m attached

to N(2, ) exist p r i m a r i l y in the f o r m of the syn i s o m e r stabilized by i n t r a m o l e c u l a r h y d r o -
gen bonding in solutions and in the c r y s t a l l i n e state. The s t r e n g t h of this hydrogen bond
i n c r e a s e s when both hydrogen a t o m s in the p r i m a r y t h i o a m i d e group a r e r e p l a c e d by alkyl
groups.

I s a t i n / 3 - t h i o s e m i c a r b a z o n e s (D and N - m e t h y l i s a t i n / 3 - t h i o s e m i c a r b a z o n e s (IT) ( " m e t h i s a z o n e " ) can

exist as syn (a) and anti (b) i s o m e r s
NH2\c~S S~.c/NH2

N/N\H H/N\ N

d r
t 1
R R
I-ll a I-II b

I R=H; II R=CFI3

To solve the p r o b l e m of the s t r u c t u r e s of I and II we c o m p a r e d t h e m with III-IV, in which an i n t r a -

m o l e c u l a r hydrogen bond (IHB) is excluded by substitution of the hydrogen atom attached to N(2, ). We also
studied d e r i v a t i v e s V-XIV, which a r e substituted at N(4, ) (Table 1).
1~2' ,~t 4 , / R 3
~ _~'N NR2CSN~R '

I
R,
I-XIV

A c c o r d i n g to the r e s u l t s of t h i n - l a y e r c h r o m a t o g r a p h y (TLC) (Table 1), II-IV, IX, XIII, and XIV, even
a f t e r r e p e a t e d r e c r y s t a l l i z a t i o n , a r e m i x t u r e s of two s u b s t a n c e s with close Rf values. We w e r e unable to
s e p a r a t e t h e s e s u b s t a n c e s , i n a s m u c h as they a r e r e a d i l y i n t e r c o n v e r t e d . Aocording to the data in [2], I and
II a r e anti i s o m e r s in p o l a r s o l v e n t s . This conclusion is b a s e d on the fact that the c h e m i c a l shifts of the
2 ' - H proton and the proton attached to the indole nitrogen in the PMR s p e c t r a in dimethyl sulfoxide (DMSO)
depend on the c o n c e n t r a t i o n , and 2 ' - H consequently p a r t i c i p a t e s in the f o r m a t i o n of an i n t e r m o l e c u l a r h y d r o -
gen bond r a t h e r than an i n t r a m o l e c u l a r hydrogen bond. To v e r i f y this, we r e c o r d e d the PMR s p e c t r a of I
and TI in solutions with c o n c e n t r a t i o n s ranging f r o m 3.5 to 20% and, f o r c o m p a r i s o n with t h e m , the PM-R
s p e c t r a of benzaldehyde t h i o s e m i c a r b a z o n e (XV) [7], acetone t h i o s e m i c a r b a z o n e (XVI) [8], and benzaldehyde

*See [1] f o r Communication XXVI.

Deceased.
S. M. K i r o v M i l i t a r y Medical Academy, L e n i n g r a d . T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i e h e s k i k h
Soedinenii, No. 4, pp. 503-509, April, 1974. Original a r t i c l e s u b m i t t e d S e p t e m b e r 25, 1972.

9 19 75 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

437
 4,4-dimethylthiosemicarbazone (XVII) [9] as models
in which participation of 2'-H in the formation of an
IHB is excluded (Table 2).
~ h0 ~
Despitethe data in [2], the signals of all of
protons including 2'-H. are independent of con-
centration. The low values of the chemical shifts
~ . - ~ ~ ~
of the 2'-H protons in derivatives I and II andtheir
0 o" 0 constancy as the temperature changes demonstrate
that I and II exist in solution p r i m a r i l y in form a,
which is stabilized by an IHB.
The 2'-H chemical shifts in the spectra of
4',4'-dialkyl derivatives VII-IX are considerably
lower than those observed for I and II (compare the
d spectra of XV andXVD. T h e s y n form therefore
also predominates in VI-IX, and the IHB in them
is even stronger. The effect of groupings in the 4'
~ o .~.~ position is not additive (Tables 2 and 3) and is ap-
Z e4 e~~ ~ ~.de~.-~...-~
parently primarily due to the steric contraction of
m ~ the chelate ring.
The conclusion presented in [2] regarding the
predominance of i s o m e r b in solutions of I and II
2 j z N was also substantiated by the fact that the f r e -
quencies of the carbonyl group for solutions of
these substances in DMSO differ from the f r e -
.,..~ quencies of the carbonyl group in the crystalline
~ZZ~Z~ZZZZZZZZ
state, in which, in the opinion of the authors, this
~dddC~dd~GGCCC substance is i s o m e r a. Data from the IR spectra
of I-XIV in DMSO and chloroform are presented
in Table 4. Substitution of the hydrogen atom at-
tached to N(2, } by a methyl group leads to an in-
c r e a s e in the frequency of the carbonyl group (> 30
o0o -o 0 ~
00 "00 '~
cm-1). This confirms that the syn form c o r r e -
sponds to compounds in which the hydrogen atom
a~g
~ 0 0 ~ ~00~00 attached to N(2, ) is not substituted (I-II and V-X).
Since the shift in the frequency of the carbonyl
~ group on passing from chloroform to carbon tetra-
chloride is insignificant, it can be a s s u m e d that
this conclusion is also valid for nonpolar solvents.

0 A comparison of the UV spectra of deriva-

t~
t i v e s I-XIV (Table 3) shows that replacement of the
o ~ .~ hydrogen atom attached to N(2, ) changes the s p e c -
.9 trum to a considerably greater extent than for the
previously investigated t h i o s e m i c a r b a z o n e s and
o ~ ~176
2 - m e t h y l t h i o s e m i c a r b a z o n e s of other carbonyl c o m -
~2 ~2"a pounds [10]. Thus, on the basis of the PMR, IR,
I and UV spectral data, it can be concluded that
9~ ~ ~ ~
I-XIV in solutions are actually the syn i s o m e r s .

I o ~ It is interesting that two bands of carbonyl

absorption are present in the IR spectra of solu-
~.~ , I::~ ~ ~
tions of some of the compounds and that their r e l a -
tive intensities depend on the solvent. The ob-
I o ~, ~,-.N s e r v e d phenomenon can hardly be explained by a s -
sociation. In the case of XIV, in which the f o r m a -
tion of hydrogen bonds is excluded, both bands c o r -
respond to a free carbonyl group. Splitting of the

438
TABLE 2. C h e m i c a l Shifts of the P r o t o n s Attached to the Nitrogen
A t o m s in D i m e t h y l Sulfoxide Solutions
NH (6. ppm)
Compound C~c.,qo T e m p . , *C
2"H I-H [ 4'-H

26 12,58 11.20 9,04 8,64

13,8 59 12,55 11,04 8,61
81 12,56 10.93 8,55
6,9 26 12,58 11.20 ] 9,03 8.64
3,5 26 12,58 11.23 [ 9,03 8,64
II 13 26 12,43 -- 8,90 8,60
81 12,46 -- 8,57
6,5 26 12.44 -- 9,04 8.65
3,8 26 12,44 -- 9,04 8,67
III 1t 26 10,90 8,70 8,38
IV 26 -- 8,74 8,49
V 12,2 26 12,65 11,22 9,23
VI 4 26 12,55 -- 9,17 9,10
VII 14 26 13,49 11,23
VIII 3,9 26 13,44
IX 14,5 26 13,62 11,27

XV 26 11,51 -- 8,1
20 59 11,30 -- 7,9
81 11,2~ -- 7,8
10 26 11,47 -- 8,1
5 26 11,44 -- 8,1
XVI 26 9.89 -- 7,94 7.51
14.1 59 9,66 -- 7,54
81 9,58 -- 7,50
I 9,4 26 9,93 -- 7,96 7,52
r 4,7 26 9,90 -- 7,96 7,52
r
XVII I 20 26 11,05

XVIII } 15,2 26 9,50 8,30 7,83

XIX ~ 8,6 26 -- 8.1--6,8 ( + A t )

TABLE 3. Positions and Intensities of the Absorption Maxima in

the UV Spectra of Isatin/3-Thiosemicarbazones in Alcohol

ComPound ~,. . . . n m log~ Compound G, ax,nm log r

247,5 4.10 246; 257,3 4,23; 4,22

I 274 4,03 IX 278 3,84
370 4,31 361 4,33
242,5 3,96 245 4,24
II 277 3,99 X 282,5 4,02
367 4,31 353 4,26
255 4,28 247,5; 253 4,39; 4,30; 4,25
lII 309 3,81 259
393 4,08 XI 291 3,90
385 4,03
248 4.33
IV 303 3,58 XII 246,5:254 4,33; 4,32
393 3,95 390 4,07
242, 248 4,11; 4,12
V 279 3,97 XIII 255 4,41
370 4,37 410 3,81
24O 3,91
VI 281 3.85 XIV 260 4,42
358 4,19 400 3,80
24O 4,17
VII 277, 279 3,95; 3.95 XVIII 250 4,21
352 4,18 360 4,32
240 4.19
VIII 280, 287 4,01; 4.01 XIX 256,5 4,05
355 4,21 364 4,39

439
 T A B L E 4. A b s o r p t i o n F r e q u e n c i e s of t h e C =O and N - H G r o u p s in
t h e IR S p e c t r a of I s a t i n ~ - T h i o s e m i c a r b a z o n e s
CO, r NH, NH:, c.,u -1
in the erystal-
Com- line state in solutions
in mineral in KBr
pound in mineral in KBr lin chloro- oil pellets
pellets in DMSO
oil form

1684b 1694 1710 3149,

3189, 3239,
3420
1682, 1710 1674, 1699c 1694 1710 3180, 3158, 3262,
3274, 3327, 3418
3346,
3428, 3530
II 1686 1679 t686 1698 3158, 3258, 3145,3249
3430 3423
Ill 1737 1725 1,7&t d 3170, 3354 3t67, 3243
3336
IV 1710, 1750 1689, 1740e 1701, 1737 1714, 1722 3220, 3380 3328, 3449
3505
V 1671,1603 1694 1706 3236
VI 1692 1685 1693 3223
VII 1707 1694 1694 1791 -- 3167,
3193
VIII t715 1692 1684 1684
IX 1682, 1695 1694 1706 3t53
X 1689 1683 1689
XI 1685, 1711 1729 1725 3140, 3357
XII 1688, 1733 1701, 1723e 1715 3361
XIII 1697, 1725 1727 1738 3297
XIV 1701, 1730e 1702, 1731 1703, 1722
XVIII 1715 1704 1711 d 314.8, 3266,
3387
XIX 1729 1712 1700 1692 3473

a T h e f r e q u e n c i e s of t h e m o r e i n t e n s e b a n d s a r e s i n g l e d out b y b o l d -
f a c e n u m b e r s , b F o r a s a m p l e w i t h m p 255 ~ e F o r a s a m p l e w i t h
m p 250~176d T h e s u b s t a n c e d i d not d i s s o l v e in c h l o r o f o r m , e T h e b a n d
i s of low i n t e n s i t y a n d a p p e a r s a s a s h o u l d e r .

c a r b o n y l b a n d i s d e t e c t e d o n l y f o r 2 ' - m e t h y l d e r i v a t i v e s , in which, a c c o r d i n g to d a t a f r o m t h r e e - d i m e n s i o n a l
m o d e l s , t h e g r o u p i n g a t t a c h e d to N(2, ) h i n d e r s t h e f o r m a t i o n of t h e a n t i i s o m e r . H e n c e , it c a n be a s s u m e d
t h a t t h i s s p l i t t i n g is c a u s e d b y t h e p r e s e n c e of c o n f o r m e r s t h a t p o s s i b l y d i f f e r b y r o t a t i o n a b o u t t h e N(1, ) -
N(2, ) bond.
T h e s t r u c t u r e of t h i o s e m i c a r b a z o n e s I a n d II in t h e c r y s t a l l i n e s t a t e a l s o h a d to b e r e l i a b l y a s c e r -
t a i n e d . T h e p a r t i c i p a t i o n of t h e NH g r o u p s in t h e h y d r o g e n b o n d s , a c c o r d i n g to t h e IR s p e c t r a l d a t a ( T a b l e
3), i n c r e a s e s in t h e o r d e r 1 - N H < 4 ' - N H 2 < 2 ' - N H . T h e s y n f o r m i s p r o b a b l y a l s o c h a r a c t e r i s t i c in t h e c r y s -
t a l l i n e s t a t e f o r c o m p o u n d s in w h i c h t h e h y d r o g e n a t o m in t h e 2' p o s i t i o n is not s u b s t i t u t e d .
W e h a v e p r e v i o u s l y d e t e c t e d t h e p r e s e n c e of two c a r b o n y l b a n d s in t h e IR s p e c t r u m of I in t h e c r y s -
t a l l i n e s t a t e [4]. H o w e v e r , a s a m p l e d i s p l a y i n g o n l y one c a r b o n y l b a n d w a s o b t a i n e d u n d e r d i f f e r e n t c r y s -
t a l l i z a t i o n c o n d i t i o n s [2]. On t h e b a s i s of t h e s e d a t a , t h e f i r s t s a m p l e w a s c o n s i d e r e d t o b e a m i x t u r e o f
s y n and a n t i i s o m e r s (a, b) [2, 11], and t h e s e c o n d s a m p l e w a s c o n s i d e r e d t o b e t h e p u r e s y n i s o m e r (a) [2].
W e h a v e shown t h a t , d e p e n d i n g on t h e r a t e of c r y s t a l l i z a t i o n , I a n d VII c a n b e i s o l a t e d a s two s a m p l e s t h a t
d i f f e r w i t h r e s p e c t t o m e l t i n g p o i n t a n d IR s p e c t r a in t h e c r y s t a l l i n e s t a t e b u t a r e i d e n t i c a l in s o l u t i o n s .
S p l i t t i n g of t h e c a r b o n y l b a n d is a l s o o b s e r v e d in t h e c r y s t a l l i n e s t a t e f o r IV, V, IX, a n d X I - X I I I . A c o m -
p a r i s o n of a l l t h e p r e s e n t e d d a t a m a k e s i t p o s s i b l e t o a s s u m e t h a t t h e p r e s e n c e of two c a r b o n y l b a n d s in t h e
s o l i d s t a t e is due not to i s o m e r i s m but r a t h e r t o t h e p e c u l i a r i t i e s of t h e c r y s t a l l a t t i c e a n d t h e f o r m a t i o n of
i n t e r m o l e c u l a r h y d r o g e n b o n d s . T h e d e c r e a s e in t h e m e l t i n g p o i n t when t h e h y d r o g e n a t o m s in t h e NH
g r o u p s a~e r e p l a c e d b y m e t h y l g r o u p s a l s o a t t e s t s to t h e p r e s e n c e of t h e s e b o n d s .
In a p r e v i o u s s t u d y of t h e t a u t o m e r i s m of t h i o s e m i c a r b a z o n e s I a n d II w e u s e d t h e i r S - m e t h y l d e r i v a -
t i v e s , XVIII and XIX, w h i c h a r e c a p a b l e of e x i s t i n g in two t a u t o m e r i e f o r m s c a n d d, a s f i x e d t h i o l f o r m s .

440
 (,.~;,, n-n=c t -n"2 ~N..",n ~ - Ic=',.n
=

R c RI d

XVIll R=H XIX R=CH 3

At the same time, the s p e c t r a l c h a r a c t e r i s t i c s of I - X I V make it possible to solve the problem of the
t a u t o m e r i s m of XVIII and XIX when they are c o m p a r e d with the c o r r e s p o n d i n g c h a r a c t e r i s t i c s of the latter.
Since the signal of the 2 ' - H proton at weak field is absent in the PMR s p e c t r a of the S-methyl derivatives
in DMSO (Table 2), but the s p e c t r a do contain signals c h a r a c t e r i s t i c for the 4'-NH 2 group, s t r u c t u r e c is
m o r e likely. When the p o l a r i t y of the solvent d e c r e a s e s , the UV s p e c t r u m of XIX, in contrast to the s p e c t r a
of I-XIV, undergoes a h y p s o c h r o m i c shift; this is possibly due to the formation of f o r m d.
The p r e s e n c e in the IR s p e c t r u m of c r y s t a l l i n e XIX of a d i s t i n c t b a n d above 3400 cm -1, w h i c h a c c o r d -
ing to our d a t a is c h a r a c t e r i s t i c for the p r i m a r y thioamide group of the t h i o s e m i c a r b a z o n e chain, makes it
possible to a s s u m e that XIX exists in f o r m c under t h e s e conditions.

EXPERIMENTAL
The PMR spectra of solutions of the compounds in DMSO were recorded with a C-60 HI spectrometer
with hexamethyldisiloxane (HMDS) as the external standard. The chemical shifts were measured on the 6
scale with an accuracy up to 0.01 ppm. The IR spectra of 0.I M solutions in DMSO (layer thickness 0.07
ram) and of 3 9 10 TM M solutions in chloroform (layer thickness 14.4 ram) were recorded with a UR-10 spec-
trometer; in both cases, compensation was made for the absorption of the solvent. The DMSO was purified
according to the specifications in [12], and its homogeneity was monitored by PMR spectroscopy. The UV
spectra of alcohol solutions were recorded with an SF-8 spectrophotometer.
4-Methylthiosemicarbazide [13] and 2,4-dimethylthiosemicarbazide [13] were obtained from methyl
methyldithioearbamate [14], while 2,4,4-trimethylthiosemicarbazfde [13] was obtained from tetramethyl-
thiuramdisulfide [15].
Benzaldehyde 4,4-Dimethylthiosemiearbazone (XVII). A solution of 1.4 g (12 mmole) of 4,4-dimethyl-
thiosemicarbazide [14] in II ml of 1 N HCI was added to a Solution of 1.47 g (12 mmole) of benzaldehyde in
II ml of alcohol. A greenish-white precipitate formed, and the temperature rose to 33 ~ After 0.5 h, the
mixture was filtered, washed with 50% aqueous alcohol (three 1.5-ml portions), and dried at 105 ~ to give
65.5~c of silvery-white needles with mp 159 ~ (from 40% aqueous alcohol) (mp 162 ~ [9]).
Isatin ~-Thiosemicarbazones. The synthesis of I, II [16], V [5], VII-X [6], and XVIII [5, 4, 11] was
previously described; we presented the method for the preparation of III, IV, and XIX in [4] (also see [Ii]).
Depending on the conditions of crystallization from aqueous alcohol, compound I was obtained as cotton-
like crystals with mp 255 ~ or needles with mp 250 ~ According to the IR spectra (KBr pellets), the two
samples were identical to those described in [2]. Compound VII was similarly obtained as crystals with
mp 230 or 217 ~ .
N-Methylisatin 4-Methylthiosemicarbazone (V I), Isatin and N-Methylisatin 2,4-Dimethylthiosemi-
c a r b a z o n e s (XI, XID, and Isatin and N-Methylisatin 2 , 2 , 4 - T r i m e t h y l t h i o s e m i c a r b a z o n e s (XIII, XIV). These
compounds were obtained via the following method. Aqueous solutions of equimolecular amounts of isatin
(or N-methylisatin) and the a p p r o p r i a t e t h i o s e m i c a r b a z i d e derivatives were mixed while boiling, 0.1 N HC1
(0.08-0.31 ml per g r a m of diketone) was added, and heating was continued for 10-15 rain. The m i x t u r e s
were filtered, and the p r e c i p i t a t e s were washed with w a t e r and dried at 105 ~. The r e s u l t s of e l e m e n t a r y
analysis and the Rf values a r e p r e s e n t e d in Table 1.

LITERATURE CITED
I. A. B. Tomchin, Ya. A.Kharit, and A. K. Kutsenko, Khim.-Farmats. Zh., No. 7, I0 (1973).
2. P. Barz and H. P. Fritz, Z. Naturf., 25, 199 (1970).
3. I. S. I0ffe, A. B. Tomchin, V. Ao Dobrego, and L. N. l~rtevtsian, Khim.-Farmats. Zh., No. 8, 7 (1973).
4. I. S. Ioffe, A. B. Tomchin, and E. N. Zhukova, Zh. Obshch. Khim., 39, 70 (1969).
5. D. J. Bauer and P. W. Sadler, J. Pharmacol., 15, I01 (1960).
6. D. J. Bauer and P. W. Sadler, Nature, 190, 1167 (1961).
7. M. Freund and A. Schander, Ber., 35, 2603 (1902).
8. F. J. Wilson and R. Burns, J. Chem. Soc., 121, 873 (1922).

441
 9. E. Lieber and C. B. L a y e r , US Patent No. 154,269 (1962); Chem. Abstr., 5_~8,4544 (1962).
10. F. Bohlman, Ber., 8_~4,490 (1951).
11. G. Doleseehall and K. Lempert, Acta, Chim. Acad. Sci. Hung., 6_~4,369 (1970).
12. B. Teichmann and D. Ziebarth, Jo Prat~. Chem., 3_22,No. 4, 230 (1966).
13. K . A . Jenssen, U. Antoni, B. K~fgi, C. Larsen, and C. Pedersen, Acta Chem. Scand., 2_22, 1 (1968).
14. A. Do Ainley, W. H. Davies, H~ Gudgeon, J. C. Harland, and W. A. Sexton, J. Chem. Soc., 151 (1944).
15. J. Braun and F. Stechele, Ber., 3__66,2275 (1903).
16. Z. Holzbechker, Chem. Listy, 4_~4,126 (1950).

442
REACTIONS OF N-ACYLATED ETHYLENEIMINES
WITH THIOACETIC ACID AND HYDROGEN SULFIDE

A. A. Yamontaite, G. K. Krasil'nikova, UDC 547.717'897

and O. V. Kil'disheva

A series of fl-(S-acetylmercapto)ethylamides of a-amino acids and raft-unsaturated acids

and bis[fl- (S-acetylmercapto)ethyl]amides of dicarboxylic acids were obtained by cleavage
of N-acylethyleneimines with thioacetic acid. The reaction of ethyleneimides of N-acyl-
amino acids with hydrogen sulfide leads to the corresponding/3-(N-acylamino)ethylmer-
captans. Bis(ethyleneimides) of azelaic and sebacic acids react with hydrogen sulfide to
form cyclic sulfides along with the corresponding bis[(fi-mercaptoethyl)amides].

Ethyleneimides of carboxylic acids react vigorously with ring opening with both electrophilic and
nucleophilic reagents [1]. We have shown that the ethyleneimides of N-acylated s-amino acids [2] and~,fl-
unsaturated acids [3] and the bis (ethyleneimides) of dicarboxylic acids [4] on reaction with thioacetic acid
readily open the ethyleneimine rings and form the corresponding f~- (S-acetylmercapto)ethylamides (I-XV)
(Table 1).
HSCOCH:
R I~\1 C CI! %('0C1tl
l-k\
I
R ~ H C I I CII SII

X'~ I-X\

The ethyleneimides of N-phthalylglycine, N-phthalylalanine, N-phthalytvaline, N-carbobenzoxyvaline.

and N-acetylvaline were isolated in the reaction with hydrogen sulfide. The corresponding N-acyl-fl-mer-
captoethylamines (XVI-XX) are formed in yields up to 80%, judging from the amount of free mercapto groups.
However, only N-(N-acetylvalyl)-fl-mercaptoethylamine (XX, Table 2) could be isolated by repeated re-
crystallization of the reaction products. In this case, /3-mercaptoethylamides XVI-XIX are gradually oxi-
dized completely to the corresponding symmetrical disulfides (XXI~XXW).
The reaction of bis(ethyleneimides) of azelaic and sebacic acids with a considerable excess of hydro-
gen sulfide leads to bis[(fl-mercaptoethylamides)] X'XV and XXVI (Table 2) and cyclic sulfides XXVII and
XXVIII. Compounds XXVH and XXVHI are apparently products of intramolecular opening of the ethylene-
imine ring by the mercapto group in the intermediate N,N-ethylene~N'-(/%mercaptoethyl)diamides ofazelaic
and sebacic acids. Cyclic sulfide XXVII are also synthesized from the bis(fl-chloroethylamide) of azelaic
acid (XIX) and sodium sulfide.
,CO~.,,~ / -'CONHCH2CH~.SH /CONHCHeCHa\

(CH2)a~CO d
+ H2S ~ (CH2)nXCONHCH2CH2SH~ (CH2)n(aCON
` S
HCH2Ctt2/

n =7,8 XXV, XXVI XXVII, XXVIII

Alkali-resistant fi-mercaptoethylamides XIX, X-X, XXV, and XXVI were purified through their sodium
thiolates (Table 2).

Institute of Biochemistry, Academy of Sciences of the Lithuanian SSR, Vilnius. Translated from
Khimiya Geterotsiklicheskikh Soedinenii, No. 4. pp. 510-514, April. 1974. Original article submittedMareh
26, 1973.

9 1975PlenumPublishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

443
 TABLE 1. f l - ( S - A c e t y l m e r c a p t o ) e t h y l a m i d e s RNHCH2CH2SCOCH~
6-XV)

I N-Phthalylglycyl i52--I~ b CmH2~N~O4S ~I

II N-Phthalyl- Oil, c CmHlsN20~S 56
alanyl
Ill N-Phthalylvalyl 1'20--1~1b CIzH2~N~O~S 78,
IV N-Phthalyl- - [28--129d C21H28N~O~S 57
phenylalanyl
V N-CarOoDenz- 111--II,2
e ClTH24N204S ~0
oxyvalyl
VI .N-Acety'lyalyl 124---126,
d C.H~oN~O~S 86
VII N-~enzoyneucyx"197--19~~ C~TH~N~OzS 62
VIII Acrylolyl f C~HnNO~S 50
IX Methacryloyl g C~H~NO~S 52
X 3,8-Dimethyl- 44--45h C~H~sNOaS 55
acryloyl
XI Cinnamoyl 83--85i C,~H~gWO~S 68
XII B-Carbofneth- J C~H~sNO~S 90,
oxypropionyl
XIII N-[l~-(S-acetyl-39--140k C~,H~,N20~Sz 75.
mercapto)-
erhyl]-adipyl 9
XIV N-[~-:(S-2a)etyl- I09--,111k C,THsoN~O,Ss 55
mercapto)- ]
ethyl]-.
aze'layx
XV N-[B-(S-acetyl- 31--133k CmH~N~O4S~ 73
rnercapto)-
ethyl]-
sebacyl

aAmino acids of the D,L s e r i e s , b F r o m ethanol. Cpurified b y c h r o -

m a t o g r a p h y with a column filled with activity II aluminum oxide; the
eluent was b e n z e n e - e t h e r (1 : 1). d F r o m b e n z e n e - p e t r o l e u m e t h e r .
e F r o m a c e t o n e - p e t r o l e u m e t h e r , fBp 93-94 ~ {3 ram), n ~ 1.5104, d 2~
1.1492. g.Bp 152-153 ~ (4 ram), n ~ .1.5069, d~~ 1.1305. h F r o m ethyl
acetate, l F r o m p e t r o l e u m e t h e r . JBp 172-174 ~ (3 ram), n ~ 1.5113,
d~~ 1.2132. k F r o m acetone.

TABLE 2. N-Aeylated f l - M e r c a p t o e t h y l a m i n e s RNHCH2CH2SH

] Empirical Found. ~ i Calc','a]~ i~"
mp,*C
formula
iC H! S i C {H s Ia
_XV_l.l_N-Phthalylalanyl 1,24--125g CI3HI4NgO3S 5~,0 4,71 11,7 ~,i 5,1 11;5 ~d5
._XV.!I.IIN-Phthalylvalyl 122--123a CIsHIsN203S 58,9 5,9J I0,5]58,9 5,~ 9,916I
XIX iN-Carbobenzoxy- 152--153a,b CIsH22N~O3S ~,1 7,0 t 9,7j58,0 7,1 1"0,3 70
valyl
XX IN- Ace tylvalyl 151--153c,d CgHIsN~OzS 49,3 8,4114,3149,5 8,3 14,7 73
XXV JN-(/~-Mercapto- 131--132a,e CI3H~N20~S~ 51,0 9,0 20,8 50,9 8,6 ~0,9 65
| ethyl)azelayl
XXVI IN-(15-Mercapto- I 141--14~,g C.H2sN202S2 52,8 8,8]19,2[52,51 8,9 20,0 75
ethyl)sebacyl i

a F r o m aqueous methanol, b2,4-Dinitrophenyl thioether: mp 197-

198 ~ (from acetone). Found: C 53.1; H 5.5; S 6.3~. C21H24N4OTS.
Calculated: C 52.9; H 5.1; S 6.7%. C F r o m e t h e r , d2,4-Dinitrophe-
nyl thioether: mp 215-216 ~ (from methanol). Found: C 47.2; H5.4;
S 8.1%. C15H20N406S. Calculated: C 46.9; H 5.2; S 8.3%. e 2 , 4 - D i -
nitrophenyl thioether: mp 126-128 ~ (from methanol). Found: C
47.0; H 5.0; S 9.9%. C25H30N6010S2. Calculated: C 46.6; H 4.7; S
10.4%. f F r o m benzene, g2,4-Dinitrophenyl thioether: mp 141-142 ~
{from methanol). Found: C 47.7; H 5.4; S 9.5~. C26Ha2N6010S2. Cal-
culated: C 47.8; H 4.9; S 9.8%.

444
 Since the synthesis of N-acylated f i - m e r c a p t o e t h y l a m i n e s f r o m ethyleneimides of acids and hydrogen
sulfide proved to be complicated by difficulties involved in purification and side reactions, to p r e p a r e them
S-acetylthioethers II, III, and V were subjected to alcoholysis under the influence of HC1, while VI, XIV, and
XV were subjected to alkaline h y d r o l y s i s . The synthesized aminothiols (XVII-XX, XXV, and XXVI) (Table 2)
required a l m o s t no f u r t h e r purification.

EXPERIME NTA L
The starting ethyleneimides of N - a c y l a m i n o acids and a,fl-unsaturated acids were obtained by the
method in [2, 3]. The p r e v i o u s l y known ethyleneimides of succinic acid monoethyl e s t e r [5] and phthalyl-
glycine [6] were also obtained by the method in [2]. The bis(ethyleneimides) of dicarboxylic acids were
obtained f r o m dicarboxylic acid chlorides and ethylene[mine [4].
fl,fl-Dimethylacrylic Acid Ethyleneimide. This compound was obtained in 80~ yield imp 143-144 ~
(from ethylacetate)] f r o m 0.03 mole of fl,fl-dimethylacrylic acid, 0.03 mole of ethylene[mine, and 0.03 mole
of 1,3-dicyclohexylcarbodiimide in c h l o r o f o r m by the method in [3]. Found: N 10.8%. CTH~NO. Calcu-
lated: N 11.2%.

Cinnamic Acid Ethyleneimide. This compound was s i m i l a r l y obtained as a m a s s , which was extracted
with p e t r o l e u m ether. Cooling of the e x t r a c t gave 66% of ethyleneimide with mp 57-58 ~ (from b e n z e n e -
p e t r o l e u m ether). Found: C 76.0; H 6.3%. CliHllNO. Calculated: C 76.3; H 6.4%.
fi-(S-Acetylmercapto)ethylamides of N-Acylamino Acids (I-VII) and a,fl-Unsaturated (VHI-XI) and
Dicarboxylic (XII-XV) (Table 1) Acids. A 0.02-mole sample of the ethyleneimide of the appropriate mono-
carboxylic acid or 0.01 mole of the bis (ethyleneimide) of a dicarboxylic acid was added i~ portions with
s t i r r i n g at 5 ~ to a solution of 0.02 mole of thioacetic acid in 15 ml of dry benzene or methanol; the r e a c -
tion mixture was prevented f r o m w a r m i n g above 10 ~ The mixture was s t i r r e d for 15 min, after which the
t e m p e r a t u r e was slowly brought up to r o o m t e m p e r a t u r e (in the synthesis of VIII-X-V) or to ~60 ~ and s t i r r e d
at this t e m p e r a t u r e for 1.5-3 h. Compounds VIII-XI were synthesized in a nitrogen a t m o s p h e r e . The end
of the reaction was monitored with r e s p e c t to Congo red or by means of t h i n - l a y e r c h r o m a t o g r a p h y (TLC).
The solvent was then vacuum evaporated, and the S-acetylthioethers were r e c r y s t a l l i z e d or vacuum dis-
tilled. Compound H was purified by c h r o m a t o g r a p h y with a column filled with activity II aluminum oxide
with elution by c h l o r o f o r m . T h i n - l a y e r c h r o m a t o g r a p h y on activity II aluminum oxide in b e n z e n e - e t h e r
(1: 1) was used to identify unsaturated S - a c e t y l t h i o e t h e r s VIII-XI. IR s p e c t r a of amides VIII-XI: 3 0 5 0 -
3070 (=CH-), 950-975 (=CH2) , 655 a m -1 (thiol sulfur); the LR s p e c t r a of I - X u have absorption bands at
1695-1700 (C = 0 in thiol e s t e r s ) and 1660-1670 c m -1 (amide I).

Reaction of Ethyleneimides of N - a c y l a m i n o Acids with Hydrogen Sulfide. A solution of 0.01 mole of

N-acylamino acid ethyleneimide in 50 ml of dry methanol was added dropwise to 150 ml of dry methanol
saturated at - 1 0 ~ with hydrogen sulfide (~2 g) by bubbling hydrogen sulfide into the mixture with vigorous
s t i r r i n g and cooling on an ice bath. The t e m p e r a t u r e of the mixture was raised slowly to room t e m p e r a t u r e ,
and the mixture was allowed to stand in a tightly sealed flask for 20 h. This p r o c e d u r e gave crude c r y s -
talline N-acylaminothiols XVI-XX, the p e r c e n t a g e of free SH groups in which was 70-80% (determinediodo-
metrically). T h i n - l a y e r c h r o m a t o g r a p h y on activity II aluminum oxide in b e n z e n e - e t h e r - m e t h a n o l (4 : 1 : 1)
was used to identify and p r e p a r a t i v e l y purify X-VII and XVIII (Table 2). For purification, crude aminothiols
XIX and XX were dissolved with shaking in 20 ml of 5% sodium hydroxide solution; the solutions were acid-
ified with concentrated hydrochloric acid, saturated with NaC1, and the resulting aminothiol was separated.
The filtrate was extracted s e v e r a l times with ether, the e t h e r e x t r a c t s were combined with the individual
aminothiol, and the mixture was washed with water and dried with m a g n e s i u m sulfate. The solvent was
evaporated, and the residue was r e c r y s t a l l i z e d one to two times to give 30-40% of pure products (Table 2).
Repeated c r y s t a l l i z a t i o n of crude N-acyl-fl-aminothiols XVI-XIX f r o m methanol gave bis ( N - a c y l - ~ - a m i n o -
ethyl) disulfides XXI-XXIV (Table 3).
Reaction of Ethyleneimides of Azelaie and Sebacic Acids with Hydrogen Sulfide. This reaction was
c a r r i e d out s i m i l a r l y . The p e r c e n t a g e of free SH groups in the crude products was ~40%. Bis(fl-mercapto-
ethylamides) XXV and XXVI (Table 2) were also purified through the thiolates. Fractional c r y s t a l l i z a t i o n
of the crude r e a c t i o n products gave XXVII and XX-VIII. Azelaic acid N,N'-(3-thiapentamethylene)diamide
(XXVII) was obtained in 42% yield and had mp 156-157 ~ (from methanol). Found: C 56.8; H 9.3; S 12.3%.
Mol. wt. (Rast method) 276. C13H24N202S. Calculated: C 57.2; H 8.9; S 11.8%; Mol. wt. 272. Sebacic acid
N,N'-(3-thiapentamethylene)diamide (XXVIII) was obtained in 35% yield and had mp 131-132 o (from ethanol).
Found: C 58.4; H 9.0; S 11.5%,- Mol. wt. 284. C14H26N2C)2S. Calculated: C 58.7; H 9.2; Sll.2}b, Mol. wt. 286,

445
 TABLE 3. B i s ( N - a e y l - f l - a m i n o e t h y l ) Disulfides (RNHCH2CH2S)2

Corn -t Empirical Found,% Calc., a]o

pound R rap, ~C i formula
i clH S C H s ~I 0

XXI N-Phthalylglycyl 222--22~'aC24HmN406S2 54,4 4,3 12,3 54,7 42 12,2 ] 40

XXII N-Phthalylalanyl 218--219~I C26H26N4OsS2 56,1 14,8 11,3 56,3 4,7 11,51 45
XXIII N-Phthalylvalyl 130--131~,1C~oH34N40~S2 58,6 [ 5,6 10,5 59,0 5,6 10,5 ] 51
XX1V N-CarboSenzoxy- 188--189b~C~0H42N406S2 58,4 7,0 9,6 58,2 6,8 10,3 50
\ [ valyl [
c
a F r o m ethyl acetate (nap 137-138 ~ [6]). b F r o m methanol. From
aqueous methanol.

Compound XXVII was obtained by the method in [7] f r o m bis (B-chloroethylamide) XXIX and Na2S in
the f o r m of an oil (in 40% yield). It was purified by TLC on activity II aluminum oxide in b e n z e n e - e t h e r -
methanol (6 : 15:4) and had mp 155-156 ~ The compound obtained was c h r o m a t o g r a p h i c a l l y identical to the
sample d e s c r i b e d above and did not d e p r e s s its melting point.
N-Acetylvaline fl-Mercaptoethylamide (XX) and Azelaic and Sebacic Acid Bis (fl-mercaptoethylamides)
(?C~V and XXVI). A 0.01-mole s a m p l e of S - a c e t y l t h i o e t h e r VI, XIV, or XV was shaken with 40 ml of 5%
sodium hydroxide solution. The m i x t u r e s w e r e then worked up as d e s c r i b e d above. The yields of a m i d e s
XX, XXV, and XXVI w e r e ~70% (Table 2).
N-Phthalylalanine, N-Phthalylvaline, and N-Carbobenzoxyvaline f i - M e r c a p t o e t h y l a m i d e s (XVII-X-IX).
A 0.01-mole s a m p l e of S - a c e t y l t h i o e t h e r II, III, and V and 20 ml of a 1% HC1 solution in absolute methanol
w e r e refluxed for 2 h. The solvent was e v a p o r a t e d to d r y n e s s , and the residue was washed with w a t e r and
r e c r y s t a l l i z e d . The yields were ~ 60% (Table 2).
Azelaic Acid Bis(fl-chloroethylamide (XXIX). E t h e r s a t u r a t e d with the calculated amount of hydrogen
chloride was added to a solution of 0.015 mole of azelaic acid bis (ethyleneimide) in 50 ml of absolute e t h e r .
Amide XXIX s e p a r a t e d . The yield of product with mp 128-129 ~ (from ethanol) was 85%. Found: C 50.6;
H 7.5%. C13H24C12N20. Calculated: C 50.4; H 7.7%.

LITERATURE CITED
1. P. A. Gembitskii, D. S. Zhuk, and V. A. Kargin, C h e m i s t r y of Ethyleneimine [in Russian], Nauka,
Moscow (1966).
2. A. A. Yamontaite, G. K. K r a s i l ' n i k o v a , K. I. Karpavichyus, and O. V. Kil'disheva, Izv. Akad. Nauk
SSSR, Set. Khim., 1856 (1969).
3. O. V. Kil'disheva, G. K. K r a s i l ' n i k o v a , K. I. Karpavichyus, L. P. P a r s h i n a , and L. I. Matskyavichyus,
USSR Author's C e r t i f i c a t e No. 278,680; Byul. Izobr., No. 26, 22 (1970).
4. C. W. Woods, A. B. Bo6kovec, and F. M. Hart, J. Med. Chem., 7, 371 (1964).
v
5. M. Semonskej and A. Cernej, Chem. Listy, 47, 281 (1953).
6. D. Fle~ and A. M a r k o v a 6 - P r i p i S , Arh. Kern., 27, 211 (1955).
7. D. T. McAllan, T. V. Cullum, R. A. Dean, and F. A. Fidler, J. A m e r . Chem. Soc., 73, 3627 (1951).

446
INDOLE DERIVATIVES
XCII.* ALKYLATION OF BARBITURIC ACIDS WITH MANNICH BASES

N. N. S u v o r o v , V . S. V e l e z h e v a , UDC 547.753'854 : 542.953

V. V. Vampilova, and E. N. Gordeev

5-Substituted(butyl, p h e n y l ) - 5 - s k a t y l ( 5 - m e t h o x y s k a t y l ) b a r b i t u r i c acids w e r e obtained by

alkylation of the c o r r e s p o n d i n g b a r b i t u r i c acids with g r a m i n e and 5 - m e t h o x y g r a m i n e An
d i m e t h y l f o r m a m i d e and dimethyl sulfoxide. 5,5-Dialkylation products w e r e obtained in
the a l k y l a t i o n o f b a r b i t u r i e and t h i o b a r b i t u r i c acids with g r a m i n e .

Alkylation with Mannich b a s e s is widely used f o r the s y n t h e s i s of d e r i v a t i v e s of fl-keto, malonie, and

n i t r o a c e t i c e s t e r s , fl-diketones, and n i t r o compounds. We have developed a method for the alkylation of
2 - t h i o b a r b i t u r i c acid (7) and b a r b i t u r i c acid (ii) and its d e r i v a t i v e s by the action of g r a m i n e (7II) or 5 - m e t h -
o x y g r a m i n e (IV). The r e a c t i o n in alcohol, dioxane, and pyridine is c o m p l i c a t e d by the fact that both c o m -
ponents a r e only slightly soluble in these solvents. Judging f r o m the l i t e r a t u r e data [2], d i m e t h y l f o r m a m i d e
(DMF) and dimethyl sulfoxide (DMSO) cannot be used, inasmuch as they condense with acids I and II on
heating and e v e n at r o o m t e m p e r a t u r e .
5 - B u t y l ( p h e n y l ) - 5 - s k a t y l b a r b i t u r i c acids (VIII-IX) w e r e obtained in 70-75% yields in the alkylation
of sodium s a l t s of 5-butyl(phenyl)barbituric acids (VI, VII) by g r a m i n e methiodide (V) by the method p r e -
viously used for the introduction of the skatyl group into malonic e s t e r s [3].
Considering that the m o r e acidic [than malonic e s t e r s (pKa ~ 13)] fi-diketones (pK 5-6) a r e alkylated
d i r e c t l y by g r a m i n e (and not in the f o r m of sodium salts) without a c a t a l y s t o r in the p r e s e n c e of catalytic
amounts of KOH [4], we applied this method f o r the alkylation of b a r b i t u r i c acids (pK 4-5).
B a r b i t u r i c acids VIII and X w e r e obtained in yields of 95 and 80% when a catalytic amount of KOH
was used:
/CO--NH\
x ~ C H 2 N (CH3)2 /CO--NH\ ~_~CH2CR CO
+ CHR CO ~ "XCO--NH/
\CO--NH /
H H
I|1. |V Yl, VII V|II-X

H2

~/C H
~X~/CO--NH-.,
C
/ \CO--NH/
C=X

III X=H; IV X=OCH3; VI R=C4Hg; hc~'~--~CH2

VII R=C6Hs; VIII X=H, R~C4H~;
IX X= H, R=C6Hs; X X=OCHw R=C4Hg; H
XI, Xlll X=O; XII, XIV X =S XIII, X|V

The yield of acid IX was 86% during alkylation with g r a m i n e of acid VII in the p r e s e n c e of 0.5-1 mole of
KOH.

*See [1] for c o m m u n i c a t i o n XCI.

D. I. Mendeleeva Moscow Institute of Chemical Technology. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l -

icheskikh Soedinenii, No. 4, pp. 515-518, April, 1974. Original a r t i c l e submitted June 4, 1973.

9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy o f this article is available from the publisher for $15.00.

447
 D i a l k y l a t i o n p r o d u c t s - 5, 5 - d i s k a t y l b a r b i t u r i c and t h i o b a r b i t u r i c
a c i d s (XII and XIV) - a r e f o r m e d in the a l k y l a t i o n of s o d i u m s a l t s XI
and XII of b a r b i t u r i e and t h i o b a r b i t u r i e a c i d s with g r a m i n e m e t h i o d i d e .
U n d e r these conditions, the f o r m a t i o n of c o n d e n s a t i o n p r o d u c t s of a c i d s
I and II was not o b s e r v e d in DMSO.
~176
D i s k a t y l b a r b i t u r i c a c i d s XIII and XIV a r e obtained in the b e s t
y i e l d s (80-85%) by the r e a c t i o n of an e q u i m o l a r amount of s a l t s XI
and XII with m e t h i o d i d e V. A c o m p l e x m i x t u r e of p r o d u c t s is f o r m e d
in the c a s e of a twofold e x c e s s of m e t h i o d i d e V as c o m p a r e d with s a l t s
~o
XI and XII.
D i a l k y l a t i o n p r o d u c t s XIII and XIV a r e a l s o the p r i n c i p a l r e a c -
tion p r o d u c t s in the a l k y l a t i o n of b a r b i t u r i c and t h i o b a r b i t u r i c a c i d s
with g r a m i n e in e q u i m o l a r r a t i o s . The m o n o a l k y l a t i o n p r o d u c t s c a n -
not be obtained in the a l k y l a t i o n of a fivefold to tenfold e x c e s s of a c i d s
I and II. The s a m e p r i n c i p l e was a l s o o b s e r v e d in the a l k y l a t i o n of
dimedone and d i h y d r o r e s o r e i n o l (pK a "~ 5.2-5.6 [4]) with g r a m i n e .
Y-
-
- - E:
D i s k a t y l b a r b i t u r i c acids XIII and XIV a r e obtained as a r e s u l t
of the r e a c t i o n in the f o r m of s t a b l e c o m p l e x e s XV and XVI containing
two DMSO m o l e c u l e s .
The f o r m a t i o n of side c o m p l e x e s due to hydrogen bonds of the
NH g r o u p s of p h e n o b a r b i t a l was p r e v i o u s l y o b s e r v e d with compounds
that a r e e l e c t r o n donors - DMSO and N , N - d i m e t h y l a c e t a m i d e (DMA)
[5]. Complex XV of acid XIII is s t a b l e in w a t e r and a l s o on p r o l o n g e d
heating (for g r e a t e r than 40 h) but d e c o m p o s e s in alkaline m e d i a at
100 ~ Complex XVI of thioacid XIV is l e s s s t a b l e and g r a d u a l l y d e c o m -
p o s e s on r e p e a t e d r e c r y s t a l l i z a t i o n s f r o m alcohol. Thioacid XIV is
r e s i n i f i e d on s t o r a g e and on heating in w a t e r and in m o s t o r g a n i c s o l -
vents and is p u r i f i e d only by r a p i d r e p r e c i p i t a t i o n f r o m methanol by
the addition of w a t e r . The s k a t y l b a r b i t u r i c acids do not c o m p l e x with
DMF.
The a b s o r p t i o n bands of c a r b o n y l g r o u p s l i e at 1680, 1700-1720,
and 1740-1760 c m -1 [6] in the IR s p e c t r a of acids VIII-X and XIII.
T h e r e a r e s e v e r a l bands a p p a r e n t l y due to d i f f e r e n t f o r m s of i n t e r -
m o l e c u l a r hydrogen bonds with p a r t i c i p a t i o n of NH g r o u p s of the b a r -
b i t u r i c acids at 3060-3300 c m - I , and bands involving the NH g r o u p s
of indoles a r e found at 3400-3480 e m -1. In addition to a b s o r p t i o n
bands of two c a r b o n y l g r o u p s , the IR s p e c t r u m of thioacid XIV con-
t a i n s a C = S a b s o r p t i o n band at 1530 e m -1 [7].
The a l i p h a t i e p o r t i o n of the PMR s p e c t r a of a c i d s XIII and XIV
contains only one s i n g l e t at 3.5 p p m with an i n t e n s i t y of four p r o t o n
u n i t s . The s p e c t r a of a c i d s VIII and IX contain the s a m e s i g n a l with
an intensity of two p r o t o n units; t h i s e x c l u d e s i s o m e r i c s t r u c t u r e s of
t h e p r o d u c t s of N- o r O - a l k y l a t i o n of the s t a r t i n g b a r b i t u r i c a c i d s .
The s i g n a l s of a r o m a t i c ring p r o t o n s in the f o r m of a m u l t i p l e t
lie at 6.8-7.3 ppm. The a b s e n c e of indole 3-H s i g n a l s at 6.4 p p m [8]

!~
and the p r e s e n c e of an indole 2-H doublet at 6.7 p p m c o n f i r m s the
5 - ( 3 - i n d o l y l m e t h y l ) b a r b i t u r i e acid s t r u c t u r e (VIII-IX, XHI-XtV).

EXPERIMENTAL
The IR s p e c t r a of m i n e r a l oil s u s p e n s i o n s of the e o m p o u n d s w e r e
r e c o r d e d with a UR-10 s p e c t r o m e t e r . The m e l t i n g points of the c o m -
pounds, the r e s u l t s of a n a l y s e s , and the IR s p e c t r a l data a r e p r e s e n t e d
in Table 1.

448
 5,5-Diskatylbarbituric Acid CKIII). A mixture of 0,64 g (5 mmole) of acid II, 1.74 g (10 mmole) of
g r a m i n e , and 0.01 g of KOH in 10 ml of DMSO was heated at 80-100 ~ in a s t r e a m of nitrogen for 6 h. The
reaction mixture was cooled and diluted with water, and the resulting precipitate was removed by filtration
to give 2.4 g (88.670) of complex XV with mp 135-137 ~ and 208-210 ~
Acid XIII [1.2 g (6270)] with mp 221-223 ~ was obtained when this reaction was c a r r i e d out in DMF with
the same amounts of starting m a t e r i a l s .
A 2.4-g sample of complex XV was dissolved in saturated sodium carbonate solution and extracted
three times with ether. The sodium carbonate solution was acidified with 5% HC1 and extracted with ether
and ethyl acetate. The e x t r a c t was dried with MgSO4, and the solvents were removed by distillation to give
1.5 g (78%) of acid XIII.
A) Gramine methiodide (V). A 3.69-g (2.5 mmole) sample of methyl iodide was added dropwise to a
solution of 4.52 g (2.5 mmole) of g r a m i n e in 10 ml of DMSO, and the mixture was allowed to stand for 10-
12 h.
B) Alkylation with methiodide V. A 3.8-g (30 mmole) sample of acid II was added to sodium ethoxide,
p r e p a r e d f r o m 0.57 g of Na (2.5 mmole) and 30 ml of absolute methanol, and the mixture was refluxed for
15 rain, after which the alcohol was evaporated to d r y n e s s . A total of 45 ml of DMSO and the e a r l i e r p r e -
pared methiodide V were added to salt XI, and the mixture was heated at 90-100 ~ for 6 h in a s t r e a m of
nitrogen. The unchanged salt XI was removed by filtration, and the filtrate was diluted with water. The
resulting precipitate was removed by filtration and washed with water to give 6.15 g (90.770) of complex XV.
5 , 5 - D i s k a t y l - 2 - t h i o b a r b i t u r i c Acid (XIV). A mixture of 1.1 g (7.5 mmole) of acid I, 2.6 g (15 mmole)
of g r a m i n e , and 0.01 g of KOH in 10 ml of DMSO was heated at 80-100 ~ in a s t r e a m of nitrogen for 6 h. It
was then diluted with water and acidified with 570 HC1. The resulting precipitate was removed by filtration
and washed with w a t e r to give 3.8 g (9270) of complex X-VI with mp 130-134 ~ To free the complex of DMSO,
3.8 g of complex XVI was p a s s e d through a column containing silicon dioxide (pure for luminophores) with
elution by a c e t o n e - c h l o r o f o r m (1 : 3) to give 2.4 g (8070) of acid XW with mp 192-195 ~
Acid XIV was obtained in 7570 yield when this reaction was c a r r i e d out in DMF with the same amounts
of s t a r t i n g m a t e r i a l s .

5 - B u t y l - 5 - s k a t y l b a r b J t u r i c Acid (VIII). This compound was obtained f r o m 2.3 g (12.5 mmole) of acid
VI, 2.17 g (12.5 mmole) of g r a m i n e , and 0.01 g of KOH in 20 ml of DMSO in analogy with the synthesis of
acid XIII. The alkylation time at 80-100 ~ was 5 h. The yield of product with mp 208-210 ~ was 3.7 g (95.970).
5 - B u t y l - 5 - ( 5 - m e t h o x y s k a t y l ) b a r b i t u r i c Acid (I). This compound was obtained f r o m 1.84 g (10 mmole)
of acid VI, 2.04 g (10 mmole) of g r a m i n e W, and 0.01 g of KOH in 10 ml of DMSO in analogy with the syn-
thesis of acid VIII. The yield was 2.6 g (75.870).
5 - P h e n y l - 5 - s k a t y l b a r b i t u r i c Acid (IX). This compound was obtained f r o m 1.3 g (6.2 mmole) of acid
VII, 1.09 g (6.2 mmole) of gramine, and 0.35 g (6.2 mmole) of KOH in 10 ml of DMSO in analogy with the
synthesis of acid XW. The yield was 1.8 g (86.570).

LITERATURE CITED
1. V. N. Rusinova, Yu. I. Smushkevich, O. V. Telenkova, M. V. Vasin, and N. N. Suvorov, Khim. Geterot-
sikl. Soedin., 212 (1974).
2. M. Dieter and Niclas H a n s - J o a c h i m . , Ber., 10__2._2,31 (1969).
3. N. N. Suvorov, V. S. Velezheva, and V. V. Vampilova, Khim. Geterotsikl. Soedin., 1512 (1973).
4. S. Swaminathan and V. T. Ramakrishnan, P r o c . Indian Acad. Sci., Sect. A, 6_~1, 294 (1965).
5. K. C. Fewari~ F. K. Schweighardt, I. Lec, and N. C. Li, J. Magn. Resort., 5, 238 (1971).
6. A. Sucharda-Sobzyk, Rocz. Chem., 44, 1435 (1970).
7. H. Feok Ch'ang and A. M. Khaletskii, K h i m . - F a r m a t s . Zh., 4, 14 (1970).
8. J. W. E m s l e y , J. Finney, and L. Sutcliffe, High-Resolution Nuclear Resonance Spectroscopy, Vol. 2,
P e r g a m o n (1966).

449
ELECTRONIC SPECTRA OF THE IONIC FORMS
OF c~,fl-UNSATURATED KETONES - INDOLE DERIVATIVES

S. V . T s u k e r m a n , A. I. B u g a i , UDC 547.756 : 543.422.6

and V. F. Lavrushin

The formation of the corresponding organic cations and anions was shown on the basis of
data on the electronic absorption s p e c t r a of 33 o4fl-unsaturated ketones - indole deriva-
tives - in solutions of strong acids and b a s e s . Observations regarding the dependence
of the c o l o r s of the investigated ionic f o r m s on the chemical s t r u c t u r e are made.

We have previously [1] reported the results of an investigation of the electronic absorption and fluo-
r e s c e n c e s p e c t r a of a, fl-unsaturated ketones - indole derivatives - in alcohol and dioxane solutions. In
connection with the fact that the indole ring simultaneously has weakly e x p r e s s e d basic and acidic p r o p e r -
ties, it seemed of interest to study the spectral c h a r a c t e r i s t i c s of these compounds in sufficiently acidic
and alkaline media, in which the corresponding organic cations and anions would be formed.
We selected the i s o m e r i c indole analogs of chalcones of the following type as the subjects of the in-
vestigation:

It U

R is phenyl (I, II), aryl groups with different e l e c t r o n - d o n o r and e l e e t r o n - a e c e p t o r substituents (III-XV),
2-furyl (X'VI, XVII), 2-thienyl (XVIII, XIX), and N-methyl derivatives of ketones (XX-XXVI) (see Table 1).
In addition to the compounds listed above, we also investigated s e v e r a l ketones containing a 6-nitro-
3-indolyl grouping in their molecules (XXVII-XXIX), cyelopentanone and cyelohexanone derivatives (XXX
and XXXI), and indole analogs of p-dichalcones (XXXII, XXXIII) (see Table 2).
All of the investigated compounds exist in the m o l e c u l a r f o r m in glacial acetic acid solutions, inas-
much as their electronic absorption s p e c t r a are p r a c t i c a l l y the same as the s p e c t r a in alcohol solutions
[1]. However, a haloehromic coloration that vanishes as the solution is diluted with w a t e r develops when
relatively small amounts of concentrated sulfuric acid (2-10~) are added to the acetic acid solutions. An
isopiestic point is observed in the s p e c t r a of ketone I in solutions of various concentrations of sulfuric
acid in glacial acetic acid (at a constant ketone concentration) on the absorption c u r v e s (Fig. 1); this at-
t e s t s to the p r e s e n c e of an acid-base equilibrium:

tt CGH5

The s t r u c t u r e of the cation, which is responsible for the appearance of a new absorption band in the
visible region of the spectrum, can be r e p r e s e n t e d by means of two principal limiting s t r u c t u r e s - a h y d r o x y
earbonium ion s t r u c t u r e and an immonium ion s t r u c t u r e .
It follows f r o m the data in Tables 1 and 2, in which the spectral c h a r a c t e r i s t i c s of solutions of the
investigated compounds in 30% sulfuric acid in glacial acetic acid are presented, that the long-wave a b s o r p -

A. M. Gor'kii Kharkov State University. Translated f r o m Khimiya Geterotsiklicheskikh Soedinenii,

No. 4, pp. 519-524, April, 1974. Original article submitted June 5, 1973.

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, N.Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy o f this article is available from the publisher for $15.00.

450
 ,3

~ ~ w o

Z ~ N N ~

....:. ..:.

.=~

o
"C-,

-~ ~
0
0

e~ ~ N ~N
r..)

0 =>>=
e~
O0
:9 c ~

c.~ oO o~ ~ ~

0"~

.o .~o

z~
~ o
o

~'~
0
~
~ "~ r CD tO cO ~ cO g'~
0
L,~ tO C~ t'~ r
~.0 r

0
~ ~
a~

O0
of:~ 0

*d 0
0

*$

451
 nv.ld3, cm-I
4

O,(

0,(

O,4 3

O,a

3oo 3~o r ~60 ~ ,6o ~o ,1o ,6o ~.ffm O O,1 0,3

. i
Or5 0,7
i i
o,g 8"
L

- . L

Fig. 1 Fig. 2

Fig. i. Absorption c u r v e s of ketone I in solutions of sulfuric acid in

glacial acetic acid: 1) 3.2% H2SO4; 2) 2.4% H2SO4; 3) 1.6% H2SO4; 4)0.8%
H2SO4 in glacial acetic acid.
Fig. 2. C o r r e c t i o n dependence between Av and the Hammett a constants
in the 1-propenone s e r i e s : R=phenyl; 2 ) R = 4 - t o l y l ; 3) R = 4 - a n i s y l ; 4)
R -- 2-furyl; 5) R = 2-thienyl; 6) R = 2,4-dimethoxyphenyl.

TABLE 2. Spectral C h a r a c t e r i s t i c s of Acidic and Alkaline Solutions of Some

Unsaturated Ketones and Diketones Containing Indole Rings
Xmax. nm (s)
Com- \ Name ~-~]0solution of sulfuric 2 N sodiumethoxide
pound acid in glacial acetic solution
acid
XXVII 1-(6 -Nitro-3-indolyl)-3- phenyl-3-propenone 475 (42100), 320 (11400) 485 (6700), 402 (17700),
307 (28400), 260 (25700)
XXVIII 1-(6 -NiUro-3-indolyl)-3-( 4- chlorophenyl)-3- 483 (47100), 320 (12480), 494 (39260), 417 (18100).
propenone 275 (9700) 258 (14800}
XXIX I -(6 -Nitro-3 -indolyl)-3-(4- nitrophenyl)-3 - 478 (35700), 325 (12550), 518 (26300), 357 (8900),
propenone 280 (13600) 265 (11500)

xxx 2,5-Di(3 -indolylm e~hylene)eyclohexanone 612 (78200), 432 (5200), 530 (58500), 555 (58500),
330 (5200), 278 (7300) 400 (6900), 290 (7100)
xxxI 2,6 -Di( 3 -indolylmethylene)cyclohex anone 610 (31100), 460 (14000), 1520 (2,0200), 45.2 (16300),
327 (11400), 261 (18400) 325 (202D0), 257 (22400)
XXXII 1,4-Di[~ -(3-indolyl)a r zene 540 (45600), 337 (2300), 515 (51880), 355 (8960),
260 (16000) 270 (17000)
XXXIII 1,4-Diicc-(3-indolyl)acrylyl]benzene 538 (28100), 338 (6800), 432 (41800), 317 (25300),
260 (8800) 285 (19850)

tion band of the protonated unsaturated ketones of the indole s e r i e s is shifted b a t h o c h r o m i c a l l y as c o m p a r e d

with the band for the analogous m o l e c u l a r f o r m s by 90-130 nm (ketone IX constitutes an exception), and this
shift amounts to 130-180 nm only for ketones XXX-XXXIII,'which contain two indole groupings.
As c o m p a r e d with the analogous ketones of the p y r r o l e s e r i e s [2], the halochromic coloration of the
indole chalcones, in general, only changes slightly; this is a consequence of the approximately identical e l e c -
t r o n - d o n o r effect of the 2:pyrr01yl and 3-indolyl groups and t h e i r N-methyl-substituted derivatives [3]. A
bathochromie shift of the long-wave band of 5-15 nm is observed in acid only when the indole ring is adja-
cent to the carbonyl group.
The introduction of donor substituents into indole chalcones I and II and r e p l a c e m e n t of the benzene
ring in them by a furan ring or thiophene ring lead to a considerable bathochromic effect; the wave numbers
of the absorption m a x i m a of the long-wave band e x p r e s s e d in r e c i p r o c a l c e n t i m e t e r s c o r r e l a t e with the a
constants (Fig. 2) according to the equation 2 . 3 ( h c / k T ) ( 1 / k H - 1 / k R) = P a, r=0o98, P =12 * 3 , w h e r e h H i s t h e
absorption m a x i m u m of I, and }'R are the absorption m a x i m a of ketones III, V, VII, XVI, and XVIII.
Lengthening of the conjugation chain by replacement of the phenyl group in I and II by a diphenylyl
group (compare XIV and XV) also causes a bathochromic shift in the halochromic coloration. The dimethyl-
amino group in ketone IX is protonated in acidic media and acquires a c c e p t o r p r o p e r t i e s ; this leads to a
h y p s o c h r o m i c shift. Chloro and nitro groups in both the benzene ring (X-XIII) and in the heterocyclic ring
(X-XVII-XXIX) do not have a substantial effect on the halochromic coloration nor does N-methylation (com-
pare XX-XXVI).
In addition, unsaturated ketones and cyclopentanone and cyclohexanone derivatives (XXX, XXXI) which
can be successfully used as indicators for very low pH v a l u e s have a p a r t i c u l a r l y deep and intense c o l o r a -

452
D I
1~2 tion in a solution of 30% sulfuric acid in glacial acetic acid.
The indole analogs of the i s o m e r i c p-dichalcones, XXXII and
1,0
0~9 XXXIII, absorb in acid solution in the l o n g e r - w a v e region
O,S than the c o r r e s p o n d i n g monochalcones I and II; this should be
0,7
0,6 a s c r i b e d to the formation of the c o r r e s p o n d i n g doubly charged
075 cations and reactions of two c h r o m o p h o r e groupings through
O,4 the benzene ring [4], but their halochromic coloration is con-
0~2 siderably less deep than that of ketones XXX and XXXI. One
0'11 should also note that the absorption m a x i m a of the long-wave
bands of 3-propenones as c o m p a r e d with the m a x i m a of the
analogous 1-propenones, are shifted to the red region of the
Fig. 3. Absorption c u r v e s of ketone II spectrum; this once more attests to the strong e l e c t r o n - d o n o r
in alcohol solutions of sodium ethoxide: effect of the 3-indolyl grouping, which s u r p a s s e s the effect of
1) 0.56% C2HsONa; 2) 0.28% C2HsONa; 3) the 4-tolyl, 4-anisyl, 2,4-dimethoxyphenyl, 2-furyl, and 2-
0.14~0 C2HsONa; 4) 0.08~ C2HsONa; 5)in thienyl groups. Similar r e g u l a r i t i e s are observed when the
alcohol. s p e c t r a l c h a r a c t e r i s t i c s of N-methylated ketones XX, XXH,
XXIV, and XXVI are c o m p a r e d .
Halochromic coloration of ketones I-IV in 80% aqueous f o r m i c acid is not observed, but m o r e basic
compounds that contain such e l e c t r o n - d o n o r groupings as 4-anisyl, 2,4-dimethoxyphenyl (V-VII), 2-furyl
and 2-thienyl (XVI and XVIII) f o r m the c o r r e s p o n d i n g organic cations, the long-wave absorption maxima of
which p r a c t i c a l l y coincide with the analogous values in solutions of 30% sulfuric acid in glacial acetic acid.
It follows f r o m this that side p r o c e s s e s such as sulfuration, oxidation, etc., do not o c c u r in the latter sol-
vent during the e x p e r i m e n t s .
Indole analogs of chalcones (unmethylated compounds) also manifest weakly acidic p r o p e r t i e s ; this is
reflected in the considerable b a t h o c h r o m i c shift in their c o l o r in 2 N sodium ethoxide solution in absolute
alcohol as c o m p a r e d with solutions in alcohol o r dioxane (see [1]). An isopiestic point was detected in an
investigation of the absorption s p e c t r a of ketone II in sodium ethoxide solutions of various concentrations
with a constant ketone concentration (Fig. 3); this attests to an equilibrium, which, for example, for 3-
propenones can be r e p r e s e n t e d as follows:

' "L-. IL ~J ,~ -I+~o"

H Ar k Ar hr
I
J

It iS interesting that the long-wave band undergoes a bathochromic shift of 70 nm as c o m p a r e d with

the i s o m e r i c anions f r o m 1-propenones f o r the anions formed f r o m 3-propenones as also for analogous
organic cations. However, an e l e c t r o n - a c c e p t o r substituent, p a r t i c u l a r l y a nitro group, which in the ben-
zene ring c a u s e s a red shift of 50-53 nm (compare XH and XIII with I and II) and in the 6-position of the
h e t e r o c y c l e c a u s e s a shfft of 15-18 nm (compare XXVH and XXVIII), has a m o r e significant bathochromic
effect on the c o l o r of the anions. Except for the dimethylamino group (IX), e l e c t r o n donors as a rule lead
to a h y p s o c h r o m i c effect.
Inasmuch as the nitro group should stabilize the s t r u c t u r e with a negative charge on the oxygen atom,
it is apparently responsible for the c h r o m a t i c i t y of the anion and is p r e f e r a b l e .
The r e s u l t s of the investigation of the s p e c t r a of indole ketones make it possible to conclude that they
may be used not only for the determination of the acidity functions (H0) but also simultaneously for the de-
t e r m i n a t i o n of the H0 values of strongly basic solutions.

EXPERIMENTAL
The e l e c t r o n absorption s p e c t r a of (2-4) 9 10-5 M solutions were r e c o r d e d with SF-4A and SF-20 s p e c -
trophotomete rs.
Except f o r III, X, XII, and XIV, which were obtained by a s i m i l a r route, the synthesis of the indole
derivative ketones was p r e v i o u s l y d e s c r i b e d in [5].

*The limiting s t r u c u r e s are p r e s e n t e d in a c c o r d a n c e with the data in [2].

453
 1 - ( 3 - I n d o l y l ) - 3 - t o l y l - l - p r o p e n o n e (III). In c o n t r a s t to the data in [6], this compound had mp 217 ~
r a t h e r than 201 ~ Found: 5.6~ C1RHlsNO. Calculated: N 5.4%.
1-(3-Indolyl)-3-(4-chlorophenyl)-l-propenone (X). This compound was obtained in 40% yield as yellow
needles with mp 256 ~ Found: N 5.0%. C17H12C1NO. Calculated: N 7.8~.
1-(3-Indolyl)-3-(4-nitrophenyl)-l-propenone {XII). This compound was obtained in 40% yield as orange
plates with mp 251 ~ Found: N9.8%. C17H12N203. Calculated: N 9.6?o.
1-(3-Indolyl)-3-diphenylyl-l-propenone (XIV). A 0.05-g sample of solid p o t a s s i u m hydroxide was
added to a solution of 1.8 g (0.01 mole) of 4-formyldiphenyl and 1.4 g (0.01 mole) of 3-acetylindole in 15
ml of ethylene glycol, and the mixture was heated at 140-160 ~ for 20 rain. It was then cooled, and the p r e -
cipitated c r y s t a l s were removed by filtration, washed with methanol, acidified with acetic acid, and washed
with boiling alcohol to give 2.2 g (V0%) of yellowish plates with mp 283 ~

LITERATURE CITED
lj S. V. Tsukerman, A. I. Bugai, and V. F. Lavrushin, Khim. Geterotsikl. Soedin., 949 (1972).
2. S. V. Tsukerman, V. P. Izvekov, and V. F. Lavrushin, Khim. Geterotsikl. Soedin., 823 (1968).
3. S. V. Tsukerman, L. A. Kutulya, and V. F. Lavrushin, Khim. Geterotsikl. Soedin., 989 (1969).
4. A. I. Kiprianov and I. L. Mushkalo, Zh. Organ. Khim., I, 744, 750 (1965).
5. S. V. Tsukerman, A. I. Bugai, V. M. Nikitchenko, and V. F. Lavrushin, Khim. Geterotsikl. Soedin.,
399 (1970).
6. F. Piozzi and C. Fuganti, Ann. Chim. (Roma), 56, 1248 (1966).

454
HYDROGENATION OF VINYLPYRIDINES AND STYRENE

IN THE PRESENCE OF THE PALLADIUM

C HLORODIMETHY LSU L FOXIDE COMPLEX

N. M. Nazarova, L. Kh. Freidlin, UDC 547.821 : 542.942.7.9

and Yu. A. Kopyttsev

The rate of hydrogenation of the vinyl group of a - , fi-, and ~/- vinylpyridines d e c r e a s e s as
its distance f r o m the nitrogen a t o m i n c r e a s e s in the p r e s e n c e of the p a l l a d i u m chlorodi-
methylsulfoxide complex. In b i n a r y m i x t u r e s of t h e s e vinylpyridines, the T- i s o m e r is r e -
duced b e f o r e the other two i s o m e r s .

It has been e s t a b l i s h e d that the adsorbabilityof(~-, fl-, and T-vinylpyridines on Raney nickel i n c r e a s e s
in the s a m e o r d e r in which the rate of hydrogenation of t h e i r vinyl groups d e c r e a s e s [1, 2]. It s e e m e d of
i n t e r e s t to a s c e r t a i n the dependence of the r e a c t i v i t y of the vinyl group on the position in the pyridine ring
under conditions of homogeneous hydrogenation. The p a l l a d i u m chlorodimethylsulfoxide complex was used
as the catalyst, inasmuch as it has been e s t a b l i s h e d that this c a t a l y s t is highly active and stable in hydro-
genation r e a c t i o n s of olefins [3].
Under the selected conditions, only the vinly groups of vinylpyridines and s t y r e n e a r e hydrogenated;
t h e i r a r o m a t i c rings are not involved. The r e a c t i o n p r o c e e d s at a high rate and is z e r o o r d e r with r e s p e c t
to the compound undergoing hydrogenation (Fig. 1). The a c c e l e r a t i o n of the r e a c t i o n that is o b s e r v e d in
the f i r s t 1-2 rain is a s s o c i a t e d with an i n c r e a s e in the concentration of the hydride f o r m e d during contact
of the s t a r t i n g complex with hydrogen. This is c o n f i r m e d by the fact that the subsequent weighed amounts
of vinylpyridine (or styrene) that a r e added to the r e a c t i o n m i x t u r e a r e hydrogenated f r o m the very s t a r t
at a constant rate without a c c e l e r a t i o n . The d e c r e a s e in the rate of hydrogenation of the vinylpyridines
does not exceed 570 when the c a t a l y s t is used again. A c o m p a r i s o n of these r e s u l t s with the r e s u l t s obtained
in [3] shows that e v e n in'the p r e s e n c e of a homogeneous catalyst, the C =C bond activated by conjugation
with the a r o m a t i c ring is reduced at a c o n s i d e r a b l y higher rate than
so ml H2/rnin the C =C bond of an olefin. The hydrogenation of the vinyl pyridine is
T
inhibited to only a slight degree by the r e a c t i o n product, i.e., the n i t r o -
gen a t o m of ethylpyridine p r e s e n t s a l m o s t no i n t e r f e r e n c e to c o o r d i n a -
tion of the vinyl group of the vinylpyridine molecule in the catalyzing
c o m p l e x . It also follows f r o m Fig. 1 that the rate of hydrogenation of
the C = C bond of ~-, /3-, and 3/-vinylpyridines depends on the position
of the vinyl group in the pyridine ring and d e c r e a s e s in the o r d e r a-
vinylpyridine > fl-vinylpyridine, T-vinylpyridine. > s t y r e n e . The vinyl-
pyridine molecule is apparently coordinated not only with the vinyl
group but also with the nitrogen atom. All of the vinylpyridines a r e
reduced at a higher rate than s t y r e n e , and a r e s a t u r a t e d c o n s i d e r a b l y
2 z: (5 8. 10 mirl
ahead of s t y r e n e in b i n a r y m i x t u r e s with it. Under the conditions of
Fig. 1. Kinetic c u r v e s of the both homogeneous c a t a l y s i s and heterogeneous c a t a l y s i s [1, 2], the
hydrogenation of c~- (1),/3- (2), individual T-vinylpyridine is reduced m o r e slowly than its a - i s o m e r ,
and 3~-vinylpyridines (3) and but its hydrogenation o c c u r s in advance in a binary m i x t u r e , y-Vinyl-
s t y r e n e (IV). pyridine is a p p a r e n t l y m o r e strongly coordinated in the p a l l a d i u m corn-

N. D. Zelinskii Institute of Organic C h e m i s t r y , Academy of Sciences of the USSR, Moscow. T r a n s -

lated f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 4, pp. 525-526, April, 1974. Original article sub-
mitted July 5, 1972.

9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

455
plex during activation. In analogy with [2], it can be a s s u m e d that the vinyl group in the s - p o s i t i o n c r e a t e s
s t e r i c hindrance to coordination of ~-vinylpyridine by the nitrogen atom, and the competitive effect of the
l a t t e r is t h e r e f o r e weakened. A vinyl group in the T-position p r e s e n t s l e s s hindrance to coordination of
the ~,-vinylpyridine molecule by the nitrogen atom, as a consequence of which, the p o s s i b i l i t y of c o o r d i n a -
tion of hydrogen or of the vinylpyridine molecule at the vinyl group d e c r e a s e s , and the r e a c t i o n is r e t a r d e d .

EXPERIME NTAL
The compounds w e r e hydrogenated in a glass, long-necked hydrogenation f l a s k set in motion with a
mechanical m i x e r (400-600 rpm) at 20 ~ and hydrogen at a t m o s p h e r i c p r e s s u r e . A 0.8-g s a m p l e of the c o m -
pound to be hydrogenated and 0.025 g of the p a l l a d i u m complex in 20 ml of dimethyl sulfoxide w e r e used in
the e x p e r i m e n t ; hydrogen, the consumption of which was m e a s u r e d with a b u r e t t e , was fed into the r e a c t i o n
v e s s e l . The composition of the c a t a l y z a t e was d e t e r m i n e d by g a s - l i q u i d c h r o m a t o g r a p h y with a 2 m by 4-
m m column at 120 ~ The s t a t i o n a r y liquid phase was polyethylene glycol-4000 (15%) on C h r o m o s o r b W
with 1~ NaOH. The d e t e c t o r was a c a t h a r o m e t e r .

LITERATURE CITED
1. N. M. Nazarova, L. Kh. Freidlin, and I. G. Rozhdestvenskaya, Izv. Akad. Nauk SSSR, Ser. Khim.,
1732 (1967).
2. L. Kh. Freidlin, N. M. Nazarova, and I. G. Rozhdestvenskaya, Dokl. Akad. Nauk SSSR, 1~.76, 1323
(1967).
3. L. Kh. Freidlin, N. M. Nazarova, and Yu. A. Kopyttsev, Izv. Akad. Nauk SSSR, Ser. Khim., 201 (1972).

456
4-A ZAI NDA NE- I, 3- DIONE DERIVATIVES
I. STUDY OF THE TAUTOMERIC AND PROTOTROPIC EQUILIBRIA

OF SOME ANALOGS OF 4-AZAINDANE-I,3-DIONES

O. Ya. Neiland, S. V. Kalnin', UDC 547.836.07 : 543.422.6

E. I. Stankevich, and A. Ya. Ozola

The acidity constants of 2,6, 6 - t r i m e t h y l - and 6 , 6 - d i m e t h y l - 2 - p h e n y l - 9 - e t h o x y c a r b o n y l -

5 , 6 , 7 , 8 - t e t r a h y d r o - 4 - a z a b e n z [ f ] i n d a n e - l , 3 , 8 - t r i o n e s were determined by a s p e c t r o p h o -
t o m e t r i c method, and the position of the t a u t o m e r i c equilibria was established for v a r i -
ous pH values.

The e l e c t r o n i c s p e c t r a of 2 , 6 , 6 - t r i m e t h y l - and 6 , 6 - d i m e t h y l - 2 - p h e n y l - 9 - e t h o x y c a r b o n y l - 5 , 6 , 7 , 8 -
t e t r a h y d r o - 4 - a z a b e n z [ f ] i n d a n e - l , 3 , 8 - t r i o n e s [1], analogs of 4 - a z a i n d a n e - l , 3 - d i o n e s , in aqueous and aque-
ous ethanol solutions at various pH values were r e c o r d e d to study the t a u t o m e r i c and p r o t o t r o p i c equilibria
of these compounds. In c o n f o r m i t y with the data for 4 - a z a i n d a n e - l , 3 - d i o n e s (see, for example, [2. 3]) in
solutions one might expect equilibria between enol a, anion b, betaine c, and N-protonated enol d.
OH O OC2H5

r,
la, lla Ib, llb ||1, I V

~H H 0 H

R 9 ~ R

~F T Y [, III R = CH3;
0 R' 0 R' 0
II, IV R=C6H~;
ICl,lld IC,IIc R'=COOC2H 5
The ratios of the c o r r e s p o n d i n g f o r m s in various solvents at various pH values are due to the r e l a -
tive magnitudes of the K1, K2, K3, and K 4 acidity constants (the diketo s t r u c t u r e s in these equilibria are not
considered, and their p r e s e n c e could not be detected).
Both alkaline and neutral solutions of I and II have identical absorption s p e c t r a (Fig. 1) and are c h a r -
a c t e r i z e d only by the p r e s e n c e of f o r m s Ib and IIb. The c h a r a c t e r i s t i c long-wave band of i n d a n e - l , 3 - d i o n e
anions [4], which is responsible for the red c o l o r of the solutions, is observed in the s p e c t r a . The a b s o r p -
tion p a t t e r n changes in solutions with s u p p r e s s e d ionization of I and II (0.1 N HC1), and h y p s o c h r o m i c shifts
with a reduction in the absorption intensity are observed; this is c h a r a c t e r i s t i c for enols r a t h e r than the
anionic f o r m s of i n d a n e - l , 3 - d i o n e [4, 5].
One's attention should be directed to the inflections of low intensity at 560-590 nm for I and 620-650
nm for II, which are absent in the s p e c t r a of the fixed enol f o r m s - enol e s t e r s III and IV (Fig. 1) - and at-
test to the p r e s e n c e of small amounts of betaine f o r m s Ic and IIc (the betaine s t r u c t u r e s of 4 - a z a i n d a n e -
1,3-diones are c h a r a c t e r i z e d by a m a r k e d l y b a t h o e h r o m i c a l l y shifted long-wave absorption, as c o m p a r e d
with the a b s o r p t i o n of the anion [2, 3]). In the case of I in aqueous solutions, m o r e of f o r m Ic is p r e s e n t
in aqueous solutions than in 50~ aqueous ethanol solutions. An e l e c t r o n i c s p e c t r u m could not be obtained
f o r II in aqueous solutions because of its low solubility (< 10-5 M).
Institute of Organic Synthesis, Academy of Sciences of the Latvian SSR, Riga. Riga Polytechnic In-
stitute. T r a n s l a t e d f r o m Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 527-529, April, 1974. Origi-
nal article submitted October 24, 1972.

9 19 75 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

457
 TABLE 1. E l e c t r o n i c Spectra of Some 4 - A z a i n d a n e - l , 3 - d i o n e s

Co~npound anion b betaine c -I enol a

9
H,O 5n0 qool~ - - ~ . H,O ~Oqo~ etha-~-- H.O 50~onol etha-
362 334 330
(96oo) (9100) (63oo)
474 478
540--580 860--5~0 4(~-410
(1800) (1~50) (leo0) (~)
2-Phenyl-4-azaindane- 393 410
1,3-dione [2, 3] (1,~900) (63o0)
.460 ] 49o--53o
(21~0) ] (2oo0) (27o0) (2500)
II 382 ] Insoluble Insoluble 352
629--45~
(1~58~2)
(280o1 ] (3too) (~W)o)
TABLE 2. OH Acidity Constants of I and II and Some Indane-1,3-
di one s
pKo~
Compound ApKoH
H20 50%ethanol
I 2,84 3,32 0,4~
2-Methylindane- 4,29 4,80 oAl
1,3-dione [4, 51 ApK=l.45 ApK=1,48
II (o,~7) 2,39 (1,s2)
2-Phenytindane- ~,oo 3,82 ,1,82
1,3-dione [4, 5] A p K = 1,43 ApK= 1,43

log The electronic s p e c t r a of anions Ib and IIb very much

recall the s p e c t r u m of the anion of 2 - p h e n y l - 4 - a z a i n d a n e -
1,3-dione but with a considerable bathochromic shift of the
two long-wave absorption m a x i m a (Table 1).
The acidity constants of I and tI were calculated. In
c o n t r a s t to 2 - p h e n y l - 4 - a z a i n d a n e - l , 3 - d i o n e , these constants
,, c h a r a c t e r i z e the OH acidity of enols Ia and IIa (Table 2).
It is seen f r o m Table 2 that the OH acidities increase
"--N
on passing f r o m a 50% aqueous alcohol solution to an aque-
\
ous solution. Moreover, the changes are identical for 2-
m e t h y l i n d a n e - l , 3 - d i o n e and its analogs (I). T h i s p r o v i d e d
a b a s i s for calculating the OH acidity in aqueous solutions
--2-5750o 550 1.00 ~o 5o0 55o 6oo 850 7o0 ~,nrn
for II using the difference APKoH = 1.82 obtained for 2-phe-
Fig. 1. Electronic s p e c t r a : 1) I in 50% nylindane-l,3-dione. It is interesting that almost identical
ethanol; 2) I in 50% ethanol (0.1 N HC1); changes in the acidities are retained for both aqueous and
3) I in water (4 N HC1); 4) III in 50% eth- 50% aqueous ethanol solutions on passing f r o m indane- l, 3-
anol. diones to their aza analogs, I and II (the OH acidity i n c r e a s e s
on the average by 1.45 o r d e r s of magnitude).
The r e a s o n for the difference in I and II f r o m 2 - p h e n y l - 4 - a z a i n d a n e - l , 3 - d i o n e , for which anion, beta-
ine, and protonated enol f o r m s were detected [2, 3], should be sought in the reduced basicity of the nitrogen
atom of the pyridine ring as a result of the e l e c t r o n - a c c e p t o r effect of the ketone and e t h o x y c a r b o n y l g r o u p s .
The NH acidity i n c r e a s e s and becomes g r e a t e r than the OH acidity of the enol, and the less acidic f o r m -
the enol - in this case begins to dominate in the equilibrium. For 2 ~ p h e n y l - 4 - a z a i n d a n e - l , 3 - d i o n e in aque-
ous solutions, PKN~H = - 3 . 9 4 [3]. The basicity of pyridine under the influence of two e l e c t r o n - a c c e p t o r groups
may change by even three to four o r d e r s of magnitude (this estimate can be made on the basis of c o r r e l a t i o n
analysis), such that PKN~H f o r s y s t e m I I in aqueous solutions m a y b e " 0-1. This value is c o m p a r a b l e to
PKOH = 0,57, and there may be 20-70% of the betaine f o r m IIc in an equilibrium mixture in aqueous medium,
as d e m o n s t r a t e d by the calculations.

458
 EXPERIMENTAL
The spectrophotometric measurements of 5 9 10 -5 and i0 -4 M aqueous solutions and 50 and 60~0 (by
volume) ethanol-water solutions of compounds I and II were measured with an SFD-2 spectrophotometer.
Hydrochloric acid (0.1-6 N) was used to create a definite acidity of the medium. The pH values of buffer
solutions were measured with an LPM-60M pH meter. The buffer solutions were prepared in accordance
with the data in [6]. The acidity constants were determined at 20 9 I~ by a spectrophotometric method [7]
with correction for the salt effect. The accuracy in the determinations was ~-0.05 pH units.

LITERATURE CITED
I. E. I. Stankevich, A. Ya. Ozola, and G. Ya. Dubur, Khim. Geterotsild. Soedin., 1147 (1973).
2. L. ]~. Neiland and G. Ya. Vanag, Khim. Geterotsikl. Soedin., 93 (1965).
3. I. V. Turovskii, O. Ya. Neiland, L. E. Neiland, and Ya. P. Stradyn', Khim. Geterotsikl. Soedin., 1382
(1972).
4. Ya. Ya. Linaberg and A. R. Veis, Izv. Akad. Nauk Latv. SSR, Ser. Khim., 437 (1964).
5. Ya. Linaberg, O. Neiland, A. Veis, and G. Vanag, Dokl. Akad. Nauk SSSR, 154, 1385 (1964).
6. J. Balodis, Prakt[skie Darbi Fizik~laj~ KTmij~, R ~ , (1956). p. 139.
7. O. Neiland and S. V. Kalnyn'. Zh. Organ. Khim., 4. 140 (1968).

459
INVESTIGATION OF LACTAMS
XXII.* PROTONATION AND HYDROLYSIS OF ~-ENAMINES
OF CAPRO-- AND VALEROLACTAMS

V. G. Smirnova, A. B. Grigor'ev, UDC 547.822.3'891 : 543.253'422.25

M. K. Polievktov, V. G. Granik,
N. P. Kostyuchenko, I. V. Persianova,
and R. G. Glushkov

F r o m an e x a m i n a t i o n of the PMR s p e c t r a , p o l a r o g r a p h i c data, and m o l e c u l a r models of a -

e n a m i n e s of c a p r o - and v a l e r o l a c t a m s , it is concluded that t h e r e is a different d e g r e e of
conjugation of the p e l e c t r o n s of the piperidine nitrogen with the enamine double bond and
that this explains the differences in the tendency of these compounds to undergo h y d r o l y s i s .

A convenient method f o r the synthesis of ~ - e n a m i n e s of v a l e r o - (I) and c a p r o l a c t a m s (II) by r e a c t i o n

of the (~,~-dichlorolactams with piperidine was p r e v i o u s l y developed in [2]. Despite the c o m p l e t e , as it w e r e ,
s t r u c t u r a l s i m i l a r i t y of e n a m i n e s I and It, they differ c o n s i d e r a b l y with r e s p e c t to t h e i r c h e m i c a l b e h a v i o r .
Thus, enamine II is readily hydrolyzed in acidic m e d i a at 0~ to ~ - o x o c a p r o l a c t a m III [1], but the ~ - e n a m i n e
of 2-piperidone (I) cannot be hydrolyzed u n d e r these conditions o r under m o r e s e v e r e conditions. The r e -
action of II with NaCN s i m i l a r l y leads to a high yield of ~ - h y d r o x y - ~ - c y a n o c a p r o l a c t a m (IV) [1], while c a -
amine I cannot be converted to the c o r r e s p o n d i n g cyanohydrin.

.so- (-3

IV II III

The b e h a v i o r of II in acidic m e d i a is typical for e n a m i n e s , the h y d r o l y s i s of which to ketones p r o c e e d s to

give p r o d u c t s in high yields [3]; however, the anomalous stability of enamine I under the s a m e conditions
has made it n e c e s s a r y to make a m o r e detailed study of its p r o p e r t i e s . The m e a s u r e m e n t of the b a s i c i t i e s
of I and II in n i t r o m e t h a n e gave unexpected results: the ApKa values of these e n a m i n e s w e r e 3.93 and 1.6,
r e s p e c t i v e l y , i.e., the b a s i c i t y of s e v e n - m e m b e r e d enamine II is higher by m o r e than two o r d e r s of m a g -
nitude than that of the s i x - m e m b e r e d I. It is apparent that the r e a s o n f o r this c o n s i d e r a b l e change in the
b a s i c i t y in a s e r i e s of s t r u c t u r a l l y s i m i l a r compounds can only be a change in the site of protonation. It is
logical to a s s u m e that C - p r o t o n a t i o n {high basicity) o c c u r s p r e f e r a b l y in the c a s e of enamine II, while p r o -
tonation of I t a k e s place at the nitrogen atom:

u I,II II a lib
I,V n = l ; II, l l a , l l b n=2

Because of the r e s o n a n c e I I a - - - - I I b , the C - p r o t o n a t e d f o r m is c o n s i d e r a b l y m o r e inclined to undergo nucleo-

philic attack (and, consequently, to undergo hydrolysis) than the N-protonated f o r m IV).

* See [1] for communication X'XI.

S. Ordzhonikidze All-Union S c i e n t i f i c - R e s e a r c h P h a r m a c e u t i c a l - C h e m i s t r y Institute, Moscow. T r a n s -
lated f r o m Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 530-532, April, 1974. Original a r t i c l e sub-
mitted June 14, 1973.

9 19 75 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retn'eval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

46O
 6

2,5 2.7-ds.c.e.) o,2 o,~ o,e o,a -e (rel, to Ag/AgC1)

Fig. 1 Fig. 2
Fig. 1. P o l a r o g r a m s of I and II with a saturated (CH3)4NI base
e l e c t r o l y t e in DMF: 1) base e l e c t r o l y t e curve; 2) cii = 0.46 mmole;
3) cii = 0.88 mmole; 4) cli = 1.25 mmole; 5) c t = 1.08 mmole; 6) c I =
1.55 m m o l e . S.eoe is saturated c a l o m e l e l e c t r o d e .
Fig. 2. P o l a r o g r a m s of II with a base e l e c t r o l y t e consisting of
0.17 N CF3COOH in MDF saturated with KCI: 1) Base e l e c t r o l y t e
curve; 2) cii = 1.56 m m o l e (the curve was r e c o r d e d immediately
a f t e r introduction of the substance into solution); 3) the same after
2 min; 4) the same after 5 min.

The signal of the vinyl proton in the PMR s p e c t r u m of enamine II (5.06 ppm) is substantially shifted
to the s t r o n g - f i e l d side as c o m p a r e d with enamine I (5.54 ppm); this is due to the higher e l e c t r o n density
on C (4) in H. It has been shown [4] that enamines in anhydrous dimethylformamide (DMF) are reduced with
substantially g r e a t e r difficulty than ethylene compounds and that the c e n t e r of attack of the e l e c t r o n is the
fl-carbon atom. Correspondingly, both enamines I and II are reduced in one step, apparently with the con-
sumption of two e l e c t r o n s [4], and enamine II is reduced at m o r e negative potentials than I. The reduction
wave of enamine II is masked to a considerable degree by the discharge c u r r e n t of the base electrolyte, and,
in this connection, the p r e c i s e m e a s u r e m e n t of the half-wave potential is difficult. To a f i r s t approximation,
the diffusion coefficients of I and lI were a s s u m e d to be equal, and the potential of that point of the curve at
which the c u r r e n t is equal to half the limiting (calculated) c u r r e n t was taken for El/2 of enamine II (the dif-
fusion coefficient of enamine I was determined f r o m the II'kovich equation and was 5.42 - 10 -6 cm~ see'2).
The half-wave potentials of I and II are, respectively, - 2 . 5 8 and - 2 . 7 3 V relative to a saturated calomel
electrode (see Fig. 1). This s o r t of substantial difficulty in the reduction of enamine II as c o m p a r e d with
enamine I is in a g r e e m e n t with the PMR s p e c t r a l data and also indicates the relatively high e l e c t r o n density
on the double bond of the f o r m e r . A p r i m a r y consequence of this is the difference in the site of protonation
of these compounds. An examination of the PMR s p e c t r u m of I in CF3COOH shows that in this case N - p r o -
tonat[on o c c u r s : the signal of the vinyl p r o t o n is shifted to the weak-field region (7.33 ppm) because of the
i n c r e a s e in the e l e c t r o n - a c c e p t o r s t r e n g t h of the substituent (the piperidinium cation) [5]. In addition to
N-protonation, C - p r o t o n a t i o n o c c u r s to a considerable degree for enamine II [5]. In the p r e s e n c e of strong
proton donors (a 0.17 N solution of CF3COOH ) the reduction of enamine II in DMF is m a r k e d l y facilitated.
In this case, two waves are observed on the p o l a r o g r a m , and the f i r s t falls rapidly with time, while the
overall c u r r e n t r e m a i n s constant (Fig. 2). The second wave is identical to the reduction wave of l a c t a m
III (the addition of III to the solution of cation I I . H + leads to a p r o p o r t i o n a l i n c r e a s e in the second wave).
The d e c r e a s e with time in the f i r s t wave with the simultaneous f o r m a t i o n of a - o x o e a p r o l a c t a m III is in
good a g r e e m e n t with the chemical data on the h y d r o l y s i s of enamine II in acidic media and provides unam-
biguous evidence that the f i r s t wave c o r r e s p o n d s to reduction of the immonium cation (IIa---~IIb). In fact,
the reduction of this cation should p r o c e e d incomparably m o r e readily [6] than reduction of the double bond
of the enamine; this is observed e x p e r i m e n t a l l y . Thus, the difference in the p r o p e r t i e s of enamines I and
II is explained by a change in the site of protonation; this is a s s o c i a t e d with the p r e s e n c e of higher e l e c t r o n
density on the ~ - c a r b o n atom of enamine II as c o m p a r e d with I. To explain the latter, the assumption of a
g r e a t e r degree of conjugation of the u n s h a r e d p a i r of e l e c t r o n s of the nitrogen atom with the C=C bond in II
has been advanced; this was completely confirmed in an examination of the m o l e c u l a r models of both en-

461
a m i n e s . The s t e r i c hindrance to conjugation in I, i.e., the overlapping of the van d e r Waals radii of the
p r o t o n s attached to C (4) of the piperidine ring and the C (2) a t o m of the piperidine ring leads to a c o n s i d e r -
able disruption of the p - 9 conjugation and, as a r e s u l t of this, to a d e c r e a s e in the e l e c t r o n density on the
enamine C =C bond. In c o n t r a s t to this, complete overlapping of the p e l e c t r o n s of the nitrogen a t o m and
the ~ e l e c t r o n s of the double bond is p o s s i b l e in enamine IL Thus, the substantial d i f f e r e n c e s in the p r o p -
e r t i e s of the ~ - e n a m i n e s of l a c t a m s I and 17[ a r e due to the different degree of conjugation of the p a i r of p
e l e c t r o n s of the nitrogen a t o m with the C =C bond as a consequence of the different s t e r i e i n t e r a c t i o n of
the hydrogen a t o m s attached to C (~) of the l a c t a m ring and the a - p r o t o n s of the piperidine ring.

EXPE RIME NTA L

The study of the p o l a r o g r a p h i c b e h a v i o r and the m e a s u r e m e n t of the ApK a (CHsNO2) values o f e n a m i n e s
I and II w e r e p e r f o r m e d via p r e v i o u s l y d e s c r i b e d methods [4, 7]. The ApKa value (CH3NO2) is the difference
in the pK a values of diphenylguanidine and the t e s t substance in n i t r o m e t h a n e . The PMR s p e c t r a w e r e r e -
corded with a JNM-4H-100 s p e c t r o m e t e r with t e t r a m e t h y l s i l a n e as the internal standard.

LITERATURE CITED
1~ V. G. Smirnova, N. A. Novitskaya, and R. G. Glushkov, K h ( m . - F a r m a t s . Zh., No. 6, 14 (1972).
2. R. G. Glushkov, V. A. Volskova, u G. Smirnova, and O. Yu. Magidson, Dokl. Akad. Nauk SSSR, 18_~7,
327 (1969).
3. R. A. Raphael et al., Advances in Organic C h e m i s t r y , Vol. 4, Wiley (1960-1965).
4. M. K. Polievktov, A. B. G r i g o r ' e v , V. G. Granik, and R. G. Glushkov, Zh. Obshch. Khim., 4__33,1162
(1973).
5. R. G. Glushkov, Doctoral D i s s e r t a t i o n [in Russian], MKhTI ira. Mendeleeva, Moscow (1971).
6. V. G. Granik, M. K. Polievktov, and R. G. Glushkov, Zh. Organ. Khim., 7, 1431 {1971).
7. V. A. Korolev and B. I. Stepanov, Izv. Vuzov SSR, Khim. i Khim. Tekhnol., 2, 1193 (1968).

462
LACTAM ACETALS

IX.* D E U T E R I U M E X C H A N G E IN THE 1 - M E T H Y L - 2 - A R Y L I M I N O L A C T A M S E R I E S

V. G. Granik, A. M. Zhidkova, UDC 5 4 6 . 1 1 . 2 : 5 4 7 . 7 4 3 .

T. F. Vlasova, R. G. Glushkov, 1'822.3:541.623:543.422.25
and Yu. N. Sheinker

The r a t e of d e u t e r a t i o n of 1 - m e t h y l - 2 - a r y l i m i n o l a c t a m s d e p e n d s on the e l e c t r o n i c c h a r a c t e r
of the s u b s t i t u e n t in t h e b e n z e n e r i n g and on the s i z e of the l a c t a m r i n g . D e u t e r i u m e x c h a n g e
p r o c e e d s at the h i g h e s t r a t e in p i p e r i d i n e d e r i v a t i v e s that have e l e c t r o n - d o n o r s u b s t i t u e n t s in
the benzene ring.

It i s k n o w n [2, 3] that l a c t a m e t h e r s e x i s t in s o l u t i o n in t a u t o m e r i c e q u i l i b r i u m with the c o r r e s p o n d i n g

~ - a l k o x y e n e s (A ~ B), and t h i s p r o t o t r o p i c t r a n s f o r m a t i o n c a n be r e a l i z e d only by m e a n s of s t r i p p i n g of a
p r o t o n f r o m the 3 - p o s i t i o n of the m o l e c u l e

J
~.N' OR '~-N ",OR
H
A B
TABLE i. 2 - A r y l i m i n o D e r i v a t i v e s of l - M e t h y l l a c t a m s

mp or bp Empirical Found,~o Ca]

(ram), *C "D2~ formula a
8 c H c
Ia 1 163--164 (5mn~ 1,5876 C12HI6N~O i0,5 7,9 70,6 7,8 79
IIa 1,5 76,0--76,5a CtsHlsN20 71,7 8,3 71,6 8,3 81
IIIa ~ 84--86b CI4H2oN20 71,8 8,5 72,4 8,6 88
IIIb 158-159 (2mm)i 1,~33/ CI4H2oN~ 77,7 9,3 77,8 9,3 87
IIIc 20 147--148 (5~)1 1,58181 CtsHtsN~ 76,5 8,7 77,2 8,9 90
IIId 20 68--~9b ! - C~aHITN2C1 66,1 7,3 66,1 7,2 69

arrom hexane, bFrom petroleum ether.

TABLE 2. P M R S p e c t r a ( c h e m i c a l shifts'i p p m )
Com-
pound H~ H4 H~ H6 Hr N-CH3 Ar p-OCH~ p-CH3

Ia 2,33 1,91 3,37 -- 2,92 6,77 3,73

IIa 2,17 1,67 374 2,95 6,71 3,72
IIIa 2,35 1,63 3,05 6,60d 3,74 m
6,80 d
IIIb 2,45 1,63 3,44 3,05 6,60d 3,74
6,80 d
IIIc 2,39 1,62 3,41 3,05 6,65 d
6,88 t
7,28 t
IIId 2,36 1,65 3,4~5 3,05 6,62 d
7,02 d
IIIe 2,44 1,68 3,50 3,09 6,80d
8,09 d

* S e e [1] f o r c o m m u n i c a t i o n VIII.

S. O r d z h o n i k i d z e A l l - U n i o n S c i e n t i f i c - R e s e a r c h P h a r m a c e u t i c a l - C h e m i s t r y Institute, Moscow. Trans-

l a t e d f r o m K h i m i y a G e t e r o t s i k l i c h e s k i k h S o e d i n e n i i , No. 4, pp. 533-536, A p r i l , 1974. O r i g i n a l a r t i c l e s u b -
m i t t e d June 6, 1973.

9 19 75Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy of this article is availablefrom the publisher for $15.00.

463
 Inasmuch as the e l e c t r o n - a c c e p t o r interaction (on the C 3 atom) of the imino e t h e r and
the amidine groupings is s i m i l a r , one might expect that the protons attached to C 3
in amidines, which are readily obtained f r o m l a e t a m acetals [4], will also be suffi-
ciently labile. This in t u r n c r e a t e s the p r e r e q u i s i t e for electrophilic substitution
in the 3-position.
In this connection, the rate of deuteration in the p r e s e n c e of a large e x c e s s of
C D3OD was investigated for 1 - m e t h y l - 2 - a r y l i m i n o l a c t a m s Ia, IIa, and IIIa-e, which
~+1 were obtained f r o m the diethyl acetals of N - m e t h y l b u t y r o - , v a l e r o - , and c a p r o l a c t a m s
(Table 1), by m e a s u r e m e n t of the integral intensities of the signals of the protons
attached to C 3 in the PMR s p e c t r a (Table 2).* The rate constants were calculated
+~ f r o m the f i r s t - o r d e r equationt by the method of l e a s t squares (see Table 3). It was
found that the amidine with a s i x - m e m b e r e d ring (IIa) is deuterated at the highest
rate. The rate of deuteration in the s e r i e s of amidines IIIa-e depends substantially
on the c h a r a c t e r of the substituent in the a r o m a t i c ring and d e c r e a s e s on passing
f r o m e l e c t r o n donors to e l e c t r o n a c c e p t o r s .

(c.o~ ["-~'n-~-r
~ \OC~H 5
+1 CH 3 CH a
N l-Ill

la c=l, R OCH3; II a n = 2 , R=0CH3; llla-e n: 3, a R=OCH3;

b R=CH3; C R=H; d R-C1; e R=N02

~-~ The dependence log K = 0 . 0 4 5 - 0 . 9 7 6 ~ i - 1.52a R with multiple c o r r e l a t i o n coefficient

R = 0.964 and So--0.19 was obtained by c o r r e l a t i o n of the rate constants obtained with
+1N the r and aft constants. The low Pi and PR values indicate that charged ions are ab-
~c5 sent in the t r a n s i t i o n state. The substantial contribution to the interaction of the con-
+1
jugation effect makes it possible to r e p r e s e n t the activated complex as follows (B is
a solvent molecule or a second amidine molecule):

'?G:" H .-:B

"-,NY x'rq--C5 H5
I i -
9 CH3 D,.,~)R
IV
Correspondingly, e l e e t r o n - a c c e p t o r substituents should l o w e r the stability of
oO the activated complex and thereby d e c r e a s e the rate of deuterium exchange; this is
actually observed. The step that limits the rate of the reaction is detachment of a
p r o t o n f r o m the 3-position. The activation p a r a m e t e r s for deuteration of amidine
0
(9 IIIa were obtained f r o m data on the rate constants of the p r o c e s s at various t e m p e r a -
~J
t u r e s (Table 3): E ~= 17.21 + 0.05 kcal/mole-1;_log A = 11.81 :e0.013; AH #= 16.62 ~0.05
kcal/mole-1; and AS #= - 6 . 5 * 0.057 e a l / m o l e -1 deg -l. The relatively low activation
!
entropy is in good a g r e e m e n t with the proposed s t r u c t u r e of the t r a n s i t i o n state. As
+~ CD3OD approaches the C 3 atom in the step involving the formation of the activated
~oO
complex, with simultaneous detachment of a proton, one should have expected con-
N +1 siderably l a r g e r AS # values. On the basis of the preceding, it is possible to explain
the change in the rate of deuterium exchange of amidines as a function of the size of
the ring. I n a s m u c h as the protons are not in a shielded conformation only in the six-
+1 m e m b e r e d ring, the approach of base B to the protons attached to the C 3 atom in this
case is l e s s s t e r i e a l l y hindered than in the case of f i v e - a n d s e v e n - m e m b e r e d amidines.

7o Deuterium exchange of protons in the 3-position of amidines I-III may be ac-

celerated in the p r e s e n c e of basic or acidic c a t a l y s t s . In the f i r s t case, the a c c e l e r a -

9 The integral intensity of the protons attached to C 3 was a s s u m e d to be one atthe s t a r t

b~ :2'
of the recording.
tA pseudo f i r s t - o r d e r reaction is confirmed by the linear dependence of In (C O- C)
on time; r > 0.96, S02 =0.07-0.0006.

464
tion is achieved due to the effective interaction of the base with the hydrogen atom attached to C3, while in
the second c a s e , a c c e l e r a t i o n is achieved by protonation of the N89 atom and c o r r e s p o n d i n g facilitation of
detachment of protons f r o m the 3-position of the molecule. This s o r t of examination c o r r e s p o n d s to the
g e n e r a l concepts of the m e c h a n i s m of a c i d - b a s e c a t a l y s i s (for example, see [5]). The detachment of a p r o -
ton f r o m C 3 during the simultaneous addition of a deuteron to N ' 2 may also not be accompanied by the addi-
tion of deuterium to f o r m the C s - D bond; this should lead to the appearance of enediamine tautomeric f o r m V .

((~H,)~ H ( C,II, )#,~HD CD3OD

IV ~ i " ndl ~ ~,." 'x etC.
~'~N~N--Ar N.~N_Ar
CH 3 D CH 3
V

The data obtained do not exclude the assumption that the investigated amidines exist in t a u t o m e r i c
equilibrium with enediamines V. However, this equilibrium is almost completely shifted to f a v o r the amidines,
inasmuch as the signals of the enamine f o r m are not detected in the PMR s p e c t r a in CD303 (see Table 2).

EXPERIMENTAL
The PMR s p e c t r a were r e c o r d e d with a JNM-4H-100 s p e c t r o m e t e r with t e t r a m e t h y l s i l a n e as the in-
ternal standard.
1 - M e t h y l - 2 - ( p - a n i s i d y l i m i n o ) p y r r o l i d o n e (Ia). A 3.46-g (0.02 mole) sample of N-methylpyrrolidone
diethyl acetal in 10 ml of dry c h l o r o f o r m was added to 2.46 g (0.02 mole) of p-anisidine in 15 ml of dry chlo-
r o f o r m , and the mixture was s t i r r e d at 60 ~ for 1 h. The solvent was evaporated, and the residue was dis-
tilled to give 2.6 g (79~) of Ia with bp 163-164 ~ (5 ram). Compounds !Ia and IIIa-d (see Table 1) were s i m -
ilarly synthesized f r o m the appropriate acetals. Compound IHe was previously described in [4].

LITERATURE CITED
1. V. G. Granik, I. V. P e r s i a n o v a , and Yu. N. Sheinker, Khim. Geterotsikl. Soedin., 385 (1974).
2. Y. T a m u r a , Y. Yoshimura, and Y. Kita, Chem. P h a r m . Bull., 1..~9, 1068 (1971).
3. V. G. Granik, B. M. Pyatin, I. V. P e r s i a n o v a , E. M. P e r e s l e n i , N. P. Kostyuchenko, R. G. Glushkov
(Gluschkov), and Y. N. Sheinker, Tetrahedron, 2_.66,4367 (1970).
4. H. Meerwein, W. Florian, N. SchSn, and G. Stopp, Ann.. 641, 1 (1961).
5. A. I. Shatenshtein and E. N. Zvyagintseva, Dokl. Akad. Nauk SSSR, 11__X7, 852 (1957).

465
REACTIONS OF CYCLAMMONIUM CATIONS
XXVIIIo* 4,9-DIAZAPYRENE IN HETARYLATION REACTIONS

A. K. Sheinkman, M . M. M e s t e c h k i n , UDC 547.834 : 541.67 : 543.422.25.4.6

A. P. Kucherenko, V. V. Artemova,
V. N. P o l t a v e t s , and Yu. B. Vysotskii

The r - e l e c t r o n c h a r g e s , bond o r d e r s , e n e r g i e s of the singlet and t r i p l e t e l e c t r o n i c t r a n s i -

tions, and the PMR s p e c t r u m of 4 , 9 - d i a z a p y r e n e w e r e calculated by the s e l f - c o n s i s t e n t -
field (SC F) method with allowance for the coulombic repulsion, and the r e s u l t s a r e c o m -
p a r e d with the e x p e r i m e n t a l l y found positions of the long-wave bands in the UV s p e c t r u m
and the e x p e r i m e n t a l PMR s p e c t r u m . 4 , 9 - D i a z a p y r e n e h e t a r y l a t e s activated a r o m a t i c and
h e t e r o a r o m a t i c rings.

Until r e c e n t l y t h e r e was no theory that enabled one to p r e d i c t the b e h a v i o r of any of the nitrogeneous
h e t e r o a r o m a t i c s y s t e m s in h e t a r y l a t i o n r e a c t i o n s of organic compounds in the p r e s e n c e of aeylating agents.
The f i r s t step in this reaction is the f o r m a t i o n of a r o m a t i c N - a c y l c y c l a m m o n i u m salts [2]. A n e c e s s a r y ,
but not always sufficient, condition for the p a r t i c i p a t i o n of the h e t e r o c y c l e in the h e t a r y l a t i o n r e a c t i o n is
t h e r e f o r e the p r e s e n c e in it of a pyridine nitrogen a t o m that is capable of interacting with the acyl halides.
Of no l e s s i m p o r t a n c e is the magnitude of the electrophilicity of the resulting h e t a r y l a t i n g agents, which,
all other conditions being equal, depends on the magnitude of the effective positive c h a r g e on the a (or y - ) -
c a r b o n atom of the ring of the s t a r t i n g molecule of the h e t e r o c y c l e and the p o l a r i z a b i l i t y of the N = C bonds
in the c o u r s e of the r e a c t i o n during the f o r m a t i o n of N - a c y l h e t e r o a r o m a t i c cations. It was recently shown
that an exocyclic C H = N group is m o r e p r e d i s p o s e d to such r e a c t i o n s than a ring C H = N group [3]. A r o m a t i c
Schiff b a s e s in the p r e s e n c e of acyl halides p r o v e to be convenient a - a m i d o m e t h y l a t i n g agents for many
nucleophilic organic compounds [3]. In this connection, it was expedient to examine the b e h a v i o r in this
reaction of 4 , 9 - d i a z a p y r e n e , in which the tendency for an i n c r e a s e in the o r d e r o f t h e r i n g n i t r o g e n - c a r b o n
bond is c l e a r l y e x p r e s s e d . To e s t i m a t e the r e a c t i v i t y of 4 , 9 - d i a z a p y r e n e , we calculated the bond o r d e r s
and distribution of the 7r-electron density; the coulombic repulsion between the e l e c t r o n s was taken into
account in o r d e r to obtain the m o s t reliable data.
We also used the p r e v i o u s l y developed method of direct calculation of the c h a r g e - b o n d o r d e r m a t r i x
[4] without p r i o r distribution of the orbital coefficients, which m a k e s it p o s s i b l e to achieve s e l f - c o n s i s t e n c y
with a high degree of a c c u r a c y . The p r o g r a m in [5] which m a k e s it p o s s i b l e to d i r e c t l y obtain analogous
values that c h a r a c t e r i z e the t r a n s i t i o n f r o m the ground state to the excited state was used in the c a l c u l a -
tion of the excited s t a t e s . This method is equivalent to a c o n s i d e r a b l e extent to the P a r i s e r - P a r r method
f o r excited states, but with the conditon that the set of excited configurations used is a standard set that
includes all of the singly excited configurations, r e g a r d l e s s of the size of the s y s t e m . This insured identi-
cal physical conditions f o r the introduction of the p a r a m e t e r s and m a k e s the calculation m o r e reliable. We
selected the p a r a m e t e r s that c h a r a c t e r i z e the c a r b o n a t o m f r o m the s p e c t r a of a l a r g e group of h y d r o c a r -
bon m o l e c u l e s [5, 6]: the r e s o n a n c e integral flCC = - 2 . 4 5 eV and the function that c h a r a c t e r i z e s the cou-
lombic repulsion is
10.1397 0.1460
~,(R) ~ _ _ (ev), (1)

*See [1] for communication XXVII.

Donetsk State U n i v e r s i t y . Donetsk P h y s i c a l - O r g a n i c C h e m i s t r y Branch, Institute of P h y s i c a l Chem-'
istry, Academy of Sciences o f the Ukrainian SSR. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i e h e s k i k h Soedinenii,
No. 4, pp. 537-541, April, 1974. Original a r t i c l e submitted May 25, 1973.

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy of this article is available from the publisher for $15.00.

466
 o
where a C = 2.2 and R is in "bond length" units of 1.4 A.
P a r a m e t r i z a t i o n of the nitrogen atom, the difference of which f r o m the c a r b o n atom w a s as usual,
c h a r a c t e r i z e d by its electronegativity & a N = - l . 6 8 eV, by f l C N = - 2 . 5 7 eV, and the shielding coefficient a N =
1.3558 f o r the determination of TNN f r o m e x p r e s s i o n (1), w a s in addition n e c e s s a r y f o r the calculation of
diazapyrene. The TcN(R) value when a C N = (a Nta C)/2 = 1.7779 is s i m i l a r l y obtained. These p a r a m e t e r s
were also selected f r o m the e l e c t r o n i c s p e c t r a of a s e r i e s of nitrogen h e t e r o c y c l e s of the 1,4-bis(2-vinyl-
pyridyl)benzene and benzoquinoline types.

~
0,0008

--0,0060

--0,0338

N ~ --0.1236~0,00fi5

~ --0,0135

0.000~

In o r d e r to verify the e l e c t r o n distribution of 4,9-diazapyrene, which is r e p r e s e n t e d by the m o l e c u l a r

d i a g r a m above, we simultaneously calculated its electronic s p e c t r u m and c o m p a r e d it with the experimental
s p e c t r u m . The e l e c t r o n i c s p e c t r u m of pyridine was also calculated for c o m p a r i s o n (Table 1). In the known
calculations of the s p e c t r a of polycyclic nitrogen-containing h e t e r o c y c l e s [7], the e l e c t r o n i c interaction is
taken into account with r e s p e c t to p e r t u r b a t i o n theory with the superimposition of two to four configurations.
As it turned out, our method of computation [4] is applicable to a m o r e extensive number of investigated
objects and is m o r e s y s t e m a t i c in a t h e o r e t i c a l r e s p e c t . A s seen f r o m Table 1, not only are the t h r e e lower ab-
sorption bands in the pyridine molecule, the a s s i g n m e n t of which c o r r e s p o n d s to the data in other studies
[10, 11], in s a t i s f a c t o r y a g r e e m e n t with the e x p e r i m e n t s [8, 9], but the lower triplet level is also in good
a g r e e m e n t With the f l u o r e s c e n c e m a x i m u m [9]. Two close and quite intense bands of the same s y m m e t r y ,
which can be c o m p a r e d with the a and p bands of pyrene, which are also close to one another (3.24 and 3.50
eV) are observed in the s p e c t r u m of 4 , 9 - d i a z a p y r e n e .

The PMR s p e c t r a of 4 , 9 - d i a z a p y r e n e and pyridine which are in good a g r e e m e n t with the e x p e r i m e n -

tal s p e c t r a {Table 2) were also calculated by the method adopted for h y d r o c a r b o n s [13], but with additive
addition to the nitrogen atom.

TABLE I. E n e r g i e s of the E l e c t r o n T r a n s i t i o n s (eV)

Singlet Triplet
Compound 8ymmetry
talc. exptl, calc. exptl.

Pyridine A 6,30 0,01 6,368 3,78 3,699, ~o

7,47 0,91 7,04 4,49
B 4,65 0,03 4,96 4,26
8,05 0,12 5,24
4,9-Diazapyrene B 3,21 0,291 3,3--3,5TM 1,19
3,36 0,214 3,35
A 4,20 4,07 3,20
5,88 5,24 4,23
Pyrene B3,,- (a) 3,24 3,3--3,5
B2,,+ (p) 3,50 O,542 3,5--3,6 1,94 2,08

TABLE 2. PMR Spectra

Pyridine, 6, ppm 4.9-Diazapyrene, 5, ppm
Hydrogen atom calc. exptl, data [14] expfl, data calc.

2-H 8,44 8,29 8,23 8,18

3-H 7,t15 6,77 9,13 9,49
4-H 7,09 7,15
5-H 8;5 85%

467
 T A B L E 3. Acyl D e r i v a t i v e s of T e t r a h y d r o d i a z a p y r e n e (II-IV)
.~ React. condition:
~mpirical ' ,~ "2-
.rap, ~C /~f formula H, ~"
- " ~ ~i '~I~ N,o~ ,~
l ~,-L
llg! 80 229--230al 0,24J C44HsoN402
180--181b] 0,14] Cs4J-I~N402
8O,5 5,~
76,3 52
8,7 625 81,7 4,7
11,11536t78,2 5,0
8,7
10,7
6461 60
50.3150
IIc 1t111--110 10--19 16D---161c]0,75[ C46H~4NJ,O2 80,5 5,~ 7,6 670181,8 5,1 8,3 6751 4~
lid 100--110 1O~-~l: 175--176d/ 0,17] C46Hs4~N40~ 79,1 5,3 8,6 671181,8 5,1 8,3 6751 45
IIel 110~120 153~154e| 0,66J C44HssN402 79,3 5,8 9,2 625 ] 80,7 5,8 8,5 6551 51
155~156f[ 0,58[ C38H3oN40~ 78,2 5,5 7,71587179,5 5,2 9,7 5~6150
IIf~l1101-~120 101--~11~10145--146e[ 0,18/CasHscN402 80,7 5,1 7,81701182'5 4,9 8,0 6981 40
216----217f.I0,27[C~HI~N202 78,2 5,8 8,3 378 ] 80,0 4,6 7~2 ~901 35
221--222f./ 0.40~C~sH2oN202 80,4 4,8 8,3 430 80,7!4,6 6,7 4P5150
a . . . . . . . . . .~ ,
F r o m p e t r o l e u m e t h e r - - p e n t a n o l , b F r o m pentanol. From aque-
ous m e t h a n o l , d F r o m c h l o r o f o r m , e F r o m e t h e r - p e t r o l e u m e t h e r .
f F r o m aqueous a c e t o n e .
The r e s u l t s of the c a l c u l a t i o n of the s p e c t r a of 4 , 9 - d i a z a p y r e n e and p y r i d i n e s a t i s f a c t o r i l y r e p r o d u c e
the e n t i r e e x p e r i m e n t a l p i c t u r e , and f o r this r e a s o n the c a l c u l a t e d d i s t r i b u t i o n of the e l e c t r o n d e n s i t y of
t h e s e m o l e c u l e s p r e s e n t e d in the d i a g r a m s m a y p r o v i d e the b a s i s f o r a d i s c u s s i o n of t h e i r c h e m i c a l p r o p -
erties.
In addition to this, the b a s i c i t y of 4 , 9 - d i a z a p y r e n e , which p r o v e d to be s o m e w h a t l o w e r than the pK a
value of p y r i d i n e and a p p r o x i m a t e l y equal to the b a s i c i t y of a n i l i n e d e t e r m i n e d in a s i m i l a r m a n n e r [16]
(10.40, 12.33, and 10.56, r e s p e c t i v e l y ) , w a s a l s o m e a s u r e d by the m e t h o d in [15].
Thus, the s e t of c a l c u l a t e d and e x p e r i m e n t a l data, which c o n f i r m the high C - N bond o r d e r , the r e l a -
tively high b a s i c i t y , and the c o n s i d e r a b l e deficit of ~ - e l e c t r o n c h a r g e on the s - c a r b o n a t o m , m a d e it p o s -
sible to a s s u m e that 4 , 9 - d i a z a p y r e n e has h i g h a c t i v i t y in h e t a r y l a t i o n r e a c t i o n s .
In fact, the c o r r e s p o n d i n g 5 , 1 0 - d i s u b s t i t u t e d 4 , 9 - d i a c y l - 4 , 5 , 9 , 1 0 - t e t r a h y d r o - 4 , 9 - d i a z a p y r e n e s (Table 3)
R"

+ RCOCI + R'H

R'
II
a R=CsH~,R~=3-indolyl;,(b)R=CH3, R'=3-ind01yl; (c)R=C~H~, R'=l-methyl-3-indolyl
(d)R=C6H~ R =2-methyl-8-indolyl(e)R=CoHs, R'=C6H4N(CHa)2-p;(f) R=C6Hs,
R' = l-methyi-2-p~rolyl(g)R= C6H5, R' = l-phenyl-2-p)~rolyl
were obtained at room tempera~re or on brief heating of a mixture of 4,9-diazapyrene and acyl halides
with nucleophilic aromatic and heteroaromatic compounds.
Heteroaromatic systems containlng two nitrogen atoms of the pyridine type usually form monosub-
stituted compounds (for example, m-phenanthroline and phth~azine in reactions with benzoyl chloride and
KCN [17]) in such reactions. For the first time we have apparently been able to obtain disubstituted If, but
monosubstituted compounds, for example, HI and IV, are also formed in some cases:

OC6ti5
~N~COE6 tls
GH2COG6H 5
I
Ctta
Ill iv
T h e r e a r e c h a r a c t e r i s t i c b a n d s of UCO s t r e t c h i n g v i b r a t i o n s at 1670-1700 c m -1 in the IR s p e c t r a of
I - I V . In c o n t r a s t to II, III and IV f o r m p i c r a t e s ; this c o n f i r m s t h e i r s t r u c t u r e s . The s t r u c t u r e of one of
the c o m p o u n d s (lie) w a s p r o v e d by a l t e r n a t i v e s y n t h e s i s v i a the s c h e m e

468
 CsH4N(CH3)2-F
NHCOC~H4NICH3}2_p
P-(CH3)'
C N"C6H4CO
I ~ <",L~/
~/~/~ /x~/ NaCI+A250_2GO_Cl,. ~Ol'- l i e

Ntt2 p-(CH3) 2NCGH4COHN

J
C6H.;N(CH3)~-P
Y VI
The LR and UV s p e c t r a of I I a - g are s i m i l a r to the s p e c t r a of He; this c o n f i r m s the s t r u c t u r e assigned to
them.

EXPERIME NTAL
The IR s p e c t r a of c h l o r o f o r m solutions were r e c o r d e d with a UR-10 s p e c t r o m e t e r . The PMR spec-
t r u m of a dimethyl sulfoxide solution was r e c o r d e d with a YaMR-5535 s p e c t r o m e t e r (40 MHz) with c y c l o -
hexane as the internal standard. C h r o m a t o g r a p h y in a loose thin l a y e r of AI203 was accomplished with
b e n z e n e - h e x a n e - c h l o r o f o r m (6 : 1 : 30).
4 , 9 - D i a z a p y r e n e was obtained by fusing 2,2'-diformamidodiphenyl with NaC1 and A1C13 at 250 ~ The
product had mp 218-220 ~ (from ethanol) (nap 220-221 ~ [12]).
Typical method of hetarylation. A solution of 0.005 mole of thoroughly dried 4,9-dtazapyrene, 0.01
mole of acyl chloride, and 0.01 mole of the compound to be hetarylated in 25 ml of anhydrous benzene was
held at 25 ~ o r 100 ~ f o r 2 to 12 h, depending on the nucleophilicity of the compound to be hetarylated (see
Table 3), after which the solution was made alkaline with ammonia and s t e a m distilled. The residue in the
flask was separated, washed with water, dried, and r e c r y s t a l l i z e d f r o m suitable solvents. The yields and
c h a r a c t e r i s t i c s of the compounds obtained are p r e s e n t e d in Table 3.
5,10-Di (p-dimethylaminophenyl)-4,9-diazapyrene (VI). A. A solution of 2.5 g (45 mmole) of KOHin
20 ml of 70% ethanol was added to 0.5 g (0.8 mmole) of lie, and the mixture was refluxed for 20 h. It was
then cooled, and the p r e c i p i t a t e was removed by filtration and r e c r y s t a l l i z e d f r o m alcohol to give 0.18 g
(4070) of a product with mp 277-278 ~ and R f 0.83. Found: C 80.8; H 7.4; N 12.1%. C~0H28N4. Calculated:
C 81.1; H 6.3; N 12.670.
]3. A m i x t u r e o f l . 9 g (0.01mole) of 2,2'-diaminodipheny], 4.6 g (0.025 mole) of p - d i m e t h y l a m i n o -
benzoyl chloride, and 2 g of p o t a s s i u m carbonate in 20 ml of e t h e r was refluxed for 3 h, after which it was
diluted with water. The resulting precipitate was separated, washed with water, dried, and r e c r y s t a l l i z e d
f r o m ethanol to give 2.4 g (50%) of 2,2'-bis(p-dimethylaminobenzamido)diphenyl (V) with mp 166-167 ~ and
R f 0.35. Found: C 74.4; H 6.6; N 12.07o. C30H30N402. Calculated: C 73.8; H 6.1; N 11.4%.
A 0.82-g (0.05 mole) sample of V was added in portions to a melt consisting of 3.7 g of NaC1 and 17.7g
of A1C13 at 150 ~ after which the t e m p e r a t u r e was r a i s e d to 250-260 ~ and maintained there f o r 8 h . The
mixture was then poured over ice, and the aqueous mixture was made alkaline and extracted with benzene.
The e x t r a c t was dried, the benzene was removed by distillation, and the residue was separated with a col-
umn filled with A1203 with elution with b e n z e n e - h e x a n e - c h l o r o f o r m (6 : 1 : 30) to give 0.1 g of diazapyrene
VI with mp 272-274 ~ which proved to be identical to the sample described above.

LITERATURE CITED
1. A . K . Sheinkman and G. V. Samoilenko, Zh. Obshch. Khim., 43 (1974).
2. A . K . Sheinkman, Khim. Geterotsikl. Soedin., 3 (1974).
3. A . K . Sheinkman and A. P. Kucherenko, Khim. Geterotsikl. Soedin., 1432 (1973).
4. M . M . Mestechkin and V. N. Poltavets, T e o r . i ]~ksperim. Khim., 3, 695 (1967).
5. M . M . Mestechkin, L. S. Gutyrya, and V. N. Poltavets, Optika i Spektroskopiya, 28, 454 (1970).
6. M . M . Mestechkin, L. S. Gutyrya, and V. N. Poltavets, Optika i Spektroskopiya, 30, 1022 (1971).
7. N. Mataga, Z. Phys. Chem., 18, 285 (1958).
8. H. Klevens and J. Platt, Technical Report of the L a b o r a t o r y of Molecular Structure and Spectra,
Chicago (1954).
9. D. Evans, J. Chem. Soc., 3885 (1957).
10. R. McWeeny and T. Peacock, P r o c . Phys., A70, 41 (1957).
11. R. Brown and M. Heffernan, Austral. J. Chem., 1_~2,554 0959).
12. W. Mosby, J. Org. Chem., 2..~2, 671 (1957).
13. Yu. B. Vysotskii, Zh. Strukt. Khim., 15, 56 (1974).

469
14~ J . H . S . Wang and W. H. Flygare, J. Chem. Phys., 52, 5636 (1970).
15. V . I . Mink[n and V. A. Bren', Reakts. Sposobnost' Organ. Soedin., 4, 112 (1967).
16. J. Coetzee and G. Padmanabhan, J. Amer. Chem. Soc., 87, 5005 (1965).
17. F. Popp, Adv. Heterocycl. Chem., 9, 1 (1968).

470
VIBRATIONAL SPECTRA OF PYRAZOLE IN VARIOUS
AGGREGATE STATES AND THEIR INTERPRETATION

V. S. Troitskaya, N. D. Konevskaya, UDC 547.772 : 543.422.4'424

V. G. Vinokurov, and V. I. Tyulin

The selection of the fundamental frequencies of p y r a z o l e and the assignment of them to

various types of vibrations were made on the b a s i s of a c o m p a r i s o n of the LR and Raman
s p e c t r a of p y r a z o l e and some of its isotopically substituted derivatives in various a g g r e -
gate states and in the f o r m of complexes with CdC12. The a s s i g n m e n t was confirmed by
p r i o r calculation of the frequencies and f o r m s of the vibrations of p y r a z o l e .

We have p r e v i o u s l y studied the vibrational s p e c t r a of polyfunctional p y r a z o l e derivatives that are

capable of undergoing t a u t o m e r i c t r a n s f o r m a t i o n s [1]. In the p r e s e n t r e s e a r c h we set out to obtain and
i n t e r p r e t the vibrational s p e c t r a of p y r a z o l e itself as the principal f r a g m e n t of the investigated class of
compounds.
The a s s i g n m e n t of the frequencies in the vibrational s p e c t r a of p y r a z o l e [2, 3] and its mono- and
polyalkyl derivatives [4, 5] has not yet been effected convincingly. It is known that p y r a z o l e exists as
twisted hydrogen-bonded chains in the c r y s t a l l i n e state [6] and as cyclic d i m e r s and t r i m e r s in solution
(CC14), even up to concentrations of 10-3 to 10-4 M [7]. Strong i n t e r m o l e c u l a r hydrogen bonds and the c r y s -
t a l - l a t t i c e field complicate the s p e c t r u m of p y r a z o l e (as c o m p a r e d with the gas), leading to shifts in the
band and splitting of them. as a consequence of which e r r o r s may a r i s e in the assignment. Special atten-
tion was therefore directed to the r e c o r d i n g and interpretation of the s p e c t r u m of the isolated m o n o m e r i c
molecule.
In o r d e r to select the fundamental frequencies of p y r a z o l e and interpret them we obtain the IR s p e c t r a
of pyrazole, 15N2-pyrazole, 4 - D r p y r a z o l e , and 3,4,5-D3-pyrazole in the gaseous and crystalline states; the
IR s p e c t r a of complexes of the compounds indicated above, and of 1 - D r p y r a z o l e , 1,4-D2-pyrazole , and D4-
p y r a z o l e with CdC12 in the c r y s t a l l i n e state; the Raman s p e c t r a of pyrazole, 15N2-pyrazole , and 1,4-D 2-
p y r a z o l e in the c r y s t a l l i n e state; the LR s p e c t r a of solutions of p y r a z o l e on s u c c e s s i v e dilution in carbon
disulfide and CC14 (concentrations f r o m 10-1 to 10-3 M); and the R a m a n s p e c t r a in CC14 (10-1 and 10-2 M)
(Tables 1 and 2 and Figs, 1 and 2).

On the basis of investigations of the microwave s p e c t r a it was established that the p y r a z o l e molecule
is p l a n a r [8, 9] and has Cs point group s y m m e t r y ; the n o r m a l vibrations, with r e s p e c t to s y m m e t r y types,
are distributed as follows: F = 15A' +6A". In the s p e c t r u m of the gas, bands of the C f o r m with an intense
Q b r a n c h and a distance of 40 c m - I between the P and R branches should c o r r e s p o n d to six vibrations of
the A" type, and bands of the A and B f o r m s with a distance of 24 c m -1 between the P and R branches
should c o r r e s p o n d to 15 p l a n a r vibrations of the A' type (see [2]).
Five bands of vibrations of the A" type - 515, 670, 746, 833, and 880 cm -~ - are readily isolated in
the s p e c t r u m of the gas (Table 1). In c o n f o r m i t y with [10] and also in analogy with imidazole [11], we a s -
signed the f i r s t band to the TNH vibration. As in [2], the bands at 746, 833, and 880 cm -1 were assigned
to the TCH vibrations, while the band at 670 c m -1 was ass~gned to ring deformation (y ring). The six v i b r a -
tions of the A" type should probably appear at 600-650cm , as in the case of imidazole [11]. It should be
noted that one of the intense bands in the s p e c t r u m of crystalline p y r a z o l e (612 cm-1) cannot be considered

S c i e n t i f i c - R e s e a r c h Institute of P h a r m a c o l o g y , Academy of Medical Sciences of the USSR, Moscow.

T r a n s l a t e d f r o m Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 542-548, April. 1974. Original article
submitted March 26, 1973.

9 19 75 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $13.00.

471
 TABLE 1. V i b r a t i o n a l S p e c t r a of P y r a z o l e in V a r i o u s A g g r e g a t e
States { f r e q u e n c i e s , e m - 1 ) *
Gas Solutions't" Crystal
10'M 10`2 M 10~s M
tR. IR Raman
IR Rarnan IR Raman IR

492I
5oi I
515} 530 523 53O m 530 s 612 s 627
535 I 612 w 611 w
1538~ 584
65o/
672} 670 w 670 672 s 652 w
695J
728/
746t 755 s 752 s 750 s 760 s 782
767) /
815/ t
833t 1 835 s 840
850)
880 ~ ] 882 s 876 875 s 880
896 J]~ 890 s
91o tl 917 915 910 915 s 917
920 Jl 934 928 966 935 ~. 944
997|
10101 1038 s 1035 1038 1001 1017 s 103os 1037
1020J 1050 s 1048 1050 1056 1050
1060 , 1092 m 1066 1064 1055s 1059
1115/
1125; ll40 s 1125 s 1123 s 1137 s
1140) 1156 s I152 1155 l155ra 1150 s
1~45~ 1218 1218 1227 w
1270j 1260 w 1258 1258 1260rn 1270 s
13401 1322 1322
13~0t 1360ra 1354 1345 1354 1347 1360m 1366 m
13,87~ 1377
1410J 1395 s 1392 1395 s 1395 1395 s 1400s 1407 m
1442~ 1430 w 1430 w
1470J 1450m 1470 1450m~ 147Cm
1480m 1475 1470
1525~ 1530 w
15551 1550 w
3tt"5
3125
3140
35101
~25}
~l~J 3485

*The a b b r e v i a t i o n s u s e d h e r e and e l s e w h e r e a r e as f o l l o w s : s
is s t r o n g , m is m e d i u m , and w is w e a k .
t T h e 4 0 0 - 1 3 0 0 c m -1 and 1 2 5 0 - 1 4 5 0 c m -1 r a n g e s w e r e i n v e s t i -
gated f o r s o l u t i o n s in CS 2 and CC14, r e s p e c t i v e l y .

to be T - r i n g v i b r a t i o n (A") [2], i n a s m u c h a s it v a n i s h e s in the s p e c t r u m of s o l u t i o n s (CS2) on d i l u t i o n w i t h t h e

s i m u l t a n e o u s d e v e l o p m e n t of a band at 530 c m -1 (Table 1), w h i c h c o r r e s p o n d s to T N H v i b r a t i o n (515 c m -1
in t h e g a s ) . Th e c h a r a c t e r of the s h if t of this band on w e a k e n i n g of the h y d r o g e n bond, in the o r d e r c r y s t a l ,
c o m p l e x , s o l u t i o n , g a s (612, 593, 530, and 515 c m - 1 ) , c o n f i r m s its a s s i g n m e n t to the TN H v i b r a t i o n . U n -
f o r t u n a t e l y , we w e r e u n a b l e to f o l l o w the i s o t o p i c s h i f t of the 515 c m -1 b a n d in t h e s p e c t r u m of 1 - D l - p y r -
a z o l e g a s . As in the c a s e of i m i d a z o l e [11], as a c o n s e q u e n c e of the high l a b i l i t y of the h y d r o g e n a t o m a t -
t a c h e d to the n i t r o g e n , t h e r e is r a p i d r e v e r s i b l e e x c h a n g e of d e u t e r i u m by h y d r o g e n . Th e s p e c t r a of the
c o m p l e x e s a r e of s u b s t a n t i a l a s s i s t a n c e in the a s s i g n m e n t . T h e l a b i l i t y of the h y d r o g e n a t o m is r e d u c e d
in c o m p l e x e s , f o r e x a m p l e , with CdC12 owing to the s t r o n g h y d r o g e n bond w i t h t h e a n i o n [12]; t h i s m a k e s
it p o s s i b l e to o b t a i n 1 - d e u t e r o d e r i v a t i v e s of p y r a z o l e with a high p e r c e n t a g e of d e u t e r i u m in t h e 1 - p o s i t i o n .
An a d d i t i o n a l a d v a n t a g e of the s p e c t r a of the c o m p l e x e s as c o m p a r e d w i t h t h e s p e c t r a of c r y s t a l s is the
p r e s e n c e at 800-950 c m -1 of n a r r o w , n o n o v e r l a p p e d b a n d s , w h i c h c a n be c o m p a r e d w i t h the c o r r e s p o n d i n g
b a n d s in the s p e c t r u m of the g a s , and the a b s e n c e of b r o a d i n t e n s e b a n d s at 2800-3300 c m -1. Th u s, the
s h i f t in the TNH v i b r a t i o n a l bands d u r i n g d e u t e r a t i o n - 7N H 593 c m -1, TN D 480 c m - i (Fig. 2) - c a n be f o l -
l o w e d by c o m p a r i s o n of the s p e c t r a of c o m p l e x e s of p y r a z o l e and 1 - D l - p y r a z o l e . We note that r e p l a c e m e n t
of the h y d r o g e n in th e 4, 3, and 5 p o s i t i o n s by d e u t e r i u m has v i r t u a l l y no e f f e c t on t h e TND v i b r a t i o n a l f r e -
q u e n c i e s (478 c m TM) (Fig. 2).

472
 3~o; . . 30o0
. . . . . . a6oo
. . . . . .~2oo
. . . . . .~eoo ~oo ~o'oo' '~;o '~;o' ' ~.ooom "~
Fig. i. ~R spectra in the gaseous state: I) pyrazole; 2) 4-D~-pyrazole;
3) 3,4,5-D3-pyrazole (3,4-D2-pyrazole and 4,5-D2-pyrazole impurities
are present).

80

40

="
o
`80

40
?
. . . . . i
[--, 80
o
' ~ '~"
I '
~0

/ t
r , p ~ i i i t t i f , f , r i ~ f i i i i t

,80

40

O . , , . . . . . . . . , . . , , . , , . . . . . . . . . . , , . t

3400 3000 2600 2200 1800 1400 1000 700 500 400 a m "1

Fig. 2. IR s p e c t r a of complexes with CdC12: 1) pyrazole; 2) 1-D 1-

p y r a z o l e ; 3) 1,4-D2-pyrazole; 4) D4-pyrazole (1,3,4,-D3-pyrazole and
1,4,5-D3-pyrazole impurities are present).

The a s s i g n m e n t of the in-plane vibrations (A') p r e s e n t considerable difficulty, and their interpretation
can only be c a r r i e d out by simultaneous study of the IR and Raman s p e c t r a in various aggregate states with
c o r r e l a t i o n of the bands f r o m the s p e c t r a of the complexes.
The VNH and vCH vibrations are most readily identified. The VNH band has a frequency of 3525 c m -t
in the s p e c t r u m of the gas and 3485 cm -I in the s p e c t r u m of a solution (CC14). The vCH vibrations in the
gas give a weak, b r o a d band at 3115-3140 c m -~ (Fig. 1) but appear as three n a r r o w bands at 3125, 3140,
and 3155 c m - I in the s p e c t r a of the complexes (Fig. 2).
Of the five ring vibrations, four should apparently be observed at 1200-1600 c m -1. The bands at 1470,
1400, 1350, and 1255 c m -1 can be adopted as the fundamental frequencies (Table 1). In c o n t r a s t to [2]. we
are inclined to c o n s i d e r the band at 1525 c m -1 (pyrazole complex, Table 2) as a composite band 939 +593
(TNH)~ inasmuch as it does not appear in the s p e c t r u m of the 1 - D l - p y r a z o l e complex, while the remaining

473
 TABLE 2. IR Spectra of Complexes of Pyrazole and Its Isotopi-
cally Substituted Derivatives with CdC12 (frequencies, cm -1)

_lSN2- 1 - D 1- 14-DI- 1 , 4 - D 2- 3 , 4 , 5 " D s - " D4-

P~azole Pyrazole Pyrazole iPyrazole Pyrazole Pyrazole* ?yrazoleT

480s 480 s 477s

521 s 523 m
535m
578 w 555 w 583 s
583 s 575 w
593 s 587 s 598 s
612 m 600s
630 w 627 w 645 m 638 m 623 m
652 s 650 m
678 w 673 s -- 682 s 695 w
763 s 762 s 761 s -- -- 672 s --
-- 787 m
783 w 780 m 790 m 813 m
835s
350 w 850 w 840
860 860 855 w 866
865 865 870 s 373 s 870 s 866 875 w
875 m
916 w 912 w 920 w )03 w 915 m 885 915 m
939 925 900 m
)65 s 965 910 977
975 w 965 ~uv w
1041 s 1030 s 1038 s 1040 s 1050 s 980 m 1050 w
1055 s 1050s 1055 m 1043 s
I068 s
1090 s ll00 w
1120 w
1128s I123s 1127w 1123s 1122 1135w
1142 m 1150 s 1135 m
lI60m I160w 1145
1191 rn 1185 w
1212 m 1185 s
1255 w 1245 m 1245 m
1232 1260 s
127(I w 1263 w 12,45 w 1275 m
1345 s 1336 s 13413m 1333 rn 1310 w
1360 s
13'5'8 s t395m 1385 s 1395 s 1388 s 1365 m 1375m
1405 m 1385
1405 m 1435 s 1400 m
1457 s 1463 m 1450 m 1452 w
1475 s 1460 w
1525 m 1523 m -- 1515 m 1483 m
1500 m
1555 w
2500 s 2500 s 2503 s
2540 w 2520 m 2544 w
3'125 3120 2595 w
3135 w 3135 w 2663 w 3135 .
3155 3150 3129 3150 w
3358 s 8350 s 3135 w 3355 s 3130.
315,0 3150w 3355 s

*A mixture of 3,4-D2-pyrazole and 4,5-D2-pyrazole.

~'A mixture of 1,3,4-D3-pyrazole and 1,4,5-Ds-pyrazole.
four bands are shifted by 10-30 cm-i to lower frequencies. The band at 1152 cm-I, which is the most in-
tense in the Raman spectrum of pyrazole and the weakest in the IR spectrum of the gas, may be the fifth
band affiliated with the ring vibrations. The bands observed in the Raman spectrum at 1258 and 1152 cm-I
are polarized. The assignment of the five bands under discussion to the ring vibrations is arbitrary, inas-
much as in the deuterium derivatives they experience strong shifts; this indicates the complex character
of these vibrations (they are shifted with the 6NH and 6CH deformation vibrations). We assign the bands
at 1125 and 1060 and at 1010 cm-I (gas) to the 6NH and 6CH deformation vibrations. Actually the band at
1127 cm- i in the spectrum of the pyrazole complex is related to the 6NH vibration, inasmuch as it is shifted
to 870 cm-I in the spectrum of 1-D1-pyrazole (Fig. 2). The 6 vibrations apparently show up at 1000-1060
cm-I, as indicated by the decrease in intensity of the corresponding band on successive replacement of the
hydrogen by deuterium.

The remaining two A' vibrations (ring 6) p r o b a b l y should be sought at 850-940 cm -1, in analogy with
imidazole [11]. The bands at 910 cm "l (gas) and 940 cm -1 (complex) can be assigned to one of them. The
second 6 ring band is possibly masked by the P and R branches of the bands at 833 and 880 cm -1 (7CH), and,
in conformity with imidazole [11], we assume it to be 865 cm TM.

474
 TABLE 3. A s s i g n m e n t of the Fundamental Frequencies in
the Vibrational Spectra of P y r a z o l e
Symmetry Observed~e- Calculated Assignment
type queney, cm -1 ~equency, :
C.dI1-1

515 515 u ~ ring, , YCH(4)

615 619 ~ ri.ng, Vcn
670 668 nng, yah
A" 745 744 u CH(4) , y N H
833 831 Y CH(5)
88O 886 u CH(3)
865 870 6 ring, 5 C H
910 915 6ring
I010 998 6 CH(3) , 6NH
1030. 1011 CH(5)
Is 1053 ~CH(4 ) , ~Ntt
A' 1125 1120 6NIt, 6CH(4 )
1152 1155 v ring, 6 N a
1258 1263 Vring' 6ca
1350 1349 v ring, 6NK,6cn
1400 1406 Vrina9 ' 6cg' 6NH
1470 1483 v ring, 6oK
3125 3128 ~VCH(4 )
3135 3138 "~CH(3)
3155 3152 x~CH(5)
3525 3520

The a s s i g n m e n t that we made on the b a s i s of a study of the IR and R a m a n s p e c t r a of p y r a z o l e in v a r i -

ous aggregate states and a c o m p a r i s o n with the s p e c t r a of complexes of isotopically substituted p y r a z o l e
was confirmed by a p r e l i m i n a r y calculation of the frequencies and f o r m s of the n o r m a l vibrations. The
results of the calculation and the assignment of the fundamental frequencies are p r e s e n t e d in Table 3.* The
calculation showed that a l m o s t all of the vibrations of p y r a z o l e except for the vCH and VNH stretching vi-
brations are composite. An examination of the f o r m s of the vibrations confirmed that the 6CH and 6NH
vibrations make a significant contribution to the ring vibrations and that the 6NH vibration is mixed with
almost all of the 6CH vibrations.

EXPE RIME NTA L

P y r a z o l e and 15N2-pyrazole were obtained by the method in [13].
1 , 4 - D 2 - P y r a z o l e . A solution of 1 g (0.015 mole) of p y r a z o l e in 15 ml of D20 and 1 ml of D2SO4 was
heated in an ampoule in an autoclave at 100 ~ for 16 h, after which half the original volume of D20 was removed
by vacuum distillation. The residue was neutralized with NaOD solution and extracted with ether. The
e t h e r solution was thoroughly vacuum evaporated, and the residue was purified by double vacuum sublima-
tion to give 0.72 g (72%) of product.

D4-Pyrazole. A solution of 0.7 g (0.01 mole) of 1,4-D2-pyrazole and sodium methoxide (from 14 ml
of CD3ODand 0.3 g of Na) was heated in an ampoule in an autoclave at 100 ~ for 22 h, after which the CD3OD
was r e m o v e d by distillation, and the residue was dissolved in D20. The solution was neutralized with D2SO4
and e x t r a c t e d with e t h e r . The e t h e r solution was thoroughly vacuum evaporated, and the residue was p u r i -
fied by vacuum sublimation. The yield of D4-pyrazole was 0.43 g (60%).t The degree of replacement of
hydrogen by deuterium was evaluated by means of the PMR s p e c t r a .
The complexes of p y r a z o l e and its isotopically substituted derivatives with CdC12 were obtained by
mixing solutions for H20 or D20 (the CDC12-to-pyrazole ratio was 1 : 2). Found: C 17.9; C122.0%. 2C3H4N2 9
CdC12. Calculated: C 17.5; C1 22.2%.
The IR s p e c t r a of pyrazole, its isotopically substituted derivatives, and their complexes were r e -
c o r d e d with a UR-10 s p e c t r o m e t e r . The s p e c t r a of c r y s t a l l i n e samples were r e c o r d e d f r o m KBr pellets.

*The a s s i g n m e n t was confirmed by calculation of isotopically substituted p y r a z o l e . The details involved

in the calculation, the method used to select the f o r c e field, and the final set of force constants will be p r e -
sented in our next p a p e r .
t A c c o r d i n g to m i c r o w a v e [9] and m a s s s p e c t r o m e t r i c data, the sample also contained 1,3,4-D3-pyrazole
and 1,4,5-D3-pyrazole in addition of D4-pyrazole.

475
The s p e c t r a of solutions of p y r a z o l e in CC14 and CS 2 w e r e r e c o r d e d during s u c c e s s i v e dilution f r o m 10 -1
to 10 -3 M and while the l a y e r thickness was i n c r e a s e d f r o m 0.1 to 50 m m . The s p e c t r a in the g a s e o u s state
w e r e obtained at 100 ~ and a p r e s s u r e of 10 m m with the use of a 100-era long m u l t i p l e - p a s s gas cuvette.
The R a m a n s p e c t r a of the p y r a z o l e solutions w e r e obtained with a 1 0 0 - c m long cuvette and a DFS-2 s p e c -
t r o m e t e r with photographic r e c o r d i n g [exposures of 75 h (10 -~ M) and 125 h (10 -2 1Y[)] and a powerful low-
p r e s s u r e m e r c u r y l a m p [14]. The R a m a n s p e c t r a of c r y s t a l l i n e s a m p l e s w e r e obtained with a C a r y 8 1 s p e c -
t r o m e t e r with an a r g o n l a s e r .

LITERATURE CITED
1. I . I . Grandberg, V. G. Vinokurov, V. S. T r o i t s k a y a , T. A. Ivanova, and V. A. Moskalenko, Khim.
Geterotsikl. Soedin., 202 (1970).
2. A. Zecchina, L. C e r r u t i , S. Coluccia, and E. Borello, J. Chem. Soc., B._z1363 (1967).
3. G . B . Bonino, R. Manzoni-Ansidei, and S. M. Betti, Atti Acc. Sci. (Lincei), 2..~2, 438, 444 (1935).
4. G. Zerbi and C. Alberti, Spectrochim. Acta, 18, 407 (1962).
5. G. Zerbi and C. Albert[, Spectrochim. Acta, 19, 1261 (1963).
6. H . W . W . Erlich, Acta C r y s t . , 13, 946 (1960).
7. D . M . V . Anderson, J. L. Duncon, and F. J. C. Rossotti, J. Chem. Soc., 140 (1961).
8. W . H . Kirchoff, J. A m e r . Chem. Soc., 8_.99, 1312 (1967).
9. R . S . Nasibullin, R. G. Latypova, V. S. T r o i t s k a y a , V. G. Vinokurov, and N. M. Pozdeev, Zh. Strukt.
Khim., 1, 49 (1974).
10. E. Borello, Atti. Acad. Sci (Torino), 94, 911 (1960).
11. C. P e r c h o r d , A. M. Bellocq, and A. Novak, J. Chim. Phys. (Paris), 1344 (1969).
12. J. Reedijk, R e c . T r a y . Chim., 88, 1451 (1969).
13. T . V . Protopopova and A. P. Skoldinov, Zh. Obshch. Khim., 2._~7,1276 (1957).
14. V . I . Tyulin and V. M. Tatevskii, Optika i Spektroskopiya, 14, 582 (1963).

476
TRANSFORMATIONS OF SUBSTITUTED
T E T R A HY D R O - 8 H - I N D E N O [ l , 2 - d ] I M I D A Z O L E S
IN CONCENTRATED SULFURIC ACID

A . K. A r e n , F. A. Grunsberg, UDC 547.759.4'785.5' : 543.422.4.6

a n d I . K. Y u r g e v i t s a

The f i v e - m e m b e r e d ring of the indene s y s t e m in 2 , 8 - d i o x o - 3 a - h y d r o x y - 8 a - R - 1 , 2 , 3 a , 8 a -

t e t r a h y d r o - 8 H - i n d e n o [ 1 , 2 - d ] i m i d a z o l e s is hydrolytically cleaved in concentrated sulfuric
acid solutions. Depending on the r e a c t i o n conditions, compounds for which substituted
4 - ( o - c a r b o x y p h e n y l ) i m i d a z o l - 2 - o n e (IIL 1 , 8 - d i o x o - l , 2 - d i h y d r o - 8 H - i m i d a z o [ 4 , 3 - a ] i s o i n d o l e
(III), and spiro[imidazolidine-4,3'-phthalide] s t r u c t u r e s were a s s u m e d were isolated.

Under the influence of strong acids (concentrated sulfuric and polyphosphoric acids), 8 - o x o - 2 - t h i o x o -
1,2,3a, 8 a - t e t r a h y d r o - 8 H - i n d e n o [ 1 , 2-d]imidazoles can be converted to 2-thioxo-4- (o-carboxyphenyl)imid-
azolines and 8 - o x o - l - t h i o x o - l , 2 - d i h y d r o - S H - i m i d a z o [ 4 , 3 - a ] i s o i n d o l e s [1-3]. In concentrated sulfuric acid,
indeno[1,2-d]imidazoles (I) are altered in the same m a n n e r . Various t r a n s f o r m a t i o n p r o d u c t s - 4 - ( o - c a r -
boxyphenyl)imidazol-2-ones 0-I), dihydroimidazo[4,3-a]isoindoles (III), o r spiro[imidazolidine-4,3'-phtha~-
lides] (IV) - are isolated, depending on the reaction conditions.

O
i, R~R
I~ ~ i COO- 1 O
tl
O
II
OH- ~N~'X"N/Ri
OH
Ia - h ,o, 1 Ilia, el, e, h
"~ -H2011El+
H,20 HOHI[-H20
Or
~J'~O Ito0 -H~O
H ~
} R:zN~
' /N~.R~
| R2./NyN\R,
IVa,d-h lla-c

l--IV a R]=R2=H; R3=OH; l, Ii b RI=CH2C6Hs; R~=Ra=C6Hs; I, II c RI=H; R2=R3=

=C6H5; I, Ill, IV d RI=CHa; R2=H; R3=OH; l, Ill, IV eRI=CH3; R2=H; R3=OCH3;
I, IV f RI=H; R2=C6Hs; Ra=OCH3; !, IV g RI=H; R2=C6Hs; Ra=OH; I, lII, IV h
RI=R2=H; Ra=OCH3

On b r i e f t r e a t m e n t of I with concentrated sulfuric acid, the f i v e - m e m b e r e d ring of the indane group-

ing opens to give substituted imidazolones II. Cleavage of the f i v e - m e m b e r e d ring in acidic media c o m -
m e n c e s with protonation of the carbonyl group, p r o m o t i n g hydrolytic cleavage of the ring [4]. Compounds
II are c o l o r l e s s c r y s t a l l i n e substances that are quite soluble in alkalis. The IR s p e c t r a of these compounds
contain a c h a r a c t e r i s t i c absorption band at 1695-1702 c m -~ that c o r r e s p o n d s to the vibrations of the c a r -
b o n y l g r o u p o f a r o m a t i c acids [5]. The vibrational frequency of imidazolinone is observed at 1666-1677
cm -1. The v C =C bands of the imidazolinone ring at 1631-1644 c m -1 [6] and the stretching vibrations of
a r o m a t i c rings at 1572-1600 c m -1 show up distinctly in the s p e c t r a of a l m o s t all of the 2-imidazolones (II).
In some c a s e s the VC=O and VC= C bands of imidazolinone overlap. The UV s p e c t r a of II contain absorption

Riga Polytechnic Institute. T r a n s l a t e d f r o m Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 549-

551, April, 1974. Original article submitted July 26, 1973.

9 19 75 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy of this article is available from the publisher for $15.00.

477
m a x i m a at ~285 nm (log e 4.15); this is in complete a g r e e m e n t with the absorption of 4-(o-carboxyphenyl)-
4 - i m i d a z o l i n e - 2 - t h i o n e [1, 2].
Yellow erystalline substances that are soluble in p o l a r solvents but insoluble in nonpolar solvents
are isolated in the ease of more prolonged action of coneentrated sulfuric acid on I and subsequent addition
of ice to the solution. Compounds that have identical physical and chemical p r o p e r t i e s were also synthe-
sized by i n t r a m o l e c u l a r cyclization of II. The substituted dihydroimidazo[4,3-a]isoindole s t r u c t u r e {lid
was adopted for these compounds on the basis of their chemical and spectral p r o p e r t i e s and also inanalogy
with the t r a n s f o r m a t i o n s of the thio derivatives of indeno[1,2-d]imidazoles in solution in dehydrating acids
[3]. Of c o u r s e , HI can be only formed f r o m those indeno[1,2-d]imidazoles (I) o r 4-(o-earboxyphenyl)imid-
a z o l - 2 - o n e s gI) that do not have a substituent attached to the nitrogen atom in the 3-position (R 2= H).
An intense broad absorption band at 1745-1769 c m -~, which is often split into a doublet at 1745-1751
and 1707-1723 c m -~, is c h a r a c t e r i s t i c for the IR s p e c t r a of solid Ill. This absorption should be assigned to
the vibrations of the C O - N - C O grouping [5]. In addition, the absorption frequeneies of a double bond at
1651-1669 c m -~ and three low-intensity absorption maxima of an a r o m a t i e ring at 1579-1608, 1556-1558,
and 1530 c m -1 are observed in the s p e e t r a of III. Absorption at 239 (log e ~4.19), 306 (log e 4.12), and 394-
398 nm (log e 3.68) is c h a r a c t e r i s t i c for the UV s p e e t r a of Ill.
In alkaline media compounds Ill undergo cleavage; this c o n f i r m s the different c h a r a c t e r of the UV
s p e c t r a of solutions of III in neutral and alkaline ethanol. The hypsochromic shift of the absorption bands
and the disappearance of the m a x i m u m at 394 nm provide evidence for disruption of the I r - p eonjugation
during cleavage of the III s y s t e m . Spiro[imidazolidine-4,3'-phthalides] (IV) are isolated when alkaline solu-
tions of III are acidified.
Compounds IV are formed like isoindoles III and imidazolones II in solutions of imidazoles I in con-
centrated sulfuric acid and also on s u c c e s s i v e alkaline-acidic hydrolysis of isoindoles III. Two absorption
bands at 230-240 nm (log e ~ 4.15) and 280 nm (log e ~3.30) appear in the UV s p e c t r a of IV. The absorption
of a phthalide grouping at 1751-1776 em -1 and the VC=O band of imidazolidone at 1660-1669 c m -1 are ob-
served in the IIR s p e c t r a of IV. The c h a r a c t e r i s t i c low-intensity bands of the benzene ring appear at 1599-
1608 and 1580-1583 cm -~.

EXPERIME NTAL
1 - B e n z y l - 4 - ( o - c a r b o x y p h e n y l ) - 3 , 5 - d i p h e n y l - 4 - i m i d a z o l i n - 2 - o n e (IIb). A 2-g (5 mmole) sample of
28-dioxo-3a-hydrxy-benzy-38a-dipheny-,2,3a8a-tetrahydro-8H-indeno[2-d]imidazoe (Ib) was
dissolved in 10 ml of concentrated H2SO4, and the mixture was poured over ice after 15 rain. The resulting
white precipitate was removed by filtration, washed thoroughly with cold water, and r e c r y s t a l l i z e d f r o m
ethanol to give 1.1 g (52%) of lib with nap 273 ~ Found: C 77.9; H 5.1; N 6.1%. C29H22N203. Calculated: C
78.0; H 5.0; N 6.3%.
Compounds IIa, C were similarly obtained (Table 1).
1 , 8 - D i o x o - 3 - h y d r o x y - l , 2 - d i h y d r o - 8 H - i m i d a z o [ 4 , 3 - a ] i s o i n d o l e (IIIa). A 0.44-g (2 mmole) sample of
Ia was dissolved in 5 ml of concentrated H2SO4, and the mixture was poured over ice after 30 rain. The
resulting yellow precipitate was removed by filtration, washed with cold water, and r e c r y s t a l l i z e d f r o m
e t h a n o l - d i o x a n e (1 : 1) to give 0.3 g (64%) of IIIa with mp 289 ~ Found: C 59.2; H 3.2; N 13.7%. C10H6N203.
Calculated: C 59.5; H 3.0; N 13.7%. The same compound was obtained in 72% yield by s i m i l a r t r e a t m e n t
of IIa.

TABLE 1. C h a r a c t e r i s t i c s of the Synthesized Compounds

Corn- I Empirical I N, 0,~ !Yield,
pound m R2 R~ mp, ~C formula ~oui~d calc.- %

If
lIa
Ilc H
C6H
H
OCH3
OCH3
OH
159
194
170--171
CITHt4N204
CllHloN204
CloHsN20*
r

11,7
12,6
7,5
90[
12,0
12,7
7,8
51
42
49
61
C6Hs C6Hs 265 C2~I16N203
llle CHs OH 295 CuHsN20~ 13,2 13,0 80
IVd CH~ OCH~ 284---285 Cl~HIoN203 12,3 12,9 72
OH 179--180 CIlHIoN204 11,7 12,0 49
IVf H OCH~ 169--170 CI~HI,N,O, 11,2 11,3 38
C6H6 OCH~ 225-----226 CtTHt4N204 9,1 9,0 35
CsHs OH 269--270 CIsH,~N204 9,2 9,5 34

478
 S p i r o [ 2 - o x o - 5 - h y d r o x y i m i d a z o l i d i n e - 4 , 3 ' - p h t h a l i d e ] (IVa). A 0.44-g (2 m m o l e ) s a m p l e of Ia was dis-
solved in 5 ml of c o n c e n t r a t e d H2SO4,and the m i x t u r e was allowed to stand overnight. The following day
it was poured o v e r ice, and the r e s u l t i n g white p r e c i p i t a t e was r e m o v e d by filtration, washed with c o l d w a t e r ,
and r e c r y s t a l l i z e d f r o m ethanol to give 0.26 g (60%) of IVa with mp 229-230 ~ Found: C 54.4; H 3.8; N
12.5%. C10H~N204. Calculated: C 54.5; H 3.7; N 12.7%.
Compounds IVd-g (Table 1) w e r e s i m i l a r l y obtained f r o m Id-g. Compound IVe was also obtained f r o m
IIIe. A 0.92-g (4 m m o l e ) s a m p l e of IIIe was dissolved in 20 ml of 5% KOH, and the solution was neutralized
a f t e r 1 h with 10% hydrochloric acid. The resulting white c r y s t a l s were r e m o v e d by filtration and r e c r y s -
tallized f r o m ethanol to give 0.41 g (41%)of IVe.
2, 8 - D i o x o - 3 a - h y d r o x y - 1 - m e t h y l - 8 a - m e t h o x y - 1,2,3a, 8a- t e t r a h y d r o - S H - i n d e n o [ 1, 2-d]imidazole (Ie).
A 1.17-g (5 m m o l e ) s a m p l e of 2 , 8 ~ d i o x o - 3 a , 8 a - d i h y d r o x y - l - m e t h y l - l , 2 , 3 a , 8 a - t e t r a h y d r o - S H - i n d e n o [ 1 , 2 - d ]-
imidazole (Id) was dissolved in 15 ml of 5% KOH, and the m i x t u r e was cooled to 5 ~ and t r e a t e d with 0.47 ml
(5 m m o l e ) of dimethyl sulfate with s t i r r i n g . The m i x t u r e was then s t i r r e d f o r 2 h without cooling, and the
r e s u l t i n g white c r y s t a l s w e r e r e m o v e d by filtration. R e c r y s t a l l i z a t i o n f r o m ethanol gives 1.0 g (81%) of Ie
with mp 179 ~. Found: C 72.8; H 4.9; N 11.0%. C12H12N204. Calculated: C 73.1; H 4.9; N 11.3%.
Compounds If, h {Table 1) w e r e s i m i l a r l y obtained f r o m Ig and Ia.

LITERATURE CITED
i. A. K. Aren and D. V. Bite, Khim. G e t e r o t s i k l . Soedin., 329 (1968).
2. D. V. Bite and A. K. Aren, Izv. Akad. Nauk L a i r . SSSR, Set. Khim., 228 (1968).
3. D. V. Bite and A. K. Aren, Khim. G e t e r o t s i k l . Soedin., 1083 (1969).
4. B. l~. A r e n and G. Ya. Vanag, Izv. Akad. Nauk Latv. SSR, Ser. Khim., 579 (1966}.
5. L. Bellamy, I n f r a r e d Spectra of Complex Molecules, Methuen (1958).
6. A. R. K a t r i t z k y (editor), P h y s i c a l Methods in H e t e r o c y c l i c C h e m i s t r y : A C o m p r e h e n s i v e T r e a t i s e ,
A c a d e m i c P r e s s (1963}.

479
 5- FLUORO- 4- ALKYL (ARYL) BARBITURIC A C I D S

I. V. V i g a l o k , Yu. A. F e d o t o v , UDC 547.854.5'221

and L. S. A f o n s k a y a

F l u o r o b a r b i t u r i c a c i d s a r e f o r m e d a s a r e s u l t of the r e a c t i o n of 5 - a l k y l ( a r y l ) b a r b i t u r i c
acid salts with perchloryl fluoride.

W h i l e 5 - c h l o r o - and 5 - b r o m o b a r b i t u r i c a c i d s a r e r e a d i l y f o r m e d by h a l o g e n a t i o n of t h e c o r r e s p o n d -
ing b a r b i t u r a t e s [1], t h e r e is not i n f o r m a t i o n a v a i l a b l e r e g a r d i n g the f l u o r i n a t i o n of b a r b i t u r i c a c i d s . We
have found t h a t p e r c h l o r y l f l u o r i d e r e a d i l y r e a c t s w i t h s a l t s of 5 - m o n o s u b s t i t u t e d b a r b i t u r i c a c i d s (I) to
give 5 - f l u o r o b a r b i t u r t c a c i d s (1I) v i a the s c h e m e
O O
II il
HN/C\N/R" HN~'C'-.N/ R"

o//C'-c~C"o - o~ x c / ~o
I
R'
K+ /\
R' F
! II

I,II a R'=C2H s, R"=H; b R'=i-CaH 7, R"=H; c R'=n-C4H 9, RO=H; d R'=s-C4Ha, R a s H ;

@ R'=i-C5ttI1, R ' = H ; f R'=%Hv R " = H ; g R'=CH2C6H5, R"=H; h R'=C6Hs, R"=H;
i R'~n-C4H 9, R"=CH 3

The n a t u r e of the g r o u p i n g in t h e 5 - p o s i t i o n d o e s not have an a p p r e c i a b l e e f f e c t on the y i e l d s of the

f l u o r o b a r b i t u r a t e s . The s t a r t i n g a c i d s a r e o b t a i n e d f r o m the s a l t s of 5 , 5 - d i s u b s t i t u t e d b a r b i t u r i c a c i d s .
The f l u o r o b a r b i t u r i c a c i d s a r e white c r y s t a l l i n e s u b s t a n c e s t h a t a r e only s l i g h t l y s o l u b l e in c o l d w a t e r
and c h l o r o f o r m and m o d e r a t e l y s o l u b l e in a l c o h o i and a c e t o n e . T h e y r e a d i l y r e a c t with s o d i u m a l k o x i d e s
to g i v e w a t e r - s o l u b l e s a l t s .

F I u o r o b a r b i t u r a t e s II a r e not toxic to w h i t e m i c e w h e n they a r e i n j e c t e d i n t r a p e r i t o n e a l l y a s a q u e o u s

s o l u t i o n s of the s o d i u m s a l t s ; t h e i r LDs0 e x c e e d s 1000 m g / k g . T h e i r d e p r e s s i v e a c t i o n is c o n s i d e r a b l y l e s s
t h a n that of a m o b a r b i t a l .

TABLE I. 5 - F l u o r o b a r b i t u r i c A c i d s (II)
Com- Empirical Found; 0]0 Calc:, %
mp, ~C formula l Yield.%
pound
F N F N

Ila 202* C6HTFN203 11,0 16,2 10,9 16,1 67

lib 215--~16 CvH9FN2Oa 10,0 14,9 10,1 14,9 80
llc 185--187 CsHItFNeOa 9,7 13,8 9,4 13,9 67
IId 177--178 CsHuFN203 9,4 13,8 9,4 13,9 68
lie 213--214 CgHIaFN203 9,4 12,5 8,8 13,0 70
IIf 163--164 CTHTFN2Os 10,2 14,8 10,2 15,0 60
224--225 CuHoFN203 7.8 11,5 8,1 11,9 73
240--242 CloHTFN203 9,2 12,5 8,5 12,6 72
IIi 92--9.5 CgHIaFN203 8,5 12,4 8,8 13,0 62

* A c c o r d i n g to [2], t h i s c o m p o u n d h a s m p 2 0 4 - 2 0 5 ~

S. M. K i r o v K a z a n I n s t i t u t e of C h e m i c a l T e c h n o l o g y . S . V . K u r a s h o v K a z a n State M e d i c a l I n s t i t u t e .
T r a n s l a t e d f r o m K h i m i y a G e t e r o t s i k l i c h e s k i k h S o e d i n e n i i , No. 4, pp. 552-553, A p r i l , 1974. O r i g i n a l a r t i c l e
s u b m i t t e d J u l y 4, 1973.

9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy o f this article is available from the publisher for $15.00.

480
 EXPERIMENTAL
The starting 5-monosubstituted barbituric acids were obtained by condensation of urea or methylurea
with the appropriate monosubstituted malonic esters in butyl alcohol at II0-I15~ in the presence of sodium
butoxide. The salts (I) were obtained from the 5-monosubstituted barbituric acids by the action of KOH or
CH3COOK in alcohol.
5-Butyl-5-fluorobarbituric Acid if[c}. A total of 2 liters (88 mmole) of perchloryl fluoride was passed
into a suspension of 12.5 g (68 mmole) of salt Ic in I00 ml of methanol with vigorous stirring while main-
raining the temperature at no higher than 20 ~ After removal of the methanol, the residue was suspended in
150 ml of water, and the solid material was removed by filtration, washed with water, and dried. Recrys-
tallization from alcohol gave 7.7 g (67~) of acid IIc. UV spectrum (in methanol). ~'max 210 nm (loga 4.0).
The remaining 5-fluorobarbituric acids, which are presented in Table I, were similarly obtained.

LITERATURE CITED
R. Ya Levina and F. K. Velichko, Usp. Khim., 29, 957 (1960).
2. Pennsalt Chemicals Co., British Patent No. 865,321 (1961); Chem. Abstr., 56, 3331 (1962).

481
STUDY OF THE NUCLEOPHILIC SUBSTITUTION REACTIONS
OF 2,4,10-TRIC HLOROPYRIMIDO[5,4-b]QUINOLI NE

N. E . B r i t i k o v a , L. A. Belova, UDC 547.831.4'854.2

a n d A . S. E l i n a

A n u m b e r of pyrimido[5,4-b]quinoline d e r i v a t i v e s w e r e synthesized. It is shown that in the

r e a c t i o n of 2,4,10-trichloropyrimido[5,4-b]quinoline {II) with s t r o n g nucleophilic r e a g e n t s
(OC'--H3 and ~H) both of the halogens of the p y r i m i d i n e ring a r e replaced, while with amines
substitution of the halogens of the p y r i m i d i n e ring p r o c e e d s s u c c e s s i v e l y ; under m o r e s e v e r e
conditions, all three halogen a t o m s of II a r e replaced by amine r e s i d u e s .

We have p r e v i o u s l y d e s c r i b e d the snythesis and p r o p e r t i e s of a n u m b e r of 2,4,10-trioxo and 2,4-dioxo

d e r i v a t i v e s of hexahydro- or, r e s p e c t i v e l y , tetrahydropyrimido[5,4-b]quinolines. In o r d e r to synthesize a
c o m p l e t e l y a r o m a t i z e d pyrimido[5,4-b]quinoline s y s t e m and obtain a n u m b e r of mono-, di-, and t r i s u b s t i -
tuted d e r i v a t i v e s of this heterocycle, which s e e m of i n t e r e s t f o r biological study, we obtained 2 , 4 , 1 0 - t r i -
chloropyrimido[5,4-b]quinoline (II) f r o m 2,4-dioxo-10-chloropyrimido[5,4-b]quinoline (I) by heating it with
PC15 and POC13 and studied its r e a c t i o n s with nucleophilic r e a g e n t s . The r e a c t i o n of II with strong nucelo-
philic r e a g e n t s (CH3ONa or NaSH) p r o c e e d s with r e p l a c e m e n t of two halogens by methoxy or m e r c a p t o
groups; we w e r e unable to obtain the c o r r e s p o n d i n g monomethoxy or m o n o m e r c a p t o d e r i v a t i v e s e v e n when
we used m o l a r ratios of the r e a g e n t s and c a r r i e d out the r e a c t i o n under mild t e m p e r a t u r e conditions. I n a s -
much as the halogens in the 4- and 2-positions in II should have higher r e a c t i v i t i e s than the halogen in the
10-position, the s t r u c t u r e s of the dimethoxy and d i m e r c a p t o d e r i v a t i v e s obtained p r o b a b l y c o r r e s p o n d to
III and IV; this was c o n f i r m e d by hydrolysis of HI to the s t a r t i n g 2,4-dioxo d e r i v a t i v e of I.
The purification of IV p r e s e n t e d c o n s i d e r a b l e difficulty, and it was t h e r e f o r e identified as the S - m e t h -
ylated derivative W).
The a p p r e c i a b l e difference in the r e a c t i v i t i e s of the halogens in the 2- and 4-positions was m a n i f e s t e d
in the r e a c t i o n s of chloro derivative II with w e a k e r nucleophilic r e a g e n t s . On r e a c t i o n with concentrated
a m m o n i u m hydroxide, II underwent r e p l a c e m e n t of only one chlorine a t o m by an amino group; the reactions
of II with p r i m a r y or s e c o n d a r y amines p r o c e e d s i m i l a r l y . In analogy with halogen d e r i v a t i v e s of p y r i m i d i n e
and condensed p y r i m i d i n e s y s t e m s [2-4], for which the r e a c t i v i t y o r d e r is 4-CI > 2-C1, we suppose that we
obtained a n u m b e r of 4-amino d e r i v a t i v e s of pyrimido[5,4-b]quinoline (Via-f).
In the r e a c t i o n of II with an e x c e s s of the c o r r e s p o n d i n g amine we o b s e r v e d r e p l a c e m e n t of both chlo-
rine a t o m s (VIIa, b). Monoamino d e r i v a t i v e s Via r e a c t with a m i n e s to give pyrimido[5,4-b]quinolines (VIIIa-
c) that a r e substituted in the 4- and 2-positions by different amine r e s i d u e s . In VIIa, a m i n o l y s i s of the
chlorine in the 10-position is realized only under m o r e s e v e r e conditions. Thus, IX was obtained by p r o -
longed refluxing of VIIa o r II with e x c e s s piperidine in d i m e t h y l f o r m a m i d e (DMF).
A c e r t a i n amount of antibacterial activity was detected in v i t r o in the c a s e of VIc and VIIb.

EXPERIMENTAL
2,4,10-Trichloropyrimido[5,4-b]quinoline (II). A m i x t u r e of 6 g (24 m m o l e ) of I, 20 ml of phosphorous
oxychloride, and 17.4 g (83 mmole) of phosphorus pentachloride was refluxed f o r 8 h, a f t e r which the POC13

S. Ordzhonikidze All-Union S c i e n t i f i c - R e s e a r c h P h a r m a c e u t i c a l - C h e m i s t r y Institute, Moscow. T r a n s -

lated f r o m Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 554-557, April, 1974. Original article sub-
mitted May 21, 1973.

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy o f this article is available from the publisher for $15.00.

482
 0 OCH3 R1

Cl C1 Cl
I III VIII a - c
~Oc/
~ CH+ONalCHaOH 1
n t

CI CI CI
vii a-b It Vl a-f

jo.<,";o
/,:, S ", SCH+
+++~+ ~+,,"v,~ !i t

i
Cl El
IV V

IX Via R I ~ N ~ ; b RI=N(C2H3)2; c Rt=NII(CH~)2-~;

d R~=NH(CH2)2N(C2Hs)2; C Rt=NH2; f RI=NH(CIt2)2CI;
VII a R=~/"~;

was removed by vacuum distillation. Ice was added to the residue, and the mixture was filtered after 1-2 h.
The filtrate was e x t r a c t e d with c h l o r o f o r m , and the c h l o r o f o r m was evaporated to give 4.6 g (66.5%) of II
with mp 226 ~ (from ethyl acetate). Found: C 46.6; H 1.6; C1 37.1; N 14.5%. CllH4N3C13. Calculated: C 46.4;
H 1.4; C1 37.4; N 14.8%.

2,4-Dimethoxy-10-chloropyrimido[5,4-b]qutnoline 0II). A 0.6-g (2 mmole) sample of II was added

to a solution of sodium methoxide, obtained f r o m 0.13 g (5.6 mmole) of Na and 40 ml of CH3OH , and the
reaction mixture was s t i r r e d at 20-25 ~ for 4 h. The precipitate was then r e m o v e d by filtration to give 0.4g
(66.5%) of III with mp 240 ~ (from alcohol). Found: C 56.3; H 3.8; C1 12.7; N 15.3%. Ct3H10N302CI. Calcu-
lated: C 56.6; H 3.7; C1 12.9; N 15.2%.

2,4-Dimethylthio-10-chloropyrimido[5,4-b]quinoline (V). A 1.2-g (4.2 mmole) sample of II in 60 ml

of c h l o r o f o r m was added gradually with s t i r r i n g to 6 ml (11 mmole) of 10% aqueous NaSH solution. After
2 h, the c h l o r o f o r m was decanted, and the residue was dissolved in 500 ml of water. The solution was
acidified to pH 4-5 with acetic acid, and the mixture was filtered to give 1.2 g (4.3 mmole) of 2 , 4 - d i m e r -
c a p t o - 1 0 - c h l o r o - l , 2 , 3 , 4 - t e t r a h y d r o p y r i m i d o [ 5 , 4 - b ] q u i n o l t n e (IV), to which a solution of 0.5 g (9 mmole) of
KOH in 60 ml of w a t e r was added. A 1.4-ml (15 mmole) sample of dimethyl sulfate was added gradually
at 20-250 to the resulting solution, and the mixture was s t i r r e d at 20-25 ~ for 2.5 h. Workup of the mixture
gave 1 g (61.8%) of V with mp 187 ~ (from acetone). Found: C 50.7; H 3.5; C1 11.6; N 13.3; S 20.8%.
C13H10N3C1S2. Calculated: C 50.7; H 3.3; C1 11.5; N 13.6; S 20.8%.
4 - P i p e r i d i n o - 2 , 1 0 - d i c h l o r o p y r i m i d o [ 5 , 4 - b ] q u i n o l i n e (Via). A 0.2-g (2.3 mmole) sample of piperidine
was added to 0.3 g (1 mmole) of II in 10 ml of alcohol, and the mixture was s t i r r e d at 20-25 ~ for 4 h. It was
then filtered to give 0.3 g (87.0%) of Via with mp 156 ~ (from alcohol). Found: C 57.9; H 4.2; C1 21.0; N
16.9%. C16H14ClzN4. Calculated: C 57.7; H 4.2; C1 21.3; N 16.8%.
Compounds Vlb-d were s i m i l a r l y obtained.

Compound VIb (65.7~0) had mp 141 ~ (from alcohol). Found: C 56.2;H4.3; C121,7; N17.3%. CisHI4C12N4.
Calculated: C 56.1; H 4.4; C1 22.1; N 17.4%. Compound VIc (60%) had mp 183 ~ (from alcohol). Found: C
59.8; H 5.0; C1 18.7; N 14.5; H20 2.1%. CIHlsN4C12-0.5H20. Calculated: C 59.7; H 5.0; C1 18.6; N 14.6;
H20 2.4%. Compound VId (52.6%) had mp 160 ~ (from alcohol). Found: C 55.8; H 5.0; C1 19.1; N 19.0%.
C17H19NsC12. Calculated: C 56.0; H 5.2; C1 19.5; N 19.2%.
4-Amino-2,10-dichloropyrimido[5,4-b]quinoline (Vie). A 0.2-g (0.7 mmole) sample of II was allowed
to stand in 10 ml of ammonium hydroxide at 20-25 ~ for 4 days, after which the precipitate was removed by

483
f i l t r a t i o n to give 0.1 g (55.0%) of Vie with mp 305-308 ~ (from aqueous DMF). Found: C 49.4; H 2.1; C1 26.5;
N 21.0~. C10H6NtC12. Calculated: C 49.8; H 2.3; C1 26.8; N 21.1~0.
4-(fl-Chloroethylamino)-2,10-dicMoropyrimido[5,4-b]quinoline (VIf). An aqueous solution of 0.23 g
(2.7 mmole) of NaHCO 3 in 5 ml of H20 was added gradually with s t i r r i n g to a m i x t u r e of 0.3 g (1 mmole)
of II and 0.15 g (1.3 m m o l e ) of/~-chloroethylamine hydrochloride in 15 ml of c h l o r o f o r m . After 1 h, the
c h l o r o f o r m was s e p a r a t e d and evaporated, and the residue was t r e a t e d with w a t e r . The aqueous m i x t u r e
was filtered to give 0.1 g (28.6%) of VIf with mp 170 ~ (dec., f r o m ethyl acetate). Found: C 47.6; H 2.9; C1
32.3;N17.5%. CIsH9NtC13. Calculated: C 47.6; H 2.7; C1 32.2; N 17.1%.

2,4-Dipiperidino-10-chloropyrimido[5,4-b]quinoline (VIIa). A m i x t u r e of 0.6 g (2.1 mmole) of II, 20

ml of alcohol, and 1.2 g (14 mmole) of piperidine was refluxed f o r 2 h, a f t e r which the p r e c i p i t a t e was r e -
moved by filtration to give 0.5 g (60.6%) of VIIa with mp 155 ~ (from alcohol). Found: C 66.9; H 6.3; C1 9.1;
N 17.7%. C22H24NsC1. Calculated: C 66.8; H 6.1; C1 9.0; N 17.8~o.
2,4-Dimorpholino-10-chloropyrimido[5,4-b]quinoline (VIIb). A m i x t u r e of 1 g (3.5 m m o l e ) of II, 25
ml of DMF, and 3.3 g (38 mmole) of morpholine was heated at 140 ~ for 6 h. It was then cooled, and the c r y s -
talline p r e c i p i t a t e was r e m o v e d by filtration to give 0.6 g (44.5%) of VIIb with mp 198 ~ (from aqueous DMF).
Found: C 59.0; H 5.0; C1 8.8; N 17.9%. CtgH20N502C1. Calculated: C 59.1; H 5.2; C1 9.2; N 18.1~.
2 - D i e t h y l a m i n o - 4 - p i p e r i d i n o - 1 0 - e h l o r o p y r i m i d o [ 5 , 4 - b ] q u i n o l i n e (VIIIa). A 0.6-g (1.8 mmole) s a m p l e
of Via was allowed to stand in 10 ml of diethylamine at 20-25 ~ for 48 h, a f t e r which the diethylamine was
vacuum e v a p o r a t e d , and the residue was t r i t u r a t e d with acetone. The m i x t u r e was filtered to give 0.3 g
(45%) of VIIIa with mp 108 ~ (from alcohol). Found: C 65.4; H 6.6; C1 9.4; N 18.9~0. C20H24NsC1. Calculated:
C 65.0; H 6.5; C1 9.6; N 18.9%.
2 - P i p e r i d i n o - 4 - c y e l o h e x e n y l e t h y l a m i n o - 1 0 - c h l o r o p y r i m i d o [5~4-b]quinoline (VIIIb). A m i x t u r e of 1 g
(2.7 mmole) of VIc and 0.46 g (5.4 mmole) of piperidine in 35 ml of alcohol was s t i r r e d at 20-25 ~ for 5 h,
a f t e r which the p r e c i p i t a t e was r e m o v e d by filtration to give 0.5 g (44.3%) of VIIIb with mp 140 ~ (from a l -
cohol). Found: C 68.2; H 6.6; C1 8.0; N 16.470. C24H28NsC1. Calculated: C 68.3; H 6.6; C1 8.4; N 16.6~o.
2-Diethanolamino-4-piperidino-10~chloropyrimido[5,4-b]quinoline (VIIIc). A m i x t u r e of 0.3 g (0.9
mmole) of Via and 0.2 g (1.8 m m o l e ) of diethanolamine was heated at 100-110 ~ for 3 h. The r e a c t i o n m i x -
t u r e was t r e a t e d s e v e r a l t i m e s with water, and the w a t e r was decanted. The solid m a t e r i a l was t r i t u r a t e d
with acetone, and the m i x t u r e was filtered to give 0.2 g (55.0%) of VIIIc with mp 187 ~ (from alcohol). Found:
C 60.2; H 5.9; C1 8.6~. C20H2402NsC1. Calculated: C 59.8; H 6.0; C1 8.8%.
2~4~102Tripiperidinopyrimido[5,4-b]quinoline (IX). A 0.3~g (0.76 mmole) s a m p l e of VIIa was refluxed
with 0.34 g (4 mmole) of piperidine in 10 ml of DMF f o r 3 h, and the p r e c i p i t a t e was r e m o v e d by filtration
to give 0.2 g (61%) of IX with mp 118 ~ (from alcohol). Found: C 72.4; H 7.9%. C26H34N6. Calculated: C 72.5;
H 7.9%. Compound IX was s i m i l a r l y obtained in 55% yield f r o m 1.8 m m o l e of II and 18 m m o l e ofpiperidine.

LITERATURE CITED

I. N. E. Britikova, L. A. Belova, O. Yu. Magidson, and A. S. Elina, Khim. Geterotsikl. Soedin., 131 (1974).
2. H. C. Koppel, R. H. Springer, R. K. Robins, and C. C. Cheng, J. Org. Chem., 2"7, 181 (1962).
3. G. D. Dares, F. Baiocehi, R. K. Robins, and C. C. Cheng, J. Org. Chem., 26, 2775 (1961).
4. E. M. Levine and T. I. Bardos, J. Heterocycl. Chem., 9, 91 (1972).

484
 HETEROCYCLIC ANALOGS OF PLEIADIENE
XII.* REDUCTION OF THE C = N BOND IN PERIMIDINES AND PERIMIDINIUM SALTS.
SYNTHESIS AND PROPERTIES OF SOME 2,3-DIHYDRO DERIVATIVES
OF PERIMIDINE AND ACEPERIMIDINE

V. I. Sokolov, A. F. Pozharskit, UDC 547.856.7.07 : 542.942.3.4.6

I. S. Kashparov, A. G. Ivanov,
and B. I. Ardashev~

2,3-Dihydro d e r i v a t i v e s of p e r i m i d i n e w e r e obtained in high yields by the action o f l i t h i u m

a l u m i n u m hydride o r sodium b o r o h y d r i d e on p e r i m i d i n i u m s a l t s and 1 , 3 - d i a l k y l p e r i m i d o n e s .

The reduction of nitrogenous h e t e r o a r o m a t i c compounds, p a r t i c u l a r l y t h e i r q u a t e r n a r y salts, with

c o m p l e x m e t a l hydrides is a good method for the p r e p a r a t i o n of t h e i r 2,3-dihydro d e r i v a t i v e s [2, 3]. The
p r e s e n t p a p e r is devoted to the utilization of this r e a c t i o n for the s y n t h e s i s of little studied 2,3-dihydro-
perimtdines.

2 , 3 - D i h y d r o p e r i m i d i n e s that do not contain substituents attached to the nitrogen a t o m s can be obtained

as a r e s u l t of the r e a c t i o n of 1,8-diaminonaphthalene with v a r i o u s aldehydes (for e x a m p l e , see [4, 5]).
It is disadvantageous to obtain N-substituted 2 , 3 - d i h y d r o p e r i m i d i n e s of the III and IV type in this m a n -
n e r b e c a u s e of the r e l a t i v e l y low a c c e s s i b i l i t y of N-substituted 1,8-diaminonaphthalenes. Up to now three
compounds of this group have been d e s c r i b e d : 1 - ( 2 - h y d r o x y e t h y l ) - 2 , 3 - d i h y d r o p e r i m i d i n e , 1,3-dimethyl-
2,3-dihydroperimidine (Ilia), and 1 , 3 - d i m e t h y l - 2 , 3 - d i h y d r o a c e p e r i m i d i n e (fVa). The f i r s t of these was ob-
tained by reduction of ethyl 1 - p e r i m i d i n y l a c e t i c acid with lithium a l u m i n i u m hydride, while IIIa and IVa
w e r e obtained as a r e s u l t of the action of aqueous alkali on the c o r r e s p o n d i n g p e r i m i d i n i u m s a l t s (I and II)
[6].
We have c o n f i r m e d the data in [4] in r e g a r d to the fact that the C = N bond in 1 - s u b s t i t u t e d p e r i m i d i n e s
is not reduced by sodium b o r o h y d r i d e but is reduced by lithium aluminum hydride to m o n o - N - s u b s t i t u t e d
p e r t m i d i n e s of the XI type.

Q u a t e r n a r y p e r i m i d i n i u m (I) and a c e p e r i m i d i n i u m (II) salts a r e readily hydrogenated in p r a c t i c a l l y

quantitative yields by lithium a l u m i n u m hydride in e t h e r and sodium borohydride in w a t e r .
N,N-Disubstituted 2 , 3 - d i h y d r o p e r i m i d i n e s (HI and IV) a r e also readily f o r m e d in the reduction of
p e r i m i d o n e s V o r VII with lithium a l u m i n u m hydride.
The fl and 3/bands with m a x i m a at 335 and 235 nm that a r e p e c u l i a r to p e r i m i d i n e s a r e retained in
the UV s p e c t r a of hydrogenated p e r i m i d i n e s III and W, but the a band at 400 rim, which is c o n s i d e r e d to be
r e s p o n s i b l e f o r the yellow c o l o r of p e r i m i d i n e s [7], vanishes. The d i s a p p e a r a n c e of this band f o r 2,3-di-
h y d r o p e r i m i d i n e s is in a g r e e m e n t with its i n t e r p r e t a t i o n b a s e d on the r e s u l t s of MO calculations for the
r-rr * e l e c t r o n t r a n s i t i o n f r o m the naphthalene p o r t i o n of the molecule to the h e t e r o r i n g [7, 8].

* See [1] f o r c o m m u n i c a t i o n XI.

tDeceased,

N o v o e h e r k a s s k Polytechnic Institute. Rostov State University, R o s t o v - o n - D o n . T r a n s l a t e d f r o m

Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 4, pp. 558-561, April, 1974. Original a r t i c l e submitted June
21, 1973.

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, ~ Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, withou ; written permission o f the publisher. A copy o f this article is available from the publisher for $15.00_

485
 It is known that 1,8-bis (dimethylamino)naphthalene is one of the s t r o n g e s t neutra! b a s e s {pKa 12.34)
[9] and is advertised by chemical f i r m s as "the proton sponge." Despite the close s t r u c t u r a l s i m i l a r i t y

v-v,,

1 \\ //-'~\\ ~ III a - c

II a , b VIII-X

a R~H; b R=CHa; C R=C6H5; V, VIII X=O; VI,IX X=S; VII, X X=Se

\CH a :\CH a
Xl
between 1,8-bis(dimethylamino)naphthalene and the 1,3-dimethyl-2,3-dihydroperimidines that we obtained,
the basicity of the l a t t e r is sharply depressed, and the pK a in 50% alcohol is ~3.9. This attests to the fact
that, in c o n t r a s t to noncoplanar (for s t e r i c reasons) 1,8-bis (dimethylamino)naphthalene, the nitrogen atoms
in III and IV are to a considerable degree coplanar with the naphthalene ring due to the binding effect of the
methylene bridge. As a result, conjugation of the unshared e l e c t r o n p a i r s of the two nitrogen atoms with
the aromatic r s y s t e m is reinforced, and this is accompanied by a d e c r e a s e in the basicity.
As a consequence of their lowered basicities 2,3-dihydroperimidines f o r m unstable hydrolyzable
h y d r o c h l o r i d e s . However, in c o n t r a s t to the s i m i l a r l y constructed benzimidazolines [3], they can be con-
verted to methiodides XII by the action of methyl iodide in DMF at 100~
In c o n t r a s t to benzimidazoles [3], 2,3-dihydroperimidines III and IV (and, to a somewhat l e s s e r de-
gree, XI) are stable in air and do not change on prolonged storage and on heating in CC14. In addition, they
are readily oxidized by iodine to starting perimidinium salts I and II; on heating with oxygen, sulfur, and
selenium they f o r m s t r u c t u r e s of the V - X type.

EXPERIME NTA L
All of the starting compounds were obtained by the methods in [6, 10, 11].
The ionization constants were m e a s u r e d by potentiometric titration of 0.01 N solutions of the c o m -
pounds in 50% aqueous alcohol with a 0.01 N HC1 solution with an L P U - 0 1 potentiometer at 20 ~-1~ The tR
s p e c t r a were r e c o r d e d with a UR-20 s p e c t r o m e t e r . The PMR s p e c t r u m was obtained with a PE-2305 s p e c -
t r o m e t e r (60 MHz) with hexamethyldisiloxane (HMDS) as the internal standard. The UV s p e c t r a of 10 -3 to
10-4 M solutions of the compounds in methanol were r e c o r d e d with an SF-4A s p e c t r o p h o t o m e t e r .
1-Methyl-2,3-dihydroperimidine (XI). A 2.7-g (0.015 mole) sample of 1-methylperimidine was added
to a solution of 2.3 g (0.06 mole) of LiA1H4 in 75 ml of absolute ether, and the mixture was s t i r r e d and r e -
fluxed for 1 h. The c o l o r l e s s solution was then cooled, 10 ml of w a t e r was added, and the mixture was
s t i r r e d for another 5-10 rain. The e t h e r l a y e r was separated, the ether was evaporated, and the residual
viscous oil was vacuum dried over P20~ and vacuum distilled to give 1.9 g (70%) of a product with bp 170 ~
(2 ram). VNH 3370 c m -1 (broad, strong; m i n e r a l oil), 3410 em -1 (broad, strong; chloroform). PMR s p e c -
t r u m (12% solution in CDCla): 5 2.78 (N-CHa, singlet), 4.05 (N-CH2, singlet), 6.25-7.40 (aromatic, c o m -
plex multiplet). UV spectrum, Xmax, nm (log e): 232 (4.66), 331 (4.08). Found: C 78.2; H 6.3; N 15.4%.
C12H12N2. Calculated: C 78.2; H 6.5; N 15.2~. The picrate was obtained as c r i m s o n c r y s t a l s with mp 230 ~
(from alcohol). Found: N 17.2%. C12H12N2"C6H3N307. Calculated: N 17.0%.
General Method for the P r e p a r a t i o n of 1,3-Dimethyl-2,3-dihydro Derivatives of Perimidine and
Aceperimidine. A) A 0.01-mole sample of the appropriate methiodide (I or II) was added with s t i r r i n g to
a solution of 1.1 g (0.03 mole) of LiA1H4 in 50 ml of absolute ether. In the case of the perimidine d e r i v a -
tives, the yellow c o l o r of the solution vanished instantaneously. The mixture was refluxed and s t i r r e d for

486
30 min, a f t e r which it was cooled to r o o m t e m p e r a t u r e and carefully decomposed with 5 ml of water. The
e t h e r l a y e r was separated, and the w a t e r l a y e r was extracted twice with 40-ml portions of ether. The e t h e r
was e v a p o r a t e d f r o m the combined e t h e r e x t r a c t s , and the c r y s t a l l i n e residue was dried at 50 ~ and c r y s -
tallized f r o m alcohol. The yields were close to quantitative. The R f values of III and IV were ~0.85 (A1203,
chloroform).
B) A 1 0 - m m o l e sample of NaBH4 was added with s t i r r i n g at 30 ~ in the c o u r s e of 10 rain to a solution
of 5 m m o l e of salt I o r II in 150 ml of water, after which the mixture was s t i r r e d for another 30 rain. The
precipitated dihydro derivative was removed by filtration and c r y s t a l l i z e d . The yields were close to quan-
titative.
C) A 0.01-mole sample of 1,3-dimethylperimidone o r 1,3-dimethylaceperimidone was added to a s o l u -
tion of 0.03 mole of LiA1H4 in 50 ml of absolute ether, and the m i x t u r e was refluxed with s t i r r i n g for 1.5 h.
The 2 , 3 - d i h y d r o p e r i m i d i n e s were isolated as in method A. The yields were close to quantitative. Com-
pound IIIa had mp 150 ~ (from alcohol) [6] and pK a 3.77. UV spectrum, 2`max, nm (log e): 233 (4.64), 330
(4.01).
Compound IVa had mp 152-153 ~ (from alcohol) [6] and pK a 3.89. UV spectrum, 2`max, nm {log ~): 232
(4.62), 338 (4.01).
Methods A and B were used to obtain 1 , 2 , 3 - t r i m e t h y l - 2 , 3 - d i h y d r o p e r i m i d i n e (IIIb) imp 125-126 ~ pKa
3.86. UV spectrum, 2`max, nm (log e): 234 (4.68), 335 (4.12). Found: C 79.3; H 7.8; N 12.7%. C14HlsN2.
Calculated: C 79.2; H 7.6; N 12.7%]; 1 , 3 - d i m e t h y l - 2 - p h e n y l - 2 , 3 - d i h y d r o p e r i m i d i n e (IIIc) imp 176-177 ~
pK a 3.75. UV s p e c t r u m , 2,max, nm (log e): 236 (4.63), 350 (4.19). Found: C 83.2; H 6.8; N 10.1%. ClsH18N2.
Calculated: C 83.2; H 6.6; N 10.2%] and 1 , 2 , 3 - t r i m e t h y l - 2 , 3 - d i h y d r o a c e p e r i m i d i n e (IVb) imp 146-147 ~
Found: C 80.5; H 7.5; N 12.0%. CTH~sN2. Calculated: C 80.6; H 7.6; N 11.8%; pK a 3.96. UV spectrum,
2 t mxa, nm (log ~): 234 (4.68), 335 (4.12)].
Methiodide. A 6.4-g (0.045 mole) sample of methyl iodide was added carefully at 100 ~ to a solution
of 3 g (0.015 mole) of IIIa in 5 ml of DMF, and the mixture was held at 100 ~ for 2 h. It was then cooled,
25 ml of e t h e r was added, and the c o l o r l e s s c r y s t a l s of methiod[de XII with mp 160-161 ~ (from a l c o h o l -
ether) were r e m o v e d by filtration. The yield was 4.1 g (80%). Found: I 36.9; N 8.2%. C14H17N2. Calcu-
lated: I 37.3; N 8.2%.

Oxidation of 1 , 3 - D i m e t h y l - 2 , 3 - d i h y d r o p e r i m i d i n e {IIIa). A) A solution of 0.2 g (1 mmole) of IIIa in

10 ml of alcohol was mixed with a solution of 0.26 g (1 mmole) of iodine in 10 ml of ether, and the mixture
was refluxed f o r 20 rain. The solvent was evaporated, and the residual methiodide (Ia) was c r y s t a l l i z e d
f r o m alcohol to give 0.29 g (90%) of a product with mp 269-270 ~ (from alcohol) [6].

B) A 1-g (5 mmole) sample of dihydroperimidine IIIa was heated in a s t r e a m of oxygen at 150 ~ for
30 rain. The melt was refluxed with 10 ml of c h l o r o f o r m , after which the mixture was filtered, and the
filtrate was p a s s e d through a column containing aluminum oxide (elution with benzene). The yield of p e r -
imidone V with mp 209 ~ (from alcohol) [6] was 0.86 g (80%).

The oxidation of IVa was c a r r i e d out s i m i l a r l y to give Xa with mp 212-213 ~ (from acetic acid) [6] in
78% yield.

Reaction of IIIa and IVa with Sulfur. A mixture of 1.5 mmole of perimidone IIIa or IVa and 0.1 g (3
mmole) of finely ground powdered rhombic sulfur was held at 130 ~ for 1 h. The melt was then dissolved
in 10 ml of c h l o r o f o r m , and the solution was p a s s e d through a column containing aluminum oxide (elution
with c h l o r o f o r m ) to give VI with mp 189-190 ~ (from alcohol) in 90% yield. UC=S 1100 c m -1 (chloroform).
Found: C 68.5; H 5.5; N 12.0%. C13H12N2S. Calculated: C 68.3; H 5.3; N 12.3%. The yield of thione VI
with mp 129-130 ~ (from alcohol) was 90%. Found: C 71.0; H 5.1; N 12.2%. C15H14N2S. Calculated: C 71.2;
H 5.1; N 12.6%.

Reaction of P e r i m i d i n e s IIIa and W a with Selenium. A mixture of 3 mmole of IIIa or IVa with 0.8 g
(10 mmole) of powdered selenium was heated at 160 ~ for 1.5 h, after which the t e m p e r a t u r e was raised to
200 ~ and the mixture was cooled to r o o m t e m p e r a t u r e . The d a r k - r e d melt was dissolved in 10 ml of chlo-
r o f o r m , and the solution was p a s s e d through a column containing A1203 (elution by dhloroform) to give the
selenoxo derivative with mp 120-121 ~ (from heptane) in 90% yield. Found: C 56.7; H 4.4; N 10.2%.
C13H12N2Se. Calculated: C 56.6; H 4.4; N 10.2%. The yield of X with mp 116-117 ~ (from heptane) was 89%.
Found: C 59.5; H 4.3%. C15H14N2Se. Calculated: C 59.8; H 4.7%.

487
 LITERATURE CITED
1. A . F . Pozharskii, L. P. Pershina, I. S. Kashparov, and A. A. Konstantinchenko, Khim. Geterotsikl.
Soedin., 418 (1974).
2. R . E . Lyle and P. S. Anderson, Adv. Heterocycl. Chem., 6, 45 (1966).
3. A . V . El'tsov, Author's Abstract of Doctoral Dissertation [in Russian], LTI ira. Lensoveta, Leningrad
(1967).
4. V. Paragamian, M. B. Baker, B. M. Pima, and I. Real, J. Heterocycl. Chem., 5, 591 (1968).
5. V. Ya. Zhitnikov and S. I. B u r m i s t r o v , Izv. Vuzov, Set. Khim., 1_22, 1069 (1969).
6. A . F . Pozharskii and I. S. Kashparov, Khim. Geterotsikl. Soedin., 860 (1972).
7. A . F . Pozharskii, I. S. Kashparov, P. J. Holls, and V. G. Zaletov, Khim. Geterotsikl. Soedin., 543
(1971).
8. V . I . Minkin and B. Ya. Simkin, Khim. Geterotsikl. Soedin., 678 (1971).
9. R . W . Alder, P. S. Bovman, W. R. S. Steele, and D. R. Winterman, Chem. Commun., 723 (1968).
10. A . F . Pozharskii and I. S. Kashparov, Khim. Geterotsikl. Soedin., 111 (1970).
11. V . I . Sokolov, B. I. Ardashev, I. S. Kashparov, and A. F. Pozharskii, Khim. Geterotsikl. Soedin., 849
(1973).

488
SYNTHESIS OF TRIAZOLONES AND C-AMINOTRIAZOLES
BY T H E R M A L CONDENSATION OF CARBAMIDOAMIDRAZONES

G. S. G o l ' d i n , V . G. Poddubnyi, UDC 547.792.5.07:542.954

a n d E . S. S m i r n o v a

E i t h e r t r i a z o l o n e s o r C - a m i n o t r i a z o l e s - o r both - are f o r m e d in the thermal condensation

of c a r b a m i d o a m i d r a z o n e s , depending on their s t r u c t u r e .

We have p r e v i o u s l y r e p o r t e d the synthesis of carbamidoimino e s t e r s and e a r b a m i d o a m i d r a z o n e s [1, 2].

The p r e s e n t p a p e r is devoted to the study of some t r a n s f o r m a t i o n s of c a r b a m i d o a m i d r a z o n e s that lead to
the f o r m a t i o n of t r i a z o l e and triazolone derivatives.
The starting c a r b a m i d o a m i d r a z o n e s (I-VI, Table 1) were synthesized by the r e a c t i o n of c a r b a m i d o -
imino e s t e r s with hydrazine, methylhydrazine, and phenylhydrazine. Heat t r e a t m e n t of the c a r b a m i d o -
a m i d r a z o n e s leads to i n t r a m o l e c u l a r condensation which only give, in a n u m b e r of cases, triazole deriva-
tives. Thus, when N " - p h e n y l c a r b a m i d o - N ' - m e t h y l a c e t a m i d r a z o n e (III) is heated, it c y c l i z e s with splitting
out of w a t e r to give 1 , 5 - d i m e t h y l - 3 - a n i l i n o - l , 2 , 4 - t r i a z o l e (VIII). Similar condensation on heat treatment
of 1,6-bis ( N ' - m e t h y l a c e t a m i d r a z o n o - N " - c a r b a m i d o ) h e x a n e (V) gives N, N ' - b i s (1, 5-dimethyl- 1, 2 , 4 - t r i a z o l -
3-yl)hexamethylenediamine (X), while N " - f l - n a p h t h y l c a r b a m i d o - N - p h e n y l a c e t a m i d r a z o n e (IV)gives 1-phe-
n y l - 3 - m e t h y l - 5 - f i - n a p h t h y l a m i n o - 1,2,4-triazole (IX).
O
//N--C--NHC6H-
CH3__c~/N~,c__NH C6H5 ~ CH3__C. a CH3__c//N\c~ O
\ // -a20 \NHNH 2 -NH2C6H5 \ /
HN--N HN--NH
VII I XI

The i n t r a m o l e e u l a r cyclization of N " - p h e n y l c a r b a m i d o a c e t a m i d r a z o n e (I) p r o c e e d s in two directions

to give 3 - m e t h y l - l , 2 , 4 - t r i a z o l - 5 - o n e (XI) and 3 - m e t h y l - 5 - a n i l i n o - l , 2 , 4 - t r i a z o l e (VII). In both cases, the
reaction p r o c e e d s through a step involving the f o r m a t i o n of an intermediate with the following s t r u c t u r e :
O
i
~N~C--NHR,,
R-(:" I
\N/NHR"'
r

Depending on the c h a r a c t e r of the substituents attached to the nitrogen atoms, e i t h e r water o r aniline
splits out to give, respectively, a triazole o r a triazolone.
The f o r m a t i o n of only triazolone derivatives is observed in the thermal condensation of some c a r b -
a m i d o a m i d r a z o n e s . Thus, when we heated a m i d r a z o n e II we were unable to isolate a t r i a z o l e derivative
but obtained 1 - p h e n y l - 3 - m e t h y l - l , 2 , 4 - t r i a z o l - 3 - o n e (XII) in 70% yield. The s i m i l a r cyclization of 1,4-
bis ( N " - p h e n y l c a r b a m i d o - N - p h e n y l a m i d r a z o n e ) b u t a n e (VI) gives 1,4-bis ( 1 - p h e n y l - 5 - h y d r o x y - l , 2 , 4 - t r i a z o l -
3-yl)butane (XIII).

The s t r u c t u r e and composition of the compounds obtained in this study are confirmed by the results
of e l e m e n t a r y anal3~sis and the IR s p e c t r a . The s p e c t r a of C - a m i n o t r i a z o l e s VII-X contain a b s o r p t i o n b a n d s
of an NH bond at 3310 c m -1 and of a C =N bond at 1610-1660 c m -1, but C = 0 vibrations are absent. The IR
s p e c t r a of triazolones XI-XIII contain absorption bands of the stretching vibrations of NH groups (3050-
3200 cm-1), C = 0 (1708-1740 cm-1), and C =N groups (1600-1610 c m - I ) .
T r a n s l a t e d f r o m Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 562-564, April, 1974. Original
article submitted September 25, 1973.

9 19 75 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

489
 jz~NCONHR'
"TABLE 1. Carbamidoamidrazones ~--c~.~R,,Nn~,,,
Corn - mp, ~C Empirical Found, qo Calc., % I~-
pound R' R" . (from formula
R'" aloo- I
hol) I
I* cHa C6Hs H H 172 CgH~2N40 56,36,628,856,16,329,2 88
II1". CHa C6Hs I H 6H5 148 C15Hm,N40 67,8] 6,1 20,3 67,3 6,012'0,81 63
I11 96
IVv cHaCHa cC:o~7. CHHa C6t{~ 190 CIoH14N40 58,0 t 6,5 27,1 58,3 6,8 27,2 70
C19HIs,N40 71,7] 5,5 17,8 71,8 5,7 ] 17,61 75
130 C14H~oN802 49,1 8,4 32,3 49,4 8,8 32,8 82
VI 140 Ca2Ha4N802 68,5 6,4 19,9 68,1 6,1 19,9 84
* W i t h m p 172 ~ [1].
? W i t h m p 147-148 ~ [1].

T A B L E 2. C - A m i n o t r i a z o l e s and T r i a z o l o n e s
rap; ~ Found, % - Calc.. %
Gore - (from Empirical Yield, ~~
pound alcohol) mrmula C H ], N C H N

VII 212 CgH,oN4 62,2 5,7 31,2 62,1 5,7 32,2 35

VIII 120 CloHI~N4 63,4 6,5 29,7 63,8 6,4 29,7 70
IX 280 CI~H,r 76,2 5,3 18,3 76,2 5,3 18,7 60
X 164 C,4H~N8 54,9 8,3 36,2 54,5 8,5 36,6 60
XI* 223 %HsNaO 36,4 4,9 41,6 36,4 5,1 42,4 50
XlI I" 152 CgHQNaO 61,8 5,1 24,0 61,8 5,2 24,9 70
XlII 270 C2oH2oN~02 63,5 5,3 22,7 63,9 5,3 22,8 70
* W i t h nap 243 ~ [4].
? W i t h nap 163-164 ~ [5].

EXPERIME NTAL
The IR s p e c t r a of K B r p e l l e t s of the c o m p o u n d s w e r e r e c o r d e d with a U R - 1 0 s p e c t r o m e t e r .
C a r b a m i d o a m i d r a z o n e s I - I V and d i c a r b a m i d o a m i d r a z o n e s I V - V I w e r e s y n t h e s i z e d by the m e t h o d in
[1] b y r e a c t i o n of the a p p r o p r i a t e c a r b a m i d o i m i n o e s t e r and d i c a r b a m i d o i m i n o e s t e r with h y d r a z i n e o r i t s
d e r i v a t i v e s in a s o l v e n t . Some of the p r o p e r t i e s and y i e l d s of the c o m p o u n d s a r e p r e s e n t e d in T a b l e 1.

C y e l i z a t i o n of C a r b a m i d o a m i d r a z o n e s I - I V and D i c a r b a m i d o a m i d r a z o n e s V and VI. A 5 - 1 0 - g s a m p l e

of the c a r b a m i d o a m i d r a z o n e o r d i c a r b a m i d o a m i d r a z o n e w a s h e a t e d in a g l a s s r e a c t o r with a n o u t l e t tube at
200-250 ~ in v a c u o (5-10 m m ) f o r 2 h. The r e s u l t i n g C - a m i n o t r i a z o l e o r t r i a z o l o n e w a s r e c r y s t a l l i z e d f r o m
hot e t h a n o l . The s y n t h e s i z e d c o m p o u n d s a r e c o l o r l e s s s u b s t a n c e s that a r e s o l u b l e on h e a t i n g in a l c o h o l ,
w a t e r , d i o x a n e , d i m e t h y l f o r m a m i d e , l e s s s o l u b l e in b e n z e n e , and i n s o l u b l e in s a t u r a t e d h y d r o c a r b o n s . The
p r o p e r t i e s and y i e l d s of the s y n t h e s i z e d C - a m i n o t r i a z o l e s (VII-X) and t r i a z o l o n e s (XI-XIII) a r e p r e s e n t e d
in T a b l e 2.

I n ' t h e c y c l i z a t i o n of I, the r e s u l t i n g C - a m i n o t r i a z o l e (VII) s u b l i m e s u n d e r the i n d i c a t e d c o n d i t i o n s ,

w h i l e t r i a z o l o n e XI r e m a i n s in the p o t . The s u b s t a n c e s w e r e r e c r y s t a l l i z e d f r o m e t h a n o l .

LITERATURE CITED

I. G. S. G o l ' d i n , V. G. P o d d u b n y i , E. S. S m i r n o v a , A. A. S i m o n o v a , and V. P. K o z y u k o v , Zh. O b s h c h .

K h i m . , 4_22, 2722 (1972).
2. G. S. G o l ' d i n , V. G. P o d d u b n y i , E. S. S m i r n o v a , and V. P . Kozyukov, Zh. O b s h c h . K h i m . , 4._~3, 344
(1973).
3. W. Ried and A. Czack, Ann., 67_~6, 121 (1964).
4. H. Rupe and A. Labhardt, Ber., 33, 239 (1900).

490
CONDENSATION OF PROTIC SALTS OF N-ALKYL-SUBSTITUTED
C-AMINO-sym-TRIAZOLES WITH fl-DIKETONES
AND fl-CHLOROVINYL KETONES

G . M. G o l u b u s h i n a , G . N. Poshtaruk, UDC 547.79'859 : 542.953 : 543.422.25

and V. A. Chuiguk

Condensation of p r o t i c s a l t s of C - a m i n o - s y m - t r i a z o l e s with fl2diketones and fl-chlorovinyl

ketones leads to the c o r r e s p o n d i n g s y m - t r i a z o l o p y r i m i d i n i u m compounds. The s t r u c t u r e
of the condensation p r o d u c t s was c o n f i r m e d by the PMR s p e c t r a .

N-Unsubstituted 3 - a m i n o - s y m - t r i a z o l e s r e a c t with fl-diketones in the p r e s e n c e of b a s i c c a t a l y s t s to

give s y m - t r i a z o l o [ 1 , 5 - a ] p y r i m i d i n e s [1, 2]. The protic s a l t s of condensed a m i n o - s y m - t r i a z o l e s r e a c t with
fl-diketones, fl-chlorovinyl ketones, and 1 , 1 , 3 , 3 - t e t r a e t h o x y p r o p a n e to give the c o r r e s p o n d i n g p y r i m i d i n i u m
s a l t s [3]. In the p r e s e n t r e s e a r c h we have investigated the analogous condensation of the protic s a l t s of
3 - a m i n o - 4 - m e t h y l - s y m - t r i a z o l e s (Ia, b), 5 - a m i n o - l - m e t h y l - s y m - t r i a z o l e s (IIa, b), and 3 - a m i n o - l - b e n z y l -
s y m - t r i a z o l e (V).

R,,,. . ~ N -...~..N,-..~/-R R"'.,.r~N"-,..c~,.N~-N

~ - -~. .~ N--N'-?cH 3 r,, ~ . . ~ n - n r,,.~ ..n-:---~.r

I
R' c~oJ r cto~
Ta,b II a, b Ill IV

I,II a R = H ; b R = E H 3

One r e a c t i o n path to give a p y r i m i d i n e ring is p o s s i b l e for I and II. The condensation p r o d u c t s are
the i s o m e r i c s y m - t r i a z o l o [ 1 , 5 - a ] p y r i m i d i n i u m (IH) and s y m - t r i a z o l o [ 4 , 3 - a ] p y r i m i d i n i u m (IV) s a l t s (Table 1).
The PMR s p e c t r a (Table 2) c o n f i r m s t r u c t u r e s III and IV and make it p o s s i b l e to d e t e r m i n e the s t r u c -
t u r e of the p r o d u c t s of condensation with u n s y m m e t r i c a l carbonyl components. The N - C H 3 chemical shifts
f o r HI and IV a t t e s t to higher e l e c t r o n density on N(3) in III than in IV. R e p l a c e m e n t of H by CH 3 in the
t r i a z o l e ring (R) shifts all of the signals a little too strong field except for the signal of the 5-C H3 group
in IVf, which is somewhat deshielded s t e r i c a l l y by the 3-CH 3 group. In c o r r e s p o n d e n c e with the p a r t i a l
localization of the bonds in HI and IV, when R" =H the R' =CH 3 peak is always l o w e r and b r o a d e r than the
R " =CH 3 p e a k b e c a u s e of coupling with R" =H ( J = 0 . 8 - 1 Hz).
P e r c h l o r a t e s IIa, b r e a c t with benzoylacetone to give IVe and IVh. The phenyl signals in the PMR
s p e c t r a of these compounds a r e not split; this is in keeping with t h e i r location in the 5 position [4]. In addi-
tion, 5 3-CH 3 in the s p e c t r u m of IVh is 1.82 ppm, as against 2.65 p p m in the s p e c t r u m of IVf; this is e x -
plained by the shielding by the phenyl group [5]. The phenyl group in IVh apparently deviates m o r e f r o m
the plane of the molecule than in IVe. All of the signals of IVh, including the peak of the phenyl group it-
self, a r e shifted a little to s t r o n g field as c o m p a r e d with IVe as a consequence of the l e s s e r conjugation
of the phenyl group with the h e t e r o c y c l i c s y s t e m . However, in IVe, the phenyl group also deviates f r o m
the plane of the h e t e r o r i n g , inasmuch as the 3-H c h e m i c a l shift here is the s a m e as in IVa, while the r e -
maining signals a r e shifted to weak-field, i.e., 3-H is shielded by the phenyl group, which is p o s s i b l e when
it is not c o p l a n a r .

T. G. Shevchenko Kiev State U n i v e r s i t y . T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii,

No. 4, pp. 565-569, April, 1974. Original a r t i c l e submitted N o v e m b e r 9, 1972.

I
9 19 75 Plenum Pablishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, withoul written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

491
 Methyl fl-chlorovinyl ketone r e a c t s with
_IIa-HC 104 to give a mixture of i some ric IVc and IVd in
a ratio of 1.5 : 1, f r o m which pure IVc was isolated
by crystallization. In c o n t r a s t to the 7-CH 3 signal,
the 5-CH 3 signal is split by coupling with 6-H (J =
1 Hz). In addition, J(5-H, 6-H) > J(7-H, 6-H), as
was observed in [6, 7].
d ~ ~ I ~ ~ ~
Benzoylacetone r e a c t s with Ia to give a mix-
ture of Hie and its i s o m e r in a r a t i o of 3 : 1, f r o m
which pure IIIe was isolated. The 7-C6H 5 signal
~ ~ I ~ ~ ~ in the PMR s p e c t r u m of IIIe is split into two groups
of bands with an intensity ratio of 2 : 3 (the lower
at weak field) and a difference of 0.37 ppm between
the c e n t e r s of these bands; this is c h a r a c t e r i s t i c for
such m o l e c u l a r f r a g m e n t s [4, 8], in which the phe-
nyl group is at a c e r t a i n angle to the plane of the
00~00 --~ ~OmO00000 h e t e r o r i n g and shifts the 6-H signal to weak field
by 0.23 ppm as c o m p a r e d with IIIa. The product of
the reaction of Ib with benzoylacetone is IIIh, in the
PMR s p e c t r u m of which the phenyl signal is split
s i m i l a r l y but with a g r e a t e r difference between
the c e n t e r s of the bands (0.66 ppm); this is c h a r -
a c t e r i s t i c for a phenyl group in the 5-position [9].
In the case of IIIh, the plane of the phenyl group
makes a considerably s m a l l e r angle with the plane
of the heteroring, inasmuch as it shifts the 6-H
signal considerably m o r e strongly to weak-field
(by 0.56 ppm as c o m p a r e d with IIIf).
Methyl /3-chlorovinyl ketone r e a c t s with Ia
to give a mixture of i s o m e r i c IIIc and Hid with p r e -
dominance of the l a t t e r (1 : 4, f r o m the PMR s p e c -
> trum). The s t r u c t u r e of Ilia was also confirmed
by alternative synthesis by methylation of the ap-
propriate sym-triazolo[1,5-a]pyrimidine deriva-
tive [10].
r
Salts III and IV, which contain methyl groups
O
in the 5- and 7- positions, give polymethine dyes.
The 7-CH 3 group is m o r e active in IIIa, as attested
~) LO
to by the s t r u c t u r e of the dye - a m o n o s t y r y l f r o m
Ilia and p-dimethylaminobenzaldehyde. The signal
of the 7-CH 3 group is absent in the PMR s p e c t r u m
.=. of this dye, but the 5-CH 3 signal r e m a i n s .
In c o n t r a s t to I and II, the f o r m a t i o n of a 1-
r substituted s y m - t r i a z o l o [ 1 , 5 - a ] p y r i m i d i n i u m salt
(VI) o r 2-substituted s y m - t r i a z o l o [ 4 , 3 - a ] p y r i m i d i -
o
nium salt (Vt) or 2-substituted s y m - t r i a z o l o [ 4 , 3 - a ] -
~ p y r i m i d i n i u m salts (VII) is possible for V on r e a c -
tion with fl-diketones. The formation of VI is less
favorable, inasmuch as the positive charge in it
would be distributed between two adjacent nitrogen
atoms. It is apparently for this same r e a s o n that
3-substituted derivatives (III), in which the positive
b~ charge is distributed between two amidine n i t r o -
gen atoms, r a t h e r than the 1-substituted d e r i v a -
tives (VI) are also f o r m e d in the alkylation of s y m -

492
 T A B L E 2. C h e m i c a l Shifts of the P r o t o n s of III, IV, and VII (5,
ppm) *

N-CH3 Or
Compound R R' R" R'" N-CH:C~Hs

IIIa 8,53 2,0 (0,8) 7,14 2,51 3,78

IIIc 2,64 8,49 (5) 3,80
IIId 8,58 (7) 722 (7) 2,55 3,76
IIIe 8,60 7.30andT,67 7,37 2,58 3,82
IIIf 2,74 2,49 7,04 2,44 3,65
IIIh 2,65 2,47 7,60 7,20 and 7,86 3,58
IVa 8,65 2,58 6,93 2,50 3,93
IVc 8,85 2,67 (l) 7,17 (5) 8,77 (5) 4,02
IVd 8,75 8,53 (7) 7,17 (7) 2,55 3,92
IVe 8,65 7,40 7,17 2,58 4,04
IVe 2,65 2,65 6,82 3,82
IVh 1,82 7,32 6,97 2,53
22,49
43 7,71 3,92
VIIa 9,541" 2,49 6.92 5,43 and 7,10
VlIc 9,57 "i" 2,70 7,25 and 5,45 and 7.12
VIId 9,53 7,25 7,43 7,22 and 7,67 5,38 and 6,99
* T h e J c o n s t a n t s in h e r t z a r e i n d i c a t e d in p a r e n t h e s e s .
"~For 6 3 - H .

t r i a z o l o [ 1 , 5 - a ] p y r i m i d i n e . A m i d i n e d e l o e a l i z a t i o n of c h a r g e is a l s o p o s s i b l e in VII, w h i c h a r e a l s o f o r m e d
a s a r e s u l t of c o n d e n s a t i o n of V ' H C I O 4 w i t h f l - d i k e t o n e s (Table 1).
R" N N\ /CH.%H- NH 2 N

~, r " '~,
Vll V V|

In c o n f o r m i t y w i t h t h i s s t r u c t u r e , 6CH 2 in the P M R s p e c t r u m of the p r o d u c t of c o n d e n s a t i o n w i t h d i -

b e n z o y l m e t h a n e (VIId) d o e s not d i f f e r s u b s t a n t i a l l y f r o m 6CH 2 of the r e m a i n i n g d e r i v a t i v e s , in w h i c h t h e r e
i s no p h e n y l g r o u p in the 5 - p o s i t i o n , w h i l e in the c a s e of s t r u c t u r e VI t h i s g r o u p s h o u l d be s h i e l d e d b y the
p h e n y l g r o u p in the 5 - p o s i t i o n [7, 11]. In a d d i t i o n , in c o n f o r m i t y w i t h f o r m u l a VII, 5-C6H 5 h a s p r e c i s e l y
t h e s a m e e f f e c t on 3 - H a s 5-C6H5 h a s on 3 - H in IV. T h e r e is no r e a s o n to doubt that the c o n d e n s a t i o n p r o -
c e e d s in the s a m e m a n n e r with d i b e n z o y l m e t h a n e a s w i t h o t h e r f l - d i k e t o n e s . C o n f i r m a t i o n f o r t h i s i s p r o -
v i d e d b y the c l o s e n e s s of the 3 - H c h e m i c a l s h i f t s of VIIa, c, d, the s i g n a l s of w h i c h a r e found in the r e g i o n
of 5 - H a b s o r p t i o n of 1 , 4 - d i s u b s t i t u t e d s y m - t r i a z o l i u m s a l t s [12].

C o n d e n s a t i o n of V 9 HC10 4 with b e n z o y l a c e t o n e g i v e s one i s o m e r WIIc, R"' =C6H5). The p h e n y l s i g n a l

in t h e P M R s p e c t r u m of VIIc i s s p l i t into two g r o u p s of b a n d s w i t h a n i n t e n s i t y r a t i o of 2 : 3 and a d i f f e r e n c e
b e t w e e n t h e i r c e n t e r s of 0.45 p p m . The 7-C6H ~ s i g n a l of VIId h a s the s a m e c h a r a c t e r , w h i l e 5-C6H 5 g i v e s
an u n s p l i t p e a k .

EXPERIMENTAL
The a m i n o - s y m - t r i a z o l e s w e r e o b t a i n e d b y the m e t h o d s in [13, 14]. The P M R s p e c t r a of t r i f l u o r o -
a c e t i c a c i d s o l u t i o n s w e r e d e t e r m i n e d w i t h a Z K R - 6 0 s p e c t r o m e t e r with h e x a m e t h y l d i s i l o x a n e (HMDS) a s
the i n t e r n a l s t a n d a r d .

C o n d e n s a t i o n of A m i n o t r i a z o l e s I, II, and V w i t h / 3 - D i k e t o n e s . A m i x t u r e of 0.01 m o l e of the a m i n o -

t r i a z o l e p e r c h l o r a t e and 0.13 m o l e of the f l - d i k e t o n e w a s h e a t e d at 120-190 ~ f o r 1-4 h (Table 1). T h e m i x -
t u r e w a s t h e n c o o l e d , and the p r o d u c t w a s t r i t u r a t e d with e t h e r o r e t h e r and a c e t o n e . T h e m i x t u r e w a s f i l -
t e r e d , and t h e s o l i d w a s c r y s t a l l i z e d f r o m a l c o h o l o r w a t e r .

C o n d e n s a t i o n of P e r c h l o r a t e s Ia and I I a w i t h M e t h y l f i - C h l o r o v i n y l K e t o n e . A 0 . 0 2 - m o l e s a m p l e of
the k e t o n e w a s a d d e d to a s o l u t i o n of 0.01 m o l e of s a l t Ia o r IIa in the m i n i m u m a m o u n t of a l c o h o l . The
r e s u l t i n g s o l u t i o n w a r m e d up and d a r k e n e d , a n d I I I e , d o r I V c , d (Table 1) p r e c i p i t a t e d f r o m the hot s o l u t i o n .
The p r e c i p i t a t e s w e r e s e p a r a t e d and c r y s t a l l i z e d f r o m a l c o h o l .

1,5-Dimethyl-7-(p-dimethylaminostyryl)-sym-triazolo[1,5-a]pyrimidinium Perchlorate. A 0.26-g

(1 m m o l e ) s a m p l e of IIIa and 0.35 g (2.3 m m o l e ) of p - d i m e t h y l a m i n o b e n z a l d e h y d e w a s r e f l u x e d in 2 m l of
a c e t i c a n h y d r i d e f o r 30 m i n . T h e r e s u l t i n g p r e c i p i t a t e w a s w a s h e d with b o i l i n g a l c o h o l and w a t e r . W o r k u p
g a v e 0.21 g (5470) of a p r o d u c t w i t h m p 258 ~ and k m a x (in a l c o h o l ) 506 n m (log e 4.95). P M R s p e c t r u m , 5,
p p m : 3.80 (N--CH3) , 3.14 [N(CH3)2] , 2.58 (5-CH3). F o u n d : C1 9.370. C17H20C1N50 4. C a l c u l a t e d : C1 9.070.

493
 LITERATURE CITED
1. C, Billow and K. Haas, Ber., 42, 4638 (1909).
2. J . D . Bower and F. P. Doule, J. Chem. Soc., 727 (1957).
3. G.M. Golubushina and V. A. Chuiguk, Khim. Geterotsikl. Soedin., 1433 (1971).
4. A. Le Berre and C. Renault, Bull. Soc. Chim. France, 3139 (1969).
5. S.I. Shul'ga and V. A. Chuiguk, Ukr. Khim. Zh., 3..~7,350 (1971).
6. A. Pollak, B. Stanovnik, and M. Tiller, J. Org. Chem., 3_~6,2457 (1971).
7. S.I. Shul'ga and V. A. Chu[guk, Khim. Geterotsikl. Soedin., 632 (1972).
8. M.K. Pordeli and V. A. Chuiguk, Khim. Geterotsikl. Soedin., 199 (1973).
9. S.I. Shul'ga and V. A. Chuiguk, Kh[m. Geterots~kl. Soedin., 637 (1972).
10. W.W. Paudler and H. S. Helm[k, J. Heterocycl. Chem., 5, 691 (1968).
11. A, M. Khmaruk, Yu. M. Volvenko, and V. A. Chuiguk, Ukr. Khim. Zh., 3_~7,262 (1972).
12. H. Becker, N. Sauder, and H. J. Timpe, J. Prakt. Chem., 311, 897 (1969).
13. C, Kr~Jger, G. Schoknecht, and H. Beyer, Ber., 97, 396 (1964).
14. K. Shirakawa, Yakugaku Zasshi, 80, 1542 (1960); Chem. Abstr., 5_~5,10,453c (1961).

494
LETTERS TO THE EDITOR

REACTIONS OF 2- AND 4-(fl-ETHOXYVINYL)PYRYLIUM

SALTS WITH NUCLEOPHILES

G. N. D o r o f e e n k o , V. V. Mezheritskii, UDC 812.814

and A. L. Vasserman

It has been shown that in reactions of 2- and 4- (fl-ethoxyvinyl)pyrylium salts with nucleophiles such
as active methylene compounds (acetylacetone, acetoacetic e s t e r , dibenzoylmethane, malonic e s t e r , phenyl-
acetic acid, and cyanoacetic e s t e r ) , charged h e t e r o c y c l i c s y s t e m s containing ~- or y-methyl groups (pyry-
lium and pyridinium salts), vinyl e t h e r s , enamines, active a r o m a t i c compounds (N,N-dimethylaniline, N,N-
diethylani!ine, anisole, phenetole, v e r a t r o l e , and indole) and organomagnesium compounds, attack by the
nucleophile is r e a l i z e d at the fl.carbon atom of the fl-ethoxyvinylpyrylium salt with subsequent splitting out
of alcohol to f o r m a conjugated s y s t e m . Uncharged m e r o c y a n i n e dyes are formed with active methylene
compounds, but in other c a s e s a p y r y l i u m salt with a new (in place of the ethoxy group) substituent is gen-
erated.

C2H

-XC]O 4 ... -C2H50 H ...

CIO~ C104"

EXPE RIME NTA L

Bisflavenetrimethylidyne P e r c h l o r a t e . This compound (mp 286 ~ was obtained in 607o yield by con-
densation of 4-methylflavylium p e r c h l o r a t e with 4- (fi-ethoxyvinyl)flavylium p e r c h l o r a t e .
2,4-Diphenyl-6-(6-ethoxyvinyl)pyrylium P e r c h l o r a t e . This compound (rap 170 ~ was obtained in 81%
yield by heating 2,4-diphenyl-6-(fl-ethoxyvinyl)pyrylium p e r c h l o r a t e (I) with ethyl vinyl e t h e r in acetic acid.
2,_4-Diphenu165 P e r c h l o r a t e , This compound imp 178 ~
was obtained in 77% yield f r o m I and 1 - m o r p h o l i n o - l - c y c l o h e x e n e in dichloroethane.
2 , 6 - D i p h e n y l - 4 - s t y r y l p y r y l i u m P e r c h l o r a t e . This compound [nap 252 ~ (from acetic acid)] [1] was ob-
tained in 69% yield f r o m 2,6-diphenyl-4-(fl-ethoxyvinyl)pyrylium p e r c h l o r a t e (fI) and phenylmagnesium
bromide.
2,6-Diphenyl-4- ( p - d i m e t h y l a m i n o s t y r y l ) p y r y l i u m P e r c h l o r a t e . This compound (nap 288 ~ was obtained
in quantitative yield by refluxing II and dimethylaniline in acetic anhydride.
Ethyl (~-Cyano- y - p y r a n y l i d e n e c r o t o n a t e . This compound (mp 152 ~ was obtained in 807O yield by r e -
fluxing I with cyanoacetic e s t e r in acetic anhydride in the p r e s e n c e of sodium acetate.
The results of e l e m e n t a r y analysis for C. H, N, and C1 were in a g r e e m e n t with the calculated values.

LITERATURE CITED
1. W. Dilthey and J. F i s c h e r , Chem. Ber., 57.7, 1653 (1924).

Rostov State University. S c i e n t i f i c - R e s e a r c h Institute of Physical and Organic C h e m i s t r y . Rostov-

on-Don. T r a n s l a t e d f r o m Khimiya Geterotsiklicheskikh Soedinenii, No. 4, p. 570, April, 1974. Original
article submitted May 24, 1973.

9 1975PlenumPublishing Corporation, 227 West 17th Street, New York, iV. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy o f this article is available from the publisher for $15.00.

495
DEBENZYLATION OF N-BENZYLAZOLES

B. A. Tertov, V. V. Bessonov, UDC 547.778 : 542.957

a n d A . S. M o r k o v n i k

In the r e a c t i o n of 1 - b e n z y l - 3 , 5 - d i m e t h y l p y r a z o l e with butyl- and naphthyllithium, 1-(o~-lithiobenzyl)-

3 , 5 - d i m e t h y l p y r a z o l e is f o r m e d in good yield in the f i r s t case, while debenzylation o c c u r s just as smoothly
in the second. I n a s m u c h as 1 - ( ~ - l i t h i o b e n z y l ) - 3 , 5 - d i m e t h y l p y r a z o l e is not c o n v e r t e d to 3 , 5 - d i m e t h y l p y r -
azole by the action of naphthyllithium, it can be concluded that rnetallation at the N - C H 2 group is not the
f i r s t step in the debenzylation reaction. Phenyl(1-benzyl-2~imidazolyl)carbinol, p h e n y l ( 1 - b e n z y l - 2 - b e n z -
imidazolyl)carbinol, and 2 - ( a - a m i n o b e n z y l ) - l - b e n z y l b e n z i m i d a z o l e undergo debenzylation under s i m i l a r
conditions. The debenzylation of p h e n y l ( 1 - b e n z y l - 2 - b e n z i m i d a z o l y l ) c a r b i n o l by our method gives b e t t e r
yields than when sodium in liquid a m m o n i a is used.
In the r e a c t i o n of naphthy!lithium with N-benzylhaloazoles the r e a c t i o n may lead to the c o r r e s p o n d -
ing debenzylated organolithium compounds. Thus, for example, f r o m 2 - i o d o - l - b e n z y l b e n z i m i d a z o l e we
obtained 1,2-dilithiobenzimidazole, the s t r u c t u r e of which was p r o v e d by c o n v e r s i o n to phenyl(2~benzimid-
azolyl)carbinol. All of the r e a c t i o n s with naphthyllithium w e r e c a r r i e d out in t e t r a h y d r o f u r a n .

Rostov State University, R o s t o v - o n - D o n . T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii,

No. 4, p. 571, April, 1974. Original a r t i c l e submitted June 11, 1973.

9 19 75 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N.Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy of this article is available from the publisher for $15.00.

496
CYCLIZATION OF 4,4-DINITROBUTENOIC ACID ESTERS
TO 3-NITROISOXAZOLINE N-OXIDES

A. L. Fridman, F. A. G a b i t o v , UDC 547.786.3 : 543.422.4'544

V. D. Surkov, a n d V . S. Z a l e s o v

It is known that salts of nitroalkanes are readily halogenated by N-halo derivatives of amides, imides,
and n i t r o a m i n e s . We have observed that the r e a c t i o n of the p o t a s s i u m salts of 4,4-dinitrobutenoic acid
e s t e r s (t) with the N - b r o m o derivatives of succinimide and N - m e t h y l - p - t o l u e n e s u l f o n a m i d e is accompanied
by cyclization to 4,5-substituted 3-nttroisoxazoline N-oxides (IIa-e).
R'--. NO2 NO~
CH--C
i CH2=CHCH20 H R ' \ C H~ ' - - " * ~ C H2
~c~op2cu=cncooR + B~R'-KB~-~ooc/C~o~\O ~ . ~ / ~ . . ~ .... ~"\
t~u,~ \0- "0/" CH2OH

l II a - e III

I l a - d R' =(-CH2CO) 2 N; a, e R = CH3; b R = C2H5; C R = n- C3H7; d r = (C6H5)2CH ; ~ R' =p-Tos-N-CH a

Compounds I I a - e display p r o p e r t i e s c h a r a c t e r i s t i c s for 3-nitroisoxazoline N-oxides. They slowly

liberate iodine f r o m KI in acetic acid and undergo 1,3-dipolar cyeloaddition with olefins to give n i t r o i s o x a -
zolizidines (III). Absorption bands of the C =N bond (1650-1665 ore-i), of a nitro group (1516-1522 and
1320-1330 cm-~), and of a C=N/O grouping (812-820 and 1220-1240 c m - I ) a r e o b s e r v e d i n t h e l t l s p e c t r a
\o--r~
of ria-e. A h y p s o e h r o m i c shift of the absorption band at 300-310 nm as c o m p a r e d with the s p e c t r a of un-
substituted 3-nitroisoxazoline N-oxides (Xmax, CH2C12 320 nm) is observed in the UV s p e c t r a . The s t r u c -
ure and individuality of IIa-e are also c o n f i r m e d by the results of e l e m e n t a r y analysis and t h i n - l a y e r c h r o -
m a t o g r a p h y [Silufol, a c e t o n e - c h l o r o f o r m (1 : 8)].
3-Nitroisoxazoline N-Oxides (IIa-e). A solution of 20 mmole of N - b r o m o derivative in 20-30 ml of
acetone was added at 20-25 ~ to a solution of 20 mmole of salt I in 15-20 ml of acetone, and the mixture was
held at this t e m p e r a t u r e for 0.5-1 h. It was then filtered, and the filtrate was evaporated. The residue was
r e c r y s t a l l i z e d f r o m ethanol. Compound IIa, with mp 208-209 ~ (dec.) and R f 0.35, was obtained in 86% yield.
IR s p e c t r u m : 1740, 1720, 1650, 1520, 1325, 1220, and 812 e m -1. UV s p e c t r u m : ~,max 306 nm (log e 4.01).
Compound rib, with mp 186-187 ~ (dec.) and R f 0.45, was obtained in 68% yield. IR s p e c t r u m : 1755, 1720,
1660, 1512, 1320, 1240, 820 c m -1. UV s p e c t r u m : Xmax 308 nm (log e 4.01). Compound IIc, with nap 192-
193 ~ (dec.) and R f 0~ was obtained in 65% yield. IR s p e c t r u m : 1765, 1725, 1670, 1520, 1330, 1218, and
820 cm -1. UV s p e c t r u m : ~-max 305 nm (log e 4.01). Compound IId, with mp 211-212 ~ (dec.) and R f 0.30,
was obtained in 61% yield. IR s p e c t r u m : 1770, 1745, 1665, 1520, 1330, 1225, 820 c m -1. UV s p e c t r u m :
~-max 307 nm (log e 4.08). Compound IIe, with mp 174-175 ~ (dec.) and R f 0.80, was obtained in 84% yield.
IR s p e c t r u m : 1755, 1650, 1515, 1320, 1235, 1178, and 813 c m -1. UV s p e c t r u m : ~-max 299 nm (log e 3.85).
Reaction of Isoxazoline IIa with Allyl Alcohol. Allyl alcohol (30 ml) was added at 60-70 ~ to a solu-
tion of 1 g of IIa in 80 ml of acetonitrile, a f t e r which the mixture was held at this t e m p e r a t u r e for 1 h. It
was then evaporated, and the residue was r e c r y s t a l l i z e d f r o m ethanol to give IIIa with mp 170-171 ~ (dec.)
in 80% yield. IR s p e c t r u m : 3540, 1735, 1568, 1380, 1310, 1185, and 820 c m -1. Found: C 42.1; H 4.5; N
12.4%. C I2H15N309. Calculated: C 41.7; H 4.3; N 12.2%.

P e r m State P h a r m a c e u t i c a l Institute. T r a n s l a t e d f r o m Khimiya Geterotsiklicheskikh Soedinenii,

No. 4, pp. 571-572, April, 1974. Original article submitted July 23, 1973.

9 1975PlenumPublishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
t stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

497
SYNTHESIS OF 1,3-DIHYDRO-5-ALKYL-2H-1,4-
BE NZ O D I A ZE P I N - 2 - O N E S

Yu. S. S h a b a r o v , T. P. Surikova, UDC 547.892.07

and S. S. M o c h a l o v

Almost all of the 1,4-benzodiazepin-2-ones described in the l i t e r a t u r e contain phenyl groups in the
5-position [1]. There is only one p a p e r [2] in which mention is made of the synthesis of 5 - a l k y l ~ l , 4 - b e n z o -
di azep in- 2- one s.
We have been able to show that 2-aminoacylbenzenes (ia, b) that contain an aliphatic acyl group (see
[3-5] for their preparation) can be readily converted to 1 , 3 - d i h y d r o - 5 - e t h y l - l , 4 - b e n z o d i a z e p i n - 2 - o n e s (III).
R R
o
C--C2H. BrCH2COCI ~ ' - - C - - C. H~

"N"2 o "N H--CO '~CH2Br

la, b Ila, b

I II ca2
L "NH--CO--CH2NH2.] ~'~N H--C~/~
O
illa, b

I-III a r=H; b r=Cl

For example, bromoacetanilides (IIa, b) are obtained by the action of b r o m o a c e t y l chloride on 2 - a m i n o -
aceylbenzenes (Ia, b). The bromine atom in IIa, b is readily replaced by an amino group by treatment with
ammonia, and the resulting amino derivatives immediately c y c l i z e t o give 1,4-benzodiazepin-2-ones (IIIa, b)**

EXPERIMENTAL
The PMR s p e c t r a of CC14 solutions were r e c o r d e d with a JNM H-60 s p e c t r o m e t e r with hexamethyl-
disiloxane (HMDS) as the internal standard. The IR s p e c t r a of m i n e r a l - o i l suspensions and CC14 solutions
were r e c o r d e d with an IKS-22 s p e c t r o m e t e r .
2-(N-Bromoacetyl)aminopropiophenone (IIa). A 6.3-g (0.04 mole) sample of brornoacetyl chloride
and 13 ml of 3 N sodium hydroxide solution were added simultaneously at 10 ~ to a solution of 4.5 g (0.03
mole) of amino ketone Ia [3] in 120 ml of dioxane, after which the mixture was s t i r r e d at 10~ for 1 h and
poured into ice water. The aqueous mixture was extracted with methylene chloride, and the e x t r a c t was
washed with water, dried with magnesium sulfate, and concentrated in vacuo to give 6.4 g (80%) of 2-(N-
bromoacetyl)aminopropiophenone (IIa) with mp 56-57 ~ [from b e n z e n e - p e t r o l e u m e t h e r (1:3)]. PMR s p e c -
trum, 5, p p m : t 1.63 t (3H), 3.34 q (2H), 4.31 s (2H), 7.30-8.30 m (4H). Found: C 49.0; H 4.6%. CllH12BrNO2 .
Calculated: C 48.9; H 4.5%.

*While this m a t e r i a l was being p r e p a r e d for publication, a G e r m a n patent appeared in which the same
scheme for the synthesis of 1,4-benzodiazepinones was proposed, but for other examples see [6].
"~The abbreviations used here and elsewhere are: s is singlet, d is doublet, t is triplet, q is quartet, m is
mnltiplet, and dd is doublet of doublets.

M. V. Lomonosov Moscow State University. N. P. Pirogov Moscow State Medical Institute. T r a n s -

lated f r o m Khimiya Geterotsiklieheskikh Soedinenii, No. 4, pp. 572-573, April, 1974. Original article sub-
mitted November 20, 1973.

9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy of this article is available from the publisher for $15.00.

498
 4 - C h l o r o - 2 - ( N - b r o m o a c e t y l ) a m i n o p r o p i o p h e n o n e ffIb). This compound (rap 103 ~ was obtained in 80%
yield f r o m amino ketone Ib [4] as d e s c r i b e d above. PMR s p e c t r u m , 6, ppm: 1.59 t (3H), 3.31 q (2H), 4.27 s
(2H), 7.83 dd H4 ( J o = 9 Hz, J m = 2.4 Hz), 8o12 d H e (Jm = 2.4 Hz), 8.98 d H3 (Jo =9 Hz). Found: C 43~ H3.6%.
CllHllC1BrNO 2. Calculated: C 43.4; H 3.6%.
5 - E t h y l - l , 3 - d i h y d r o - 2 H - 1 , 4 - b e n z o d i a z e p i n - 2 - o n e ffIIa). An e t h e r solution of 2.7 g (0.01 mole) of 2-
( N - b r o m o a c e t y l ) a m i n o p r o p i o p h e n o n e (IIa) was added at - 10 to 0 ~ to 150 ml of a 1570 solution of a m m o n i a in
methanol, and the m i x t u r e was then allowed to stand at r o o m t e m p e r a t u r e for 24 h. The solvent was then
e v a p o r a t e d , and the residue was c h r o m a t o g r a p h e d with a column containing activity II a l u m i n u m oxide (elu-
tion by ethyl acetate) to give 1.2 g (80%) of 1 , 4 - b e n z o d i a z e p i n - 2 - o n e IIIa with mp 123-124 o (from ethyl a c e -
'tate)o PMR s p e c t r u m , 5 , p p m : 1.43 t (3H), 3.07 q (2H), 4.32 s (2H), 7.30-7.90 m (4H)o IR s p e c t r u m : 1692
( C = Q~, 1610 (C = N)93215 ( N - H ) cm-1. Found: C 69.9; H 6.5%o CilH12N2Oo Calculated: C 70.2; H 6.4%.
7 - C h l o r o - 5 - e t h y l - l , 3 - d i h y d r o - 2 H - 1 , 4 - b e n z o d i a z e p i n - 2 - o n e ffIIb). This compound [1.5 g (7570)] with
mp 134 ~ [2] was obtained as d e s c r i b e d above f r o m 3.1 g (0.01 mole) of 4 - c h l o r o - 2 - ( N - b r o m o a c e t y l ) a m i n o -
propiophenone {lib). The r e s u l t s of a n a l y s i s for C and H w e r e in a g r e e m e n t with the calculated values.

LITERATURE CITED
1. G. A. A r c h e r and L. H. Sternbach, Chem. Rev., 6_.88, 747 (1968).
2. I. Schmitt, F r e n c h Patent No. 1,391,752 {1965); Chem. A b s t r . , 6__33,4316 {1965).
3. Yu. S. Shabarov and S. S. Mochalov, Zh. Organ. Khim., 8, 293 {1972).
4. Yu. S. Shabarov and S. S. Mochalov, Khim. G e t e r o t s i k l . Soedin., 1334 (1973).
5. Yu. S. Shabarov and S. S. Mochalov, USSR A u t h o r ' s C e r t i f i c a t e No. 367,099 (1973); Byul. Izobr., No. 8
{1973).
6. A. Bauer, K. Weber, P. Dannebug, and K. Minck, West G e r m a n Patent No. 2,117,438 (1973); Chem.
Abstr., 7_~8, 400 {1973).

499
INDOLYLALKYLAMINES FROM ARYLHYDRAZINES
AND 3,- OR 6-HALOCARBONYL COMPOUNDS (REVIEW)

I. I. G r a n d b e r g UDC 547.754'759.3 : 541.67

A series of papers devoted to the synthesis of tryptamines and related structures (tryptophols,
homotryptamines, eserines, azatryptamines, etc.) from halocarbonyl compounds and arylhy-
drazines a r e correlated. The data on the mechanism of the reaction can be successfully ap-
plied to the F i s c h e r indole synthesis.

In 1966 it was observed that phenylhydrazine, on heating in alcohol solution with "/-chlorobutyraldehyde
[1, 2], forms tryptamine in quite a high yield instead of the expected 1-phenyltetrahydropyridazine. In the
following six years a detailed study of the mechanism of the process, which leads to the formation of the
most important biogenetic amines, made it possible not only to ascertain the details of this interesting r e -
action but also to obtain extremely important results related to the Fischer indole synthesis. The goal of
this review is a correlation of all of the data on this most promising method at present for the synthesis
of tryptamine and other similar structures.
Several arylhydrazines and "/-halocarbonyl compounds have reacted like phenylhydrazine and 3,-chlo-
robutyraldehyde, but the formation of tryptamines did not seem very clear, especially since Sletzinger had
previously obtained 3- (#-chloroethyl)indoles from 5-chloro-2-pentanone under the usual conditions of the
Fischer reaction [3, 4]. The scheme for the process that had already been proposed in one of the first
papers [5] satisfactorily explained all of the experimental facts and was then confirmed in detail (see below).
According to this scheme, arylhydrazine I r e act s with a T-halo ketone or -/-halo aldehyde to give hydra-
zone II, which is cyclized to 1-anilinopyrroline salt III.

/ C H2CH2CH2X', ~ ~ H2CH2cH2X ~
o=c\ = R--~ c ~R---+- 11 I.+ I
R ~m~'I\NR'_NH2 R" ~NRL# \R'' ~ ' R v N QN"'k~R,,

'HX NR "HX
X-

t -

K. A. Tirniryazev Agricultural Academy, Moscow. Translated from Khimiya Geterotsiklicheskikh

Soedinenii, No. 5, pp. 579-590, May, 1974. Original article submitted March 9, 1973.

9 19 75 Plenum Publishing Corporation, 22 7 West 1 7th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
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501
The l a t t e r , b e c a u s e of its weak basicity, exists p a r t i a l l y in the f o r m of unprotonated enamine IV. which
f o r m s s t r u c t u r e V via a s c h e m e involving a s i g m a t r o p i c [3. 3] shift with cleavage of the N--N bond and f o r -
m a t i o n of a C--C bond. Stabilization to an a r o m a t i c s y s t e m leads to o r t h o - s u b s t i t u t e d aniline VI. which
through addition of a NHR' group to the C = N double bond gives e s e r i n e d e r i v a t i v e VII. which is stabilized
by 3- elimination with ejection of a proton and opening of the p y r r o l i d i n e ring to the a r o m a t i c s t r u c t u r e of
t r y p t a m i n e salt VIII. This s c h e m e p r o v e d to be e x t r e m e l y p r o m i s i n g for subsequent studies in this field.
T r y p t a m i n e s and H o m o t r y p t a m i n e s . No difficulties w h a t s o e v e r w e r e o b s e r v e d when the substituents
in the benzene ring and those attached to the a - n i t r o g e n atom of the a r y l h y d r a z i n e w e r e v a r i e d and different
1.4-halocarbonyl compounds w e r e used. The yields in m o s t c a s e s w e r e quite high and r e a c h e d 90% [5-13].
It was found that 5 - h a l o c a r b o n y l compounds r e a c t with a r y l h y d r a z i n e s via a s i m i l a r s c h e m e to give 3- (~/-
aminopropyl)indoles (homotryptamines) [9. 12-14].
" /(CH2) 4 C~

~L~J~XNRINH2 ~R"
HCt HC~,
. R~(CHz)3 ?H2
"~ "-~R; "" R" Hc,

Eserine Systems. a - A l k y l - s u b s t i t u t e d ~ - h a l o ketones have f o r m e d t r i e y c l i c e s e r i n e s y s t e m s in high

/ CH(CH3)CH2CH2Cl CH3
R--~ -f- O=C R ~
NR~"--'NH2 ~CH3 h" " HCI.
CH3
yields [15-18]. H o m o e s e r o l i n e s y s t e m s and echiboline d e r i v a t i v e s [17, 18] could be obtained when the c o r r e -
sponding h a l o c a r b o n y l compounds w e r e used.

CH3 H

The r i n g - c h a i n t a u t o m e r i s m of s a l t s of such s y s t e m s with the e s t a b l i s h m e n t of the regions of e x i s -

tence of t a u t o m e r s as a function of the pH and s t r u c t u r e of the compounds was investigated in detail in a
n u m b e r of p a p e r s [19, 20].

-- 2.H +
R CH2CHzNH3
+2Ht
!,IN CH3
R CH3

A z a t r y p t a m i n e s . a - P y r i d y l h y d r a z i n e has f o r m e d the c o r r e s p o n d i n g 7 - a z a t r y p t a m i n e s in this reaction

u n d e r somewhat m o r e s e v e r e conditions [21]. However, u n d e r the usual conditions (at 70~ in methanol)
the r e a c t i o n stopped at the step involving a compound s i m i l a r to f o r m IV, and p y r i d y l a m i n o p y r r o l e existed
as a d i m e r in neutral m e d i a [22].

~ ~ H CHzCH2NH2 HCf,
,

CH3

~'~NHNH 'x'~~

502
 Reaction Mechanism. According to the r e a c t i o n scheme, the ~ - n i t r o g e n atom of the a r y l h y d r a z i n e
p a r t i c i p a t e s in the formation of the amino group of the aminoethyl portion of the t r y p t a m i n e molecule. In
o r d e r to confirm this assumption, a-15N-phenylhydrazine was converted to 2 - m e t h y l t r y p t a m i n e by heating
u n d e r the usual conditions with T - c h l o r o p r o p y l methyl ketone. If the s c h e m e is valid, the 2 - m e t h y l t r y p t -
amine f o r m e d should contain the 15N isotope in the 1 position, while the 2 - m e t h y l t r y p t a m i n e obtained f r o m
B-~SN-phenylhydrazine should contain the lSN isotope in the amino group of the side chain of the indole. In
fact, m a s s - s p e c t r a l analysis of the t r y p t a m i n e s proved the p r e s e n c e of the label at the sites of the molecules
c o r r e s p o n d i n g to the s c h e m e below [23].

--~CH2CH2NH2

CH2CH2NH2
0.. NHNH2 CH 3

When one examines the scheme, a question naturally a r i s e s regarding the prevailing direction of the
cyclization, i.e., regarding the quaternization of the a - or B- nitrogen atoms in the hydrazone molecule.
This question was solved p a r t i a l l y by calculations of s e v e r a l systems by the MS LCAO method within the
Huckel approximation [24].
A c o m p a r i s o n of the ~r-electron densities on the e - and /~-nitrogen atoms of the hydrazones shows
distinctly that the B-nitrogen atom is always m o r e basic, although the basicity of hydrazones is less than
the basieity of hydrazines, on the average by two o r d e r s of magnitude [25].

'~N H - - N = C - - C H 3
cc
XII

~+ / (cH2)3c[ [ ~ ~ H(CH2)2c[
0,1514-02256 /
N H ~ N~C--CsH 5 NH--NH--C--CsH 5
E~T= 19.O870j3 E~I"= 10.92OO

The formation of 1-anilinopyrroline III r a t h e r than a t e t r a h y d r o p y r i d a z i n e s y s t e m of the IX type during

quaternization is in complete conformity with the established rule [26].
Despite the fact that the "hydrazone" f o r m for the resulting anilinopyrroline salt (III ~ I V ) is m o r e
favorable f r o m an e n e r g y point of view (see E~ for X and Xa and [24]), the t a u t o m e r i c and, apparently, un-
protonated enehydrazine f o r m (IV), in which the atoms in the 1 and 6 positions a r e situated closely enough
f o r formation of a C--C bond, naturally undergoes reaction [24].
One should especially note the following fact. According to the general scheme for the F i s c h e r indole
synthesis, the r a t e - d e t e r m i n i n g step of the p r o c e s s is the formation of the enamine f o r m as a r e s u l t of p r o -
totropic catalysis [27] (see also [28] for the role of enamines in the F i s c h e r reaction).

CHR~ ,, CI= ~ I -H+~ tl

//\ /,F\ ~ L ~ N H NH/ \R

A B

However, not e v e r y act of protonation should lead to the enamine form, and, in connection with the "energie
disadvantageousness" of the enamine form, the t i m e during which it exists may be so short that t h e r e is
not enough t i m e for the next s t e p - a sigmatropie [3,3] s h i f t - to be r e a l i z e d (see below). The situation dif-
f e r s sharply for the analogous 1-anilinopyrroline fragment in the s c h e m e of the synthesis of tryptamines.
Unprotonated f o r m IV cannot exist in the hydrazone f o r m but exists only in the enamine form: this sharply
i n c r e a s e s the possibility for the o c c u r r e n c e of the next s t e p - sigmatropie [3,3] shift.

503
 C6Hr Results that attest to the significant effect of con-
R _C6H5f o r m a t i o n a l f a c t o r s as well on the trend of the p r o c e s s
._----- w e r e obtained in a m o r e detailed study of the reaction.
,~_ H J"'~C, F o r example, the r e a c t i o n of phenylhydrazine with I/-
"Y chloropropyl phenyl ketone, which p r o c e e d s through a
step involving the f o r m a t i o n of hydrazone X, gives t e t r a -
anti -form syn-form h y d r o p y r i d a z i n e XI instead of the expected t r y p t a m i n e
(XII). Moreover, cyclization o c c u r r e d at the a - n i t r o g e n
Fig. 1. Conformations of hydrazone m o l e c u l e s atom even during the r e a c t i o n with a - b e n z y l p h e n y l h y d r a -
(Dreiding models).
zinc and the f o r m a t i o n of the s a m e pyridazine (XI) due to
splitting out of benzyl chloride f r o m the unstable q u a t e r n a r y salt. The d i f f e r e n c e s in the ~r-electron den-
sities of the nitrogen a t o m s in the m o l e c u l e s of h y d r a z o n e s X and XII a r e not so significant as to induce r e -
orientation during i n t r a m o l e c u l a r cyclization. A conformational analysis of the hydrazoue m o l e c u l e s suc-
c e s s f u l l y explained the r e a s o n for the change in the c o u r s e of the r e a c t i o n [24].
According to the g e n e r a l concepts r e g a r d i n g the configuration of m o l e c u l e s with a multiple bond, the
1- 5 a t o m s should lie in a single plane (Fig. 1). The s t e r i c p r e r e q u i s i t e s for convenient attack of the C-C1
f r a g m e n t a r e p r e s e n t in the anti f o r m only on the m o s t b a s i c /~-nitrogen atom (Drei_ding model). In addition,
the distance between the 2 and 7 a t o m s is close to the length of the C--N bond ( ~ 2/~).

(~H2)3C[
{~~ CH2CH2NH2*
HCL-= ~ ~ 1 ~ NH_N~C~C6Hs"~~
C6H5 @
x,q o g c""5

Usual con-_
N_NH2diti~
I i c,.5
C6H5 C6H5 C6H5
xl~! xl._!

In the c a s e of hydrazone X by v i r t u e of ~r,v conjugation, the phenyl ring attached to the carbon a t o m
s t r i v e s to position i t s e l f in the plane of the 1.2,3 f r a g m e n t (Fig. 1). as a consequence of which the p r e s e n c e
of the anti f o r m b e c o m e s s t e r i c a l l y i m p o s s i b l e , and the hydrazone can exist in the syn f o r m . The r e l a t i v e
position of the nitrogen a t o m s and the C-C1 f r a g m e n t in it is such that only the a a t o m r a t h e r than the B
a t o m can undergo electrophilic attack, although the l a t t e r is also m o r e basic.
The c o r r e c t n e s s of these concepts was c o n f i r m e d by the isolation of phenyl ~ - c h l o r o p r o p y l ketone
diphenylhydrazone (XIII) u n d e r the usual conditions of the r e a c t i o n [24]. In this case, p y r i d a z i n e was not
f o r m e d b e c a u s e of the m a r k e d l y i n c r e a s e d b a s i c i t y of the a - n i t r o g e n atom, but t h e t r y p t a m i n e w a s f o r m e d
b e c a u s e of the fact that the hydrazone exists in the syn f o r m . I s o m e r i z a t i o n of the syn f o r m to the anti
f o r m o c c u r r e d only under c o n s i d e r a b l y m o r e s e v e r e conditions (160 ~ for 5 h), and the c o r r e s p o n d i n g t r y p t -
a m i n e (XIV) was f o r m e d .
Thus, calculation of the rr:-electron density of hydrazone molecules, t h e i r conformational analysis,
and the directed change of the b a s i c i t y of the e - and B-nitrogen atoms of the h y d r a z o n e s m a d e it possible
to explain one of the b a s i c steps that d e t e r m i n e s the direction of the p r o c e s s - the step involving i n t r a m o -
l e c u l a r quaternization (H --* III).
All of the i n t e r m e d i a t e s w e r e isolated and t h e i r s t r u c t u r e s w e r e established during a detailed study
of the r e a c t i o n to f o r m the t r y p t a m i n e s [24, 29. 30]. It is e a s y to note that hydrazone XII (mentioned above)
is i n t e r m e d i a t e II ( R = H , R'~=R"~C6Hs, X=C1).
It p r o v e d to be p o s s i b l e to s y n t h e s i z e T - c h l o r o p r o p y l methyl ketone phenylhydrazone (XIIa) by c a r r y -
ing out the r e a c t i o n in benzene (rather than in alcohol as is usually done) without heating [29].
Compound XVI. which is s i m i l a r in s t r u c t u r e to i n t e r m e d i a t e III, was obtained f r o m 1,3, 5 - t r i m e t h y l -
phenylhydrazine (X-V) [29].

504
 (CH2} 3 CL CH 3 CH 3

NHNH 2 CH 3 NH CH 3
CH3 CH 3 HCl
xv x v_!

It has been p r o p o s e d that the m o s t i m p o r t a n t step of the p r o c e s s - f o r m a t i o n of the C - C bond (IV ~ V) -

be c o n s i d e r e d to be a s i g m a t r o p i c [3,3] r e a r r a n g e m e n t [31]. The a p p r o a c h f r o m the point of view of the
W o o d w a r d - H o f f m a n n g e n e r a l principle, which is c o n s i d e r e d below, had a l r e a d y been s u c c e s s f u l l y applied in
the examination of the Claisen r e a r r a n g e m e n t [32]. In [31] it is p r o p o s e d that the p r i n c i p a l step in the
F i s c h e r indole s y n t h e s i s (formation of the C - C bond) and in a n u m b e r of other r e l a t e d p r o c e s s e s (for ex-
ample, the benzidine r e a r r a n g e m e n t ) be c o n s i d e r e d to be a sig-matropic [3.3] shift.
As applied to the step under consideration, it is p r o p o s e d that the s i g m a t r o p i c [3.3] shift o c c u r s in the
following m a n n e r . Simplifying, it is n e c e s s a r y to examine only the f r a g m e n t of the m o l e c u l e consisting of
the six a t o m s of the IV f o r m that p a r t i c i p a t e d i r e c t l y in the p r o c e s s . The nitrogen a t o m s can be f o r m a l l y
c o n s i d e r e d to be c a r b o n a t o m s and, consequently, it can be supposed that t h e i r p e l e c t r o n s do not p a r t i c i p a t e
in the p r o c e s s .

3 a/
N--N--

Under the condition of retention of the orbital s y m m e t r y , within a rough approximation, the s i g m a t r o p i e
[3,3] shift o c c u r s a p p r o x i m a t e l y in this m a n n e r f o r the 1.5-hexadiene f r a g m e n t . The lobes of the N - N
bond in the 3, 4 position swing around and b e c o m e f u r t h e r away f r o m one another, while the t e r m i n a l .lobes
of the ~ bonds in the 1-6 position begin to a p p r o a c h one another as they swing around. In this case, r e h y -
b r i d i z a t i o n of the a t o m s (sp 3 --*sp2 for the 3 and 4 a t o m s and sp 2 ~ sp 3 for the 1 and 6 atoms) also gradually
takes place.

N--N N N

1 6

2 5 ,~ 2 5

The t r a n s i t i o n state is a f o u r - c e n t e r s t a t e - chair c o n f o r m a t i o n - and has the f o r m of the two u p p e r

occupied m o l e c u l a r orbitals of allyl r a d i c a l s , for which the 3 - 4 bond is not yet definitely b r o k e n and the 1-6
bond is not yet definitely f o r m e d . The development of the c h a i r conformation (rather than the boat c o n f o r -
mation) is d e t e r m i n e d by its g r e a t e r advantageousness b e c a u s e of l o w e r repulsion of the nonbonding m o -
l e c u l a r orbitals in the t r a n s i t i o n s t a t e [31].

Ill

Only a t r a n s i t i o n - s t a t e s t r u c t u r e that p e r m i t s s u p r a - s u p r a m i g r a t i o n of the ~ bond in the ground state

is p o s s i b l e for the p l a n a r s t r u c t u r e of the N - a r y l f r a g m e n t .
The use of a - a c y l a r y l h y d r a z i n e s in the r e a c t i o n p r o v e d to be e x t r e m e l y i n t e r e s t i n g f r o m the point of
view of the elucidation of the detailed m e c h a n i s m of the p r o c e s s . In an a t t e m p t to synthesize a t r y p t a m i n e
a r y l a t e d in the 1 position of the indole ring it was unexpectedly o b s e r v e d that a - a c e t y l - / ~ - ( 3 - a c e t y l p r o p y l ) -
phenylhydrazine (XVII) - the p r o d u c t of alkylation of a - a c e t y l p h e n y l h y d r a z i n e (XVIII) with a chloro k e t o n e -

505
r a t h e r than the expected tryptamine [30] is formed when equimolar amounts to the starting compounds are
refluxed.

~ CHzCHzNH29HCt

"i
COCH3
~N__NHz -I- cH3COcHzCHzcH2cI" (IH2)3 Ct

I #c
COCH3 ~N__N//, ~CH 3
xw,j I
COCH3
XIX

[
~N~NH (CHz)3COCH3= - "N--N I ~ N~
t I c., I ct-
COCH3 COCH . COCH
XVll xx-'-i xx

A thorough study of this reaction showed that XVII is not formed by direct alkylation of hydrazineXVII.
a-Acetylphenylhydrazine {XVIII) reacts with the carbonyl group of the chloro ketone to give phenyl-
hydrazone XIX. The hydrazone then cyclizes to 1-anilinopyrroline hydrochloride (XX}, which undergoes
hydrolytic opening of the ring to give hydrazine XVII. The proof of this scheme was based on a study of the
dynamics of the intensity of the absorption band of the ketone carbonyl group in the IR spectrum [30].
Compound XVH ver y readily loses a water molecule. Thus, even during treatment with picric acid,
it cyclizes with splitting out of water to form the picrate of 1-acetylanilino-2-methyl-A2-pyrroline (XXII)-
an intermediate of the IV type {R=H, R' =COCH3, R"=CH3).
Base XXIII, which exists as dimer XXIV under these conditions, is isolated on treatment of picrate
XXII with liquid ammonia with simultaneous removal of the acetyl group. Dimer XXIV is converted to the
salt of monomer XXV in acidic media (at pH < 1.6) [30] (see also [22]).
Base XXVI, which corresponds to 1-anilinopyrroline IV, was obtained by refluxing XVII in xylene
with removal of an equimolar amount of water by distillation.

-- H20"- ~ N~'~ C H3
I
COCH3 J coc H~[%H2N3%]-
-- XXll

I NH

H 3

XX._~V XXIV XXIII

Crystalline substance XXVII, which is similar in structure to intermediate VI (R=H, R' =COCH~, R"=CH3) ,
was isolated on distillation of XXVI.
Treatment of intermediate XXVII with boiling acetic anhydride gives diacetylated 2-methyltryptamine
XXVIII, which readily converted to 2-methyltryptamine during acid hydrolysis [30].

506
 xv~

,
COCH3 / COCH3
xw'--"i XX~",i / x',x'V[;

~ H
CH2CH2NH2

CH3
~CH2CH2NHCOCH

'i CH3
3

COCH3
XXVIII

The l a t t e r i n t e r m e d i a t e of the VII type was obtained as a r e s u l t of the r e a c t i o n of phenylhydrazine

with 5 - c h l o r o - 3 - m e t h y l - 2 - p e n t a n o n e [17] (see the s c h e m e on p~ 502).
The s t r u c t u r e of all of the i n t e r m e d i a t e s d e s c r i b e d above was p r o v e d r i g o r o u s l y by IR. UV, and PMR
s p e c t r o s c o p y and m a s s s p e c t r o m e t r y [33-37].
An attempt has been m a d e to study the k i n e t i c s of the f o r m a t i o n of t r y p t a m i n e s [38]. Two r e a c t i o n s -
the synthesis of 9 - b e n z y l t e t r a h y d r o c a r b a z o l e [39] and the synthesis of 2 - m e t h y l t r y p t a m i n e - have been
s e l e c t e d as m o d e l r e a c t i o n s . The m e c h a n i s m s of these r e a c t i o n s a r e s i m i l a r , but in the c a s e of the f o r -
m a t i o n of 2 - m e t h y l t r y p t a m i n e , quaternization of the ~ - n i t r o g e n a t o m of the a r y l h y d r a z i n e o c c u r s i n t r a -
m o l e c u l a r l y , while quaternization o c c u r s i n t e r m o l e c u l a r l y in the c a s e of the f o r m a t i o n of N - b e n z y l t e t r a -
hydrocarbazole.
According to the data obtained by McLean and c o - w o r k e r s [40] and P a u s a c k e r and Schubert [41], the
r a t e of the F i s c h e r r e a c t i o n c o r r e s p o n d s a p p r o x i m a t e l y to a f i r s t - o r d e r equation. A study of the kinetics
of the f o r m a t i o n of 9 - b e n z y l t e t r a h y d r o c a r b a z o l e also gave a f i r s t - o r d e r equation for this r e a c t i o n [39].

I
CH2C6H5 CBH5CH2 CH2CH---~CH2]

C6HsCH2 CH2CH~CH2

+ C H ~ C H CH2NH2" HS,r"

I
I C~H5CH2 NH2CH2CH~CH2 CH2C6H5
L

Ionic halogen (bromine in this case) a p p e a r s in the step involving quaternization of the B-nitrogen
a t o m of hydrazine. If the Br concentration at each given instant coincides with the concentration of the
final p r o d u c t - a l l y l a m i n e h y d r o b r o m i d e - the a s s u m p t i o n that the step that d e t e r m i n e s the r a t e of the
o v e r a l l r e a c t i o n is quaternization is valid. In fact, this s o r t of coincidence of the concentrations has been
o b s e r v e d [38].
As one should have expected, the slowest stop in the f o r m a t i o n of 2 - m e t h y l t r y p t a m I n e also should be
quaternization of the nitrogen atom, wMch leads to the f o r m a t i o n of 1 - a n i l i n o p y r r o l i n e (II - - I I I ) . This was
shown in the following way. First, it was e s t a b l i s h e d that the step involving the f o r m a t i o n of the hydrazone
is not the limiting step. With this in mind, the dependence of the intensity of the a b s o r p t i o n of the carbonyl
group of ~/-chloropropyl methyl ketone on t i m e during its r e a c t i o n with phenylhydrazine was studied s p e c -
t r o p h o t o m e t r i c a l l y . It was found that the r e a c t i o n is c o m p l e t e (~90%) a f t e r 2 mill, while the s a m e d e g r e e
of c o n v e r s i o n of the s t a r t i n g compounds to 2 - m e t h y l t r y p t a m i n e (under the s a m e conditions) r e q u i r e s > 300
rain. Second, the C1- concentration at any instant coincided with the t r y p t a m i n e concentration: as in the

507
c a s e of the f o r m a t i o n of the carbazole, this indicated the c o r r e c t n e s s of the selection of the step involving
quaternization as the limiting step. Third, a s h a r p i n c r e a s e in the r e a c t i o n r a t e was o b s e r v e d when the
alcohol was diluted with water. This c o n f i r m e d the point of view that the step involving quaternization de-
t e r m i n e s the r a t e of the p r o c e s s . T h e r e a r e s i m i l a r e x a m p l e s that d e s c r i b e this s o r t of a c c e l e r a t i o n during
the cyclization of w-aminoalkyl halides in the l i t e r a t u r e [42]. Despite the fact that the r a t e of f o r m a t i o n of
2 - m e t h y l t r y p t a m i n e was determined, as a t t e s t e d to by d i r e c t and indirect data, by the r a t e of the second
s t e p - quaternization of the B - n i t r o g e n a t o m - no d e f i n i t e o r d e r could be assigned to this reaction: the r e a c -
tion o r d e r was found to be 1.28. The deviation of this value f r o m unity apparently indicated the effect of
other i n t e r m e d i a t e steps also on the r a t e of the p r o c e s s .
IndolyIalkylamines f r o m Cyclic Enamines. In attempts to f u r t h e r extend the range of application of
the r e a c t i o n it was found that a r y l h y d r a z i n e salts r e a c t with the salts of cyclic enamines via the s c h e m e
below to give the c o r r e s p o n d i n g t r y p t a m i n e s or h o m o t r y p t a m i n e s [43-48].

__ NRI--~H3
i"~"(CH2)m

H
R f,"~"~ f----CH2)n

r1:1 u.~u 2

. _ _ ~

(CH2)n+~-NH3 R F~'~
1 it,-,,-,-(CH2)n
R _NHt
NR--NH2 H3
R~
Tryptophols and Homotryptophols f r o m Cyclic Vinyl Ethers. Similarly. participation of cyclic vinyl
e t h e r s in p l a c e of cyclic e n a m i n e s led to the c o r r e s p o n d i n g tryptophols [49, 50] and homotryptophols [49-54].

o : , or 2 '.,

The method was l a t e r modernized, and the tryptophols w e r e obtained f r o m a - a c y l b u t y r o l a c t o n e s , which

f o r m e d the tryptophols in a o n e - s t e p p r o c e s s a f t e r h y d r o l y s i s and decarboxylation [55].

(CH-)-OH CH.CFLOH
d'c H+
R + O/~ = R"-~ C--R-'iz-'. lJ 1]

NRi--NH2 O" - R~

Physovenine S t r u c t u r e s . The u s e of t h e o r e t i c a l r e p r e s e n t a t i o n s of the F i s c h e r synthesis and s o m e

modified methods f o r its r e a l i z a t i o n [56-58] have m a d e it p o s s i b l e to w o r k out an i m p o r t a n t (in a p r a c t i c a l
sense) s c h e m e f o r the p r e p a r a t i o n of physovenine s t r u c t u r e s [36, 59-63].
R It

Ring-chain t a u t o m e r i s m , which was investigated in detail in [36]. is c h a r a c t e r i s t i c f o r s a l t s of the

l a t t e r and for s a l t s of e s e r i n e s in acidic m e d i a [36].
P h y s i c o c h e m i e a l Investigations. The investigation of the indole d e r i v a t i v e s d e s c r i b e d above by m e a n s
of p h y s i c o c h e m i c a l methods is p a r t i a l l y r e f l e c t e d in the p a p e r s a l r e a d y cited. In addition, one m a y f a m i l i a r -
ize h i m s e l f with m a s s - s p e c t r a data [64-69], with PMR s p e c t r o s c o p i c data [34, 35]. and g a s - l i q u i d c h r o m a -
t o g r a p h i c a n a l y s i s [70-74] in special p a p e r s .

LITERATURE CITED
1. I . I . Grandberg, T. I. Zuyanova. and N. I. Afonina. USSR A u t h o r ' s C e r t i f i c a t e No. 192,818 (1966): Byul.
Izobr.. No. 6 (1967).
2. I . I . Grandberg. Izv. Akad. Nauk SSSR. Ser. Khim., 1682 (1966).

508
 3. M. Sletzinger, W. Ruyle, and W. Gainess, US Patent No. 2.995,566 (1957); Chem. Abstr., 56, 1431
(1962).
4. M. Sletzinger, W. Gainess, and W. Ruyle. Chem. Ind.. 1215 (1957).
5. L I. Grandberg and T. I. Zuyanova, Khim. Geterotsikl. Soedin., 875 (1968).
6. L I. Grandberg, T. L Zuyanova, N. I. Afonina, and T. A. Ivanova. Dokl. Akad. Nank SSSR, 176, 583
(1967).
7. I.I. Grandberg, T. I. Zuyanova,N. I. Afonina, and T. A. Ivanova, DoLl. Timiryazevskoi Sel'skoI~oz.
Akad., 124. 325 (1967).
8. I.I. Grandberg and T. I. Zuyanova,USSRAuthor's Certificate No. 196,852 (1966): Byul. Izobr., No. 12
(1967).
9. I.I. Grandberg, N. I. Afonina, and T. I. Zuyanova,USSRAuthor's Certificate No. 201,412 (1966): Byul.
Izobr., No. 18 (1967).
10. I.I. Grandberg. N. I. Afonina, and T. I. Zuyanova,Khim. Geterotsikl. Soedin.. 1038 (1968).
11. I.I. Grandberg, N. M. Przheval'skii, T. A. Ivanova, T. I. Zuyanova,N. I. Bobrova, S. N. Dashkevich,
S. B. Nikitina, T. P. Shcherbina. and N. G. Yaryshev, Izv. Timiryazevskoi Sel'skokhoz. Akad., No. 5,
208 (1969).
12. L I. Grandberg and T. I. Zuyanova. Khim. Geterotsikl. Soedin., 51 (1971).
13. I. L Grandberg and N. I. Bobrova, Khim. Geterotsikl. Soedin.. 213 (1973).
14. I. L Grandberg and T. I. Zuyanova, Khim. Geterotsikl. Soedin., 1495 (1970).
15. I . I . Grandberg and T. A. Ivanova, USSR Author's Certificate No. 201,411 (1966): Byul. Izobr., No. 18
(1967).
16. I . I . Grandberg and T. A. Ivanova, Dokl. Timiryazevskoi Sel'skokhoz. Akad., 160, 232 (1970).
17. I . I . Grandberg and T. A. Ivanova, Khim. Geterotsikl. Soedin., 480 (1970).
18. L I. Grandberg and T. A. Ivanova, Khim. Geterotsikl. Soedin., 939 (1970).
19. I, L Grandberg, T. A. Ivanova. and N. G. Yaryshev, Khim. Geterotsikl. Soedin.. 1276 (1970).
20. I . I . Grandberg and T. A. Ivanova, Khim. Geterotsikl. Soedin., 1489 {1970).
21. I . I . Grandberg and N. G. Yaryshev, Khim. Geterotsikl. Soedin., 1070 (1972).
22. I . I . Grandberg and N. G. Yaryshev, Khim. Geterotsikl. Soedin.. 1702 (1972).
23. I . I . Grandberg, N. M. Przheval'skii, V. I. Vysotskii, and R. A. Khmel'nitskii, Khim. Geterotsikl.
Soedin., 447 (1970).
24. I . I . Grandberg, T. I. Zuyanova. N. M. Przheval'skii. and V. I. Minkin, Khim. Geterotsikl. Soedin.,
750 (1970).
25. V.I. Sorokin, Master's Dissertation [in Russian], Moscow (1973).
26. I . I . Grandberg and N. M. Przheval'skii, Khim. Geterotsikl. Soedin., 1273 (1970).
27. I. L Grandberg and V. I. Sorokin, Khim. Geterotsikl. Soedin.. 31 (1973).
28. I . I . Grandberg and N. M. Przheval'skii. Khim. Geterotsikl. Soedin.. 943 (1969).
29. L I. Grandberg, N. M. Przheval'skii, and V. I. Vysotskii, Khim. GeterotsiLl. Soedin., 1499 (1970).
30. I. L Grandberg, T. I. Zuyanova, and K. K. Zhigulev, Khim. Geterotsikl. Soedin., 1708 (1972).
31. I . I . Grandberg, Izv. Timiryazevskoi Sel'skikhoz. Akad., No. 5, 188 (1972).
32. R. Woodward and R. Hoffmann, Conservation of Orbital Symmetry, Academic Press.
33. I . I . Grandberg, T. A. Ivanova, and T. I. Zuyanova, Izv. Timiryazevskoi Sel'skokhoz. Akad., No. 3,
212 (1970).
34. V.I. Vysotskii, R. A. Khmel'nitskii, and I. I. Grandberg. Izv. Timiryazevskoi Sel'skokhoz. Akad.,
No. 5, 204 (1970).
35. I . I . Grandberg and S. N. Dashkevich, Izv. Timiryazevskoi Sel'skokhoz. Akad., No. 1, 189 (1971).
36. I . I . Grandberg and S. N. Dashkevich, Khim. Geterotsikl. Soedin., 1194 (1971).
37. K . K . Zhigulev, R. A. Khmel'nitskii, I. I. Grandberg, and V. I. Vysotskii. Khim. Geterotsikl. Soedin.,
1065 (1972).
38. I . I . Grandberg and N. M. Przheval'skii, Izv. Timiryazevskoi Sel'skokhoz. Akad., No. 2, 192 (1972).
39. I . I . Grandberg, D. V. Sibiryakova, and L. A. Brovkin, Khim. GeterotsiLl. Soedin., 94 {1969).
40. T. McLean. S. McLean, and R. Reed, J. Chem. Soc., 2519 (1955).
41. K. Pausacker and C. Schubert, J. Chem. Soe., 1814 (1950).
42. H. Freundlich and H. Kroepelin. Z. Phys. Chem...122, 39 (1926).
43. I . I . Grandberg and S. B. Nikitina, Khim. Geterotsikl. Soedin., 54 (1971).
44. I. L Grandberg. S. B. Nikitina, and N. G. Yaryshev, Izv. Timiryazevskoi Sel'skokhoz. Akad., No. 2,
196 (1970).
45. I . I . Grandberg and S. B. Nikitina, Dokl. Timiryazevskoi Sel'skokhoz. Akad., 162, 374 (1971).
46. I . I . Grandberg and S. B. Nikitina, Khim. GeterotsiLl. Soedin., 1204 (1971).

509
47. I . I . Grandberg and S. B. Nikitina, Khim. Geterotsikl. Soedin., 1216 (1972).
48. I . I . Grandberg, N. M. Przheval'skii, and T. A. Ivanova, USSR Author's Certificate No. 248.689 (1968):
Byul. Izobr., No. 24 (1969).
49. I . I . Grandberg and N. I. Afonina. USSR Author's Certificate No. 239.341 (1967): Byul. Izobr., No. 11
(1969).
50. I . I . Grandberg and T. P. Moskvina, Khim. Geterotsikl. Soedin., 1366 (1972).
51. I . I . Grandberg and T. P. Moskvina. Khim. Geterotsild. Soedin., 942 (1970).
52. I . I . Grandberg and T. P. Moskvina, Dokl. Timiryazevskoi Sel'skokhoz. Akad., 162, 380 (1971).
53. I . I . Grandberg and T. P. Moskvina. Khim. Geterotsild. Soedin.. 90 (1974).
54. I . I . Grandberg and T. P. Moskvina, Izv. Timiryazevskoi Sel'skokhoz. Akad., No. 4, 167 (1973).
55. I . I . Grandberg and G. P. Tokmakov, Khim. Geterotsitd. Soedin., 205 (1974).
56. I . I . Grandberg and D. V. Sibiryakova, USSR Author's Certificate No. 199,892 (1966): Byul. Izobr.,
No. 16 (1967).
57. I . I . Grandberg, L. V. Brovkin, T. A. Belyakova, and D. V. Sibiryakova, Khim. Geterotsikl. Soedin.,
97 (1969).
58. I . I . Grandberg, T. I. Zuyanova, N. I. Afonina, and T. A. Ivanova, USSR Author's Certificate No.
242,901 (1967); Byul. Izobr., No. 16 (1969).
59. I . I . Grandberg and S. N. Dashkevich. USSR Author's Certificate No. 276,062 (1969): Byul. Izobr.,
No. 23 (1970).
60. I. L Grandberg and S. N. Dashkevich, Khim. Geterotsikl. Soedin., 1631 (1970).
61. I . I . Grandberg and S. N. Dashkevich. Dokl. Timiryazevskoi Sel'skokhoz. Akad.. 160. 243 (1970).
62. I . I . Grandberg and S. N. Dashkevich. Khim. Geterotsikl. Soedin., 342 (1971).
63. I . I . Grandberg and S. N. Dashkevich, Khim. Geterotsikl. Soedin., 782 (1971).
64. V. I. Vysotskii, R. A. Khmel'nitskii, I. I. Grandberg, and G. V. Fridlyandskii, Izv. Timiryazevskoi
Sel'skokhoz. Akad., No. 3, 206 (1971).
65. R . A . Khmel'nitskii, E. A. Kunina, S. N. Dashkevich, and I. I. Grandberg, Izv. Timiryazevskoi Sel'sko-
khoz. Akad., No. 4, 214 (1971).
66. R . A . Khmel'nitskii. N. A. Klyuev, A. F. Dolgikh, T. P. Moskvina, and I. I. Grandberg, Izv. Timirya-
zevskoi Sel'skokhoz. Akad., No. 3. 192 (1973).
67. R . A . Khmel'nitskii, V. I. Vysotskii, and I. I. Grandberg, Zh. Organ. Khim., 5, 417 (1969).
68. V.I. Vysotskii, R. A. Khmel'nitskii, I. I. Grandberg, and V. A. Budylin, Izv. Timiryazevskoi Sel'sko-
khoz. Akad., No. 4, 221 (1970).
69. R . A . Khmel'nitskii. V. I. Vysotskii, I. I. Grandberg, A. N. Kost, and V. A. Budylin, Zh. Organ. Khim.,
7, 1514 (1971).
70. L.B. Dmitriev and L I. Grandberg, Izv. Timiryazevskoi Sel'skokhoz. Akad., No. 5, 206 (1973).
71. I . I . Grandberg, L. D. Belyaeva, and L. B. Dmitriev, Khim. Geterotsikl. Soedin., 37 (1973).
72. I . I . Grandberg, L. D. Belyaeva, and L. B. Dmitriev, KhLm. Geterotsikl. Soedin., 1204 (1971).
73. I . I . Grandberg, L. B. Drnitriev, and L. D. Belyaev, Dokl. Timiryazevskoi Sel'skokhoz. Akad., 1_~62.
398 (1971).
74. I . I . Grandberg, L. D. Belyaeva, and L. B. Dmitriev. Khim. Geterotsikl. Soedin., 58 (1971).

510
SYNTHESIS OF COUMARANS FROM ALKENYLPHENOLS

V. I. I s a g u l y a n t s , * V, R . M e l i k y a n , UDC 547.728.1 -. 543.422.6

E . M. L ' v o v a , A . U. S t e p a n y a n t s ,
a n d V. P . L e z i n a

A number of substituted coumarans, the s t r u c t u r e s of which w e r e confirmed by UV and PMR

spectroscopy, w e r e synthesized by the reaction of phenols with 4 - ~ n y l - l - c y c l o h e x e n e in
the p r e s e n c e of KU-2 cation-exchange resin.

The cyclization of o-alkenylphenols to e h r o m a n s and coumarans is one of the simple methods for the
synthesis of compounds of this class [1]. We have synthesized a number of substituted coumarans that have
not been d e s c r i b e d in the l i t e r a t u r e by r e a c t i o n of phenols with 4 - v i n y l - l - c y e l o h e x e n e in the p r e s e n c e of
KU-2 cation-exchange resin.

o. e+ o. .
.+ /
]

The s t r u c t u r e of the compounds was confirmed by means of UV and PMR spectroscopy. The UV spec-
t r u m contains maxima at 285-289 nm (log ~ 3.45-3.47), which is c h a r a c t e r i s t i c for the s p e c t r a of coumarans
[2]. The PMR s p e c t r a l data a r e p r e s e n t e d in Table 1.

*Deceased.

TABLE 1. Chemical Shifts in the PMR Spectra of Coumarans

"~! Substiments Chemical shifts, ~ , ~ m
." -:c~--IcHo,c. [ oH:, c. I c0.
I
[i1-I t~tt3 /I-I 2,,88m* 1,02--2,20 1 -
i 0,85t 6,35--7,00m
/=7.5Hz I
! I CH3 tI H 2,89m 11,10--1,94 2,07s 0,90t I 6,20--6,90m
l.lH H 2,89m 11,18--2,00[ 2,18s i 0,92t ,6,65d I=8,0 Hz
I 6,44s 6,38 d
lv[H ] H CI-~ 2,83m 1,00--1,90 2,10s -- 0,84t ~6,69q659d 1=
= 2,0 Hz 6,58 d
s I 1=8,0 Hz
V/H H C(_.tt~)3 2,83m 1,10--1,90 -- 1,90 0,86t 6,92 q 6,7"9d ] =
=2,5 Hz6,54 d
s ~ ]=85, Hz
VI C(Clla)s H !CI-[3 ] 2,89m]1,18--2,00 2,l 4 s 1,29 0,93t !6,74d 6,48d
' J=2,0 Hz

*The abbreviations used h e r e and subsequently a r e as follows: s is

singlet, d is doublet, t is triplet, q is quartet, and m is multiplet.

I. M. Gubkin Moscow Institute of the P e t r o c h e m i c a l and Gas Industry. T r a n s l a t e d f r o m Khimiya

Geterotsiklicheskikh Soedinenii, No. 5, pp. 591-592, May, 1974. Original a r t i c l e submitted April 11, 1973.

9 1975Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy of this article is availablefrom the publisher for $15.00.

511
 TABLE 2. Properties of Cotunarans
Corn - bpo ~ i MRo IEmperl- Found, ~% Calc.
pound Yield,
(ram) d r~
" ' ~ 'Ifound calm cal for- C H
I i Imula

II 120 (2) 1,0296 1,53811 65,61 65,11 C,sH2oO 83,1 9,3 83,3 9,3 33
III 123 (2) 1,030611,54011 65,77 65,11 C,sH2oO 82,9 9,3 83,3 9,3 68
IV 124 (2) 1,0324]1.54121 65,75 65,11 ClsH2oO 83,1 9,2 83,3 9,3 89
v 146 (2) 1,0130 1,5288 78,00 77,82 CLsH~O 83,9 9,9 83,8 10,1 66
VI [35 (2) 1,0007 1,5313 84,09 83,58 C19H280 83,5 t 0,9 83,8 10,3 30

EXPERIMENTAL
The PMR s p e c t r a of CC14 solutions w e r e r e c o r d e d with a J N M - C 6 0 - H L s p e c t r o m e t e r at 60 MHz with
h e x a m e t h y l d i s i l o x a n e (HMDS) as the i n t e r n a l standard. The UV s p e c t r a of CC14 solutions w e r e r e c o r d e d
with a Hitachi r e c o r d i n g s p e c t r o p h o t o m e t e r .
2 - E t h y l - 2 , 3 , 4 , 5 , 1 1 , 1 2 - h e x a h y d r o d i b e n z o f u r a n {I). A 5.4-g (0.05 mole) s a m p l e of 4 - v i n y l - l - e y c l o h e x e n e
was added dropwise with s t i r r i n g at 127-128 ~ to a m i x t u r e of 9.4 g (0.1 mole) of phenol and 3 g of KU-2
c a t i o n - e x c h a n g e resin, a f t e r which the m i x t u r e was held at the s a m e t e m p e r a t u r e for 2 h. The c a t a l y s t was
s e p a r a t e d , and the r e a c t i o n p r o d u c t s w e r e dissolved in sulfuric acid. The sulfuric acid solution was t r e a t e d
with a C l a i s e n solution to r e m o v e n e u t r a l compounds f r o m the acidic compounds. The e t h e r l a y e r was neu-
t r a l i z e d , dried, and distilled to give 3 g (30%) of I with bp 120 ~ (2 ram), d42~ 1.0452. and nD 2~ 1.5443. Found
%. C 83.1. H 8.8: M 201; MR D 60.99. Ci4H180. Calculated %. C 83.2; H 8.9. M 202: MR D 60.50.
Compounds I I - V I w e r e s i m i l a r l y obtained (Table 2).

LITERATURE CITED
1. E. A. Viktorova, N. I. Slmikin. and B. G. Bubnova. Zh. Obshch. Khim., 31 , 479 (1961).
2. D. Gagniant and P. Gagniant, Bull. Soc. Chim. F r a n c e , 838 (1957).

512
RESEARCH ON P O L Y F U N C T I O N A L OXIDES
VIII.* PREPARATION, PMR SPECTRA, CONFIGURATIONS,
AND CONFORMATIONS OF SOME 1, 3-DIOXOLANES

L. P . G l u s h k o , T . M. M a l i n o v s k a y a , UDC 547.729.7 : 541.63 : 543.422.25

M. S. M a l i n o v s k i i , M. M. K r e m l e v ,
N. I. P o k h o d e n k o , T. A. Z y a b l i k o v a ,
a n d N. A. Z h i k h a r e v a

N,N-Diethylcarbamoyl-4,5-epoxy-2-hexenoic acid reacts with ketones in the presence of an-

hydrous FeC13 to give 2,2, 4-trialkyl- 5- [2- N.N-diethylearbamoyl (vinylene)]- 1,3-dioxolane.
2,2,4-Trimethyl-5-(1-propenyl-3-hydroxy)-l.3-dioxolane is formed in the reduction of 2,2,4-
trimethyl-5-[2-carbethoxy(vinylene)]-l,3-dioxolanewithlithinm aluminum hydride.

Esters of 4,5-epoxy-2-hexenoic acid react with ketones in the presence of acid catalysts to give 2,2.4-
trialkyl-5- [2-carbalkoxy(vinylene)]-l,3-dioxolanes [2]. In contrast to the esters, substituted amides of 4, 5-
epoxy-2-hexenoie acid react with ketones in the presence of a large excess of FeC13. We have carried out
the reaction of N, N-diethylcarbamoyl-4. 5-epoxy-2-hexenoic acid with acetone and methyl ethyl ketone:

CHz--CH--CH--CH=CH--CON(C2HSL\o
/ - +rcoca a~ CHa--CH--CH--Ctt=CH--CON(C~H~) 2
I O 0 II
~ ~ \//\
R CH a
c.~ -cH--c.--(c,9~--coN(c.,up~
0 0
\/ /\ m
R CH a II R=C2H~ ~ I1 a R=CH a

The IR spectra of II contain absorption bands at 1025-1055 cm -1, which are due to vibrations of
C--O--C bonds, but do not contain the absorption bands of the epoxide ring (840 cm-l). Compounds II are
readily hydrogenated by hydrogen in the presence of Raney Ni to 2,2, 4-trialkyl- 5- [2- N, N-diethylcarbamoyl-
(ethyl)]- 1, 3-dioxolanes (III).

0 0 - ~ 0 O
\/ \/
/\ /\
CH 3 CH a IV CHa CH3 V

In2. Raney Ni tu2. Raney Ni

c.o-c.-c.-(c.o)~cooc,H
I I " ~ " LiAIH4
cx3-cH-c.-(c.p~ou
0 0 0 0
\/ \/
/\ /\
CH3 CH3 VI CHa CHa VII

The reduction of 2,2,4-trimethyl- 5- [2- carbethoxy (vinylene)]- 1,3-dioxolane (IV) with lithium aluminum
hydride gave 2,2,4-trimethyl-5-{1-propenyl-3-hydroxy)-l,3-dioxolane (V). which is hydrogenated by hydrogen
over Raney Nickel to saturated alcohol VII, which is also obtained by alternative synthesis from ester VI.
* See [1] for communication VII.
Dnepropetrovsk State University. A. E. Arbuzov Institute of Organic and Physical Chemistry, Kazan.
Translated from Khirniya Geterotsiklieheskikh Soedinenii, No. 5. pp. 593-596. May. 1974. Original article
submitted April 2. 1973.

J
9 1975Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

513
 II
LO r

pp m 6. . . .4 . ppm
Fig. I, PMR spectrum of IIa.
O O O

The PMR s p e c t r a (Table 1) c o n f i r m the a s s i g n e d s t r u c t u r e

f o r all of the 1,3-dioxolanes obtained. The s p e c t r u m of IIa is
OD O cO t~
p r e s e n t e d in Fig. 1 as an example. The magnitude of the JCD
vicinal constant (15 Hz) in the s p e c t r u m of Ha indicates t r a n s
orientation of the coupling protons attached to the double bond.
According to the K a r p l u s - C o n r o y angular c o r r e l a t i o n [3], a JCB
constant of 4 Hz c o r r e s p o n d s to the gauche conformation between
the two coupling H B and H C p r o t o n s .
The configuration of substituents r e l a t i v e to the 1,3-dioxo-
lane ring is usually established f r o m the coupling constants of
the H A and H B vicinal p r o t o n s . It is seen f r o m T a b l e 1 that
t h e s e p r o t o n s couple with a constant of 6.3 Hz. It is known [4]
that the t r a n s constant is l o w e r than the cis constant for s m a l l
rings, including f i v e - m e m b e r e d rings. We t h e r e f o r e a s s u m e
that the JAB constant of 6.3 Hz indicates t r a n s orientation of the
substituents.
L e t us c o n s i d e r the conformation of the d i e t h y l c a r b a m o y l
group r e l a t i v e to the u n s a t u r a t e d bond. The H C and H D protons
a r e nonequivalent (ASCD = 0.27 ppm), and the H C p r o t o n (Fig. 1)
is shifted to weak field as a consequence of the p a r a m a g n e t i c
a n i s o t r o p i c effect of the c a r b o n y l group: this is p o s s i b l e ff it is
u
u--o
I. \/ O not in conjugation with the double bond. A consequence of this
is the s - c i s c o n f o r m a t i o n of the u n s a t u r a t e d f r a g m e n t .
I
ff The s t r u c t u r e of the s a t u r a t e d 1,3-dioxolanes (IIIa) was
r~ also e s t a b l i s h e d by m e a n s of the PMR s p e c t r a . It can be seen
=
0
u _~ ~_ ~ o~ ,-, f r o m Table 1 that the position of the substituents r e l a t i v e to the
rr
U 1,3-dioxolane ring is r e t a i n e d during reduction, as indicated by
O the a l m o s t equal JAB values, but the chemical shifts of the HA
and H B p r o t o n s a r e inverted b e c a u s e of r e m o v a l of the p a r a -
! 2::=
UU
\/ m a g n e t i c effect of the double bond.
U
O
0 EXPERIMENTAL
N
The PMR s p e c t r a * of 1% solutions of the compounds in
u :z
@ z ~ CCI 4 w e r e r e c o r d e d with a V a r i a n HA-100D s p e c t r o m e t e r at
O 100 MHz and with a Varian T - 6 0 s p e c t r o m e t e r at 60 MHz at
r o o m t e m p e r a t u r e . Stabilization of the r e s o n a n c e conditions
w a s a c c o m p l i s h e d f r o m the line of t e t r a m e t h y l s i l a n e . The IR
~ :? = = s p e c t r a of solutions o f the compound in CC14 w e r e r e c o r d e d with
N a UR-10 s p e c t r o m e t e r . G a s - l i q u i d - c h r o m a t o g r a p h i c analysis
was p e r f o r m e d with an LKhM-7a c h r o m a t o g r a p h with a 1 - m long
punod
-tuo~)
* The authors thank P r o f e s s o r Yu. Yu. Samitov for his a s s i s t a n c e
in this r e s e a r c h .

514
column filled with C h r o m o s o r b W, 18% Apiezon L, and 5% polyethylene glycol distearate: the column t e m -
p e r a t u r e was 120-140 ~ and the c a r r i e r gas was N2.
N, N- Diethylc a r b a m o y l - 4.5- epoxy- 2-hexenoic acid (I) and 2,2.4- t r i m e t h y l - 5- [2- carbethoxy (vinylene)]-
1,3-dioxolanes (IV) w e r e obtained by the method in [2, 5].
2 , 4 - D i m e t h y l - 2 - e t h y l - 5- [2-N,N-diethylearbamoyl (vinylene)]-l,3-dioxolane (II). This compound was
obtained f r o m 23.6 g (0.032 mole) o2 methyl ethyl ketone and 4 g (0.021 mole) of N,N-diethylcarbamoyl-4,5-
epoxy-2-hexenoic acid in the p r e s e n c e of 3.85 g (0.023 mole) of anhydrous f e r r i c chloride by heating to 45-
50 ~ f o r 12 h. The m i x t u r e was t r e a t e d with potassium carbonate and worked up to give 1.72 g (31%) of the
dioxolane with bp 147-150 ~ (2 ram) and nD 20 1.4857. Found %: C 64.1: H 9.8- N 5.5. C~4H2~NO3. Calculated
%: C 63.9: H 9.5: N 5.2.
2 . 4 - D i m e t h y l - 2 - e t h y l - 5 - [ 2 - N , N - d i e t h y l c a r b a m o y l ( e t h y l ) ] - l , 3 - d i o x o l a n e (III). This compound was ob-
tained by reduction of 1 g (0.030 mole) of II with hydrogen over Raney nickel under standard conditions.
The yield of product with bp 118-120 ~ (2 ram) and nD 2~ 1.4511 was 0.6 g (61%). Found %: C 67.1: H 11.3;
N 5.2. C~4HzTNO3. Calculated ~c: C 66.4t H 9.0: N 5.4.
2,2,4- T r i m e t h y l - 5- [2- N, N-diethylcarbamoyl (vinylene)]- 1,3-dioxolanes {IIa and IIIa). Thes e corn-
pounds w e r e obtained by the method in [6].
2, 2. 4- T r i m e t h y l - 5- ( 1 - p r o p e n y l - 3 - h y d r o x y ) - l , 3 - d i o x o l a n e {V). A solution of 2.14 g (0.01 mole) of IV
in 10 ml of ether was added dropwise to 0.4 g (0.01 mole) of LiA1H4 in 40 ml of dry e t h e r at such a r a t e that
the e t h e r refluxed gently. The m i x t u r e was heated up to the boiling point and t r e a t e d with a small amount
of water. The p r e c i p i t a t e was r e m o v e d by filtration and washed s e v e r a l t i m e s with e t h e r and alcohol. The
e t h e r - a l c o h o l e x t r a c t s were dried with MgSO4. The solvents were removed, and the residue was vacuum
distilled to give 0.7 g (40%) of the dioxolane with bp 98-100 ~ (3 ram), nD 2~ 1.4540, and d42~ 1.0231. Found %:
C 62.5: H 10.2: MR D 49.04. C9H~60~. Calculated ~c: C 62.7: H 10.3: MR D 47.04. IR s p e c t r u m . 1650.(C~C),
3450 (OH), and 1080-1090 ( C - O - C ) cm -~.
2 , 2 , 4 - T r i m e t h y l - 5 - ( 3 - p r o p y l h y d r o x y ) - l , 3 - d i o x o l a n e (VII). A) A 2.16-g (0.01 mole) sample of VI was
reduced with 0.4 g (0.01 mole) of LiA1H4 by heating in 30 ml of d r y ether. Workup of the m i x t u r e gave 1 g
(60%) of dioxolane with bp 96 ~ (5 mm}. nD 2~ 1.4430. and R f 0.18 [ e t h e r - h e x a n e (3 : 1)]. Found %~ C 62.3:
H 10.1. CgH~O 3. Calculated %: C 62.0: H 10.3.
B. A 1.72-g (0.01 mole) sample of V was reduced with hydrogen in the p r e s e n c e of 1.5 g of Raney
nickel in 20 ml of alcohol under standard conditions until 225 ml of hydrogen had been absorbed. Distilla-
tion gave 1.4 g (80~) of the dioxolane with the physical constants p r e s e n t e d above. G a s - l i q u i d - c h r o m a t o -
graphic analysis of a m i x t u r e of the substances obtained by the two different methods gave one peak: this
c o n f i r m e d that they w e r e identical. IR spectrum: 3450 (OH) and 1080-1090 ( C - O - C ) cm -1.

LITERATURE CITED
10 M. S. Malinovskii. L. P. Glushko. and N. I. Pokhodenko, Khim. Geterotsikl. Soedin., 164 (1974).
2. Yu. Yu. Samitov. L. P. Glushko, M. S. Malinovskii, and N. I. Pokhodenko. Khim. Geterotsikl. Soedin.,
447 (1972).
3. V. F. Bystrov, Usp. Khim., 41, 531 (1972).
4. A. A. Bottmer-By. Advances in Magnetic Resonance, Vol. 1, New York {1965), p. 195.
5. M. S. Malinovskii, L. P. Glushko, Yu. Yu. Samitov, T. M. Malinovskaya, and N. I. Pokhodenko, Izv.
Vuzov, Khim. i KMm. Technol., 14, 89 (1971).
6. L. P. Glushko, M. M. Kremlev, Yu. Yu. Samitov. and T. M. Malinovskaya, Ukr. Khim. Zh.. 39, 807
(1973).

515
RESEARCH IN THE ISOXAZOLE SERIES

XXVIH.* NITRATION OF 3, 5-DIPHENYLISOXAZOLE

S. D. S o k o l o v . T . N. Egorova, UDC 547.786.2 : 542.958.1

a n d I . M. Y u d i n t s e v a

The 4 - n i t r o d e r i v a t i v e is f o r m e d in the nitration of 3, 5-diphenylisoxazole (I) in acetic anhy-

dride. Mononitration of isoxazole I in concentrated H2SO4 gave 3 - p h e n y l - 5 - ( p - n i t r o p h e n y l ) -
isoxazole, while polynitration gave a m i x t u r e of dinitro d e r i v a t i v e s , among which 3- ( m - n i t r o -
p h e n y l ) - 5 - ( p - n i t r o p h e n y l ) i s o x a z o l e was identified. The s t r u c t u r e s of the isolated p r o d u c t s
w e r e e s t a b l i s h e d by m e a n s of the s p e c t r a , by r e a c t i o n - c h r o m a t o g r a p h y methods, and g a s -
liquid c h r o m a t o g r a p h y , as well as by a c o m p a r i s o n with genuine s a m p l e s of the two mono-
n i t r o and four dinitro d e r i v a t i v e s of isoxazole I.

The nitration of 3- and 5-phenylisoxazoles has been studied in detail in recent y e a r s [2-4]. However,
Musante [5] a s s i g n e d the 3, 5-di(p-nitrophenyl)isoxazole s t r u c t u r e to the only isolated product of the n i t r a -
tion of 3,5-diphenylisoxazole {I). We decided to r e i n v e s t i g a t e the b e h a v i o r of 3,5-diphenylisoxazole under
the conditions of the n i t r a t i o n reaction, i n a s m u c h as this compound is a single conjugation s y s t e m [6-7],
and it is difficult to p r e d i c t the site of e n t r y of one o r s e v e r a l n i t r o groups. In addition, the r e s u l t s might
p o s s i b l y be of a s s i s t a n c e in finding the site of e n t r y of n i t r o groups in a n u m b e r of other s i m i l a r s y s t e m s
(see [8-11]).
In c o n t r a s t to diphenyl, which is r e a d i l y n i t r a t e d in acetic acid [12].(I) r e m a i n e d unchanged in acetic
acid at 20-120~ Nitration in acetic anhydride at ~ 20 ~ with an e q u i m o l a r amount of nitric acid in the
p r e s e n c e of catalytic amounts of c o n c e n t r a t e d H2SO4 [13] gives a m i x t u r e of m o n o n i t r i c d e r i v a t i v e s , in
which the p r i n c i p a l p r o d u c t is 3, 5 - d i p h e n y l - 4 - n i t r o i s o x a z o l e (II). The s t r u c t u r e of II follows f r o m a c o m -
p a r i s o n of its s p e c t r a with the s p e c t r a of 3 - p h e n y l - 4 - n i t r o i s o x a z o l e [2, 14]. The UV s p e c t r a of both sub-
s t a n c e s contain an a b s o r p t i o n m a x i m u m at 204 nm (log e 4.3-4.4), and a second m a x i m u m lies in the l o n g e r -
wave region f o r II, which has a l a r g e conjugation chain. Strong a b s o r p t i o n bands at 756 and 830 c m -1, which
a r e c h a r a c t e r i s t i c for a r y l - 4 - n i t r o i s o x a z o l e s [14], a r e found in the IR s p e c t r u m of n i t r o d e r i v a t i v e II.
Finally, the s i m i l a r paths of disintegration of the m o l e c u l a r ions in the m a s s s p e c t r a ~ of both substances
also p r o v i d e evidence in f a v o r of the p r o p o s e d s t r u c t u r e .
A fraction, which, f r o m its m e l t i n g point and c h r o m a t o g r a p h i c behavior, is phenyl(p-nitrophenyl)isox-
azole containing s t a r t i n g I, was isolated f r o m the s a m e reaction.
A m i x t u r e containing n i t r o d e r i v a t i v e II is f o r m e d by the action of a tenfold e x c e s s of nitric acid on
i s o x a z o l e I.
The r e a c t i v i t y of the h e t e r o c y c l i c ring of i s o x a z o l e I during nitration in acetic anhydride is i n f e r i o r
to the r e a c t i v i t y of the benzene ring in chlorobenzene [13]. However. here, as in the c a s e of chlorobenzene,
the ion attacks the dipole of the (I) molecule; this l e a d s to s e l e c t i v e nitration of the h e t e r o r i n g . In this r e -
spect.(I) differs f r o m c o n j u g a t e d s y s t e m s of the p-polyphenylene type, which a r e n i t r a t e d p r e d o m i n a n t l y in
the 4 and 4' positions u n d e r the s a m e conditions [11].
* See [1] f o r c o m m u n i c a t i o n XXVII.
t The m a s s s p e c t r a will be d i s c u s s e d in detail s e p a r a t e l y . The authors thank K. K. Zhigulev for r e c o r d i n g
the m a s s s p e c t r a .

S. Ordzhonikidze All-Union S c i e n t i f i c - R e s e a r c h P h a r m a c e u t i c a l C h e m i s t r y Institute, Moscow.

T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii. No. 5, pp. 597-601, May, 1974. Original a r t i c l e
s u b m i t t e d M a r c h 2, 1973.

9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy of this article is available from the publisher for $15.00.

516
 TABLE 1. 3.5-Di(nitrophenyl)isoxazoles (Va-d), Dinitrochalcones
(Via-d), and Dibromides (VIIa-d)
Corn - mp, ~ ~ield Com- ~ield Corn- ~ ! Found,%* Cale.
pound ;% pound mp'~ i % pound mp, c JH ~o
i

Via 208 --209 68 VIIa 186 --188,5 96 Va 256--256,5 ,58,0[ 3,0 33

VIb 224,5--225 34 VIIb 146,5--147,5 96 Vb 261--261,5 57,9I 2,9 12
VIc 211,5--212 94 VIIq 178,5--180,5 94 Ve 263--263.5 57,8I 2,9 37
VI d 195 --196 58 VIIO 147 --150 94 Vd 287--289
(dec.) 57,6 2,8 29

*C15HgN305. Calculated %: C 57.9: H 2.9.

A mononitro derivative, which does not d e p r e s s the melting point of a m i x t u r e with s a m p l e s of both
3 - p h e n y l - 5 - (p-nitrophenyl)isoxazole (Ill) and 3- {p-nitrophenyl)-5-phenylisoxazole (IV), was obtained by
nitration of isoxazole I in concentrated H2SO4 at 0 ~ (as p r e v i o u s l y d e s c r i b e d in [5]).
The s i m i l a r l y c o n s t r u c t e d i s o m e r i c arylphenylisoxazoles a r e i s o m o r p h i c [15], and it has been p r o -
posed that they be c h a r a c t e r i z e d by c o n v e r s i o n to N - m e t h y l i s o x a z o l i u m c h l o r o f e r r a t e s , which a r e not iso-
m o r p h i c [16]. We obtained N - m e t h y l i s o x a z o l i u m c h l o r o f e r r a t e s f r o m the r e a c t i o n products and r e f e r e n c e
compounds III and IV and established that the monouitro derivative has the III s t r u c t u r e .

O2N~/C6H5 HNO3 ~ - - ~ C6H5

(CH3CO)20 C6H5~.,.O/N
II o / i
llUNo3
]H2SO4

p. OoNC6H4~O/N C6H~NO2-m
p. O2NC6H4/~,.o/N
Va III

+ several isomers

The m i x t u r e of dinitro derivatives obtained by nitration of isoxazole I with e x c e s s nitric acid was
s e p a r a t e d into fractions A. B, and C by c r y s t a l l i z a t i o n f r o m benzene. C h r o m a t o g r a p h i c a l l y p u r e substances
were isolated f r o m fraction's A and B, and f r a c t i o n C was found to be a mixture of i s o m e r s . *
We also synthesized the four i s o m e r i c 3 . 5 - d i a r y l i s o x a z o l e s {Va-d), which contain NO2 groups in the
m e t a or p a r a positions of the benzene rings (Table 1).
All t h r e e steps of the s c h e m e can be s u c c e s s f u l l y realized only under specially selected conditions.
When this was done, we w e r e able to r a i s e the yield of all of the dinitrochalcones (Via-d) as c o m p a r e d with
the yields p r e s e n t e d in the l i t e r a t u r e [17]. The b r o m i n a t i o n of chalcones VI p r o c e e d s smoothly only in
acetic acid. Finally, p r i o r formation of oximes is n e c e s s a r y for s u c c e s s f u l cyclization.
A c h r o m a t o g r a p h i c a l l y pure substance with mp 254-255 ~ was isolated by c r y s t a l l i z a t i o n of the high-
melting A fraction. Oxidation of the q u a t e r n a r y salt of this substance gave m - and p - n i t r o b e n z o i c acids,
9 which w e r e identified as the methyl e s t e r s by g a s - l i q u i d c h r o m a t o g r a p h y (GLC).

C~HsONa Br2 I:NH20H ~_~Ar

Ar'CHO + CH3COAr~ Ar'CH=CHCOAr~CH3COO Ar'CHBrCHBrCOAr
Vl a - d VIIa- d 2: OH- Ar,~.OQ4
YaM
aAr=m-O2NC6H4.Ar'=p-O2NCsH4; r Ar=Ar'=m-O2NC6H,:
bAr=p-O2NC~H4,Ar'=rn-O2NC6H4; d Ar=Ar'=p-O2NC~H+

* Because of the v e r y low solubility of the dinitro derivatives in organic solvents, we were unable to r e c o r d
t h e i r PMR spectra.

517
Hence, the substance in f r a c t i o n A p r o v e d to be 3 - ( m - n i t r o p h e n y l ) - 5 - { p - n i t r o p h e n y l ) i s o x a z o l e (Va): this was
p r o v e d by c o m p a r i s o n of the m a s s s p e c t r a with the s p e c t r a of genuine s a m p l e s of Va and Vb [by c o m p a r i s o n
of the intensities of the C7H402 + ( m / e 120) and C7H4O+ ( m / e 104) c h a r a c t e r i s t i c ions f o r m e d during disinte-
g r a t i o n of the O2NCsH4CO + f r a g m e n t s ] . * Consequently, the h i g h e r - m e l t i n g 3,5-di(p-nitrophenyl)isoxazole
(Vd) is not f o r m e d during polynitration as was p r e v i o u s l y r e p o r t e d [5].
I n a s m u c h as the s u b s t a n c e s in f r a c t i o n s B and C w e r e r e s i n i f i e d by methylation with dimethyl sulfate,
they w e r e analyzed by " r e a c t i o n c h r o m a t o g r a p h y " [18]. Samples of the s u b s t a n c e s on p l a t e s containing
s i l i c a gel w e r e r e d u c e d with stannous chloride (--NO 2 --*-NH2) , and the p r o d u c t s w e r e oxidized with p o t a s -
s i u m p e r m a n g a n a t e , during which the aniline and isoxazole rings w e r e c o m p l e t e l y destroyed. Under the
conditions of this t r e a t m e n t , the unsubstituted phenyl groups in the a r y l i s o x a z o l e s w e r e converted to benzoic
acid, which was detected a f t e r c h r o m a t o g r a p h y . The method was t e s t e d on III and Va and gave positive r e -
sults: benzoic acid was found only in the p r o d u c t s of degradation of III. All of the substances of f r a c t i o n B,
a c c o r d i n g to the r e s u l t s of this analysis, contained only nitrophenyl groups. One of the compounds, with
m p 228 ~ could be i s o l a t e d in c h r o m a t o g r a p h i c a l l y p u r e f o r m , and it contained at l e a s t one n i t r o group in
the ortho position.

On the o t h e r hand, a dinitro d e r i v a t i v e with an unsubstituted phenyl group e n t e r s into the composition
of the l o w - m e l t i n g C fraction. I n a s m u c h as dinitration of one benzene ring cannot o c c u r under the mild
conditions u s e d [3], the 4 - n i t r o i s o x a z o l e s t r u c t u r e should be assigned to this substance. Despite r e p e a t e d
c r y s t a l l i z a t i o n , it could not be obtained in analytically p u r e f o r m .
Thus the nitration of 3, 5-diphenylisoxazole is a c o m p l e x p r o c e s s that depends on m a n y f a c t o r s . Both
the d i r e c t i o n of eleetrophilic attack of this compound and the r e a c t i o n r a t e change as a function of the m e -
dium. Electronic effects in this s y s t e m can a p p a r e n t l y be r e a l i z e d by different paths.

EXPERIMENTAL $
The UV s p e c t r a w e r e r e c o r d e d with a P e r k i n - E l m e r 402 s p e c t r o p h o t o m e t e r , and IR s p e c t r a w e r e
r e c o r d e d with a P e r k i n - E l m e r 457 s p e c t r o m e t e r , and the m a s s s p e c t r a w e r e r e c o r d e d with a Varian F H - 6
spectrometer.
Chromatographic Methods. Two v a r i a n t s of t h i n - l a y e r c h r o m a t o g r a p h y (TLC) w e r e used f o r
the a n a l y s i s of the r e a c t i o n m i x t u r e s and e s t a b l i s h m e n t of the p u r i t y of the isolated substances: a) on a
fixed l a y e r of KSK s i l i c a gel in b e n z e n e - m e t h a n o l (9 : 1) and detection of the substances with iodine: b) on
Silufol UV-254 p l a t e s in c y c l o h e x a n o n e - - e h l o r o f o r m - d i e t h y l a m i n e (15:35 : 1) and development in UV light.
The a n a l y s i s b y GLC was p e r f o r m e d with a JGC-810 c h r o m a t o g r a p h on an X E - 6 0 s t a t i o n a r y p h a s e at 140 ~
R e a c t i o n c h r o m a t o g r a p h y was developed to e s t a b l i s h the s t r u c t u r e of the n i t r o d e r i v a t i v e s obtained.
A l - r a g s a m p l e of the m i x t u r e was applied to a p l a t e (13 x 18 cm) with fixed KSK s i l i c a gel. A 10% solution
of stannous chloride in c o n c e n t r a t e d HC1 was applied at the s a m e point, and the plate was heated at 180 ~ f o r
~ 40 rain. It was then cooled, a m i x t u r e of a 1% solution of p o t a s s i u m p e r m a n g a n a t e and a 2% solution of
sodium c a r b o n a t e (1 : 1) was added to this point, and the plate was again heated under the s a m e conditions.
It was then cooled and c h r o m a t o g r a p h e d in a l c o h o l - w a t e r - 2 . 5 % a m m o n i u m hydroxide (25 : 3 : 4), and the
benzoic acid (Rf 0.7) was detected in UV light a f t e r sprinkling with a solution of B r o m c r e s o l Purple.
Nitration of 3,5-Diphenylisoxazole (I) i n A c e t i c Anhydride. A solution of 0.63
m l (0.015 mole) of n i t r i c acid (sp. gr. 1.5) in 12 m l of acetic anhydride and two drops of concentrated H2SO 4
w e r e added at 0~ to a solution of 3.32 g (0.015 mole) of isoxazole I in 220 ml of acetic anhydride, and the
m i x t u r e was held at ~ 2 0 ~ for 8 days. It was then p o u r e d o v e r ice, and the aqueous m i x t u r e was allowed to
stand f o r 2 days. The r e s u l t i n g p r e c i p i t a t e was r e m o v e d by filtration, washed on the filter with sodium b i -
c a r b o n a t e solution (two 5 0 - m l portions) and cold w a t e r (~ 500 ml), and dried to give 2.8 g of a m i x t u r e of
s u b s t a n c e s with mp 127-130 ~ c r y s t a l l i z a t i o n of which f r o m alcohol and r e p e a t e d c r y s t a l l i z a t i o n of which
f r o m b e n z e n e - h e x a n e gave 0.1 g of c h r o m a t o g r a p h i c a l l y p u r e 3, 5 - d i p h e n y l - 4 - n i t r o i s o x a z o l e {II) with nap
170.5-171 ~ Found %: C 67.8t H 4.0. C15H10N203. Calculated %: C 67.7: H 3.8. UV s p e c t r u m (alcohol),
Xmax, n m (log ~): 204 (4.44) and 238 (4.20).
N i t r o i s o x a z o l e II. a b a s i c substance, s t a r t i n g compound I, and a n i t r o d e r i v a t i v e of the III o r IV type
w e r e found in the o t h e r f r a c t i o n s and the m o t h e r l i q u o r s b y TLC (variant b).

* The m a s s s p e c t r a will be examined in g r e a t e r detail s e p a r a t e l y .

T P e r f o r m e d with the p a r t i c i p a t i o n of N. F. Belova.

518
 Nitration of 3,5-Diphenylisoxazole I in Concentrated H 2 S O 4. 1. Mononitration.
A 0 . 4 - m l s a m p l e of nitric acid (sp. g r . 1.5) was added dropwise with s t i r r i n g at 0~ to a solution of 2.2 g of
i s o x a z o l e I in 10 m l of c o n c e n t r a t e d H2SO 4, and the m i x t u r e was held at 0 ~ f o r 1 h. It was then p o u r e d o v e r
ice, and the p r e c i p i t a t e was r e m o v e d by filtration, washed with water, and dried. F r a c t i o n a l c r y s t a l l i z a t i o n
of the p r o d u c t f r o m h e x a n e - b e n z e n e (3 : 2), benzene, and alcohol gave 0.2 g of a c h r o m a t o g r a p h i c a l l y p u r e
s u b s t a n c e with mp 222-225 ~ This s a m e s u b s t a n c e was identified by TLC (variant ~ ) as the b a s i c s u b s t a n c e
in the m o t h e r liquors. N - M e t h y l i s o x a z o l i u m c h l o r o f e r r a t e [16], with mp 110 ~ was obtained to e s t a b l i s h its
s t r u c t u r e : no m e l t i n g - p o i n t d e p r e s s i o n was o b s e r v e d f o r a m i x t u r e of it with 2 - m e t h y l - 3 - p h e n y l - 5 - ( p - n i t r o ~
p h e n y l ) i s o x a z o l i u m c h l o r o f e r r a t e . The c h l o r o f e r r a t e of the i s o m e r i c 2 - m e t h y l - 3 - ( p - n i t r e p h e n y l ) - 5 - p h e n y l -
i s o x a z o l i u m ion had mp 138-140 ~
2. Polynitration. The r e a c t i o n was c a r r i e d out s i m i l a r l y by t r e a t i n g 5.5 g (0.025 mole) of i s o x a z o l e I
in 50 ml of c o n c e n t r a t e d H2SO4 with a m i x t u r e of 5 m l (0.119 mole) of nitric acid (sp. gr. 1.5) and 5 m l of
c o n c e n t r a t e d H2SO4 at 0 ~ f o r 2 h. Workup of the m i x t u r e gave 8 g of a m i x t u r e of p r o d u c t s with mp 200-210 ~
Two c r y s t a l l i z a t i o n s f r o m benzene gave 1.3 g of a s u b s t a n c e with mp 245-251 ~ (fraction A). F r a c t i o n a l
c r y s t a l l i z a t i o n f r o m benzene and alcohol of the r e s i d u e f r o m the m o t h e r liquor f r o m the second c r y s t a l l i z a -
tion of f r a c t i o n A gave 1.4 g of a s u b s t a n c e with m p 220-230 ~ (fraction B). The benzene m o t h e r liquor f r o m
the c r y s t a l l i z a t i o n of f r a c t i o n B was diluted with heptane and e v a p o r a t e d to give 1.8 g of a p r o d u c t with mp
140-156 ~ (fraction C).
Two c r y s t a l l i z a t i o n s of 0.8 g of the s u b s t a n c e (from f r a c t i o n A) f r o m t o l u e n e - d i c h l o r o e t h a n e (1 : 1)
gave 0.3 g of c h r o m a t o g r a p h i c a l l y p u r e 3- ( m - n i t r o p h e n y l ) - 5 - (p--nitrophenyl)isoxazole with mp 254-255 ~
Found %: C 57.6: H 2.9. C15HgN3Os. Calculated %: C 57.9: H 2.9. No m e l t i n g - p o i n t d e p r e s s i o n was ob-
s e r v e d f o r a m i x t u r e with a genuine s a m p l e of Va, and a m i x t u r e with a s a m p l e of Vb m e l t e d at 257.5-258.5 ~
A 0.5 g s a m p l e of the s u b s t a n c e f r o m f r a c t i o n A was m e t h y l a t e d for 6 h b y adding 3 m l of dimethyl sulfate
to 30 m l of dichloroethane. The s~lvent was decanted, and 0.32 g of N - m e t h y l i s o x a z o l i u m c h l o r o f e r r a t e with
mp 134-136 ~ was obtained f r o m the solid by the method in [16]: the q u a t e r n a r y salt was oxidized w i t h a q u e o u s
p o t a s s i u m p e r m a n g a n a t e solution at 100 ~ c o n c e n t r a t e d HC1 was added to the solution, and the m i x t u r e was
t r e a t e d with bisulfite until it was d e c o l o r i z e d . The aqueous solution was then e x t r a c t e d with ether, and the
acids in solution w e r e m e t h y l a t e d with diazomethane. The methyl e s t e r s of In- and p - n i t r o b e n z o i c acids
w e r e identified b y GLC.
R e c r y s t a l l i z a t i o n of f r a c t i o n B f r o m acetone gave 0.16 g of a c h r o m a t o g r a p h i c a l l y p u r e s u b s t a n c e with
mp 227-228 ~ Found %: C 57.9: H 3.1. CtsHgN305. Calculated %: C 57.91 H 2.9. According to r e a c t i o n
c h r o m a t o g r a p h y , it contained n i t r o groups in the benzene rings, just as in the c a s e of other s u b s t a n c e s f r o m
this fraction, which could not be purified. Complete r e s i n i f i c a t i o n o c c u r r e d under the m e t h y l a t i o n conditions.
Despite the u s e of solvents of different p o l a r i t y - toluene, dichloroethane, m e t h a n o l - f r a c t i o n C could
not be c r y s t a l l i z e d into individual compounds. The f r a c t i o n as a whole is a m i x t u r e of i s o m e r i c dinitro
d e r i v a t i v e s : it was shown by r e a c t i o n c h r o m a t o g r a p h y that at l e a s t s o m e of t h e m contain unsubstituted
benzene rings. Found%: N 13.4. CIsHgN305. C a l c u l a t e d % : N 1 3 . 5 .
P h e n y l ( p - n i t r o p h e n y l ) i s o x a z o l e s . T h e s e compounds w e r e obtained f r o m e q n i m o l a r amounts of the ap-
p r e p r i a t e a r y l a c e t y l e n e and a - c h l o r a l d o x i m e in refluxing toluene by the method in [19]. The yield of 3-
p h e n y l - 5 - ( p - n i t r o p h e n y l ) i s o x a z o l e III with mp 220.5-222 ~ [20] was 30%. while the yield of 3 - ~ ) - n i t r o p h e n y l ) -
5 - p h e n y l i s o x a z o l e IV with mp 220-221 ~ [21] was 20%.
3.5-Di(nitrephenyl)isoxazoles (Va-d). E q n i m o l a r amounts of the a p p r o p r i a t e nitrobenzaldehyde and
n i t r o a c e t o p h e n o n e w e r e d i s s o l v e d by heating to 50-60 ~ in the m i n i m u m amount of absolute alcohol, a f t e r
which a few d r o p s of 10% sodium ethoxide solution w e r e added with s t i r r i n g , and the m i x t u r e was acidified
to pH ~ 5 a f t e r 5 rain with 8% HC1. The r e s u l t i n g p r e c i p i t a t e d chalcone (Via-d) was r e m o v e d by filtration
and r e c r y s t a l l i z e d . A solution of 0.16 m o l e of b r o m i n e in 10 m l of glacial acetic acid was added dropwise
with s t i r r i n g at 60-70 ~ to a solution of 0.134 m o l e of chalcone V I a - d in 240 m l of glacial acetic acid, a f t e r
which the m i x t u r e was heated f o r another hour, cooled, and added d r o p w i s e to 1.4 l i t e r of cold w a t e r . The
p r e c i p i t a t e d b r o m i d e s (VIIa-d) w e r e r e m o v e d by filtration, washed with w a t e r until the washings gave a
n e u t r a l r e a c t i o n to Congo Red. and dried at 30-35 ~ A solution of 6.6 m m o l e of h y d r o x y l a m i n e hydrochloride
was added to a solution of 4.4 m m o l e of d i b r o m i d e s VIIa-d in alcohol, a f t e r which the m i x t u r e was refluxed
f o r 2 h and cooled to 0 ~ A 4 - m l s a m p l e of a 50% p o t a s s i u m hydroxide solution in alcohol was added drop-
wise, and the m i x t u r e was held at .~20 ~ f o r 20 h. The p r e c i p i t a t e d d i a r y l i s o x a z o l e (Va-d) was r e m o v e d by
filtration, washed with hot w a t e r until the washings gave a negative t e s t f o r b r o m i d e ions, dried, and c r y s -
tallized f r o m d i c h l o r o e t h a n e - t o l u e n e or acetone. Data on Va-d. Via-d. and VIIa-d a r e p r e s e n t e d in T a b l e 1.

519
 LITERATURE CITED
1. S. D. Sokolov, T. N. Egorova, and N. S. Kuryatov, Khim. Geterotsikl. Soedin., 1329 (1973).
2. M. R. Langella and P. Vita Finzi, Chim. Ind. (Milano), 47, 996 (1965).
3. B. M. Lynch and L. Shiu, Canad. J. Chem., 43, 2117 (1965).
4. S. D. Sokolov and I. M. Yudintseva, Zh. Organ. Khim., _4, 2057 (1968).
5. C. Musante, Farm. Sci. Tec. (Pavia), 6, 32 (1951): Chem. Abstr., 45, 5879 (1951).
6. S. D. Sokolov, L. A. Kazitsyna, and L. K. Guseva, Zh. Organ. Khim., 2, 731 (1966).
7. T. A. Babushkina, G. K. Semin, S. D. Sokolov, and I. M. Yudintseva, Izv. Akad. Nauk SSSR, Set. Khim.,
2376 {1970).
8. G. E. Lewis, J. Org. Chem., 30. 2798 (1965).
9. G. P. Sharnin, I. E. Moisak, E. E. Gryazin, and I. F. Falyakhov, Zh. Organ. Khim., 3, 1836 {1967).
10. V. V. Zverev, G. P. Sharnin, and I. D. Morozova, Izv. Akad. Nauk SSSR. Set. Khim., 404 (1968).
11. M. L. Scheinbaum, Chem. Commun., 1235 (1969).
12. F. Bell, J. Kenyon. and P. H. Robinson, J. Chem. Soe.. 1239 (1926).
13. M. A. Paul, J. Amer. Chem. Soe., 80, 5332 (1958).
14. S. D. Sokolov, I. M. Yudintseva, P. V. Petrovskii, and V. G. Kalyuzhnaya, Zh. Organ. Khim., 7, 1979
(1971).
15 R. P. Barnes and L. B. Dodson, J. Amer. Chem. Soc., 67, 132 (1945).
16 A. H. Blatt, J. Amer. Chem. Soc., 71, 1861 (1949).
17 P. Klinke and H. Gibian, Chem. Ber., 94, 26 (1961).
18 J. Frank and K. Pospisilova, J. Chromatogr., 48, 207 (1970).
19 M. Arbasino and P. Grtinanger, Rie. Sei., 34, (II-A), 561 (1964).
20 U. T*firck and H. Behringer, Chem. Ber., 98, 3020 (1965).
21 G. Bianchetti, D. Pocar, and P. Dalla Croce, Gazz. Chim. Ital., 93, 1714 (1963).

520
 RESEARCH IN THE ISOXAZOLE SERIES

XXIX.* STUDY OF HOMOLYTIC BROMINATION

OF METHYLISOXAZOLES BY PMR SPECTROSCOPY

S. D. S o k o l o v , T . N. Egorova, UDC 547.786 + 66.094.404: 543.422

a n d P . V. P e t r o v s k i i

The d i r e c t i o n of homolytic b r o m i n a t i o n of 4 - X - 3 , 5 - d i m e t h y l i s o x a z o l e s (X ~-~CH3, C1, Br, p -

O2NC6H4) with N - b r o m o s u c c i n i m i d e (NBS) was studied by PMR s p e c t r o s c o p y . Two of the
t h r e e CH 3 groups in 3,4, 5 - t r i m e t h y l i s o x a z o l e r e a c t with NBS, and t h e i r activity d e c r e a s e s
in the o r d e r 4-C > 5-C >>3-C. Only the CH 3 groups in the 5 position r e a c t in the r e m a i n i n g
compounds.

The b r o m i n a t i o n of a n u m b e r of m e t h y l i s o x a z o l e s with N - b r o m o s u c c i n i m i d e (RIBS) has b e e n i n v e s t i -

gated [2, 3], and the b e h a v i o r of c o m p l e t e l y r i n g - s u b s t i t u t e d compounds was d e t e r m i n e d by the position of
the CH 3 groups and the c h a r a c t e r of the o t h e r substituents [3]. To p r o v e the s t r u c t u r e of the b r o m o d e r i -
v a t i v e s obtained f r o m 3,4, 5 - t r i m e t h y l i s o x a z o l e {I) and 3 , 5 - d i m e t h y l - 4 - c h l o r o i s o x a z o l e (II), they w e r e oxi-
dized to i s o x a z o l e c a r b o x y l i c acids [3]. This r e a c t i o n did not p r o c e e d quantitatively, and one could t h e r e -
f o r e speak only of p r e f e r r e d b r o m i n a t i o n of the CH 3 groups in the 4 position of isoxazole I and in the 5 p o s i -
tion of i s o x a z o l e H.
To obtain m o r e n e a r l y c o m p l e t e i n f o r m a t i o n r e g a r d i n g the activity of the CH 3 groups in homolytic
bromination, we r e i n v e s t i g a t e d the r e a c t i o n of I, II, and analogs of II that contain weak e l e c t r o n - a c c e p t o r
substituents attached to the 4-C a t o m - 3 , 5 - d i m e t h y l - 4 - b r o m o - (III) and 3 , 5 - d i m e t h y l - 4 - ( p - n i t r o p h e n y l ) i s o x -
a z o l e s (IV) - with an equivalent amount of NBS. ~ A f t e r s e p a r a t i o n of the succinimide, the r e a c t i o n m i x t u r e s
w e r e subjected to a n a l y s i s by PMR s p e c t r o s c o p y , which was b a s e d on the different signals f r o m all of the
CH 3 groups [5] and, consequently, on the p r o t o n s of the b r o m o m e t h y l groups.
The m o s t c o m p l e x PMR s p e c t r u m was obtained f o r the p r o d u c t s of b r o m i n a t i o n of I. Its i n t e r p r e t a t i o n
(Table 1) showed that two i s o m e r i c b r o m o m e t h y l i s o x a z o l e s (Va and Vb) and a d i b r o m o d e r i v a t i v e (VI) a r e
f o r m e d in yields of 58, 23, and 6%, r e s p e c t i v e l y : the sum of all of the s u b s t a n c e s in solution was a s s u m e d to
be 100%, and the solution a l s o contained s t a r t i n g I. The signals of the p r o t o n s of the m e t h y l e n e groups s e r v e
as the k e y to the i n t e r p r e t a t i o n of the s p e c t r u m . According to the l i t e r a t u r e data, the c h e m i c a l shifts of
t h e s e p r o t o n s in the h y d r o c a r b o n side chain a r e found at ~ 2 . 5 p p m (on the 6 scale) [6], and the p r e s e n c e of
a halogen a t o m on the s a m e c a r b o n a t o m leads to a shift in the signals to weak field by ~ 2 p p m [7, 8]. The
magnitude of the c h e m i c a l shift of the p r o t o n s of the side chain of 4 - b r o m o m e t h y l i s o x a z o l e (4.2 ppm) [7] is
a l m o s t equal to that o b s e r v e d in the s p e c t r u m of a m i x t u r e of i s o m e r s V for the m o s t intense signal in this
region. A c o m p a r i s o n of the r e l a t i v e intensities of the signals of the methyl and m e t h y l e n e protons leads
to the conclusion that the c h e m i c a l shifts at 2.27, 2.39, and 4.25 p p m c h a r a c t e r i z e the p r o t o n s of 3 , 5 - d i m e t h -
9 y l - 4 - b r o m o m e t h y l i s o x a z o l e (Va).

* See [1] f o r c o m m u n i c a t i o n XXVIII.

See [4] f o r the m e c h a n i s m of b r o m i n a t i o n by m e a n s of NBS.

S. Ordzhonikidze All-Union S c i e n t i f i c - R e s e a r c h P h a r m a c e u t i c a l C h e m i s t r y Institute, Moscow.

T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii. No. 5, pp. 602-603, May, 1974. Original a r t i c l e
s u b m i t t e d M a r c h 2, 1973.

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

521
 TABLE i. Chemical Shifts of the P r o t o n s of the Side Chains of
Methylisoxazoles I-IX (on the 6 scale, ppm)* R,--N----~R3~
RS - - ~ N

Com-
6~ R~ 65
pound

I CH3 2,12 CH3 1,87 CHs 2,27

II CH3 2,24 CI -- CH3 2,38
Ill CH3 2,17 Br -- CH3 2,33
IV CH3 2,25 p-O2NCsH4 4~5 CH3 2,38
Va CH3 2,27 BrCH2 CH3 2,39
CH3 2,18 CH3 1,96 BrCH2 4,39
CH3 2,27 BrCH.~ 4,30 BrCH2 4,47
VII CH3 2,25 CI BrCH2 4,41
VIII CH3 2,22 Br -- BrCHs 4,35
IX CH3 2,25 p-O2NCsH4 -- BrCH2 4,33

*The chemical shifts of the protons of the benzene rings in IV

and IX a r e not p r e s e n t e d in Table 1.

Similarly, the protons of 3 , 4 - d i m e t h y l - 5 - b r o m o m e t h y l i s o x a z o l e (vb) have chemical shifts of 1.96, 2.18, and
4.39 ppm. Finally, the chemical shifts at 2.27, 4.30, and 4.47 ppm should be assigned to the protons of
3- methyl- 4, 5- di (bromomethyl)isoxazole (VI).

CH3~CH 3 NBS BtCHz~CH3 CH3--~-~CI'I3 BrCH2--~-~l CH 3

c"~-%o.~ cH,-%o-s + s"c"C~o-~ + s~c"2-~,.o.~
I v a vb Vl

Judging f r o m the PMR spectra, only the CH 3 groups in the 5 position r e a c t in the remaining t h r e e
isoxazoles (II-IV), and 5 - b r o m o m e t h y l i s o x a z o l e s (VII-IX) are formed. Here also, the reactions do not go
to c o m p l e t i o n - all of the r e a c t i o n m i x t u r e s contain starting m a t e r i a l s .

X--~]----~-Cti~ NB___~S X --~T---~-C tl3

C H3-<I...o.N BrCH2"-~O~N

H-IV VII-IX

II,Vll X : C | , IILVIII X=Br; IV,IX X=p-O2NCsH4

Thus the methyl group in the 3 position does not undergo r e a c t i o n with NBS in any of the four investi-
gated compounds. A simi.'lar observation was p r e v i o u s l y made for other methylisoxazoles [3].

EXPERIMENTAL
The PMR s p e c t r a w e r e r e c o r d e d with a P e r k i n - E l m e r R-12 s p e c t r o m e t e r at 60 MHz with hexamethyl-
disfloxane (HMDS) as the internal standard at ~ 35 ~
General Method. A 30-40-rag sample of benzoyl peroxide and (in portions) 5 m m o l e of NBS were
added with s t i r r i n g to a refluxing solution of 5 m m o l e of isoxazole I-IV in 10 m l of CC14, after which the
mixture was refluxed for 4 h. It was then cooled to 0~ and the p r e c i p i t a t e d sueeinimide was r e m o v e d by
filtration and washed on the filter with 3 ml of carbon t e t r a c h l o r i d e . The filtrate was vacuum evaporated
to 5 ml to give 10% solutions, which w e r e investigated by PMR s p e c t r o s c o p y .
LITERATURE CITED
I. S. D. Sokolov, T. N. Egorova, and I. M. Yudintseva, Khim. Geterotsikl. Soedin., 597 (1974).
2. N. K. Koehetkov, S. D. Sokolov, and N. M. Vagurtova. Zh. Obshch. Khim., 32, 325 (1962).
3. S. D. Sokolov and N. K. Koehetkov, Zh. Obsheh. Khim., 33, 1192 (1963).
4. J. H. Incremona and J. C. Martin, J. Amer. Chem. S.c., 92, 627 (1970).
5. S. D. Sokolov, I. M. Yudintseva, and P. V. Petrovskii, Zh. Organ. Khim. 6. 2584 (1970).
6. Kyong Pae Park, Chyng-yann Shiue. and L. B. Clapp, J. Org. Chem.. 6, 2584 (1970).
7. P. Maggioni, G. Gaudiano, and P. Braro. Gazz. China. Ital., 96, 443 (1966).
8. R. G. Mieetieh, Canad. J. Chem., 48, 3753 (1970).

522
RESEARCH ON AROMATIC HETEROCYCLES

XX.* COMPARISON OF THE E L E C T R O C H E M I C A L BEHAVIOR

OF NAPHTH-1,2,5-OXADIAZOLES AND THEIR N-OXIDES
AND 4, 5-DIHYDRO DERIVATIVES IN APROTIC MEDIA

Z . V. T o d r e s , Z. I. Fodiman, UDC 547.793.2'652 : 543.422.27

a n d /~. S. L e v i n

Naphthofurazan is reduced in t h r e e s t a g e s . The anion r a d i c a l f o r m e d in the f i r s t o n e - e l e c t r o n

step is r e c o r d e d by its ESR s p e c t r u m . The a b s e n c e of a o n e - e l e c t r o n step in the reduction of
naphthofuroxan and dihydro d e r i v a t i v e s of sulfonaphthofurazan and sulfonaphthofuroxan should
be a s s o c i a t e d with weakening of the a r o m a t i c p r o p e r t i e s of t h e i r m o l e c u l e s .

O n e - e l e c t r o n t r a n s f e r m a y be the d e t e r m i n i n g step in m a n y organic r e a c t i o n s . The i m m e d i a t e t r a n s -

f e r of s e v e r a l e l e c t r o n s in one act is l e s s likely than a n u m b e r of s u c c e s s i v e o n e - e l e c t r o n t r a n s f e r s [2].
The elucidation of the c a p a c i t y of organic m o l e c u l e s p a r t i c i p a t i n g in r e a c t i o n s for c a p t u r e of one or s e v e r a l
e l e c t r o n s is of g r e a t significance. M o r e o v e r , p o l a r o g r a p h y m a y p r o v e to be e x t r e m e l y useful in those
c a s e s in which one m u s t i s o l a t e the individual s t e p s of e l e c t r o n t r a n s f e r . Multielectron reduction should
p r o c e e d in s e v e r a l steps. However, the a p p e a r a n c e of a o n e - e l e c t r o n wave a r i s i n g as a r e s u l t of the t r a n s -
f e r of one e l e c t r o n to f o r m an anion r a d i c a l can be r e c o r d e d only in a p r o t i e solvents.
In the c a s e of a r o m a t i c and h e t e r o c y c l i c m o l e c u l e s , including 1,2,5-oxadiazoles, stable r a d i c a l s that
a r e c h a r a c t e r i z e d by the fact that the unpaired e l e c t r o n is a p o r t i o n of the r r - e l e c t r o n cloud d i s t r i b u t e d
along the e n t i r e a r o m a t i c m o l e c u l e [3] a r e f o r m e d during o n e - e l e c t r o n t r a n s f e r .
In the p r e s e n t r e s e a r c h we i n v e s t i g a t e d the e l e c t r o c h e m i c a l reduction of n a p h t h - l , 2 , 5-oxadiazole
(naphthofurazan) (I). its N-oxide (iI) (naphthofuroxan), and the dihydro d e r i v a t i v e s of naphthofurazan (III),
naphthofuroxan (IV). 8-hydroxynaphthofuroxan (V), and 7-hydroxynaphthoquinone dioxime (VI).

N~O N--O N~O

OW ~ "
I
SOaH
! II Ill

SOaH SO3H S03H

IV V VI

*See [1] f o r c o m m u n i c a t i o n XIX.

Institute of H e t e r o o r g a n i n Compounds, A c a d e m y of Sciences of the USSR. S c i e n t i f i c - R e s e a r c h

Institute of Organic I n t e r m e d i a t e s and Dyes, Moscow. T r a n s l a t e d f r o m K h i m i y a G e t e r o t s i k l i c h e s k i k h
Soedinenii. No. 5, pp. 604-608, May, 1974. Original a r t i c l e submitted May 24. 1973.

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy o f this article is available from the publisher for $15.00.

523
 G TABLE 1. P o l a r o g r a p h i c C h a r a c -
t e r i s t i c s of Naphthofurazan

Wave No. ~%. V A* n' t

I
I -- 1,43 1,89 ] 1,3
II -- 1,82 3,78 2,6
II! --2,14 2,99 2,1
Fig. 1. ESR s p e c t r u m obtained during
the e l e c t r o l y s i s of naphthofurazans in * This is the value of the c u r r e n t r e -
dimethylformamide. lative to the d e p o l a r i z e r concentration.
This is the n u m b e r of electrons, t r a n s -
f e r r e d , which is d e t e r m i n e d f r o m the
slope and the height of the c o r r e s p o n d i n g
G
waves,

In the c a s e of reduction of naphthofurazan in dimethyl-

f o r m a m i d e (DMF) (c = 2 9 10-4 M, with 0.1 M t e t r a e t h y l a m m o n i u m
iodide as the b a s e electrolyte), t h r e e waves, each of which c o r -
r e s p o n d s to t r a n s f e r of a p p r o x i m a t e l y one, three, and two e l e c -
trons, a r e s e e n on the p o l a r o g r a m (Table 1).
An anion r a d i c a l is a p p a r e n t l y f o r m e d in the f i r s t wave.
another t h r e e e l e c t r o n s a r e t r a n s f e r r e d in the second wave, and
Fig. 2. ESR s p e c t r u m obtained during a diimine s i m i l a r to b e n z o f u r a z a n [4] is f o r m e d . Two e l e c t r o n s
the e l e c t r o l y s i s of n a p h t h o f u r a z a n - 5 - a r e t r a n s f e r r e d in the third wave.
sulfonic acid in acetonitrile. Protonation p r o c e s s e s a r e e x t r e m e l y h a m p e r e d in DMF
and m a y p r o c e e d only to a s m a l l e x t e n t - to the extent that sub-
m i l l i m o l a r amounts of w a t e r a r e p r e s e n t o r p a r t i a l detachment of a p r o t o n f r o m the solvent o r b a s e e l e c -
t r o l y t e m o l e c u l e s is p o s s i b l e .

This is p o s s i b l e when active anions or negatively charged p r o d u c t s of the e l e c t r o c h e m i c a l r e a c t i o n a r e

f o r m e d . When one is examining s t e p s II and III of the indicated m e c h a n i s m , one m u s t t h e r e f o r e b e a r in
mind that the p r o d u c t s of these steps a r e written only in the c u s t o m a r y f o r m {NH). In actuality, t h e s e sub-
s t a n c e s exist p r i m a r i l y as the c o r r e s p o n d i n g " a p r o t i c equivalents."
The e l e c t r o c h e m i c a l reduction of naphthofurazan in DMF [with a (C2Hs)4N C104- b a s e electrolyte] at a
potential of - 1 . 4 - 1 . 6 V, i.e., b e f o r e the beginning of the second wave, leads to the f o r m a t i o n of p a r a m a g n e t i c
p a r t i c l e s . The ESR s p e c t r u m of the naphthofurazan anion r a d i c a l contains nine lines of the hyperfine i n t e r -
action of the u n p a i r e d e l e c t r o n with the nitrogen nuclei (Fig. 1). The s p e c t r u m was obtained with higher
r e s o l u t i o n than in [5]. The nonequivalenee of the nitrogen a t o m s is r e v e a l e d in this c a s e . It can be a s s u m e d
that the a - and ~ - nitrogen a t o m s have different affinities for an electron. However, calculation of the
c o n s t a n t s of the hyperfine i n t e r a c t i o n on these nitrogen a t o m s shows that the difference is not p a r t i c u l a r l y
g r e a t and is e x p r e s s e d by 0.5 G (aN1 ffi 5.2 G, aN2 ffi 5.7 G). The hJfs of the s p e c t r u m also contains splittings
f r o m six nonequivalent protons united in two different groups: this is a p p a r e n t l y d e t e r m i n e d by t h e i r o r i e n -
tation on the a - o r f l - e a r b o n a t o m s of the naphthalene ring (all1 = 1.1 G, all2 = 2.5 G).
The introduction of a sulfo group c o m p l i c a t e s the s p e c t r u m even m o r e (Fig. 2) (by e m p h a s i z i n g the
noneqnivalence of the atoms) and r e d u c e s its extent (there a r e f e w e r unsubstituted hydrogen a t o m s in the
naphthalene ring).
The splitting of the wave o b s e r v e d during the reduction of naphthofurazan in anhydrous DMF is ap-
p a r e n t l y explained b y the i m p o s s i b i l i t y of protonation of the i n t e r m e d i a t e l y f o r m e d anion radical: this dif-
ficulty v a n i s h e s in aqueous solutions [6]. Thus it t u r n s out that. just as in the c a s e of n i t r o compounds and
quinones [7], p r o t o n a t i o n of the i n t e r m e d i a t e s p l a y s a substantial r o l e in the m e c h a n i s m of the reduction of
1.2.5- oxadiazoles.

524
TABLE 2. P o l a r o g r a p h i c C h a r a c t e r i s t i c s of TABLE 3. Polarographic Characteris-
Naphthofuroxan tics of Dihydrosulfo Derivatives
Com-
Working solution ~P'/2'V A n pound c, mM ~'/2' V A

DMF -0,38 2,92 2,0 III 1.01 - - 1,95 4,2

O,1 N (C2Hs)4N+I- -1,38 8,60 6,0 IV 0,79 -- 1,45; --2,10 2.8; 7,04
V 0.79 --1,46; --2,06 1,1; 7,0
80% DMF +20% H20 -0,11 VI 0,76 --2,03 7,0
0,1 N (CzHs)4N+I - -0,39 1,79 1,9
-0,96 5,62 6,1
Universal buffer -0,15 1,60 1,47
pH 8.80 -0,56 6,00 5,57
The development of a o n e - e l e c t r o n wave is not
o b s e r v e d in the reduction of naphthofuroxan u n d e r the
s a m e conditions (in anhydrous DMF): the p o l a r o g r a m s a r e congruent with those obtained in weakly alkaline
aqueous alcohol solutions [two waves with n - 2 and n -~ 6 (Table 2)].
The absence of a o n e - e l e c t r o n step apparently should be a s s o c i a t e d with weakening of the a r o m a t i c
c h a r a c t e r of the molecule on p a s s i n g f r o m furazans to furoxans.
A c o m p a r i s o n of the p o l a r o g r a p h i c behavior of furoxans, which a r e the N-oxides of furazans, with
other h e t e r o c y c l i c N-oxides shows the difference in the m e c h a n i s m s of their reduction. H e t e r o c y c l i c N-
oxides a r e reduced in a c c o r d a n c e with a general rule., the exocyclic oxygen is always initially split out to
give a t w o - e l e c t r o n wave, which c o r r e s p o n d s to reduction of the N--* O group [8, 9]. In contrast, the r e d u c -
tion of furoxans c o m m e n c e s with cleavage of the oxadiazole ring [6, 10]. It has been shown [11, 12] that
t r a n s i t i o n between s t r u c t u r e s Ia and Ib through the i n t e r m e d i a t e f o r m a t i o n of o - d i n i t r o s o compound Ic oc-
c u r s in furoxans.

NO
j o
,. .

Ia Ic Ib

The low e n e r g y b a r r i e r to t r a n s i t i o n of one of these s t r u c t u r e s to the other p r o v i d e s a p o s s i b i l i t y f o r a s -

suming weakening of the N 9 9 O bond in the ring. This in all likelihood is the chief r e a s o n for the cleavage
of the oxadiazole ring that is o b s e r v e d during the reduction of furoxans. R e a r r a n g e m e n t of the Ia ~ Ib type
p r o c e e d s r e a d i l y in a r o m a t i c furoxans, while the analogous i s o m e r i z a t i o n of aliphatic furoxans is much
m o r e difficult [13]. This means that the i n t e r m e d i a t e dinitroso derivative f o r the aliphatic furoxan is sub-
stantially l e s s stable than the c o r r e s p o n d i n g i n t e r m e d i a t e s of naphthofuroxan and benzofuroxan. An evalua-
tion of the e l e c t r o c h e m i c a l b e h a v i o r of dihydro derivatives of naphthofuroxan showed that they a r e c l o s e to
the a r o m a t i c analogs but not to the aliphatic analogs.
The reduction of dihydronaphthofurazan III p r o c e e d s in one step in DMF and in aqueous alcohol. As in
the c a s e of naphthofurazan, splitting of the wave is not observed. This apparently also can be explained by
the d e c r e a s e in the stability of the product of o n e - e l e c t r o n reduction as a consequence of disruption of the
a r o m a t i c c h a r a c t e r of the naphthofurazan molecule during hydrogenation of the C4-C ~ bond.
Dihydronaphthofuroxan IV is reduced in the same way as naphthofuroxan in DMF. Two waves with
a p p r o x i m a t e l y the s a m e height r a t i o a r e observed on the p o l a r o g r a m .
It is seen f r o m a c o m p a r i s o n of the p o l a r o g r a m s of dihydro derivatives of 8-hydroxynaphthofuroxan
(V) and 7-hydroxynaphthoquinone dioxime WI) and f r o m a c o m p a r i s o n of the n u m e r i c a l ~1/2 values (Table 3)
that a s m a l l additional wave at a m o r e positive potential than the principal wave is o b s e r v e d in the c a s e of
hydroxynaphthofuroxan. The c l o s e n e s s of the ~1/2 values (except f o r the f i r s t wave of dihydronaphthofur-
oxan) of these compounds makes it possible to a s s u m e that the reduction of the sulfo derivative of naphtho-
furoxan V p r o c e e d s through the i n t e r m e d i a t e f o r m a t i o n of dioxime VI. just as in the c a s e of the reduction
of naphthofuroxan in aqueous alcohol [6].

EXPERIMENTAL

The p o l a r i z a t i o n c u r v e s were r e c o r d e d with Pt~-312 and L P - 6 0 electronic p o l a r o g r a m s . Capillaries

with the following c h a r a c t e r i s t i c s w e r e used. m = 2.11 m g / s e c , t = 2.9 sec, hHg = 400 ram, and m = 1.43

525
m g / s e c : t = 3.07 sec, and hHg = 400 ram. Anhydrous DMF, purified by the method in [14], was used as the
solvent. A 0.1 M solution of t e t r a e t h y l a m m o n i u m iodide was used as the base electrolyte.
A diffusion coefficient (D) of -~ 8" 10-6 cm 2. sec -1, in analogy with the coefficient d e t e r m i n e d for naph-
thalene derivatives f r o m polarographic data [15], was adopted f o r calculation of the number of electrons (n)
f r o m the ll'kovich equation i d = 607 nDl/2cm2/~t 1/6. The diffusion c h a r a c t e r of the waves follows f r o m the
l i n e a r dependence of the wave height on the d e p o l a r i z e r concentration.
An e l e c t r o l y t i c bridge with a stopcock, half of which was filled with a saturated solution of (C2Hs)4N+r"
in DMF, the other half of which was filled with a saturated aqueous KC1 solution, was used to m e a s u r e the
potential of the dropping e l e c t r o d e .
R e c r y s t a l l i z e d (from alcohol) 1,2-naphthofurazan [16] (rap 79-79.5~ 1,2-naphthofuroxan [17] (rap 124-
125~ dihydro derivatives of s u l f o - l , 2 - n a p h t h o f u r a z a n [18], sulfo-l,2-naphthofuroxan [19], s u l f o - 8 - h y d r o x y -
naphthofuroxan, and sulfo-7-hydroxynaphthoquinone dioxime [20] w e r e used in this study.
The ESR s p e c t r a w e r e m e a s u r e d with a Varian-E12 s p e c t r o m e t e r . The p r e p a r a t i o n of the anion radi-
cals was accomplished by an e l e c t r o c h e m i c a l method in a glass ampule with an outer d i a m e t e r of 0.4 cm and
a length of 15 cm. Platinum e l e c t r o d e s w e r e soldered to the bottom of the ampule andat a point 10 cm above
the bottom of the ampule. Contact with the solution was r e a l i z e d through a m e r c u r y drop coating the lower
e l e c t r o d e (cathode) and through a platinum lead connected to the upper electrode (anode). Dimethylform-
amide was used as the solvent, and t e t r a e t h y l a m m o n i u m p e r e h l o r a t e s e r v e d as the base electrolyte.

LITERATURE CITED
1~ A. M. Gyul'maliev, I. V. Stankevieh, and Z. V. Todres. Khim. Geterotsikl. Soedin., 1473 {1973).
2. N. N. Semenov, Some P r o b l e m s of Chemical Kinetics and Reactivity [in Russian]. Izd. Akad. Nauk
SSSR, Moscow (1958), Chap. 5.
3. W. Waters, Zh. Vsesoyuzn. Khim. Obshchestva ira. Mendeleeva, 11, 178 (1966).
4. V. Sh. Tsveniashvili, Z. V. Todres, and S. I. Zhdanov, Zh. Obsheh. Khim., 38, 1894 (1968).
5. S. P. Solodovnikov and Z. V. Todres, Khim. Geterotsikl. Soedin.. 811 (1967).
6. F. S. Levin, Z. I. Fodiman, and Z. V. Todres, ]~lektrokhimiya, 2, 175 (1966).
7. l~. S. Levin and Z. I. Fodiman, Zh. Obshch. Khim., 34, 1055 (1964).
8. S. G. Mairanovskii, N. V. Barashkova, F. D. Alashev, and V. K. Zvoryldna, Izv. Akad. Nauk SSSR,
Otd. Khim. Nauk, 938 (1960).
9~ T. Okano and K. Ohira, J. P h a r m . Soc. Japan, 88, 1170 (1968).
10 C. D. Thompson and R. T. Foley, J. E l e c t r o c h e m . Soc., 119, 177 (1972).
11 R. R. H a r r i s , A. R. Katritzky, S. Oksne. A. S. Bailey. and W. G. Paterson, J. Chem. Soc., 197 (1963).
12 P. Diehl, H. A. Christ, and F. B. Mallory, Helv. Chim. Acta, 45, 504 (I962).
13 A l t a f - u r Rahman, A. Boultan, D. Clifford, and C. Tiddy, J. Chem. Soc.. B, 1516 (1968).
14 A. B. Thomas and E. G. Rochow, J. Amer. Chem. Soc., 79, 1843 (1957).
15 l~. S. Levin and Z. I. Fodiman. Zh. Fiz. Khim., 28, 601 (1954).
16 S. V. Bodganov, Zh. Obshch. Khim., 2, No. 9, 770 (1932).
17 S. V. Bodganov and I. N. Koroleva, Zh. Obshch. Khim., 26, 265 (1956).
18. S. V. Bogdanov and S. F. Petrov, Zh. Obshch. Khim., 24, 532 (1954).
19. S. V. Bogdanov and B. I. Karavaev, Zh. Obshch. Khim., 23, 1757 (1953).
20. S. V. Bogdanov and Z. V. Todres, Zh. Vsesoyuzn. Khim. Obshchestva ira. Mendeleeva, 6, 584 (1961).

526
SYNTHESIS AND TRANSFORMATION OF AMIDES

OF 4H- 3,1- B ENZ OXAZIN- 4- ONE- 2- CARBOXYLIC ACID*

P. A. Petyunin, V. A . Bulgakov, UDC 547.867.2.07 : 543.422,4

a n d G. P . P e t y u n i n

A method for the p r e p a r a t i o n of amides of 4 H - 3 , 1 - b e n z o x a z i n - 4 - o n e - 2 - c a r b o x y l i c acid was

developed, and N-R- amides of 3-R- 4 (3H)-quinazdone- 2- carboxylic acid w e r e synthesized
f r o m them.

Amides of 4 H - 3 , 1 - b e n z o x a z i n - 4 - o n e - 2 - c a r b o x y l i c acid a r e unknown. The synthesis of N - R - s u b s t i -

tuted amides of 4 H - 3 , 1 - b e n z o x a z i n - 4 - o n e - 2 - c a r b o x y l i c acid {II) is accomplished b y heating N - R - o x a m o y l -
anthranilic acids (I) with acetic anhydride:

I II a-k

Benzoxazinones II (Table 1) are r e a d i l y converted to the starting acids (I) by the action of aqueous
alkalis and acids and also by heating with water.
The s p e c t r a l p r o p e r t i e s of benzoxazinones II a r e p r e s e n t e d in Table 2. The uCO bands a r e absent in
the s p e c t r a of solutions, and the amide band is shifted by 50 e m - l . This indicates that association of II is
r e a l i z e d through the amido group. The UV s p e c t r a a r e c h a r a c t e r i z e d by the p r e s e n c e of two absorption
bands at 270 and 300 nm. As c o m p a r e d with I [R=CH3, }'max, nm (log e)-. 260 (4.95) and 305 (4.88)], the
band is shifted to longer wavelengths by 10 ran.

* Communication LVII f r o m the s e r i e s " R e s e a r c h on the C h e m i s t r y of H e t e r o c y c l e s . " See [1] for the p r e -
ceding communication.

TABLE 1. Amides of 4H- 3,1- Benzoxazin- 4- one- 2- earboxylic Acid

Com- N,~
Empirical
pound mp, *C Yield, qo
formula found e.ale.

Ila H 205 CgHaN20a 14,9 14,,7 75

lib CHa 190--191 CIoHsN20~ 14,0 13,7 85
IlIa C2Hs
n-CaHr
125--126
80--81
CtIHloN2Oa
Ct~Hl~N2Oa
12,8
12,5
12,8
12,0
75
77
lie n-C4H9 I00--I01 ClaHt4N20a 11,5 11,4 65
IIf
,iIi
i-C4H9
n-C5H,,
120--121
70--71
C~aH14N2Oa
C~4H~6N2Oa
11,6
11,1 111:1 71
73
n-C6H,a 78--79 CasHlsNeOa 10,3 10,2 54
IIi n-CrHls 81--82 CI6H=oN=Os 10,1 9.7 39
CH2=CH--CH= 116--117 C12HioN2Oa 12,2 12,2 87
C6HsCH2 138--139 C~H12N2Oa 10,2 10,0 40

Kharkov P h a r m a c e u t i c a l Institute. T r a n s l a t e d f r o m Khimiya Geterotsiklieheskikh Soedinenii. No. 5,

pp. 609-612, May, 1974. Original a r t i c l e submitted April 11, 1973.

9 1975PlenumPublishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy o f this article is available from the publisher for $15.00.

527
 TABLE 2. Spectra of N-R-Amides of 4H-3,1-Benzoxazin-4-one-2-
carboxylic Acid
IR spectrum, am -I
UV spectrum, [
Com- kmax, nm ring amide ! ring
poun( (log e) in vco[~] vco ! l]
dioxane ccl, i KBr Cr I iCe,, I KBr

lla 270 (4,91); 303 (4,67) i -- 1790 - - 11690

1 ]
1~011640' 1610, 1330
3360, 3300
lib 270 (4,93); 303 (4,73) 0 3360, 3300
lie 3370, 3390 -- 1680 ~ [1640, 1610. 1320
lli 3370, 3310 -- !1700~ -- 11650, 1610, 1330

T A B L E 3. N-R-Amides of 3 - R ' - R - 4 ( a H ) - Q u i n a z o l o n e - 2 - c a r b o x y l i c
Acids

Com- Imp'C (from Empirical for- ': .... N, %

pound ~' ~ aqueous i Yield,
DMF) mula Ifound calc. ~o

IVa H 192--194 CIoHgNaOu 21,0 20,7 78

IVb CHa 212--213 CuHIINaO2 19,3 19,3 75
IVc n-CsHv 176--178 C1aHIs,NaO2 17,1 17,1 58
IVd n-C4H~ 172--173 CI4HIrNaO2 16,3 16,2 72
IVe iso-C4Ho 180~181 C14HlTNaO~ 16,0 16,2 72
IVf lerl-C4Hu 212--213 CI4HIrNaO~ 15,9 16,2 83
IVg n-CsHI, 180--181 CI~HIgN~O2 15,1 15,4 75
IVh CH2CH2CI 206--207 CI2HI2CINaO~ 16,0 15,8 62
IVi CH2COOC~Hs 251 CI4HI5N304 14,7 14,5 53
IVj C~Hs 249--251 CI6HI~Na02 14,9 15,0 81
IVk o-CHaC~H4 CH~ 228--229 CITHIsNa02 14,1 14,3 7O
IV I o-CIC8H4 226--227 C16Ht2C1Na02 13,5 13,4 74
IVm o-CHaOC~H4 226--227 CirHlsN~Oa 13,9 13,6 77
IVn tn-CHaOCsH4 201--202 CITHI~NaOa 13,8 13,6 87
IVo p-CI-laOCsH4 179--180 C=THI~NaOa 13,4 13,6 86
IVp o-HOOCCsH4 248--249 CITHIaNaO4 13,3 13,0 85
IVq m-HOOCCsH4 232--233 CtrHlaNaO4 13,1 13,0 93
IVr n-HOOCC6H~ 262--263 CIzHIsNaO4 12,7 13,0 76
IVs cyclo-C6Hll 247--248 Ct6H19NsO2 14,6 14,7 71
IVt p-H~NSO~C6tt4 266--267 CI6H14N404S 15,9 15,6 66
IVU a-Pyridyl 199--200 CIsH~aN40= 20.2 19,9 87
IVy -Quinolyl :1 241--242 CIgHI,N40~ 17.2 17,0 59
IV w
IV x
IVy
iso-C4Ho
CsH~
p-HOOCCsH4
/" 235--236
262--264
262--263
ClaHlsNaO=
C~sHl~NaO=
C~HIINaO4
17,3
15,6
13,4
17,1
15,8
13,6
92
69
88,

B e n z o x a z i n o n e s II a r e s t r o n g e l e c t r o p h i l e s : N - R - o x a m o y l a n t h r a n i l i c a c i d a m i d e s (III) a r e f o r m e d
w i t h a m m o n i a , w h i l e N - R - s u b s t i t u t e d a m i d e s of 4 ( 3 H ) - q n i n a z o l o n e - 2 - c a r b o x y l i c a c i d g V a - y ) ( T a b l e 3) a r e
f o r m e d w i t h p r i m a r y a m i n e s . 4 ( 3 H ) - Q u i n a z o l o n e - 2 - c a r b o x y l i c a c i d m e t h y l a m i d e (IVa) i s f o r m e d w h e n
a m i d e (Ill) i s h e a t e d w i t h a c e t i c a n h y d r i d e . T h e s t r u c t u r e of IV w a s p r o v e d b y i n d e p e n d e n t s y n t h e s i s i n
t h e c a s e of 3 - p h e n y l - 4 ( 3 H ) - q u i n a z o l o n e - 2 - c a r b o x y l i c a c i d N - m e t h y l a m i d e (IVj) a s a r e s u l t of t h e r e a c t i o n
of 2 - e t h o x a l y l - 3 - p h e n y l - 4 ( 3 H ) - q u i n a z o l o n e (V) w i t h m e t h y l a m i n e . T h e s p e c t r a l p r o p e r t i e s of a m i d e s IV
a r e p r e s e n t e d i n T a b l e 4.
T e r t i a r y (VI) a n d s e c o n d a r y (VII) a m i d e s of N - R - o x a m o y l a n t h r a n i l i c a c i d s a r e f o r m e d , r e s p e c t i v e l y ,
w i t h s e c o n d a r y a m i n e s a n d w i t h d i m a g n e s y l a m i n e s o n r e a c t i o n w i t h b e n z o x a z i n o n e s II.

H20
l ~ II

o o

coocX
V IV a - x i||
Ill R=CH3; V R'=C6H 5

T h e s t r u c t u r e of s e c o n d a r y a m i d e VII w a s c o n f i r m e d b y a l t e r n a t i v e s y n t h e s i s b y r e a c t i o n of m e t h y l a m i n e
w i t h N - e t h o x a l y l a n t h r a n i l i e a c i d a n f l i d e (VIII).

528
 T A B L E 4. S p e c t r a of N - R - A m i d e s of 3 - R ' - 4 ( 3 H ) - Q u i n a z o l o n e - 2 -
carboxylic Acids

Com- IR speclzum, cm "I

UV specu'um, kma x,
pound nm (log s) in dioxane VNH uC0 quinazolone
(KBr) [4] ring

IVa 262 (4,0); 300 (3,81) 3320, 3280 1705 1685 1530 1650, 1610, 1450
IV e 3370, 3329 1700 1690 1530 1650, 1610, 1450
I'v j 255 (5,20); 305 (5,03) 3370, 3'320 1710 1690 1530 1650, 1610, 1450
IV k 265 (5,15); 305 (4,95) 3370, 3300 1710 1700 1530 1650, 1610, I450

HN O O--
CONHCsHs~c6HsN(MgBr)2 I1 ~ - / - ,
~ ~'NliCOCONHR ~/ "NHCOCONHR

Vl! VI

VIII IX
VI, VII R = E H 3

I n the c a s e of q u i n a z o l o n e IVj it w a s shown t h a t 3 - p h e n y l - 4 ( 3 H ) - q u i n a z o l o n e i s f o r m e d on b r i e f h e a t i n g

with a q u e o u s a l k a l i . S i m i l a r b e h a v i o r w a s n o t e d f o r 3 - R - 4 ( 3 H ) - q u i n a z o l o n e - 2 - c a r b o x y l i c a c i d e s t e r [2]. A
s m a l l a m o u n t of a n t h r a n i l i c a c i d a n i l i d e , w h i c h i s c o n v e r t e d to IX on t r e a t m e n t with f o r m i c acid. is p r o b a b l y
a l s o f o r m e d a l o n g w i t h IX.

EXPERIMENTAL
The UV spectra of dioxane solutions (c 2 9 10-3-2 9 10 -5 M) were recorded with an SF-4A spectrophoto-
meter. The IR spectra of KBr pellets (containing 0.5% of the compounds) and CCI4 solutions (c 0.0015 M)
were recorded with a UR-20 spectrometer.
4H-3,l-Benzoxazin-4-one-2-carboxylic Acid N-R-Amides (II). One part of I and two parts of acetic
anhydride were heated until the solid dissolved, and the solution was then heated for another I0 rain. The
mixture was then cooled, and the resulting precipitate was removed by filtration and washed with absolute
ether. Analytically pure products were obtained.
N-Methyloxamoylanthranilic Acid Amide (III). Dimethylformamide (6 ml) was saturated with dry am-
monia, after which 2 g of IIb was added. The mixture was allowed to stand for 12 h, after which the precipi-
tate was removed by filtration and crystallized from aqueous DMF to give 1.3 g (62%) of needles with mp
236-237 ~ Found %. N 19.3. CIoHIIN303. Calculated %: N 19.0.
4(3H)-Quinazolone-2-carboxylic Acid Methylamide (IVa). A solution of 1 g of III in 2 ml of acetic
anhydride was heated for 2.5 h, after which it was cooled and diluted with water. The resulting precipitate
was removed by filtration and crystallized. The product dissolved in cold aqueous alkali.
3-Phenyl-4(3H)-quinazolone-2-carboxylic Acid Methylamide (IVj). A) A mixture of 1.02 g of lib and
0.5 g of aniline in 3 ml of DMF was heated for 30 rain, after which it was poured into 20 ml of water. The
resulting precipitate was removed by filtration and crystallized to give a product with nap 248-249 ~
B) A l-ml sample of a 40% solution of methylamine was added to a solution of 2.8 g of V in 15 ml of
ethanol, and the mixture was allowed to stand at room temperature for 16 h. The resulting precipitate was
removed by filtration and washed with ethanol to give a product with nap 248-249 ~ No melting-point depres-
sion was observed for a mixture with the product obtained by method A. Compounds IVb-i, k-y were ob-
tained by method A.
Methyloxamoylanthranilic Acid Morpholide (VI). A mixture of 2.04 g of lib and 0.87 g of morpholine
in 6 ml of DMF was heated for 30 rain, after which it was poured into 40 ml of water, and the resulting
precipitate was removed by filtration and crystallized from glacial acetic acid to give 1.0 g (35.7%) of
needles with mp 277-278 ~ Found %: N 14.2. C14HI4N304. Calculated %: N 14.4.

529
 N - M e t h y l o x a m o y l a n t h r a n i l i c Acid Anilide {VII). A) A suspension of 4 g of IIb in 20 m l of dioxane was
added to N,N-bis (bromomagnesyl)anfline, obtained f r o m 0.96 g of m a g n e s i u m , 5.5 g of butyl b r o m i d e , and
1.8 g of aniline in 30 m l of absolute ether, a f t e r which the m i x t u r e was heated for 30 min and then d e c o m -
p o s e d with 10% h y d r o c h l o r i c acid. The p r e c i p i t a t e was r e m o v e d by filtration and c r y s t a l l i z e d f r o m aqueous
DMF to give 3.7 g (64%) of needles with mp 256-258 ~
B) A 0 . 3 - m l s a m p l e of a 40% m e t h y l a m i n e solution was added to a solution of 0.9 g of VIII in 10 m l of
ethanol, and the m i x t u r e was allowed to stand at r o o m t e m p e r a t u r e for 18 h. It was then diluted with 30 m l
of w a t e r and acidified with h y d r o c h l o r i c acid. The r e s u l t i n g p r e c i p i t a t e was worked up as in the p r e c e d i n g
e x p e r i m e n t to give 0.85 g (94%) of a p r o d u c t with mp 256-258 ~ No m e l t i n g - p o i n t d e p r e s s i o n was o b s e r v e d
f o r a m i x t u r e of this p r o d u c t with the m a t e r i a l obtained by method A. Found %: N 14.2. C16HI4N303. Calcu-
lated %. N 14.1.
3-Phenyl-4(3H)-quinazolone (IX). A 1.5-g s a m p l e of IVj was refluxed for 30 rain with 15 ml of sodi-
u m hydroxide solution, a f t e r which the hot solution was acidified with 10% h y d r o c h l o r i c acid. After v i g o r -
ous c a r b o n dioxide evolution had ceased, a 10% sodium hydroxide solution was added until the m i x t u r e was
s t r o n g l y alkaline. The r e s u l t i n g p r e c i p i t a t e was r e m o v e d by filtration and a i r dried. It was then drenched
with 1.5 m l of 85% f o r m i c acid, and the m i x t u r e was refluxed for 1 h and p o u r e d into 10 ml of water. The
solution was t r e a t e d with e x c e s s 10% sodium c a r b o n a t e solution, and the r e s u l t i n g p r e c i p i t a t e was r e m o v e d
by f i l t r a t i o n and c r y s t a l l i z e d f r o m aqueous ethanol to give 0.9 g (75%) of needles with mp 137-138 ~ [5]. No
m e l t i n g - p o i n t d e p r e s s i o n was o b s e r v e d f o r a m i x t u r e of this p r o d u c t with a genuine s a m p l e .

LITERATURE CITED

1. P. A. Petyunin and V. V. Bolotov, Zh. Organ. Khim., 9, 806 (1973).

2. P. A. Petyunin. V. P. Chernykh, G. P. Petyunin. and Yu. V. Kozhevnikov, Khim. Geterotsikl. Soedin..
1575 (1970).
3~ K. L e m p e r t and G. Doleshall, T e t r a h e d r o n Lett., 781 (1963).
4. H. Culbertson, I. C. Decins, and B. E. C h r i s t e n s ~ J. A m e r . Chem. S.c., 74, 4834 (1952).
5. P. Ao Petyunin and Yu. V. Kozhevnikov, Zh. Obshch. Khim., 30. 2355 (1960).

530
ATRANES
XXXV.* CONFORMATIONAL ANALYSIS
OF THE 1-METHYLSILATRANE MOLECULE

M. G . V o r o n k o v , V . V. K e i k o , UDC 547.895'245 : 541.63

V. F . S i d o r k i n , V. A . P e s t u n o v i c h .
and G. I. Zelchan

The c o n f o r m a t i o n a l e n e r g y of the 1 - m e t h y l s i l a t r a n e m o l e c u l e for sp 3 and sp3d hybridization

of the silicon a t o m was calculated. The known data on the s t r u c t u r e of the a t r a n e p o r t i o n of
the m o l e c u l e a r e in good a g r e e m e n t with the r e s u l t s of the calculation f o r sp3d hybridization
and differ r a d i c a l l y f r o m the r e s u l t s of the calculation f o r sp 3 hybridization of the silicon
atom. The c o n f o r m a t i o n a l f a c t o r s constitute a c o n s i d e r a b l e contribution (11.4 k c a l / m o l e ) to
the f o r c e d change in the hybridization of the silicon a t o m . An a n a l y s i s of the dependence of
the e n e r g y of the 1 - m e t h y l s i l a t r a n e m o l e c u l e on the distance between the Si and N a t o m s
shows that a stable exo f o r m , i s o l a t e d to any extent by a c o n s i d e r a b l e c o n f o r m a t i o n a l b a r r i e r
f r o m the r e a l s t r u c t u r e with an Si 4-N t r a n s a n n u l a r interaction, does not exist.

The p r e s e n c e of a t r a n s a n n u l a r bond in m o l e c u l e s of cyclic inorganic e t h e r s and alkoxides of t r i e t h a -

9t; r
n o l a m i n e (atranes) Xn_3M~n)(OCH2CHs)3N h a s b e e n c o n f i r m e d by a n u m b e r of p h y s i c o c h e m i c a l methods [1-7].
It has been e s t a b l i s h e d f o r the m o s t i n v e s t i g a t e d r e p r e s e n t a t i v e s of this i n t e r e s t i n g c l a s s of h e t e r o o r g a n i c
compounds - s f l a t r a n e s (M = Si) - that the e l e c t r o n i c effects of substituent X and of s u b s t i t u e n t s in the a t r a n e
half r i n g s affect the s t r e n g t h of the i n t r a m o l e c u l a r S i * - N coordinate bond. An intimate r e l a t i o n s h i p between
the i n t r a m o l e c u l a r coordination of the silicon and nitrogen a t o m s and the c o n f o r m a t i o n a l f a c t o r s has also
b e e n o b s e r v e d . To begin with, this is the a b s e n c e of a t r a n s a n n u l a r i n t e r a c t i o n of the Si and N a t o m s in
(CH3)2Si(OCH2CH2)2NR m o l e c u l e s and the c o n s i d e r a b l y l o w e r s t r e n g t h of the i n t r a m o l e c u l a r Si ~-N c o o r d i -
nate bond in 1 - e t h o x y - 2 - c a r b a s i l a t r a n e as c o m p a r e d with 1 - m e t h y l s i l a t r a n e and 1 - e t h o x y s i l a t r a n e . A bi-
p y r a m i d a l s t r u c t u r e in which the deviation of the X - S i - O angle f r o m the equilibrium value c h a r a c t e r i s t i c
f o r sp3d h y b r i d i z a t i o n is also explained by i n t e r a c t i o n of substituent X with the oxygen a t o m s of the a t r a n e
half r i n g s [1-5, 7] has b e e n p r o p o s e d for the silicon a t o m in s f l a t r a n e m o l e c u l e s .
The indications of the i m p o r t a n c e of c o n f o r m a t i o n a l f a c t o r s f o r an understanding of the p r o p e r t i e s of
a t r a n e s have up until now b e e n p u r e l y qualitative [3-6]. The p r e s e n t p a p e r is devoted to the elucidation of
two p r o b l e m s : the extent to which the r e a l s t r u c t u r e of the a t r a n e p o r t i o n of the m o l e c u l e c o r r e s p o n d s to
the m i n i m u m of the c o n f o r m a t i o n a l e n e r g y and the e n e r g y expenditures r e q u i r e d f o r one o r another d e f o r -
m a t i o n of the m o l e c u l e . The f o r m u l a t i o n of the l a t t e r p r o b l e m is r e l a t e d to the p r o b l e m of the stability of
the exo- a t r a n e s t r u c t u r e .

* See [1] f o r c o m m u n i c a t i o n XXXIV.

t W e c o n s i d e r the exo f o r m to be the s t r u c t u r e in which the u n s h a r e d p a i r of the nitrogen a t o m is d i r e c t e d
away f r o m the h e t e r o r i n g [6].

I r k u t s k Institute of Organic C h e m i s t r y . Siberian Branch, A c a d e m y of Sciences of the USSR. Institute

of Organic Synthesis, A c a d e m y of Sciences of the Latvian SSR, Riga. T r a n s l a t e d f r o m K h i m i y a G e t e r o -
t s i k l i c h e s k i k h Soedinenfi, No. 5, pp. 613-617, May, 1974. Original a r t i c l e s u b m i t t e d F e b r u a r y 27. 1973.

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

531
 HI? t ZHr~ H13 IZ H14
I HI, ~,C'2 H13
H2O H23 / ~

L .L :

"~ I c"
Fig. 1. Spiral (I) and zigzag {II) s t r u c t u r e s of the 1 - m e t h -
y l s i l a t r a n e m o l e c u l e with a silicon atom in sp a hybridization.*

TABLE 1. Dependence of the A g e o m e t r i c a l a n a l y s i s of the 1 - m e t h y l s i l a t r a n e m o l e c u l e with a

Conformatioual E n e r g y (E) of t e t r a h e d r a l a r r a n g e m e n t of the valences of the silicon a t o m s shows that
the 1 - M e t h y l s i l a t r a n e Molecule only a n a r r o w r a n g e of distances between the Si and N a t o m s - 2.35-2.45
on the T o r s i o n Angle of the and 2.9-3.0/~, r e s p e c t i v e l y - is p o s s i b l e for the endo and exo s t r u c t u r e s
O - C 0) Bond of this m o l e c u l e without d e f o r m a t i o n of the valence angles and bond
lengths. In this case, the C(4 ) a t o m deviates by a distance of 0.9-1.1/~
E, kcal/mole f r o m the p l a n e of the SiON t r i a n g l e .
sp 3 sp3d
t6
150 10,9 9 H\/H 23 H\c/H
160 11,9 2,5
H ;sC /H
170 14.0 0,2
180 17,1 -0,5 .\(/ " \:( . .
:'X o-..I
t"l~ ~ o /%'
~/\
o } endoform* ~ ~m

Two c o n f o r m a t i o n s of the half ring, which c o r r e s p o n d to t o r s i o n angles of the C ( 0 - C (7) bond of 45-50 and
90-95 ~ a r e p o s s i b l e f o r each of the s t r u c t u r e s . The p r o j e c t i o n s of the a t r a n e p o r t i o r / o f the m o l e c u l e on
the p l a n e p e r p e n d i c u l a r to the S i - N axis a r e p r e s e n t e d in Fig. 1. P r o j e c t i o n I c o r r e s p o n d s to a t o r s i o n
angle of 45-500' while p r o j e c t i o n II c o r r e s p o n d s to a t o r s i o n angle of 90-95 ~ As s e e n f r o m Fig. 1, c l o s e
location of the a t o m s of adjacent h a l f rings {H9C12, H9Ct5), which c o r r e s p o n d to t h e i r r e p u l s i o n under the
influence of v a n - d e r - W a a l s f o r c e s , is c h a r a c t e r i s t i c for both f o r m s .
The c o n f o r m a t i o n a l e n e r g y of 1 - m e t h y l s i l a t r a n e was calculated for a fixed S i - N distance of 2.19/~.
This value was t a k e n f r o m x - r a y diffraction data f o r 1 - p h e n y l s i l a t r a n e [7], i n a s m u c h as it is known that the
S i - N distance depends only slightly on the nature of the substituent attached to the silicon atom. Under the
a s s u m p t i o n of sp3 hybridization of the silicon atom, the m i n i m u m c o n f o r m a t i o n a l e n e r g i e s for the I and II
f o r m s a r e 13.0 and 10.9 k c a l / m o l e . The s u b s t a n t i a l l y nonplanar s t r u c t u r e of the a t r a n e half ring is optimum
f o r both f o r m s . The deviation of the C(4 ) a t o m f r o m the SiON plane is 0.6-0.8/~. The dependence of the
c o n f o r m a t i o n a l e n e r g y on the t o r s i o n angle of the O - C (4) bond which is p r e s e n t e d in Table 1, was obtained
f o r the e n e r g i c a l l y m o r e advantageous II f o r m .
As s e e n f r o m Table 1, t r a n s i t i o n f r o m the o p t i m u m g e o m e t r y to a r r a n g e m e n t of the SiOC 0)N a t o m s
in one p l a n e (~0 = 180 ~ r e q u i r e s the expenditure of 6.2 k c a l / m o l e . The m i n i m u m conformational e n e r g y f o r
spad hybridization of the silicon a t o m (a b i p y r a m i d a l a r r a n g e m e n t of the substituents) o c c u r s for a p l a n a r
a r r a n g e m e n t of the SiOC(4)N a t o m s . The deviation of the C (4) a t o m f r o m the SiON plane r e q u i r e s c o n s i d e r a -
b l e e n e r g y expenditure {Table 1).
A c o m p a r i s o n of the r e s u l t s obtained with the e x p e r i m e n t a l data shows that the o b s e r v e d s t r u c t u r e of
the a t r a n e p o r t i o n of the m o l e c u l e c o r r e s p o n d s to the m i n i m u m of the conformational e n e r g y only fo r sp3d

*The n u m b e r i n g of the a t o m s in the 1 - m e t h y l s i l a t r a n e m o l e c u l e in the s c h e m e and F i g u r e 1 is chosen

f o r o p t i m a l calculation and is not in a c c o r d with o r d i n a r y chernical usage.

532
 120 120i
110 110
'~00 ~00
i
9O

8O 3C J
70 7C

~ ~i~ 21.
%_..s -s~_..~
E,kcal/ ~ E,kcal/
mole ~,~ / mole ,.~

:i6i\ Aonv....
~.~ ~ zigzag form ,! ~...~ _.~

2,3 2,5 2,7 2,g 3, I o 2,3 2,5 2,7 2,9 3,1

T rs~-,'A E "S.-N'A
Fig. 2. Dependence of the S i - N - C (7) angle (~P) and the en-
e r g y (E) on the S i - N distance for the spiral (I) and zigzag
(IT) f o r m s of the 1 - m e t h y l s i l a t r a n e molecule.

hybridization of the silicon atom. It must be noted that the optimum configuration calculated for sp3d hy-
bridization of the silicon atom is in a g r e e m e n t with the known s t r u c t u r e of s i l a t r a n e s not only with r e s p e c t
to the p l a n a r a r r a n g e m e n t of the SiOC (DN atoms: close values of the CjI)SiO angle (94~ e x p e r i m e n t a l value
98% and of the distance of the C (7) atom f r o m the SiOC(4)N plane (0.45 A x - r a y diffraction value 0.5 l ) w e r e
also obtained. Calculation f o r this hybridization also showed that the low b a r r i e r to t r a n s i t i o n of the C (,.~
atom through the SiOC (4)N plane (< 0.3 k c a l / m o l e ) coincides with the r e s u l t s of PMR spectroscopy, which
indicate equivalence of the H(8) and H(9) protons [3-5].
The data in Table 1 make it possible to conclude that a change in the hybridization of the silicon atom
f r o m sp 3 to sp~d is accompanied by a gain in the conformational e n e r g y of 11.4 k c a l / m o l e . Conformational
f a c t o r s thus play a l a r g e r o l e in the 1 - m e t h y l s i l a t r a n e molecule, promoting a change in the valence state of
the silicon atom.
Inasmuch as an unstrained configuration with an S i - N distance of 2.9-3.0 ~ m a y c o r r e s p o n d to a
t e t r a h e d r a l d i r e c t i o n of the valence bonds of the Si atom, it is e x t r e m e l y i n t e r e s t i n g to calculate the con-
formational e n e r g y of the optimum s t r u c t u r e s as a function of the distance between the Si and N atoms.
This dependence for s t r u c t u r a l f o r m s I and II is p r e s e n t e d in Fig. 2. The calculated values of the S i - N - C (7)
angle a r e also p r e s e n t e d in Fig. 2. As seen f r o m Fig. 2, exo f o r m I of the 1 - m e t h y l s i l a t r a n e molecule is
absolutely unstable: it is spontaneously c o n v e r t e d to the endo s t r u c t u r e at S i - N distances f r o m 2.7 to 2.8 ~.
An i n c r e a s e in the S i - N distance for endo f o r m I to 2.85/~ leads to a b a r r i e r l e s s c o n v e r s i o n to endo f o r m
II. In c o n t r a s t to f o r m I, exo f o r m II has a minimum on the conformational e n e r g y c u r v e that c o r r e s p o n d s
to a stable configuration with an S i - N distance of 3.1/~ and an S i - N - C (0 angle of 95 ~ A b a r r i e r that does
not exceed 1.5 k c a l / m o l e s e p a r a t e s this stable state f r o m endo f o r m IL This b a r r i e r is apparently insuf-
ficient for isolation of the exo s t r u c t u r e during synthesis. A c o m p a r i s o n of the minimum e n e r g i e s of the
exo and endo s t r u c t u r e s with the coordinately bonded nitrogen and silicon atoms shows that the f o r m a t i o n
of a t r a n s a n n u l a r bond is accompanied by a d e c r e a s e in the conformational e n e r g y of 1.5 k c a l / m o l e . Con-
sequently, shortening of the S i - N distance in the 1 - m e t h y l s i l a t r a n e molecule below 3.1/~ should be a s s o -
ciated with a still s m a l l e r b a r r i e r as c o m p a r e d with the value calculated for sp 3 hybridization of the silicon
atom.
The relationship between the conformational e n e r g i e s of the r e a l s t r u c t u r e and the hypothetical exo
f o r m of 1 - m e t h y l s i l a t r a n e obtained in this study s a t i s f a c t o r i l y explains the difficulty involved in implicating
the nitrogen atom of a t r a n e s in i n t e r m o l e c u l a r complexing: the expenditure of e n e r g y not only in disruption
of the t r a n s a n n u l a r Si ---N bond but also in o v e r c o m i n g the f o r c e s of i n t e r a c t i o n of the nonvalence-bonded
atoms is r e q u i r e d f o r this.

533
 EXPERIMENTAL
The conformational energy of 1-methylsilatrane was calculated by means of a special program that
p e r m i t s one to fix any internal coordinates of the molecule. Optimization was accomplished by the method
of fastest descent with variation of the torsion and valence angles. The interaction of the nonvalence-bonded
atoms was extrapolated by means of the exp-6 potential. The van-der-Waals interaction potential of the
methyl group was assumed to be equal to that for the carbon atom. The electrostatic interactions were dis-
regarded. The p a r a m e t e r s for the calculation were taken from [8-13]. The equilibrium values of the
S i - O - C angle were assumed to be identical for both sp a and spad hybridization of the silicon atom. Inasmuch
as the magnitude of this angle depends on the nature of the substituents attached to the silicon atom [12], the
calculation was made for 113 and 123 ~ and practically identical values of the conformational energies were
obtained. The b a r r i e r to the inversion of nitrogen was assumed to be 9.14 keal/mole on the basis of data
on the f o r ce constant of the deformation vibrations of methylamine [13].

LITERATURE CITED
1. Ya. Ya. Bleidelis, A. A. Kemme, G. I. Zelchan. and M. G. Voronkov, Khim. Geterotsikl. Soedin., 617
(1973).
2. M . G . Voronkov, Vestnik Akad. Nauk SSSR, 38, No. 10, 48 (1968).
3. M . G . Voronkov, Pure and Applied Chem., 1_33,35 (1966).
4. M . G . Voronkov (Woronkow), G. I. Zelchan (Seltschans), A. F. Lapsin' (Lapsina), and V. A. Pestuno-
vich (Pestunowitsch), Z. Chem., 8, 214 (1968).
5. V.A. Pestunovich, M. G. Voronkov, G. I. Zelchan. E. Ya. Lukevits, L. I. Libert, A. N. Egorochkin.
and A. I. Burov, Khim. Geterotsikl. Soedin.. No. 2, 339 (1970).
6. V . A . Pestunovich, M. G. Voronkov, G. I. Zelchan, A. F. Lapsin', ]~. Ya. Lukevits, and L. I. Libert,
Khim. Geterotsikl. Soedin., No. 2, 348 (1970).
7. J . W . Turleu and F. P. Boer, J. Amer. Chem. Soc., 90. 4026 (1968).
8. N . C . Cohen, Tetrahedron, 27, 789 (1971).
9. N . L . Alllnger, M. Tribble. M. A. Miller, and D. H. Wertz, J. Amer. Chem. Soc., 93, 1637 (1971).
10. A . I . Kitaigorodskii and V. G. Dashevskii. Tetrahedron, 24. 5917 (1968).
11. N . L . Allinger, J. A. Hirsch, M. A. Miller, and J. F. Timin.ski. J. Amer. Chem. Soc., 93, 5773 (1968).
12. W. Aireu, C. Glidwell, A. G. Robiette, and G. M. Sheldriek, J. Mol. Struct., 8, 413 (1971).
13. M . R . Yagudaev. E. M. Popov, I. P. Yakovlev, and Yu. N. Sheinker, Izv. Akad. Nauk SSSR, Set. Khim.,
1189 (1964).

534
ATRANES

XXXVI. * 1,1-DIOXOMOLYBDATRANIC ACIDS

M. G . V o r o n k o v , A. F. Lapsinya, UDC 547.895: 546.776:543.422.25

a n d V. A . P e s t u n o v i e h

A study of the PMR s p e c t r a of 1 , 1 - d i o x o m o l y b d a t r a n i c acids m a k e s it p o s s i b l e to p r o p o s e p r o t o -

t r o p i c i s o m e r i z a t i o n of t h e i r m o l e c u l e s in solutions, during which the M o * - O coordinate bond
is r e d i s t r i b u t e d between the t h r e e oxygen a t o m s of the 2 - h y d r o x y e t h y l groups, t h e r e b y a v e r -
aging the t h r e e - d i m e n s i o n a l and e l e c t r o n i c s t r u c t u r e s of each of the a t r a n e half rings. This
s o r t of r e a r r a n g e m e n t is a b i m o l e e u l a r p r o c e s s , and its r a t e - d e t e r m i n i n g step p r o v e s to be
attack on the convalently bonded (with the m o l y b d e n u m atom) oxygen by a solvated proton.
The r a t e of i s o m e r i z a t i o n depends s u b s t a n t i a l l y on the p r o t o n - a e c e p t o r c a p a c i t y of the solvent.

We have obtained chelate compounds, to which we a s s i g n e d the 1 - h y d r o x y - l - o x o m o l y b d a t r a n e s t r u c -

t u r e (1), by r e a c t i o n of molybdenic anhydride, molybdenic acid, or ammonimm m o l y b d a t e with t r i s (2-hy-
d r o x y a l k y l ) a m i n e s [1].

/ ~Vto
6 / I I ~-o.
0
I
tl :0
11

(~ Denotes an unsubstituted or substituted -CH2CH2-grOup)

A subsequent x - r a y diffraction investigation of the s i m p l e s t compound of this type showed that the
length of one Mo--OC bond (2.34 ~) is c o n s i d e r a b l y g r e a t e r than that of the o t h e r two Mo--OC bonds (1.91
and 1.94 ~). At the s a m e time, the lengths of the Pr162r e m a i n i n g bonds between the m o l y b d e n u m and oxygen
a t o m s a r e c o n s i d e r a b l y l e s s and a l m o s t identieal (1.80 and 1.75 ~). This indicates that both of t h e s e bonds
a r e M o ~ O bonds and that the M o - O H bond is not p r e s e n t in the m o l e c u l e . On the b a s i s of this. the c o m -
pounds that we s y n t h e s i z e d should be a s s i g n e d the l . l - d i o x o m o l y b d a t r a n i c acid s t r u c t u r e (If).
The p r o t o n a t e d hydrogen a t o m in c r y s t a l s of compounds of this type r e m a i n s bonded to the oxygen
a t o m of the 2 - h y d r o x y e t h y l group, which f o r m s an elongated coordinate bond with the c e n t r a l m o l y b d e n u m
a t o m . Both of the coordinate bonds in the II m o l e c u l e (Mo ~-N and Mo ~-O) a r e in the t r a n s position r e l a -
t i v e to the Mo=:O bonds. The H[MoO2(OCH2CH2)3 N] s t r u c t u r e assigned to it in [2], which has a delocalized
proton, is l e s s likely, i n a s m u c h as all t h r e e Mo--OC bonds should be a p p r o x i m a t e l y equivalent in this c a s e .
1 , 1 - D i o x o m o l y b d a t r a n i c acid has weakly acidic p r o p e r t i e s (a 0.1 N aqueous solution has pH 5.5). We
w e r e able to i s o l a t e only a s a l t of this acid with p i p e r i d i n e - C6HI3MoNO5 9 C s H I I N - which was obtained as
c o l o r l e s s c r y s t a l s that d e c o m p o s e d without m e l t i n g at N 280~

* See [6] f o r c o m m u n i c a t i o n XXXV.

I r k u t s k Institute of Organic C h e m i s t r y , Siberian Branch, A c a d e m y of Sciences of the USSR. Institute

of Organic Synthesis, A c a d e m y of Sciences of the Latvian SSR, Riga. T r a n s l a t e d f r o m K h i m i y a G e t e r o -
t s i k l i c h e s k i k h Soedinenii, No. 5, pp. 618-621, May, 1974. Original a r t i c l e s u b m i t t e d May 24, 1973.

9 19 75 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

535
 TABLE 1. P a r a m e t e r s of the PMR Spectrum of a 5% Solution of
1,1-Dioxomolybdatranic Acid in d6-Dimethyl Sulfoxide

Chemical shifts, ~', ppm J, Hz

NCH~ OCH2 H* HA] HB HC HD }NCH2CH20-:AB[]CD 1AC "~D 1BC :BD

i
00010 0o 079j044 532 54 37 0]0 j 2
The v i b r a t i o n s of the M o ~ O bond in the IR s p e c t r a of acids II a p p e a r as a doublet at 900-930 c m -1.
This indicates the cis s t r u c t u r e of the dioxo group of MoO3 [3] and is in good a g r e e m e n t with configuration
II, which was e s t a b l i s h e d b y m e a n s of x - r a y diffraction a n a l y s i s .
Notwithstanding the x - r a y diffraction data [2], which r e v e a l the c l e a r l y i n c r e a s e d length of one of the
M o - O bonds in the 1 , 1 - d i o x o m o l y b d a t r a n i c acid c r y s t a l , the PMR s p e c t r u m * of an aqueous solution of it in-
dicates equivalence of the t h r e e a t r a n e half rings, the p r o t o n s of which r e s o n a t e as a single multiplet of
the A2B2 type (TCH2N 6.59 p p m and ~OCH2 6.05 ppm). This m a y be i n t e r p r e t e d as a consequence of dis-
sociation of the 1 , 1 - d i o x o m o l y b d a t r a n i c acid m o l e c u l e and its rapid i n t r a m o l e c u l a r i s o m e r i z a t i o n in aque-
ous solution, during which the Mo ~ O coordinate bond is r e d i s t r i b u t e d between t h r e e oxygen atoms,

O O 0"
II f~ U
O--Mo--O ~ O--Mo--O--~---- O~Mo--O H+[O2Mo(OCff2CH2)3N] -
t I i
O- O O
III

t h e r e b y a v e r a g i n g the t h r e e - d i m e n s i o n a l and e l e c t r o n i c s t r u c t u r e s of each of the half rings.

Consequently, the s t r u c t u r e of 1 , 1 - d i o x o m o l y b d a t r a n i c acid in aqueous solution can be r e p r e s e n t e d by
f o r m u l a III. We had hoped that in dimethyl sulfoxide (DNISO) the f o r m a t i o n of a quite strong hydrogen bond
between the hydroxyl p r o t o n of the 1,1-dioxomolybdatranic acid m o l e c u l e and DMSO would m a k e it p o s s i b l e
to l o c a l i z e the Mo ~ O coordinate bond and enable us to s p e c t r o s c o p i c a l l y detect the nonequivalence of the
a t r a n e half rings.

0
O--Mo--O
1
O Ch 3
\ H .." 0 -~ S ( C H3

In fact, the r e s o n a n c e of the p r o t o n s of the two a t r a n e half rings in the PMR s p e c t r u m r of 1,1-dioxo-
m o l y b d a t r a n i c acid in anhydrous d6-DMSO is r e p r e s e n t e d b y a multiplet of the ABCD type, while the r e s o -
nance of the p r o t o n s of the t h i r d a t r a n e half r i n g is r e p r e s e n t e d by two t r i p l e t s of a d e g e n e r a t e A2B2 s y s t e m .
This constitutes evidence f o r a c o n s i d e r a b l e t h r e e - d i m e n s i o n a l and e l e c t r o n i c difference between the a t r a n e
half r i n g s with covalent and coordinate bonds between the molybdenum and oxygen a t o m s . In the l a t t e r of
these, the g e m i n a l p r o t o n s in the OCH 2 and CH2N groups a r e equivalent b e c a u s e of a v e r a g i n g during rapid
c o n f o r m a t i o n a l t r a n s f o r m a t i o n s of the flexible half ring, which is f o r m e d by two coordinate bonds (O ---Mo
and N - * M o ) . In the two r e m a i n i n g half rings the magnitudes of the c h e m i c a l shifts and the s p i n - s p i n c o u p l -
ing constants f o r the g e m i n a l p r o t o n s a r e s u b s t a n t i a l l y different in both the OCH2 groups and the CH2N
g r o u p s . The r e a s o n f o r this s o r t of nonequivalence m a y c o n s i s t in the conformational rigidity of t h e s e non-
p l a n a r half rings. The shielding of t h e i r protons is a p p r e c i a b l y l o w e r (see Table 1) than is the c a s e f o r the
c o r r e s p o n d i n g p r o t o n s of the m o r e flexible half ring of the molecule.
It is e x t r e m e l y i m p o r t a n t to note that the signal of the "hydroxyl" p r o t o n is v e r y n a r r o w without any
hits of s p i n - s p i n coupling with the OCH2 p r o t o n s . This s o r t of coupling should be o b s e r v e d in the c a s e of
the f o r m a t i o n of a s t r o n g hydrogen bond between the hydroxyl p r o t o n and the DMSO m o l e c u l e . Consequently,
o u r r e s u l t s r e p u d i a t e the p o s s i b i l i t y of the r e t e n t i o n of a covalent bond between the labile hydrogen and the
oxygen a t o m of the 1 . 1 - d i o x o m o l y b d a t r a n i c acid molecule, t h e r e b y providing evidence in f a v o r of p r o t o n a -
tion of the DMSO m o l e c u l e s .

* The s p e c t r u m was obtained with a BS487B s p e c t r o m e t e r with an operating f r e q u e n c y of 80 MHz.

The PMR s p e c t r a w e r e obtained with the p a r t i c i p a t i o n of S. N. T a n d u r a and M. F . L a t i n .

536
 Thus p r o t o t r o p i c r e a r r a n g e m e n t of the 1 , 1 - d i o x o m o l y b d a t r a n i c acid m o l e c u l e in a solution in d r y
DMSO o c c u r s e x t r e m e l y slowly, and the m o l e c u l e itself, due to the high p r o t o n - a c c e p t o r capacity of the s o l -
vent, e x i s t s e x c l u s i v e l y in the d i s s o c i a t e d f o r m .

H~. /0~ ~?~0__ 1

\c/ -o~,~ ~c/HC|

The addition of small amounts of D20 (<0.5%) to a solution of 1,1-dioxomolybdatranio acid in DMSO
slowly leads to smoothing out of the fine structure of the I)MR spectrum (particularly for the OCH2 protons).
The subsequent addition of h e a v y w a t e r l e a d s to a gradual broadening of all of the signals and then to m e r g -
ing of t h e m into two t r i p l e t s - f o r the CH2N and OCH 2 p r o t o n s . This indicates that the r a t e of p r o t o t r o p i c
r e a r r a n g e m e n t of the 1 , 1 - d i o x o m o l y b d a t r a n i c acid m o l e c u l e i n c r e a s e s as the p e r c e n t a g e of w a t e r in solu-
tion i n c r e a s e s .
An i n c r e a s e in t e m p e r a t u r e a l s o b r i n g s about the s a m e effect. At ~ 150 ~ the signals of all of the CH2N
p r o t o n s in the PMR s p e c t r u m a r e united in a c o m m o n triplet, while the signals of the OCH2 p r o t o n s a r e
united in an u n r e s o l v e d t r i p l e t . * The broadening of the l a t t e r is a p p a r e n t l y a s s o c i a t e d with the p r e s e n c e
of s p i n - s p i n coupling of the OCH 2 p r o t o n s with the labile proton, the position of which is a v e r a g e d at high
t e m p e r a t u r e s with r e s p e c t to all of the oxygen a t o m s of the acid m o l e c u l e . The c h e m i c a l shifts of the OCH 2
and CH2N p r o t o n s a r e equal to the a r i t h m e t i c m e a n of the values o b s e r v e d in the s p e c t r u m at r o o m t e m -
p e r a t u r e . Cooling of the s a m p l e l e a d s to r e s t o r a t i o n of the initial s p e c t r o g r a m s .
The r e s u l t s m a k e it p o s s i b l e to a s s u m e that p r o t o t r o p i c i s o m e r i z a t i o n of the 1 , 1 - d i o x o m o l y b d a t r a n i c
acid m o l e c u l e is a b i m o l e c u l a r p r o c e s s ; its r a t e - d e t e r m i n i n g step p r o v e s to be attack on the covalently
bonded (with the m o l y b d e n u m atom) oxygen by a s o l v a t e d proton.

0 0 0
II Jl II
O--Mo~O ----"" O--Mo---O ~ O--Mo~O
i' i' "H--B + I \H..,B
0 -0 0
~'H .'-B

1 , 1 - D i o x o m o l y b d a t r a n e - 3 , 7 , 1 0 - t r i o n i c acid, which we a l s o synthesized [4] and to which the II s t r u c -

t u r e (~=--CH2C(-----O)--) should also be assigned, is also a 1 , 1 - d i o x o m o l y b d a t r a n i c acid d e r i v a t i v e .
Judging f r o m the P i e r s p e c t r u m of an aqueous solution of it, r a p i d p r o t o t r o p i c i s o m e r i z a t i o n is a l s o in-
h e r e n t in its m o l e c u l e s . It is p r e c i s e l y this s t r u c t u r e r a t h e r than the p l a n a r s t r u c t u r e o r c o n f o r m a t i o n a l
lability of the a t r a n e half rings of this molecule, as was p r e v i o u s l y supposed [4, 5], that leads to equivalence
of the g e m i n a l p r o t o n s in the PMR s p e c t r u m of 1 , 1 - d i o x o m o l y b d a t r a n e - 3 , 7 , 1 0 - t r i o n i c acid. in c o n t r a s t to
d e r i v a t i v e s of m e t h y l i m i n o a c e t i c and e t h y l e n e d i a m i n e t e t r a c e t i c acid [5], in which this s o r t of i s o m e r i z a t i o n
cannot occur.

LITERATURE CITED
1. M. G. Voronkov and A. F. Lapsin', Khim. Geterotsikl. Soedin., 561 (1967).
2. L. O. Atovmyan and O. N. Krasochka, Chem. Commtm.. 1670 (1970).
3. P. C. H. Mitchell, Quart. Rev., 20, 1036 (1966).
4. M. G. Voronkov, S. V. Mikhailova, V. A. Pesttmovich, D. E. Zaruma. and I. V. Zuika, Khim. Getero-
tsikl. So.din., 606 (1972).
5. S. I. Chan, R. J. Kula, and D. T. Sawyer, J. Amer. Chem. S.c.. 86, 377 {1964).
6. M. G. Voronkov. V. V. Keiko. V. F. Sidorkin, V. A. Pestunovich, and G. I. Zelchan, Khim. Geterotsikl.
Soedin., 613 (1974).

* P a r t i a l d e c o m p o s i t i o n of 1 , 1 - d i o x o m o l y b d a t r a n i c acid is o b s e r v e d at higher t e m p e r a t u r e s .

537
EXCHANGE OF THE AMINO GROUP
IN B-AMINO DERIVATIVES OF SULFOLANE

T. 1~. B e z m e n o v a and P. G. D u l ' n e v UDC 547.732.07

The lability of the C - N bond in a n u m b e r of B - a m i n o d e r i v a t i v e s of sulfolane was investigated.

A l k y l - a r y l t r a n s a m i n a t i o n and a n u m b e r of r e a c t i o n s of s a l t s of aminosulfolanes with nucleo-
philic r e a g e n t s w e r e r e a l i z e d .

The amino group In B - a m i n o ketches [1], B - a m i n o acids [2]. and B - a m i n o n i t r i l e s [3] has the c a p a c i t y
to undergo substitution c a u s e d by elimination of a m i n e and f o r m a t i o n of the c o r r e s p o n d i n g olefin. E l i m i n a -
tion is not o b s e r v e d in fl-piperidinoethyl phenyl sulfone [4]. although the h y d r o c h l o r i d e and methiodide r e -
act quantitatively with thiophenols via an e l i m i n a t i o n - a d d i t i o n m e c h a n i s m [5]. In the p r e s e n t r e s e a r c h we
have investigated the c a p a c i t y of the amino group of s o m e B - a m i n o d e r i v a t i v e s of sulfolane to undergo sub-
stitution. We have p r e v i o u s l y d e s c r i b e d [6] c a s e s involving exchange of the alkoxy group. It s e e m e d of in-
t e r e s t to study the lability of the C - N bond for c o m p a r i s o n of the p r o p e r t i e s of f l - h e t e r o a t o m substituted
sulfolanes and f o r elucidation of the p o s s i b i l i t i e s of the p r a c t i c a l utilization of a c c e s s i b l e amino d e r i v a t i v e s
f o r the p r e p a r a t i o n of v a r i o u s sulfolane d e r i v a t i v e s in p l a c e of the difficult-to-obtain 2-sulfolene.
We have found that p r i m a r y , secondary, and t e r t i a r y fl-alkylaminosulfolanes a r e r e s i s t a n t to t h e r m a l
action and nucleophilic exchange. Heating of 3 - N - m e t h y l a m i n o s u l f o l a n e (IIa) and 3 - N - d i m e t h y l a m i n o s u l f o l a n e
(iIIa) at 170-175~ for 7 h leads to p a r t i a l r e s i n i f i c a t i o n and the f o r m a t i o n of a v e r y s m a l l amount of 2 - s u l -
folene, the p r e s e n c e of which was e s t a b l i s h e d by t h i n - l a y e r c h r o m a t o g r a p h y (TLC) on aluminum oxide. The
C - N bond in h y d r o c h l o r i d e s Ib-II]b and s u l f o l a n y l t e t r a m e t h y l a m m o n i u m iodide (IV) is a p p r e c i a b l y weakened,
and the amino group is r e a d i l y c l e a v e d to give 2-sulfolene. Considering this. we a t t e m p t e d to combIne the
elimination of f l - a m i n o s u l f o l a n e s a l t s to 2-sulfolene with addition of a r y l a m i n e s to it. The c o r r e s p o n d i n g
a r y l a m i n o s u l f o l a n e s {X-XIV), which w e r e identical to those p r e v i o u s l y d e s c r i b e d [7], w e r e obtained by heat-
ing h y d r o c h l o r i d e s Ib-IIIb and IV with a r y l a m i n e s V-IX at 170-175 ~ and a m o l a r r a t i o of 1 : 2. The influence
of s t e r i c and inductive effects of the substituents of a r y l a m i n e s V-IX in a l k y l - a r y l t r a n s a m i n a t i o n and addi-

ArNH= ~NHAr
l-Ill
+ HN R'R". HX V-IX

~ NR'R"R"' 9X

X-X~V

IV

la R'=R'=H; I5 R:=R"=H; X=CI; Ila R'=CH3. R'=H; Ilb R'=CH3, R'=H, X=CI;
IIIaR'=R'=CH3; IIIbR'=R'=CH3, X=CI; IV R'=R"=R"=CH3; X=I; V, X At=Cells;
VI, XI Ar=p-CI=C~H4; VII, XII Ar=p-CHaC6H4; VIII. XIII Ar=rn-CH~C6H4; IX, XIT
Ar= o-CHzC6H~.

tion of a r y l a m i n e s to 2 - s u l f o l e n e [7] is a p p a r e n t l y s i m i l a r . The p r e s e n c e of 2-sulfolene in the p r o d u c t s of

the a l k y l - a r y l t r a n s a m i n a t i o n r e a c t i o n m a k e s it p o s s i b l e to a s s u m e that the p r o c e s s o c c u r s via a cleavage -

Institute of the C h e m i s t r y of H i g h - M o l e c u l a r - W e i g h t Compounds, A c a d e m y of Sciences of the

Ukrainian SSR, Kiev. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii. No. 5, pp. 622-624, May,
1974. Original a r t i c l e submitted June 13, 1972.

9 1975Plenum Publishing Corporation, 227 West 17th Street, New York, N.Y. 100ll. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is availablefrom the publisher for $15.00.

538
addition s c h e m e . I n a s m u c h as h y d r o c h l o r i d e Ib is m o r e a c c e s s i b l e than 2 - s u l f o l e n e , the r e a c t i o n under
c o n s i d e r a t i o n is of p r a c t i c a l i n t e r e s t as a method f o r the synthesis of a r y l a m i n o s u l f o l a n e s [8].
The r e s u l t s of alkylation of methiodide IV b y m e a n s of the sodium d e r i v a t i v e of malonic acid and the
r e a c t i o n of I - I V with alkoxides and m e r c a p t i d e s can a l s o b e explained by c l e a v a g e - a d d i t i o n . The high yields
of the diamide (XV) and diethyl e s t e r (XVI) of 3 - s u l f o l a n y l m a l o n i c acid a r e in a g r e e m e n t with the i n c r e a s e d
(as c o m p a r e d with C2H50-) nucleophilicity o f - C H X V e a r b a n i o n s in nucleophilie addition r e a c t i o n s [9]. The
d e c r e a s e in the yields of the p r o d u c t s of alcoholysis with n-butanol (XVII) and of m e r c a p t o l y s i s with n - b u t y l -
m e r c a p t a n {XIX) in the o r d e r IV > IIIb-Ib > I I I a - I a c o r r e s p o n d s to the known lability of the C - N bond in such
compounds [1-5]. An effect of the alcohol s t r u c t u r e that is s i m i l a r to the addition in [10] was e s t a b l i s h e d in
the r e a c t i o n of IV with i s o m e r i c n-, s e c - , and t e r t - b u t y l alcohols. The c o r r e s p o n d i n g butoxysulfolanes
{XVII-XVIII) w e r e identified by TLC. 3-Cyanosulfolane (XX). 3 - m e r c a p t o s u l f o l a n e , which was isolated as
s u l f o l a n e - 3 - s u l f o n y l chloride (XXI), the sodium s a l t of s u l f o l a n e - 3 - s u l f o n i e acid (XXII), and 3-sulfolanyl
phenyl sulfone (XXIII), r e s p e c t i v e l y , w e r e obtained by heating IV with aqueous solutions of p o t a s s i u m c y -
anide, p o t a s s i u m sulfide, p o t a s s i u m sutfite, and sodium benzenesulfinate. The p r o d u c t s w e r e identified
f r o m the IR s p e c t r a and m i x e d - m e l t i n g - p o i n t d e t e r m i n a t i o n s with compounds synthesized by r e a c t i o n with
2- sulfolene.

EXPERIMENTAL
Starting compounds I-IV were obtained by the methods presented in [II]. Chromatography was car-
ried out in a thin layer of activity II aluminum oxide by elution with diethyl ether and development with
iodine vapors.
3-Phenylaminosulfolane (X). A mixture of 1.9 g (0.01 mole) of lib and 4.9 g (0.02 mole) of aniline was
heated at 175 ~ for 6 h. The reaction mixture was then cooled and treated successively with ether and chlo-
roform. The solid material (0.7 g) was methylamine hydroehloride. The solvents were removed from the
ether and chloroform extracts to give 1.3 g (60%) of X with mp 118-119 ~ (from 20% aqueous ethanol). The
yield of X in the reaction of V with Ib was 54%, while the yields with IIIb and IV were 60% and 58%,
respectively.
Products XI-XIV were similarly obtained by reaction of IIIb with VI-IX. The yields of XI-XIII were,
respectively, 25, 71, 70%. and the melting points were 123-124, 124-125. and 90-92 ~ Product XIV was not
isolated [7].
3-Sulfolanylmalonie Acid Diamide (XV). A 0.46-g (0.02 mole) sample of sodium was dissolved in 10
ml of absolute ethanol, 2.0 g (0.02 mole) of malonie acid diamide and 6.0 g (0.02 mole) of IV were added,
and the mixture was heated at 60 ~ for 8 h. The reaction mixture was cooled and neutralized with hydro-
chloric acid. The resulting precipitate was removed by filtration, washed with 2-3 ml of ice water, and
reerystallized from 40% aqueous ethanol to give 3.5 g (80%) of XV with mp 268-270 ~ [12]. Diethyl 3-sul-
folanylmalonate (XVl) was similarly obtained. The yield of product with rap 61- 63 ~ (from ethanol) was
60% [12].
3 - n - B u t o x y s u l f o l a n e (XVII). A 0.2-g (0.01 g - a t o m ) s a m p l e of sodium was dissolved in 17 m l (0.1 mole)
of n-butanol, 3.3 g (0.02 mole) of IIIa was added, and the m i x t u r e was heated at 65-70 ~ f o r 10 h. The e x c e s s
n-butanol was r e m o v e d , and the r e s i d u e was d i s s o l v e d in ether. Hydrogen chloride was p a s s e d through the
e t h e r solution, and the p r e c i p i t a t e d HIb was r e m o v e d by f i l t r a t i o n and washed with ether. The ether e x t r a c t
was e v a p o r a t e d to give 0.6 g (15%) of XVII, which was identified by TLC (Rf 0.56). The r e a c t i o n s of n-
butanol with Ia and IIa w e r e c a r r i e d out under the s a m e conditions. P r o d u c t XVH was detected by TLC.
The r e a c t i o n of IV with n-butanol gave XVII (92%), and the r e a c t i o n of IV with s e c - b u t a n o l gave XVIII (64%)
(Rf 0.54): r e s i n i f i c a t i o n of the m i x t u r e , in which 2 - s u l f o l e n e was detected by TLC, was o b s e r v e d with t e r t -
butanol.
3-Sulfolanyl Butyl Sulfide (XIX). A 0.3-g (0.012 g - a t o m ) s a m p l e of sodium was dissolved in 10 m l
(0.1 mole) of butyl m e r c a p t a n , 3.0 g (0.01 mole) of IV was added, and the m i x t u r e was heated at 65 ~ f o r 10 ho
The e x c e s s butyl m e r c a p t a n was r e m o v e d . The r e s i d u e was washed with 3 ml of w a t e r and dried to give
2.0 g (96%) of XIX. The p r o d u c t was oxidized with hydrogen p e r o x i d e in acetic acid to 3-sulfolanyl butyl
sulfone, which was identified by a m i x e d - m e l t i n g - p o i n t d e t e r m i n a t i o n with the compound obtained by the
method in [13]. Sulfide XIX was obtained u n d e r the conditions used to obtain XVII by r e a c t i o n of n-butyl
m e r c a p t a n with IIIa (18% yield): XIX was detected only b y TLC (Rf 0.45) in the r e a c t i o n with Ia and IIa.

539
 3-Cyanosulfolane (XX). A solution of 3.0 g (0.01 mole) of IV and 0.9 g (0.014 mole) of potassium cy-
anide in 3 ml of water was heated at 55-60 ~ for 10 h. The water was evaporated, and the dry residue was
extracted with chloroform-dioxane (1 ~1). The solvent was removed from the extract to give 0.5 g (41%) of
3-cyanosulfolane with mp 118-119 ~ (from ethanol) [14].
Sulfolane-3-sulfonyl Chloride (XXI). A mixture of 3.0 g (0.01 mole) of IV. 10.0 g of a 25% solution of
sodium hydrosulfide, and 5 ml of water was heated at 60 ~ for 10 h. Chlorine was passed through the cooled
solution while maintaining the temperature at 30-40 ~. The resulting precipitate was crystallized from ace-
tone to give 0.5 g (22%) of sulfolane-3-sulfonyl chloride with mp 117-118 ~ [15].
Sodium Sulfolane-3-Sulfonate {XXII). A solution of 3.0 g (0.01 mole) of IV and 1.3 g (0.01 mole) of
sodium sulfite in 3 ml of water was heated at 60~ for 10 h. after which the water was evaporated. The r e s i -
due was recrystallized from 40% aqueous methanol to give 1.8 g (81%) of sodium sulfolane-3-sulfonate.
Found %: S 31.2. C4H~OsOsS2Na. Calculated%: S 31.1.
3-Sulfolanyl Phenyl Sulfone (XXIII). Similarly, 1.6 g (60%) of 3-sulfolanyl phenyl sulfone with mp 158-
160~ (from methanol) [16] was obtained from 3.0 g (0.Ol mole) of IV and 1.8 g (0.011 mole) of sodium
benzenesulfinate.

LITERATURE CITED
1. V. Horak and P. Zuman, Coll. Czech. Chem. Commun., 26, 173 (1961).
2. R. Fuson, J. Amer. Chem. Soc., 50, 1448 (1928).
3. P . F . Butskus and G. I. Denis, Khim. i Khim. Tekhnol., 743 (1958).
4. J. Sestakova, P. Zuman, and V. Horak, Coll. Czech. Chem. Commun., 31, 827 (1966).
5. A . S . Angeloni, P. De Maria, A. Fine, and I. Salvadori, Tetrahedron, 21, 5601 (1970).
6. T. I~. Bezmenova and R. A. Dorofeeva, USSR Author's Certificate No. 203,698 (1966); Byul. Izobr.,
No. 21, 32 (1967).
7. T. ]~. Bezmenova and P. G. Dul'nev, Dokl. Akad. Nauk Ukr. SSR, 34, 45 (1972).
8. T. ]~. Bezmenova and P. G. Dul'nev, USSR Author's Certificate No. 371,232 (1972): Byul. Izobr.. No.
12, 74 (1973).
9. I . O . Edwards and R. I. Pearson, J. Amer. Chem. Soc., 84, 16 (1962).
10. H. Zimmermannova and M. Prochazka, Coil. Czech. Chem. Commun., 30, 286 (1965).
11. H. Faith, M. P. Kautsky, and B. E. Abreu, J. Org. Chem., 27. 2889 (1962).
12. T. l~. Bezmenova, Yu. N. Usenko, A. F. Rekasheva, I. S. Lushnik, and A. V. Misyura, Khim. Getero-
tsikl. Soodin., 767 (1972).
13. R . C . Morris and E. C. Shokal, U.S. Patent No. 2,452,949 (1948) $ Chem. Abstr., 43, 2237 (1949).
14. B. Loev. J. Org. Chem., 26, 4397 (1961).
15. C . S . Argyle, S. C. Coadby, K. G. Mason, R. A. Reed, M. A. Smith, and E. S. Stern, J. Chem. Soc.,
2156 (1967).
16. T. ]~. Bezmenova, A. A. Dolgalev, and A. P. Soboleva, USSR Author's Certificate No. 311,909 (1971):
Byul. Izobr., No. 25, 98 (1971).

540
REACTION OF S U L F O L A N Y L SULFONATES
W I T H SOME N U C L E O P H I L I C REAGENTS

S. M. L u k a s h k o v a n d T. E . B e z m e n o v a UDC 547.733.07

The corresponding #-substituted sulfolane derivatives were isolated in the reaction of 3-sul-
folanyl arene(alkane)sulfonates with amines, alcohols, and mercaptans. Depending on the
nature of the nucleophile. 3,4-disubstituted sulfolanes and 4- and 3-substituted 2-sulfolenes
were obtained with 3,4-sulfolanyl disulfonates and 4-sulfolen-2-yl sulfonates.

The preparation of sulfolanyl and sulfolenyl arene(alkane)sulfonates [1. 2] and their use as convenient
sulfolanylating agents for aromatic hydrocarbons [3, 4] have been reported. In the present research we in-
vestigated the reactions of these compounds with amines, alcohols, and mercaptans.

~ .osooR z.~__(oso2R~.
) .so, ~so~/7--(~176 A.~ u o ~ o s % R

A A A A A OH HO A

2 . 2 2

Z=halogen OSO2R,,where R=C~Hs, CTH~,CH~

The corresponding 3-substituted sulfolanes, which were

identified by their IR spectra and mixed-melting-point deter-
minations with the previously described compounds, were ob-
tained in 70-90% yields in the reaction of I with butylamine,
morpholine, butyl and allyl alcohols, and 11- and tert-butyl
mercaptans. 2-Sulfolene. the presence of which in small
b ~ ~-~ -~ amounts in all of the remaining cases was noted by thin-layer
chromatography (TLC) (Rf 0.38), was isolated in 96% yield in
the reaction with diethylamine.
Considering the increased a - C - H acidity of/3-deriva-
E;I: tives of sulfolanes [5] and the appreciable activation of cleavage
of CH30- and PhO- groups [6] from the corresponding sulfolan-
yl ethers, it might be assumed that the reaction of I with nucleo-
philic reagents is also realized completely or partially via an
elimination-addition scheme with the formation of substitution
products or 2-sulfolene if addition of the nueleophile is hindered.
1700 1500 1300 1100 90{0 700' 600 cm--1
Sulfonates II-V react in a more complex manner. A mix-
Fig. 1. IR spectra: a) 4-morpholino-2- ture of products, which Prochazka and Horak were unable to
sulfolene: b) 3-morpholino-2-sulfolene. completely identify, was obtained in the reaction of III and IV

Institute of the Chemistry of High-Molecular-Weight Compounds, Academy of Sciences of the

Ukrainian SSR, Kiev. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 625-630, May,
1974. Original article submitted April 15, 1973.

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

541
 b

b~

, r i r , i ~1
'~00 ~ioo ,3~0 ,,00 goo ~ 7o0 600 ~ - ' ,700 ~00 doo ,~0 ~00 ~,~0 7~0 6~0 ~m
Fig. 2 Fig. 3
Fig. 2. lit s p e c t r a : a) 4--butoxy-2-sulfolene: b) 3-butoxy-2-sulfolene.
Fig. 3. IR s p e c t r a : a) 4 - t e r t - b u t y l t h i o - 2 - s u l f o l e n e : b) 4 - n - b u t y l t h i o - 2 - s u l f o l e n e .

with liquid a m m o n i a [7], while the c o r r e s p o n d i n g 4 - N - s u b s t i t u t e d 2-sulfolenes. identified as the hydrochlo-

r i d e s , a r e obtained with morpholine, butylamine, and diethylamine in t e t r a h y d r o f u r a n (THF) and methanol.
The position of the double bond in the ring was p r o v e d by the p r e s e n c e of the IR s p e c t r u m of the 6C_ H f r e -
quency c h a r a c t e r i s t i c f o r a cis double bond at 660 c m -1, which is absent in the IR s p e c t r u m of the i s o m e r -
ized p r o d u c t (Fig. 1). It was e s t a b l i s h e d that 4 - N - s u b s t i t u t e d 2 - s u l f o l e n e s a r c i s o m e r i z e d to 3 - N - s u b s t i -
tuted 2 - s u l f o l e n e s in 1 N aqueous alkali solutions.

/zCH2--CH2~ NJCH2--CH2~O /CH2--CH2~

N\C"~176 ' \C"2--C"S ~ F--~ --CH~--C~
" ~ 2
" s o~ " 2 '

Although we w e r e unable to i s o l a t e 3 - N - s u b s t i t u t e d 3-sulfolenes. the i s o m e r i z a t i o n p r o b a b l y p r o c e e d s b y

s u c c e s s i v e m i g r a t i o n of the double bond f r o m the 4 position to the 3 position and then to the 2 position, which
is s t a b i l i z e d b y the d o n o r - a c c e p t o r i n t e r a c t i o n of the u n s h a r e d p a i r of e l e c t r o n s of the nitrogen a t o m with
the d orbitals of the sulfur a t o m of the sulfonyl group.
3 - B u t y l a m i n o - and 3 - m o r p h o l i n o - 4 - h y d r o x y s u l f o l a n e s w e r e obtained in yields of 86 and 92%, r e s p e c -
tively, in the r e a c t i o n of V with butylamine and m o r p h o l i n e . As in the c a s e of I, elimination of a sulfonate
group was o b s e r v e d with diethylamine, and 4 - h y d r o x y - 2 - s u l f o l e n e , which was identified by TLC (Rf 0.1),
was isolated.
The composition of the p r o d u c t s of the r e a c t i o n of sulfonates IV-V with alkoxides and m e r c a p t i d e s
depends on the n a t u r e of the nucleophflic r e a g e n t and the conditions. At r o o m t e m p e r a t u r e , I I - I V r e a c t e d
with the alkaxides of allyl and butyl alcohols to give 3,4-dialkoxysulfolanes, but the yields of e t h e r s w e r e
l o w e r with i s o - and s e c - b u t y l alcohols. The n a t u r e of the alcohol had a s i m i l a r effect on the yield of 3 - a l k -
o x y - 4 - h y d r o x y s u l f o l a n e s in the r e a c t i o n with sulfonate V. The yields of hydroxy e t h e r s fell s u c c e s s i v e l y
in the o r d e r allyl alcohol, n-. i s o - . and s e c - b u t y l alcohols. In all c a s e s , the p r e s e n c e of t r a c e s of 3,4-di-
alkoxysulfolanes was detected b y T L C . Mixtures of two p r o d u c t s with R f 0.65 and 0.50 and 0.65 and 0.25,
r e s p e c t i v e l y , which w e r e s e p a r a t e d by column c h r o m a t o g r a p h y , w e r e obtained in the r e a c t i o n of IV with
sodium butc~ide in e x c e s s butanol at - 1 0 and 70-80 ~ The product with R f 0.65 was identified as 3.4-dibut-
oxysulfolane. The p r o d u c t s with R f 0.50 and 0.25 w e r e butoxysulfolenes in which the position of the double
bond was e s t a b l i s h e d b y c o m p a r i s o n of t h e i r IR s p e c t r a (Fig. 2). As in the c a s e of Ib, an a p p r e c i a b l e shift
of the a s y m m e t r i c a l s t r e t c h i n g a b s o r p t i o n of the SO2 group as a consequence of the d o n o r - a c c e p t o r i n t e r a c -
tion of the h e t e r o a t o m with the sulfonyl group and the p r e s e n c e of the intense a b s o r p t i o n band of a double
bond, which is c h a r a c t e r i s t i c f o r 3 - s u b s t i t u t e d 2 - s u l f o l e n e s [9, 11], a r e c h a r a c t e r i s t i c f o r 3 - b u t o x y - 2 -

542
 u ~ O O d O d u u ~ v @ d @ ~ ~
U ~
U =
~ U

I i I ~-i

~ tl
9 ~ ~ '~ " ~ / "
0
m = G d ~ G 6 G ,3 j d G d G ~ o c~ o
-g Z Z ~: Z Z Z 0 0 0 0 0 0 0 0 0 ~ ~

,4

543
sulfolene (Rf 0.25) (Fig. 2b). The 3,4-dibutoxysulfolanes and butoxysulfolenes w e r e identified by TLC in
the r e a c t i o n s of sulfonates II and III with e x c e s s (1 : 2) sodium butoxide.
It has been r e p o r t e d [8] that 3,4-diehlorosulfolane r e a c t s with m e r c a p t i d e s to give 3,4-dithio e t h e r s .
Refluxing of sulfonates II-IV with e x c e s s (1:2) sodium b u t y l m e r c a p t i d e in methanol f o r 4-5 h gave 3,4-di-
{butylthio)sulfolane {Rf 0.40) containing butylthiosulfolene (Rf 0.45). The p r o d u c t s w e r e isolated and identi-
fied as the sulfones. At - 1 0 to - 5 ~ a m i x t u r e of sulfides w i t h R f 0.62 and 0.45 and a disulfide with R f 0.40
w e r e obtained with the s a m e r e a g e n t s . To e s t a b l i s h the s t r u c t u r e s of the compounds obtained we c a r r i e d
out the r e a c t i o n of IV with sodium t e r t - b u t y l m e r c a p t i d e under s i m i l a r conditions. At low t e m p e r a t u r e we
obtained the p r e v i o u s l y u n d e s c r i b e d 4 - t e r t - b u t y l t h i o - 2 - s u l f o l e n e , which differed f r o m known is o m e r s with
r e s p e c t to m e l t i n g point, R f value (0.55). and IR s p e c t r u m (Fig. 3). The positions of the frequencies of the
SO 2 groups in the IR s p e c t r a of 4 - t e r t - b u t y l t h i o - 2 - s u l f o l e n e and the sulfide isolated in the r e a c t i o n of IV
with n-C4HgSNa at - 1 0 ~ w e r e s i m i l a r .
The c o r r e s p o n d i n g 3 - b u t y l t h i o - 2 - s u l f o l e n e s , which had identical IR s p e c t r a and of which 3 - t e r t - b u t y l -
t h i o - 2 - s u l f o l e n e was p r e v i o u s l y d e s c r i b e d in [9], w e r e obtained by refiuxing IV with sodium t e r t - and
n-butylmercaptides.
J

EXPERIMENTAL
The s t a r t i n g sulfonates (I-V) w e r e p r e v i o u s l y obtained in [1, 2]. T h i n - l a y e r and column c h r o m a t o -
g r a p h y on activity II a l u m i n u m oxide with elution by diethyl e t h e r w e r e u s e d to identify and s e p a r a t e the
p r o d u c t s . The t h i n - l a y e r e h r o m a t o g r a m s w e r e developed with iodine v a p o r s . The IR s p e c t r a of K B r p e l -
l e t s or liquid f i l m s between K B r p l a t e s w e r e r e c o r d e d with a UR-20 s p e c t r o m e t e r .
R e a c t i o n of Sulfolanyl Sulfonates with Amines. A m i x t u r e of 0.03 m o l e of sulfolanyl sulfonate and
0.06 m o l e of a m i n e in 40 m l of d r y THF was s t i r r e d at r o o m t e m p e r a t u r e for 2 h, a f t e r which the p r e c i p i -
t a t e was r e m o v e d by filtration, the f i l t r a t e was evaporated, and the r e s i d u e was r e c r y s t a l l i z e d f r o m m e t h a -
nol. The liquid aminosulfolanes w e r e identified as the h y d r o c h l o r i d e s .
Reaction of Sulfolanyl Sulfonates with Alcohols. A 0 . 0 3 - g - a t o m s a m p l e of sodium m e t a l was dissolved
in 40 ml of alcohol, and 0.03 m o l e of sulfolanyl sulfonate was added. The m i x t u r e was then s t i r r e d at r o o m
t e m p e r a t u r e for 4-6 h, a f t e r which it was acidified to pH 6 with h y d r o c h l o r i c acid, and the p r e c i p i t a t e was
r e m o v e d by filtration. The f i l t r a t e was evaporated, and the r e s i d u e was e x t r a c t e d with t h r e e 2 5 - m l p o r -
tions of diethyl ether. The e t h e r e x t r a c t s w e r e d r i e d o v e r anhydrous sodium sulfate, the e t h e r was r e m o v e d
b y distillation, and the r e s i d u e was v a c u u m distilled.
4 - B u t a x y - 2 - s u l f o l e n e . This compound was obtained by the above method, except that the m i x t u r e was
s t i r r e d at - 1 0 ~ f o r 3 h, and the m i x t u r e of 3,4-dibutoxysulfolane and 4 - b u t o x y - 2 - s u l f o l e n e was s e p a r a t e d
with a column filled with a l u m i n u m oxide with m o n i t o r i n g by TLC.
3-Butoxy-2-sulfolene. This compound was s i m i l a r l y obtained, except that the m i x t u r e was s t i r r e d
at 70 ~ f o r 3 h .
Reaction of Sulfolanyl Sulfonates with Thiols. The r e a c t i o n s w e r e c a r r i e d out as in the c a s e of the
r e a c t i o n s with alcohols. The sulfides w e r e isolated by c r y s t a l l i z a t i o n f r o m methanol or by v a c u u m distilla-
tion. The liquid sulfides w e r e oxidized to sulfones in glacial acetic acid with 30% H202 solution. The sul-
fones w e r e c r y s t a l l i z e d f r o m methanol.
The compounds obtained for the f i r s t t i m e a r e p r e s e n t e d in Table 1.
I s o m e r i z a t i o n of 4 - M o r p h o l i n o - 2 - s u l f o l e n e . A m i x t u r e of 2 g of 4 - m o r p h o l i n o - 2 - s u l f o l e n e and 10 m l
of a 1 N KOH solution was refluxed for 1 h. It was then cooled, and the p r e c i p i t a t e was r e c r y s t a l l i z e d f r o m
w a t e r . The p h y s i c a l c o n s t a n t s of 3 - m o r o p h o l i n o - 2 - s u l f o l e n e a r e p r e s e n t e d in Table 1.

LITERATURE CITED
1. Yu. N. Usenko, S. M. Lukashov, and T. l~. Bezmenova, Khim. G e t e r o t s i k l . Soedin., 1489 (1972).
2. Yu. N. Usenko, T. M. Popovich. S. M. Lukashov, and T. ]~. Bezmenova, USSR A u t h o r ' s C e r t i f i c a t e
No. 374,312 (1973): Byul. Izobr., No. 15, 50 (1973).
3. T. ]~. B e z m e n o v a and T. V. Lysukho. Khim. G e t e r o t s i k l . Soedin., 1481 (1971).
4. T. t~. B e z m e n o v a , S. M. Lukashov. and Yu. N. Usenko. Khim. G e t e r o t s i k l . Soedin.. 746 (1973).
5. T. l~. Bezmenova, Yu. N. Usenko, A. F. Rekasheva, I. S. Lushnik, and A. V. Misyura, Khim. G e t e r o -
tsikl. Soedin., 767 (1972).

544
 6. T. 1~. Bezmenova and R. A. Dorofeeva, in: Chemical Structure. Properties, and Reactivities of Or-
ganic Compounds [in Russian]. Kiev (1969). p. 73.
7. M. Prochazka and V. Horak, Coll. Czech. Chem. Commun., 24, 2278 (1959).
8. Albert A. Pavlic. U.S. Patent NO. 2,408,094 (1946); Chem. Abstr., 41, 775 (1947).
9. E . N . Prilezhaeva, V. N. Petrov, V. A. Sil'ke, and A. V. Kessenikh, Izv. Akad. Nauk SSSR, Set. Khim..
2223 (1966).
10. H . J . Backer and T. A. H. Blass, Rec. Travo Chim., 61, 785 (1942).
11. K . D . Gundermann and P. Holt-mann, Angew. Chem., 678 (1966).

545
SYNTHESIS AND STRUCTURE OF ANILS

OF 2- FORMYL- 3- M ERCAPTOBENZ O[b] THIOPHE NE

AND 2- FORMYL- 3- MERCAPTOBENZ O FURAN*

V. A . B r e n ' , V. I . U s a c h e v a . UDC 547.728D1' 735' 867,4.07 + 541,623

Z h . V. B r e n ' , B. Ya. Simkin,
a n d V. I . M i n k i n

As a r e s u l t of a study of the electronic, vibrational, and PMR s p e c t r a of alkyl- and a r y l -

i m i n e s of 2 - f o r m y l - 3 - m e r c a p t o b e n z o [ b ] t h i o p h e n e and 2 - f o r m y l - 3 - m e r e a p t o b e n z o f u r a n and
of the s p e c t r a of model compounds the t h i o n e - e n a m i n e s t r u c t u r e was a s s i g n e d to the i m i n e s .
The s t a b i l i t y of the l a t t e r s t r u c t u r e is in a g r e e m e n t with the r e s u l t s of q u a n t u m - m e c h a n i c a l
calculations of the e n e r g i e s of atomization of the individual t a u t o m e r i c f o r m s : the c a l c u l a -
tions w e r e m a d e b y m e a n s of the P a r i s e r - P a r r - P o p l e (PPP) method with the D e w a r cr,~
parametrization.

We have p r e v i o u s l y synthesized a r y l - and a l k y l i m i n e s of 2 - f o r m y l - 3 - h y d r o x y b e n z o f u r a n and 2 - f o r m -

yl-3-hydroxybenzo[b]thiophene (I. X = O, S; Y = O) and d i s c u s s e d t h e i r s t r u c t u r e [2, 3]. The a i m of the
p r e s e n t study was elucidation of the effect of r e p l a c e m e n t of the hydroxyl group in the indicated compounds
b y a m e r c a p t o group on the position of the p o s s i b l e t a u t o m e r i c equilibrium and the c h a r a c t e r of the m o s t
stable form.

__:,/,itl ... Y "

IA IB IC

c.~\R ~c./N,~___/~
II X = O , S ; Y = S ; R=Ar, AIk III

The eompounds with s i m i l a r t h r e e - c e n t e r t a u t o m e r i s m (Y = S) that have been studied up to now exist

p r i m a r i l y in the f o r m of the t h i o n e - e n a m i n e t a u t o m e r (for example, s e e [4-7]). However. according to the
data in [8, 9], the t r a n s i t i o n f r o m 3-hydroxythiophenes to the 3 - m e r e a p t o d e r i v a t i v e s p r o m o t e s stabilization
of the h e t e r o a r o m a t i c ring. and this m a k e s it p o s s i b l e to hope f o r m o r e labile c h a r a c t e r of the t a u t o m e r i c
equilibrium than in the c a s e of the p r e v i o u s l y studied antis of f o r m y l - 3 - h y d r o x y b e n z o f u r a n and f o r m y l - 3 -
hydroxybenzo[lo]thiophene.
Compounds of the I type (Table 1) w e r e synthesized via the s c h e m e

~c, ,.NaS. ~ s " ,N.~_.

CliO 2 UCl ~x/~CHO
IV V X=O,S

* Communication XVII f r o m the s e r i e s "Benzoid-Quinoid T a u t o m e r i s m of A z o m e t h i n e s and T h e i r Struc-

t u r a l Analogs." See [1] f o r c o m m u n i c a t i o n XVL

R o s t o v State University, R o s t o v - o n - D o n . T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i e h e s k i k h Soedinenii,

No. 5, pp. 631-639, May, 1974. Original a r t i c l e s u b m i t t e d July 31. 1973.

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

546
 TABLE 1. Azomethines of the I - I I I Type (Y = S)

CO1TI- Empirical Fou~d, qo Calculated, %

pound rap, ~ formula
c His C H S
,

Ia C~Hs o 12519126 C,sHnNOS 12,6 71,1 12,7

l'b C~Hs CIsHuNS2 23,6 66,9 23,8
Ic p-CH~OC~H~ o
181--76185 C16Ht~NO2S 11,6 67,9 I 1,3
Id p-CH~OC~H~ CI~Ht3NOS= 21,2 64,2 21,4
p-CH~C~H4 o 172,~8173 CI6HI~NOS 11,8 71,9 12,(~
p-CH~C~H4 CI6H,3NS2 22,2 67,8 22,6
p-C1C~H4 o 18719188 C,sHtoCINOS 11,5 62,6 1t. l
p-CIC6H4 C~sHtoCINS2 20,6 59,3 21.I
Ii rn-C1C~H4 o 147--148 CIsHtoCINOS 11,3 62,6 I l, l
I j m-CICsH,~ 199--200 CIsHtoCINS~, 20,6 59,3 21,1
Ik p-NO~C~H4 o 216 C15HtoN203S 10,5 60,4 10,7
I1 m-CH~C~H~ 18181188 C16H~3NS2 22,9 67,8 22,6
Im p-CeH~0COC6H~ C18HIsNO~Sz 18,6 63,3 18,8
1 n p-CHzCOC~H~ 201--202 C~7HiaNOS2 20,4 65,6 20.6.
Io CH~ 1831"~184 C~0H~NS~ 30,5 57,9 30,9
Ip tz-C4H9 CI~H~sNS~ 25,5 62,6 25,7
|q
Ir
CHzC~H~
C6HsCH2
o
181144182 Cr
C~HIaNS2
t2,4 71,9
22,8 67,8
12,0
22,6
III o 1657164 CI~HI~NO~S 12,9 63,1 13,0
lla C~H~ CI~H~aNOS 11,5 71,9 12,0.
lib C6H~ 74--75 CI6HI3NS~ 22,5 67,8 22,6
IIc p-CH~OC6H4 10510106 CITH~sNOS2 20,1 65,1 20,5
lid p-CIC6H4 C16HI2CINOS 10,5 63,7 10,6

S,103
22 22
i'
1~ "Jff 16
i

'~
// 14

6 6

2
[ i i r J i , j
^, nYl2
320 400 480 560 640 32o ,~oo ,*ho 5~o 280 36o ~ 620

Fig. I Fig. 2
Fig. 1. Electronic absorption s p e c t r a of acetone solutions: 1) 2-(N-phenylamino-
methylene)-3 (2H)-benz ofuranthione (Ia): 2) 2- (N-benzylaminomethylene)- 3 (2H)-
benzofuranthione (Ic): 3) 3-benzofuranthione 2-morpholinomethide {III); 4) 2 - f o r m y l -
3 - m e t h y l m e r c a p t o b e n z o f u r a n anil 0/a).
Fig. 2. Electronic absorption s p e c t r a of 2-(N-phenylaminomethylene)-3(2H)-benzo-
furanthione (a) and 2- (N-n-butylaminomethylene)-3 (2H)-benzo[b]thiophenethione 0o):
1) in d i m e t h y l f o r m a m i d e : 2) in acetone; 3) in benzene; 4) in methanol: 5) in carbon
tetrachloride.

Mercapto aldehydes V are rapidly oxidized, and they were t h e r e f o r e subjected to r e a c t i o n with the
a p p r o p r i a t e amines i m m e d i a t e l y after p r e p a r a t i o n without isolation in p u r e form.
The electronic s p e c t r a of all of the compounds of the I type contain a long-wave absorption band at
510-540 nm, which undergoes a h y p s o c h r o m i c shift (30-40 nm) in alkyl- and aralkylimines (Fig. 1 and
Table 2). This band is only slightly sensitive to a change in the s t r u c t u r e of substituent R and to the effect
of a solvent within each h e t e r o a r o m a t i c s e r i e s of anils, although its intensity i n c r e a s e s in the s p e c t r a of
2 - f o r m y l - 3 - m e r c a p t o b e n z o f u r a n derivatives as c o m p a r e d with the s p e c t r a of the c o r r e s p o n d i n g benzothio-
phene analogs. The insensitivity of the e l e c t r o n i c s p e c t r a of compounds of the I type to s t r u c t u r a l changes
(X, R) and to variation of the medium (Fig. 2) attests to stabilization of one of the possible t a u t o m e r i c f o r m s .
It can be identified as a r e s u l t of a c o m p a r i s o n with the absorption s p e c t r a of model s t r u c t u r e s II and III
and the r e s u l t s of q u a n t u m - m e c h a n i c a l calculations. The experimental electronic s p e c t r a of I a r e c l o s e to
the s p e c t r a of t h i o n e - a m i n e s t r u c t u r e III (Fig. 1 and Table 2).

547
 TABLE 2. Spectral C h a r a c t e r i s t i c s of A z o m e t h i n e s I. II, and III
UV spectra ................... m ?peetya. % c_m't
Com- mineral perfluoro=
pound solvent Xmax, nm (s .10 -3)
oil hydrocarbon

DMF 3~8(19.5),
385 (12,8), 510 (17,41 1590, 1600, 2880, 29,50,
Ia Benzene 368(21,01,
385 (19,2). 500 07,3). 522 (19,91 1645 3070
CC14 370 (24,5),
385 (21,6), 500 (18,4), 520 (20,3)
Acetone 378 (18,7), 5,10 (,20,81
3e2 (20,8),
DMF 297 (12,8).
365 (12,8), 510 (11,3) 1592, 1632. 2940, 3050
Ib Benzene 375 (19,51, 540 (13,7)
3oo (1o,2), 1655
Acetone 370 (18,3), 530 ([ t,51
DMF 375(14,2), 395 (1~2,4), 515 (17,2) 1590, 1615, 2870, 2955,
Ic Benzene 375(21,2}, 390 (19,5), 5'15 (~1,2), 530 (20,4) 166O 30~
Acetor~ 370(19,0), 385 (17,7), 508 (19,9), 525 (19,6)
DMF 370 (18.5), 385 (16,11. 523 (19,7) 1585, 1610, 2870, 2940,
le Benzene 370 (23,1), 387 (20,9), 523 (23,11 1~0 3060
Acetone 308(21,6), 380 (19,3), 5~15(23,01
DMF 300 (12,31, 375 (16,01, 530 (12,8} I~0, I~0 2940, 3040,
If Ben~.ene 302 (11,5), 375 (18.7), 545 (13,41 3070
Acetone 370 (20,7), 532 (14,81
DMF 370 (18.1), 383 (15,8). 520 (19,6) 15~, 1615, 2875. 2955,
Ig Benzene 370 (22,0). 387 (20.0), 500 (17,6), 525 (20,4) 1645 3070
Acetone 370 (2"2,2), 3,~0 (~0.4), 5~0 (21,7)
I DMF 297 (10,6), 370 (14,9), 530 (I 1,3) 1590, 1620, 2950, 3565
Ih i Benzene 300 01,21, 378 (20,5), 540 (16.5) 1640
Acetone 375 (20,1), 540 (13,7)
DMF 380 (18.1), 526 (15,1), 558 (18,1) 1600, 1605. 2950, 3045.
Ik Benzene 386 ( 16,71, 396 (18,3). 5,08 (13,7), 536 (17,7) 1650 3110
Acetone 393 (21,11, 510 (18,0), 530 (21,1)
DMF 297 (I 1,5), 340 (14,9), 490 (9,0) 1590, 1618, 2965, 3070
[P t Benzene: 3O'3 (I 1,1), 345 (19,5), 498 (11,2) 1650
Acetone I 340 (17,5), 485 (10.81
Methanol i 292 (11,11, 343 (19,9), 485 (t0,21
I DMF ~ 338 (18,2), 346 (19,91, 476 (13,7) 1580, 1650, 2950--3000,
I q Benzene 300 (18,7), 350 (26,5), 460 (115) 1640 .3080
Acetone : 343 (24,9), 450 (12,1), 470 (15.01
[DMF 297 (12,6), 340 (19,3), 492 (10.7) 1560, 1600, 2955. 3065
It. t Benz.ene 3OO ( 11,9), 350 (22,7), 500 (10.81 1635
Acetone 340 (21,81, 490 (11,5)
DMF 338 (14,81, 347 (17,4). 480 (15,8), 508 (17.2) 1590. 1610, 2890, 2950.
II I Benzene 338 (15,4), 350 (2J,7), 490 (16,1), 510 (16,6) 1640 299.0, 3050
Acetone 338 (17.9). 347 (,23,2). 480 (19.8), 510 (20,61
II a Acetone 354 (20,9) 1585, 162C,
DMF 350 (19,81 1590, 1615
llb }Methanol 348 (18.6)
Acetone 3.5"O(15,0)

The r e s u l t s of a calculation of the e n e r g i e s and intensities of the e l e c t r o n transitions in s t r u c t u r e s

of the IA and IC types are c o m p a r e d with the experimental data in Table 3. It can be s e e n that only the r e -
sults of calculation for t a u t o m e r IC a r e in good a g r e e m e n t with the o b s e r v e d e l e c t r o n i c absorption s p e c t r u m .
The r e s u l t s of redistribution of the ~ - e l e c t r o n c h a r g e s on the a t o m s during e l e c t r o n transitions
c a u s e d by l o n g - w a v e (S O- - S1) and s h o r t - w a v e (SO- - $2, the values in p a r e n t h e s e s ) excitation in m o l e c u l e s
of the IC type a r e shown in the m o l e c u l a r d i a g r a m s of VI and VII.
S+0,41
-0,03 / (+0,071
( +0,01 /--0,19 -0,01 0~00
- - O,O~l " / ~ O , 0 4 ) ~ - - O , O g ) -/.-~------%(0'00
) (0700)
(+ 0'01)[~ ~(~ \ -0,20 + O . 0 1 / \
+o 061
I I
I
NtY CH
/~-,.o,o9! i .... <+o.o2k
\-~176
1(+o,o21
, t 9. / " ,-o,2,,(-o,c",'v'~"~ /
(- %04 ) ~ Z ^~'~ /
v.-~'~2,'O +o,o3 - o,o~ 0700
+ 0712 (-0,051 ("-0,02)
(+0,01 ) ~] (0,00) (
+0,43

-
0,04 s
.~ (b,06)
- -0,01 0,00
(+0704)_n ~, /-0,22 (+0 01) (0 00)

(o,00)I" "r \ -of19 +%22 i \ ooi

\ /
9 O~.OO(.-(3,Oll +~.O~ O~OO O,OO
(0,04)
+ (+o,J)
~'~ 9-~ (0' 00) (*0701)

548
 T A B L E 3. C a l c u l a t e d and E x p e r i m e n t a l C h a r a c t e r i s t i c s of I and II
Calc. Exptl.
Compound*
E, eV (S~; E, eV(f)

la 2,49 (0,20), 3,55 (0.38) 2,44 (0,:~6) 3,z}2(0,84)

lb o,50 (0,12), 3,5,4 (0,48) 2,34 (0,15) 3,36 (0,38)
Iq 2.61 (0,1~8), 3,80 (0,12) 2,64 (0,28) 3,62(0,2,2)
IP 2,62 (0,11), 3,78 (0,18) 2,56 (0,14) 3,64 (0,11)
[Ia 3,62 (0,50) 3,50 (0,81)
IIb 3,4,6 (0A3) 3,54 (0,25)

* T h e n u m b e r s c o r r e s p o n d to t h o s e in Table 1: the s p e c t r a w e r e ob-

tained from acetone solutions.
The o s c i l l a t o r s t r e n g t h .

T A B L E 4. C h e m i c a l Shifts (6) of the NH P r o t o n s in C o m p o u n d s of

the IB T y p e in D i m e t h y l Sulfoxide

x Y ~ I 6, ppm x Y R 6, ppm

o C+H5 10,3 oo C+Hs 10,2

AIK 14,3 AIK 12,9"
s C6Hs 12,3 o C+H5 12,1

* In m e t h y l e n e c h l o r i d e .

T A B L E 5. D i f f e r e n c e s in the H e a t s of A t o m i z a t i o n of the Quinoid and

B e n z o i d T a u t o m e r s of I, with A l l o w a n c e f o r the D i f f e r e n c e s in the
Solvation E n e r g i e s
AAH a' kcal/mole
gas 8=2,2 e=48,9

H 7,4 18,1 21,4

C~H~ 4,7 16,8 19,9
H 2,7,7 24,8 21,3
C+H5 24,4 21,0 1,8,4
H 6,1 17,8 20,9
C6H5 3,2 14,7 18,1
tt 27,0 24,,0 20,8
C+H5 24,2 21,3 18,4

A n a l y s i s of the m a g n i t u d e of the i n c r e a s e in the 7r c h a r g e s on the a t o m s m a k e s it p o s s i b l e to d r a w the

following c o n c l u s i o n s : 1) the l o n g - w a v e t r a n s i t i o n s (So --*St) is d e t e r m i n e d b y c h a r g e t r a n s f e r f r o m the sul-
f u r a t o m to the m e t h y l i d y n e c a r b o n a t o m . 2) r e d i s t r i b u t i o n of the ~ - e l e c t r o n d e n s i t y f r o m the a n n e l a t e d
a r o m a t i c s y s t e m to the m e t h y l i d y n e c a r b o n a t o m without s u b s t a n t i a l p a r t i c i p a t i o n of the e l e c t r o n s of the
e x o c y c l i c s u l f u r a t o m is r e s p o n s i b l e f o r the s h o r t - w a v e t r a n s i t i o n (So -+$2) (in both c a s e s the v - e l e c t r o n
s y s t e m of the a m i n o p h e n y l f r a g m e n t s u s t a i n s p r a c t i c a l l y no p e r t u r b a t i o n by the indicated t r a n s i t i o n s ) ; 3)
t h e a b s o r p t i o n at 350 n m f o r b e n z o i d s t r u c t u r e II o r IA has t h e n a t u r e of l o n g - w a v e c h a r g e t r a n s f e r as in
t h e quinoid f o r m (So ---St) but is of l o w e r i n t e n s i t y .
The s i g n a l s c h a r a c t e r i s t i c f o r the splitting of the p r o t o n s in the > C H - C H - N = group, which c o r r e -
s p o n d s to s t r u c t u r e IB, a r e a b s e n t in the P M R s p e c t r a of anils I, and this m a k e s it p o s s i b l e to exclude this
f o r m f r o m c o n s i d e r a t i o n . T h e P M R s p e c t r a of all of the anils c o n f i r m s t r u c t u r e IC. Thus, t h e r e is a
s i g n a l of an NH p r o t o n with J = 13 Hz at w e a k field (5 > 10 ppm). this is c h a r a c t e r i s t i c f o r the > C H - N H -
AB s y s t e m [10]. Upon d e u t e r a t i o n the p r o t o n s of the m e t h y l i d i n e g r o u p give a s i n g l e t p e a k (6 ~ 8 p p m ) .
S p e c t r a of this s o r t a r e c h a r a c t e r i s t i c only f o r a s y s t e m of the IC t y p e . In addition to the s i g n a l s p r e s e n t e d
above, the P M R s p e c t r u m of b e n z y l a m i n o d e r i v a t i v e IC c o n t a i n s a doublet at 4.60 p p m f r o m the b e n z y l
g r o u p CH 2 p r o t o n s with J = 4 Hz, w h i c h is c l o s e to the coupling c o n s t a n t of the b e n z y l p r o t o n s of Schiff
b a s e s with a t h i o n e - e n a m i n e s t r u c t u r e [11]. A f t e r d e u t e r a t i o n ; the CH 2 p r o t o n s a p p e a r as a singlet. The
o b s e r v e d s p i n - s p i n coupling c o n s t a n t s (SSCC) of ( > C H - N I I - ) and ( - N H - C H 2 ) and t h e i r v i r t u a l i n d e p e n d e n c e
on the s o l u t i o n t e m p e r a t u r e a t t e s t to the r e a l i z a t i o n of a s i n g l e s t r u c t u r e - IC - and its high r e l a t i v e stability.
One c a n judge the s t r e n g t h of t h e i n t r a m o l e c u l a r h y d r o g e n bond in the I m o l e c u l e s f r o m the m a g n i t u d e of the
shift of the NH p r o t o n s (Table 4). The s i g n a l of t h e NH p r o t o n in the s p e c t r a of thione c o m p o u n d s (Y = S)

549
 is at w e a k e r field by ~ 2 ppm a s c o m p a r e d with the c o r r e s p o n d -
ing signal of keto amines (Y = O). This is evidence for the
p r e s e n c e of a s t r o n g e r hydrogen bond in molecules of the f i r s t
type. The signals of the p r o t o n s of the amino group a r e also
CC ~ s i m i l a r l y shifted to weak field when aryl radical R is r e p l a c e d
by alkyl groups: this is a consequence of r e i n f o r c e m e n t of the
i n t r a m o l e e u l a r hydrogen bond in derivatives of aliphatie amines.
Replacement of the cyclic h e t e r o a t o m does not have a substan-
tial effect on the magnitude of the NH shift and, consequently,
~C ~C on the e n e r g y of the i n t r a m o l e c u l a r bond.
[ I I I
The t h i o n e - a m i n e s t r u c t u r e of I is also confirmed by t h e i r
IR s p e c t r a (Table 2), which eontain a band at 1630-1650 cm -i,
c o r r e s p o n d i n g to the s t r e t c h i n g vibrations of a conjugated axe-
eyclic C - C bond. which appears at 1640 cm - i in the s p e c t r u m
~ cc of Ill. The band at ~1640 em - i is absent in the s p e c t r a of azo-
I I I I
methines II (with an imine structure), but the absorption at
1610-1620 em - i that is c h a r a c t e r i s t i c for the C = N bond in azo-
--.- o o
cc o~o methines of this type [6] is observed.
In o r d e r to i n t e r p r e t the experimental r e s u l t s that we ob-
tained, we estimated the relative stabilities of t a u t o m e r s IA
CC CC CC C~
I ] I ] and IC and of the c o r r e s p o n d i n g 3-hydroxy compounds [2, 3]
(X = O, S: Y = O, S) by means of the P a r i s e r - P a r r - P o p l e (PPP)
dd dd dd dd s e l f - c o n s i s t e n t field (SCF) MO method with the Dewar ~,~ p a r a -
m e t r i z a t i o n [12-14]. The differences in the heats of atomiza-
tion (AAHa) of the qninoid and benzoid f o r m s , with allowance
f o r the differences in the solvation energies of the indicated
C~O CO ~D~ t a u t o m e r s , a r e p r e s e n t e d in Table 5. The calculations in all
~ I I I ~ I i I I c a s e s p r e d i c t the complete p r e f e r a b l e n e s s of the ketone- and
t h i o n e - e n a m i n e f o r m IC~ r e g a r d l e s s of the c h a r a c t e r of the
h e t e r o a t o m in the ring. The introduction of a phenyl group in
c~ cfc~ c~c~ cfc~
p l a c e of an alkyl group as a substituent attached to the nitrogen
atom does not have a substantial effect on the position of the
o.o oo o o o o
9 I equilibrium. In a11 cases, r e p l a c e m e n t of the noncyclie oxygen
I i I I I I I [
atom by a sulfur atom stabilizes the s t r u c t u r e of the IC type.
NN NN The r e s u l t s of the calculation of the heats of solvation
p r e d i c t that the solvation e n e r g y of the quinoid t a u t o m e r s in the
c a s e of the 3-hydroxy derivatives is higher (by 18-21 k c a l / m o l e )
~c than that of the benzoid t a u t o m e r s in a solvent with a Mgh di-
I [ I I I I [ I e l e c t r i c p e r m e a b i l i t y . In the c a s e of m e r c a p t o a z o m e t h i n e s l e s s
hO p o l a r solvents stabilize the quinoid s t r u c t u r e b e t t e r than highly
p o l a r solvents. The data in Table 6 r e f l e c t the distribution of
0 the v c h a r g e s in the ground state of the s t r u c t u r e s of I. calcu-
lated with the Dewar p a r a m e t r i z a t i o n for the qninoid and b e n z o i d
s t r u c t u r e s . It can be seen that the nature of the h e t e r o r i n g
I I [ I 1] I I and the amino group has r e l a t i v e l y little effect on the c h a r g e
o
distribution in each t a u t o m e r i c f o r m .
O~D CDC OO
A study of the calculated g e o m e t r i c a l c h a r a c t e r i s t i c s of
benzoid and quinoid t a u t o m e r s IA and IC also r e v e a l s a s i m i l a r
o ~ o ~ o-c~ o~o ~ ~o-
p e c u l i a r i t y (Table 7). In the case of the benzoid t a u t o m e r s , the
11 [ I g e o m e t r y of the mercaptovinyl f r a g m e n t of the IA molecule is
retained, r e g a r d l e s s of which ring includes it. The s a m e is
N valid for the quinoid t a u t o m e r s with r e s p e e t to the aminothione
f r a g m e n t of IC. A s i m i l a r p a t t e r n is observed for the 3 - h y -
d r o x y derivatives of I (Y = O).
All of the r e s u l t s of the calculations p r e s e n t e d above con-
f i r m the experimental conclusion that compounds of the I type

550
 TABLE 7. Calculated Bond Lengths in the Mercaptovinylimine and
Aminothione F r a g m e n t s of the T a u t o m e r s of I (g = S)
I l

2 5
~.x3~:4 n~CN"-R
s ~X/~CH/ Nn \ R

Com - Bond length, A

pound I--2 2--3 ] 3--4 4--5

O H 1,740 1,364 1,452 1,293

IA C6H~ 1,737 1,366 1,447 1,302
S H 1,748 1,365 1,458 1,989
C6H5 1,764 1,366 1,453 1,989
O H 1,598 1,463 1,350 1,411
IC CsH5 1,598 1,4~4 1,350 1,411
S H 1,597 1,467 1,350 1,415
C6Hs 1,597 1,467 I,~50 1,415

exist p r i m a r i l y in the IC f o r m in both the gas phase and in m e d i a with different polarities, r e g a r d l e s s of
the variations of the s t r u c t u r a l f r a g m e n t s of the m o l e c u l e s .

EXPERIMENTAL

The absorption spectra in the UV and visible regions were recorded with a Specord UV-vis spectro-
photometer. The m spectra were obtained with a UR-20 spectrometer. The PMR spectra of 15-20% solu-
tions of the compounds were obtained with a Tesla BS-407-C spectrometer (80 MHz) at 25 ~ with hexamethyl-
disiloxane (HMDS) as the internal standard.
In the calculations of the relative stabilities of the benzoid and qninoid tautomers by means of the PPP
method, allowance for the solvation energy was made with a formula that is a development of the well known
Born equation for the solvation of an ion:

~olv = - 2 - ( Zq~2Ym~+2E Yq~%Yuu) 1- ,

p. ~<u

w h e r e qp is the c h a r g e on atom p and e is the d i e l e c t r i c p e r m e a b i l i t y of the solvent. The details of the

calculations by the Dewar method are set forth in g r e a t e r detail in [16]. The calculations were p e r f o r m e d
with the p r o g r a m c o m p o s e d by V. A. Kosobutskii.
The electronic absorption s p e c t r a and the c h a r a c t e r i s t i c s of the excited states were calculated by the
standard P P P method within the approximation of a variable ~ constant [17] with allowance for 20 singly
excited configurations. The t w o - e l e c t r o n coulombic integrals (7#~) w e r e calculated f r o m the standard
M a t a g a - N i s h i m o t o f o r m u l a [18]. We p r e s e n t e d the principal p a r a m e t e r s used in the calculation of the s p e c -
t r a l c h a r a c t e r i s t i c s in [19, 20].
2 - F o r m y l - 3 - m e r c a p t o b e n z o [ b ] t h i o p h e n e (V, X = S) and 2 - F o r m y l - 3 - m e r c a p t o b e n z o f u r a n {V, X = O).
T h e s e compounds w e r e obtained f r o m c h l o r o aldehydes IV (X = S [15] and O [3]) in analogy with the method
in [7]. A solution of 0.03 mole of sodium hydrosulfide in 2.5 ml of water was added to a cooled solution of
0.01 mole of aldehyde IV in 80 ml of acetone, and the m i x t u r e was then heated on a w a t e r bath for 2 h. It
was then cooled, and the p r e c i p i t a t e d sodium chloride was r e m o v e d by filtration. The filtrate was vacuum
evaporated, and the residue was diluted with ice w a t e r and neutralized carefully with 15% h y d r o c h l o r i c acid.
The resulting yellow flakes of aldehyde V w e r e extracted rapidly with ether. The ether extracts w e r e c o m -
bined, dried with anhydrous Na2SO4, and used i m m e d i a t e l y for the p r e p a r a t i o n of anils I.
2- F o r m y l - 3- (methylmercapto)benzo[b]thiophene (VIII) and 2 - F o r m y l - 3 - (methylmercapto)benzofuran
(IX). A 1-ml (0.011 mole) sample of dimethyl sulfate was added with s t i r r i n g to a solution of 0.01 mole of
aldehyde V in 20 ml of 5% alkali, whereupon yellow methylation p r o d u c t s VI or VII precipitated. The yield
was ~ 60%. Two r e c r y s t a l l i z a t i o n s f r o m alcohol gave yellow c r y s t a l s . Compound VIII: mp 80-81~ IR
s p e c t r u m : 1670 c m -1 (C=O). Found %: C 58.0: H 4.1'- S 30.5. C10H802S. Calculated %: C 57.7,. H 3.9:
S 30.8. Compound IX: mp 72~ IR s p e c t r u m : 1680 e m - I (C=O). Found %: C 62.1; H 4.0. S 16.6. CIoH802S.
Calculated %: C 62.3. H 4.2: S 16.8.

551
 Imines I and III were obtained by reaction of solutions of the aldehydes in ether with the appropriate
amines and recrystallization from ethanol or propyl alcohol. Compounds I were obtained as shiny orange
or red-brown substances.
Azomethines II were synthesized by reaction of equimolecular amounts of aldehydes VIII or IX with
the appropriate amines in alcohol. Crystallization from alcohol gave light-yellow crystals in 60-70% yields.

LITERATURE CITED
1. V. I. Minkin, L. P. Olekhnovieh, A. E. Lyubarskaya, M. I. Knyazhanskii. and I. E. Mikhailov, Zh.
Organ. Khim., 1_.00.817 (1974).
2. V. A. Bren', V. I. Usacheva, and V. I. Minkin, Khim. Geterotsikl. Soedin., 920 (1972).
3. V. A. Bren', Zh. V. Bren'. and V. I. Minkin, Khim. Geterotsikl. So.din., 154 (1973).
4. J. Bignebaut, H. Quiniou, and N. Lozac'h, Bull. S.c. Chim. France. 127 (1969).
5. V. S. Bogdanov, Ya. L. Danyushevskii, and Ya. L. Gol'dfarb, Izv. Akad. Nauk SSSR. Ser. Khim., 675
(1970).
6. L. E. Nivorozhkin, M. S. Korobov, B. Ya. Simkin, and V. I. Minkin. Zh. Organ. Khim., _8, 1677 (1972).
7. I. Ya. Kvitko and B. A. Porai-Koshits, Zh. Organ. Khim., 5. 1685 (1969).
8. R. A. Koffman and S. Gronowitz, Arkiv Kemi, 16, 515 (1960).
9. S. Gronowitz, Arkiv Kemi, 17, 237 (1961).
10. N. M. D. Brown and D. C. Nonhebel. Tetrahedron, 24, 5655 (1968).
11. Do H. Gerlach and R. H. Holm, J. Amer. Chem. S.c., 91, 3457 (1969).
12. M. Dewar, Molecular Orbital Theory of Organic Chemistry, McGraw-Hill (1969).
13. A. L. H. Chung and M. J. S. Dewar, J. Chem. Phys.. 42, 756 (1965).
14. M. J. S. Dewar and A. J. Harget, Proc. Roy. S.c., A315, 443, 457 (1970).
15. A. Ricci, D. Balucani, and N. P. Buu-Hoi, J. Chem. S.c., C, 779 (1967).
16. V. I. Minkin. V. A. Kosobutskii (Kosobutskij), B. Ya. Simkin, and Yu. A. Zhdanov, J. Mol. Struct.,
No. 3. 22 (1974).
17. K. Nishimoto and L. S. For s t er , Theor. Chim. Acta, 7, 207 (1967).
18. N. Mataga and K. Nishimoto. Z. Phys. Chem., 13, 140 {1957).
19. V. I. Minkin, V. Ya. Simkin, and L. P. Olektmovich (Olechnovitch), Ind. J. Sulfur Chem., 3A, No. 3
(1973).
20. V. I. Minkin, L. P. Olekhnovich, and B. Ya. Simkin, Zh. Organ. Khim., 7, 2364 (1971).

552
SYNTHESIS AND REACTIONS OF AZIDES

OF HETEROCYCLIC COMPOUNDS
HI.* CYANINE DYES BASED ON AZIDES OF BENZOTHIAZOLE AND BENZIMIDAZOLE

I. A. Ol'shevskaya and V. Ya. Poehinok UDC 547.789.6.07:668.8

Cyanine dyes containing azido groups in the 5 or 6 position of the benzazole ring were obtained
f r o m q u a t e r n a r y salts of azides of benzothiazole and benzimidazole. The introduction of an
azido group into the dye molecule r e s u l t s in a considerable b a t h o c h r o m i c effect.

5-Azido- (I) and 6 - a z i d o - 2 - m e t h y l b e n z o t h i a z o l e methiodides (i1) and 5 - a z i d o - l - p h e n y l - 2 - m e t h y l - (HI)

and 6-azido-1, 2-dimethylbenzimidazole ethiodides (IV), which were d e s c r i b e d in [2], were used for the syn-
t h e s i s of cyanine dyes containing azido groups in the 5 or 6 position of the benzazole ring.

S\
r ~ ( - ~ . , / / c _ c u = c u _ c # __n {c.~ ~ ..~'....-s.,
1 I- / %

CH 3 CH3 R"
V, VI VII-XII

XN
R--4-' II +.C--CH=CIt--CI~ =C II 1
~*-~ o=r s %Aver ,- \n--v.JI
R' I C2H s C=H s
C2H5 XV-XVIII
XIII, XIV, XlX, XX

V R=5-Na; VI R=6-Na; VII R=5-Na, R'=H, R"=C=,Hs, n=0; VIII R=L6-Na, R'=H,
R"=C_~Hs, n=0; IX R=R'=f-Na, R"=CHa, n=l; X R=R'=6-Na, R"=CHa, n=l; XI
R=5-Na, R'=H, R"=CHa. n=l; XII R=6-Na, R'=H, R"=CHa, n=l; XIII R=5-Na.R'=
=CH3, X=S; XIV R=6-Na, R'=CH3, X=S; XV R=5-Na. X=N-C6Hs,Y=S; XVI R=6-Na,
X=N-CHa, Y=S; XVII R=5-Na, X=N-C6Hs, Y=CH=CH; XVIII R=6-Na, X=N-CHa,
Y=CH=CH; XIX R=5-Na, R'=CzHs. X=N-C6Hs; XX R=6-Na, R'=C2Hs, X=N-CHa

In c o n t r a s t to the q u a t e r n a r y salts of benzothiazole azides, the q u a t e r n a r y salts of the benzimidazole

azides do not f o r m s y m m e t r i c a l c a r b o c y a n i n e s in either acetic anhydride or pyridine. When we c a r r i e d out
the r e a c t i o n in nitrobenzene, the azide q u a t e r n a r y salts decomposed.
On the b a s i s of data f r o m the IR s p e c t r a of the cyanine dyes (V-XX), it can be concluded that on p a s s -
ing f r o m q u a t e r n a r y salts to cyanine dyes the azido group in the latter is retained and p a r t i c i p a t e s in the
conjugation s y s t e m . The IR s p e c t r a of the cyanine dyes contain bands of the a s y m m e t r i c a l stretching v i b r a -
tions of the azido group at 2105-2123 cm -~ (Tables 1 and 2).
To c l e a r up the question of the effect of the azido group on the c o l o r of the cyanine dyes we used dyes
of the benzothiazole s e r i e s , for which s t y r y l s (V, VI), monomethylidynecyanines (VII, VIII), s y m m e t r i c a l
(IX, X) and u n s y m m e t r i c a l (XI, XII) carbocyanines, and m e r o c y a n i n e s (XIII, XIV) were obtained. We were
unable to obtain this s e r i e s for imidacyanines. F r o m a c o m p a r i s o n of the absorption m a x i m a of the dyes
that we obtained and the c o r r e s p o n d i n g unsubstituted dyes the following conclusions can be drawn. The in-
troduction of an azido group into the benzazole ring of the cyanine dye leads to a considerable shift in the

* See [1] for c o m m u n i c a t i o n II.

T. G. Shevchenko Kiev State University. T r a n s l a t e d f r o m Khimiya Geterotsiklieheskikh Soedinenii.

No. 5, pp. 640-642, May, 1974. Original article submitted F e b r u a r y 16, 1973.

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, N.Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

553
 TABLE I. Cyanine Dyes f r o m B e n z o t h i a z o l e A z i d e s
Xma x of the dye
Compound kmax, nm log without an azido Empiricalformula YasN3' c m ' l
group, nm (log ~ )
V* 540 4,70 528 (5,04) 6 12 212,3
VI* 535 4.74 528 (5,,04) 9 7 2116
VI 1 430 4,97 422 (4,91) 7 8 2115
VIII 434 4,91 422 (4,91) 7 12 2105
IX* 576 5,15 558 (5,16) s 18 2114
X* 580 5,15 558 (5~16)6 22 2110
XI* 566 5,07 558(5,,15) s 8 2120
XII* 570 5,09 55~ (5,15) s 12 2114
XIII* 530 4,78 5~1 (<96p 9 2114
" XIV* 536 4,79 521 (4,96) 6 15 2120

*See [2] for the s y n t h e s i s of the dyes.

TABLE 2. Cyanine Dyes f r o m B e n z i m i d a z o l e Azides

Corn- Empirical Fo a~
pound mp~ ~ formula _ _ _ _
N ;:~'.,.'~ ~.., [ 0 9

N [ S, N [ S I

XV 2 1 4 ~ 1 6 C27HzsINgS '14,6 5,6 14,2 5,4 522 5,03 5179 5 2110 60

XVI 2 I0~2:h2 C92H23IN6S 1,6,0 I 6,2 15,8 I 6,0 522 4~7 500~ 22 2115 40
XVII C~gH231N6 14,01 - - 14,,3[ - - 574 5599 15 2110 50
XVIII Co4H2slN6 16,2 - - 16,0 - - 5,34 4,92 5219 l~ 2112 57
XlX 169----170 C22H29N6OS2 18,8 18,9 18,9 13,9 5,24 5,13 5119 2110 34
XX 1981200 C'17H,oN6OS2 21,6 1,6,4 21,9 16,1 526 -- 5119 15 2110 45

absorption m a x i m u m to the l o n g - w a v e portion of the spectrum, and this shift is s o m e w h a t g r e a t e r for thia-
cyanines than for i m i d a c y a n i n e s . Two azido groups in the 5,5' or 6.6' positions of the thiacarbocyanine
c a u s e a b a t h o c h r o m i c effect that is t w i c e that of one azido group in the 5 or 6 p o s i t i o n (Table 1). The ab-
sorption m a x i m a of the cyanine dyes containing an azido group in the 6 position of the b e n z o t h i a z o l e ring
differ only slightly f r o m the absorption m a x i m a of the 5 - a z i d o d e r i v a t i v e s .
In [3] it is noted that the slight difference in the c o l o r of the 5,5'- and 6,6'-substituted thiacarbocya-
nines is a s s o c i a t e d with the equal p o s s i b i l i t y of conjugation of the substituents with the polymethine chain
of the dye through both the nitrogen atom and the sulfur atom. The sulfur atom of the t h i a z o l e ring is an
e l e c t r o n conductor only with r e s p e c t to e l e c t r o n - d o n o r substituents and does not participate at all or p a r -
ticipates only w e a k l y in conjugation if there is an e l e e t r o n - a c c e p t o r substituent in t h e s e positions [4]. The
a b s e n c e of conjugation through the sulfur atom for e l e c t r o n - a c c e p t o r substituents explains the great differ-
e n c e in the color of thiacarbocyanines that contain e l e c t r o n - a c c e p t o r substituents in the 5, 5' and 6, 6' p o s i -
tions. The s m a l l difference in the absorption m a x i m a of thiacarbocyanines that contain azido groups in the
5, 5' and 6, 6' p o s i t i o n s provides a b a s i s for a s s u m i n g that the azido group acts as an e l e c t r o n - d o n o r substi-
tuent in this c a s e . In n u m e r i c a l value its bathoehromic effect approaches the effect of the a c e t a m i d o group
[4]. The a e e t a m i d o group does not c a u s e deviations when it is introduced into one ring of the thiaearbo-
eyanine [5]. We o b s e r v e the s a m e thing when an azido group is introduced into one b e n z o t h i a z o l e ring of
the dye.
It is known that the c o l o r of m e r o c y a n i n e s is shifted b a t h o c h r o m i c a l l y when the b a s i c i t y of the h e t e r o -
c y c l i c r e s i d u e bonded to the rhodanine ring by a polymethine chain i n c r e a s e s . T h i a m e r o c y a n i n e s containing
an a z i d o group as a substituent are m o r e deeply c o l o r e d (by 9-15 n_m) than the unsubstituted dyes, and this
is an indirect c o n f i r m a t i o n of the fact that the azido group acts as an e l e c t r o n - d o n o r substituent. The s i -
m i l a r i t y , in an optical r e s p e c t , of thiacarbocyanines that contain an azido group in the 5. 5' and 6, 6' p o s i -
tions can be explained by the equal p o s s i b i l i t y of conjugation of the azido group in t h e s e dyes through both
the n i t r o g e n atom and the sulfur atom.

EXPERIMENTAL

The IR s p e c t r a of KBr p e l l e t s w e r e r e c o r d e d with a UR-10 s p e c t r o m e t e r . The UV s p e c t r a of ethanol

solutions w e r e r e c o r d e d with an S F - 4 s p e c t r o p h o t o m e t e r .
( 3 - M e t h y l - 5 - a z i d o - 2 - b e n z o t h i a z o l y l ) ( 3 ' - E t h y l - 2 ' - b e n z o t h i a z o l y l ) m o n o m e t h y l i d y n e c y a n i n e Iodide (VII).
A mixture of 0.33 g (1 m m o l e ) of 5 - a z i d o - 2 - m e t h y l b e n z o t h i a z o l e methiodide0 0.38 g (1 m m o l e ) of 2 - m e t h y l -
m e r c a p t o b e n z o t h i a z o l e ethyltosylate, and 1 m m o l e of triethylamine in absolute ethanol w a s refluxed for

554
30 rain. The dye began to precipitate as the mixture was heated. The mixture was cooled, and the precipi-
tate was removed by filtration and washed with alcohol to give 0.28 g (45%) of a product with mp 262-264 ~
(dec., from ethanol). Found %: N 14.3. S 13.0. C18HI6INsS 2. Calculated %. N 14.2: S 13.0.
(3-Methyl- 6-azido-2-benzothiazolyl) (3'- Ethyl-2'-benzothiazolyl)monomethylidynecyanine Iodide (VIII).
This compound was similarly obtained from 0.33 g (I mmole) of 6-azido-2-methylbenzotbiazole and 0.38 g
(I mmole) of 2-methylmercaptobenzothiazole ethyltosylate. The yield of product with mp 225-228 ~ (dee.,
from ethanol) was 0.32 g (56%). Found %: N 14.17 S 13.2. CtsHt61NsS2. Calculated %: N 14.2. S 13.0.
Unsymmetrical Carbocyanines XV and XVI. These dyes were obtained by heating equimolecular
amounts of the corresponding quaternary salts (III or IV) with 3-ethyl-2-formylmethylenebenzothiazoline
in acetic anhydride. The resulting dyes were removed by filtration, washed with alcohol and ether, and
crystallized from alcohol (Table 2).
Unsymmetrical Carboeyanines XVII and XVIII. These compounds were obtained by heating equi-
molecular amounts of the appropriate quaternary salt (Ill or IV) and 2-w-acetanilidovinylquinoline in acetic
anhydride in the presence of triethylamineo The dyes were purified by chromatography of chloroform
solutions of them with a column filled with activity II aluminum oxide (Table 2).
Merocyanines XIX and XX. These dyes were obtained by heating equimolecular amounts of the cor-
responding ethiodides (Ill or IV) with acetanilidomethylene-N-ethylrhodanine in ethanol in the presence of
triethylamine. The products were purified by chromatography of chloroform solutions of them on activity
II aluminum oxide (Table 2).

LITERATURE CITED
1. I. A. Ol'shevs'ka, V. Ya. Pochinok, N. A. Pasmurtseva, and N. F. Parkhomenko, Visnik Kiivs'k.
Univ.. Set. Khim.. No. 14, 61 (1973).
2. I. A. Ol'shevskaya, V. Ya. Pochinok, and L. F. Avramenko, Khim. Geterotsikl. Soedin., 898 (1968).
3. E. D. Sych and L. P. Umanskaya, Zh. Obshch. Khim., 33, 80 (1963).
4. E. D. Sych, Ukr. Khim. Zh., 18, 159 (1952).
5. A. I. Kiprianov, Doctoral Dissertation [in Russian], Kharkov (1940).
6. A. I. Kiprianov and F. A. Mikhaflenko, Zh. Obshch. Khim., 31. 781 (1961).
7. A. I. Kiprianov and I. K. Ushenko, Zh. Obshch. Khim., 20, 135 (1950).
8. A. I. Kiprianov and F. A. Mikhailenko, Zh. Obshch. Khim., 31, 786 (1961).
9. A. V. Stetsenko and L. I. Fflfleeva. Ukr. Khim. Zh., 32, 853 (1966).

555
SYNTHESES IN T H E PHENOTHIAZINE SERIES
XXXVII.* SOME PROPERTIES OF QUATERNARY SALTS
OF 2-METHYLMERCAPTOTHIAZOLO[4, 5-b] PHENOTHIAZINE

V. V. S h a v y r i n a and S. V. Z h u r a v l e v UDC 547.869.2'789.6.07

Some nucleophilic substitution reactions of 2-methylmercapto-3-methylthiazolo[4,5-b]pheno-

thiazinium methosulfate w e r e studied. Cleavage of the l a t t e r with alcoholic alkali gives bis-
(2-2-methylamino-3-phenothiazinyl) disulfide: cleavage and subsequent alkylation gives new
disubstituted phenothiazines.

Continuing our investigation of the chemical p r o p e r t i e s of thiazolo[4, 5-b]phenothiazine derivatives

[2, 3], we have studied some r e a c t i o n s of q u a t e r n a r y salts of 2-methylmercaptothiazolo[4, 5-b]phenothi-
azine (I).
It is known that q u a t e r n a r y salts of 2-alkylmercaptobenzothiazole have i n c r e a s e d r e a c t i v i t y as com-
p a r e d with benzothiazole itself. Owing to the considerable positive charge on the carbon atom bonded to the
a l k y l m e r c a p t o group, benzothiazolium salts r e a d i l y undergo nucleophilic substitution r e a c t i o n s at this
atom [4- 6].
Inasmuch as the q u a t e r n a r y salts of I a r e s i m i l a r in s t r u c t u r e to the q u a t e r n a r y salts of 2 - a l k y l m e r -
captobenzothiazole, it might have been expected that they would also p r o v e to have s i m i l a r chemical
properties.
Heating of I with dimethyl sulfate in dioxane gave 2-methylmereapto-3-methylthiazolo[4, 5-b]phene-
thiazinium methosulfate {Irb), which, in c o n t r a s t to methiodide Ha [2], is m o r e soluble in hot w a t e r and in
hot alcohol. We t h e r e f o r e c a r r i e d out our study of the reactions of the q u a t e r n a r y salts p r i m a r i l y with
methosulfate IIb.
3-Methyl-2,3-dihydrothiazolo[4, 5-b]phenothiazin-2-one (III) is f o r m e d by refluxing IIb with water or
by the action of a concentrated alkali solution on an aqueous solution of IIa o r IIb at r o o m t e m p e r a t u r e .
3-Methyl-2,3-dihydrothiazolo[4, 5-b]phenothiazin- 2- one (IV), which was p r e v i o u s l y obtained by i s o m e r i z a -
tion of IIa, was synthesized by the action of sodium sulfate solution on an aqueous solution of IIb. The

I! I| X.- H
, ,,,-v

N NHCH3 NIICH.1 ~/-~'N / ~ ~NHCHI

VII VI VIII-X

lla X~ I. D X=CH3$O4; III X = o ; IV X=S; V X=NCH3; VIII R=CH~; IX R=C2IIs; X R=C411,)

* See [1] f o r communication XXXVI.

Institute of Pharmacology, Academy of Medical Sciences of the USSR, Moscow. T r a n s l a t e d f r o m Khimiya

Geterotsiklicheskikh Soedinenii, No. 5, pp. 643- 645. May. 1974. Original a r t i c l e submitted D e c e m b e r 7, 1972.

9 1975Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

556
r e a c t i o n of an aqueous solution of IIb with m e t h y l a m i n e gave 2 - m e t h y l i m i n o - 3 - m e t h y l - 2 , 3 - d i h y d r o t h i a z o l o -
[4, 5]phenothiazine (V).
When IIb is refluxed with an alcohol solution of p o t a s s i u m hydroxide the thiazole ring is opened, but
bis ( 2 - m e t h y l a m i n e - 3 - p h e n o t h i a z i n y l ) disulfide (VII) was isolated f r o m the r e a c t i o n m i x t u r e instead of the
expected 2 - m e t h y l a m i n o - 3 - m e r e a p t o p h e n o t h i a z i n e (VI) a f t e r acidification. S i m i l a r r e s u l t s w e r e obtained
in the r e a c t i o n of an alcohol solution of alkali with IIa and III. If the alkaline c l e a v a g e of t h e s e s u b s t a n c e s
is c a r r i e d out in a s t r e a m of nitrogen, the initially f o r m e d VI can be alkylated with alkyl halides without
isolation f r o m the r e a c t i o n m e d i u m . This method was u s e d to obtain 2 - m e t h y l a m i n o - 3 - a l k y l m e r c a p t e p h e n o -
t h i a z i n e s (VIII-X).

EXPERIMENTAL
2-Methylmereapto-3-methylthiazolo[4,5-b]phenofhiazininm Methosulfate (lib). A 5-ml (0.05 mole)
sample of dimethylsulfate was added to a suspension of 9 g (0.03 mole) of I in 40 ml of dioxane, and the mix-
ture was heated on a boiling-water bath for 3 h. It was then cooled, and the precipitate was removed by
filtration and washed with alcohol and ether to give 10.6 g (83%) of IIb. The orange powder was insoluble in
most organic solvents but soluble in hot water: it did not have a characteristic melting point aRer recrys-
tallization from alcohol or water. Found %: N 7.0: S 30.1. C16HI6N204S4. Calculated %: N 6.5: S 29.9.
3-Methyl-2,3-dihydrothiazolo[4, 5-b]phenothiazin-2-one (III). A) A total of 5 ml of a 30% solution of
sodium hydroxide was added at room temperature to a solution of 6.3 g (0.015 mole) of IIb in 300 ml of
water. After 15-20 rain, the grayish precipitate was removed by filtration, washed with water, and dried
to give 3.1 g (72gc) of III with mp 266-269 ~ (dee., from diehloroethane) and R/ 0.57 [A1203, benzene-methanol
(10:2)]. IR spectrum: 1706 (CO), 3335 em -~ (NH). Found %: N 9.9: S 22.3. CI4HIoN2OS 2. Calculated %:
N 9.8: S 22.4.
B) A solution of 0.4 g (0.001 mole) of IIb in 50 ml of water was refluxed for 6 h, and the resultihg
grayish precipitate was removed by filtration and dried to give 0.2 g (71~c) of product.
The identical character of the compounds obtained by these methods was confirmed by the absence of
a melting-point depression for a mixture of the two products, by thin-layer chromatography (TLC), and by
IR spectroscopy.
3-MeflwI-2,3-dihydrothiazolo[4.5-b]phenothiazin-2-thione (IV). A solution of 0.7 g (0.003 mole) of
sodium sulfate in 2 ml of water was added with stirring at 50 ~ to a solution of 1 g (0.0023 mole) of IIb in
50 ml of water, and the mixture was then stirred at 50 ~ for 1 h. It was then cooled, and the precipitate was
separated and washed with water to give 0.4 g (60~c) of a product with nap 252-255 ~ (dee., from toluene) and
R/ 0.35 [A1203. chloroform-benzene (I:I)]. Found %: N 9.1: S 31.4. CI4HIoN2S3. Calculated %: N 9.3:
S 31.8:
2-Methylimine-3-methyl-2,3-dihydrothiazolo[4,5-b]phenothiazine (V). A 2.5-mi (0.02 mole)sample
of a 25~c aqueous solution of methylamine was added dropwise with stirring to a solution of 1.5 g (0.0035
mole) of IIb in I00 ml of water, after which the mixture was stirred for 30 rain. The precipitate was sepa-
rated, dried, and ehromatographed in chloroform with a column filled with aluminum oxide. Elution with
chloroform gave 0.3 g (30%) of III (R/ 0.57, A1203, chloroform) and 0.4 g (40%) of V (R/ 0.52) with mp 225-
229 ~ (from benzene). IR spectrum: 1630 cm -I (C=N). Found %: N 14.0~ S 21.9. C15HI3N3S2 . Calculated %:
N 14.0: S 21.4.
Bis(2-methylamine-3-phenothlazinyl) Disulfide (VII). A suspension of 2.1 g (0.005 mole) of IIb in a
solution of 5 g (0.09 mole) of potassium hydroxide in 90 ml of alcohol was refluxed for 1 h. It was then
cooled, and diluted with water. The aqueous mixture was acidified with dilute hydrochloric acid, and the
precipitate was separated and washed with alcohol to give 1 g (77%) of VII with mp 228-230 ~ (dec., from
aniline). IR spectrum: 3405, 3340 cm -i (NH). Found ~ N 10.7; S 24.3; M 527 (by the Rast method).
C26H22N4S4. Calculated %: N 10.8; S 24.7; M 519.
2-Methylamino-3-methylmercaptephenothiazine (VIII). A mixture of I g (0.0023 mole) of IIb and 2.5 g
(0.045 mole) of potassium hydroxide in 25 ml of alcohol was refluxed for 2 h in a stream of nitrogen on an
oil bath. The bath temperature was lowered to 35-40 ~ and 15 ml of hot water was added to the reaction
mixture. A solution of 0.3 ml (0.005 mole) of methyl iodide in 2 ml of alcohol was added drepwise, and the
mixture was stirred at 40-45 ~ (bath temperature) for 1 h. If was then filtered, and the filtrate was diluted
with water until it became turbid. The precipitate was separated and washed with water to give 0.5 g (78%)
of VIII. After chromatography on aluminum oxide in a benzene-chloroform system (2 : I) and reerystallization

557
f r o m methanol the p r o d u c t had mp 149-151 ~ IR s p e c t r u m : 3398, 3325 c m -1 (NH). Found %: N 10.3,. S 23.1.
C14HI4N2S2. Calculated %. N 10.2: S 23.4.
2- Methylamino- 3- e t h y l m e r e a p t o p h e n o t h i a z i n e (IX). This compound, with mp 144-146 ~ (from aqueous
methanol), was obtained in 74% yield f r o m IIb and ethyl b r o m i d e by the method used to p r e p a r e VIII. Found
%: N 9.45 S 21.9. CI~H16N2S2. Calculated %: N 9.7: S 22.2.
2 - M e t h y l a m i n o - 3 - b u t y l m e r c a p t o p h e n o t h i a z i n e (X). A m i x t u r e of 1.2 g (0.04 mole) of III and 5 g (0.09
mole) of p o t a s s i u m hydroxide in 60 m l of alcohol was refluxed f o r 2 h in a s t r e a m of nitrogen, a f t e r which
30 m l of w a t e r and a solution of 0.6 m l (0.005 mole) of butyl iodide in 7 m l of alcohol w e r e added s u c c e s s i v e -
ly, and the m i x t u r e was heated at 60-70 ~ f o r 1.5 h. The hot solution was filtered, and a s m a l l amount of
w a t e r was added to the filtrate. Cooling of the f i l t r a t e gave 1 g (83%) of X with mp 153-154 ~ (from alcohol).
Found ~c: N 9.0: S 20.6. Ct~H20N2S2. Calculated %: N 8.8: S 20.3.

LITERATURE CITED

. Z. I. E r m a k o v a , A. N. Gritsenko, and S. V. Zhuravlev, Khim. Geterotsikl. Soedim, 372 (1974).

2. V. V. Shavyrina and S. V. Zhuravlev, Khim. G e t e r o t s i k l . Soedin., 42 (1971).
3. V. V. Shavyrina and S. V. Zhuravlev, Khim. Geterotsikl. Soedin., 38 (1972).
4. W. A. Sexton, J. Chem. Soc., 470 (1939).
5. R. R i e m s e t m e i d e r . B. BSttscher. and S. Georgi, Monatsh.. 91, 630 (1960).
6. A. I. K i p r i a n o v and Z. N. Pazenko, Zh. Obshch. Khim., 19, 1523 (1949).

558
 INDOLE DERIVATIVES

XCIII.* SYNTHESIS OF 5- (3-INDOLYLMETHYL)BARBITURIC

AND 5- (3-INDOLYLMETHYL)THIOBARBITURIC ACIDS

N. N. S u v o r o v , V. S. V e l e z h e v a , UDC 547.753'854.07 : 542.941.7

a n d V. V . V a m p i l o v a

5- (3-Indolylmethyl)barbituric and 5- (3-indolylmethyl)thiobarbituric acids w e r e obtained by

condensation of 3 - i n d o l y l m e t h y l m a l o n i c e s t e r with u r e a and t h i o u r e a in m o n o g l y m e (1,2-di-
methoxyethane) in the p r e s e n c e of lithium methoxide. The f i r s t of the two acids was a l s o
obtained b y catalytic hydrogenation of 5- (3-indolylmethylene)barbituric acid.

Sekija and c o - w o r k e r s [2] have shown that the reduction of 5- (3-indolylmethylene)barbituric acid (I)
by m e a n s of t r i e t h y l a m m o n i u m f o r m a t e gives the t r i e t h y l a m m o n i u m s a l t of 5 - m e t h y l b a r b i t u r i c acid, indole,
and di(3-indolyl)methane r a t h e r than 3 - i n d o l y l m e t h y l b a r b i t u r i c acid {II). A dialkylation p r o d u c t is f o r m e d
e x c l u s i v e l y instead of acid II in the alkylation of b a r b i t u r i c acid (HI) with g r a m i n e [1].
We have a c c o m p l i s h e d the s y n t h e s i s of acid II by s e v e r a l methods. One of t h e m involved the h y d r o -
genation of chalcone II o v e r p a l l a d i u m o r R a n e y nickel.

/CO-- NH\ //~O--Nn\

~ E H = C C=O H ~ /CH2CH C=O
x"CO--NH/ pd ~ ~ ~CO--NH/
H !t
I II

B e c a u s e of the low solubility of chaleone I. the reduction was c a r r i e d out either in 10% NaOH (method
A) or in highly p o l a r aprotic s o l v e n t s - d i m e t h y l f o r m a m i d e (DMF) and dimethyl sulfoxide (DMSO) (methodB}.
Reduction via method A is a c c o m p a n i e d by c l e a v a g e of chalcone I to s t a r t i n g b a r b i t u r i e acid III and 3 - f o r m -
ylindole (IV), in which c a s e the yield of acid II is 48%. A b e t t e r yield (65%) is obtained b y reduction by
method B, but in this c a s e h i g h - m e l t i n g unidentified p r o d u c t s a r e f o r m e d along with acid IL
We w e r e able to i s o l a t e acid II in the c r y s t a l l i n e s t a t e only in the f o r m of c o m p l e x e s with the solvents
( c h l o r o f o r m or m e t h y l e n e chloride). The c o m p l e x could not be d e c o m p o s e d by drying. Acid II d e c o m p o s e d
a f t e r v a c u u m drying at 80 ~ f o r 50 h. The f o r m a t i o n of stable c o m p l e x e s of b a r b i t u r i c acid d e r i v a t i v e s with
such solvents as alcohol, acids, toluene, d i m e t h y l a c e t a m i d e . DMSO, and DMF has b e e n p r e v i o u s l y ob-
s e r v e d [3, 4].
The a b s o r p t i o n bands of C = O groups in the IR s p e c t r u m of acid II lie at 1680, 1701, and 1750 c m -1,
while the a b s o r p t i o n bands of the NH groups lie at 3200 {broad), 3390, and 3450 c m -1. The a b s o r p t i o n bands
of the C = O groups in the IR s p e c t r u m of the c o m p l e x of two m o l e c u l e s of acid I with one m o l e c u l e of chlo-
9 r o f o r m a r e found at 1700 and 1730 c m -1, while those of the NH groups a r e at 3150, 3220, 3280, 3420, and
3450 e m -1.
A q u a r t e t at 3.9 ppm, which is affiliated with 5-CH of b a r b i t u r i c acid, and an u n s y m m e t r i c a l doublet
at 3.2 p p m f r o m the protons of the CH 2 group of the 3-indolylmethyl grouping a r e o b s e r v e d in the PMR

* See [1] f o r c o m m u n i c a t i o n XCII.

D. I. Mendeleev Moscow Institute of C h e m i c a l Technology. T r a n s l a t e d f r o m K h i m i y a G e t e r o t s i k l i -

eheskikh Soedinenii, No. 5, pp. 646-649, May, 1974. Original a r t i c l e submitted June 4, 1973.

9 19 75 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy of this article is available from the publisher for $15.00.

559
s p e c t r u m of the complex of acid II in (CD3)2CO. The signals of the indole ring protons a r e o b s e r v e d as a
m u l t i p l e t at 6.9-7.5 ppm, while the signals of the t h r e e NIt protons a r e o b s e r v e d as a singlet at 10 p p m .
The a b s e n c e of a 3-H indole signal at 6.4 p p m [5] c o n f i r m s the 3 - i n d o l y l m e t h y l - s u b s t i t u t e d s t r u c t u r e of
acid II. Chalcones I and V w e r e obtained in high yields via a modified method [6] by heating 3 - f o r m y l i n d o l e
with b a r b i t u r i c and t h i o b a r b i t u r i c acids in acetic acid.
We w e r e unable to c o n v e r t thiochalcone V to 5- (3-indolylmethyl)-2-thiobarbiturie acid VI by catalytic
hydrogenation o v e r Raney nickel and palladium, by i n d i r e c t eleetroreduction, by reduction with sodium in
liquid a m m o n i a , or by reduction with sodium b o r o h y d r i d e .
We a l s o t r i e d another route to obtain acid II by condensation of 3-indolylmethylmalonic e s t e r (VII)
with u r e a (X). When the condensation is c a r r i e d out in alcohol in the p r e s e n c e of sodium hydroxide. 3-
indolylmethylmalonic acid e s t e r (VIII) is f o r m e d along with acid II. The f o r m e r is a p p a r e n t l y obtained as
a r e s u l t of p a r t i a l h y d r o l y s i s of e s t e r VII in the p r e s e n c e of sodium ethoxide. M o n o e s t e r VIII is obtained
in 53% yield in the condensation of e s t e r VII with t h i o u r e a (XI). In fact. heating of e s t e r VII in alcohol
with sodium ethoxide gives m o n o e s t e r VIII in 62% yield.

/CO0%H~ /COOH
X XXI ~ /CH2CH ~ ~ /Cfl2CH
il, Vl
C H~OC--HTCH2OCHa
~ ~ \cooc2.~ ^' U IT--~
C2HsONa, ~ N / P
\coo%. 5
+ II
H C2HsOH H
VII VIII

]l,g X=O; VI, X! X = S

The b e s t yield of acid II (75%) was obtained when the condensation of e s t e r VII with u r e a in 1,2-di-
methoxyethane (monoglyme) was c a r r i e d out with a twofold e x c e s s of lithium methoxide (method C). Only
by this method w e r e we able to obtain thio acid VI (in 89% yield).
The PMR s p e c t r u m of thio acid VI is s i m i l a r to the s p e c t r u m of its oxygen analog. The s t r u c t u r e of
thio acid VI was also c o n f i r m e d by c o n v e r s i o n of its lithium salt to 3-indolylmethylmalonic acid diamide
(IX) on heating in w a t e r with Raney nickel. The PMR s p e c t r u m of diamide IX is s i m i l a r to the s p e c t r a of
acids II and VI.

EXPERIMENTAL
The IR spectra of mineral oil suspensions of the compounds were recorded with a UR-10 spectro-
meter. The PMR spectra were recorded with a JNM-4H-100 spectrometer with tetramethylsilane as the
internal standard (s is singlet, d is doublet, t is triplet, q is quartet, and m is multiplet).
Chromatography was carried out on plates with a fixed layer of Silufol UV-254 silica gel. Acetone-
chloroform (I : 1) was the eluent.
5- (3-1ndolylmethylene)barbitaric Acid (I). A 2.6-g (20.0 mmole) sample of barbiturie acid was dis-
solved by heating in 30 ml of acetic acid, and the resulting solution was mixed with a hot solution of 2.9 g
(20 mmole) of 3-formylindole in I0 ml of acetic acid. The resulting mixture was heated for another 15 rain,
after which it was cooled. The precipitate was removed by filtration and washed with hot acetic acid and
ethanol to give 4.2 g (82%) of chaleone I. Found %: C 61.4: H 3.8: N 16.4. C~3HgN303. Calculated %: C 61.1:
H 3.5: N 16.5. IR spectrum: 1550, 1650, and 1690 [CH=C(CO)2], 1730 (CO), and 3170, 3290, and 3380
c m - I (NH).
5- ( 3 - i n d o l y l m e t h y l e n e ) - 2 - t h i o b a r b i t u r i e Acid (V). This compound was obtained f r o m 0.7 g (5 m m o l e )
of t h i o b a r b i t u r i c acid in 11 m l of acetic acid and 0.7 g (5 m m o l e ) of 3 - f o r m y l i n d o l e in 6 ~ of acetic acid
in analogy w i t h t h e s y n t h e s i s of acid I. The yield was 1.2 g (85.5%). Found %: C 57.3: H 3.2; N 15.2; S 11.5.
C13HgN302 s. Calculated %: C 57.5: H 3.3: N 15.5: S 11.8. IR s p e c t r u m : 1540, 1620, 1640 [CH=C(CO)2],
1690 (CO). and 3100-3200, 3450 c m - I (NH).
5- ( 3 - I n d o l y l m e t h y l ) - 2 - t h i o b a r b i t u r i e Acid (VI). A solution of 2.89 g (10 m m o l e ) of e s t e r VII, 0.76 g
(10 m m o l e ) of thiourea, and d r y lithium methoxide [from 0.14 g (20 m m o l e ) of lithium] in 30 ml of m o n o -
g l y m e was heated with s t i r r i n g at 80-90 ~ in a s t r e a m of N2 f o r 3 h. It was then cooled, and the p r e c i p i t a t e
was r e m o v e d by filtration to give 2.6 g of the lithium s a l t of acid VI. The salt was d i s s o l v e d in the m i n i m u m
amount of water, and 5% HC1 was added to the solution with s t i r r i n g . The p r e c i p i t a t e [2.5 g (89.5%)] was

560
r e m o v e d by f i l t r a t i o n and washed with w a t e r . R e p r e c i p i t a t i o n f r o m methanol by the addition of w a t e r gave
a p r o d u c t with nap 134-135 ~ (dec.). Found %: C 57.4: H 4.2: N 14.9. S 11.3. C13HlIN302S. Calculated %:
C 57.1: H 4.1: N 15.3: S 11.7. IR spectrum-. 1590-1630, 1670 (CO): 3220-3240. 3380, and 3420 (NH)~ 2500-
2700 (SH): and 3580 (OH) e m -1. PMR s p e c t r u m in (CD3)2CO: 3.2 p p m (unsyrn., d, 3-CH2), 3.5 p p m (q. CH),
6.8-7.4 p p m (m, a r o m a t i c p r o t o n s ) .
5- (3-Indolylmethyl)barbituric Acid (II). A) A 0.85-g (3.3 m m o l e ) s a m p l e of ehalcone I was h y d r o -
genated in 20 ml of 5% NaOH at 50 ~ o v e r Raney Ni. A f t e r the t h e o r e t i c a l amount of hydrogen had b e e n ab-
sorbed, the c a t a l y s t was r e m o v e d by filtration, and the f i l t r a t e was e x t r a c t e d with ether and ethyl acetate
to r e m o v e the 3 - f o r m y l i n d o l e . The r e s i d u e was acidified with 5% HC1 and e x t r a c t e d with ether. The e t h e r
e x t r a c t s w e r e washed with w a t e r and dried with MgSO4. The ether was evaporated, and the r e s u l t i n g oil
w a s c r y s t a l l i z e d by the addition of e t h e r to give 0.5 g (48%) of a p r o d u c t with mp 130 ~ (dec.). R e c r y s t a l l i z a -
tion f r o m a c e t o n e - c h l o r o f o r m gave a p r o d u c t with R f 0.45. A s a m p l e was p r e p a r e d f o r analysis by drying
in vacuo (0.5 ram) at 80 ~ for 1 h and at r o o m t e m p e r a t u r e f o r 48 h. Found %: C 51.6: H 3.7, C1 16.2: N 13.5.
C27H23CI3N606. Calculated %: C 51.2: H 3.6:C1 16.8. N 13.3.
B) A 2-g (7.8 mmole) sample of chalcone I was heated in 150 ml of DMF to 80~ and the resulting sus-
pension was hydrogenated over freshly reduced palladium (0.4 g of PdO/CaCO3). The hydrogenation was
carried out at 60~. After the theoretical amount of hydrogen had been absorbed, the precipitate was removed
by filtration and washed with ether. The ether and DMF were evaporated, and the residual oil crystallized
after the addition of chloroform to give 1.53 g (62%) of acid II with an initial decomposition temperature of
125~ and Rf 0.45.
C) This compound was also obtained in analogy with the synthesis of thioacid VI from 2.89 g (10mmole)
of ester VII, 0.6 g (10 mmole) of urea. and lithium methoxide [from 0.14 g (20 mmole) of lithium] in 30 ml
of monoglyme at 80-90~for 10 h. The yield of the lithium salt of acid II was 2.5 g (82%). Acid II was iso-
lated from its lithium salt in 75% yield by the method used to isolate thioacid VI.
Ethyl 3-Indolylmethylmalonate (VIII). A) A 0.76-g (20 mmole) sample of thiourea and 2.89 g (10
mmole) of ester VII were added to sodium ethoxide obtained from 0.23 g (20 mmole) of Na and 15 ml of ab-
solute ethanol, and the mixture was heated with stirring in a stream of N2 for 9 h. It was then cooled, di-
luted with water, and extracted with ether and ethyl acetate. The aqueous solution was acidified with 10%
HC1 and e x t r a c t e d with ether. The e t h e r e x t r a c t s w e r e washed with w a t e r and d r i e d with MgSO4. The e t h e r
was evaporated, and the r e s i d u a l oil c r y s t a l l i z e d on standing to give 1.7 g (53%) of a p r o d u c t with mp 106-
108 ~ (from water). Found %: C 64.1: H 5.9: N 5.3. C14HIsNO4. Calculated %: C 64.4: H 5.8: N 5.4. IR
s p e c t r u m : 1710, 1740 (CO), 2500-2700 (associated OH), 3400 (NH) c m -1. PMR s p e c t r u m [in (CD3)S~O-CC14,
(1,7)]: 1.2 and 4.0 p p m (t and q, C2H5) , 3.3 p p m (unsym., d, 3-CH2) , 3.6 p p m (q, CH), 6.9-7.3 p p m (m, a r o -
m a t i c protons), i n t e n s i t y r a t i o 3 : 2 , 2 : 1 : 5.
B) A 1-g (3.5 m m o l e ) s a m p l e of e s t e r VII and 0.2 g (3.5 m m o l e ) of u r e a w e r e added to sodium eth-
oxide obtained f r o m 0.08 g (3.4 m m o l e ) of Na and 10 m l of absolute alcohol in a s t r e a m of N2, and the m i x -
t u r e was heated at 90 ~ for 12 h. The p r e c i p i t a t e was r e m o v e d by filtration, and washed with absolute a l c o -
hol and e t h e r to give 1.2 g of the s a l t of acid II, f r o m which acid II was obtained in analogy with the syn-
t h e s i s of thio acid VI f r o m its lithium salt. The m o t h e r liquor f r o m the filtration of the p r e c i p i t a t e was
evaporated, and the r e s i d u e was d i s s o l v e d in water, e x t r a c t e d with 5% HC1, and e x t r a c t e d with ether. The
e t h e r e x t r a c t s w e r e washed with w a t e r and dried with MgSO4. The e t h e r was r e m o v e d by distillation to
give 0.4 g (44.5%) of e s t e r VIII with mp 106-108 ~
C) A 0.58-g (2 m m o l e ) s a m p l e of e s t e r VII was added to sodium ethoxide obtained f r o m 0.09 g (4
m m o l e ) of Na and 3 m l of absolute alcohol, and the m i x t u r e was heated f o r 8 h. The alcohol was evapo-
rated, and the r e s i d u e was diluted with w a t e r and e x t r a c t e d with ether. The aqueous alkaline solution was
acidified with 5% HC1 and e x t r a c t e d with ether. The e t h e r e x t r a c t s w e r e washed with w a t e r and d r i e d with
MgSO4. The e t h e r was r e m o v e d by distillation to give 0.2 g (62.5%) of e s t e r VIII with mp 106-108 ~ The
p r o d u c t did not d e p r e s s the m e l t i n g point of the compound obtained by method A.
3 - I n d o l y l m e t h y l m a l o n i c Acid Diamide (IX). A m i x t u r e of 0.8 g (2.9 m m o l e ) of the lithium salt of acid
VI, 5 g of Raney Ni, 5 ml of methanol, and 15 ml of w a t e r was refluxed f o r 10 h, a f t e r which the c a t a l y s t
was r e m o v e d by filtration and washed with hot methanol. The f i l t r a t e was e v a p o r a t e d to half its volume.
acidified with 10% HC1. cooled, and f i l t e r e d to give 0.5 g (71.2%) of diamide IX with mp 206--208 ~ (from
water). Found %: C 62.9: H 5.3: N 18.2. CI2HI3N302. Calculated %: C 62.4: H 5.6: N 18.2. IR spectrum,
1620, 1670-1680 (CO): 3200, 3370, 3400, and 3480 c m -1 (N-H). PMR s p e c t r u m [in (CD3)2S=O-CC14 (2:3)]:
3.3 p p m (unsym. d. 3-CH2) , 3.6 p p m (q, CH), 6.9-7.3 p p m (m, a r o m a t i c p r o t o n s ) .

561
 LITERATURE CITED
1. N. N. Suvorov, V. S. Velezheva. V. V. Vampflova. and E. N. Gordeev, Khim. Geterotsikl. Soedin., 515
(1974).
2. M. Sekija, M. Ianaihara, and C. S. Iiro, Chem. and Pharm. Bull., 17. 752 (1969).
3. K. C. Fewari, F. K. Schweighardt, I. Lec, and N. C. Li, J. Magn. Reson., 5, 238 (1971).
4. L. P. Zalukaev and V. L. Trostyanetskaya. Trudy Voronezhsk. Univ., 95, 52 (1972).
5. J. Emsley, J. Finney, and L. Sutcliffe, High-Resolution Nuclear Resonance Spectroscopy, Pergamon
(1966).
6. R. B. Van Order and H. G. Lindwall. J. Org. Chem.. 10. 128 (1945).

562
AZAINDOLE DERIVATIVES
XLIV.* PECULIARITIES OF THE SYNTHESIS OF 7-AZAINDOLINES
DURING THE REACTIONS OF 2 , 6 - D I C H L O R O - 3 - ( f l - C H L O R O E T H Y L - 4 -
METHYLPYRIDINE (TRICHLOROCOLLIDINE) WITH PRIMARY AROMATIC
AND STERICALLY HINDERED AMINES

D. M. K r a s n o k u t s k a y a and L. N. Y a k h o n t o v UDC 547.759.07

As in the c a s e of N - s u b s t i t u t e d anilines, t r i c h l o r o c o l l i d i n e f o r m s 6 - e h l o r o - 7 - a z a i n d o l i n e d e r i v -
atives r a t h e r than 6 - a m i n o - 7 - a z a i n d o l i n e d e r i v a t i v e s with s t e r i c a l l y hindered p r i m a r y a m i n e s
of the ~ - p h e n y l i s o p r o p y l a m i n e type. On p a s s i n g to t e r t - b u t y l a m i n e , nucleophilic attack at the
a and a ' positions of the pyridine ring p r o v e s to be s t e r i c a l l y i m p o s s i b l e , and dehydrohalogena-
tion of t r i c h l o r o c o l l i d i n e to 2 . 6 - d i c h l o r o - 3 - v i n y l - 4 - m e t h y l p y r i d i n e b e c o m e s the p r i n c i p a l
reaction.

The r e a c t i o n of 2 , 6 - d i c h l o r o - 3 - ( # - c h l o r o e t h y l ) - 4 - m e t h y l p y r i d i n e (trichlorocollidine) (I) with N - a l k y l -

anilines at 190~ leads to 1 - p h e n y l - 4 - m e t h y l - 6 - c h l o r o - 7 - a z a i n d o l i n e (IIa). while 1 - p h e n y l - 4 - m e t h y l - 6 -
a n f l i n o - 7 - a z a i n d o l i n e (IH) is obtained with aniline under the s a m e conditions [2-4].
A study of the r e a c t i o n s of I with p-toluidine and p - c h l o r o a n i l i n e showed that 6 - a r y l a m i n o - 7 - a z a i n d o -
lines (III) r a t h e r than 6 - c h l o r e - 7 - a z a i n d o l i n e d e r i v a t i v e s (II) a r e f o r m e d at 190 ~ in t h e s e c a s e s . The differ-
ence in the p r o d u c t s of the r e a c t i o n s of I with N - s u b s t i t u t e d and N-unsubstituted anilines is a s s o c i a t e d with
the different r e a c t i v i t i e s of the chlorine a t o m s in the I m o l e c u l e . This difference shows up distinctly in
r e a c t i o n s with N - a l k y l ( a r a l k y l ) a n i l i n e s but l e v e l s off in the c a s e of p r i m a r y a r o m a t i c a m i n e s at 190 ~ How-
e v e r . a d e c r e a s e in the t e m p e r a t u r e to 140 ~ m a k e s it p o s s i b l e to expose the different labilities of the a and
a ' chlorine a t o m s of I in the l a t t e r c a s e also: thus, heating it with aniline, p-toluidine, p-chloroanfline, or
p - a n i s i d i n e at 140 ~ for 7 h leads to 1 - a r y l - 4 - m e t h y l - 6 - c h l o r o - 7 - a z a i n d o l i n e s (II), and not even t r a c e s of
6- a r y l a m i n o - 7-azaindolines (III) a r e detected by g a s - l i q u i d c h r o m a t o g r a p h y (GLC).

CH 3 CH3 CH3

CI CI/"~N/~'CI p-RC6H4HN
l
C6H4R-P I ~6H4R. p
lla-d ~ III a-d
CH3
(~H3 CH3 CH~CH2 ~H3
~ + ~ + Ilia
l C6HsHN [
I 1
,~ C6Hs C6H5 CHaCHCH2C6H5 CH3CHCH2C6H5
IV V VI Vll
II, III a R=H; b R=CH3; c R=CI; d R=OCH 3

* See [1] f o r c o m m u n i c a t i o n XLIH.

S. Ordzhonikidze All-Union S c i e n t i f i c - R e s e a r c h P h a r m a c e u t i c a l C h e m i s t r y Institute. Moscow.

T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i e h e s k i k h Soedinenii, No. 5, pp. 650-654, May, 1974. Original a r t i c l e
s u b m i t t e d April 26, 1973.

I
9 1975Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

563
 The yields of azaindolines a r e d i r e c t l y dependent on the pKa of the s t a r t i n g amine, and i n c r e a s i n g the
r e a c t i o n t i m e f r o m 7 to 14 h, f o r example, in the c a s e of p-anisidine, m a k e s it p o s s i b l e to only somewhat
r a i s e the yield of II (from 48% to 52~) but does not lead to the f o r m a t i o n of a m i n e III.
It is evident that it is n e c e s s a r y to o v e r c o m e a c e r t a i n e n e r g y b a r r i e r for r e p l a c e m e n t of the chlorine
a t o m in the a ' position of I. This b a r r i e r is a p p a r e n t l y lower f o r p r i m a r y a r o m a t i c amines than for N - a l k y l -
(aralkyl)anilines. As was d e m o n s t r a t e d in [3], 6 - a r y l a m i n o - 7 - a z a i n d o l i n e s a r e f o r m e d only at ~ 300 ~ on r e -
action of I with, for example, N-methylanfline. The r e s u l t s of the p r e s e n t study p r o v i d e evidence that s i m -
i l a r r e a c t i o n s a r e r e a l i z e d even at 190 ~ f o r N-unsubstituted anilines.
We have p r e v i o u s l y shown [5] that the r e a c t i o n of 6 - c h l o r o - 7 - a z a i n d o l i n e s with p r i m a r y and s e c o n d a r y
a m i n e s at high t e m p e r a t u r e s p r o c e e d s ambiguously, in addition to nucleophilic substitution of the chlorine
a t o m in the 6 position t h e r e a r e redox p r o c e s s e s to give p r o d u c t s of the dehalogenation of the 7-azaindoline
and the c o r r e s p o n d i n g oxidized c o m p o u n d s - 6 - a m i n o - 7 - a z a i n d o l e d e r i v a t i v e s . In p a r t i c u l a r , a m i x t u r e of
a m i n e IIIa, 1-phenyl- 4- m e t h y l - 7- azaindoline (IV). and 1-phenyl- 4- m e t h y l - 6- anilino- 7- az aindol e {V) is ob-
tained f r o m 1 - p h e n y l - 4 - m e t h y l - 6 - c h l o r o - 7 - a z a i n d o l i n e {IIa) and aniline (after 10 h at 250~ C a r r y i n g out
the s a m e r e a c t i o n at 190 ~ for 7 h with GLC analysis of the p r o d u c t s made it p o s s i b l e to show that r e s i n i f i c a -
tion is r e d u c e d u n d e r t h e s e conditions, and the yields of azaindoline IIIa and azaindole V t h e r e f o r e i n c r e a s e .
In addition, 6 - c h l o r o - 7 - a z a i n d o l i n e (II) does not oxidize IIIa under such mild conditions, i.e., oxidation ap-
p a r e n t l y p r o c e e d s v i a a different m e c h a n i s m , and 6-unsubstituted 1 - p h e n y l - 4 - m e t h y l - 7 - a z a i n d o l i n e (IV) is
not detected in the r e a c t i o n m i x t u r e by GLC.
C o m p a r i n g the unambiguous c o u r s e of the r e a c t i o n s of I with p r i m a r y a r o m a t i c a m i n e s at 190 ~ the
high yields of r e s u l t i n g azaindolines III, the absence in the r e a c t i o n m i x t u r e s of 6 - a r y l a m i n o - 7 - a z a i n d o l e s ,
and the ambiguous c o u r s e , u n d e r the s a m e conditions, of the substitution of the chlorine a t o m in c h l o r o a z a -
indoline II by an a r y l a m i n e residue, which is a c c o m p a n i e d by the f o r m a t i o n of significant amounts of 6 - a r y l -
a m i n o - 7 - a z a i n d o l e , one should acknowledge that the c o n v e r s i o n of I to azaindoline III on reaction with p r i -
m a r y a r o m a t i c a m i n e s does not p r o c e e d through a step Involving 6 - e h l o r o - 7 - a z a i n d o l i n e d e r i v a t i v e II.
In analyzing the r e a s o n s f o r the different t e m p e r a t u r e b a r r i e r s to substitution of the a ' chlorine a t o m
in I under the influence of p r i m a r y a r o m a t i c a m i n e s and N-alkyl(aralkyl)anilines, one should note that they
cannot b e r e d u c e d to a d i f f e r e n c e in the b a s i e i t i e s of the compounds. In fact, aniline (:pKa 4.58*) and p-
ehloroaniline ~pKa3.98) a r e w e a k e r b a s e s than, f o r example, N - m e t h y l - (PKa4.85) or N-ethylaniline (pKa
5.11), while p-toluidine ~pKa 5.12) has m o r e b a s i c p r o p e r t i e s . N e v e r t h e l e s s , the t e m p e r a t u r e b a r r i e r s to
substitution of the a ' - c h l o r i n e a t o m in I under the influence of aniline, p-chloroaniline, and p-toluidine is
a p p r o x i m a t e l y the s a m e and c o n s i d e r a b l y l o w e r than for N - m e t h y l - or N-ethylanilines. In these c a s e s ,
s t e r i c f a c t o r s r a t h e r than the d e g r e e of b a s i c i t y of the a m i n e s evidently p l a y the leadIng role. The nitrogen
a t o m in ~primary a r o m a t i c a m i n e s is shielded to a c o n s i d e r a b l y l e s s extent than in N-substituted anilines,
and the e n e r g y b a r r i e r to nucleophilic attack f o r n i t r o g e n - u n s u b s t i t u t e d anilines should be substantially
lower.
The fact that even a b a s e as strong as n - b u t y l a m i n e (pKa 10.6), which has a m o r e shielded nitrogen
a t o m than aniline, f o r m s at 190 ~ only the 6 - c h l o r o d e r i v a t i v e of 7-azaindoline [7] with collidine I r a t h e r than a 6 -
butylamino d e r i v a t i v e is also in good a g r e e m e n t with this a s s u m p t i o n .
A b r a n c h e d p r i m a r y a m i n e - B - p h e n y l i s e p r o p y l a m i n e - a l s o b e h a v e s s i m i l a r l y on r e a c t i o n with I: it
f o r m s 1- ( a - m e t h y l - B - p h e n y l e t h y l ) - 4 - m e t h y l - 6 - e h l o r o - 7- azaindoline (VI), which is dehalogenated to 1- ( a -
m e t h y l - B - p h e n y l e t h y l ) - 4 - m e t h y l - 7 - a z a i n d o l i n e {VII) on a p a l l a d i u m catalyst. F u r t h e r branching of the c a r -
bon chain in a p r i m a r y a m i n e - t r a n s i t i o n to t e r t - b u t y l a m i n e - l e a d s to such significant s t e r i e hindrance
that nucleophilic attack in the a and a ' positions of the pyridine ring is excluded, and the only r e a c t i o n path
b e c o m e s dehydrohalogenation of I to give 2, 6 - d i c h l o r o - 3 - v i n y l - 4 - m e t h y l p y r i d i n e (VIII).

EXPERIMENTAL
A n a l y s i s b y GLC was p e r f o r m e d with a P y e - U n i c a m 104 c h r o m a t o g r a p h with a f l a m e - i o n i z a t i o n de-
t e c t o r and a 1.5 m b y 4 - m m column filled with 2% SE-30 silicone e l a s t o m e r on C h r o m o s o r b W (80-90 mesh).
The nitrogen flow r a t e was 27 m l / m i n , the p r o g r a m conditions w e r e f r o m 150 to 250 ~ the initial p e r i o d was
10 rain. and the t e m p e r a t u r e - r i s e r a t e was 32 d e g / m i n . The retention t i m e s w e r e : I 2.4, IIa 14.3. IIb 9.4,
IIc 9.1, IIIa 20.0, IIIb 14.6, IIIc 16.0, V 18.3, and VI 13.9. The retention t i m e s w e r e as follows when the

*All of the pKa values given a r e f r o m [6].

564
p r o d u c t s w e r e c h r o m a t o g r a p h e d under the s a m e c ~ d i t i o n s but at 250 ~ without p r o g r a m m e d operation: IIa
1.2, Ilia 5.0, IV 0.8, and V 3.6 rain.
1 - P h e n y l - 4 - m e t h y l - 6 - e h l o r o - 7 - a z a i n d o l i n e (IIa). A m i x t u r e of 2.24 g (10 m m o l e ) of t r i e h l o r o c o l l i d i n e
(I) and 1.86 g (20 m m o l e ) of aniline was heated at 140 a for 7 h. It was then cooled, and 30 m l of c h l o r o f o r m
was added. The m i x t u r e was f i l t e r e d to give 0.84 g of aniline hydrochloride. The f i l t r a t e was washed with
a 25% aqueous p o t a s s i u m c a r b o n a t e solution, d r i e d with p o t a s s i u m carbonate, e v a p o r a t e d to a s m a l l volume.
and analyzed b y GLC. F o r p r e p a r a t i v e s e p a r a t i o n , it was a l s o applied to a column (height 75 cm. d i a m e t e r
23 ram) containing 240 g of a l u m i n u m oxide and eluted with p e t r o l e u m ether. The f i r s t 200 m l of eluate
{containing 0.07 g of substance) was discarded, and e v a p o r a t i o n of thenext 500 m l of eluate gave 1.11 g (50%)
of s t a r t i n g I with mp 69-70 ~ E v a p o r a t i o n of the next 200 m l of eluate gave 0.23 g (9.5%) of azaindoline Ha
with mp 116.5-117~ no melting-point d e p r e s s i o n was o b s e r v e d f o r a m i x t u r e of this p r o d u c t with the product
obtained f r o m I and N-ethylaniline [3]. The r e s u l t s of GLC a n a l y s i s w e r e in good a g r e e m e n t with the r e s u l t s
of p r e p a r a t i v e s e p a r a t i o n of the s u b s t a n c e s .
Reaction of 1 - P h e n y l - 4 - m e t h y l - 6 - c h l o r o - 7 - a z a i n d o l i n e (IIa) with Aniline. A m i x t u r e of 1.22 g (5
m m o l e ) of azaindoline IIa and 1.12 g (12 m m o l e ) of aniline was heated at 190 ~ f o r 7 h, a f t e r which 5 m l of a
25% p o t a s s i u m c a r b o n a t e solution was added, and the m i x t u r e was e x t r a c t e d with benzene. The e x t r a c t was
d r i e d with p o t a s s i u m c a r b o n a t e and e v a p o r a t e d , and the r e s i d u e was analyzed by GLC. The yield of a z a -
indoline liIa was 59%, and the yield of azaindole V was 29%. Compound IV was not detected in the r e a c t i o n
p r o d u c t s . Azaindoline IIa was r e c o v e r e d quantitatively when the r e a c t i o n t e m p e r a t u r e was lowered to
140 ~ (7 h).
1 - { p - T o l y l ) - 4 - m e t h y l - 6 - c h l o r o - 7 - a z a i n d o l i n e (lib). A m i x t u r e of 3.36 g (15 m m o l e ) of I and 3.21 g
(30 m m o l e ) of p-toluidine was heated at 140 ~ f o r 7 h. a f t e r which it was cooled, and 5 m l of 25% aqueous
solution of p o t a s s i u m c a r b o n a t e was added. The m i x t u r e was e x t r a c t e d with benzene, and the e x t r a c t was
d r i e d with p o t a s s i u m c a r b o n a t e . The e x t r a c t was evaporated, and the r e s i d u e was v a c u u m distilled to give
1.57 g of a f r a c t i o n with bp 140-210 ~ (3 ram), which, a c c o r d i n g to GLC. contained 1.44 g (43%) of s t a r t i n g I.
0.13 g of azaindoline IIb, and 1.35 g of a f r a c t i o n with bp 210-212 ~ (3 ram), which was p u r e azaindoline IIb.
The o v e r a l l yield of Kb was 38%. The c o l o r l e s s c r y s t a l s had mp 129-130 ~ (from alcohol) and w e r e quite
soluble in ether, benzene, c h l o r o f o r m , acetone, and ethyl a c e t a t e , l e s s soluble in alcohol and heptane, and
insoluble in water. Found ~c: C1 13.6: N 10.7. C~sHIsC1N2. Calculated %: C1 13.7. N 10.8. Compound liIb
was not detected in the r e a c t i o n p r o d u c t s by GLC.
1 - { p - T o l y l ) - 4 - m e t h y l - 6 - ( p - t o l u i d i n o ) - 7 - a z a i n d o l i n e (IIIb). A m i x t u r e of 2.24 g (10 m m o l e ) of I and
3.21 g (30 m m o l e ) of p-toluidine was heated at 190 ~ for 7 h, a f t e r which it was worked up as in the p r e c e d i n g
e x p e r i m e n t . The benzene e x t r a c t was evaporated, and the r e s i d u e was distilled. The f r a c t i o n with bp 243-
245 ~ (1 ram) (2.76 g) was collected and t r i t u r a t e d thoroughly with alcohol. The yield of azaindoline IIIb with
mp 133-134 ~ was 2.42 g (75%). The p r o d u c t was quite soluble in benzene, acetone, c h l o r o f o r m , and hot ethyl
acetate, only slightly soluble in e t h e r and heptane, and insoluble in w a t e r . Found %: C 80.6: H 6.7: N 12.6.
C22H23N3. Calculated %: C 80.2, H 7.0. N 12.8.
1 - ~ - C h l o r o p h e n y l ) - 4 - m e t h y l - 6 - e h l o r o - 7 - a z a i n d o l i n e (IIe). A m i x t u r e of 3.36 g (15 m m o l e ) of I and
3.82 g (30 m m o l e ) of p - c h l o r o a n i l i n e was heated at 140 ~ for 7 h. a f t e r which it was worked up as in the p r e -
ceding e x p e r i m e n t . Distillation gave 0.46 g of a f r a c t i o n with bp 238-240 ~ (2 ram), which, a c c o r d i n g to GLC,
contained 47% of azaindoline IIc. The yield of IIc was 5.3%. The s u b s t a n c e was isolated f o r a n a l y s i s by
c h r o m a t o g r a p h y on A1203 with elution with CHC13 to give c o l o r l e s s c r y s t a l s with mp 145-147 ~ (from i s o p r o p y l
alcohol). The product was quite soluble in ether, benzene, acetone, c h l o r o f o r m , and ethyl acetate, l e s s solu-
ble in alcohols and heptane, and insoluble in w a t e r . Found %: C 60.3: H 4.3, C1 25.3: N 10.4. C14Ht2C12N2.
Calculated %: C 60.2: H 4.3, C1 25.4: N 10.1.
1 - { p - C h l o r o p h e n y l ) - 4 - m e t h y l - 6 - { p - e h l o r o a n i l i n o ) - 7 - a z a i n d o l i n e (IIIc). A mLxture of 2.24 g (10 m m o l e )
of I and 3.82 g (30 m m o l e ) of p - c h l o r o a n i l i n e was heated at 190 ~ for 7 h. A total of 1.28 g of sublimed p -
e h l o r o a a i l i n e h y d r o c h l o r i d e s e p a r a t e d . The r e s i d u e was m a d e alkaline with 50% aqueous p o t a s s i u m c a r b o -
nate solution and e x t r a c t e d with benzene. The e x t r a c t was dried with p o t a s s i u m c a r b o n a t e mud v a c u u m
e v a p o r a t e d . The r e s i d u e was r e e r y s t a l l i z e d f r o m acetone to give 1.58 g of azaindoline IIIc with mp 150-
151 ~ The acetone m o t h e r liquor was e v a p o r a t e d , and the r e s i d u e was v a c u u m distilled. The f r a c t i o n with
bp 238-240 ~ (2 ram). which was 1.15 g of azaindoline IIIc, was collected. The o v e r a l l yield of IIIc with mp
150-151 ~ was 2.73 (74%). The p r o d u c t was quite soluble in c h l o r o f o r m , hot benzene, and acetone, but insolu-
ble in w a t e r . Found %: C 64.6: H 4.7:C1 19.3: N 11.1. C20HtTC12N3. Calculated %: C 64.8: H 4.6:C1 19.2:
N 11.4.

565
 1- ( p - M e t h o x y p h e n y l ) - 4 - m e t h y l - 6 - c h l o r o - 7 - a z a i n d o l i n e (IId). A m i x t u r e of 4.48 g (20 mmole) of I and
4.92 g (40 mmole) of p-anisidine was heated at 140 ~ for 7 h. It was then cooled, made alkaline with a 25%
solution of p o t a s s i u m carbonate, and e x t r a c t e d with c h l o r o f o r m . The e x t r a c t was dried with potassium c a r -
bonate and evaporated, and the r e s i d u e was vacuum distilled. The f i r s t fraction (5.2 g), with bp 87-218 ~
(1 rara), was dissolved in benzene, and the benzene solution was washed t h r e e t i m e s with 8% hydrochloric
acid to s e p a r a t e the p-anisidine. The benzene l a y e r was dried with p o t a s s i u m carbonate and evaporated to
give 1.65 g (37%) of I. The second fraction, with bp 218-220 ~ (1 rmra), was azaindoline IId (rap 122-123~
The yield was 2.64 g (48%). The product did not d e p r e s s the melting point of a sample of IId obtained by
r e a c t i o n of I with N - r a e t h y l - p - a n i s i d i n e [8]. The IR s p e c t r a of the two samples w e r e identical.
1- ( a - M e t h y l - f l - p h e n y l e t h y l ) - 4 - r a e t h y l - 6 - c h l o r o - 7 - a z a i n d o l i n e (VI). A raixture of 4.8 g (21 raraole) of
I and 5.8 g (43 raraole) of fi-phenylisopropylamine was heated at 190 ~ for 7 h. It was then cooled, made
alkaline with a 25% solution of p o t a s s i u m carbonate, and e x t r a c t e d with benzene. The benzene extract was
d r i e d with p o t a s s i u m c a r b o n a t e and evaporated, and the residue was vacuum distilled. Redistillation of the
f i r s t fraction, with bp 120-130 ~ (2 ram), gave 1.15 g (26%) of I with rap 69-70 ~ The second fraction, with
bp 184-186 ~ (1 ram), was 3.0 g (49%) of azaindoline VI. The c o l o r l e s s c r y s t a l s had mp 68-69 ~ (from p e t r o -
leum ether). The product was quite soluble in ether, benzene, acetone, ethyl acetate, and chloroform, less
soluble in alcohol and p e t r o l e u m ether, and insoluble in water. Found %: C 71.0: H 6.4; C1 12.47 N 9.5.
C17H19C1N2. Calculated %: C 71.2$ H 6.7; C1 12.3: N 9.8.
1- ( a - M e t h y l - f l - p h e n y l e t h y l ) - 4 - r a e t h y l - 7 - a z a i n d o l i n e (VII). A solution of 2.36 g (8.2 raraole) of ehloro-
azaindoline VI in 100 ral of alcohol was hydrogenated in the p r e s e n c e of a palladium catalyst, obtained f r o m
2 g of palladous chloride, at 18-20 ~ with an an e x c e s s hydrogen p r e s s u r e of 18-20 era (water column). After
the calculated amount of hydrogen had been absorbed, the catalyst was r e m o v e d by filtration, the solution
was vacuum evaporated, and the r e s i d u e was dissolved in 10 ml of 18% h y d r o c h l o r i c acid. The acid solution
was w a s h e d b y e x t r a c t i o n with e t h e r and made alkaline with a 50% solution of p o t a s s i u m hydroxide. The
l i b e r a t e d b a s e was e x t r a c t e d with ether, and the e x t r a c t was dried with p o t a s s i u m carbonate and evaporated.
The r e s i d u e was vacuum distilled at 185-187 ~ (4 ram) to give 1.78 g (86%) of azaindoline VII as a c o l o r l e s s
oily substance that was quite soluble in the common organic solvents but only slightly soluble in water~ it
had nD 2~ 1.5775. Found %: C 80.6. H 8.0,. N 10.9. CITH20N2. Calculated %- C 80.9; H 8.0. N 11.1.
Reaction of T r i c h l o r o e o l l i d i n e {I) with t e r t - B u t y l a r a i n e . A m i x t u r e of 4.48 g (20 raraole) of I and 10 ral
(95 raraole) of t e r t - b u t y l a r a i n e was heated at 140 ~ in a steel autoclave for 7 h. The r e a c t i o n m i x t u r e was
t r e a t e d with 50 ral of 18% h y d r o c h l o r i c acid and 50 ral of ether, and the e t h e r solution was separated and
washed additionally with 18% h y d r o c h l o r i c acid. The acid solution was e x t r a c t e d with ether, and the com-
bined e t h e r e x t r a c t s w e r e dried with p o t a s s i u m carbonate and vacuum distilled to give 1.63 g (41%) of 2,6-
d i c h l o r o - 3 - v i n y l - 4 - r a e t h y l p y r i d i n e (VIII), with bp 140-143 ~ (14 rara) and nD 2~ 1.5712 [2], and 1.83 g (41%) of
I, with bp 174-177 ~ (14 ram) and rap 69-70 ~ The h y d r o c h l o r i c acid solution contained only tert-butylaraine
hydrochloride.

LITERATURE CITED

1. M. Ya. Uritskaya, V. A. Loginova, and L. N. Yakhontov. Khim. Geterotsikl. Soedin.. 1370 (1973).
2. L. N. Yakhontov and M. V. Rubtsov, Zh. Obshch. Khira., 30, 3300 (1960).
3. L. N. Yakhontov and M. V. Rubtsov, Zh. Obsheh. Khira., 34, 493 (1964).
4. L. N. Yakhontov, M. S. Sokolova, and M. V. Rubtsov, Khim. Geterotsikl. Soedin., No. 1, 455 (1967).
5. L. N. Yakhontov. D. M. Krasnokutskaya, A. N. Akalaev. I. N. Palant, and Yu. I. Vainshtein, Khira.
Geterotsikl. Soedin.. 789 (1971).
6. A. A l b e r t and E. Serjeant, Determination of Ionization Constants: A P r a c t i c a l Manual, Chapman and
Hall (1972).
7. L. N. Yakhontov, M. S. Sokolova, and M. V. Rubtsov, Khira. Geterotsikl. Soedin., 74 (1966).
8. L. N. Yakhontov, D. M. Krasnokutskaya, and M. V. Rubtsov, Khira. Geterotsikl. Soedin., 66 (1966).

566
VITAMIN B 6 ANALOGS
XVI.* SYNTHESIS AND PROPERTIES OF 2'- AND 5'-MODIFIED
ANALOGS OF PYRIDOXAL 5-PHOSPItATE

L . I. K o l o b u s h k i n a , N. I . S p i r i d o n o v a , UDC 547.823.824.07
a n d V. L . F l o r e n t ' e v

The synthesis of 2'- and 5'-modified analogs of p y r i d o x i n e f r o m which analogs of pyridoxal

and pyridoxal 5-phosphate w e r e obtained is described. The t r a n s i t i o n to analogs of p y r i d a x -
amine and p y r i d o x a m i n e 5-phosphate is r e a l i z e d by hydrogenation of the oximes of these
aldehydes.

The synthesis of analogs of pyridoxal 5-phosphate and pyridoxamine 5-phosphate that a r e modified
in the 2 and 5 positions of the pyridine ring was undertaken.
The synthesis of the 2-modified analogs (Ia, b) was c a r r i e d out by a p r e v i o u s l y developed s c h e m e [2].t
The analogs modified in the 5 position w e r e obtained f r o m pyridoxine.

CH2OH . CH~3~ c.o R'Mg.~ "~

CH2(CO2H) II a,b

~H2OH CH2OH
Ho~CH~CH__CO2 H ~ HO~/CH2CH2CO2H
CH2OH
HO~j/CH2CH2CH2OH . ,

C H:~/~.~-./ CH~ / ~ " ~ / C%~ ~-N /

V Ill IV

Ila R'=CH3;bR'=C6Hs

According to the PMR s p e c t r a l data, the product of the condensation of 3 . 4 ' - O - i s o p r o p y l i d e n e i s o p y r i -

doxal with malouic a c i d - unsaturated acid V - has the t r a n s configuration in relation to the double bond (the
s p i n - s p i n coupling constant of the ethylene protons is 16 Hz).
The oxidation of the 4-hydroxymethyl group of the pyridoxine analogs to a f o r m y l group was a c c o m -
plished with manganese dioxide in sulfuric acid or [in the oxidation of III and IV to carboxy analogs of p y r i -
doxal 5-phosphate (VI and VII)] with active manganese dioxide in a nonpolar solvent. The corresponding
aldehydes w e r e isolated as the oximes o r Schiff b a s e s with p-anisidine. Compounds VI and VII w e r e iso-
lated in s a t i s f a c t o r y yields as the aldehydes, and retention of the t r a n s configuration of starting unsaturated
acid III during oxidation was c o n f i r m e d f o r VII by means of PMR s p e c t r a l data.
o
* See [1] f o r communication XV.
t In the final stages of our r e s e a r c h , a p a p e r was published by Takuichi and Taisuke [3] in which the syn-
t h e s i s of t h e s e two pyridoxine analogs was d e s c r i b e d .

Institute of Molecular Biology. Academy of Sciences of the USSR. Moscow. T r a n s l a t e d f r o m Khimiya

Geterotsiklicheskik_h Soedinenii. No. 5, pp. 655-660, May, 1974. Original a r t i c l e submitted D e c e m b e r 14, 1972.

9 19 75 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

567
 TABLE 1. Assignment of the Absorption Maxima to Ionic Forms
in the UV Spectra of Vitamin B6 Analogs
Lma x, nm (e)

Compounds cation
.
(O.l N HCI) Dipola~r, form (pH 7) anion (0.i N NaOH)

Pyridoxine analogs:
Ia 292 (9300) 253 (4700); 321 (71~0) '248 (6590); 307 (7~))
Ib 294 (10490) ,256 (49OO); ,~3 (~400) 248 (~800); ~)0 (7900)
IIb 290 (11'200) 256 (4900); ,318 (9300) ,248 (7000); 304 (7400)
Pyfidoxamine analogs:
V Ilia 299 (9800) 25,4 (4800); 330 (6700) 248 (6700); 311 (7900)
VIIIb 302 (1070O) 252 (4700); a28 (7600) ,249 (6100); 314 (93OO)
VIIIc 296 (96oo); '2~4 (5100); 322 (7,400) 24@(6400) ; 312 (8290)
VIIId 296 (11500) ,~54 (49O0); a26 (1049O) 250 (5800); 310 (9000)
VIIIe 304 (.8300) 255 (31oo); 332 (640o) 249 (4790); 318 ('6900)
VIIIf 295 (950o) 25~ (46,OO); 325 (7590) 245 (6100); ,306 (8000)
Pyridoramine 9
5-phosphate
anal%s:
IXa 299 (mgoo) 254 (4000); ,322 (11190) 24~ (5700) ; 313 (7~200)
IXb 298 (10500) ,25~ (43oo) 331 (82oo) 248 (6900); 314 (9500)
IXc 298 (10200) 254 (450O); 323 (9200) ,248 (5,800); 313 (7400)
IXd 295 (7~00) 9 L~2 (2900); 324 (7,290) 244 (4100); 308 (r~)
Pyridoxal 5-phosphate
analogs:
Xa 299 (92O0)a ,3~4 (3100) a 306 (22oo)a
340 ( 1150)b 399 (2600)b 399 (7600)b
Xb 3 ~ (7000)a 3~8 (l~oo) a 305 (1700)a
0000b 387 (13oo) o 396 (4~)0) b
Xe (8300) a ~9~ (35oo) a 304 (2100)a
(1400)b (4300) o 305 (500) D
Xd 296 (7400)a ,3~o (r a 306 U300) a
3~4 (2700)o 384 (3800) 389 ( 7 5 9 0 )
VII 294 (6400)a 321 (2700) a 303 (noo)a
302 (4600)b 395 (58OO)b 393 (~20o)D
aHydrated form. bAldehyde form. The numbers in parentheses are
not the true molecular extinctions of the given forms but show the ab-
s o r p t i o n at t h e e q u i l i b r i u m c o n c e n t r a t i o n .

,,:Vx CH~NH2
I "

VIII

R =sec -C4Ho, X=CH~OH; b R=CH2C6Hs, c R=CH~,

d R=CH3, X=CH(CH)C6Hs; e R=CH~, X=CH~OH2COOH; f R=CH~, X=CH~CH2CH20H

H y d r o g e n a t i o n of t h e o x i m e s l e a d s to p y r i d o x a m i n e a n a l o g s ( V H I a - d , f). H o w e v e r , t h e h y d r o g e n a t i o n
of 5 ' - d e s o x y - 5 ' - e a r b o x y m e t h y l e n e p y r i d o x a l o x i m e i s a c c o m p a n i e d b y r e d u c t i o n of t h e d o u b l e b o n d a n d g i v e s ,
a s i n t h e c a s e of 5 ' - d e s o x y - 5 ' - c a r b o x y m e t h y l p y r i d o x a l , a m i n e VIIIe.
P h o s p h o r y l a t i o n of t h e S c h i f f b a s e s a n d t h e p y r i d o x a m i n e a n a l o g s w i t h p o l y p h o s p h o r i c a c i d ( P P A )
u n d e r t h e c o n d i t i o n s t h a t w e d e s c r i b e d i n [2] m a k e s i t p o s s i b l e t o o b t a i n a n a l o g s of p y r i d o x a l p h o s p h a t e a n d
pyridc~mmine phosphate:
CH20 H CHO CflzNH2

, R R~ "<N/-

la, b VI,VII, X a - ~ VIII a - f IX a=e

t~= SeC-C4H9; b R=CH2C6Hs; c - - f R=CH3; I X=CH2OH; VI R=CH3, X=CHzCH2OH;

VII R=CH3, X=CHCHCO2H; VIIta X=CH2OH, b X=CH2OH, c x=CH(OH)CH3;
dX=CH(OH)C6Hs; e X=CH2CH2CO2H. f X=CH2CH2CH2OH; IX, Xa, X=CH2OPO3H~.
b X=CHeOPO3H, c X=CH(CH3)OPO3H~, d X=CH2CH2CH2OPO~H2

I n t h e p h o s p h o r y l a t i o n of 5 ' - p h e n y l p y r i d o x a m i n e (VIIId) a n d t h e S c h i f f b a s e of 5 ' - p h e n y l p y r i d o x a l w i t h

polyphosphoric acid we were unable to isolate identifiable products, this, in our opinion, is associated with
the high reactivity and lability of the pyridylphenylcarbinol grouping involved in this reaction.

568
 TABLE 2. Derivatives of Pyrid()xal Analogs . . . .

Compound mp, *C UV spectrum, kma x, nm (~) ~Yield, %

2'-Is.opropylpyridoxal ,203--206 (dec.) 278 (6020)an4 329 (5400)~ 77

oxlme
2' -Phenylpyridoxal 175--176 (dee.) 289 (9160)and 330 (8710)a 58
oxime
5'-Methylpyridoxal 202--203 (dec.) 270 (,6300) and 330 (5600)~ 64
oxime
5'-Phenylpyridoxal 214--215 (dec.) 281 (9400) and 332 (9050)a 23
oxime
5'-Desoxy-5'- 8-hydro- 1'87--189 (dee.) 278 (6200) and 326 (4400,)a 6~
xyethylpyridoxaloxime
Schiff bases with p-
anisidine.
2'-I~oprop~lpyridoxal 149--141 352 (13300) and 365 (136(D)b 7~
2'-Phenylpyrfdoxal 152--153 9 356 (13800) and 366 (14309)b 63
5'~ 173--174 (dec) 354 (13400) and 366 (13600)b 68
5'-Phenylpyridoxal 180--181 (dec:) 358 (14000) and 308 (14890)b 31
5'-Desoxy -5' -/3 - 149--151 (dec.) 230 (10500) and 300 (4500) b 74
hydroxyethylpyridoxal 35,1 (8900).and

aIn 0.1 N HC1. bin ethanol.

T A B L E 3. P y r i d o x a m i n e A n a l o g s
Dihydro- Calculated, %
mp, *C Empirical formula
chloride C H C H

Vllla 228--230(dec.) CHH,sNzO2 92HCI 46,3 7,4 46,6 7,1

VIII b 193--195(dec.) C~4HI6NuO2.2HCI 52,8 5,6 53,0 5,7
Vltlc 184--186(dec.) CgHI,N202 92HC1 42,3 6,4 42,4 6,3
VIIId ,204--206(dec.) Ct4HI6N20z"2HCI 53,4 5,5 53,0 5,7
vIItt 195--197(dec.)
VIII f 191--193(dec.) CIoHI6N202.2HC1 44,8 6,6 44,6 6,7

T h e a s s i g n m e n t of t h e a b s o r p t i o n m a x i m a i n t h e UV s p e c t r a of t h e c o m p o u n d s t o i o n i c f o r m s i s p r e -
s e n t e d i n T a b l e 1.

EXPERIMENTAL

T h e UV s p e c t r a w e r e r e c o r d e d w i t h a n E S P - 3 T s p e c t r o p h o t o m e t e r (Japan). T h e P M R s p e c t r a w e r e
r e c o r d e d w i t h an R - 2 0 s p e c t r o m e t e r (60 MHz, J a p a n ) w i t h h e x a m e t h y l d i s i l o x a n e (HMDS) o r t e r t - b u t y l a l c o -
h o l (1.20 p p m ) a s t h e i n t e r n a l s t a n d a r d . T h i n - l a y e r c h r o m a t o g r a p h y w a s c a r r i e d out a s d e s c r i b e d in [4].
5 - E t h o x y o x a z o l e s . T h e s e c o m p o u n d s w e r e o b t a i n e d b y c y c l i z a t i o n of e t h y l e s t e r s of N - f o r m y l a m i n o
a c i d s u n d e r t h e c o n d i t i o n s d e s c r i b e d in [2]. 4 - s e c - B u t y l - 5 - e t h o x y o x a z o l e , w i t h bp 6 2 - 6 4 ~ (4 m m ) , w a s o b -
t a i n e d i n 59% y i e l d f r o m N - f o r m y l l e u c i n e e t h y l e s t e r . F o u n d %: C 63.6: H 9.1. C9H1502. C a l c u l a t e d ~ :
C 63.9; H 8.9.
4 - B e n z y l - 5 - e t h o x y i s o x a z o l e , w i t h bp 1 1 1 - 1 1 5 ~ (3 m m ) , w a s o b t a i n e d in 35% y i e l d f r o m N - f o r m y l p h e n -
y l a l a n i n e e t h y l e s t e r . F o u n d ~ : C 70.9: H 6.6. C12H1302. C a l c u l a t e d %: C 70.9: H 6.4.
D i m e t h y l E s t e r s of 5 - H y d r o x y c i n c h o m e r o n i c A c i d s . A m i x t u r e of 0.1 m o l e of 5 - e t h o x y o x a z o l e and
0.2 m o l e of d i m e t h y l m a l e a t e w a s h e a t e d at 110 ~ f o r 6 h, a f t e r w h i c h i t w a s c o o l e d , and 20 m l of a 2 5 ~ s o l u -
t i o n of d r y HC1 i n m e t h a n o l and 200 m l of e t h e r w e r e a d d e d to i t s u c c e s s i v e l y . T h e m i x t u r e w a s s t i r r e d
t h o r o u g h l y and a l l o w e d to s t a n d o v e r n i g h t in a r e f r i g e r a t o r . T h e c r y s t a l s w e r e r e m o v e d b y f i l t r a t i o n ,
w a s h e d w i t h e t h e r , and r e c r y s t a l l i z e d f r o m a c e t o n e .
6-see-Butyl-5-hydroxycinchomeronic Acid Dimethyl Ester Hydrochloride. This compound, with mp
152-153 ~ w a s o b t a i n e d in 51% y i e l d . F o u n d ~ : C 51.4: H 5.9. C13H17NOs.HC1. C a l c u l a t e d %: C 5 1 . 4 : H 6 . 0 .
P M R s p e c t r u m . 6, p p m (CF3COOH*). 4- and 5-CO2CH3, 3.74 and 3.76 s: 6-H 8.20 s: 2 - C H 2 2.77 d (J = 7.3
Hz): 2 ' - C H 1.98 m : 2"-CH3, 0.66 d (J = 6.6 Hz).
D i m e t h y l 6 - B e n z y l - 5 - h y d r o x y c i n c h o m e r o n a t e H y d r o c h l o r i d e . T h i s c o m p o u n d w i t h nap 146-147 ~ w a s
o b t a i n e d in 79% y i e l d . F o u n d %: C 57.2: H 4.7. C16H15NO 5.HC1. C a l c u l a t e d %- C 56.9: H 4.8. P M R s p e c -
t r u m . 5, p p m (CF3COOH): 4 - and 5-CO2CH3, 3.75 and 3.82 s: 6-H, 8.21 s: 2-CH2. 4.29 s: 2'-C6H5. 7.12 s .
T h e h y d r o c h l o r i d e s w e r e c o n v e r t e d t o t h e f r e e b a s e s b y t h e a c t i o n of s o d i u m b i c a r b o n a t e .

* H e r e and s u b s e q u e n t l y , s i s s i n g l e t , d i s d o u b l e t , a n d m i s m u l t i p l e t .

569
 TABLE 4. P y r i d o x a m i n e 5 - P h o s p h a t e Analogs a
Found, % Calculated, %
Dihydrate Empirical formula Yield,%
H C H

IXa CIIHmN~OsP-2H~O 40,2 7,3 40,5 7, I 57

IXb C14HITN2OsP'2H20 46,2 5,6 46,7 5,9 39
IXc CgHIsN2OsP "2~20 35.9 6,5 36,2 6,4 35
IXd CmHITN2OsP'2H20 38,4 6,9 38,4 6,8 43

aAll of the compounds w e r e c h r o m a t o g r a p h i c a l l y and e l e e t r o p h o r e t i -

cally homogeneous, b p M R s p e c t r u m , & p p m (2 N NaOD): 2-C6H 5,
7.2 s. 2-CH 2. 4.12 s: 4--CH2, 3.75 s. 5-CH2, 4.05 d (J = 5.5 Hz). 6-H,
7.50 s.

TABLE 5. P y r i d o x a l 5- Phosphate Analogs a

Phosphom]la- Found, % Cale~loated,
Monohydrate tion formula Empirical formula Yield,
C H C H q0

Xa 60~ 4 h CIIHt~NO6P 9HeO 42,6 5,7 43,0 5,9 72

Xb 60~ 6h C,4H,4NO6P 9H:O 48,9 4,5 49,3 4,7 38
Xc 45~ 6 h CoHt2NO6P"H20 38,3 5,2 38,7 5,0 47
Xd 45~ 6h C,0H,4NO6P 9H20 40,7 5,6 41,0 5,5 65

aAll of the compounds obtained w e r e c h r o m a t o g r a p h i c a l l y and e l e c t r o -

p h o r e t i e a l l y homogeneous, b p M R s p e c t r u m . 6, p p m (2 N NaOD). 2-
C6H5. 7.25 s: 2-CH2, 4.32 s- 5-CH2, 4.03 d (J = 5.5 Hz). 6-H. 7.59 s.

p y r i d ~ i n e Analogs. 2 ' - I s o p r o p y l p y r i d o x i n e (Ia) and 2 ' - p h e n y l p y r i d o x i n e 01o) w e r e obtained by r e d u c -

tion of the f r e e b a s e s of d i e s t e r s of 5 - h y d r o x y e i n e h o m e r o n i e acids via the method in [2]. The hydrochloride
of Ia, with mp 211-213 ~ (dec., f r o m a l c o h o l - e t h e r ) , was obtained in 74% yield. Found %: C 53.5: H 7.5.
CltHI~NO3. HC1. Calculated %: C 53.4: H 7.3. The h y d r o e h l o r i d e of Ib, with mp 198-200 ~ (dec., f r o m
a l c o h o l - e t h e r ) , was isolated in 71% yield. Found %: C 59.7; H 5.5. C14HtsNO 3 9 HC1. Calculated %: C 59.7:
H 5.7.
5 ' - M e t h y l p y r i d o x i n e (IIa). This compound was obtained by the method in [2].
5 ' - P h e n y l p y r i d o x i n e (fib). A solution of 4 g (19.3 m m o l e ) of 4 ' , 3 - O - i s o p r o p y l i d e n e i s o p y r i d o x a l [5] in
20 m l of absolute e t h e r was added slowly with cooling and s t i r r i n g to a solution of a G r i g n a r d r e a g e n t p r e -
p a r e d f r o m 0.5 g of m a g n e s i u m and 3.3 g of b r o m o b e n z e n e in 20 m l of absolute ether. At the end of the ad-
dition, the m i x . r e was refluxed f o r 2 h, cooled, and d e c o m p o s e d b y the addition of 10 g of ice. The ether
l a y e r was s e p a r a t e d , and the aqueous l a y e r was e x t r a c t e d with t h r e e 1 0 - m l p o r t i o n s of ether. The c o m -
bined e t h e r e x t r a c t s w e r e dried and e v a p o r a t e d to d r y n e s s . The residue was dissolved in 100 m l of 10%
h y d r o c h l o r i c acid, and the solution was refluxed for 30 rain and vacuum e v a p o r a t e d to d r y n e s s . The residue
w a s t r i t u r a t e d thoroughly with d r y acetone, and the m i x t u r e was filtered. The yield of the hydrochloride
w a s 1.9 g (35%). Found %: C 59.0: H 5.5. C14H~sNO3"HC1. Calculated %: C 59.7: H 5.7.
5 ' - D e s o x y - 5 ' - c a r b o x y m e t h y l p y r i d o x i n e (IV)and 5 ' - D e s o x y - 5 ' - f l - h y d r o x y e t h y l p y r i d o x i n e (V). T h e s e
compounds w e r e obtained by the method of Korytnik and c o - w o r k e r s [5].
5 ' - D e s o x y - 5 ' - e a r b o x y m e t h y l e n e p y r i d o x i n e (III). A 0.5-g (2 m m o l e ) s a m p l e of 3 . 4 ' - O - i s o p r o p y l i d e n e -
5 ' - d e s o x y - 5 ' - e a r b o x y m e t h y l e n e p y r i d o x i n e [5] was d i s s o l v e d in 25 m l of 0.1 N HC1, and the solution was
h e a t e d at 80 ~ f o r 2 h. It was then e v a p o r a t e d to d r y n e s s in vacuo, and the r e s i d u e was t r i t u r a t e d with d r y
acetone. The r e s u l t i n g c r y s t a l s w e r e r e m o v e d by filtration, washed with acetone and ether, and dried. The
yield of the h y d r o e h l o r i d e of III with mp 293-297 ~ (dec.) was 0.4 g (81.5%). PMR s p e c t r u m , 6, p p m (2 N
NaOD): 2-CH 3, 2.32 s: 4-CH2, 4.82 s $ 5-CH, 7.56 d (5 = 16 Hz): 5'-CH, 6.34 d: 6-H, 7.71 s. According to
[5], the h y d r o c h l o r i d e m e l t s at 295-300 ~ (dee.). The h y d r o c h l o r i d e was c o n v e r t e d to the f r e e b a s e by the
action of sodium acetate.
Oxidation of P y r i d o x i n e Analogs. A) 2 ' - I s o p r o p y l - . 2 ' - p h e n y l - , and 5 ' - d e s o x y - 5 ' - B - h y d r o x y e t h y l -
p y r i d o x i n e s w e r e oxidized with m a n g a n e s e dioxide in sulfuric acid by the method in [2]; The pyridoxal
analogs w e r e i s o l a t e d f r o m the r e a c t i o n m i x t u r e s as e i t h e r the oximes or the Sehiff b a s e s with p - a n i s i d i n e .
The compounds obtained a r e p r e s e n t e d in T a b l e 2.

570
 B) 5'-Desoxy-5'-carboxymethyl- (VI) and 5'-Desoxyl-5'-carboxymethylenepyridoxals (VII). A 4 - g
sample of "B" manganese dioxide [6] was added to a suspension of 4 mmole of free base III or IV in a mix-
ture of 20 ml of chloroform and 40 ml of dioxane, after which the mixture was refluxed for 5 h. It was then
filtered, and the solid was washed with dioxane. The combined filtrates were evaporated to dryness, and
the residue was extracted with five 50-ml portions of boiling chloroform. The chloroform extracts were
filtered, and the filtrate was evaporated to a small volume. The precipitated base (VI or VII) was removed
by filtration and dried. The yield of VI with mp 165-166 ~ (rap 167-168 ~ [7]) was 44%. The yield of VII was
32%. Found %: C 57.8: H 4.3. C10HgNO4. Calculated %. C 57.9~ H 4.4. PMR spectrum, 5, ppm (2 N NaOD):
2-CH3, 2.29 s: 4-H, 10.15 s: 5-CH, 7.5 d (J = 16 Hz); 5'-CH. 6.21 d; 6-H. 7.44 s.
Pyridc~amine Analogs. The pyridoxamine analogs presented in Table 3 were obtained by hydrogena-
tion of the c~imes over Pd/C. Chromatographically pure substances in yields that were close to quantitative
were obtained in all eases.
Pyridoxamine Phosphate Analogs. These compounds were obtained by phosphorylation of the pyridox-
amine with polyphosphoric acid under the conditions described in [2]. The compounds obtained are presented
in Table 4.
Pyridoxal 5-Phosphate Analogs. These compounds were obtained by phosphorylation of the Sehiff
bases of the pyridoxal analogs with polyphosphoric acid and subsequent separation on Dowex-50 (H+ form)
via the method we described in [2]. The compounds obtained are presented in Table 5.

LITERATURE CITED
1. M. Ya. Karpeiskii, N. Sh. Padyukova, and V. L. Florent'ev, Khim. Geterotsikl. Soedin., 499 (1971).
2. N. A. Doktorova, L. V. Ionova, M. Ya. Karpeiskfi (Karpeisky), N. Sh. Padyukova (Padjukova), K. F.
Turchin, and V. L. Florent'ev (Florentiev), Tetrahedron, 25, 3527 (1969).
3. M. Tak~iehi and M. Taisuke. Yakugaku Zasshi. 91, 1030 (1971).
4. E. N. Dement'eva, N. A. Drobinskaya, L. V. Ionova, M. Ya. Karpeiskii, and V. L. Florent'ev, Bio-
khimiya, 33. 350 (1968).
5. W. Korytnik, J. Med. Chem., 8, 112 (1965).
6. M. Harnfest. A. Bavely, and W. A. Lazier, J. Org. Chem., 19, 1608 (1954).
7. C. Iwata and D. Metzler, J. Heteroeycl. Chem., 4, 319 (1967).

571
MASS SPECTROMETRY OF NEGATIVE IONS
OF PYRIDINE N-OXIDES

V. S. F a l ' k o . U. M . D z h e m i l e v , UDC 543.51 -. 547.821

V. I . K h v o s t e n k o , and G. A. Tolstikov

The d i s s o c i a t i v e c a p t u r e of e l e c t r o n s b y N - o x i d e s of p y r i d i n e and a - , fl-. and T - p i c o l i n e s

was i n v e s t i g a t e d by m a s s s p e c t r o m e t r y [1]. The m a s s s p e c t r a of the negative ions w e r e studied.
The c u r v e s of the effective yields of the negative ions as a function of the e n e r g i e s of the
e l e c t r o n s w e r e obtained.

The i n t e r a c t i o n of e l e c t r o n s with p y r i d i n e and its alkylated d e r i v a t i v e s [2] l e a d s to the f o r m a t i o n of

two excited s t a t e s of negative m o l e c u l a r ions, which then d i s i n t e g r a t e via the e n e r g e t i c a l l y possible d i s i n t e -
g r a t i o n channels to f o r m stable negative ions. Alkyl substituents in the p y r i d i n e m o l e c u l e do not c a u s e the
a p p e a r a n c e of new s t a t e s of the m o l e c u l a r ions.
The e x p e r i m e n t a l data on the d i s s o c i a t i v e c a p t u r e of e l e c t r o n s b y N-oxides of m e t h y l p y r i d i n e s a r e
p r e s e n t e d in T a b l e 1. The m a s s s p e c t r u m of the negative ions is a set of r e l a t i v e intensities of p e a k s of
ions a t the m a x i m a of t h e i r effective yields, so that s e v e r a l p e a k s with r e s p e c t to the n u m b e r of r e s o n a n c e
p r o c e s s e s involving the f o r m a t i o n of the given ions m a y c o r r e s p o n d to one m a s s n u m b e r . The r e l a t i v e in-
t e n s i t i e s of p e a k s f o r two p o o r l y r e s o l v e d (from one another) r e s o n a n c e p e a k s a r e p r e s e n t e d for the p e a k
of m a x i m u m intensity.
The oxygen a t o m in pyridine N-oxides has a s u b s t a n t i a l effect on the p r o c e s s e s of d i s s o c i a t i v e c a p t u r e
of e l e c t r o n s , causing both the a p p e a r a n c e of new excited s t a t e s of the negative m o l e c u l a r ions and a change
in the n u m b e r of p o s s i b l e channels of disintegration of the m o l e c u l a r ions. Five ground s t a t e s of the ex-
cited m o l e c u l a r ions, which a r e designated by the l e t t e r s a - e , can b e distinguished f r o m the position of the
m a x i m a of t h e e f f e c t i v e yield of ions on the s c a l e of the e n e r g y of the e l e c t r o n s and f r o m the paths of disin-
t e g r a ~ o n . We will e x a m i n e the indicated s t a t e s f o r the pyridine N-oxide m o l e c u l e .
L o w - e n e r g y s t a t e a of the negative m o l e c u l a r ions is r e p r e s e n t e d in the m a s s s p e c t r u m of pyridine
N-oxide by the lines of the (M - H)-, NC3H3-, NC 3H2-, and NC 3- f r a g m e n t ions. The r e l a t i v e intensities of the p e a k s
of the indicated ions a r e r e l a t i v e l y low, and the m a x i m u m e f f e c t i v e n e s s of the f o r m a t i o n of ions during the
d i s i n t e g r a t i o n of the negative m o l e c u l a r ions of s t a t e a is o b s e r v e d at e l e c t r o n e n e r g i e s of 0.2-0.5 eV.
The d i s i n t e g r a t i o n of m o l e c u l a r ions of the b s t a t e is a c c o m p a n i e d b y ejection of a C2H 3 group (ions
with m / e 68). The m a x i m u m of the r e s o n a n c e p e a k on the c u r v e of the effective yield of 0VI-C2I-I3)- ions is
found at an e l e c t r o n e n e r g y of 0.8 eV.
The m o s t intense p e a k s in the m a s s s p e c t r u m of p y r i d i n e N-oxide a r e affiliated with the ions f o r m e d
during the d i s s o c i a t i o n of the negative m o l e c u l a r ions of the c state, and the m a x i m u m effective yield of
ions is o b s e r v e d at e l e c t r o n e n e r g i e s of 3-3.2 eV. The disintegration of the m o l e c u l a r ions of this s t a t e
is r e p r e s e n t e d in the m a s s s p e c t r u m by p e a k s of the (M--H)-, (M-OH)-. (M--OCH)-. O-, and OH- ions and
of ions with m / e 64.
The s t a t e s of the m o l e c u l a r ions e n u m e r a t e d above a r e o b s e r v e d only during the i n t e r a c t i o n of e l e c -
t r o n s with the p y r i d i n e N-oxide m o l e c u l e s , and the oxygen a t o m linked by a s e m i p o l a r bond to the p y r i d i n e
n i t r o g e n a t o m affects t h e i r f o r m a t i o n . The h i g h e r - e n e r g y s t a t e s of the negative m o l e c u l a r ions have

Institute of C h e m i s t r y , B a s h k i r Branch. A c a d e m y of Sciences of the USSR, Ufa. T r a n s l a t e d f r o m

K h i m i y a G e t e r o t s i k l i e h e s k i k h Soedinenii. No. 5, pp. 661-665, May, 1974. Original a r t i c l e submitted
A p r i l 2, 1973.

9 1975Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy of this article is available from the publisher for $15.00.

572
T A B L E 1. M a s s S p e c t r a of t h e N e g a t i v e I o n s of N - O x i d e s of l>yri -
dine and Its Methyl Derivatives

m/e Pyridine a-Pieoline S-Picoline ),-Picoline

N-oxide N-oxide N-oxide N-oxide '
l 2 3 4 5

16,8 (8,8) 17,8 (8,55) 37,6 (8,95)

108 I00 (3,26) 100 (3,1'2) 67,5 (4,25)
62 (o,2) 19,2 (0,4) '53. (0,2)
5,2 (8,8) 0,98 (8,5) 27,3 (8,56)
107 1,0 (3,6) 2,2 (3,2) 2,6 (4,8)
0,89 (0,3) 3,6 (0,2)
0,67 (.8,8) 1,43 (8,6)
106 0,6 (3,6) 0,79 (3,2) 1,04 (4,8)
0,29 (0.3)
6,61 (8,8) * 3,78 (8,5) 0.5 (8,6) 2,6 ('8,23)
94 lOO (3,1) 65,3 (3~24) 15,7 (3,14) 16,1 (3,4)
5,7 (0,3) 10 (0,36) 3,0 (0,3) 1,0,4 (0,34)
0,4 (8,5) 0,29 (8,6) 5,71 (8,6)
93 4 (4,2) 1,86 (4) 0,74 (3,2) 1,95 (4,35)
0,24 (0,3) 3,9 (0,3)
0,25 (8,5) 5,05 (8,7) 2,32 (8,55) 67,5 (9,2)
92 9,3 (3~3) 3,94 (3,2) 9,1 (4,35)
0,67 (0,34) 0,07 (0,3) 13 (0,32)
1,46 (8,64) 0,39 (8,9) 8,3 (9,1)
91 5 (3,3) 1,38 (3) 3,9 (3,2)
1,3 (,0,24) 0,07 (5,3)
3,84 (8,25) 0~ (8,56) 29,9 (9.12)
90 4,27 (3,2) 0,99 (3,32) 8,85 (4,64)
1,27 (0,2) 0,14 (0.48) 23,4 (0,2)
o,8 (8,5) 0,08 (8,48) 1,55 (9)
82 0,16 (4,2) 8,4 (1,l)
2,'33 (1,2) 1,3 (1,1)
0,67 (8,6) 2,08 (9)
81 0,47 (3,3) 1,57 (4,1) 6,35 (4,5)
1,13 (8,8) 0.15 (8.4) 13 (9,2)
80 2,67 7,9 (3,2) 83 (Z26)
0,2 (0,28) 1,3 (0.2)
0,29 (8,8) 0,27 (9) 0,29 (8,2) 2,08 (9,2)
79 2 (4,7) 6,4 (4,25) 14,5 (4,56)
12 (8,45) 2.96 (8,7) 0,49 (8,8) 5,7 (9,1)
78 3,14 (3,16) 2,3,3 (6,8) 0,69 (4,4) 8,85 (3,28)
0,23 (4,8) 3,6 (0,24)
1.07 (8,55) 0,23 (8,7) 0,78 (9,1)
76 1,15 (4,08) 0.53 (3,7) 0,1 (4) 1,04 (4,5)
2,06 (~8,1) 0,67 (8.8) 1,~2 (8,45) 3,38 (8,8)
68 1,24 (3,8) 10 (4,28)
1,87 (0,8) 26,7 (1,24) 18,5 (1,10) 1,04 (1,1)
1,2.4 (8, I ) 0,6 (8,6) 0,6 (8.56) 1o,4 (9,28)
67 1'5 (5,84)
6,2 (3,8) 14 (3,6) 0,74 (3,6) 100 (4,28}
1,1 (9) 0,6 (8,6) 5,2 (9,2)
66 5,1.5 (3.2) 47,5 (3,7) 4,33 (3,52) 6 (4,32)
1,65 (0,28)
0,91 (8,3) 0,6 (8,65) 0,34 (8,6) 3,9 (9,1)
65 8,26 (4,2) 0,25 (425) 0,1'2 (3,6) 0,78 (4,2)
0,36 (0,24)
3,47 (8,2) 1,6 (8,85) 0,94 (8,7) 46,7 (K28)
64 0,57 (3,4) 0,26 (4,36) 10,9 (4,31)
10,4 (0,2)
058 (8.3) 0,8 (8,72) 0,69 (8,8) 1,82 (9,1)
63 0,16 (4,3) 0,13 (4)
53 0,49 (8,2) 2,8 (8,96) 0,44 (8,7) 4,42 ( 9 , 2 )
0,44 (4,3) o,13 (4,~2) 0,40 (4,2) 0,78 (4,5)
o,3 (o,2)
0,91 (8,1) 0,93 (9,16) 1,5 (s,~) 1,09 (9,2)
52 0,88 (4,0) 1,16 (3,64) 10,3 (4) 0,91 (4,2)
0,22 (o,21"
1,65 (8,1) 1,93 (9) 0,49 (8,5) 2,47 (9,2)
51 0,13 (3,56)
6,83 (8,2) 4,0 (8,96) 1,72 (9) 1,,95 (9,2)
5O 1,93 (3,02) 1,0 (4,4) 0,29 (4,5) 1,18 (4,5)
2,24 (0,2) 1,3 (0,2) 4,92 (0,,2) 19,5 (O,3)
3,72 (8,3) 0,87 (9) 0,2,4 (9) 1,3 (9)
49
o,~2 (.8) 0,4 (8,5) 0,40 (8,8) 2,86 (9)
43 0,33 (4,.6) 0,49 (4,2) 2,6 (4,2)
6,83 (8,28) 4,66 (8,6) 1,97 (8,48) 3,12 (8,9)
42 1,46 (3,28) 2,0 (4,3) 0,5 (3,9)
3,3 (0,12) 8,68 (0,2) 1,2 (0,12) 23 (0,2)
6,Z2 (8,1) 7,34 (8,92) 11,3 (8,6) 10,4 (a,9)
41 3,06 (3,Z2) 5,33 (4,4) 1,48 (4,26) 5,7 (4,2)
4,55 (8,3) 7,0 (8,95) 23 (8,4) 22,4 (8.95)
4O 14 (3,94) 16,6 (3,88) 2,46 (3,8) 28,6 (5,8)
57 (4.32)

573
 TABLE 1 (Continued)
m/e .:. Pyridine r /~-Picoline I-Picoline
N-oxide N-oxide N-oxide N-oxide
1 2 3 4 5
s.

6,61 (7,92) 8 (8,68) 3,45 (825) 2,86 (8,9)

39 1,23(4,52) 0,34 (4,,16)
24,8 (8,2) 18,6 (8,72) 8,1.3 (82) 12,5 (9)
25'
24,8(&:5,) 21,8 (8,8) 8,2 (8,2) 6,23 (9,1)
17 14 ,(3,2) 48 (3,54) 18,5 (3,64) 3,9 (4,4)
89,5 (8) 120 (8) 1Z,3 (&,92) 33,8 (825)
16 ~68 (3A2) 6~) (3,48) 185 (,3,16) 83 (4,3~)
0,49 (82) 2,8 (8,96) 0,44 (&7) 4,42 (9,,2)

* The e n e r g y of the electrons of the m a x i m u m yield is given in p a r e n -

t h e s e s in e l e c t r o n volts.

a l r e a d y been o b s e r v e d during a study of the dissociative capture

of e l e c t r o n s by pyridine molecules.

= lp8(.o,o25)111 ~ ^ The d state of the m o l e c u l a r ions is revealed distinctly

f r o m the c u r v e s of the effective yield of O- ions, on wkich t h e r e

~ "111 1 II a r e two p o o r l y r e s o l v e d peaks (see Fig. 1). The f i r s t peak has a

m a x i m u m at an electron e n e r g y of 3.2 eV and c o r r e s p o n d s to
"t l IIN\ l I \ state c of the negative m o l e c u l a r ions. The second peak, with a
it I III/\\ \\ m a x i m u m at an electron e n e r g y of 4 eV, shows the existence of
yet another state of the negative m o l e c u l a r ions. which disinte-
o
0
g r a t e s with the f o r m a t i o n of O- ions. The dissociation of the
N 0 1 2 3 4 5 6 7 8 9 1011
Electron energy, eV negative m o l e c u l a r ions of the indicated state also leads to the
formation of (M-CH3)-, (M-OCH)-, (M-NO)-, NC3H3- , NC3H2- ,
Fig. 1. Dependence of the effective
NC3-, and (M-2H)- ions and of ions with m / e 68, 41, 40, and 39.
yield of negative ions on the electron
In c o n t r a s t to p r o c e s s e s of dissociative capture of electrons by
e n e r g y in pyridine N-oxide (the m a s s
pyridine molecules [only (M-H)-, NC3-, C2H-, and C2- ions a r e
n u m b e r s a r e indicated by the n u m b e r s
f o r m e d in this range of e l e c t r o n energies], the disintegration of
beside the curves).
the m o l e c u l a r ions of pyridine N-oxide p r o c e e d s via a c o n s i d e r a -
bly l a r g e r n u m b e r of channels. Moreover. a channel for the f o r -
m a t i o n of C2H- and C2 ions is opened. Ions with m / e 65 a r e f o r m e d by detachment of an NO group and ap-
p a r e n f l y have the s t r u c t u r e of the eyelopentadienyl anion. The inflection of the peak on the curve of the
effective yield of ions with m / e 65 on the l o w e r e l e c t r o n - e n e r g y side shows that the ions a r e also f o r m e d
during the disintegration of the m o l e c u l a r ions of the c state, but with a lower probability. Similar
p r o c e s s e s a r e also noted on the c u r v e s of the effective yield of ions with m / e 53, 52, and 50.
The disintegration of the m o l e c u l a r ions of h i g h - e n e r g y state e f o r m s a m a s s s p e c t r u m with many
m a s s peaks, although t h e i r r e l a t i v e intensities a r e r e l a t i v e l y low. In addition to the p u r e l y "pyridine"
NC3H2- , NC3H-, NC2H2- , NC2H- , and CzH- ions, one also o b s e r v e s f r a g m e n t s , the formation of which is ex-
plained by p a r t i c i p a t i o n of the oxygen atom in the dissociation p r o c e s s e s : (M-OH)-. (M-H30)-, (M-OC)-,
(M-OCH)-, O-. and OH-, and ions with m / e 68, 49, 43, 42, and 41. The m a x i m a of the r e s o n a n c e peaks of
the f o r m a t i o n of the indicated ions a r e situated at 8-9 eV along the e l e c t r o n - e n e r g y scale.
Just as in the c a s e of alkylpyridines, r e p l a c e m e n t of the hydrogen atom in the pyridine N-oxide m o l e -
cule by a methyl group does not cause the f o r m a t i o n of new states of the negative m o l e c u l a r ions. One ob-
s e r v e s only a c e r t a i n r e d i s t r i b u t i o n of the probabilities of the various disintegrative channels.
Detachment of a methyl group f r o m the m o l e c u l a r ions o c c u r s during the dissociative capture of elec-
t r o n s by N-oxides of m e t h y l p y r i d i n e s with a quite high probability, while for the methylpyridines t h e m s e l v e s
the indicated p r o c e s s is noted only during the capture of e l e c t r o n s by 2 - m e t h y l p y r i d i n e molecules, and the
probability of the p r o c e s s is v e r y low. Depending on the e l e c t r o n energy, the c u r v e s of the effective yield
of (M-CH3)- ions contain t h r e e peaks of r e s o n a n c e p r o c e s s e s . The f i r s t peak c o r r e s p o n d s to disintegration
of the m o l e c u l a r ions of the a state at an electron e n e r g y of 0.2 eV. The m a x i m u m of the second peak is
situated at 3-3.2 eV on the e l e c t r o n - e n e r g y scale, and (M--CH3)- ions a r e f o r m e d during the disintegration
of the negative m o l e c u l a r ions of the e state. The third p e a k - a m a x i m u m at 8-8.6 e V - is caused by dis-
soeiation of the m o l e c u l a r ions of the e state.

574
 P e a k s of (M-H30)- ions a r e o b s e r v e d in the m a s s s p e c t r a of all of the i n v e s t i g a t e d compounds. It
should be noted that during the c a p t u r e of e l e c t r o n s b y N-oxides of pyridine and T-picoline, 0VI-H30)- ions
a r e f o r m e d during the disintegration of the m o l e c u l a r ions of the c state. Capture of e l e c t r o n s b y N-oxides
of a - p i e o l i n e and fl-picoline is a c c o m p a n i e d by the f o r m a t i o n of (M-H30)- ions. which a r e c a u s e d by disin-
t e g r a t i o n of the m o l e c u l a r ions of both s t a t e c and s t a t e d with different d e g r e e s of e f f e c t i v e n e s s of f o r m a -
tion: this is c o n f i r m e d by the p r e s e n c e of inflections on the c u r v e s of the effective yield of ions.
The p e a k s of the r e s o n a n c e p r o c e s s e s involved in the f o r m a t i o n of {M-H)- ions during the d i s i n t e g r a -
tion of the negative m o l e c u l a r ions of the e s t a t e have a s y m m e t r i c a l f o r m f o r the m o l e c u l e s of the f i r s t
t h r e e compounds. The f o r m a t i o n of (M-H)- ions during the i n t e r a c t i o n of e l e c t r o n s with T - p i e o l i n e N-oxide
m o l e c u l e s o c c u r s in a m o r e complex m a n n e r . T h e r e a r e two b r e a k s on the c u r v e of the effective yield of
ions at e l e c t r o n e n e r g i e s of 2.8 and 3.1 eV,. in addition, (M--H)- ions a r e f o r m e d during the d i s i n t e g r a t i o n of
the negative m o l e c u l a r ions of 7 - p i c o l i n e N-oxide of the d s t a t e with a high effective yield. The r e l a t i v e
intensity of the lines of the f r a g m e n t ions f o r m e d by disintegration of the negative m o l e c u l a r ions of the d
s t a t e i n c r e a s e s in the m a s s s p e c t r u m of ~/-picoline N-oxide.

EXPERIMENTAL
The m a s s s p e c t r a w e r e r e c o r d e d with an MKh-1303 s p e c t r o m e t e r r e m o d e l e d f o r the r e c o r d i n g of
negative ions. The conditions m a i n t a i n e d during the r e c o r d i n g of the m a s s s p e c t r a w e r e as follows: the
ionizing e l e c t r o n c u r r e n t was 1 pA. and the ionization c h a m b e r t e m p e r a t u r e was 150 ~ The e l e c t r o n - e n e r g y
s c a l e was m o n i t o r e d f r o m the c u r v e of the effective yield of SF 6- ions. The c u r v e s of the effective yield
of negative ions as a ftmetion of the e l e c t r o n e n e r g y w e r e obtained by m e a n s of an automatic r e c o r d i n g
device with a PDS-021M t w o - c o o r d i n a t e p o t e n t i o m e t e r .

LITERATURE CITED
11 V. I. Khvostenko and I. I. Furlei, Teor. i l~ksperim. Khim., 4..816 (1968).
2. V. I. Khvostenko, I. I. Furlei, and I. Kh. Aminev. Khim. Vys. Energ., 3. 502 (1969).

575
HYDRAZONES

XXXIX.* POLAROGRAPHIC STUDY OF N-BENZYLIDENEIMINOPYRIDINIUM IODIDES

Yu. P. Kitaev, T. V. T r o e p o l ' s k a y a , UDC 547.821.3:543.253

and L. N. O r l o v a

The p o l a r o g r a p h i c b e h a v i o r of a n u m b e r of N - b e n z y l i d e n e i m i n o p y r i d i n i u m iodides in aqueous

alcohol b u f f e r solutions was studied o v e r a wide r a n g e of pH values. The m e c h a n i s m of t h e i r
reduction on a dropping m e r c u r y e l e c t r o d e and the f a c t o r s affecting the cleavage of the N - N
bond a r e d i s c u s s e d . The reduction p r o d u c t - the p y r i d i n i u m i o n - induces the catalytic evolu-
tion of hydrogen.

The p o l a r o g r a p h i c b e h a v i o r of N - a l k y l p y r i d i n i u m s a l t s has b e e n d e s c r i b e d in quite s o m e detail. On

a dropping m e r c u r y e l e c t r o d e (DME) they f o r m o n e - e l e c t r o n r e v e r s i b l e diffusion reduction waves that c o r -
r e s p o n d to the f o r m a t i o n of a r a d i c a l [2].

9 I
R

The h a l f - w a v e potential and the wave height a r e independent of the pH. The r a d i c a l that a r i s e s di-
m e r i z e s or r e a c t s with the solvent, as a r e s u l t of which the n i t r o g e n a t o m l o s e s its a m m o n i u m c h a r a c t e r
and b e c o m e s capable of accepting a proton, t h e r e b y inducing catalytic hydrogen c u r r e n t s . The catalytic
w a v e s on the p o l a r o g r a m s of a l k y l p y r i d i u m s a l t s have been e x a m i n e d in detail in a n u m b e r of p a p e r s [3-5].
In a p o l a r o g r a p h i c r e s p e c t , the p r e v i o u s l y uninvestigated N - b e n z y l i d e n e i m i n o p y r i d i n i u m iodides {I)
that we studied in the p r e s e n t r e s e a r c h should be c l o s e r to h y d r a z o n e s than to alkylpyridininm s a l t s . How-
e v e r , one should a l s o note s e v e r a l d i f f e r e n c e s , i n a s m u c h as compounds (I) have a p o s i t i v e l y c h a r g e d n i t r o -
gen a t o m included in a h e t e r o r i n g of a r o m a t i c c h a r a c t e r , while a r y l h y d r a z o n e s should be p r o t o n a t e d at the
m o r e basic imine nitrogen atom.

R = H, P and m-CH~, p and m-NO2,m-C1, p OCH3, p -Br, p N (CHa)2, P CH(CH3)2.

In fact, with r e s p e c t to t h e i r b e h a v i o r on a DME, s a l t s (I) display a g r e a t s i m i l a r i t y to both a r y l h y d r a -

zones [6] and to 1,2.4--triazolylimines of the benzaldehyde s e r i e s [7]. In acid buffer solutions they all f o r m
two t w o - e l e c t r o n w a v e s of equal height (the n u m b e r of e l e c t r o n s going into the reduction of the investigated
compounds was e s t a b l i s h e d f r o m the II'kovich equation).
The El/2 value of t h e s e w a v e s depends on the pH, and this a t t e s t s to p r i o r protonation of the c o m -
pounds. It can b e a s s u m e d that the p r o t o n a t i o n c e n t e r is the nitrogen a t o m of the C ~ N bond, although one

*See [1] f o r c o m m u n i c a t i o n XXXVIH.

A. E. A r b u z o v Institute of Organic and P h y s i c a l C h e m i s t r y , A c a d e m y of Sciences of the USSR. K a z a n ' .

T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii. No. 5, pp. 666-669, May, 1974. Original a r t i c l e
s u b m i t t e d F e b r u a r y 13, 1973.

9 1975Plenum Publishing Corporation, 227 West 17th Street, New York, N.Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

576
cannot exclude protonation at both nitrogen a t o m s . The first of these waves, which has a m o r e positive E1/2
value, has a constant height at pH ~ 4, which rapidly d e c r e a s e s to z e r o as the pH is i n c r e a s e d further, while
the second wave i n c r e a s e s simultaneously on its own account, reaching the height of a f o u r - e l e c t r o n wave.
This s o r t of phenomenon has also been o b s e r v e d for some a r y l h y d r a z o n e s , dimethylhydrazones, and 1,2,4-
t r i a z o l y l i m i n e s [6, 7]. It can evidently be explained by a change in the m e c h a n i s m of the electrode reaC-
tion - by t r a n s i t i o n f r o m a t w o - s t e p reduction with the i n t e r m e d i a t e formation of an imine as a kinetically
independent p a r t i c l e to a l m o s t simultaneous addition of four electrons of the d e p o l a r i z e r molecule as the
electrode r e a c h e s a sufficiently negative potential due to a d e c r e a s e in the pH of the medium. In both c a s e s
the final products a r e the same.
In some c a s e s [(I), R = p - B r , m - C l , and m-NO2], the overall height of these waves was somewhat de-
p r e s s e d , although h y d r o l y s i s did not take place in acidic media (in c o n t r a s t to 1,2.4-triazolylimines). In
these instances, substantial kinetic limitations were observed: specifically, the t e m p e r a t u r e coefficients
exceeded the values c h a r a c t e r i s t i c for p u r e l y diffusion p r o c e s s e s . Because of the high adsorbability of the
d e p o l a r i z e r on the DME, its desorption as the t e m p e r a t u r e r i s e s could even lead to a negative t e m p e r a t u r e
coefficient. Phenomena of this type have been observed for a r y l h y d r a z o n e s [6] and w e r e explained by the
kinetics of the dehydration of these compounds in acidic media, which p r e c e d e s the s t r i c t l y electrode
p r o c e s s . It can be a s s u m e d that the p o s i t i v e l y - c h a r g e d nitrogen atom in (I) p r o m o t e s their hydration in
aqueous solutions, shifting the electron density on the c a r b o n atom of the C = N bond toward the positive
center.
An analysis of the g r a p h of the dependence Ilim/~-H =f(~-H-) (Illm is the limiting c u r r e n t and H is the
height of the m e r c u r y r e s e r v o i r ) provided evidence for the kinetic c h a r a c t e r of the f i r s t wave. The second
wave p r o v e d to be a diffusion wave. F o r it. Ilim/~rH = const. The kinetic limitations imposed by the dehy-
dration reaction apparently also reduce the m a x i m u m limiting c u r r e n t s of reduction for (I) as well. As one
should have expected, these phenomena a r e most distinctly seen in compounds with e l e c t r o n - a e c e p t o r R
substituents that d e c r e a s e the electron density on the c a r b o n atom of the azomethine grouping.
The N - N + bond in N-benzylideneiminopyridinium iodides is cleaved m o r e r e a d i l y than the N - N bond
in benzaldehyde a r y l h y d r a z o n e s because of its g r e a t e r p o l a r i t y (its disintegrative c h a r a c t e r ) . The overall
height of the waves of the investigated compounds r e a c h e s a m a x i m u m at pH 5- 6 and then d e c r e a s e s rapidly
to approximately the t w o - e l e c t r o n level. The reduction also o c c u r s in alkaline solutions. An adsorption
wave with El/2 f r o m - 0 . 8 to - 1 . 0 V is o b s e r v e d for pH > 6.
In the case of some of the slightly soluble substances {R = p - B r , p-NO2), at p H ~ 4 . 0 t h e r e appears a
s m a l l elongated wave (caused by a change in the capacity of the DME because of desorption of a l a r g e p o r -
tion of the d e p o l a r i z e r f r o m the electrode s u r f a c e [6]) with El/2 f r o m - 1 . 2 to - 1 . 6 V. which is masked by
the base e l e c t r o l y t e at lower pH values. It r e a c h e s a m a x i m u m and then d e c r e a s e s in neutral media. The
dependence of the height of this wave on the p r e s s u r e on the dropping m e r c u r y and the t e m p e r a t u r e indicates
its kinetic c h a r a c t e r . Anomalously high catalytic waves f o r hydrogen evolution with E1/2 = - 1 . 7 3 V, which
m e r g e d with the base e l e c t r o l y t e at pH < 3 and vanished at pH ~ 7.0, were o b s e r v e d f o r all of the compounds
in acidic media.
The overall s c h e m e of the reduction of N-benzylideneiminopyridinium iodides in acidic media can be
r e p r e s e n t e d in the following m a n n e r :

pH<4,5: ~<! '~--N=CH--C6H4RI- ~.~=c.-c6.,R

-H
~+|~/L~'N-N=CH-CsH4R'
[ I - J ........ (/
~ / 'NH+
I- ~f2e'2H~
t
+
catalytic H2 evolution N.3~_CH2--C6B,LR

l
catalytic H2 evolution

The unprotonated f o r m of these compounds at pH > 7.0 is also reduced. However, we w e r e unable to
detect t h e s i g n a l of a f r e e radical in C2HsN+NH2I" and (CsHsN+N = CH-C6Hs)I- solutions atpH 9 . 2 b y m e a n s
of ESR s p e c t r o s c o p y . The o n e - e l e c t r o n wave of the f i r s t compound apparently c o r r e s p o n d s to the f o r m a -
tion of a r a d i c a l that is not sufficiently stable under these conditions.

577
 All of the investigated compounds a l s o have an anode wave at - 0 . 2 4 V, which is due to the f o r m a t i o n
of an insoluble m e r c u r y s a l t with the iodide anion. In the c a s e of compounds that contain a p o l a r . g r a p h i c a l l y
a c t i v e NO2 group, one a l s o o b s e r v e s its reduction waves, which have a l r e a d y been adequately studied and~
a r e t h e r e f o r e not d e s c r i b e d h e r e .
The reduction of the s t a r t i n g N - a m i n o p y r i d i n i u m iodide may, to a c e r t a i n degree, s e r v e as a model
of the f i r s t step in the e l e c t r o d e r e a c t i o n with the p a r t i c i p a t i o n of its d e r i v a t i v e s {I). This compound is r e -
duced in acidic b u f f e r e d m e d i a via one t w o - e l e c t r o n wave of diffusion c h a r a c t e r , the E1/2 value of which
depends s u b s t a n t i a l l y on the pH (AE l f i / A p H = 90 m V / p H unit). This AE~/2/ApH value can be explained by the
p a r t i c i p a t i o n in the e l e c t r o d e r e a c t i o n of a l a r g e r n u m b e r of protons {han e l e c t r o n s as a consequence of
p r o t o n a t i o n of the a m i n o group.

. .+ ,
,.l+,,"
.j.7 =,_

When pH > 6.0. the wave falls r a p i d l y to the o n e - e l e c t r o n l e v e l with El/2 = - 1 . 6 V. It is p o s s i b l e that the
u n p r o t o n a t e d N - a m i n o p y r i d i n i u m iodide u n d e r g o e s o n e - e l e c t r o n reduction in alkaline m e d i a to give a f r e e
r a d i c a l , as d e s c r i b e d for N - a l k y l p y r i d i n u m s a l t s [2].

~I-~--NH2 e" f "~--~/N--NH2~C~TNH2

] ~ 1 - . dimerizationor reactionwiththe solvent.,

It is i n t e r e s t i n g to note that m a x i m a ( s u p p r e s s e d by gelatin), which a r e a p p a r e n t l y a s s o c i a t e d with

the g r e a t e r a d s o r b a b i l i t y of the d i m e r s as c o m p a r e d with the s t a r t i n g d e p o l a r i z e r (see [8]). a p p e a r on the
p o l a r . g r a m s at pH > 6.0. An anode wave f r o m i n t e r a c t i o n of the iodide ion with the e l e c t r o d e m a t e r i a l and
a catalytic wave of hydrogen evolution a r e a l s o o b s e r v e d f o r N - a m i n o p y r i d i n i u m iodide.

EXPERIMENTAL
The m e t h o d s f o r the p r e p a r a t i o n of the i n v e s t i g a t e d compounds and t h e i r s p e c t r a l and p h y s i c . c h e m i -
cal c h a r a c t e r i s t i c s have been d e s c r i b e d in a p r e v i o u s c o m m u n i c a t i o n [1]. The p o l a r . g r a m s of 20~ e t h a n o l -
w a t e r B r i t t o n - R o b i n s o n b u f f e r solutions with pH 1.7-11 w e r e r e c o r d e d with a M e t r o h m P o l a r e c o r d p o l a r . -
graph: the d e p o l a r i z e r concentration in the cell was 5" 10-4 m o l e / l i t e r . The c o m p a r i s o n e l e c t r o d e was a
s i l v e r chloride e l e c t r o d e . The dropping m e r c u r y e l e c t r o d e has the following c h a r a c t e r i s t i c : tl/6m 2/3 =
(1.554 m g / s e c ) 2/3. sec 1/6 = 1.342.

LITERATURE CITED

I. T. V. T r o e p o l ' s k a y a and Yu. P. Kitaev. Khim. G e t e r o t s i k l . Soedin., 1219 (1973).

2. P. Tompkins, Anal. Chem., 21, 64 (1949).
3. S. G. Mairauovskii, Dokl. Akad. Nauk SSSR, 110. 593 {1956).
4. S. G. Mairanovskii, Dokl. Akad. Nauk SSSR, 114, 1272 (1957).
5. L. Floch. M. S. S p r i t z e r . and P. J. Elving, Anal. Chem., 38. 1074 (1966).
6. Yu. P. Kitaev and T. V. T r o e p o l ' s k a y a . Izv. Akad. Nauk SSSR, Ser. Khim., 1903 (1967).
7. Yu. P. Kitaev. I. M. Skrebkova, and L. I. Maslova, Izv. Akad. Nauk SSSR. Set. Khim., 2194 (1970).
8. S. G. Mairanovskii, J. E l e c t r o a n a l . Chem., 12. 547 (1966).

578
LACTAM ACETALS
X.* SYNTHESIS AND SOME PROPERTIES OF 1H.1-METHYL-6-OXO-2,3,4,5,6,11-
HEXAHYDROAZEPINO[2,3-b]QUINOLINE AND ITS ANALOGS

A . M. Z h i d k o v a , V. G. G r a n i k . UDC 547.743.1'836.07 : 542.953

R . G. G l u s h k o v , T. F. Vlasova,
O. S. A n i s i m o v a . T , A. G u s ' k o v a .
a n d G. N. P e r s h i n

Derivatives of p y r r o l o - , pyrido-, and azepino[2,3-b]quinolones w e r e synthesized by condensa-

tion of N-methylbutyro-, N - m e t h y l v a l e r o - , and N - m e t h y l c a p r o l a c t a m diethyl acetals with ethyl
anthranilate. The corresponding ethoxy derivatives w e r e obtained by reaction of these com-
pounds with triethyloxonium t e t r a f l u o r o b o r a t e , and condensed 4-chloroquinolines were synthe-
sized with POC13.

It has been d e m o n s t r a t e d [I] that the amidine grouping in various 2 - a r y l i m i n o derivatives of N - m e t h -

y l l a c t a m s activates the /3 position of the molecule to such an extent that the protons attached to the C 3 atom
a r e exchanged by d e u t e r i u m even u n d e r mild conditions. Although participation of the solvent is specified
in the p r o p o s e d [1] m e c h a n i s m of d e u t e r i u m exchange, one cannot exclude the possibility of t h e r m a l detach-
ment of a proton f r o m C 3. In this connection. 1 - m e t h y l - 2 - (o-earbethoxyphenylimino)hexahydroazepine (III)
was synthesized by reaction of N - m e t h y l c a p r o l a c t a m diethyl acetsl (1) with ethyl anthranilate (If). Heating
of III to 180-200~ is accompanied by i n t r a m o l e c u l a r cyclization to give 1H, l - m e t h y l - 6 - o x o - 2 , 3 , 4 , 5 , 6 - 1 1 -
hexahydroazepino [2,3- b] quinoline (IVa).
In the cyclization of amidine III~ in the p r e s e n c e of catalytic amounts of p-toluenesulfonic acid, the
yield of IVa i n c r e a s e s c o n s i d e r a b l y (from 44 to 80%): this is in a g r e e m e n t with the concept of acid catalysis
of cleavage of the C s - H bond [1]. Derivatives IVb, c were s i m i l a r l y synthesized but without isolation of the
i n t e r m e d i a t e amidines of the HI type.

C2H5OOC ?
- L.XN
I -- I t H
CH 3 CH 3 CH 3

I a-c Ill IV a - c

I, IV a n = 3 ; b n=~; an=l; M n=3

Compounds IVa-c w e r e subjected to alkylation with t e r t i a r y oxonium salts, which a r e usually m o r e

inclined to undergo O-alkylation r e a c t i o n s [2], although products of both (3- and N-alkylation w e r e isolated
in the r e a c t i o n of triethyloxonium t e t r a f l u o r o b o r a t e (V) with u r e a vinylogs [3].
T e t r a f l u o r o b o r a t e salts (Via and VIIa) w e r e isolated f r o m the r e a c t i o n of IVa with t e t r a f l u o r o b o r a t e
V in c h l o r o f o r m . The IR s p e c t r u m of salt Via contains the absorption bands of an OH group at 3530 and

* See [1] for communication IX.

It is not n e c e s s a r y to isolate i n t e r m e d i a t e amidine HI (see the experimental section).

S. Ordzhonikidze All-Union S c i e n t i f i c - R e s e a r c h P h a r m a c e u t i c a l C h e m i s t r y Institute, Moscow.

T r a n s l a t e d f r o m Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 670-674, May, 1974. Original article
submitted June 7. 1973.

9 1975PlenumPublishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

579
 TABLE 1. PMR S p e c t r a (ppm)

Compound CH2-2 CH~-3 CH2-4 CH2-5 N-CHa H(Ar) CH3 ] CH2 Solvent
(O=et)](Ofst)

IVa 3,40 1,75 1,75 235 3,08 7,05--8,00 d-DMSO

vIIa
VIII a
3,81
3,21
1,96
1,77
1,96 2,98 3,36 7,40--8,00
2,86 3,05 7,05--7,76
1,5-i 4,76 d=DMSO
137 1,46 3,98 CC14
VIIIb 3,32 1,85 239 3,18 6,92--7,65 1,44 3,92 ' CCt4
VIIIC 3,29 3,00 2,95 6,92--7,82 1,40 4,17 CC14

3590 c m -1. Signals of a C2H 5 group a r e not p r e s e n t in the PMR s p e c t r u m of Via, and decomposition of it by
both aqueous alkali and t r i e t h y l a m i n e in benzene gives s t a r t i n g IVa. Hence it is a p p a r e n t that s a l t Via is the
t e t r a f l u o r o b o r a t e of IVa. The PMR s p e c t r u m of salt VIIa c o r r e s p o n d s to the s p e c t r u m of the ethylation p r o -
duct (see T a b l e 1). T r e a t m e n t of this s a l t with alkali gives a compound which, a c c o r d i n g to the r e s u l t s of
e l e m e n t a r y a n a l y s i s and the PMR s p e c t r u m , is 1 H . l - m e t h y l - 6-ethoxy- 2,3,4, 5 - t e t r a h y d r o a z e p i n o [ 2 , 3 - b ] -
quinoline WIIIa). An intense m o l e c u l a r ion p e a k with m / e 256 is o b s e r v e d in the m a s s s p e c t r u m of VIIIa.
The c h a r a c t e r i s t i c p a t h of d i s i n t e g r a t i o n of s u b s t a n c e s of the ViIIa type is elimination of an ethyl group
f r o m the m o l e c u l a r ion (to give a f r a g m e n t with m / e 227) with subsequent ejection of CO, as a consequence
of which a stable ion ( m / e 199) with the azepino[2,3-b]indole s t r u c t u r e [4] is f o r m e d . In addition to the m e t a -
s t a b l e p e a k s c o r r e s p o n d i n g to this s c h e m e , the s p e c t r u m a l s o contains c h a r a c t e r i s t i c (for f r a g m e n t a t i o n of
the compounds with an ethoxy group) p e a k s of [M-CH3] @, [M-OC2Hs] @, and [M-OC2H4] @ ions.
M i x t u r e s * of s a l t s VIb, c and Vllb,c, w h i c h w e r e subjected to alkaline t r e a t m e n t without separation,
w e r e obtained by alkylation of IVb, c. The s t r u c t u r e of ethoxy d e r i v a t i v e s VIIIb, c was p r o v e d by m e a n s of
IR, PMR (see Tables 1 and 2), and m a s s s p e c t r a .
R
r
IVa-c ,., (~"2)"---~/~

CH 3

VIII, IX a - c

VIIla-c R=OC2H5; IXa-C R=CI

The c o r r e s p o n d i n g chloro d e r i v a t i v e s (IXa-c) w e r e then s y n t h e s i z e d b y r e a c t i o n of oxo d e r i v a t i v e s

I V a - c with POC13. In the c a s e of IVa, b, i n t e r m e d i a t e salts, to which the dichlorophosphate s t r u c t u r e
(IX-Xa, b) was a s s i g n e d on the b a s i s of m o d e r n concepts [5] of the s t r u c t u r e of dimethylformamide/POC13
c o m p l e x e s , w e r e isolated in this r e a c t i o n .
The halogen a t o m in I X a - c p l o v e d to be i n a c t i v e - the s t a r t i n g m a t e r i a l was r e c o v e r e d c o m p l e t e l y
even a f t e r chloro d e r i v a t i v e IXa was heated with C2H5ONa in a b o m b at 200-215 ~ f o r 6 h. Negative r e s u l t s
w e r e a l s o obtained on prolonged heating of IXa with a m i n e s at high t e m p e r a t u r e s . This deactivation of the
halogen is a s s o c i a t e d with the s t r o n g - e l e c t r o n - d o n o r effect of the N - m e t h y l group in the 2 position of the
quinoline ring.
All of the i n v e s t i g a t e d compounds had a b a e t e r i s t a t i c effect on m i c r o b a c t e r i u m t u b e r c u l o s i s (15-125
p g / m l ) in e x p e r i m e n t s in vitro. Substances of the azepine s e r i e s (IVa and IXa) have the m o s t pronounced
a n t i t u b e r c u l a r activity (15 # g / m l ) . Compounds Xa, b have a weak fungistatic effect with r e s p e c t to M i c r o -
s p o r o m lanosum, Irichophyton gypseum, and Achorion schSnleini (250-500 #g/ml), while IVa, b have a
weak effect with r e s p e c t to Candida albicans (250-500 p g / m l ) . All of the s u b s t a n c e s w e r e inactive with r e -
s p e c t to inducers of acute b a c t e r i a l i n f e c t i o n s , except f o r IXa, which had a weak b a c t e r i o s t a t i c effect with
r e s p e c t to g r a m - p o s i t i v e b a c t e r i a (500/~g/ml).

EXPERIMENTAL

The PMR spectra were recorded with a JNM-4H-100 spectrometer with tetramethylsilane as the in-
ternal standard. The IR spectra of mineral oil pastes were recorded with a Perkin-Elmer 457 recording
s p e c t r o m e t e r . The UV s p e c t r a of alcohol solutions (~ 10 -4 M) w e r e r e c o r d e d with an EPS-3 s p e c t r o p h o t o -
m e t e r . The m a s s s p e c t r a w e r e obtained with an MKh-1303 s p e c t r o m e t e r , equipped with a d i r e c t inlet into
the s o u r c e , at an ionizing voltage of 50 eV.
* The f o r m a t i o n of s a l t s V I a - c is the r e s u l t of r e a c t i o n of t e t r a f l u o r o b o r a t e V with the alcohol p r e s e n t in the
c h l o r o f o r m . The yield of ethoxy d e r i v a t i v e VIIIa was 95% in the alkylation of IVa in CH2C12.

580
 c~l eo c,i

i b--

~4
~ i ~,
,4 u-xl e,'~

II II ~ II

91~ ~ .,4,.,

o Oll
"~g~g E8 ~ a

I I 1 l I I I I I I I ~ -I I I I I

~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~I ~ ~

I I I t I I I I I I I t o ~1 I I I 1

r.0

0
c~

O~

c~ o 6 o 6 o 6 oo6 o o ~ _zo_~ ~ :~

= ~ ~ ~-~

581
 1 - M e t h y l - 2 - ( o - c a r b e t h o x y p h e n y l i m i n o ) h e x a h y d r o a z e p i n e {IIa). A m i x t u r e of 12.1 g (60 m m o l e ) of
a c e t a l Ia and 9.9 g (60 m m o l e ) of II w a s heated at 50-55 ~ f o r 3.5 h, a f t e r which it was e v a p o r a t e d and the
r e s i d u e was distilled to give 14.3 g (87%) of IIIc with bp 197-198 ~ (3 ram).
1 H , 1 - M e t h y l - 6 - o x o - 2 , 3 , 4 , 5 , 6 , 1 1 - h e x a h y d r o a z e p i n o [ 2 , 3 - b ] q u i n o l i n e (IVa), 1 H . 1 - M e t h y l - 5 - o x o - 2 , 3 , 4 , 5 , 1 0 -
p e n t a h y d r o p y r i d o [2,3-b]quinoline {IVb), and 1H, 1 - M e t h y l - 4 - oxo- 2,3.4, 9 - t e t r a h y d r o p y r r o l o [ 2 , 3 - b ] q u i n o l i n e
(IVc). A) A solution of 1.3 g (5 m m o l e ) of IIIa in 15 m l of diethylene glycol and 0.05 g of p-toluenesulfonic
acid (TsOH) was heated at 180-200 ~ f o r 40 rain, a f t e r which it was evaporated, and the solid was r e m o v e d by
filtration. Workup gave 0.95 g (83%) of IVa with nap 293-295 ~ (from methanol).
B) A m i x t u r e of 5.2 g (25 m m o l e ) of acetal Ia and 4.1 g (25 m m o l e ) of e s t e r II was heated at 50-55 ~
f o r 3.5 h, a f t e r which 0.1 g of TsOH was added, and the m i x t u r e was heated at 180-200 ~ for 40 rain. It was
then evaporated, and the r e s i d u e was f i l t e r e d to give 4.2 g {76%) of IVa. The s a m e method was used to syn-
t h e s i z e IVb. with nap > 300 ~ (from methanol), in 71% yield and IVc, with nap > 300 ~ (from methanol), in 43%
yield f r o m IIIb and IIIc, r e s p e c t i v e l y .
C) Similarly, but without TsOH. IVa was obtained in 44% yield.
1H,1- Methyl- 6-ethoxy-2,3,4, 5-tetrahydroazepino[2,3-b]quinoline T e t r a f l u o r o b o r a t e (Via). A solution
of 1.9 g (10 m m o l e ) of t r i e t h y l o x o n i u m t e t r a f i u o r o b o r a t e (V) in 15 m l of d r y c h l o r o f o r m was added to a s u s -
pension of 2.28 g (10 m m o l e ) of IVa in 15 m l of d r y c h l o r o f o r m , and the m i x t u r e was allowed to stand f o r
2 h, a f t e r which the p r e c i p i t a t e d Via was r e m o v e d b y f i l t r a t i o n to give 1.1 g (35%) of a p r o d u c t wi~h mp 154-
157 ~ The p r o d u c t had mp 178-179 ~ (from alcohol) a f t e r it was washed t h r e e t i m e s with boiling c h l o r o f o r m .
The c h l o r o f o r m solutions w e r e e v a p o r a t e d to give 1.7 g (49%) of ethoxy d e r i v a t i v e ViIa with nap 170-172 ~
The p r o d u c t was c r y s t a l l i z e d f o r a n a l y s i s to give a s a m p l e with mp 195-197 ~
1H. 1- Methyl- 6- ethoxy- 2, 3,4, 5- t e t r a h y d r o a z epino [2, 3-b] quinoline (VIHa), 1H, 1- Methyl- 5- ethoxy- 2,3, 4-
t r i h y d r o p y r i d o [ 2 , 3 - b ] q u i n o l i n e (vIIIb). and 1H, 1 - M e t h y l - 5- ethoxy- 2,3-dihydropyrrolo[2, 3-b]quinoline (VIIIc).
Ethanol (150 ml) and a 20% aqueous NaOH solution w e r e added to a m i x t u r e of s a l t s Via and VIIa, obtained
f r o m 30 g (0.13 mole) of IVa, until the pH was 9, a f t e r which the alcohol was evaporated. C h l o r o f o r m (50 ml)
w a s added, and the m i x t u r e was f i l t e r e d to give 10.8 g of IVa with m p 270-272 ~ The l a y e r s w e r e s e p a r a t e d ,
and the aqueous l a y e r was e x t r a c t e d with c h l o r o f o r m (three 2 0 - m l portions). The e x t r a c t s w e r e dried o v e r
Na2SO4, filtered, and e v a p o r a t e d . The r e s i d u e was distilled to give 20.0 g (55%) of ethoxy d e r i v a t i v e VIHa
with bp 177 ~ (1 ram) and nD 2~ 1.6171. Compounds VIIIb, with mp 71-72 ~ (from hexane), and VIIIc, with nap
131-132 ~ ( f r o m p e t r o l e u m ether), w e r e s i m i l a r l y synthesized in yields of 34% and 57%. r e s p e c t i v e l y .
1H - 1 - M e t h y l - 6 - c h l o r o - 2 , 3 , 4 , 5 , 1 1 - p e n t a h y d r o a z e p i n o [ 2 , 3 - b ] q u i n o l i n e Diehlorophosphate (Xa) and
1 H, 1- Methyl- 5- c h l o r o - 2,3,4,1 0- t e t r a h y d r o p y r i d o [2,3-b] quinoline Dichl orophosphate (Xb). A 3.2- g (15
m m o l e ) s a m p l e of IVb was refluxed in 15 m l of POC13 f o r 3 h, a f t e r which the m i x t u r e was cooled, and the
p r e c i p i t a t e was r e m o v e d by f i l t r a t i o n and washed with ether. The yield of c o m p l e x Xb, with mp 176-178 ~
(dec.). was 4.45 g (82%). Compound Xa, with nap 131-133 ~ was s i m i l a r l y obtained in 78% yield.
1H, 1- Methyl- 6 - c h l o r o - 2 , 3 , 4 . 5 - t e t r a h y d r o a z e p i n o [ 2 , 3 - b ] quinoline (IXa), 1H, 1-Methyl- 5- c h l o r o - 2, 3,4-
t r i h y d r o p y r i d o [2,3-b]quinoline (IXb). and 1H, 1- M e t h y l - 4 - e h l o r o - 2,3-dihydropyrrolo[2,3-b]quinoline (IXc).
W a t e r (20 ml) and 20 m l of c h l o r o f o r m w e r e added to dichlorophosphate Xc, obtained f r o m 4.5 g of oxo
compound IVe, and the m i x t u r e was m a d e alkaline to pH 9 with 20% aqueous NaOH. The l a y e r s w e r e s e p a -
r a t e d , and the aqueous l a y e r was e x t r a c t e d with c h l o r o f o r m (two 2 0 - m l portions). The e x t r a c t was dried
with Na2SO 4 and f i l t e r e d . The f i l t r a t e was e v a p o r a t e d to give 2.9 g (60%) of IXc with mp 137.5-138.5 ~ (from
acetone). At s i m i l a r p r o c e d u r e was u s e d to obtain LXb, with m p 73 ~ {from hexane), in 83% yield. Compound
IXa, with bp 173-175 ~ (3 ram), was s i m i l a r l y s y n t h e s i z e d in 79% yield, but the i n t e r m e d i a t e dichlorophos-
p h a t e was not purified.

LITERATURE CITED

1. V. G. Granik. A. M. Zhidkova, T. F. Vlasova, R. G. Glushkov. and Yu. N. Sheinker. Khim. G e t e r o t s i k l .

Soedin.. 533 (1974).
2. V. G. Granik, B. M. Pyatin, and R. G. G h s h k o v . Usp. Khim., 40, No. 9, 1593 (1973).
3. Z. Arnold and A. Holy, Coll. Czech. Chem. Commun., 27, 2886 (1962).
4. H. Budzikiewiez, C. D j e r a s s i . and D. Williams. I n t e r p r e t a t i o n of the M a s s S p e c t r a of Organic C o m -
pounds, Holden-Day (1964).
5. H. Meerwein, W. Florian, N. Sch~n. and G. Stopp, Ann., 641, 1 (1961).

582
 MECHANISM OF THE OXIDATIVE CONDENSATION

OF ACRIDINES WITH NUCLEOPHILES

I. KINETICS OF THE CONDENSATION OF ACRIDINES
WITH M E T H Y I ~ S U B S T I T U T E D HETEROCYCLIC ALKIODIDES

V. E. Kirichenko and O. N . C h u p a k h i n UDC 547.835.9.07 : 541.127

The kinetics of the r e a c t i o n of acridine h y d r o c h l o r i d e with the alkiodides of 2- and 4-picolines,

2- and 4-methylquinolines, 2-methylbenzothiazole. and 1 , 2 - d i m e t h y l b e n z i m i d a z o l e in the
p r e s e n c e of a i r oxygen w e r e investigated. It is shown that the r e a c t i o n is second- o r d e r o v e r -
all and f i r s t o r d e r in each of the components at a constant oxygen concentration. The r e a c -
tion r a t e constants w e r e calculated, and a m e c h a n i s m is p r o p o s e d f o r the r e a c t i o n .

In [1, 2] we d e s c r i b e d the r e a c t i o n of acridine and its s a l t s with h e t e r o c y c l e s containing an active

methyl group. The r e a c t i o n p r o c e e d s in the p r e s e n c e of a oxidizing agent (sulfur or a i r oxygen) and gives
9- acridinylhet e r y l m e t h a n e s .
This r e a c t i o n can f o r m a l l y b e r e g a r d e d as nucleophilic substitution of the hydride ion. It is known
that substitution of the hydride ion is r e a l i z e d in s t r o n g l y alkaline m e d i a (the Chichibabin reaction) [3] or
in the p r e s e n c e of an oxidizing agent (including oxidation by the s u b s t r a t e itself) [4].
In o r d e r to a s c e r t a i n the m e c h a n i s m of the r e a c t i o n d e s c r i b e d above, we investigated the k i n e t i c s of
the condensation of acridine h y d r o c h l o r i d e with a s e r i e s of alkiodides of m e t h y l - s u b s t i t u t e d h e t e r o c y c l e s
in the p r e s e n c e of a i r oxygen in d i m e t h y l f o r m a m i d e (DMF). The r e a c t i o n of acridine h y d r o c h l o r i d e (AHC)
with 4-picoline methiodide (PMI) was studied in g r e a t e r detail. It was e s t a b l i s h e d that the p y r i d y l a c r i d i n y l -
m e t h a n e (PAM) f o r m e d as a r e s u l t of the r e a c t i o n is oxidized f u r t h e r to a c r i d o n e (AC) u n d e r the r e a c t i o n
conditions.

cn 3 ~ n o - C n - c r q ~-
" -- 0
i

H CI- ~H a II Cl H

AHC PlviI PAM AC

The r e a c t i o n is c o m p l i c a t e d by s l o w e r p a r a l l e l p r o c e s s e s involving the oxidation of the s t a r t i n g AHC

to a c r i d o n e and s e l f - c o n d e n s a t i o n of the alkiodides to the c o r r e s p o n d i n g m o n o m e t h y l i d y n e c y a n i n e s : t h e s e
r e a c t i o n s p l a y an a p p r e c i a b l e r o l e in the p r e s e n c e of a l a r g e e x c e s s of a given r e a g e n t . Side r e a c t i o n s can
b e d i s r e g a r d e d when the component r a t i o is e q n i m o l a r .
Oxidation p r o c e e d s through a i r oxygen d i s s o l v e d in the DMF. A i r was bubbled through the r e a c t i o n
m i x t u r e at a flow r a t e of 15 cm3/min.
The r a t e constants at 110-130~ were measured. The c o u r s e of the r e a c t i o n was m o n i t o r e d by s p e c -
trophotometry.
The kinetic c u r v e s , which w e r e t r e a t e d by the i n t e g r a l method, s a t i s f i e d a s e c o n d - o r d e r equation (Fig.
1). We d e t e r m i n e d the p a r t i a l o r d e r with r e s p e c t to AHC and PMI at the s t a r t of the r e a c t i o n [5].

S. M. K i r o v U r a l Polytechnic Institute. Sverdlovsk. T r a n s l a t e d f r o m K h i m i y a G e t e r o t s l k l i c h e s k i k h

Soedinenii, No. 5, pp. 675-678, May. 1974. Original a r t i c l e submitted D e c e m b e r 27, 1972.

9 1975 PlenumPublishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication maybe reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy of this article is availablefrom the publisher for $15.00.

583
 TABLE 1. Rate Constants for the Condensation of AHC with Methyl-
Substituted H e t e r o c y c l i c Alkiodides *
Reaction k 910s, liter/mole 9
Methyl substituted heterocycle temp., ~ sec

4-Picoline methiodide 110 0,345_+0,01

120 0,50 _-_0,006
130 0,77 _+0,01
2-Pieoline methiodide If0 0,098_+0,004
120 o,132-+0,007
130 0,176_0,005
4-Pic61ine ethiodide 120 0,51 _+0,01
4-Picblineisopropiodide 120 0,47 _+0,01
Lepidine methiodide 120 0,51 ___0,02
Qu|naldinemethiodide 120 0,25 +_0,02
2-Methylbenzothiazolemcthiodide 120 0,183--+0,003
1,2-Dimethylbenzimidazole methiodide 120 0,031+-0,003
Acridine base + 4-picolinemethiodide
- - 120 0,062_+0,003

*c 0 of acridine = c 0 of m e t h y l - s u b s t i t u t e d h e t e r o c y c l e = 0.184 m o l e / l i t e r .

C,
mole/ / ~0 = K[AHC]n' [::PMI ]n,.
liter
0,2
The values d e t e r m i n e d in this m a n n e r were. rgspectively,
nl = 1.2 and n2 = 0.74 (Figs. 2 and 3).
0,I6 ++/ 3~..r
In the p r e s e n c e of a 10-40-fold e x c e s s of PMI, the kinetic
c u r v e s of the consumption of AHC follow a f i r s t - o r d e r equation.
0,12
C a r r y i n g out of the reaction in a l a r g e excess of one of
the components is impossible, inasmuch as the r a t e s of the
side r e a c t i o n s b e c o m e c o m p a r a b l e to the rate of the p r i m a r y
reaction, and they cannot be taken into account.
Consequently. it can be a s s u m e d that under the conditions
0 K+,'- i r f i I of z e r o o r d e r with r e s p e c t to the oxidizing agent the reaction
2 4 6 S 10 t~ l l
is second o r d e r o v e r a l l - f i r s t o r d e r with r e s p e c t to acridine
Fig. 1. Kinetic c u r v e s of the buildup of- and f i r s t o r d e r with r e s p e c t to the methyl-substituted h e t e r o -
1) PAM: 2) AC: 3) overall c u r v e : 4) de- cycle. The c e r t a i n understatement in the o r d e r with r e s p e c t
pendence of 1/(c0-x) on t (c0AHC = to PMI is apparently explained by the effect of the d i s r e g a r d e d
c0PMI = 0.184 m o l e / l i t e r ) . s e l f - c o n d e n s a t i o n side reaction.

The s e c o n d - o r d e r r a t e constants w e r e calculated graphically. The calculation was made by the meth-
od of least squares, and the c o r r e l a t i o n coefficients w e r e 0.97-0.99 (Table 1).
The r e a c t i o n rate constant i n c r e a s e s on p a s s i n g f r o m acridine to its hydrochloride by a factor of
eight, i.e., the r e a c t i o n r a t e depends on the magnitude of 6(+) on C-9 of acridine. The o r d e r of change in
the r a t e constants in the s e r i e s of h e t e r o e y c l e s is in a g r e e m e n t with the lability of the protons of the methyl
groups f r o m data on d e u t e r i u m exchange [6. 7]. The dependence of the rate constant of the investigated r e -
action on the pK a values of the protons of the methyl groups attests to the nucleophilie c h a r a c t e r of the
m e t h y l - s u b s t i t u t e d h e t e r o c y e l e in this reaction.
The r e s u l t s of the kinetic investigations indicate that: a) the reaction is heterolytic, the m e t h y l - s u b -
stituted h e t e r o c y c l e acts as the nucleophilic p a r t n e r , and the a c r i d i n i u m compounds act as the electrophilie
p a r t n e r : b) both r e a g e n t s p a r t i c i p a t e in the r a t e - l i m i t i n g step of the p r o c e s s .
Considering the l i t e r a t u r e data on a r o m a t i c nucleophilic substitution [4, 8] and taking into account the
c h a r a c t e r i s t i c (for acridine) ability to add nucleophiles at the 9 position to give products with the acridan
s t r u c t u r e [9-11], the following r e a c t i o n m e c h a n i s m can be proposed:

CH3 H CH+'--~'~+N--CH_l- C!t2--~+ N--C H I -

+ kI O~
14 CI- I-~-~ + H+ + CI- ~ + H20
CH 3 'H

584
 log w0+ 2

0,4 log w0+ 2

,

/J 0~2 014 0,61ogc0AHC.1

0~4

o',z o14log ~MI

Fig. 2 Fig. 3
Fig. 2. D_ependence of log w0 on log c0AHC for c0PMI = 0.184 m o l e / l i t e r
and e0AHC = 0.184. 0.092, 0.0368, 0.0184, and 0.0123 m o l e / l i t e r .
Fig. 3. Dependence of log w0 on log c0PMI for c0AHC = 0.184 m o l e / l i t e r
and c0PMI = 0.184. 0.092, 0.0368, and 0.0184 m o l e / l i t e r .

The e x p r e s s i o n for the reaction r a t e is written as follows:

KIK2
w [AHC] [PMI]
K-I+K2

when k_ 1 << kx. kob s = kl, while when k_l >> k2. kob s = k2keq.
The formation of an i n t e r m e d i a t e was not o b s e r v e d chemically, chromatographically, or by means of
UV s p e c t r o s c o p y . The p r e s e n c e in a n u m b e r of c a s e s of an induction period, the duration of which i n c r e a s e s
as the reagent concentration d e c r e a s e s and the r e a c t i o n t e m p e r a t u r e d e c r e a s e s , speaks in favor of its f o r -
mation. The equilibrium in the f i r s t step is p r o b a b l y shifted almost completely to favor the starting m a -
t e r i a l s , and the addition product t h e r e f o r e cannot be detected.

EXPERIMENTAL

The c h a r a c t e r i s t i c s of the q u a t e r n a r y salts and their anhydro b a s e s a r e p r e s e n t e d in [2].

Acridine Hydrochloride. Chemically p u r e g r a d e acridine hydrochloride was converted to the base
and c r y s t a l l i z e d f r o m ethanol t h r e e to four times to give a product with mp 110-111 ~ Hydrogen chloride
was p a s s e d through a solution of this pure acridine in benzene, and the precipitated hydrochloride was c r y s -
tallized two to t h r e e t i m e s f r o m ethanol and dried at 110 ~
Methyl-Substituted Heteroeyclic Alldodides. The alkiodides used for this study had p u r i t y c r i t e r i a
that were in good a g r e e m e n t with the l i t e r a t u r e data [12, 13].
Dimethylformamide. The DMF was dried with P205 and vacuum distilled over P20~.
Method Used to Make the Kinetic M e a s u r e m e n t s . Weighed samples of the reagents were dissolved in
10 ml of DMF, and the solutions were placed in a t h e r m o s t a t , the t e m p e r a t u r e in which was maintained with
an a c c u r a c y of ~ The solutions w e r e held at the r e a c t i o n t e m p e r a t u r e for 10 min after which a i r was
bubbled in; the flow rate of the air was monitored by means of a s y s t e m including a monostat and a mano-
m e t e r and was maintained at 15 cm3/min. Under these conditions the reaction p r o c e e d s in the k i n e t i e r e g i o n .
The analysis was p e r f o r m e d by selection of s a m p l e s : PAM was analyzed as the anhydro base. A 0.1-
ml sample was diluted with a f r e s h l y p r e p a r e d alcohol solution of NaOH (e = 1 0 - 2 m o l e / l i t e r or, in the c a s e
of the methylquinolines, 5" 10-4 m o l e / l i t e r ) , during which the q u a t e r n a r y salts of the diheterylmethanes
were converted to the anhydro b a s e s a l m o s t instantaneously and quantitatively [2], The resulting solution
was then subjected to s p e c t r o p h o t o m e t r y with an S F - 4 s p e c t r o p h o t o m e t e r . The initial acridine c o n c e n t r a -
tion was d e t e r m i n e d f r o m the optical density at 376-378 nm (shoulder) or 355 nm (maximum). The anhydro
base concentration was d e t e r m i n e d f r o m the absorption in the visible region of the spectrum, while the
acridine concentration was d e t e r m i n e d f r o m the optical density at 400 nm.

585
 LITERATURE CITED
1. V . E . Posazhennikova, O. N. Chupakhin, and I. Ya. Postovskii, Khim. Geterotsikl. Soedin.. 1384 (1970).
2. O.N. Chupakhin, V. E. Kirichenko, and I. Ya. Postovskii, Khim. Geterotsikl. Soedin., 1116 (1974).
3. L . A . Pozharskii and A. M. Simonov, Chichibabin Amination of Heterocycles [in Russian], Izd. Rostov-
skogo Univ. (1971).
4. J. Miller, Aromatic Nucleophflic Substitution, Academic Press, London (1968).
5. N.M. l~manu~l' and D. G. Knorre, Course in Chemical Kinetics [in Russian], Moscow (1969).
6. N.N. Zatsepina, Yu. N. Kaminskii, and I. F. Tupitsyn, Reakts. Sposobnost' Organ. Soedin., 3, 433
(1967).
7. N.N. Zatsepina, Yu. N. Kaminsldi, and I. F. Tupitsyn, Reakts. Sposobnost' Organ. Soedin., 3, 505
(1967).
8. F. Pietra. Quart. Rev. Chem. Soc.. 4. 505 (1969).
9. F. Kr~hnke and H. L. Honig, Ann., 624, 97 (1959).
10. A . K . Sheinkman. S. G. Potashnikova, and S. N. Baranov, Zh. Organ. Khim., 6. 614 (1970).
11. A . K . Sheinkman. A. K. Tokarev, S. G. Potastmikova, A. A. Deikalo, A. A. Kucherenko, and S. N.
Baranov. Khim. Geterotsild. Soedin., 643 (1971).
12. E . N . Kosower and P. E. Klinedinst, J. Amer. Chem. Soc., 78, 3493 (1956).
13. L M. Heilbron and G. M. Banbury, Dictionary of Organic Compounds [Russian translation], Vols. 1-3,
Inostr. Lit., Moscow {1949).

586
6 H - A N T H R A [ 1 . 9 , 8 - c, d, e , f ] - 2 , 7 - N A P H T H Y R I D I N E DERIVATIVES

S. V. R e z n i c h e n k o , S. 5. P o p o v , UDC 547.673.5'834.2
a n d N. S. D o k u n i k h i n

Derivatives of a new heterocyclic s y s t e m - 6H- anthra [1,9,8- c. d, e. f]- 2,7-naphthyridine - were

obtained by condensation of 1.8-diaminoanthraquinone with malonic ester, acetoacetic ester,
and benzoylacetic ester.

Of the anthracene derivatives condensed with two pyridine rings in the peri positions, only the 1,9-4,10-
and 1,9-5,10 i s o m e r s (I and II) [I] were known up until now. The 1,9-9,8 i s o m e r - 6H-anthra[1.9,8-c,d,e,f]-
2,7-naphthyridine {III)-has not been described in the literature.
i1 i

8 4

H H

ill

The synthesis of 1,6,11-tricarbonyl derivative (IV) seemed of particular interest. Owing to the p e ri
orientation of the carbonyl groups, the properties of anthranaphthyridone IV may differ fundamentally from
the properties of the corresponding 2.6- and 2,8-dicarbonyl derivatives of I and II. which have isolated
pyridine rings.
2H, 10H-Anthra[1.9.8-e. d. eft]-2.7-naphihyridine- 1.6. l l - t r i o n e (IV) was obtained by condensation of
1,8-diaminoanthraquinone with diethyl malonate in the presence of potassium acetate.

O R O O

II II Ii
O O O

V, VI IV

V R:CH3; VI I~=C6H~

It is known that 1-aminoanthraquinone reacts with e s t e r s of B-ketocarboxylic acids in the presence

of alkali metal acetates to give 1-acylanthrapyridones [2] and in the presence of acidic agents to give
1-carbalkoxyanthrapyridines [3]. 1-Aminoanthraquinones that contain such substituents as halogens or
sulfo groups in the 8 position cannot be converted to the corresponding 1-aeylanthrapyridines because of
steric hindrance [4]. However, when the 8 position is occupied by a group that is capable of cyclization,
one might expect the formation of two condensed rings simultaneously. In fact, methyl- and phenyl-substi-
tuted anthrapyridinepyridones (V and VI), respectively, are formed from 1,8-diaminoanthraquinone and
ethyl acetoacetate and ethyl benzoylaeetate under the conditions used to obtain IV.
Treatment of anthranaphthyridone IV with phosphorus oxychloride in the presence of dimethylform-
amide (DMF) gives, in high yield. 1, ll-dichloroanthranaphthyridine (VII), the structure of which was proved

Scientific-Research Institute of Organic Intermediates and Dyes. Moscow. Translated from Khimiya
Geterotsiklicheskikh Soedinenii, No. 5, pp. 679-681, May. 1974. Original article submitted May 18, 1973.

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, N.Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

587
 TABLE 1. Anthranaphthyridines IV-VIII

Com- Crystalliza. Empirical Found, % Calc., % U V spectra,

tion sol- formula Yield
pound
Vent )'max, n m %
C H N C H
s n m (log s)
I

IV -- CIzH~N20~ 70,7 240 (4,55) 91

340 (4,08)
42O (3,87)
(B H2SO,)
V p-Xylene C,eH,oN20~ 75,2 242 (4.60) 8@
295 (4,67)
4a5 (3,96)
(in CI-bOO0I-I)
VI CH3COOH C:3H,~203 79,5 245 (4,51) 92
29o (4~37)
402 (3.94)
(n H=SO,)
VII p-Xylene CIzH6CI~N20*62,8 24s (4.58) 99
290 (4,42)
330 (3.88)
34o (3,s4)
38o (3,80)
380 (3,77) "
410 (3,85)
(in dioxane)
VIII Nitroben- C,gHI2N20~ 72,4 240 (4,a7) 47
zene ~o (3,~2)
(,SH~SO4)

*Found %. C1 21.2. Calculated ~: C1 21.8.

b y m a s s s p e c t r o m e t r y . The s t a r t i n g IV is f o r m e d when VII is t r e a t e d with an aqueous dioxane solution of

alkali. A t t e m p t s to obtain a m o n o c h l o r o d e r i v a t i v e f r o m IV have not yet been s u c c e s s f u l .
It was of i n t e r e s t to i n v e s t i g a t e the p o s s i b i l i t y of the cyclization of N - a l k y l - s u b s t i t u t e d 1 , 8 - d i a m i n o -
anthraquinone to give a t r i e a r b o n y l d e r i v a t i v e incapable of k e t o - e n o l t a u t o m e r i s m .
Under the conditions u s e d to obtain IV, we s y n t h e s i z e d 2 , 1 0 - d i m e t h y l - 2 H , 1 0 H - a n t h r a [ 1 , 9 , 8 - e , d , e . f ] -
2,7-naphthyridine-1, 6, l l - t r i o n e (VIII) in 47% yield.

EXPERIMENTAL
2 H , 1 0 H - [ 1 , 9 , 8 - c . d , e , f ] - 2 , 7 - n a p h t h y r i d i n e - l , 6 , 1 1 - t r i o n e (IV). A m i x t u r e of 1.2 g (0.005 mole) of 1,8-
diaminoanthraquinone, 1.5 g of p o t a s s i u m acetate, and 30 g (0.185 mole) of malonic e s t e r was s t i r r e d at
180 ~ for 15-20 rain until a thick yellow s u s p e n s i o n had f o r m e d . It was diluted with alcohol, and the p r e c i p i -
t a t e was r e m o v e d by f i l t r a t i o n and washed with alcohol and w a t e r to give 1.2 g (91%) of product. F o r p u r i f i -
cation, the p r o d u c t was d i s s o l v e d in 30 m l of c o n c e n t r a t e d H2SO4, and the solution was g r a d u a l l y diluted with
w a t e r until the H2SO4 concentration was 70%. A f t e r 20 h, the p r e c i p i t a t e was r e m o v e d by filtration and
washed s u c c e s s i v e l y with 2 5 - m l p o r t i o n s of 70%, 55%, and 30% H2SO4 to give yellow p r i s m s . The p r o d u c t
was a l m o s t insoluble in m o s t organic solvents but could be r e c r y s t a l l i z e d f r o m l a r g e volumes of nitroben-
zene or N - m e t h y l p y r r o l i d o n e . The analytical and s p e c t r a l data a r e p r e s e n t e d in Table 1.
Under s i m i l a r conditions, compounds V and VI w e r e obtained f r o m 1, 8-diaminoanthraquinone and
a c e t o a c e t i c and b e n z o y l a c e t i c e s t e r s , while VIII was obtained f r o m 1, 8 - b i s m e t h y l a m i n o a n t h r a q u i n o n e and
malonic e s t e r .
1 , 1 1 - D i c h l o r o a n t h r a [ 1 . 9 , 8 - c . d . e , ~ ] - 2 , 7 - n a p h t h y r i d i n - 6 - o n e (VII). A m i x t u r e of 2.0 g (0.008 mole) of
anthranaphthyridone IV, 127.5 g (0.83 mole) of p h o s p h o r u s oxychloride, and 10 m l of DMF was refluxed f o r
30 rain, a f t e r which it was cooled and p o u r e d o v e r ice. Workup gave 2.2 g (99%) of dichloro d e r i v a t i v e VII.
F o r purification, the p r o d u c t was r e c r y s t a l l i z e d f r o m p - x y l e n e to give a m a t e r i a l with mp 310 ~ (dec.).

LITERATURE CITED

1. E. P. Fokin and R. P. Ivanova. Izv. Sibirsk. Otd. Akad. Nauk SSSR. 1, 62 (1962).
2. W e s t G e r m a n Patent No. 578,995, F r e d l . . XIX (1964). Chem. Abstr., 28, 782 (1934).
3. I. Gunthard, A m e r . Dyestuffs Rep., 46, 9 (1957).
4. S. I. Popov, T. N. Kurdyumova, and A. A. E v s e e v a , Khim. G e t e r o t s i k l . Soedin., 50 (1966).

588
SYNTHESIS AND PROPERTIES OF 6-(p-TOLYL)PHENANTHRIDINES
AND 5,1 0- DI (p- TOLYL) DIAZAPYRENES

A. S t o e n e h u , O. Y a . Fedotova, UDC 547.836.3.07:543.422.4

a n d V. V. K o r s h a k

10-Amino-, 10-phthalimido-, and 10- (p-toluamido)- 6- (p-tolyl)phenanthridines and 5,10-di (p-

tolyl)-4,9-diazapyrene, the oxidation of which gives the 4,9-dioxide, were synthesized.

One of the methods for the preparation of derivatives of phenanthridine and 4,9-diazapyrene involves
cyclodehydration of 2, 2'-diacylaminodiphenyls under the influence of phosphorus oxychloride [1].
In order to obtain a heteroaromatic dicarboxylic acid that contains a 4,9-diazapyrene ring and is suit-
able for the preparation of polymers, we synthesized a number of new 6- (p-tolyl)phenanthridines (III-V) and
5,10-di(p-tolyl)-4,9-diazapyrenes (VI. VII).

, ~--N H~ ? ~-~NHCOC6H~CHa- p

121 0
! II

0
I1! IV

~--C6~ C~ p POCl~ ~ e-ca~c,a 4 - c ~ N ~O

p.CHsC~H4COH N ~ 4 3" ~ = p.CHaCaH4 N CsHICH . p ~ O 1 ~ ' ~.,~ 1{- CE'H'~CH3"p

V VI VII

It is known [2] that substituents (CH3, C6H5) generally do not undergo oxidation during the action of
chromic, perphthalic, and peracetic acids, potassium permanganate in acidic media, and sodium dichromate
in glacial acetic acid on 4.9-diazapyrene and its derivatives. Oxidation of 5,10-di(p-tolyl)-4,9-diazapyrene
WI) with potassium permanganate in aqueous pyridine and with hydrogen peroxide in glacial acetic acid
gave, instead of the expected diacid. 5.10-di(p-tolyl)-4,9-diazapyrene 4.9-dioxide (VII). which was identified
by means of IR spectroscopy. It has been established [3] that the stretching vibrations of the NO group of
heterocyclic pyridine N-oxides lie at 1230-1319 cm -1, and the precise value of the frequencies depends on
the degree of substitution and the nature of the substituents in the ring. In the given case, the band at 1365
cm -1 is characteristic for the NO group in 5 , 1 0 - d i ( p - t o l y l ) - 4 , 9 - d i a z a p y r e n e 4.9-dioxide. In addition, bands
at 850 and 1155 cm -1. which sometimes [3. 4] are also assigned to the stretching vibration of the NO group
in N,N-dioxides, were also observed for this compound.

D. I. Mendeleev Moscow Institute of Chemical Technology. Translated from Khimiya Geterotsiklicheskikh

Soedinenii, No. 5. pp. 682-684, May, 1974. Original article submitted October 16, 1972: revision submitted
October 9. 1973.

9 19 75Plenum Publishing Corporation, 22 7 West 17th Street, New York, iV. Y. 1001 l. No part of this publication may be reproduced,
stored in a retn'evaI system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is availablefrom the publisher for $15.00.

589
 N,N-Dioxide VII has the s a m e p r o p e r t i e s as the analogous h e t e r o c y c l i c N-oxides; it does not give a
c o l o r r e a c t i o n with f e r r i c chloride o r with cupric acetate in ethanol [2, 5]. The starting 5,10-di(p-tolyl)-4,9-
diazapyrene was obtained by reduction of VII with iron powder in the p r e s e n c e of glacial acetic acid or with
stannous chloride in the p r e s e n c e of h y d r o c h l o r i c acid.

EXPERIMENTAL
The IR s p e c t r a of KBr pellets of the compounds w e r e r e c o r d e d with a UR-10 s p e c t r o m e t e r .
2-Amino-2'-phthalimidodiphenyl {I). This compound was obtained by the method in [6] by the action
of phthalie anhydride on 2,2'-diaminodiphenyl [7].
2-(p-Toluamido)-2'-phthalimidodiphenyl {II). A m i x t u r e of 9.45 g (0.03 mole) of 2 - a m i n o - 2 ' - p h t h a l -
imidodiphenyl (I). 4.63 g (0.03 mole) of p-toluyl chloride, and 20 ml of chlorobenzene was refluxed until HC1
evolution ceased. It was then cooled, and 80 ml of p e t r o l e u m ether was added. The resulting p r e c i p i t a t e
was r e m o v e d by filtration and washed with alcohol to give a product with mp 253-254 ~ {from chlorobenzene)
in 89% yield. Found %~ C 77.5; H 4.7- N 6.5. C28H20N203. Calculated %-. C 77.4; H 4.6: N 6.5. IR s p e c t r u m
[8], c m - l : 1375, 1450 (Ar-CH3), 1525 (amide II), 1670 (Ar-CONH-), 1710. 1760 (imide ring), 1740 (1,4-At).
6- ~-Tolyl)-10-phthalimidophenanthridine (1YI). A m i x t u r e of 25.9 g (0.06 mole) of II, 46 ml (0.2 mole)
of phosphorus oxyehloride, and 50 rnl of anhydrous nitrobenzene was refiuxed for 16 h, a f t e r which it was
cooled and p o u r e d o v e r ice. The nitrobenzene was r e m o v e d by s t e a m distillation and the residue was worked
up to give a p r o d u c t with mp 231 ~ {from ethanol) in 85% yield. Found %- C 81.2; H 4.4; N 6.8. C28H18N202.
Calculated %: C 81.1; H 4.4: N 6.8. IR spectrum, cm -1$ 1375, 1450 (Ar-CH3): 1570, 1610 (phenanthridine
ring); 1740 (1,4-Ar).
6- (p-Tolyl)-10-aminophenanthridene (IV). A 3 - m l sample of 100% hydrazine hydrate was added drop-
wise in the c o u r s e of 30 rain to a refluxing solution of 8.22 g (0.02 mole) of 6-{p-tolyl)-10-phthalimidophen-
anthridine (III) in 60 ml of alcohol, and the resulting p r e c i p i t a t e was r e m o v e d by filtration and dissolved in
dilute h y d r o c h l o r i c acid. Addition of solid NaOH to the acid solution gave amine IV. with mp 191-192 ~
{from ethanol), in 96% yield. Found %. C 84.5. H 5.7: N 9.8. C20HI6N2. Calculated %: C 84.5; H 5.7; N 9.8.
IR spectrum, c m ' t : 1370, 1450 (Ar-CH3). 1570, 1610 (phenanthridene ring); 1740 (1,4-Ar); 3200, 3310,
3380 (- NH2).
6-{p-Tolyl)-10-(p-toluamido)phenanthridine (V). This compound, with mp 268-269 ~ (from ethanol),
was obtained in 80% yield f r o m 6- {p-tolyl)-10-aminophenanthridine (IV) by the method used to p r e p a r e II.
Found %: C 83.6: H 5.5; N 7.0. C28H22N20. Calculated %. C 83.6: H 5.5: N 7.0. IR spectrum, era-l: 1370,
1450 (Ar-CH3): 1570, 1610 (phenanthridine ring); 1670 ( A r - C O N H - ) : 1740 (1,4-At).
5 , 1 0 - D i ~ - t o l y l ) - 4 , 9 - d i a z a p y r e n e (VI). This compound, with mp 328-329 ~ {from chlorobenzene), was
obtained in 42% yield f r o m 6- (tolyl )-10- (p-toluamido)phenanthridine (V) by the method used to p r e p a r e III.
Found %: C 87.5; H 5.1; N 7.3. C28H20N2. Calculated %: C 87.5; H 5.2: N 7.3. IR spectrum, cm-1; 1370,
1450 (Ar-CH3): 1335, 1445. 1475, 1565, 1635 (4,9-diazapyrene ring): 1740 (1,4-Ar).
5,10-Di(p-tolyl)-4,9-diazapyrene 4,9-Dioxide (VII). A) A m i x t u r e of 3.84 g (0.01 mole) of 5,10-di{p-
t o l y l ) - 4 , 9 - d i a z a p y r e n e {VI), 50 ml of glacial acetic acid, and 10 m_l of 30% hydrogen peroxide solution was
heated at 70 ~ for 8 h. It was then cooled, and 70 ml of distilled w a t e r was added. The mixture was filtered
to give 1.2 g (29%) of a yellow p r e c i p i t a t e with mp 329-331 ~ (dec., f r o m ehlorobenzene). Found %: C 80.9:
H 4.5. N 6.8. C20H20N202. Calculated %: C 80.8 $ H 4.8; N 6.8. IR spectrum, em -~. 1370, 1450 (Ar-CH~)$
1345, 1465, 1490, 1575, 1640 (4,9-diazapyrene ring). 1740 (1,4-At): 850, 1155, 1365 (~N--* O) [9].
B) A m i x t u r e of 3.84 g (0.01 mole) of 5,10-di(p-tolyl)-4,9-diazapyrene (VI), 50 ml of pyridine, and
30 ml of distilled w a t e r was heated to 70 ~ and 50 g of p o t a s s i u m p e r m a n g a n a t e was added in small portions
at such a r a t e that the m i x t u r e boiled gently. Distilled water (20 ml) was then added, and the m i x t u r e was
heated at 90 ~ for 6 h. It was then cooled, and the pyridine was r e m o v e d by s t e a m distillation. The residue
was f i l t e r e d to r e m o v e the p r e c i p i t a t e d manganese dioxide, and the filtrate was evaporated to 40-50 ml.
The residual solution was cooled and t r e a t e d with 20% hydrochloric acid until it was weakly acidic. The r e -
sulting light-yellow precipitate was r e m o v e d by filtration to give 1.1 g (28%) of a substance with rap 330-
331 ~ (dec.), which was identical to the product obtained by method A.

LITERATURE CITED
1. G . S . Matvelashvili. S. F. Belevskfi, O. Ya. Fedotova, and G. S. Kolesnikov, Khim. Geterotsikl. Soedin.,
1044 (1969).

590
2. R. F. Robbins, J. Chem. S.c., 2553 (1960).
3. A. R. Katritzky. J. A. Beard, and N. A. Coates, J. Chem. S.c., 3680 (1959).
4. B. Klein and J. Berkowitz, J. Amer. Chem. S.c., 8_~1, 5160 (1959).
5. M. Gawlak and R. F. Robbins, J. Chem. S.c., 5135 (1964).
6. A. E. S. Fairf~ll, D. A. Peak, W. F. Short, and T. I. Watkins. J. Chem. S.c., 4700 (1952).
7. R. E. Moore and A. Furst, J. Org. Chem., 2_~3.1504 (1958).
8. L. Bellamy, Infrared Spectra of Complex Molecules, Methuen (1958).
9. L. Bellamy. Advances in Infrared Group Frequencies, Methuen (1968).

591
N- P H E N Y L - 1- N A P H T H Y L A M I N E *

S. I. K u t k e v i c h u s a n d E. A. S a m a r s k i s UDC 547.832-542.95

Heating N-phenyl-1-naphthylamine with epichlorohydrin gives N-phenyl-N-(3-chloro-2-hydroxy-

propyl)-l-naphthylamine, which cyclizes with the participation of the phenyl ring.

Heating diphenylamine with epichlorohydrin gives 1-phenyl-3-hydroxy- 1,2,3,4-tetrahydroquinoline

through a step involving N-(3-chloro-2-hydroxypropyl)diphenylamine [2], while the reaction of N-phenyl-2-
naphthylamine with epichlorohydrin gives 1-phenyl- 2-hydroxy- 1,2.3,4-tetrahydrobenzo[f]quinoline [3]. N-
Phenyl-N- (3-chloro-2-hydroxypropyl)-l-naphthylamine (i), which is formed in the case of N-phenyl-1-
naphthylamine, can be cyclized to give both 1-(1-naphthyl)-3-hydroxy-l.2,3,4-tetrahydroquinoline {II) and
1-phenyl-3-hydroxy- 1,2,3,4-tetrahydr obenzo[h]-quinoline (HI).

C6Hs"~NH C6H5-~.N/CH2C HOfl CH 2CI

/o\
CH2--CHCH2CI

/ , _,_J
1
I

~ OH .
i

III II

The aim of the present study was to isolate the intermediately formed 3-chloro-2-hydroxypropyl deri-
vative, to establish the direction of its cyclization, and to study the chemical properties of (I) and (II).
We have shown that primarily (I) is formed when N-phenyl-l-naphthylamine is heated to 65~ with epi-
chlorohydrin in the presence of acetic acid. The chlorine atom in (I) is readily replaced by the action of

/CH~
CH ~ "7/~ ,. 2 CH3

IV

,/CH3

~ H2\CH~ II /O N
CsHs.,.,.N./CH2CHOH CsHs'~.N/CH2CH--CH
2 CgHs~,.N,,-.CH2CHOHCH2CN

VIII VII VI

* Communication XVIII from the series "Investigation of the Products of the Reaction of Epichlorohydrin
with Aromatic Amines." See [1] for communication XVII.
Kaunas Polytechnic Institute. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp.
685-688. May, 1974. Original article submitted May22.1972: revision submitted June 18, 1973.
9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

599
amine dimethylformamide (DMF) [4], potassium cyanide, etc. The transformations of (I) are presented in the
scheme on the previous page.
When (I) is heated to 150~ it cyclizes to (iI). To determine the direction of this cyclization, product
(II) was heated with polyphosphorie acid (PPA). The free base, corresponding t o 1- (1-naphthyl)-l,2, 3,4-
tetrahydroquinoline (IX). was isolated. The formation of (IX) can apparently be explained by disproportiona-
tion [5, 6] of the dihydro compound, which is formed by splitting out of a water molecule from (II). Base
(IX) was synthesized independently by arylation of 1,2, 3,4-tetrahydroquinoline with 1-iodonaphthalene in the
presence of potassium fluoride [7].

X IX

Consequently, the hydrogen in the ortho position in the benzene ring in N-phenyl-N- (3-chlore-2-hy-
droxypropyl)-l-naphthylamine is more active than the hydrogen in the 2 position in the naphthalene ring,
and the 1 position in the naphthalene ring in N-phenyl-N- (3-chloro-2-hydroxypropyl)-2-naphthylamine [3]
is more active than the ortho position of the benzene ring.
The hydroxyl group is replaced by chlorine to give (X) during the action of phosphorus oxychloride
on (II). The corresponding benzoyl (XI) and acetyl (XTI) derivatives were obtained by benzoylation and acet-
ylation of (II). The acetyl derivative (XII) w a s a l s o obtained by the action of sodium acetate in alcohol of X.
Acetyl derivative (XII) is converted to (II) by alkaline saponification.

EXPERIMENTAL
Chromatography was carried out by the thin-layer method and with a column using activity (II) alu-
minum oxide.
N-Phenyl-N-(3-cbloro-2-hydroxypropyl)-l-naphthylamine (I). A) A mixture of II.0 g (0.05 mole) of
N-phenyl-l-naphthylamine, 9.2 g (0.i mole) of epiehlorohydrin, and 6.0 g (0.i mole) of concentrated acetic
acid was heated at 60-65 ~ for 6 days, after which it was treated with water and extracted with ether. The
solvent was removed, and the residue was chromatographed with a column with elution with ether-petroleum
ether (2 : I) to give an oily substance with Rf 0.5, which began to crystallize on prolonged standing in a de-
siccator to give 11.6 g (75%) of a product with mp 71-73 ~ (from petroleum ether). Found %: C1 10.9; N 4.5.
CIgHIsCINO. Calculated ~: C1 11.2: N 4.5.
B) Hydrogen chloride gas was passed into a solution of 13.8 g (0.05 mole) of VII in 50 ml of methanol
for 20 rain. After removal of the methanol. (1) was isolated as in method A. The yield of product with rap
71-73 ~ (from petroleum ether) was 9.2 g (62%). No melting-point depression was observed for a mixture of
this product with the product of method A.
l-(l-Naphthyl)-3-hydroxy-l.2,3,4-tetrahydroquinoline (II). A mixture of 15.5 g (0.05 mole) of (I), and
9.2 g (0.1 mole) of epichlorohydrin was heated at 150 ~ for 5 days, after which it was diluted with water and
extracted with ether. The solvent was removed, and the residue was subjected to column chromatography
with elution by ether-petroleum ether (4 : I) to give 10.3 g (75%) of a substance with mp 108-110 ~ (from
ether) and Rf 0.6. Found %. C 82.9: H 6.3: N 5.1. C19HnNO. Calculated %: C 82.9; H 6.2. N 5.1.
B) A mixture of II.0 g (0.05 mole) of N-phenyl-l-naphthylamine and 9.2 g (0.I mole) of epichloro-
hydrin was heated at 150-160 ~ for 6 days, after which (II) was isolated as in method A to give 8.6 g (62%) of
a product with mp 108-110 ~ (from ether).
C) A mixture of 3.2 g (0.01 mole) of (XII), 1.7 g (0.03 mole) of potassium hydroxide. 25 ml of alcohol,
and 5 ml of water was refluxed for 6 h. after which (II) was isolated as in method A to give 1.9 g (70%) of a
product with nap 108-110 ~ (from ether).
l-[(l-Naphthyl)anilino]-3-dimethylamino-2-prepanol (IV) [4]. A mixture of 4.6 g (0.015 mole) of (I),
4 ml of DMF, and 2 g (0.05 mole) of ground sodium hydroxide was shaken for 15 rain, after which 3 ml of
water was added, and the mixture was heated at 60 ~ for 2 h. Water was then added, and the mixture was ex-
tracted with petroleum ether. The resulting crystals were removed by filtration to give 1.2 g (25%) of a
product with mp 89-90 ~ (from petroleum ether). Found %.- N 8.7. C21H24N20. Calculated %: N 8.8.

593
 ,1-[3- (1-Naphthyl)anilino-2-hydroxypropyl]pyridinittm Chloride (V). A m i x t u r e of 4.7 g (0.015 mole)
of {I), 3.6 g (0.045 mole) of pyridine, and 6 ml of chlorobenzene was heated at 120 ~ f o r 12 h. The resulting
c r y s t a l s w e r e r e m o v e d by f i l t r a t i o n and washed with acetone to give 1.8 g (37%) of a p r o d u c t with mp 268-
269 ~ (from acetone). Found %: C1 9.0: N 7.2. C24I~3C1N20. Calculated %: C1 9.0: N 7.2.
3 - [ (1-Naphthyl)anilino]-2-hydroxybutyronitrile (VI). A m i x t u r e of 15.5 g (0.05 mole) of (I), 20 m l of
methanol, 6.5 g (0.1 mole) of p o t a s s i u m cyanide, and 20 m l of w a t e r was refluxed f o r 3 h. The methanol
w a s r e m o v e d by distillation, and the r e s i d u e was t r e a t e d with w a t e r and e x t r a c t e d with ether. The solvent
was r e m o v e d , and the r e s i d u a l c r y s t a l s w e r e r e m o v e d by filtration to give 10.5 g (70%) of a product with
mp 116-118 ~ (from methanol). Found %: N 9.2. CuoHlsN20. Calculated %: N 9.2.
N - P h e n y l - N - ( 2 , 3 - e p o x y p r e p y l ) - l - n a p h i h y l a m i n e {VII). A) A m i x t u r e of 22.2 g (0.1 mole) of N-phenyl-
1-naphthylamine, 18.4 g (0.2 mole) of epichlorohydrin, and 6 g (0.1 mole) of c o n c e n t r a t e d acetic acid was
heated at 60-65 ~ for 5 days, a f t e r which it was diluted with w a t e r and e x t r a c t e d with ether. The e t h e r solu-
tion was refluxed f o r 3 h with 20 g (0.5 mole) of ground sodium hydroxide, a f t e r which it was washed with
w a t e r . The e t h e r was r e m o v e d , and the r e s i d u e was v a c u u m distilled in a s t r e a m of nitrogen. The f r a c -
tion with bp 206-210 ~ (1 m m ) was collected. The yield was 16.5 g (60%). Found %.. N 5.2. C19HITNO.
Calculated %: N 5.1.
B) A 31.1-g (0.1 mole) s a m p l e of (I) was d i s s o l v e d in 200 ml of ether, 20 g (0.5 mole) of ground sodi-
u m hydroxide was added, and the m i x t u r e was refluxed for 3 h and worked up as in method A to give 19.0 g
(70~) of product.
1 - [ ( 1 - N a p h t h y l ) a n f l i n o ] - 3 - i s o p r o p y l a m i n o - 2 - p r o p a n o l (VIII). A m i x t u r e of 8.3 g (0.03 mole) of (VII)
and 3.5 g (0.06 mole) of i s o p r o p y l a m i n e was m a i n t a i n e d at r o o m t e m p e r a t u r e f o r 6 days, a f t e r which it was
d i s s o l v e d in ether, and the r e s u l t i n g c r y s t a l s w e r e r e m o v e d by filtration and washed with e t h e r to give 4 g
(40%) of a p r o d u c t with mp 102-103 ~ (from ether). Found %: N 8.5. C22H26N20. Calculated %: N 8.4.
1 - { 1 - N a p h t h y l ) - l , 2 , 3 , 4 - t e t r a h y d r o q u i n o l i n e (IX). A) A m i x t u r e of 5.5 g (0.02 mole) of (II) and 28 ml
of polyphosphoric acid (PPA) w a s heated at 200 ~ for 2 h, a f t e r which it was cooled and n e u t r a l i z e d with 50%
sodium hydroxide solution. The m i x t u r e was e x t r a c t e d with ether, the e t h e r was r e m o v e d , and the r e s i d u e
w a s c h r o m a t o g r a p h e d (elution with p e t r o l e u m ether) to give 1.02 g (20%) of a product with mp 134-136 ~
(from methanol) and R f 0.5. Found %: C 87.9: H 6.7: N 5.4. C19HITN. Calculated %: C 88.0: H 6.6: N 5.4.
B) A m i x t u r e of 13.3 g (0.1 mole) of 1,2,3,4~tetrahydroquinoline, 25.4 g (0.1 mole) of iodonaphthalene.
18.03 g (0.31 mole) of anhydrous p o t a s s i u m fluoride, 2 g (0.014 mole) of cuprous oxide, and 1 g (0.016 g-
atom) of c o p p e r powder was s t i r r e d at 220-230 ~ f o r 30 h. It was then cooled, t r e a t e d with water, and ex-
t r a c t e d with ether. The e t h e r was r e m o v e d , and the r e s i d u e was c h r o m a t o g r a p h e d as in method A. Two
r e c r y s t a l l i z a t i o n s f r o m m e t h a n o l g a v e 2.6 g {10%) of c r y s t a l s with mp 134.5-136 ~
1 - { 1 - N a p h t h y l ) - 3 - c h l o r o - l . 2 , 3 , 4 - t e t r a h y d r o q u i n o l i n e (X). A 13.8-g (0.05 mole) s a m p l e of {II) was dis-
solved in 15.2 g (0.1 mole) of p h o s p h o r u s oxychloride, and the m i x t u r e was allowed to stand at r o o m t e m -
p e r a t u r e f o r 2 d a y s . It was then t r e a t e d with ice. n e u t r a l i z e d with 20% sodium hydroxide solution, and ex-
t r a c t e d with benzene. The solvent was r e m o v e d , and the r e s u l t i n g c r y s t a l s w e r e s e p a r a t e d by filtration to
give 5.8 g (40%) of a p r o d u c t with mp 144.5-146 ~ (from benzene). Found %: C1 12.1: N 4.8. C19HI6C1N.
Calculated %, C1 12.1: N 4.8.
1 - ( 1 - N a p h t h y l ) - 3 - b e n z o x y - l , 2 , 3 , 4 - t e t r a h y d r o q u i n o l i n e (XI). A m i x t u r e of 2.8 g (0.1 mole) of {II). 10
m l of pyridine, and 4.2 g (0.03 mole) of benzoyl chloride was heated at 85 ~ f o r 3 h, a f t e r which it was cooled.
t r e a t e d with 20% sulfuric acid solution, and diluted with w a t e r . R e c r y s t a l l i z a t i o n f r o m e t h a n o l - e t h e r (5- 1)
gave 2.3 g (60%) of c r y s t a l s of (XI) with mp 109.5-111 ~ Found %, N 3.8. C26H21NO2. Calculated %, N 3.6.
1-r (XII). A) A m i x t u r e of 2.8 g (0.01 mole) of {II).
12 m l of pyridiue, and 4 g (0.05 mole) of acetyl c h l o r i d e was heated at 70 ~ f o r 2 h. a f t e r which it was t r e a t e d
with 25% s u l f u r i c acid and e x t r a c t e d with ether. The e t h e r was then removed, and the r e s u l t i n g c r y s t a l s
w e r e r e m o v e d by f i l t r a t i o n and washed with e t h e r to give 1.6 g (50%) of a product with mp 130-132 ~ (from
ethanol). Found %: N 4.4. C21H10NO2. Calculated %: N 4.4.
B) A 2.9-g (0.01 mole) s a m p l e of (X) was d i s s o l v e d in 50 m l of ethanol, and an aqueous solution of
sodium a c e t a t e (3.5 g of CH3COONa" 3H20 and 3 m l of water) was added. The m i x t u r e was heated on a
b o i l i n g - w a t e r bath for 12 h. a f t e r which the alcohol was r e m o v e d , and the r e s i d u e was t r e a t e d with w a t e r
and e x t r a c t e d with e t h e r . The r e s u l t i n g c r y s t a l s w e r e r e m o v e d by filtration to give 1.3 g (40%) of a product
with mp 130-132 ~ (from ethanol). No m e l t i n g - p o i n t d e p r e s s i o n was o b s e r v e d f o r a m i x t u r e of s a m p l e s of
(XII) obtained by methods A and B.

594
 LITERATURE CITED

lg S. I. Kutkevichus, K. S. Sherenas, and R. I. Poshyunas, Khim. Geterotsikl. Soedin.. 342 (1973).

2. S. I. Kutkevichus and N. N. Vorozhtsov, Jr., Khim. Geterotsikl. Soedin., 549 (1965).
3. S. I. Kutkevichus, B. I. Milukas, and E. A. Samarskis, Khim. Geterotsikl. Soedin., 1228 (1972).
4. S. I. Kutkevichus and S. I. Rutkauskas, USSR Author's Certificate No. 186,505 (1965). Byul. Izobr.,
No. 19 (1966).
5o S. I. Kutkevichus and K. S. Sherenas. Khim. Geterotsikl. Soedin., 1526 (1970).
6. N. N. Vorozhtsov. Jr.. and S. I. Kutkevichus. Khim. Geterotsikl. Soedin., 374 (1965).
7. N. N. Vorozhtsov, Jr., G. G. Yakobson, and A~ E. Ioffe, USSR Author's Certificate No. 166,585 (1956);
Byul. Izobr.. No. 6, 26 (1957).

595
DIAZO COMPOUNDS OF THE HETEROCYCLIC SERIES

I. 2- (N-NITROSAMINO)BENZIMIDAZOLES

A . M. S i m o n o v , S. N . K o l o d y a z h n a y a , UDC 547.785.5 : 542.958.3

a n d L . N. P o d l a d c h i k o v a

Stable p r i m a r y N - n i t r o s a m i n e s of the benzimidazole s e r i e s were obtained by the action of

sodium amide and isoamyl nitrite on 1-substituted 2-aminobenzimidazoles and subsequent
acidification of the resulting b e n z i m i d a z o l e - 2 - d i a z o t a t e s . The effect of the acidity of the
solution on the activity of the b e n z i m i d a z o l e - 2 - d i a z o n i u m salts f o r m e d f r o m the n i t r o s a -
mines was t r a c e d .

Although p r i m a r y N - n i t r o s a m i n e s of azoles have been known for a long time (see [1] for the l i t e r a t u r e
data), the study of the s t r u c t u r e and p r o p e r t i e s of diazo compounds of azoles with t h r e e or m o r e h e t e r o -
a t o m s in the ring was begun only r e c e n t l y [2-7]: they were unknown in the imidazole s e r i e s .
Considering the ease of c o n v e r s i o n of the various f o r m s of diazo compounds of azoles to n i t r o s a m i n e s
[8], we synthesized t h e i r n i t r o s o derivatives (III) f r o m 2 - a m i n o - l - s u b s t i t u t e d benzimidazoles {I) through
the i n t e r m e d i a t e diazotates (II).* We were able to synthesize diazotates II by the B a m b e r g e r method [9] by
the r e a c t i o n of e x c e s s isoamyl nitrite with the Na derivatives of amines I. In c o n t r a s t to the diazotates of
the benzene s e r i e s , which a r e converted to diazo anhydrides at pH 5.5-7.5 [10], benzimidazolediazotates II
under t h e s e conditions give N - n i t r o s a m i n e s III, which are yellow c r y s t a l l i n e substances that a r e only slight-
ly soluble in organic solvents and b u r s t into flames on heating (see Table 1). Nitrosamines III a r e ampho-
t e r i c and r e a d i l y soluble in dilute acids and alkalis, a m m o n i u m hydroxide, and alcohol solutions of alk-
oxides. When they a r e added to concentrated sulfuric acid they cause an intense blue coloration: this m a y
be used as a qualitative reaction.
The s t r u c t u r e of III~ was confirmed by reduction of some of them to substituted hydrazines V, which
w e r e identified as the benzylidene derivatives (VI).

2. CsHHONO W"/~"'~/\N/~'N=NONa R' ' / ~ \N / \N H--NO

I E I
R' R' R'
l[ II Ill[

"1
Rrr N

R'/~"~/~ ~N/ N H--N=CH--C6 5 NH--NH 2

I
R'
VI V

a R'=CH~, tU'=R'"=H; b R'=R"=CH3, R'"= H, c R'= R" = W"= CH3, d I~'=CH3, R"=
=OCH3, R"=H; e R' =CH3, R"=OC~H~, R'"=H; f R'=C6H5, W'= I~'"= H",g R'=
= CH2C6Hs, R"=I~'=H

* Direct nitrosation, which was s u c c e s s f u l for the p r e p a r a t i o n of 2 - ( N - m e t h y l - N - n i t r o s a m i n o ) - l - m e t h y l -

benzimidazole IV, did not give positive r e s u l t s in the remaining c a s e s .
? Most of these compounds were analyzed for their nitrogen content only, inasmuch as they explode during
attempts to d e t e r m i n e C and H.

R o s t o v State University, Rostov-on-Don. T r a n s l a t e d f r o m Khimiya Geterotsiklicheskikh Soedinenii,

No. 5, pp. 689-692, May, 1974. Original a r t i c l e submitted May 24, 1973.

9 19 75Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy of this article is available from the publisher for $15.00.

596
 The u s e of IR s p e c t r o s c o p y to p r o v e the s t r u c t u r e of HI
p r o v e d to be difficult b e c a u s e of the a b s e n c e of i n f o r m a t i o n on
the a b s o r p t i o n of p r i m a r y n i t r o s a m i n e s and b e c a u s e of t h e i r
Z p o o r solubility in organic solvents. Only the intense band at
3250 c m -I, which is absent in the s p e c t r a of a m i n e s I and n i t r o s -
~ ~ ~ ~ I a m i n e IV, can be c o n s i d e r e d to be sufficiently c h a r a c t e r i s t i c for
n i t r o s a m i n e s Ill. In analogy with the c o r r e s p o n d i n g band of
s e c o n d a r y a m i d e s [11], it can be a s s i g n e d to the absorption of a
bonded NH group, although this band m a y also be due to the v i -
- - ~ ~ oo
Z b r a t i o n of the NH group of the imidazoline ring of the t a u t o m e r i c
i m i n o f o r m [12]. The second a s s u m p t i o n is also c o n f i r m e d by
the s i m i l a r i t y between the UV s p e c t r a of III and 2 - N - n i t r o s i m i n o -
1 , 3 - d i m e t h y l b e n z i m i d a z o l I n e (VII) [13], which is a compound
with a fixed i m i n o s t r u c t u r e .
The s t a b i l i t y of p r i m a r y n i t r o s a m i n e s Ill p r o v e d to be
9 quite high: they a r e stable on prolonged s t o r a g e in the d a r k at
20~ (see [1]). B a s e s of the diethylamine type do not induce
d e n i t r o s a t i o n of t h e s e compounds- the addition of a m i n e s I even
--/ p r o m o t e s stabilization of Ill. Rapid d e n i t r o s a t i o n is o b s e r v e d
during the action of c o n c e n t r a t e d h y d r o c h l o r i c acid. In addition
P to a m i n e I, s m a l l amounts of the 2 - c h l o r o d e r i v a t i v e and the
c o r r e s p o n d i n g benzimidazolone a r e f o r m e d in this e a s e .
r~
o Concentrated sulfuric acid has a different effect on III.
e[ > > > > I P a r t i a l denitrosation is a p p a r e n t l y also o b s e r v e d in this c a s e ;
the r e s u l t i n g a m i n e I then undergoes diazo coupling with the
o s i m u l t a n e o u s l y g e n e r a t e d diazonium salt, and a m i x t u r e of i s o -
(D m e r i c 5- and 6 - a z o b e n z i m i d a z o l e s (of the VIII type) is obtained.
N ~ The l a t t e r also give the a b o v e - m e n t i o n e d blue coloration in con-
c e n t r a t e d sulfuric acid.

cone. H2SO4
Ilia

,=
CH 3
VIII

Azo compounds VIII w e r e isolated f r o m n i t r o s a m i n e Ilia

in 73% yield and p r o v e d to be identical to the p r o d u c t s of " s e l f -
coupling" of a m i n e la p r e v i o u s l y obtained in [15]. The yields of
t~ a z o compounds VIII fall when the sulfuric acid is diluted (50 and
~ m
42% for 75 and 50% acid. r e s p e c t i v e l y , and only t r a c e s of p r o -
ii
ducts in 25% acid solution). P r o d u c t s VIII a r e a p p a r e n t l y f o r m e d
I I ~ N N only at acid concentrations adequate for the generation of the
o active b e n z i m i d a z o l e - 2 - d i a z o n i u m salt, which contains a p r o t o -
o
o nated i m i d a z o l e ring [16]. The n i t r o s a m i n e s a r e not c o n v e r t e d
o o O ~ q q
to azo compounds VIII in acetic acid, but diazo coupling with
r//
o ~d active azo components is p o s s i b l e . Thus IIIa and IIIc r e a c t with
B-naphthol to give the c o r r e s p o n d i n g benzimidazoleazonaphthols
2: (IXa, b). while the f o r m a t i o n of azo compounds with m e s i t y l e n e
~'~,~ ~ ~ .~ can b e detected only by c h r o m a t o g r a p h y . In the a b s e n c e of acids,
I
n i t r o s a m i n e s IV do not undergo diazo coupling. Compounds IV
a r e a p p a r e n t l y c o n v e r t e d to diazouium s a l t s with an unprotonated
i m i d a z o l e ring in acids with a low protonating capacity. The a c -
tivity of t h e s e s a l t s should not be a n o m a l o u s l y high, as also in
=
the e a s e of t h i a z o l e - 2 - d i a z o n i u m s a l t s [17].

597
 EXPERIMENTAL
The IR s p e c t r a w e r e m e a s u r e d with a UR-20 s p e c t r o m e t e r . The s a m p l e s w e r e p r e p a r e d as. 1)
m i n e r a l oil p a s t e s (3700-3800 cm-~). 2) hexafluorobutadiene p a s t e s (1400-1500 c m "t and 2000-3600 c m - I )
f o r III. 3) c h l o r o f o r m solutions (complete s p e c t r u m ) f o r IV.
2 - B e n z i m i d a z o l e n i t r o s a m i n e s (III). A m i x t u r e of 10 m m o l e of a m i n e I [18] and 12 m m o l e (0.47 g) of
ground sodium a m i d e in 30 m l of absolute diethyl ether was refluxed and s t i r r e d v i g o r o u s l y f o r 1 h, a f t e r
which 80 m m o l e (12.4 ml) of f r e s h l y distilled i s o a m y l n i t r i t e in 10 m l of absolute e t h e r was added, and the
m i x t u r e was refluxed f o r 2-3 h. The p r e c i p i t a t e d sodium diazotate (II) was r e m o v e d by filtration, washed
with ether, dried in vacuo, and dissolved with cooling in the m i n i m u m amount of water. The solution was
acidified to pH 6-7 with dilute a c e t i c acid, and the p r e c i p i t a t e d n i t r o s a m i n e (HI) was r e m o v e d by filtration,
washed with ice water, dried, and c r y s t a l l i z e d f r o m acetone o r alcohol (see Table 1).
Reduction of N i t r o s a m i n e s . A 1 0 - m l s a m p l e of 15% acetic acid was added to a m i x t u r e of 10 m m o l e
of n i t r o s a m i n e III and 20 m m o l e (1.3 g) of zinc powder at r o o m t e m p e r a t u r e . A f t e r 30 rain, 13 m m o l e (1.4 g)
of benzaldehyde was added, and the m i x t u r e was shaken at 30-35 ~ f o r another 30 rain. It was then filtered,
and the f i l t r a t e was m a d e alkaline with a m m o n i a until it was weakly alkaline. The y e l l o w - g r e e n c r y s t a l s of
h y d r a z o n e VI w e r e r e m o v e d by filtration, washed with water, and r e c r y s t a l l i z e d (see Table 1).
B e h a v i o r of N i t r o s a m i n e III with R e s p e c t to Sulfuric Acid Solutions. A 0.18-g s a m p l e of n i t r o s a m i n e
I I I a was added in p o r t i o n s , r e s p e c t i v e l y , to 12.5, 25. 50, and 98% sulfuric acid solutions, cooled to 0 ~ A f t e r
the m i x t u r e s had been allowed to stand at r o o m t e m p e r a t u r e for 24 h. they w e r e diluted with a s:nall amount
of w a t e r and t r e a t e d with sodium c a r b o n a t e until they w e r e weakly alkaline. They w e r e then t r e a t e d with
t h r e e 1 0 - 1 5 - m l p o r t i o n s of c h l o r o f o r m , and the c h l o r o f o r m e x t r a c t s w e r e e v a p o r a t e d . The r e s i d u e was
s e p a r a t e d with a column filled with A1203. A b r i g h t - y e l l o w f r a c t i o n was eluted with c h l o r o f o r m , a f t e r which
a z o compound VIII and a m i n e Ia w e r e e x t r a c t e d by refluxing the A1203 in alcohol. The alcohol was r e m o v e d
by distillation, and the r e s i d u e was t r e a t e d with two 5 - m l p o r t i o n s of hot H20, f r o m which amine Ia c r y s -
tallized out on cooling. The r e s i d u e contained a m i x t u r e of i s o m e r i c azo compounds VIII. The yields of the
a z o compounds a r e p r e s e n t e d in the t h e o r e t i c a l p a r t of this p a p e r .
2 - ( N - M e t h y l n i t r o s a m i n o ) b e n z i m i d a z o l e (IV). A 0.35-g (5 m m o l e ) s a m p l e of NaNO 2 was added with
s t i r r i n g at 40-50 ~ in the c o u r s e of 30-40 rain to a solution of 0.2 g (1 m m o l e ) of 2 - N - m e t h y l a m i n o b e n z i m i d -
azole h y d r o c h l o r i d e in 10 m l of w a t e r acidified with two d r o p s of acetic acid. A f t e r 10 rain, the t e m p e r a t u r e
w a s r a i s e d to 60 ~ and then cooled i m m e d i a t e l y . The product was e x t r a c t e d with ether. N i t r o s a m i n e IV was
obtained as l i g h t - y e l l o w c r y s t a l s with mp 88-89 ~ (from p e t r o l e u m ether). The yield was 0.17 g (89~c).
Found %: C 56.5: H 5.3: N 29.4. CgHIoN40. Calculated %: C 56.8. H 5.3: N 29.5.
2- ( 2 ' - H y d r o x y n a p h t h y l a z o ) - l - m e t h y l b e n z i m i d a z o l e (IXa). A 1.7-g (10 m m o l e ) s a m p l e of n i t r o s a m i n e
IVa was added to a cooled (to 10 ~ solution of 1.4 g (10 m m o l e ) of ~-naphthol in 10 ml of glacial CH3COOH.
A f t e r 24 h, the m i x t u r e was diluted to twice its volume with water, m a d e alkaline with ammonia, and f i l t e r e d
to r e m o v e azo compound Xa. The p r o d u c t was purified by c h r o m a t o g r a p h y with a column filled with A1203
and subsequent e x t r a c t i o n f r o m the A1203 with alcohol. The yield of product with mp 197-198 ~ (from butanol)
w a s 2.5 g (79%). Found %: C 71.3: H 4.9, N 18.3. C18HI4N40. Calculated %s C 71.5~ H 4.7. N 18.5.
2 - ( 2 ' - H y d r o x y n a p h t h y l a z o ) - l , 5 . 6 - t r i m e t h y l b e n z i m i d a z o l e (iXb). This compound, with mp 201-203 ~
(from butanol), was obtained in 76~c yield by the method used to p r e p a r e IXa. Found %: C 72.7: H 5.5: N
17.1. C20H18N40. Calculated %: C 72.7, H 5.5; N 17.0.

LITERATURE CITED

1o I. G o e r d e l e r and K. D e s e l a e r s . Chem. Ber., 91, 1025 (1958).

2. H. G e b l e r and I. Gost. Ann., 665, 144 (1963).
3. I. G o e r d e l e r , K. D e s e l a e r s . and H. Ginsberg. Chem. Ber., 93, 963 (1960).
4. I. G o e r d e l e r and M. Roegler. Chem. B e r . , 103, 112 (1970).
5. I . C . Tobin. R. N. Butler. and F. Z. Scott. Chem. Commun.. 112 (1970).
6. R . N . Butler, M. Lambe, and F. Scott, Chem. Ind., No. 1, 628 (1970).
7. M. Lambe. I. C. Tobin, and F. Z. Scott, Chem. Commun., 411 (1970).
8. Houben-Weyl, Methoden der O r g a n i s c h e n Chemic, 10/3, Stuttgart (1965). p. 56.
9. A . E . Chiehibabin and M. D. R y a z a n t s e v . Zh. Russk. F i z . - K h i m . Obshchestva. 47. 1571 (1915).
10. T. Kauffman, H. O. F r i e s t a d , and H. Henkler, Ann., 634, 64 (1960).
11. L. Bellamy. I n f r a r e d S p e c t r a of Complex Molecules, Methuen (1958).

598
12. YU. N. Sheinker, A. M. Simonov, Yu. M. Yutilov, V. N. Sheinker, and I. I. P e r e l ' s h t e i n . Zh. Organ.
Khim., 2, 917 (1965).
13. V.G. Sayapin and A. M. Simonov. Khim. Geterotsikl. Soedin., 1120 (1967).
14. R.N. Williams, R. I. Pace, and G. I. lacoeke, Spectrochim. Aeta, 20, 225 (1964).
15. S.N. Kolodyazhnayaand A. M. Simonov, Khim. Geterotsikl. Soedin., 186 (1967).
16. A.M. Simonovand S. N. Kolodyazhnaya,Zh. Organ. Khim., 3, 1146 (1967).
17. I. Goerdeler and H. Haubrich. Chem. Ber., 93, 397 (1960).
18. A.F. Pozharskii and A. M. Simonov, ChiehibabinAminationof Heteroeycles [in Russian], Rostov-on-
Don (1971).

599
RESEARCH IN THE IMIDAZOLE SERIES

LXXIX.* REACTION OF 8 - T H I O T H E O P H Y L L I N E WITH a - H A L O KETONES

M. I . Y u r c h e n k o , P. M. K o c h e r g i n . UDC 547.857.4'789
a n d A . N. K r a s o v s k i i

It was e s t a b l i s h e d that the r e a c t i o n of 8-theophylline with a - h a l o ketones gives 8 - a c y l a l k y l -

thiotheophyllines o r t h e i r e y c l i z a t i o n p r o d u c t s - thiazolo[2.3-f]xanthine d e r i v a t i v e s - depend-
ing on the conditions u s e d to c a r r y out the r e a c t i o n and the s t r u c t u r e of the halo ketones.
D e r i v a t i v e s of two new h e t e r o c y c l i c s y s t e m s - eyclopentathiazolo[2.3-f]purine and benzothia-
z o l o [ 2 . 3 - f ] p u r i n e - w e r e synthesized f r o m 2 - b r o m o c y c l o p e n t a d i e n o n e and cyclohexanone.
The s t r u c t u r e and the conditions f o r the cyclization of 8-acylalkylthiotheophyllines to t h r e e -
(four)- r i n g compounds w e r e studied. The s t r u c t u r e of the thiazolo[2,3-f]xanthines was p r o v e d
b y r e d u c t i v e desulfuration to 1 , 3 , 7 - t r i a l k y l x a n t h i n e s .

Little study has b e e n devoted to the r e a c t i o n of 8-thioxanthines with a - h a l o ketones [2. 3], w h e r e a s it
s e e m s of g r e a t i n t e r e s t , i n a s m u c h as it opens up p o s s i b i l i t i e s f o r the synthesis of 8-acylalkylthioxanthines
and thiazolo[2,3-f]xanthine d e r i v a t i v e s . We have found that the r e a c t i o n of 8-thiotheophylline (I) with a - h a l o
ketones of the aliphatic, alicyclic, a l i p h a t i e - a r o m a t i c , and h e t e r o c y c l i c s e r i e s p r o c e e d s unambiguously and,
depending on the conditions used ( t e m p e r a t u r e and pH of the medium) and the s t r u c t u r e of the halo ketone.
gives 8-acylalkylthiotheophyllines or t h e i r cyclization p r o d u c t s - t h i a z o l o [ 2 . 3 - f ] x a n t h i n e d e r i v a t i v e s . Thus
8-acylalkylthiotheophyllines (II-XIII, Table 1) a r e obtained in high yields by r e a c t i o n of I with halo ketones
in alcohol or d i m e t h y l f o r m a m i d e (DMF) in the cold and even on heating to 60-100 ~ in the p r e s e n c e of an
alkaline r e a g e n t . Refluxing of thioxanthine I with halo ketones in organic solvents (alcohols, CH3COOH,
DMF) in the a b s e n c e of an alkaline r e a g e n t gives different compounds. 8-Acylalkylthiotheophyllines {VIII-
XIII) a r e f o r m e d in the c a s e of a l i p h a t i c - a r o m a t i c and h e t e r o c y c l i c halo ketones, while the p r o c e s s does not
stop in the f i r s t step with aliphatic and alicyclic halo ketones but p r o c e e d s f u r t h e r with closing of the thia-
zole ring to give the c o r r e s p o n d i n g t h r e e - and f o u r - r i n g compounds (XIV-XVII. XXIII. and XXIV).
This d i f f e r e n c e in the c o u r s e of the r e a c t i o n of I with a - h a l o ketones with different s t r u c t u r e s is ex-
plained by the different tendencies of the acylalkylthiotheophyllines (II-XIII) to undergo cyclization with
closing of a thiazole ring. Compounds I I - V I I a r e r e a d i l y cyclized to t h r e e - and f o u r - r i n g XIV-XVII and
XXIV on refluxing in l o w e r alcohols in the p r e s e n c e of HC1, on heating in POC13 and organic or m i n e r a l
acids (HCOOH, CH3COOH, HC1. HBr, and H3PO4). and a l s o on t r e a t m e n t with cold concentrated H2SO4. In
c o n t r a s t to H-VII, IX-XHI a r e v e r y s t a b l e and c y c l i z e to XVIII-XXII only on prolonged refiuxing in POC13
o r 85-90% H3PO 4.
The closing of the thiazole r i n g is c a t a l y z e d by acids. Thus V does not change when it is refluxed in
ethanol, while u n d e r the s a m e conditions, but in the p r e s e n c e of HC1, it is cyclized a l m o s t quantitatively to
XVI. Thus, t h r e e ( f o u r ) - r i n g compounds (XIV-XVH, XXIII, and XXIV) a r e f o r m e d in the r e a c t i o n of thiotheo-
phylline I with halo k e t o n e s of the aliphatic o r alicyelie s e r i e s in ethanol, while in the p r e s e n c e of alkali,
which n e u t r a l i z e s the evolved HC1 or HBr, the p r o c e s s stops in the f i r s t stop to give acylalkylthiotheophyl-
lines ([I-VII).

* See [1] f o r c o m m u n i c a t i o n LXXVIII.

Z a p o r o z h e Medical Institute. S. Ordzhonikidze All-Union S c i e n t i f i c - R e s e a r c h P h a r m a c e u t i c a l

C h e m i s t r y Institute, Moscow. T r a n s l a t e d f r o m K h i m i y a G e t e r o t s i k l i c h e s k i k h SoedInenii. No. 5. pp. 693-
696, May, 1974. Original a r t i c l e submitted M a r c h 30, 1973.

9 19 75Plenum Publishing Corporation, 22 7 West 17th Street, New York, N.Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

600
 I~/ z 6~WWWW~aW~W I = = d ~ 4 W ~ W 6 W

O)
o

L~
qqqqqqqq~qqqqqqqq~qqqqq
C~
gg~gggggffg~gg~ggggggggg
-o _ _ _ m

~C9
~W

oa

0 ~Z

Z->>~--215
>> 2 1 5 2 1 5 2 1 5 2 1 52 1 5 2 1 5
"'N t'Mx ~rj

601
 It was e s t a b l i s h e d by m e a n s of p h y s i c o c h e m i c a l methods that r i n g - c h a i n t a u t o m e r i s m is c h a r a c t e r i s t i c
f o r II-XIII. T h e s e compounds display the p r o p e r t i e s of k e t c h e s and give d e r i v a t i v e s at the carbonyl group,
f o r example, 2 , 4 - d i n i t r o p h e n y l h y d r a z o n e s (XXV). At the s a m e t i m e , judging f r o m the IR and PMR s p e c t r a
[4, 5], t h e s e k e t o n e s a r e in e q u i l i b r i u m with the c o r r e s p o n d i n g 3-hydroxythiazolino[2,3-f]xanthines insolution.
As a consequence of t a n t o m e r i s m in the 8-thiopurine s e r i e s , closing of the thiazole ring during c y c l i -
zation of II-XIII might have p r o c e e d e d with the p a r t i c i p a t i o n of the NH group in both the 7 and 9 positions of
the p u r i n e r i n g to give thiazolo[2.3-f]xanthines XIV-XXIV and the i s o m e r i c thiazolo[2,3-e]xanthine d e r i v a -
t i v e s . In all c a s e s we i s o l a t e d only one of the i s o m e r s (as m o n i t o r e d by c h r o m a t o g r a p h y ) . The affiliation
of XIV-XXIV with the s e r i e s of thiazolo[2,3-f]xanthine d e r i v a t i v e s was p r o v e d in the c a s e of the reductive
desulfuration of XIV u n d e r the influence of Raney nickel to 7-isopropyltheophylline (XXVI).

EXPERIMENTAL

The IR s p e c t r a of m i n e r a l oil s u s p e n s i o n s of the compounds w e r e r e c o r d e d with a UR-10 s p e c t r o m e t e r .

C h r o m a t o g r a p h y on a fixed l a y e r of s i l i c a gel for XV. XVI, XVIII, and XX was r e a l i z e d in a CC14-
CH3COOH (4: 1) s y s t e m , and the c h r o m a t o g r a m s w e r e developed with iodine v a p o r s . The R f values w e r e :
XV 0.91, XVI 0.94, XVIII 0.83, and XX 0.90.

0 O
CHa\N/~'~___NH O=c/(C"2)'-.CNB~cH3-.N 9 r__N 1__~-~.2)

I H I
CH a CHa
I XXIII, XXIV
0 IRCHX: OR' O
o' ]L II CH J ! . ~oH

I I
CH 3 CH 3

II-XII1

0 0
CH - I CH II
3 " N @ N ~ R' Ni/H a"" N' / " " r : ~ N'~C3H;'"L

I 1
CH3 CHs

XIV-XXH XXVI

XXIII n=-~; XXIV n = 4 ; X=C|, Br

8-Acylalkylthiotheophyllines (II-XIII. s e e Table 1). A) A 0.05-0.055-mole s a m p l e of the a - h a l o ketone

(chloro k e t c h e s w e r e u s e d f o r the s y n t h e s i s of II, VII, and XIII. while b r o m o ketches w e r e used in all of the
r e s t of the c a s e s ) was added to a solution of 0.05 m o l e of I and 0.05 m o l e of sodium ethoxide in 100-150 m l
of ethanol, and the m i x t u r e was s t i r r e d at 60-65 ~ for 1-1.5 h, refluxed for 10 min, and cooled. The p r e c i p i -
t a t e was then r e m o v e d by filtration and washed with w a t e r .
B) A solution of 0.05 m o l e of I and 0.055 m o l e of the a - h a l o ketone in 150 m l of ethanol o r DMF was
s t i r r e d at 18-20 ~ for 5-6 h. a f t e r which it was p o u r e d into water, and the p r e c i p i t a t e was r e m o v e d b y f i l t r a -
tion to give IV and IX in 84 and 79% yields, r e s p e c t i v e l y . Compound IX was isolated in 79-87% yield when I
was refluxed with phenacyl b r o m i d e in ethanol, hexanol, DMF, and glacial CH3COOH for 5-8 h. The sub-
s t a n c e s w e r e p u r i f i e d f o r a n a l y s i s by c r y s t a l l i z a t i o n f r o m aqueous ethanol (II. VII. and IX), ethanol (IV. V.
and VI). butanol (III. X. and XII). dioxane {VIII). o r glacial CH3COOH (XI, XIII).
D e r i v a t i v e s of Thiazolo[2,3-f]-. Cyclopentathiazolo[2,3-f]-, and T e t r a h y d r o b e n z o t h i a z o l o [ 2 , 3 - f ] x a n -
thines (XZV-XXlV, see Table 1). A) A solution of 0.01 m o l e of I and 0.011-0.012 m o l e of a - h a l o ketone (a
c h l o r o ketone was u s e d f o r the s y n t h e s i s of XIV, while a b r o m o ketone was u s e d f o r the s y n t h e s i s of the
other compounds) in 30-60 m l of ethanol was refluxed f o r 4-5 h (in the p r e p a r a t i o n of XIV, XV, and XVII)
o r 7 h (in the p r e p a r a t i o n of XXIII and XXIV), a f t e r which it was cooled, and the p r e c i p i t a t e was r e m o v e d
by filtration. E v a p o r a t i o n of the m o t h e r liquor to a s m a l l volume gave additional amounts of the compounds.
B) A solution of 0.01 m o l e of HI in 15 m l of glacial CH3COOH, 85% HCOOH, concentrated HC1, or
HBr was refluxed f o r 4-5 h, a f t e r which the solvent was r e m o v e d by vacuum distillation. The r e s i d u e was

602
m a d e alkaline with NH3, and the p r e c i p i t a t e was r e m o v e d by filtration and washed with w a t e r . The yield of
XV was 87-98%.
C) A solution of 0.01 m o l e of V or IX in 15 m l of 85% H3PO 4 was heated, r e s p e c t i v e l y , at 95-98 ~ f o r
1 h or at the reflux t e m p e r a t u r e of the m i x t u r e f o r 2.5 h, a f t e r which it was worked up as d e s c r i b e d in
method A. The yields of XVI and XVIII w e r e 93 and 98%.
D) A solution of 2.8 g (0.01 mole) of Ill in 15 m l of 96% H2SO4 was allowed to stand at 18-20 ~ f o r 24 h,
a f t e r which it was worked up as d e s c r i b e d above. The yield of XV was 91%.
E) A m i x t u r e of 0.01 m o l e of IX-XIII in 30-35 m l of POC1S was refluxed f o r 6-10 h, a f t e r which the
POC13 was r e m o v e d by v a c u u m distillation, the r e s i d u e was d e c o m p o s e d with water, and the p r e c i p i t a t e d
XVIII-XXII w e r e r e m o v e d by filtration. The compounds w e r e purified by c r y s t a l l i z a t i o n f r o m e t h a n o l -
CHC13 (XIV), ethanol (XVI), aqueous ethanol (XVII), acetone (XXII), glacial CHsCOOH (XV), butanol (XXI,
XXIV), DMF (XIX, XX, XXIII), or butanol-DMF (1 : 1) (XVIII).
8 - A c e t o n y l m e r c a p t o t h e o p h y l l i n e 2,4-Dinitrophenylhydrazone (XXV). This compound was obtained f r o m
II and 2 , 4 - d i n i t r o p h e n y l h y d r a z i n e in ethanol (after refluxing f o r 1 h). The yield of p r o d u c t with mp 252-253 ~
(from DMF) was 80%. Found %: C 42.8. H 3.7: N 25.0: S 6.8. C16HI6N806S. Calculated %: C 42.8. H 3.6.
N 25.0: S 7.1.
7 - I s o p r o p y l t h e o p h y l l i n e (XXVI). A) A m i x t u r e of 2.37 g (0.01 mole) of the h y d r a t e d p o t a s s i u m salt of
theophylline and 2.55 g (0.015 mole) of isopr~pyl iodide in 30 m l of ethanol was refluxed f o r 8 h, a f t e r which
the solvent was r e m o v e d b y distillation, and the r e s i d u e was washed with water. The yield of XXVI, with
mp 174-176 ~ (from p e t r o l e u m ether) (rap 140 ~ [6]), was 1.44 g (65%). IR s p e c t r u m : 1660, 1700 c m -1 (CO).
Found %: C 53.9: H 6.2; N 25.3. C10HI4N402. Calculated %: C 54.0: H 6.3: N 25.2.
B) A m i x t u r e of 1 g of XIV. 15 g of an alcohol p a s t e of Raney nickel, and 50 m l of ethanol was refluxed
f o r 2 h, a f t e r which it was filtered. The f i l t r a t e was evaporated, and the r e s i d u e was c r y s t a l l i z e d f r o m
p e t r o l e u m ether. The yield of XXVI, with mp 174-176 ~ was 0.7 g (79%). No m e l t i n g - p o i n t d e p r e s s i o n was
o b s e r v e d f o r a m i x t u r e of this p r o d u c t with a s a m p l e of XXVI obtained by method A.

LITERATURE CITED
1. N. P. Grin', A. N. K r a s o v s k i i , and P. M. Kochergin. Khim. G e t e r o t s i k l . Soedin., 1271 (1972).
2. E. Ochiai, Ber., 69. 1650 (1936).
3. A. P. Todd and F. Bergel, J. Chem. S.c., 1559 (1936).
4. L. M. A l e k s e e v a , E. M. P e r e s l e n i , Yu. N. Sheinker, and P. M. Kochergin. M a t e r i a l s f r o m the All-
Union C o n f e r e n c e on the Investigation of the S t r u c t u r e s of Organic Compounds b y P h y s i c a l Methods
[in Russian], Kazan (1971). p. 291.
5. L. M. A l e k s e e v a , E. M. P e r e s l e n i , Yu. N. Sheinker, P. M. Kochergin, A. N. K r a s o v s k i i , and B. V.
K u r m a z . Khim. G e t e r o t s i k l . Soedin.. 1125 (1972).
6. E. Schmidt and W. Schwabe. Arch. P h a r m a c i e , 245, 312 (1907).

603
MASS SPECTRA AND STRUCTURE OF 4-AMINOURACILS

R. A. K h m e l ' n i t s k i i , N. A. Klyuev, UDC 543.51 : 5 4 7 . 8 5 4 . 4

E. A. Kunina, and A. A. Kropaeheva

T h e s t a b i l i t y of t h e m o l e c u l e s of s u b s t i t u t e d 4 - a m i n o u r a c i l s w i t h r e s p e c t t o e l e c t r o n i m p a c t
d e p e n d s o n t h r e e f a c t o r s : t h e r a t i o of t h e v a r i o u s t a u t o m e r i c f o r m s of t h e e x c i t e d m o l e c u l a r
ion, t h e s t a b i l i z i n g e f f e c t of e l e c t r o n - d o n o r s u b s t i t u e n t s b o n d e d t o t h e n i t r o g e n a t o m s i n t h e
u r a c i l m o l e c u l e , a n d t h e p o s s i b i l i t y of t h e e x i s t e n c e o f i n t r a m o l e c u l a r h y d r o g e n b o n d i n g i n
t h e m o l e c u l a r i o n . T h e l a t t e r f a c t o r i s d u e t o t h e d e v e l o p m e n t of t h e c o r r e s p o n d i n g
conformation.

A s t u d y of t h e m a s s s p e c t r a of a n u m b e r of s u b s t i t u t e d 4 - a m i n o p y r i m i d i n e s [1-3] h a s m a d e it p o s s i b l e
t o d r a w d e f i n i t e c o n c l u s i o n s r e g a r d i n g t h e s t r o n g e f f e c t of t h e r a t i o of t h e v a r i o u s t a u t o m e r i c f o r m s of t h e
e x c i t e d m o l e c u l a r i o n o n t h e d i s s o c i a t i v e i o n i z a t i o n . T h e e f f e c t i v e i n f l u e n c e of v a r i o u s f u n c t i o n a l g r o u p s i n
t h e r i n g on t h e i s o m e r i z a t i o n of t h e m o l e c u l a r i o n a n d t h e p a t h of d i s i n t e g r a t i o n i n t h e f i r s t s t e p s h a s a l s o
been noted.
I n t h e p r e s e n t c o m m u n i c a t i o n t h e m a s s s p e c t r a of 4 - a m i n o u r a c i l (I), 4 - a m i n o - 3 - m e t h y l u r a c i l ffl), 4 -
amino-1-methyluracfl (HI), 4, 5 - d i a m i n o u r a c i l (IV), 4, 5 - d i a m i n o - 3 - m e t h y l u r a c i l (V). a n d 4, 5 - d i a m i n o - 1 , 3 -
d i m e t h y l u r a c i l (VI) a r e d i s c u s s e d . T h e m a s s s p e c t r a of t h e s e c o m p o u n d s ( T a b l e 1) w e r e o b t a i n e d f o r t h e

T A B L E 1. M a s s S p e c t r a of A m i n o - S u b s t i t u t e d U r a c i l s *
4-Aminouracil (I)
26 (7,5), 27 (29,2), 29 (34,2), 30 (10,0), 31 (66,7), 36 (9,6), 38 (5,8), 39 (12,9), 40 (20,8),
4t {38,3) 42 (42,5), 43 (100,0), 45 (24,2), 46 (8,6), 51 (3,3), 53 (3,3), 54 (2,5), 55 (14,2),
56 (8,3), 57 (13,3), 60 (10,3), 61 (3,3), 65 (2,1), 66 (3,3), 67 (9,2), 68 (43,3), 69 (4,6),
71 {5,6), 73 (3,3), 79 (4,6), 81 (4,2), 82 (2,5). 83 (6,7), 84 (16,7). 85 (8,8), 87 {2,5).
95 (2,5), 97 (5,0), 98 (3,3), 99 (20,8), 100 (3,8), 109 (3,3), Ill (3,3), 127 (83,3), 128 (6,3)
4-Amino- 3- methyluracfl (II)
27 (8,6), 29 (6,1), 30 (35,5), 31 (5,1), 39 (4,6), 40 (19,4), 41 (32,3), 42 (32,3), 43 (16,5),
52 (3,6), 53 (5,1), 54 (6,3), 55 (17,6), 56 (8,2), 57 (45,2), 58 (4,9), 68 (21,7), 69 (8.6),
70 (14,8), 82 (75,8), 83 (4,9), 97 (12,5), 98 (21,7), ll3 (8,6), 141 (100,0), 142 (7,9)
4-A mino-l-methyluracil (HI)
27 (5,9), 29 (8,9), 3,3 (10,5), 39 (5,3). 40 (16,0), 41 (24,5), 42 (30,6), 43 (48,4), 45 (4,4),
54 (3,3), 55 (8,7), 56 (13,3), 57 (4,3), 58 (6,3), 67 (5,9), 68 (64,5), 69 (8,7), 70 (3,1).
84 (46,8), 85 (5,9), 98 (4,3), 99 (3,5), lll (19,7), 112 {6,6), ll3 (10,2), 141 (100.0), 142 (8,4}
4,5-Diaminouracil (IV)
26 (5,5), 27 (15,2), 29 (19,5), 39 (4,8), 31 (9,5), 39 (5,7), 41 (19,5), 42 (18,6), 43 (85,6),
45 {25,5), 46 (5,0), 51 (6,0), 53 (6,4), 54 (9,0), 55 (17,4), 56 (8,3), 57 (16,2), 60 (12,9),
G7 {5,7), 68 (3,8), 69 (16,4), 70 (13,3), 71 (73,8), 72 (6,7), 73 (9,5), 77 (12,9), 78 (4,8),
81 {7,4), 82 (5,5), 83 (9,5), 84 (5,0), 85 (5,7), 87 (3,8), 95 (5,0), 96 (4,3), 97 (11,4), 98 (6,4).
99 {4,8), 100 (3,8), 105 (13,3), III (4,0), 114 (2~,3), 122 (5,5), 125 (10,2), 129 (4,5),
142 (100,0), 143 (9,0), 147 (4,0), 148 (4,5), 149 (6,2)
4,5-Diamino-3-methyluracil (V)
27 (6,5), 29 (13,2), 30 (36,2), 40 (3,5), 41 (5,0), 42 (21,3). 43 (38,3), 45 (8,0), 53 (II,3).
54 (6,9), 55 (12,7), 56 (17,4), 57 (66,0), 58 (66,0), 68 (5,9), 69 (4,8), 70 (8,6), 71 (4,1).
83 (4,8), 84 (9,8), 85 (16,5), III (4,3), 139 (15,6), 156 (100,0), 157 (8,3)
4, 5-Diamino- 1,3-dimethylur acil (VI)_
27 (3,6), 29 (7,6), 30 (25,7), 41 (3,8), 42 (18,1), 43 (22,7), 53 (6,7), 54 (4,7), 55 (I0,2),
56 (15,5), 57 (45,7), 58 (83,9), 59 (6,1), 68 (4,4), 69 (3,4), 70 (5,1), 83 (4,4), 84 (14,0),
8.5 (22,2), 170 (I'00,0), 171 (9,5)

* T h e p e a k s w i t h i n t e n s i t i e s g r e a t e r t h a n 3% of t h e m a x i m u m p e a k
are presented.

K. A . T i m i r y a z e v M o s c o w A g r i c u l t u r a l A c a d e m y . T r a n s l a t e d f r o m K h i m i y a G e t e r o t s i k l i c h e s k i k h
S o e d i n e n i i . No. 5, p p . 6 9 7 - 7 0 1 , M a y , 1974. O r i g i n a l a r t i c l e s u b m i t t e d F e b r u a r y 20, 1973.

9 1975 PlenumPublishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

604
 TABLE 2. W M and St/2 Values ~md Intensities of the C h a r a c t e r i s t i c
Ions* i n t h e M a s s Spectra of I-III for an I o n i z i n g - E l e c t r o n Energy of
70 eV
Compound
I II III
Ionic composition R=H R=H R=CHa
R'=H R'=CHa R'=H
R"= NH_, R"=NH2 R"=NH~

WM 11,1 18,0 20,0

&/2 <6,0 5,0 4,0
Structure C (path 1)
M - RNCO)+ %2 3,9 9,4
fragment ion d)
(d-R") + 5,8 13,6 12,9
(d- CO) + 1,1 2,7 2,7
[(d-CO) -R"] + 2,8 1,1 3,2
(d- C2HO) + 13,3 8,1 9,7
(d-R"CN) + 5,7 1,5 6,1
(M- RR'N~CO)+
(fragment ion 0 1,4 1,5 1,7
(f-H) + 5.8 3,9 19,9
(I-co)+ 5,1 5,8 4,9
El 43,2 42,1 63.5
Structure D (path 2)
~M- co) +
fragment ion k) 2s 1,5 2,0
(M- C2H20) + 1,2 0,5 0,6
(k--R'N=NR) + 1,4 1,5 1,7
I(k-R'N=NR) -CO] + 5,1 5,8 4,9
2]2 10,5 9,3 9,2
EriE2 4,3 ] 4,5 6,9

* In p e r c e n t of the t o t a l c u r r e n t .

f i r s t t i m e u n d e r s p e c t r a l r e c o r d i n g c o n d i t i o n s s i m i l a r to t h o s e d e s c r i b e d in [2, 3]. F o r a m o r e c o r r e c t
c o m p a r i s o n , we a l s o o b t a i n e d t h e m a s s s p e c t r u m of u r a c i l i t s e l f , w h i c h was d i s c u s s e d i n d e t a i l i n [4].
T h e s t a b i l i t i e s of the m o l e c u l e s of I - V I r e l a t i v e to e l e c t r o n i m p a c t (WM), w h i c h a r e the r a t i o s of the
i n t e n s i t y of t h e p o l y i s o t o p i c p e a k of the m o l e c u l a r i o n to t h e t o t a l c u r r e n t i n p e r c e n t , and t h e d i s i n t e g r a t i v e
s e l e c t i v i t i e s (S1/2), which a r e e q u a l to the n u m b e r of the m o s t i n t e n s e p e a k s in the m a s s s p e c t r a t h a t c o n -
s t i t u t e h a l f of the t o t a l ion c u r r e n t , a r e g i v e n i n T a b l e s 2 and 3. The i n t e n s i t i e s of the p e a k s of s o m e c h a r -
a c t e r i s t i c ions a r e a l s o p r e s e n t e d i n T a b l e s 2 and 3.
It is known that p r e d o m i n a n c e of the keto f o r m is c h a r a c t e r i s t i c f o r 2 . 4 - d i h y d r o x y p y r i m i d i n e s , b u t i n
o u r e x a m i n a t i o n of the d i s s o c i a t i v e i o n i z a t i o n of t h e s e c o m p o u n d s we a l s o took i n t o a c c o u n t the p o s s i b i l i t y
of the e x i s t e n c e of a n e x c i t e d m o l e c u l e as one of the m o n o e n o l f o r m s . A m i n o - - s u b s t i t u t e d u r a c i l s m a y a l s o
e x i s t in the i m i n e f o r m , but the t a u t o m e r i c e q u i l i b r i u m is p r o b a b l y s h i f t e d m o r e i n f a v o r of t h e f o r m a t i o n
of the a m i n o f o r m b e c a u s e of the s l i g h t l a b i l i t y of t h e h y d r o g e n a t o m s of the a m i n o g r o u p . T h u s the 4-
a m i n o u r a c i l m o l e c u l e i n the e x c i t e d s t a t e m a y e x i s t i n d i f f e r e n t t a u t o m e r i c f o r m s ( s t r u c t u r e s A-D), and the
s t a b i l i t y of the m o l e c u l a r ion and the p a t h of d i s i n t e g r a t i o n a r e t h e n d e t e r m i n e d to a c o n s i d e r a b l e e x t e n t b y
t h e p r e d o m i n a n c e of o n e o r a n o t h e r s t r u c t u r e .

F o r e x a m p l e , the i n t r o d u c t i o n of a n a m i n o g r o u p into the 4 p o s i t i o n of the u r a c i l r i n g l e a d s to a s h a r p

d e c r e a s e i n t h e W M v a l u e (23.7 f o r u r a c i l and 11.1 f o r I). T h i s d e c r e a s e in t h e s t a b i l i t y is a s s o c i a t e d not

OH olt 6

H
A B1 B2

H~N~/ HN
O Nit-- O NH2
H H
D C

605
 T A B L E 3. W M a n d St/2 V a l u e s and I n t e n s i t i e s of t h e C h a r a c t e r i s t i c
I o n s * in t h e M a s s S p e c t r a of I V - V I f o r an I o n i z i n g - E l e c t r o n E n e r g y
of 70 eV
Compound
IV V VI
Ionic composition R=H R=H R=CH~
R'=H ~ R'~CH~ R'=CH3

12,9 18,8 [ 22,1

S,/2 9.0 4,0 ! 3,0
Disintegrative processes observed at 70 and 15 eV
fM- NH3)+ 1,3 2,9
(3'I-CONRCO) + 9,6 3,1 4,9
(/~aKment ion g)
---14), 1,7 1,8 3,1
(g-2H)+
{g-HC,N)+
2,1
8,4
I
0,9
12.4
0,9
18,3
[(g-HCN) --R']+ 11,1 7,2 5,0
Disintegrative processes observed only at 70 eV
[(g-- HCN) -,H]+ or
[ ( g - H) -- HCN]+ II,I 12,4 I0,I
[(g-HCN)-2H]+ or
[ ( g - H) - HzCN]+ 2,4 3,3 3,4
[ ( g - HEN) - NH2]+ 4,0 4,0

* In p e r c e n t of t h e t o t a l c u r r e n t .

o n l y w i t h an i n c r e a s e in t h e v o l u m e o f t h e m o l e c u l e and t h e a p p e a r a n c e of an a d d i t i o n a l c h s n n e l f o r d i s i n -
t e g r a t i o n b u t r a t h e r with t h e p o s s i b i l i t y of the e x i s t e n c e of I in i m i n e f o r m D. T h e h i g h e r W M v a l u e s f o r
II and III (18.0 and 20.0 r e s p e c t i v e l y ) a s c o m p a r e d with I a r e a s s o c i a t e d with the s t a b i l i z i n g e f f e c t of t h e
e l e c t r o n - d o n o r m e t h y l s u b s t i t u e n t a t t a c h e d to the n i t r o g e n a t o m . A n e f f e c t of t h i s s o r t w a s p r e v i o u s l y o b -
s e r v e d f o r N - m e t h y l d e r i v a t i v e s of p i p e r i d i n e [5] and i n d o l e [6].
One m i g h t h a v e e x p e c t e d a d e c r e a s e i n t h e W M v a l u e w i t h t h e i n t r o d u c t i o n of a s e c o n d a m i n o g r o u p
i n t o the r i n g of t h e u r a c i l m o l e c u l e , e s p e c i a l l y s i n c e t h e s e l e c t i v i t y of t h e d i s i n t e g r a t i o n of IV f a l l s s h a r p l y
($1/2 of I i s 6.0 a s c o m p a r e d w i t h 9.0 f o r IV). H o w e v e r . t h e s t a b i l i t y of t h e IV m o l e c u l e w i t h r e s p e c t t o e l e c -
t r o n i m p a c t i n t h i s c a s e not o n l y d o e s not d e c r e a s e but, on t h e c o n t r a r y , i n c r e a s e s b y 16 r e l . %: t h e W M
v a l u e of IV is 12.9. T h i s f a c t p r o v i d e s e v i d e n c e t h a t t h e d e v e l o p m e n t of a n e w c h a n n e l of d i s i n t e g r a t i o n i s
n o t a f a c t o r t h a t d e t e r m i n e s t h e c h a n g e i n W M . S t a b i l i z a t i o n of t h e m o l e c u l a r i o n i s m o s t l i k e l y r e a l i z e d
t h r o u g h c o n f o r m a t i o n a l p h e n o m e n a , which, in t h e g e n e r a l c a s e . m u s t b e t a k e n into a c c o u n t in the s a m e w a y
a s t h e p r e s e n c e of t a u t o m e r i c s t r u c t u r e s . A n e x a m i n a t i o n of D r e i d i n g m o d e l s s h o w s t h a t t h e r e l a t i v e o r i -
e n t a t i o n of the 4 - a m i n o and c a r b o n y l g r o u p s in IV a l l o w s f o r t h e p o s s i b i l i t y of t h e e x i s t e n c e of an i n t r a m o - -
l e c u l a r h y d r o g e n bond t h a t s t a b i l i z e s t h e r i n g .
T h e p r e s e n c e of one o r t w o m e t h y l s u b s t i t u e n t s a t t a c h e d t o t h e r i n g n i t r o g e n a t o m s (V and VI) i n -
c r e a s e s W M (18.8 and 22.1, r e s p e c t i v e l y ) , and t h i s s o r t of p h e n o m e n o n w a s o b s e r v e d f o r m o n o a m i n o - s u b ~
s t i t u t e d u r a c i l s (II and III).
T h e d i s i n t e g r a t i o n of I - I I I m a y p r o c e e d v i a two p a t h s : f r o m t h e m o l e c u l a r i o n of s t r u c t u r e C w i t h
l o c a l i z a t i o n of t h e p o s i t i v e c h a r g e on t h e o x y g e n a t o m in t h e u r a c i l m o l e c u l e ~oath 1) and f r o m s t r u c t u r e D,
in w h i c h t h e c h a r g e i s l o c a l i z e d on t h e i m i n o g r o u p (path 2). The prevailing tautomeric form is the molecular
i o n w i t h s t r u c t u r e C. T h e r a t i o of t h e s u m s of t h e f r a g m e n t ions obtained during disintegration via a me-
c h a n i s m p r o c e e d i n g v i a p a t h 1 i s g r e a t e r b y a f a c t o r of f o u r to s e v e n t h a n t h e s u m of the f r a g m e n t i o n s
f o r m e d a s a r e s u l t of d i s i n t e g r a t i o n v i a p a t h 2.
A s t h e i o n i z i n g - e l e c t r o n e n e r g y d e c r e a s e s (to 15 eV). t h e i n t e n s i t i e s of t h e p e a k s of i o n s w i t h m a s s e s
113, 99. 98. 84. and 69 ( s t r u c t u r e s d. f, and k). w h i c h a r e f o r m e d in t h e f i r s t s t e p s of the d i s i n t e g r a t i o n , i n -
c r e a s e b y a f a c t o r of two o r t h r e e . T h e m a j o r i t y of t h e p a t h s of d i s i n t e g r a t i o n of t h e m o l e c u l a r ion a r e c o n -
f i r m e d b y t h e p r e s e n c e of t h e c o r r e s p o n d i n g m e t a s t a b l e p e a k s . T h e m a x i m u m p e a k i n t h e s p e c t r a of I - I I I
i s t h e m o l e c u l a r ion p e a k .
I s o m e r i c c o m p o u n d s II and III a r e r e a d i l y i d e n t i f i e d f r o m t h e p r e s e n c e of i n t e n s e p e a k s of i o n s w i t h
m a s s e s 98 and 82 f o r II a n d 84 and 68 f o r III, w h i c h a r e f o r m e d a s a r e s u l t of d e t a c h m e n t of an R N C O p a r -
t i c l e f r o m t h e m o l e c u l a r i o n and s u b s e q u e n t d e t a c h m e n t of an R" p a r t i c l e . Thus, t h e p o s i t i o n of the m e t h y l
g r o u p (R o r R ' ) in t h e u r a c i l r i n g i s f i x e d c l e a r l y d u r i n g t h e a n a l y s i s of t h e m a s s s p e c t r a of t h e s e i s o m e r s .
D e t a c h m e n t of a n e u t r a l CO p a r t i c l e f r o m t h e m o l e c u l a r i o n i s p o s s i b l e o n l y when the m o l e c u l a r ion
o f I - I l l e x i s t s in t h e f o r m of s t r u c t u r e D.

606
 In contrast to the uracil m o l e c u l e itself and the m o l e c u l e s of I-Ill, w h e r e the p o s i t i v e charge in the
m o l e c u l a r ion is l o c a l i z e d p r i m a r i l y on the oxygen atom (structure C), during the disintegration of IV-VI
the charge is concentrated p r i m a r i l y on one of the nitrogen a t o m s of the amino group. A study of the dis-
s o c i a t i v e ionization of these compounds l e a d s to the c o n c l u s i o n that the structure o f the m o l e c u l a r ion c o r -
r e s p o n d s p r i m a r i l y to imine structure D (Table 3).
Thus the m o l e c u l a r ion in the investigated s e r i e s of compounds (I-VI) exists as t a u t o m e r i c f o r m s with
s t r u c t u r e s C and D. The peaks of f r a g m e n t ions, the f o r m a t i o n of which is a s s o c i a t e d with elimination of an
RNCO p a r t i c l e f r o m the m o l e c u l a r ion (structure d for I-III), and the peaks of quite a number of fragment
ions of s e c o n d a r y origin,
R--N--N--R' ~)" O
\ /C II ~i
- I1 R"N~ R'N/~'~ O%,~--CH2
o ]" 11 - = O:/NN/'~N
O'/NI~/ "R"
;/ i + . - %
H t R ' N ~ NH" ~IN+"
"f ~ R' r' R'

L
+O~C--CH=C=N H C R
, , .
7+ "4-RNCO D
%~x
-
t
iO+
d~ O+
~ /N\ +. /~C
+ -(o=c=(~.) " o=c c=n. O= =~h
R,N=CR" -R",
"~ \N / I
* --CO
, R" C [
I II r' _it
R,C=C=O74. R' N
R'
CH~=C~NH
-

I R=H, R'=H, R"=NH2;

+ . 9 II R=H, R'=CH3,R"=NII2,
CH=C-NR' -R" +
I , "' CH=C=NR' I I I R=CH3,R'=H, R"=NH2
R"

which a r i s e d i r e c t l y f r o m s t r u c t u r e d, a r e absent in the m a s s s p e c t r a of these compounds.

The i n c r e a s e in the selectivity of disintegration of the IV-VI molecules as the i o n i z i n g - e l e c t r o n energy
d e c r e a s e s makes it possible to determine the m e c h a n i s m of dissociative ionization and to d e s c r i b e the f o r -
mation of the c h a r a c t e r i s t i c ions in the f i r s t stages. The number of disintegrative paths is confirmed by
the p r e s e n c e of the c o r r e s p o n d i n g m e t a s t a b l e peaks.
The dissociative ionization of i s o m e r i z e d m o l e c u l a r ion D (the imine form) c o m m e n c e s with d e s t r u c -
tion of the u r a c i l ring with elimination of a neutral CONRCO particle; this leads to the f o r m a t i o n of a cyclic
ion radical with m a s s [M- (CONRCO)] + (structure g). The indicated f r a g m e n t disintegrates via two paths:
1) by a p r o c e s s a s s o c i a t e d with s u c c e s s i v e loss of two hydrogen atoms, wMch leads to the formation of the
c o r r e s p o n d i n g f o r m s of the t r i a z o l e ion: 2) by elimination of a neutral HCN p a r t i c l e with the development
of an ion with m a s s (g-HCN) + and subsequent detachment of an R' radical f r o m this f r a g m e n t to give an ion
of the H E - C - N H 2 f o r m .

o -]~ ~ oII
R~N~NH2

IV-VI I l

*I -CONRCO OI[-NHa

/cH=~H II
/C.=N7 t ,_. r'-n~cn--nH~ r\n-"~. ' +

P'--N\CH=NI -H R'--N\CH= !
~CN R'
R'--N~CH7 +
N R'N~CH -
+ -NH2 [ R,N=CH--NH 2I t ~--H R,N=C=NH 2
+

HN~C--NH2
_. ~ N~C--NH27"
R'N= ~NH
]+.

All of the p r o c e s s e s d e s c r i b e d above are l o w - e n e r g y p r o c e s s e s , inasmuch as they p r o c e e d under

conditions of b o m b a r d m e n t by 20 and 15 eV electrons, during which the fraction of s t r u c t u r e g in the total
ion c u r r e n t of the ion r a d i c a l itself i n c r e a s e s by a f a c t o r of two to four f o r a nominal i o n i z i n g - e l e c t r o n en-
e r g y of 15 eV. and this peak b e c o m e s s e c o n d a r y in intensity (after the m o l e c u l a r peak) in the s p e c t r u m .

607
 LITERATURE CITED
1. R. A. Khmel'nitsldi, E. A. Kunina, A. B. Belikov, and Yu. P. Shvaehkin, Izv. Timiryazeva Sel'skokhoz.
Akad. No. 2. 231 (1971).
2. R. A. Khmel'nitskii. N, A. Klyuev, E. A. Kunina, and A. A. Kropacheva, Khim, Geterotsikl. Soedin.,
1689 (1973).
3. R. A. Khmel'nitskii. N. A. Klyuev, E. A. Kunina, and A. A. Kropacheva, Khim. Geterotsild. Soedin.,
127 (1974).
4. J. M. Rice. G. O. Dudek. and M. Barber, J. Amer. Chem. Soc., 87, 4569 (1965).
5. R. A. Khmel'nitskii. N. A. Klyuev. S. B. Nikitina, and A. I. Vinogradova, Zh. Organ. Khim., 7, 391
(1971).
6. J. C. Powers, J. Org. Chem., 38, 2044 (1968).

608
HETEROCYCLIC ANALOGS OF PLEIADIENE
XIII.* NITRATION OF ACEPERIMIDINE AND ITS DERIVATIVES

V. N. Koroleva and A. F. Pozharskii UDC 547.856.7 : 542.958.1

A c e p e r i m i d i n e and its 1- and 2 - s u b s t i t u t e d d e r i v a t i v e s a r e n i t r a t e d in the 4 and 9 positions to

give m o n o - or dinitro d e r i v a t i v e s , depending on the amount of nitric acid.

V e r y little study has been devoted to electrophilic substitution in the p e r i m i d i n e s e r i e s [2, 3]. The
r e s u l t s of q u a n t u m - m e c h a n i c a l calculations show that the r e a c t i v i t i e s of the 6 and 7 and 4 and 9 positions in
p e r i m i d i n e with r e s p e c t to electrophilic p a r t i c l e s should be c l o s e [4, 5]. In o r d e r to s i m p l i f y the analysis
of the s t r u c t u r e s of the s u b s t a n c e s f o r m e d and to s e l e c t a method, we t h e r e f o r e began an investigation of
electrophflic substitution r e a c t i o n s with a e e p e r i m i d i n e (Ia). in which the 6 and 7 positions a r e blocked. In
the p r e s e n t study we have examined the nitration o f a c e p e r i m i d i n e and its 1- and 2 - a l k y l - s u b s t i t u t e d
derivatives.

I a-d II a - d I|1 a - c

l"ll| a R = R ' = H ; b R=CH3, b R ' = H ; c R = H , R ' = C H 3 ; I,II d R = R ' = C f f y

The action of nitric acid at r o o m t e m p e r a t u r e on an acetic acid solution of Ia p r e c i p i t a t e d a c e p e r i m i -

dine nitrate, which was c o n v e r t e d to n i t r o compound IIa when it was introduced into c o n c e n t r a t e d sulfuric
acid at - 8 ~ The yield of IIa, however, does not exceed 40% under these conditions. In addition, e x p e r i -
m e n t s in sulfuric acid a r e difficult to reproduce, a p p a r e n t l y b e c a u s e of the fact that concentrated sulfuric
acid, as we will point out in one of our following communications, p r o t o n a t e s p e r i m i d i n e in the 4 (9) and
6 (7) positions, and in the p r e s e n c e of an oxidizing agent (HNO3) a c o n s i d e r a b l e portion of the s t a r t i n g c o m -
pound undergoes profound t r a n s f o r m a t i o n s with the disrupted (as a r e s u l t of protonation) a r o m a t i c s t r u c t u r e .
This p r o b a b l y explains the fact that n i t r o compound IIa could not be obtained by d i r e c t nitration of a e e p e r -
imidine with nitric acid o r p o t a s s i u m n i t r a t e .
It is c o n s i d e r a b l y m o r e convenient to u s e glacial acetic acid instead of sulfuric acid in the nitration
of a c e p e r i m i d i n e s . Up to 50% of m o n o n i t r o compound II and a s m a l l amount (7-17%) of dinitro d e r i v a t i v e
III a r e obtained for an e q u i m o l a r r e a g e n t ratio. Mononitration p r o c e e d s only in v e r y dilute solutions (less
than 0.5-1%) b e c a u s e of the low solubility of the n i t r a t e of the s t a r t i n g a c e p e r i m i d i n e . Thus if Ia is p r e s e n t
as 7% of the total amount of acetic acid used. p r a c t i c a l l y no nitration o c c u r s even at 100 ~ f o r 6 h.
Resinffieation of the p e r i m i d i n e s during nitration is undoubtedly a consequence of t h e i r high s e n s i t i v i t y
to oxidizing agents [2]. I n a s m u c h as the nitro group i n c r e a s e s the r e s i s t a n c e of the compounds to the action
of oxidizing agents, the introduction of a second n i t r o group into the a c e p e r i m i d i n e s o c c u r s without r e s i n i f i -
cation and in c o n s i d e r a b l y higher yield. F o r example, the yield of 1 - m e t h y l - 4 , 9 - d i n i t r o a c e p e r i m i d i n e in
the n i t r a t i o n of 1 - m e t h y l - 4 - n i t r o a c e p e r i m i d i n e is 80%.

* See [1] f o r c o m m u n i c a t i o n XII.

R o s t o v State University, R o s t o v - o n - D o n . T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii.

No. 5, pp. 702-705. May. 1974. Original a r t i c l e submitted June 21, 1973.

I
9 1975Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

609
 The s e l e c t i o n of the s t r u c t u r e of the m o n o n i t r o a c e p e r i m i d i n e s as 4(9) i s o m e r s r a t h e r t h a n 5(8) i s o -
m e r s was m a d e on the b a s i s of the following data: 1) all of the q u a n t u m - m e c h a n i c a l indexes of the r e a c t i v i t y
a r e c o n s i d e r a b l y m o r e f a v o r a b l e with r e s p e c t to electrophflic substitution f o r the ortho r a t h e r than for the
m e t a p o s i t i o n s of the naphthalene ring: 2) n i t r o p e r i m i d i n e s a r e deeply c o l o r e d o r c r i m s o n colored, which
indicates the p r e s e n c e of d i r e c t conjugation between the donor 7r s y s t e m of the h e t e r o r i n g and the n i t r o
group [the l a t t e r is p o s s i b l e in the 4(9) i s o m e r but not in the 5(8) i s o m e r ] : 3) the band of the NH group in the
IR s p e c t r a of dilute c h l o r o f o r m solutions of n i t r o p e r i m i d i n e s IIa,b and IIIa,b is b r o a d e n e d and is o b s e r v e d
at 3325-3335 e m -1, which is m o r e than 100 c m -1 l o w e r than the VNH band in the s p e c t r a of I. This is m o s t
likely a s s o c i a t e d with the f o r m a t i o n of a weak i n t r a m o l e c u l a r hydrogen bond, which is p o s s i b l e only in the
4(9) i s o m e r .

--N~!

0
ua,b

Both of the ring p r o t o n s in the PMR s p e c t r u m of d i n i t r o a c e p e r i m i d i n e HIa give one signal: this a t t e s t s
to t h e i r equivalence and, consequently, to the identical c h a r a c t e r of the two n i t r o groups, which a r e thus
situated in the 4 and 9 positions.
In the nitration of 1 - m e t h y l a c e p e r i m i d i n e {Ic) with an e q u i m o l a r amount of nitric acid the n i t r o group
e n t e r s e x c l u s i v e l y the s t e r i e a l l y l e s s hindered 4 position. This is evidenced both by the v e r y fact of the
f o r m a t i o n of only one i s o m e r , despite the c l o s e values of the v - e l e c t r o n density in the 4 and 9 positions of
1 - m e t h y l p e r i m i d i n e s [4, 5], and by the f o r m a t i o n of e x c l u s i v e l y the s a m e i s o m e r during methylation of
n i t r o compound I I a in alkaline m e d i a . In the l a t t e r c a s e , the n i t r o group should i n t e r f e r e with methylation
at the n e a r e s t nitrogen a t o m not only due to s t e r i c hindrance but also due to its own s t r o n g inductive effect.
We obtained a s m a l l amount of 1 - m e t h y l - 9 - n i t r o a c e p e r i m i d i n e (8%) and n i t r o compound IIIc, t o g e t h e r with
t r a c e s of 1 - m e t h y l - 4 , 9 - d i n i t r o a e e p e r i m i d i n e , in the nitration of a c e p e r i m i d i n e Ic under the conditions u s e d
f o r the p r e p a r a t i o n of dinitro d e r i v a t i v e IIIa f r o m a c e p e r i m i d i n e Ia. However, when the amount of acetic
acid and the nitration t i m e w e r e i n c r e a s e d , we w e r e able to obtain 1 - m e t h y l - 4 , 9 - d i n i t r o a c e p e r i m i d i n e in
66% yield.
The compounds s y n t h e s i z e d in tMs r e s e a r c h a r e the f i r s t r e p r e s e n t a t i v e s of the p r e v i o u s l y unknown
n i t r o p e r i m i d i n e s . We will r e p o r t the p r o p e r t i e s of the l a t t e r in a future p a p e r .

EXPERIMENTAL

The UV s p e c t r a of methanol solutions w e r e obtained with an SF-4A s p e c t r o p h o t o m e t e r . The PMR

s p e c t r a of t r i f l u o r o a c e t i c acid solutions w e r e r e c o r d e d with a T e s l a s p e c t r o m e t e r (80 MHz) with h e x a m e t h -
yldisiloxane (HMDS) as the i n t e r n a l standard.
A c e p e r i m i d i n e N i t r a t e . A solution of 0.22 m I (5 m m o l e ) of n i t r i c acid (sp. gr. 1.4) in 3 m l of glacial
~tcetic acid was added to a s u s p e n s i o n of 0.97 g (5 m m o l e ) of a c e p e r i m i d i n e in 10 m l of glacial acetic acid.
A f t e r 30 rain. the a c e p e r i m i d i n e n i t r a t e was r e m o v e d by f i l t r a t i o n and washed s u c c e s s i v e l y with glacial
acetic acid and e t h e r to give yellow p l a t e s with mp 282-283 ~ (from ethanol). The yield was 0.92 g (72%).
Found %: C 61.0, H 4.3, N 16.3. C13HIoN2- HNO 3. Calculated %~ C 60.7~ H 4.3: N 16.3.
4 - N i t r o a c e p e r i m i d i n e (Ha). A) A 0.55-g s a m p l e of a c e p e r i m i d i n e n i t r a t e was added in s m a l l portions
in the c o u r s e of 45 rain to cooled (to - 8 ~ c o n c e n t r a t e d sulfuric acid (5 ml), a f t e r which the m i x t u r e was
s t i r r e d at this t e m p e r a t u r e f o r 15 rain. It was then p o u r e d o v e r ice, and the m i x t u r e was n e u t r a l i z e d with
a m m o n i a . The p r e c i p i t a t e was r e m o v e d by filtration, washed with water, dried, and c h r o m a t o g r a p h e d with
a column (A120 a and CHC13) to jgive 0.2 g (40%) of 4 - n i t r o a c e p e r i m i d i n e as c r i m s o n needles with m p > 350 ~
(from DMF). YN--H 3335 c m -1. Xma x 486 rim, log a 4.04. PMR s p e c t r u m . ~, p p m : 3.00 (s. CH2CH2), 6.76
(d. ~-H), 7.14 (d. 5-H). 7.40 (s. 8-H). 8.04 (d, 2-H). 11.5 (broad s. NH).* Found %: C 65.4; H 4.0. N 17.0.
CI3HaN302. Calculated %: C 65.3: H 3.8: N 17.5.
B) A 0.105-ml (2.5 m m o l e ) s a m p l e of nitric acid (sp. g r . 1.5) was added dropwise to a solution of
0.48 g (2.5 m m o l e ) of a c e p e r i m i d i n e in 100 m l of glacial acetic acid, and the r e s u l t i n g yellow p r e c i p i t a t e

* The a b b r e v i a t i o n s u s e d h e r e and subsequently a r e s f o r singlet and d for doublet.

610
of a c e p e r i m i d i n e n i t r a t e dissolved when the m i x t u r e was heated to 80 ~ to give a d a r k - r e d solution. The m i x -
t u r e was s t i r r e d at 40- 50 ~ f o r 2 h, a f t e r which it was cooled and p o u r e d into cold water. The p r e c i p i t a t e
was r e m o v e d by filtration, washed with water, dried, and c h r o m a t o g r a p h e d (with a column filled with A120 ~
and elution with CHC13) to give, initially, 0.28 g (47%) of m o n o n i t r o a c e p e r i m i d i n e and then 0.12 g (17%) of
dinitr oacep erimidine.
4 , 9 - D i n i t r o a c e p e r i m i d i n e {IIIa). A solution of 0.21 m l (5 m m o l e ) of nitric acid (sp. gr. 1.5) in 3 ml of
acetic acid was added dropwise to a solution of 0.48 g (2.5 m m o l e ) of a c e p e r i m i d i n e in 25 m l of glacial
acetic acid, and the m i x t u r e was s t i r r e d at 60-70 ~ f o r 3 h. It was then cooled, and the p r e c i p i t a t e was r e -
m o v e d b y filtration, washed with water, and dried to give 0.5 g (70%) of a r e d s u b s t a n c e that darkened and
c h a r r e d without melting at 280-305 ~ (from dioxane). VN_ H 3330 c m - l . ~max 475 urn, log ~ 4.23. PMR
s p e c t r u m , 5, p p m : 3.16 (s, CH2CH2), 3.61 (s. NH), 7.85 (s, 5- and 8-H). 8.48 (s, 2-H). Found %.. C 55.2:
H 3.2: N 19.5. C13HsN404. Calculated %: C 54.9: H 2.8: N 19.7.
1 - M e t h y l a c e p e r i m i d i n e N i t r a t e . TMs compound was obtained by the method used to p r e p a r e a c e p e r -
imidine nitrate. The yellow p l a t e s had mp 257-258 ~ (from ethanol). The yield was 70%. Found %: C 61.8:
H 4.9: N 15.6. Ct4HI2N2 9 HNO 3. Calculated %: C 62.0: H 4.8: N 15.5.
1 - M e t h y l - 4 - n i t r o a e e p e r i m i d i n e (IIc). A) The e x p e r i m e n t was c a r r i e d out under conditions s i m i l a r to
t h o s e in the s y n t h e s i s of I I a in sulfuric acid. The red n e e d l e s had mp 268-269 ~ {from DMF). The yield was
54%. kma x 470 nm. log e 3.99. PMR s p e c t r u m , 6, p p m : 3.0 (s, CH2CH2) , 3.42 (s, N-CH3), 6.75 (d. 9-H),
7.2 (d, 8-H), 7.4 (s, 5-H), 8.1 (d. 2-H), 10.05 (broad s, NH). Found %: C 66.3: H 4.4: N 16.5. C14H~tN303.
Calculated %: C 66.4: H 4.3: N 16.6.
B) The method used to p r e p a r e IIa in glacial acetic acid was u s e d to obtain IIc in 58% yield.
C) A solution of 0.148 g (1.87 m m o l e ) of KOH in 20 m l of alcohol was added to a s u s p e n s i o n of 0.3 g
(1.25 m m o l e ) of n i t r o a c e p e r i m i d i n e in 30 m l of ethanol, a f t e r which 0.355 g (2.5 m m o l e ) of methyl iodide
w a s added, and the m i x t u r e was s t i r r e d f o r 3 h while the t e m p e r a t u r e was g r a d u a l l y r a i s e d to 100 ~ The
alcohol was then r e m o v e d by distillation, and the r e s i d u e was t r e a t e d with water, and the s t a r t i n g n i t r o -
a c e p e r i m i d i n e was then washed out with alkali (with m o n i t o r i n g by c h r o m a t o g r a p h y ) . The r e s i d u e was
washed with w a t e r and dried to give 0.15 g (47%) of product.
1 - M e t h y l - 4 , 9 - d i n i t r o a c e p e r i m i d i n e (IIIc). A) A 0.21-ml (5 m m o l e ) s a m p l e of HNO3 (sp. gr. 1.5) was
added d r c p w i s e to a solution of 0.52 g (2.5 m m o l e ) of a c e p e r i m i d i n e Ic in 60 ml of glacial acetic acid. and
the m i x t u r e was s t i r r e d at 70-80 ~ for 4 h. It was then cooled and p o u r e d into cold water. The p r e c i p i t a t e
was r e m o v e d by filtration, washed with water, dried, and c h r o m a t o g r a p h e d (with a column filled with A1203
and elution with CHC13) to give 0.49 g (66%) of dinitro d e r i v a t i v e IIIc as an orange p o w d e r with 261-262 ~
(dec., f r o m dioxane). ~'max 450 nm, log e 4.17. Found %: C 56.4: H 3.4- N 19.1. Ct4HIoN404. Calculated %:
C 56.4: H 3.4: N 18.8.
B) A 0.05-ml (1.2 m m o l e ) s a m p l e of HNO 3 (sp. gr. 1.5) was added d r o p w i s e to a solution of 0.3 g (1.2
m m o l e ) of n i t r o a c e p e r i m i d i n e IIc in 50 m l of glacial acetic acid, and the m i x t u r e was s t i r r e d at 60-70 ~ for
2 h, a f t e r which was cooled and p o u r e d into cold water. The p r e c i p i t a t e was r e m o v e d by filtration, washed
with water, dried, and c r y s t a l l i z e d f r o m dioxane to give 0.28 g (80%) of product.
Nitration of 2 - M e t h y l a c e p e r i m i d i n e . A solution of 0.21 ml (5 m m o l e ) of HNO 3 (sp. g r . 1.5) in 3 m l of
acetic acid was added dropwise to a solution of 1.04 g (5 m m o l e ) of a c e p e r i m i d i n e Ib in 100 m l of glacial
acetic acid. When the m i x t u r e was heated to 80 ~, the p r e c i p i t a t e that had f o r m e d dissolved. The m i x t u r e
was heated at 70-80 ~ f o r 3 h. a f t e r which it was cooled and n e u t r a l i z e d with a m m o n i a . The p r e c i p i t a t e was
r e m o v e d by filtration, washed with water, and dried. The m i x t u r e of n i t r o compounds was e x t r a c t e d with
c h l o r o f o r m and s e p a r a t e d with a c h r o m a t o g r a p h i c column (filled with A1203, elution with CHC13) to give 0.45
g (36%) of 4 - n i t r o - - 2 - m e t h y l a c e p e r i m i d i n e (lib) with mp 265-266 ~ {from dioxane). VN_ H 3325 c m -1. kma x
480 nm, log e 4.4. PMR s p e c t r u m . 6, ppm: 2.38 (s. CH3) , 3.02 (s. CH2CH2) , 6.71 (d, 4-H), 7.14 (d, 5-H), 7.4
(s. 8-H). Found %: C 66.0: H 4.5: N 16.6. C14H~lN302. Calculated %: C 66.4: H 4.3: N 16.6. The second
r e a c t i o n p r o d u c t was 4 , 9 - d i n i t r o - 2 - m e t h y l a c e p e r i m i d i n e (IIlb) [0.1 g (7%)]. which d a r k e n e d and c h a r r e d
f r o m 245 to 260 ~ {from DMF). YN--H 3325 c m - t . ~max 485 nm. log e 3.75. Found %: C 56.2: H 3.7: N 18.5.
C14H10NaO4. Calculated %: C 56.4: H 3.4: N 18.8.
Nitration of 1 . 2 - D i m e t h y l a c e p e r i m i d i n e . A solution of 0.3 ml (7 m m o l e ) of HNO 3 (sp. gr. 1.5) in 3 m l
of acetic acid was added dropwise to a solution of 0.78 g (3.5 m m o l e ) of a c e p e r i m i d i n e Id in 12 m l of glacial
a c e t i c acid. When the m i x t u r e was heated to 70 ~ the p r e c i p i t a t e d n i t r a t e g r a d u a l l y d i s s o l v e d to give a d a r k -
r e d solution. The solution was s t i r r e d at 70-80 ~ for 3 h. a f t e r which it was cooled and n e u t r a l i z e d with

611
ammonia. The precipitate was removed by filtration, washed with water, and dried. Separation with a
chromatograpMc column gave, initially. 0.07 g (8%) of 1,2-dimethyl-9-nitroaeeperimidine (IId) with mp 169-
170 ~ (from ethanol) (Found %: C 66.8: H 4.9: N 15.6. C15H13N302. Calculated %. C 67.4. H 4.9: N 15.7) and
then 0.42 g of 1,2-dimethyl-4-nitroaceperimidine with mp 220-222 ~ (from dioxane). Xmax 465 nm, log
3.98. Found %: C 67.2: H 4.6: N 16.0. C15Hi3N302. Calculated %: C 67.4: H 4.9$ N 15.7.

LITERATURE CITED
1. V. I. Sokolov, A. F. Pozharskii, I. S. Kashparov, A. G. Ivanov, and B. I. Ardashev, Khim. Geterotsikl.
Soedin.. 558 (1974).
2. I. S. Kashparov, Master's Dissertation [in Russian], Rostov State University, Rostov-oa-Don (1971).
3. I. H. Richmond. Six-membered Heterocyclic Nitrogen Compounds with Three Condensed Rings, New
York (1958), p. 518.
4. A. F. Pozharskii and E. N. Malysheva, Khim. Geterotsild. Soedin.. 103 (1970).
5. V. I. Minkin. I. I. Zakharov. and L. L. Popova, Khim. Geterotsikl. Soedin., 1552 (1971).

612
ALKYL AND 2-HYDROXY DERIVATIVES OF
IMIDAZO]4,5-b]PYRAZINE AND THEIR N-OXIDES

A~ S. E l i n a and I . S~ M u s a t o v a UDC 547.785.5'861.07

N-Monoxides and N,N-dioxides of s o m e alkyl and hydroxy d e r i v a t i v e s of imidazo [4,5-b]pyrazine

w e r e synthesized. It was p r o v e d that the nitrogen a t o m s of the p y r a z i n e ring a r e oxidized; a l -
kylation of N 1 s t e r i c a l l y hinders oxidation of NT. The hydrolytic cleavage of i m i d a z o [ 4 , 5 - b ] p y -
r a z i n e s and t h e i r N - o x i d e s was studied.

We have p r e v i o u s l y shown that i m i d a z o [ 4 , 5 - b ] p y r a z i n e s a r e oxidized by hydrogen p e r o x i d e in acetic

acid o r by p e r a c e t i c acid solution to N - m o n o x i d e s and N , N - d i o x i d e s , during which the p r e s e n c e of methyl
groups in the p y r a z i n e ring p r o m o t e s the f o r m a t i o n of N,N-dioxides. Thus a m i x t u r e of N - m o n o x i d e s and
N,N-dioxides IIa and Ilia, with p r e d o m i n a n c e of the f o r m e r , was obtained in the N-oxidation of Ia, while p r e -
dominantly N ~N-dioxide Ilib was f o r m e d f r o m Ib [1 I.
O O

R,..~S\ i N - - R'-.~ST~_Ra
I
R4 R' 0 R~

I a-g II a-g m a-g

I--III a RI=R2=R4=H, R~=CHa; b RI=R~=CH3, Ra=R4=H; c RI=R2=R+=CHz. R3=H;
d RI=R2=CI-ta, Ra=H, R~=CH2C6Hs; e RI=R2=C,H3, Ra=OH, R4=H; f RI=R2=R4=CH.~+
Ra=OIf; g Rt=R~=R4=H, Ra=OH

In the p r e s e n t r e s e a r c h we have studied the N-oxidation of i m i d a z o [ 4 , 5 - b ] p y r a z i n e d e r i v a t i v e s I e - g .

One of the ring nitrogen a t o m s in 1 , 5 , 6 - t r i m e t h y l i m i d a z o [4,5-b]pyrazine (lc) is p r e f e r a b l y oxidized to
give N - m o n o x i d e IIc, and the oxidation of the second nitrogen a t o m is difficult. This s o r t of difficulty in the
oxidation of a second ring nitrogen a t o m was also o b s e r v e d in the c a s e of 1 - b e n z y l - 5 , 6 - d i m e t h y l i m i d a z o [ 4 ,
5 - b ] p y r a z i n e (Id): in addition to the s t r o n g spot f r o m N - m o n o x i d e lid, a v e r y weak spot with a l o w e r Rf
value, which in analogy with the Rf values of o t h e r N,N-dioxides of imidazo [4,5-b]pyrazine. can be a s s i g n e d
to N,N-dioxide IIId. was detected in the r e a c t i o n solution by t h i n - l a y e r c h r o m a t o g r a p h y (TLC)~ The s a m e
r e s u l t s w e r e also obtained with the c o r r e s p o n d i n g 2 - h y d r o x y d e r i v a t i v e s (ie-f): only N,N-dioxide IIIe was
i s o l a t e d in the oxidation of Ie, and N - m o n o x i d e IIe was not detected even by c h r o m a t o g r a p h y ~ In addition,
N - m o n o x i d e IIf and a v e r y s m a l l amount of N,N-dioxide IIIf w e r e obtained in the oxidation of If, 2 - H y d r o x y
d e r i v a t i v e Ig, which does not have m e t h y l groups in the 1, 5, and 6 positions, is c o n v e r t e d to a m i x t u r e of
a p p r o x i m a t e l y equal amounts of N - m o n o x i d e and N ,N -dioxide IIg and HIg on oxidation with p e r a c e t i c acid.
In analogy with the N - o x i d e s of imidazo[4,5-b]quinoxaline [1 ], it m i g h t have been a s s u m e d that the nitrogen
a t o m s of the p y r a z i n e ring fN4 and N 7) undergo oxidation in the investigated i m i d a z o [ 4 , 5 - b ] p y r a z i n e d e r i v a -
tives. As a f i r s t a p p r o x i m a t i o n , we a s s i g n e d s t r u c t u r e s IIc, I[d, and IIf to the N - m o n o x i d e s of N l - m e t h y l o r
N~-benzyl d e r i v a t i v e s of i m i d a z o [ 4 , 5 - b ] p y r a z i n e , i n a s m u c h as alkylation o r a r a l k y l a t i o n of N 1 m a y s t e r i c a l -
ly hinder the oxidation of NT~ T h e s e a s s u m p t i o n s w e r e c o n f i r m e d by hydrolytic c l e a v a g e of N - m o n o x i d e s
IIc and IIf and N ,N -dioxide IHb; in this c a s e , the s a m e compound - N - m o n o x i d e VI - was obtained f r o m IIc
and IIf. The position of the N-oxide group in VI was p r o v e d by a l t e r n a t i v e s y n t h e s i s of this compound f r o m
2 - b r o m o - 3 - a m i n o - 5 , 6 - d i m e t h y l p y r a z i n e (IV). It is known that N-oxidation of 2-halo d e r i v a t i v e s of p y r a z i n e
So Ordzhonikidze All-Union S c i e n t i f i c - R e s e a r c h P h a r m a c e u t i c a l C h e m i s t r y Institute. T r a n s l a t e d f r o m
K h i m i y a G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 5, pp. 706-710, May, 1974. Original a r t i c l e s u b m i t t e d N o v e m -
b e r 15, 1972; r e v i s i o n s u b m i t t e d M a r c h 10, 1973.

9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

613
with p e r a e e t i c acid solution o r 30% H202 in acetic acid gives the c o r r e s p o n d i n g 4 - N - m o n o x i d e s , and oxida-
tion of the cyclic N t a t o m in compounds of this type p r o c e e d s only when m o r e powerful oxidizing agents
( t r i f l u o r o p e r a c e t i c acid o r C a r o ' s acid) a r e used [2,3]~ In c o n f o r m i t y with this, oxidation of IV with 7%
p e r a c e t i e acid solution gave 4 - N - o x i d e V, which on t r e a t m e n t with FeC13 solution gave the c o l o r r e a c t i o n
c h a r a c t e r i s t i c f o r h e t e r o c y c l i c N - o x i d e s containing an NH 2 group in the ~ position r e l a t i v e to the oxidized
ring n i t r o g e n a t o m . 2 - M e t h y l - a m i n o - 3 - a m i n o p y r a z i n e 4 - N - o x i d e , which was identical to VI, was obtained
f r o m V by heating with m e t h y l a m i n e .
O O
9I c ~ ~ t

II f "-" ~ ' ~ " " ~ CH3"~N/P~NHCH3 CH3"~N/~'Br CH3COOH cga"~N"~"Br

Vl V IV
O

0
Vll X

Hydrolytic c l e a v a g e of IIIb gave N,N-dioxide VII, the s t r u c t u r e of which was p r o v e d by reduction of it to the
known 2 , 3 - d i a m i n o - 5 , 6 - d i m e t h y l p y r a z i n e {X) [4]. The imidazole ring is cleaved by heating IIf, IIc, and IIIb
in aqueous acid o r alkali solutions. It was o b s e r v e d that IIf and IIIb, which contain an "acidic" hydrogen
a t o m , a r e stable when they a r e h e a t e d in alkalis and a r e c l e a v e d only in m i n e r a l a c i d s , while I I c , in which
acidic groupings a r e a b s e n t , undergo hydrolytic cleavage in both acidic and alkaline media. Unoxidized
i m i d a z o [ 4 , 5 - b ] p y r a z i n e s also behave s i m i l a r l y : Ic and Id a r e cleaved when they a r e heated in acids and
a l k a l i s , while Ib is c l e a v e d only in acids. The a b o v e - i n d i c a t e d p e c u l i a r i t i e s in the b e h a v i o r of i m i d a z o [ 4 , 5 -
b ] p y r a z i n e d e r i v a t i v e s and t h e i r N - o x i d e s that contain an unsubstituted hydrogen in the 1 position o r a h y -
d r o x y group in the 2 position a r e a p p a r e n t l y a s s o c i a t e d with the f o r m a t i o n , in alkaline m e d i a , of the c o r -
r e s p o n d i n g anions, which a r e m o r e r e s i s t a n t to hydrolytic c l e a v a g e .
Only 2 , 3 - d i a m i n o d e r i v a t i v e s of p y r a z i n e w e r e obtained during opening of the imidazole ring of i m i d -
a z o l e ring of i m i d a z o [4,5-b]pyrazine N - o x i d e s , r e g a r d l e s s of w h e t h e r the r e a c t i o n was c a r r i e d out in acidic
o r alkaline m e d i a . The nitrogen unoxidized i m i d a z o [ 4 , 5 - b ] p y r a z i n e s Ic and Id w e r e also c l e a v e d to 2 , 3 -
diamino d e r i v a t i v e s VIIIc,d, in alkaline m e d i a , but 2 - a m i n o - 3 - h y d r o x y d e r i v a t i v e s IXc,d o r (in the c a s e of
Ib) a m i x t u r e of diamino and a m i n o h y d r o x y d e r i v a t i v e s X and XI w e r e obtained in acidic media. T h e s e r e -
sults a r e in a g r e e m e n t with the i n c r e a s e d stability of the amino group in 2 - a m i n o p y r a z i n e 1 - N - o x i d e and
1,4-N ,N-dioxide r e l a t i v e to acid h y d r o l y s i s [5 ].
The IR s p e c t r a of 2 - h y d r o x y d e r i v a t i v e s of i m i d a z o [ 4 , 5 - b ] p y r a z i n e (Ie-g) and t h e i r N - o x i d e s (IIf, g,
I I I e - g ) contain s t r o n g bands of a m i d e c a r b o n y l s at 1738-1780 c m -1 and bands of the s t r e t c h i n g v i b r a t i o n s of

CH3"2~N~NltR

,c,
d s
IX c, d
N"2

CH3-'~N-:~'N HR
VIIIc, " d
-v c.3 NyN.,+c..:Nyo,
Ib ~
CH3.,~N.~,~N H2
X
CH /~N.~'~N 1.12
X!

a s s o c i a t e d NH groups at 2260-3130 c m - i ; this a t t e s t s to the existence of these compounds p r i m a r i l y in the

oxo f o r m in the c r y s t a l l i n e state.

EXPE RIM ENT A L

The IR s p e c t r a of m i n e r a l oil s u s p e n s i o n s of the compounds w e r e r e c o r d e d with a P e r k i n E l m e r 457
s p e c t r o m e t e r . The PMR s p e c t r a w e r e r e c o r d e d with a J N M - 4 H - 1 0 0 s p e c t r o m e t e r with t e t r a m e t h y l s i l a n e
as the i n t e r n a l s t a n d a r d . The compounds w e r e c h r o m a t o g r a p h e d on p a p e r with an n - b u t a n o l - 5 % acetic
(1:1) s y s t e m with d e v e l o p m e n t in UV light.
2 - M e t h y l a m i n o - 3 - a m i n o - 5 , 6 - d i m e t h y l p y r a z i n e (VIIIc).. A m i x t u r e of 5 g (25 m m o l e ) of IV, 35 m l of
i s o p r o p y l alcohol, and 50 m l of a 30% aqueous solution of m e t h y l a m i n e was heated in an autoclave at 170 ~

614
f o r 8 h, a f t e r which it w a s v a c u u m e v a p o r a t e d to a s m a l l v o l u m e , cooled, and f i l t e r e d to give 3.55 g (94%)
of VIIIe with mp 157.5-158.5 ~ (from water) and Rf 0.5 (bright b l u e - v i o l e t spot). Found: C 55.4; H 7.9; N
36.9%. CTHI2N4. Calculated: C 55.3; H 7.9; N 36.8%.
1 , 5 , 6 - T r i m e t h y l i m i d a z o [ 4 , 5 - b ] p y r a z i n e (Ic). A m i x t u r e of 1.9 g (12.5 m m o i e ) of VIIIc and 13 ml (82
m m o l e ) of f r e s l y p r e p a r e d ethyl o r t h o f o r m a t e was s t i r r e d at 75-80 ~ for 4 h, a f t e r which it was cooled and
f i l t e r e d to give 1.4 g (70%) of le with m p 193.5-194.5 ~ (from methanol) and Rf 0.58 ( d a r k - v i o l e t spot). PMR
s p e c t r u m (in CDCI3): 6 2.64 (5-CH 3 and 6-CH3) , 3.90 (N-CH3) , 8.12 p p m (2-H). Found: C 59.6; H 6.2; N
34.3%. CsHIoN4. Calculated: C 59.3; H 6.2; N 34.5%.
1 - M e t h y l - 2 - h y d r o x y - 5 , 6 - d i m e t h y l i m i d a z o [ 4 , 5 - b ] p y r a z i n e (If). A 6 - g (40 m m o l e ) s a m p l e of VIIIc was
t r i t u r a t e d with 6.66 g (100 m m o l e ) of u r e a , and the m i x t u r e was h e a t e d at 160-165 ~ for 2 h. It was cooled
to 20 ~ and the solidified m a s s was d i s s o l v e d in 50 m l of ~% NaOH solution. The solutionwas t r e a t e d with
c h a r c o a l and f i l t e r e d , and the f i l t r a t e was acidified to pH 5 with acetic acid and cooled to give 5.6 g (80%)
of If with mp 261-262 ~ (from 50% alcohol) and Rf 0.59 ( b r i g h t b l u e - v i o l e t spot). IR s p e c t r u m : 1748 c m -I
(vC----o); 2680-2760, 3120 e m -I (broad, w, VNH). PMR s p e c t r u m (in CF3COOH): 6 2.79 (5-CH 3 and 6-CH3) ,
3~ p p m (> NCH3). Found: C 53~ H 5.7; N 31.5%o CsHIoN40. Calculated: C 53.9; H 5.7; N 31.5%.
N-Oxidation of I m i d a z o [ 4 , 5 - b ] p y r a z i n e D e r i v a t i v e s . A) A m i x t u r e of 1.5 g (9.2 m m o l e ) of Ic, 6.15 m l
of 6.2% p e r a c e t i c acid (50 mmole)~ 0.01 g of Na4P2OT, and 0.93 g of CI~COONa was heated at 60-65 ~ for 8 h,
a f t e r which it was cooled to 2 ~. The inorganic s a l t s w e r e s e p a r a t e d , and the solution was v a c u u m e v a p o r a t e d
a t 40-45 ~ to one t h i r d of its original volume. E t h e r was added to the r e s i d u e , the m i x t u r e was cooled, and
1.7 g of a m i x t u r e of IIc and IIIe, in which l e s s than 20% IIIc was detected by quantitative p a p e r c h r o m a t o -
g r a p h y , was s e p a r a t e d . The m i x t u r e was e x t r a c t e d with boiling e t h e r in a Soxhlet a p p a r a t u s until only one
s p o t (from IIIc) was detected in the r e s i d u e by p a p e r c h r o m a t o g r a p h y . C r y s t a l l i z a t i o n of the r e s i d u e f r o m
aqueous alcohol gave an a n a l y t i c a l l y p u r e s a m p l e of IIIc with mp 254 ~ (dec., f r o m aqueous alcohol) and
0.17 ( d a r k - v i o l e t spot). Found: C 49.6; H 5.1; N 29.0%. CsHIoN402. Calculated: C 49.4; H 5.2; N 28.9%.
The e t h e r e x t r a c t was e v a p o r a t e d , the r e s i d u e was d i s s o l v e d in w a t e r , and the solution was e x t r a c t e d with
c h l o r o f o r m . Many r e p e t i t i o n s of this o p e r a t i o n gave N-oxide lie with m p 252-253 ~ (from methanol) and R f
0.36 ( d a r k - v i o l e t spot). Found: C 53.8; H 6.0; N 32.0%. CsH94 Calculated: C 54.0; H 5.7; N 31.5%.
B) A m i x t u r e of 5 g (28 m m o l e ) of If, 188 m l of 6.2% p e r a c e t i c acid (153 m m o l e ) , 0.01 g of Na4P2OT,
and 2.83 g of CH3COONa was kept at 20-25 ~ for 6 days, a f t e r which the p r e c i p i t a t e was r e m o v e d by f i l t r a -
tion, and a n o t h e r s m a l l amount of c r y s t a l l i n e substance was isolated f r o m the f i l t r a t e by e x t r a c t i o n with
e t h e r . The combined solids w e r e r e c r y s t a l l i z e d f r o m w a t e r to give 3.2 g of N - o x i d e IIf. The aqueous s o l u -
tions f r o m the r e c r y s t a l l i z a t i o n w e r e e x t r a c t e d with boiling c h l o r o f o r m to give a n o t h e r 1.32 g of Ilf. The
o v e l a l l yield of IIf with m p 250-251.5 ~ (from alcohol) and Rf 0.33 ( d a r k - v i o l e t spot) was 83%. IR s p e c t r u m :
1740 c m -~ (vC----O); 2540-2660, 3080 cm -I (broad, VNH). PMR s p e c t r u m (in CF3COOH): 6 2.77 (5-CH 3 and
6-CH3), 3.68 p p m (>NCH3). Found: C 49.3; H 5.2; N 28.9%. CsHIoN402. Calculated: C 49.5; H 5.2; N28.9%.
The aqueous solutions r e m a i n i n g a f t e r e x t r a c t i o n with c h l o r o f o r m w e r e e v a p o r a t e d to d r y n e s s to give 0.29
g (5%) of IIIf with mp 238-239 ~ (dec., f r o m 80% alcohol) and Rf 0.26 ( d a r k - v i o l e t spot). Found: C 45.8;
H 4.9; N 27.0%. CsH10N403 . Calculated: C 45.7; H 4.8; N 26.7%.
C) A m i x t u r e of 0.5 g (2.8 m m o l e ) of If, 13.5 ml of 8.2% p e r a c e t i c acid (15 m m o l e ) , 0.21 g of C H 3 -
COONa, and 0.01 g of Na4P207 was heated at 60-65 ~ for 10 h. The solution was then v a c u u m e v a p o r a t e d at
40 ~ to one third of its original v o l u m e , and e t h e r was added to the r e s i d u e to isolate 0.48 g of a substance
that c o n s i s t e d p r i m a r i l y of N - m o n o x i d e IIf. Only a weak spot f r o m N ,N -dioxide IIIf was detected in it by
paper chromatography.

D) A m i x t u r e of 8.5 (52 m m o l e ) of Ie, 262 m l of 8.2% p e r a c e t i c acid(277 m m o l e ) , 3.96 g of CH3COONa ,

and 0.01 g of Na4P20 ~ was heated at 65-70 ~ f o r 9 h, a f t e r which the p r e c i p i t a t e was r e m o v e d by filtration,
and the solution was v a c u u m e v a p o r a t e d at 40 ~ to one third of its original volume. An additional amount of
a c r y s t a l l i n e s u b s t a n c e was i s o l a t e d f r o m the r e s i d u e by ether. The combined solids w e r e c r y s t a l l i z e d
f r o m w a t e r and f r o m aqueous alcohol to give 3.2 g of N ,N -dioxide Hie. The solutions f r o m the r e c r y s t a l -
lization w e r e v a c u u m e v a p o r a t e d to d r y n e s s , and the r e s i d u e was c r y s t a l l i z e d f r o m w a t e r to give a n o t h e r
0.9 g of IIIe. T h e o v e r a l l y i e l d of IIIe with mp 252 ~ (dec.) and Rf 0.06 ( d a r k - v i o l e t spot) was 4.1 g (40%).
IR s p e c t r u m : 1738, 1758 c m -1 (VC=O); 2260-2640 c m -1 (broad, VNH). PMR s p e c t r u m (in DMSO): ~ 2.4
p p m (5- and 6-CH3). Found: C 42,4; H 4.1; N 28.2%. CTH3N403. Calculated: C 42.8; H 4 . 1 ; N 28.6%.
E) A m i x t u r e of 2 g (15 m m o l e ) of Ig, 59 m l of 10.2% p e r a c e t i c acid (79 m m o l e ) , 0.9 g of CH3COONa ,
and 0.01 g of Na4P207 was s t i r r e d at 65-70 ~ f o r 13 h, a f t e r which it was cooled, and the p r e c i p i t a t e was

615
r e m o v e d by filtration. S e v e r a l r e c r y s t a l l i z a t i o n s of the p r e c i p i t a t e f r o m w a t e r and then f r o m dilute acetic
acid gave 0.5 g (22%) o f N - o x i d e IIg with m p 265 ~ (dec.) and Rf 0.18 (blue-violet spot). IR s p e c t r u m : 1715,
1765 c m -1 (vC----O); 2645-2720, 3105 c m -1 (broad, VNH). Found: C 39.7; H 2.7; N 37.1%. CsH4N402. C a l -
culated: C 3 9 . 5 ; H 2+7;+N:36.5%. The solution r e m a i n i n g f r o m the s e p a r a t i o n of IIg was e x t r a c t e d with
e t h e r to give a solid, f r o m which 0.5 g of N-oxide IIIg with R f 0.07 ( d a r k - v i o l e t spot), which did not m e l t
up to 300 ~ was obtained a f t e r s e v e r a l r e c r y s t a U i z a t i o n s . IR s p e c t r u m : 1790, 1760 c m -1 (vC = O ) ; 2660-
2720, 3130 c m -1 (broad, PNH). Found: C 35.4; H 2.5%. CsH4N403o Calculated: C 35.7; H 2.4%.
F) A m i x t u r e of 2 g (0.8 m m o l e ) of Id, 2.8 ml of 12.2% p e r a c e t i c acid (4.5 m m o l e ) , 0.04 g of CH 3-
COONa, and 0.01 g of Na4P207 was heated at 60-65 ~ for 15 h. The s a m e amounts of p e r a c e t i c acid, CH 3-
COONa, and Na4P207 w e r e added, and the m i x t u r e was s t i r r e d at 60-65 ~ for a n o t h e r 7 h. A s t r o n g d a r k -
violet spot f r o m IId, with Rf 0.71 [1], and a v e r y weak d a r k - v i o l e t spot with R f 0.19, which can be a s s i g n e d
to IIId, w e r e detected by c h r o m a t o g r a p h y of the r e a c t i o n m i x t u r e .
2 - B r o m o - 3 - a m i n o - 5 , 6 - d i m e t h y l p y r a z i n e 4 - N - O x i d e (V). A m i x t u r e of 4 g (20 m m o l e ) of IV, 45 m l of
7% p e r a c e t i c acid (40 m m o l e ) , 0.68 g of CHaCOONa , and 0.01 g of NaaP207 was heated at 60-65 ~ f o r 2.5 h,
a f t e r which the p r e c i p i t a t e d inorganic s a l t s w e r e r e m o v e d by filtration, and the solution was n e u t r a l i z e d to
pH 7 and e x t r a c t e d with c h l o r o f o r m . R e m o v a l of the c h l o r o f o r m gave 2.82 g (65%) of V with mp 145.5-146 ~
(from a c e t o n e - h e x a n e ) and R f 0.5 ( d a r k - v i o l e t spot), which gave an intense blue coloration with FeC13.
Found: B r 36.5; N 19.5%. C6HsBrN30. Calculated: B r 36.6; N 19.3%o
2 - M e t h y l a m i n o - 3 - a m i n o - 5 , 6 - d i m e t h y l p y r a z i n e 4 - N - O x i d e (VI). A 0.5-g s a m p l e of V was heated with
5 m l of 30% aqueous solution of m e t h y l a m i n e in 35 m l of i s o p r o p y l alcohol in an autoclave at 100 ~ for 7 h
and then at 120 ~ for 5 h. It was then cooled and f i l t e r e d to give 0.1 g of VI. The r e a c t i o n solution was
e v a p o r a t e d to d r y n e s s , and the r e s i d u e was t r e a t e d with a s m a l l amount of w a t e r to give another 0.13 g of
VI. The o v e r a l l yield of VI with m p 222-223 ~ (dec., f r o m alcohol) and R f 0.53 (bright b l u e - v i o l e t spot),
which gave an intense b l u e - g r e e n coloration with aqueous FeC13, was 60%. Found: C 5004; H 7.2; N 33.3%.
C7H12N40. Calculated C 50.0; H 7.2; N 33.3%.
Hydrolytic Cleavage of I m i d a z o [4,5-b]pyrazine D e r i v a t i v e s . A) A 0.2-g (1.2 m m o l e ) s a m p l e of Ic was
refluxed in 2 m l of 2.5 N NaOH for 4 h, a f t e r which the m i x t u r e was cooled and f i l t e r e d to give 0.13 g (69%)
of VIIIc, which, a c c o r d i n g to a m i x e d - m e l t i n g - p o i n t d e t e r m i n a t i o n and Rf value, was identical to VIHc o b -
tained f r o m IV (see above).
B) A 0.5-g (3 m m o l e ) s a m p l e of Ic w a s refluxed in 5 m l of 3 N HC1 f o r 4 h, a f t e r which the solution
was n e u t r a l i z e d to pH 5-6 and e x t r a c t e d with c h l o r o f o r m to give 0043 g (91%) of IXc with m p 223-224 ~
(from ethyl a c e t a t e - m e t h a n o l ) and R f 0.43 (violet spot). Found: N 27.0%. CTHllN30. Calculated: N 27.4%.
C) A 0 . 2 - g (0.84 m m o l e ) s a m p l e of Id was refiuxed in 2 m l of 2.5 N NaOH for 2 h, a f t e r which it was
w o r k e d up to give 0.18 g (94%) of VIIId with m p 144.5-145.5 ~ (from ethyl acetate) and Rf 0089 (bright-violet
spot). Found: 24.4%. C13H16N4. Calculated: N 27.4%.
D) A 1 - g (4.2 m m o l e ) s a m p l e of Id was refluxed in 10 m l of 20% HC1 for 1.5 h, a f t e r which the s o l u -
tion was n e u t r a l i z e d to pH 7 and cooled. The p r e c i p i t a t e (0.87 g) was r e m o v e d and c r y s t a l l i z e d r e p e a t e d l y
f r o m methanol to give p u r e 2 - b e n z y l a m i n o - 3 - h y d r o x y - 5 , 6 - d i m e t h y l p y r a z i n e (IXd) with mp 171.5-172 ~ (from
methanol) and R f 0.81 (bright-blue spot). Found: C 67.5; H 6.7; N 17.8%. C13H15N30. Calculated: C 6800;
H 6.6; N 18.3%.
E) A 0.5-g (3.4 m m o l e ) s a m p l e of Ib was refluxed in 5 ml of 3 N HC1 for 4 h, a f t e r which it was cooled
to 20 ~ and the p r e c i p i t a t e d h y d r o e h l o r i d e of X was r e m o v e d by filtration. The p r e c i p i t a t e was d i s s o l v e d in
w a t e r , and the solution was m a d e alkaline to pH 8 and e x t r a c t e d with c h l o r o f o r m to give 0.15 g (32%) of X,
which, a c c o r d i n g to the Rf value (0.34, b l u e - v i o l e t spot) and a m i x e d - m e l t i n g - p o i n t d e t e r m i n a t i o n , was
identical to X obtained by the method in [2 ]. The acid solution r e m a i n i n g a f t e r the s e p a r a t i o n of the h y d r o -
chloride of X was cooled to 2 ~ and the r e s u l t i n g p r e c i p i t a t e was r e m o v e d by filtration and dissolved in
w a t e r . The solution was n e u t r a l i z e d to pH 7 and f i l t e r e d to give 0.12 g (26%) of XI, which a c c o r d i n g to the
.Rf value (0.22, violet spot) and a m i x e d - m e l t i n g - p o i n t d e t e r m i n a t i o n , was identical to XI obtained by the
method in [6].
Hydrolytic Cleavage of I m i d a z o [ 4 , 5 - b ] p y r a z i n e N - O x i d e s . A) A 0.4-g (2 mmole) s a m p l e of Hf was
reflu_xed in 4 m l of 60% H2SO4 for 1 h and 15 rain, a f t e r which it was p o u r e d o v e r ice, and the r e s u l t i n g s o l u -
tion was n e u t r a l i z e d and e x t r a c t e d with c h l o r o f o r m to give 0.16 g (46%) of VI, which, a c c o r d i n g to its Rf
value, its c o l o r r e a c t i o n with FeC13, and a m i x e d - m e l t i n g - p o i n t d e t e r m i n a t i o n was identical to VI obtained

616
f r o m V (see above). Starting IIf was detected c h r o m a t o g r a p h i c a l l y in the aqueous solution a f t e r extraction
with c h l o r o f o r m .
B) A 0.2-g (1.1 mmole) sample of IIc was refluxed in 2 ml of 30% I I2SO4 for 2 h, a f t e r which the mixL
ture was worked up as in method A to give 0.1 g (55%) of VI.
C) A 0.4-g (2.2 mmole) sample of IIc was refluxed in 4 ml of 2.5 N NaOH for 1 h, a f t e r which the
m i x t u r e was cooled and filtered to give 0.35 g (93%) of VI.
D) A 0.5-g (2.8 mmole) sample of IIIb was refluxed in 5 ml of 60% H2SO4 for 30 mill, a f t e r which the
m i x t u r e was worked up as in method A and e x t r a c t e d with c h l o r o f o r m to give 0.27 g (57%) of VH with mp
257-258 ~ (dec., f r o m methanol) and Rf 0.12 (blue-violet spot) that gave an intense coloration with FeC13
solution. Found: C 43.0; H 5.9%. CgHgN303. Calculated: C 42.5; H5.9%.
Reduction of 2 , 3 - D i a m i n o - 5 , 6 - d i m e t h y l p y r a z i n e 1,4-N,N-Dioxode (VII). A 0.3-g (1.8 mmole) s a m -
ple of VII was hydrogenated in 5 ml of anhydrous alcohol at 20-25 ~ in the p r e s e n c e of Raney nickel until
3.6 mmole of hydrogen had been absorbed. The c a t a l y s t was s e p a r a t e d , and the solution was vacuum evap-
o r a t e d to d r y n e s s to give 0.24 g (96%) of X with mp 212.5-213.5, which, according to the Rf value and m i x e d -
melting-point determination, was identical to X obtained by the method in [2].

LITERATURE CITED

1. A. S. Elina, I. S. Musatova, and L. G. T s y r u l ' h i k o v a , Khim. Geterotsikl. Soedin., 1266 (1972).

2. R. C. Ellingson and R. L. Henry, J. A m e r . Chem. Soc., 70, 1257 (1948).
3. R. A. B a x t e r , G. T. Newbold, and F. S. Spring, J. Chem. Soc., 1859 (1948).
4. K. W. Blake and P. G. S a m m e s , J. Chem. Soc., C, 1070 (1970).
5. A. S. Elina, L. G. T s y r u l ' n i k o v a , and I. S. Musatova, K h i m . - F a r m a t s . Zh., No. 5, 11 (1968).
6. E. Schipper and A. Day, J. A m e r . Chem. Soc., 7 4 , 3 5 0 (1952).

617
L E T T E R S TO THE EDITOR

CONDENSATION OF DIMETHYLIDYNEHEMICYANINES
WITH KETONES

Yu. L. Slominskii and I. D. Radehenko UDC 547.789:543 : 422.25.4.6

A general method has been found for the synthesis of h e t a r y l i d e n e - s u b s t i t u t e d unsaturated ketones of
the II type, which a r e rnerocyanines. The method consists in condensation of/3-(dialkylarnino)vinyl d e r i v a -
tives of q u a t e r n a r y salts of nitrogen h e t e r o c y c l e s (I) with aliphatic o r alicyclic ketones. The reaction is
c a r r i e d out in a mixture of methanol solution of sodium rnethoxide with pyridine.

'L.

i II a - h

Hernicyanines I, which contain dirnethylamino o r diethylarnino groups, as well as rnorpholic or

piperidine r e s i d u e s , may be used. It is m o r e convenient to use the dirnethylarnino derivative be-
cause of the volatility of the evolved amine. Hemicyanines with p r i m a r y a r o m a t i c or s e c o n d a r y al-
i p h a t i c - a r o m a t i c amine r e s i d u e s , as well as acyl derivatives of the f o r m e r , cannot be used in the
condensation under consideration because of their lability under the r e a c t i o n conditions. Merocyanines
(II) with 1,3,3-trimethylindolenine r e s i d u e s can be obtained by using 1,3,3-trirnethyl-2-forrnylrnethyl-
eneindoline in place of the hernicyanine {IIe-h w e r e obtained in this way).
2,5-Bis[(3-ethyl-2-benzothiazolinylidene)ethylidene]cyclopentanone (IIa) was obtained by refluxing 5
rnmole of cyclopentanone and 11 rnmole of 2-(/3-dirnethylaminovinyl)-3-ethylbenzothiazolium iodide in a
mixture of 8 rnl of 2 N sodium rnethoxide solution and 3 rnl of dry pyridine for 30 rnin. The PMR s p e c t r u m
in t r i f l u o r o a c e t i c acid, in which IIa f o r m s a cation, contains a singlet at 2.50 pprn (4H), doublets at 3.99 pprn
(2H) with J = 8.0 Hz, and 6.45 pprn (1H) with J = 15.0 Hz, two triplets at 1.36 ppm (6H) and 5.98 ppm (1H),
a multiplet with a weakly e x p r e s s e d fine s t r u c t u r e at 4.43 pprn (4H), and a rnultiplet at 7.20-824 pprn (9H).
1,3-Bis [(1,3,3-trirnethyl-2-indolinylidene)ethylidene]acetone (IIe) was obtained by refluxing 0.01 mole of

TABLE 1. Merocyanines I I a - h

Com - Empirical !Found,ICalc.,I kmad Yield,

pound R A mp, ~ formula % i ~176 nm "'l %

lla C~H8 (CIt2)~ 227--228* C27H26N2OS2 S 14,0 S 14.0 602 65

llb C2H5 (CH2)3 214--215 C28H2sN2OS2 513,6[$13,51 556 63
llC CH=CH C~H~ (CH2)2 229--230 C3,HzeN20
lid CH~C'H C2H~ (CHDB 231--232 C3~H32N20 N 6,3,
6.3 N 6,35,6 616
6,1 665 34
37
lie C{CH3)~ CH3 H,H 193--194 C29H3~N20 6.6 N 6,6 520 24
IIf C(CH3)2 CHz (CH~)~ 242--243T C3,tt34,N~O N 6,1 N 6.2 563 51
C(CH3}2
lille C CHa (Ct12)3 247--248 C32H3~N20 N 6 0 N 6,0 525 24
(CH3)2 Ctt3 o-C6H4 232--233$ C35H34N20 N 5,8 N 515 t6

* The decomposition point (246 ~ was in agreernent with the value in [1].
#The decomposition point (264 ~ was in a g r e e m e n t with the value in
~].
S P r i o r to c r y s t a l l i z a t i o n , the compound was chrornatographed in
benzene on aluminum oxide.
Institute of Organic C h e m i s t r y , A c a d e m y of Sciences of the Ukrainian SSR, Kiev. T r a n s l a t e d from
Khirniya Geterotsiklicheskikh Soedinenii, No. 5, pp. 711-712, May, 1974. Original article submitted July 26,1973.

9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

618
d r y acetone and 0.02 m o l e of 1 , 3 , 3 - t r i m e t h y I - 2 - f o r m y l m e t h y l e n e i n d o l i n e in 10 m I of a 2 N sodium methoxide
solution for 2 h. The p r o d u c t was p r e c i p i t a t e d by the addition of w a t e r and c h r o m a t o g r a p h e d in benzene on
a l u m i n u m oxide. The PMR s p e c t r u m of IIe in carbon t e t r a c h l o r i d e contains two singlets at 1.68 p p m (12H)
and 3.30 p p m (6H), doublets at 5.37 p p m (2H), with J = 12.0 Hz, and at 5.97 p p m (2H), with J = 16.0 Hz, a
t r i p l e t at 7.83 p p m (2H), and a m u l t i p l e t at 6.55-7.19 p p m (SH). The m e r o c y a n i n e s p r e s e n t e d in Table 1
w e r e s i m i l a r l y obtained.
The UV, IR, and PMR s p e c t r a of IIa, which was s y n t h e s i z e d via the method d e s c r i b e d h e r e , and of a
s a m p l e obtained by a l t e r n a t i v e s y n t h e s i s [1 ] w e r e identical. The PMR s p e c t r a w e r e r e c o r d e d with a T e s l a
BS 487B s p e c t r o m e t e r (80 MHz) with t e t r a m e t h y l s i l a n e as the internal standard.

LITERATURE CITED
1o L~ B r o o k e r and A. Fumia, F r e n c h P a t e n t No. 1,574,253 (1969); Chem. A b s t r . , 73, 26,632 (1970).

619
NEW METHOD FOR THE SYNTHESIS OF
THIOPHENETHIOLS

M. G . V o r o n k o v , t~. N . D e r y a g i n a , UDC 547,569 : 1 '732'734

A . S. N a k h m a n o v i c h , and L. G. Klochkova

The existing methods for the synthesis of thiols of the thiophene s e r i e s a r e based on the reaction of
sulfur with 2-1ithiothiophenes and subsequent decomposition of the resulting lithium salts of thiophene-2-
thiols [1, 2 ].
We have developed a new method for the synthesis of thiophenothiols that is based on the reaction of
chloro d e r i v a t i v e s of thiophene and benzothiophene with hydrogen sulfide at 450-550~ The chloro d e r i v a -
tives of thiophene fia-d) r e a c t with hydrogen sulfide to give the corresponding thiols in 20-40% yields via
the s c h e m e

t a-d II a-d

J\
I, IIaR=l-t; bR=C2Hs; eR=CI;dR= I H ~__-benzothienylgroup
"%/

S y m m e t r i c a l sulfides of thiophene and benzothiophene a r e f o r m e d simultaneously with the thiols:

II I III

Compounds IIa and IIIa (22 and 60% yields), IIb and IIIb (33 and 67~0), IIc and IIIc (17 and 40%), IId and
IIId (39 and 47% yields, based on the Ia-d consumed), r e s p e c t i v e l y , w e r e obtained by passing dry hydrogen
sulfide at 9 l i t e r s / h and, simultaneously, vapors of chlorides Ia-d at 10 m l / h through a heated (to 450-
550~ empty quartz tube (655-mm long and 30 m m in diameter)~ The compounds obtained (I, II, and III)
w e r e s e p a r a t e d by vacuum distillation with a fractionating column and identified f r o m the l i t e r a t u r e physi-
cochemical constants.

LITERATURE CITED
1~ Ya. L. Gol'dfarb, M. A. Kalik, and M. L. K i r m a l o v a , Zh. Obshcho Khim., 3_~2,222 (1962).
2. Ya. L. Gol'dfarb and Mo Ao Kalik, Khim. Geterotsikl. Soedin., 788 (1968)o

Irkutsk Institute of Organic C h e m i s t r y , Siberian Branch, Academy of Sciences of the USSR. T r a n s l a t e d

f r o m Khimiya Geterotsiklicheskikh Soedinenii, No. 5, p. 712, May, 1974. Original article submitted Octo-
b e r 16, 1973.

9 1975Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

620
FORMATION OF SUBSTITUTED 1,3-DITHIOLANES IN
REACTIONS OF 3 - A M I N O - 2 - A R Y L I D E N E - I - T H I O N E S
WITH DIAZOMETHANE

N~ A. K o r c h e v i n , V. A. U s , v , UDC 547.665'738
and M. G. Voronkov

N ,N-Disubstituted 3 - a m i n o - 2 - a r y l i d e n e - l - t h i o n e s (I), which a r e vinylogs of thioanaides, r e a c t r e a d i l y

with diazomethane in e t h e r solution at r o o m t e m p e r a t u r e to give substituted 1,3-dithiolanes (II). A s i m i l a r
r e a c t i o n path is o b s e r v e d only for thioketones [i] and is unknown for thioamides [2].
When the 1,3-dithiolanes obtained (II) a r e refluxed in high-boiling solvents, they a r e , as usual [3 ],
c l e a v e d into two p r o d u c t s , one of which is the s t a r t i n g aminothione (I). When II is t r e a t e d with an aqueous
alcohol solution of s i l v e r n i t r a t e , the dithiolane ring is c l e a v e d with simultaneous h y d r o l y s i s of the amino
groups in the II m o l e c u l e s to give the c o r r e s p o n d i n g 3 , 3 ' - d i o x o - 2 , 2 ' - d i a r y l d i i n d a n y l i d e n e s (III)~ Cleavage
of 1,3-dithiolanes under such conditions has not been d e s c r i b e d in the l i t e r a t u r e .

NRR
'2 9
~ nr'r ~ c.ono r~ H~/R"S.O

S RIR2N R= ((~)

I 11 Ill

l - l l l a R~,R2= (CH~):, R:= C~H~; b R'. R: =(CH2)s,R=---p-CH~OC~I~4; C R~, R: = CH~, RJ:-CBHs

EXPERIMENTAL
D i s p i r o [ b i s ( 3 - p i p e r i d i n o - 2 - p h e n y l i d e n e ) - 4 , 1 ' : 5 . 1 ' ] - l , 3 - d i t h i o l a n e (IIa). This compound, with m p
160 ~ ( d e c , b e n z e n e - m e t h a n o l ) w a s obtained in 90% yield. Found: C 78.9; H 6.4; N 4.6; S 10~ M 600.
C41H40N2S2~ Calculated: C 7808; H 6.4; N 4~ S 1003~o; M 622~
Dispiro [his (3 - p i p e r i d i n o - 2 - (p-methoxyphenylidene) -4,1 ' ;501 ' ]-1,3-dithiolane (IIb). This compound,
with m p 135 ~ (dec.), was obtained in 81% yield. Found: C 75.6; H 6~ N 3.9; S 9.4~0o C43H44N202S2. C a l -
culated: C 75.4; H 604; N 4.1; S 9~
Dis piro Ibis (3 -dinaethylamino-2 -phenylidene)-4,1 ' ;5.1 ' ]-1,3-dithiolane {IIc). This compound, with nap
120 ~ (dec.), was obtained in 70% yield. Found: C 77~ H 6~ S 11.8%. C35H32N2S2. Calculated: C 77.2;
H 5.9; S 11o8%o IR s p e c t r u m (in KBr), c m - l : 1495, 1610 ( a r o m a t i c ring C = C), 1580 (C = C in a f i v e - m e n a -
b e r e d ring). PMR s p e c t r u m (in CDC]~ with t e t r a m e t h y l s i l a n e as the standard): T 5.69 ppm.
3,3' -Dioxo -2,2 '-diphenyldiindanylidene (IIIa). This compound, with m p 2 37-2 38 ~ (benz erie - hexane),
was obtained in 99~0 yield. Found: C 87.1; H 4.6%~ C30H2002~ Calculated: C 8704; H 4~
3 , 3 ' - D i o x o - 2 , 2 ' - d i ( p - m e t h o x y p h e n y l ) d i i n d a n y l i d e n e {IIIb)~ This compound, with m p 219-220 ~ was o b -
tained in 92% yield. Found: C 81.6; H 4o9~. C32H24040 Calculated: C 81.4, H 5.1~o. Intense bands at 1708
c m -1 (C -- O) a r e p r e s e n t in the IR s p e c t r a of diketones IIL

I r k u t s k Institute of Organic C h e m i s t r y , Siberian Branch, A c a d e m y of Sciences of the USSRo T r a n s -

lated f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 5, p. 713, May, 1974o Original a r t i c l e s u b m i t t e d
N o v e m b e r 26, 1973.

9 19 75Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without weitten permission o f the publisher. A copy o f this article is availablefrom the publisher for $15.00.

621
 LITERATURE CITED
1. A. Sch(inberg, B. Kiinig, and E. Singer, Chem. Ber., 100,767 (1967)o
2. K. A. Petrov and L. N. Andreev, Usp. Khim., 40, 1014 (1971).
3o A. Schiinberg and S. Nickel~ Ber., 64, 2323 (1934).

622
PREPARATION OF SUBSTITUTED THIIRANES AND
ETHYLENES IN T H E REACTION OF
3-PIPE RIDINO-2-PHENYLIDENE-1 -THIONE WITH
MONO- AND DIPHENYLDIAZOMETHANES

N. A. Korchevin, V. A. Us,v, UDC 547.665'717'828

a n d M. G . V o r o n k o v

Both t h i i r a n e s and 1,3-dithiolanes a r e obtained in the r e a c t i o n s of thioketones with substituted di-

azoraethanes [1]. fl-Aminothiones of the indene s e r i e s r e a c t with diazoraethane to give the c o r r e s p o n d i n g
1,3-dithiolanes [2 ]. We have o b s e r v e d that 3 - p i p e r i d i n o - 2 - p h e n y l i d e n e - l - t h i o n e (I) r e a c t s r e a d i l y with
diphenyldiazoraethane at r o o m t e m p e r a t u r e in benzene o r e t h e r solution to give good yields of the c o r r e -
sponding thiiranes (II). As is the c a s e with m a n y t h i i r a n e s [3], when II a r e heated even gently, e l e m e n t a l
sulfur is split out, and II a r e converted to ethylene d e r i v a t i v e IIIa.
Only the c o r r e s p o n d i n g ethylene (IIIb) is obtained in the reaction of arainothione I with p h e n y l d i a z o -
methane in e t h e r o r benzene, inasmuch as i n t e r m e d i a t e thiirane IIb a p p a r e n t l y v e r y r e a d i l y splits out a
sulfur atom.

R~R2CN2

~ ' ~ "C,~H5 (-N:t) C6H5 (-S) C6H5-

/\
R2 R~ R-~
I II Ill

I1-111 a R',R:=C6Hs; R,=H; R~-=C6H5

EXPERIMENTAL
Spiro [(3-pipe ridino-2 - p h e n y l i d e n e ) - i ,2 ' ]-3' ,3 ' -diphenylthiirane {IIa). This compound, with rap 115 ~
(dec.), was obtained in 80% yield. Found: C 84.3; H 6.2; N 3.1; S 6.8%. C33H2sNS. Calculated: C 84.1;
H 6.2; N 3.0; S 6.8%~
1 - D i p h e n y l r a e t h y l e n e - 2 - p h e n y l - 3 - p i p e r i d i n o i n d e n e (IIIa). This compound, with rap 165-167 ~ ( i s o p r o -
pyl alcohol), was obtained in 98% yield. Found: C 89.9; H 6.6; N 2.9%. C33H29N. Calculated: C 90.2; H 6.6;
N 3.2%~
1 - B e n z y l i d e n e - 2 - p h e n y l - 3 - p i p e r i d i n o i n d e n e (IIIb). This compound, with rap 150-152 ~ was obtained in
64% yield. Found: C 89.5; H 7.1; N 3.4%. C27H25N. Calculated: C 89.3, H 6.9; N 3.9%. The s t r u c t u r e s of
the compounds obtained in this study w e r e c o n f i r m e d by the IR and PMR s p e c t r a .

LITERATURE CITED
1, A. Sch~nberg, B. KSnig, and E. Singer, Chem. B e r . , 100,767 (1967).
2. N. A. K o r c h e v i n , V. A. Usev, and M. G. Voronkov, Khira. G e t e r o t s i l d . Soedin., 713 (1974).
3~ A. SchSnberg and R. Ardenne, Chem. B e r . , 101,346 (1968).
I r k u t s k Institute of Organic Chemistry., Siberian Branch, Acaderay of Sciences of the USSR. T r a n s -
lated f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 5, p. 714, May, 1974. Original a r t i c l e s u b m i t t e d
N o v e m b e r 26, 1973.

9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

623
CHRONICLES

SYMPOSIUM ON THE CHEMISTRY AND TECHNOLOGY

OF THE HETEROCYCLIC COMPOUNDS OF
FOSSIL FUELS

S. N . Baranov and A. K. Sheinkman

The Second S y m p o s i u m on the C h e m i s t r y and Technology of H e t e r o c y c l i c Compounds of F o s s i l Fuels

was held in Donetsk on O c t o b e r 3-6, 1973. M o r e than 200 s c i e n t i s t s f r o m the v a r i o u s scientific c e n t e r s of
the Soviet Union and w o r k e r s in the c o a l - t a r - c h e m i c a l industry p a r t i c i p a t e d in the activities of the s y m -
p s i u m . M o r e than 50 p a p e r s w e r e p r e s e n t e d in the s e s s i o n s of the following s e c t i o n s : " C h e m i s t r y and
Technology of Nitrogen-Containing Compounds," " C h e m i s t r y and Technology of Sulfur-Containing C o m -
pounds," and " S e a r c h f o r Methods for the Utilization of P r o d u c t s f r o m the Refining of H e t e r o c y c l i c C o m -
pounds." In addition, two p l e n a r y s e s s i o n s w e r e held.
The p r o d u c t s of the refining of fossil fuels a r e c u r r e n t l y the p r i n c i p a l s o u r c e of n i t r o g e n - and s u l f u r -
containing h e t e r o c y c l i c compounds. The advances in the c o a l - t a r - c h e m i c a l and p e t r o c h e m i c a l industries
a r e having a substantial effect on the introduction of c h e m i c a l p r o c e s s e s into the national economy, having
p r o v i d e d the c h e m i c a l industry with r a w m a t e r i a l s and the o t h e r b r a n c h e s of industry with c h e m i c a l p r o -
ducts.
At the s y m p o s i u m it was noted that s o m e n i t r o g e n - c o n t a i n i n g h e t e r o c y c l i c compounds obtained f r o m
colin (for e x a m p l e , fl-picoline) have an unlimited m a r k e t and a r e s c a r c e , while others (quinoline, isoquino-
line, c a r b a z o l e , etc.), the r e s o u r c e s of which amount to thousands or even tens of thousands of tons, a r e
not being skillfully utilized and a r e b u r d e n s o m e industrial w a s t e products. Considering that the s o u r c e of
r a w m a t e r i a l s f o r h e t e r o e y c l i c compounds is constantly i n c r e a s i n g due to the growth of the c o a l - t a r - c h e m -
ical and p e t r o c h e m i c a l i n d u s t r i e s and will p r o b a b l y also i n c r e a s e significantly in the i m m e d i a t e future due
to s e m i c o k i n g t a r , the s e a r c h for methods f o r t h e i r utilization should be c o n s i d e r e d to be p a r t i c u l a r l y u r -
gent.
Methods f o r the utilization of c o n s i d e r a b l e amounts of pyridine and ~ - p i c o l i n e have been found thanks
to r e s e a r c h c a r r i e d out in the Institute of Organic C h e m i s t r y of the Ukrainian SSR and the Chlorine I n s t i -
tute (Kiev) on the s y n t h e s i s of and development of technology f o r the p r e p a r a t i o n of k h l o r a m p (an effective
h e r b i c i d e to c o m b a t r o s e s m a r t w e e d ) and katapin (a s u r f a c e - a c t i v e agent). New methods f o r the utilization
of c o a l - t a r thiophene have been sought by m e a n s of studies by the Institute of H e t e r o o r g a n i c Compounds of
the A c a d e m y of Sciences of the USSR (Moscow), the Makeevskii C o a l - T a r - C h e m i c a l Plant, and a n u m b e r
of o t h e r e n t e r p r i s e s . An effective method for the acidic e x t r a c t i o n of indole f r o m coal t a r has been p r o -
p o s e d by the Phenol P l a n t and Donetsk State University; this is e x t r e m e l y e s s e n t i a l for the s a t i s f a c t i o n of
the r e q u i r e m e n t s of industry, which u s e s indole for the synthesis of tryptophan.
The ozonolysis of quinoline has been i n v e s t i g a t e d by the c o - w o r k e r s of the E a s t e r n Institute of Carbon
C h e m i s t r y , and technology for the production of nicotinic acid f r o m quinoline has been developed. A m e t h -
od for the isolation of c a r b a z o l e f r o m crude a n t h r a c e n e by complexing has been p r o p o s e d .
I m p o r t a n t and i n t e r e s t i n g r e s e a r c h on the catalytic synthesis of pyridine d e r i v a t i v e s was r e p o r t e d
by the c o - w o r k e r s of the Institute of Organic Synthesis of the A c a d e m y of Sciences of the Latvian SSR. A
r e p o r t by c o - w o r k e r s of the Donetsk B r a n c h of the Institute of P h y s i c a l C h e m i s t r y of the A c a d e m y of Scien-
ces of the Ukrainian SSR and Donetsk State U n i v e r s i t y on the h e t a r y l a t i o n of organic compounds by m e a n s
of N - a c y l s a l t s of s i x - m e m b e r e d h e t e r o a r o m a t i c cations, which has m a d e it p o s s i b l e , in one step, to o b -

T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 5, pp. 715-716, May, 1974.

9 1975 PlenumPublishing Corporation, 227 West 17th Street, New York, N.Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy of this article is available from the publisher for $15.00.

624
tain diverse derivatives of phenols, aromatic amines, carbonyl compounds, indole, pyrrolothiophene, etc.,
caused an extensive exchange of ideas.
The possibility of the preparation of effective inhibitors of metal corrosion, antioxidants, dyes, stabi-
lizers for polymers or binders, adhesives, vulcanization accel erat ors and antioxidants for raw and cured
rubbers was reported. Special attention in connection with the problem of the protection of the biosphere
was directed to the problem of the utilization of pickling baths inhibited by salts of pyridine bases and to
methods for the possible microbiological transformation of such substances.
Considerable interest was generated by a report by Irkutsk chemists regarding the possibility of the
preparation of efficient extracting agents for precious metals during the refinement of sulfurous components
of Bashkirian oils.
The symposium notes that, despite the fact that a number of universities and several academic estab-
lishments (the Institute of Organic Synthesis of the Academy of Sciences of the Latvian SSR, the Institute of
Organic Chemistry of the Academy of Sciences of the Ukrainian SSR, and the Donetsk Branch of the Institute
of Physical Chemistry of the Academy of Sciences of the Ukrainian SSR) have participated with the branch
institutes in the development of c o a l - t a r chemistry in recent y e a r s , the number of scientists doing r e -
search on this problem is, in general, clearly inadequate and is not in line with the significance that it has
in the national economy of our country. The scientific forecasting of requirements with respect to the
chemical products of coking is undergoing only weak development; this does not enable industry to develop
p r o ces s es for the isolation of heterocyclic compounds from the products of c o a l - t a r refining.
The conference demonstrated the considerable efficiency of r e s e a r c h workers active in this field.
We also note that the theoretical level has also risen substantially in recent years and that diverse meth-
ods for the isolation and analysis of substances have come to be used considerably more extensively.

625
FIRST ALL-UNION CONFERENCE ON T H E CHEMISTRY
OF HETEROCYCLIC COMPOUNDS

A. N. Kost

C o n f e r e n c e s devoted to one o r another a s p e c t of the c h e m i s t r y of h e t e r o c y c l i c compounds have been

held r e p e a t e d l y in the c o u r s e of the l a s t two decades in o u r country; h o w e v e r , all of them w e r e d e p a r t m e n -
tal c o n f e r e n c e s and could not b r i n g t o g e t h e r s c i e n t i s t s working in aI1 of the m i n i s t r i e s and d e p a r t m e n t s of
the country. F o r this r e a s o n , the All-Union Conference on the C h e m i s t r y of H e t e r o c y c l i c Compounds, the
chief t a s k of which w a s e x p o s u r e of the o v e r a l l f r o n t of the development of s c i e n c e in this field, was o r g a -
n i z e d in Moscow f r o m D e c e m b e r 24 to 26, 1973, at the initiative of the Scientific Council on Fine Organic
Synthesis in affiliation with the A c a d e m y of Sciences of the USSR (AS of the USSR). In view of the fact that
a v e r y wide c i r c l e of s p e c i a l i s t s a r e engaged in the c h e m i s t r y of h e t e r o c y c l i c compounds, the t h e m e of the
c o n f e r e n c e was l i m i t e d to the c h e m i s t r y of n i t r o g e n h e t e r o c y c l e s . However, even when the t h e m e was n a r -
rowed down in this way, although s e v e r a l scientific schools p r o v e d to be outside the scope of the activity
of the c o n f e r e n c e , m o r e than 500 applications for p a p e r s w e r e , n e v e r t h e l e s s , submitted, f r o m wLich 106
c o m m u n i c a t i o n s w e r e s e l e c t e d and p r e s e n t e d (there w e r e m o r e than 350 p a r t i c i p a n t s in the conference).
A f t e r the opening a d d r e s s by A s s o c i a t e d M e m b e r of the A c a d e m y of Sciences N. K. Kochetkov, who
opened the c o n f e r e n c e , p l e n a r y p a p e r s w e r e p r e s e n t e d by P r o f e s s o r Ya. L. G o l ' d f a r b (Moscow) and B. V.
Ioffe (Leningrad). The f i r s t p a p e r e x a m i n e d the h i s t o r i c a l d e v e l o p m e n t of concepts r e g a r d i n g the a m i n a -
tion of the pyridine ring, c o m m e n c i n g with the r e s e a r c h of A. E. Chichibabin (in which the s p e a k e r h i m -
s e l f had participated) and ending with the data obtained in the l a b o r a t o r y of Yao L. G o I ' d f a r b in r e c e n t y e a r s .
The second p a p e r was devoted to the r e s e a r c h of B. V. Ioffe and his students on the s y n t h e s i s , i s o m e r i z a -
tion, and r e a c t i o n s ( p a r t i c u l a r l y those involving ring opening) of pyrazolineso The conference also c o n -
cluded with two p l e n a r y p a p e r s . A s s o c i a t e M e m b e r of the AS of the USSR V. P. M a m a e v (Novosibirsk) gave
an i n t e r e s t i n g r e v i e w of c a s e s involving ring opening and r e c y c l i z a t i o n s in the p y r i m i d i n e s e r i e s while
s i m u l t a n e o u s l y giving the p h y s t e o c h e m i c a l b a s i s for the r e a c t i v i t y of the molecule. P r o f e s s o r A. N. K o s t
(Moscow) r e l a t e d new r e a r r a n g e m e n t of a r y l h y d r a z i n e d e r i v a t i v e s that substantially amplify the p o s s i b i l i t y
of the F i s c h e r synthesis (the synthesis of t r y p t a m i n e and h o m o t r y p t a m i n e s by the method p r o p o s e d by Io I.
G r a n d b e r g , the s y n t h e s i s of 2 - a m i n o i n d o l e s f r o m a c y l a r y l h y d r a z i n e s , new syntheses of c a r b o l i n e s , etc.,).
T h r e e s e c t i o n s - m o n o c y c l i c h e t e r o c y c l e s , condensed s y s t e m s , and p h y s i c . c h e m i c a l methods for the in-
v e s t i g a t i o n of h e t e r o c y c l e s - o p e r a t e d at the c o n f e r e n c e . We at once note that this s o r t of division p r o v e d
to be unfortunate, i n a s m u c h as studies devoted to the synthesis and p r o p e r t i e s of compounds w e r e s a t u -
r a t e d with data f r o m p h y s i c . c h e m i c a l methods of investigation in those c a s e s in which they w e r e a c c o m -
plished at a high level. Only the m a s s s p e c t r a l studies w e r e distinguished by a c e r t a i n independent c h a r -
acter.
In the f i r s t section, the g r e a t e s t e m p h a s i s was upon studies involving the synthesis of h e t e r o c y e l i c
s t r u c t u r e s with the use of c a r b e n e s and n i t r e n e s , cycloaddition, p a r t i c u l a r l y 1 , 3 - d i p o l a r addition, and the
s y n t h e s i s , s t e r e . c h e m i s t r y , and r e a c t i o n s of s m a l l rings. One should e s p e c i a l l y note the c o m m u n i c a t i o n s
of A c a d e m i c i a n B. A. A r b u z o v on d i a z a c y c l o b u t a n e s , of B. V. Ioffe on a l k o x y a z i r i d i n e s , of P r o f e s s o r S. S.
Novikov on d i a z i r i d i n e s , and of A s s o c i a t e M e m b e r of the AS of the USSR B. M. Mikhailov on r i n g s that in-
clude nitrogen and b o r o n a t o m s .
The second section p r o v e d to be m o r e d i v e r s i f i e d with r e s p e c t to the subjects c o v e r e d , although h e r e ,
as in the f i r s t section, the p r i m a r y attention of the s p e a k e r s was d i r e c t e d to h e t e r o c y c l i z a t i o n and, to a
l e s s e r d e g r e e , to the p r o p e r t i e s of the s t r u c t u r e s t h e m s e l v e s . A l a r g e n u m b e r of the c o m m u n i c a t i o n s p e r -

T r a n s l a t e d f r o m K h i m i y a G e t e r o t s i k l i c h e s k i k h Soedinenni, No. 5, pp. 716-717, May, 1974.

9 1975 Plenum Publishing Corporation, 227 West 17th Street, N e w York, N.Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

626
tained to the c h e m i s t r y of h e t e r o a r o m a t i c s y s t e m s . " The studies of Academician of the AS of the Ukrainian
SSR F. S. Babichev (Kiev) on the c h e m i s t r y of isoindoles, in which shifting reagents were used extensively
for the e s t a b l i s h m e n t of the s t r u c t u r e s of s u b s t a n c e s , the lengthy communication of A s s o c i a t e M e m b e r o f .
the AS of the Ukrainian SSR A. V. Bogat-skii on benzodiazepines and their e i g h t - and n i n e - m e m b e r e d analogs,
a group of p a p e r s on the synthesis and p r o p e r t i e s of benzimidazole derivatives, two p a p e r s by V. Io Shvedov
on new methods for the synthesis of condensed s t r u c t u r e s with a p y r a z i n e ring, a communication by A. K.
Sheinkman on new developments of the hetarylation reaction, a p a p e r by Academician I. Ya. Postovskii on
a z a a r o m a t i c phenanthrenoid compounds, etc., can be singled out f r o m the b r o a d s p e c t r u m of the p a p e r s
p r e s e n t e d in this section~
P a p e r s relating to both m o n o c y c l i c and condensed s t r u c t u r e s were p r e s e n t e d in the section devoted to
p h y s i c o c h e m i c a l methods. As we stated above, a s e r i e s of p a p e r s on the m a s s s p e c t r o m e t r y of organic c o m -
pounds was a p r o m i n e n t feature of the conference. Thus this method, the development of which has lagged
somewhat in our country, has acquired r a t h e r w i d e s p r e a d significance. The c o n c r e t e p r o b l e m s involved in
the evaluation of the fine s t r u c t u r e and the p r o p e r t i e s of molecules (conformation, t a u t o m e r i c equilibrium,
kinetic evaluation of r e a c t i v i t i e s , ete.) with the use of various s p e c t r o s c o p i c methods; for example, F o u r i e r
C ~3 s p e c t r o s c o p y in the studies by P r o f e s s o r K. M. Dyumaev and Academician A. S. Sadykov, w e r e solved
in a l a r g e n u m b e r of the remaining p a p e r s in this section. Several p a p e r s were devoted to q u a n t u m - c h e m i -
cal calculations.
Although the papers p r e s e n t e d at this conference did not have a p p l i e d - c h e m i s t r y c h a r a c t e r , there a r e
however, communications dealing with t h e r m o c h r o m i c dyes, p e s t i c i d e s , new medicinal s u b s t a n c e s , a n t i -
oxidants for oils and fuels, additives for p o l y m e r s , s e n s i t i z e r s extracting agents for r a r e e l e m e n t s , etc.
The p r o s p e c t s for the further development of r e s e a r c h on nitrogen h e t e r o c y c l i c substances in quite a n u m -
b e r of directions was e s p e c i a l l y e m p h a s i z e d in a resolution of the conference. The conference was un-
doubtedly interesting and useful. Unfortunately, only a v e r y small n u m b e r of copies of the s u m m a r i e s of
the p a p e r s w e r e r e p r o d u c e d , and this limited the possibility for f a m i l i a r i z a t i o n with the m a t e r i a l s of the
conference for those who could not be p r e s e n t .

627
INTERCONVERSIONS OF SOME NITROGEN-CONTAINING
HETEROCYCLIC SYSTEMS (REVIEW)

C . W. R e e s and R. C. Storr UDC 547.718'872.31'892.89~

Most of our recent r e s e a r c h has been devoted to the synthesis and c h e m i s t r y of five-, six-, and s e v e n -
m e m b e r e d h e t e r o c y c l e s containing t h r e e adjacent nitrogen atoms: 1 , 2 , 3 - t r i a z o l e s , 1,2,3-triazines, and
1,P,3-triazepines, Special attention was directed to t h e i r conversion to other heterocyclic s y s t e m s .
Although these t r i a z a h e t e r o e y c l e s are of interest in t h e m s e l v e s , our r e s e a r c h a r o s e as a result of
attempts to c r e a t e t h r e e types of reactive compounds: dehydrogenated a r o m a t i c s y s t e m s , 1 H - a z i r i n e s ,
and azacyclobutadiene (azete) derivatives (I, II). The last two types are s i m i l a r to cyclobutadiene and ben-
zocyclobutadiene - highly reactive antiaromatic c a r b o c y c l e s - and are the simplest 47r-electron nitrogen-
containing h e t e r o c y c l i c s y s t e m s . Heterocyclic analogs of this sort which, despite a n u m b e r of e a r l y at-
tempts [1] to obtain them, are still unknown, will have great t h e o r e t i c a l and synthetic value.

_T
Of the very small number of published papers on the preparation of azetes, the method in [2],which
was based on reverse Diels-Alder reactions of IT[ and IV, is of interest. A certain amount of dimethyl
phthalate was obtained from diester HI, but methoxydimethylazete was not detected. Compound IV was also
converted to dimethyl phathalate, but the azetine, which might have given strictlythe azete on subsequent
elimination, was not obtained.

~/~..I. cH3
CH3 CH3SO2--N~
COzCH3
~ --
co2cM3

"CO2CH~
m

We decided to commence our r e s e a r c h with a study of benzazete (II), feeling that it would be e a s i e r
to obtain it and that it would be stabilized by the benzene ring. Our synthesis was based on the following
facts, c i s , c i s - l , 4 - D i e y a n o b u t a d i e n e (VI) is the stable product of a n u m b e r of reactions in which o - d i n i t r e n o -
benzene (V) formally participates: oxidation of o-phenylenediamine [3, 4] o r 2-aminobenzotriazole [5] and
t h e r m a l decomposition of o-diazidobenzene [6]. In contrast to this, c i s , c i s - o c t a - 3 , 5 - d i e n e - l , 7 - d i y n e (VII)
is unstable and is readily cycltzed to benzocyelobutadiene [7]. In this connection, p a r t i c l e s of the o - n i t r e n o -
phenylcarbene (VIII) type seem of great interest, inasmuch as they may be cyclized to give the r e q u i r e d
benzazete (II) o r m a y be cleaved to give cyanoacetylene IX. The eyanoacetylene In turn may be t h e r m a l l y
or photochemically cyelized in analogy with diacetylene VII to benzazete II.
The apparent p r e c u r s o r of the carbenonitrene of the VIII type is the corresponding diazoazide (for e x -
ample, XI). It was found that X is obtained with c e r t a i n difficulties, inasmuch as the usual synthesis of
azidohydrazone X from ketone and hydrazine in hot ethanol In the p r e s e n c e of acetic acid gave 3 - m e t h y l -
Indazole in v e r y high yield. This usual but smooth and, apparently, general reaction is a good method for

Liverpool University, England. T r a n s l a t e d from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp.

723-736, June, 1974. Original article submitted October 12, 1973.

9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

629
 C
CN
CN

vt__J

i~ wl-'3

the p r e p a r a t i o n of indazoles and is worthy of f u r t h e r study. However, azidohydrazone X can be obtained

f r o m the azidoketone and hydrazine at r o o m t e m p e r a t u r e in the p r e s e n c e of iodine as a c a t a l y s t . Diazo-
azide XI, which was c o n v e r t e d to 4 - m e t h y l b e n z o t r i a z i n e (XII) in high yield by t h e r m a l decomposition in hot
benzene, was obtained by oxidation of the hydrazone with m e r c u r i c oxide. Thus, only one mole r a t h e r than
two m o l e s of nitrogen was split out, but this result is, n e v e r t h e l e s s , interesting, inasmuch as simple a r o -
m a t i c 1 , 2 , 3 - t r i a z i n e s are c u r r e n t l y a l m o s t unknown [8]. The decomposition of the diazoazide u n d e r m o r e
s e v e r e conditions led to unidentified m i x t u r e s . When the m e t h y l group in diazoazide XI was r e p l a c e d by a
hydrogen atom, the dtazoazide proved to be unstable, and a t t e m p t s to replace it by a phenyl group were u n -
s u c c e s s f u l because cyclization to 3-phenylindazole could not be avoided.
CH 3 CH 3 CH 3

~',~.,,,.~.,. N 3 N

Oxidation of readily a c c e s s i b l e o - a m i n o h y d r a z o n e s XlII (R =CH3, C6H5) [9] with lead t e t r a a c e t a t e in

methylene chloride at r o o m t e m p e r a t u r e proved to be a s i m p l e r method f o r the p r e p a r a t i o n of the t r i a z i n e s .
In this c a s e , t r i a z i n e s XIV were obtained in m o d e r a t e yields along with the c o r r e s p o n d i n g o - a c e t a m i d o -
ketones.
R R

NH2
xll__A xi__~v

Another approach to the synthesis of compounds with the s t o i c h i o m e t r y o f a c a r b e n o n i t r e n e was based

on the r e s u l t s of our investigation of the oxidation of 1-and 2 - a m i n o b e n z a t r i a z o l e s [5]. The f i r s t of these
compounds gave the 1 - n i t r e n e , which, on splitting out two m o l e s of nitrogen, was c o n v e r t e d to d e h y d r o b e n -
zene; the second compound gave the 2 - n i t r e n e , which split out one m o l e of nitrogen to give dicyanobutadiene
VI. The analogous oxidation of 1- and 2-aminoindazoles should have led to l~-nitrenes XV and XVI, which
would undergo cleavage to give, r e s p e c t i v e l y , dehydrobenzene and (or) benzazete (H) and benzazete and (or)
cyanoaeetylene IX.

I
_ IN:
x...X ~ N
9 OH- J ~ - ~

xv_J
N.
C ~N

However, aminoindazoles XVH and XVIII [10] a r e oxidized v e r y rapidly by lead t e t r a a c e t a t e u n d e r

mild conditions, to give benzotriazines XIV in high yields. They a r e p o s s i b l y f o r m e d f r o m the i n t e r m e d i a t e
n i t r e n e s with ring expansion.

630
 R R

xv,~ I
_ _ _ NH 2
R = CH 3 ~ C6H5 , O C H 3 XVlll

The above-indicated methods for the p r e p a r a t i o n of b e n z o t r i a z i n e s a r e inapplicable when 1R=H, and

the oxidation of unsubstituted N - a m i n o i n d a z o l e leads to benzotriazine XIV (R =H) only when absolutely no
nucleophilic r e a g e n t s are p r e s e n t . It is not s u r p r i s i n g that the C 4 atom in benzotriazine is v e r y e l e c t r o -
philic and that benzotriazine XIV is hydrated at the 3, 4 bond to give o - a m i n o b e n z a l d e h y d e .
Yet another method for the s y n t h e s i s of b e n z o t r i a z i n e s , which also includes r e a r r a n g e m e n t of n i t r e n e s ,
is based on the oxidation of 1- and 3-aminoquinazolones XIX and XX. In this c a s e the b e n z o t r i a z i n e s a r e
H2~ H,~ H

N=N-NH 2 NH 2

possibly formed from the nitrenes by ring expansion with subsequent splitting out of carbon monoxide (eom~
pare XXI and X~TDo
R

__ NH 2
x,_~x
R
H

xx

This type of r e a c t i o n was f i r s t o b s e r v e d in the m o n o c y c l i c s e r i e s during the oxidative t r a n s f o r m a t i o n

of 1 - a m i n o - 2 - p y r i d o n e s to p y r i d a z i n e s [11]. A s i m i l a r t r a n s f o r m a t i o n of 1-aminoquinoxalones XXI to benzo-
1 , 2 , 4 - t r i a z i n e s XXII is also known [12]. This sequence of amination and oxidation r e a c t i o n s is a t e m p t i n g
method for the synthesis of 1 , 2 , 4 - t r i a z i n e s f r o m the r e a d i l y a c c e s s i b l e s t a r t i n g r e a g e n t s .

N"~- O ~ ~'N" ~ O ~ N ~ N
H I
_ _ NH 2
XXI XXII

In the attempt to obtain carbenonitrenes VIII from indazolonitrenes XV and XVI, the reaction conditions
w e r e evidently insufficiently s e v e r e to bring about splitting off of nitrogen up to the point of ring expansion
to give b e n z o t r i a z i n e s . Thus we should have obtained indazolonitrenes under c o n s i d e r a b l y m o r e s e v e r e
conditions, u n d e r which, however, i n t r a m o l e c u l a r t r a n s f o r m a t i o n s would have been s u p p r e s s e d . I n s t a n t a n -
R R
o cH S-----:
Pb(OAc)4 ~ II/ 3 ~ r~
--NH~ -- l I N--N=S ~-
~ N / ~ (CH3)2 SO ~1...~./~ N / ~CH3 ~ N
XVJ_~I XXIII xxIV

eous p y r o l y s i s in the v a p o r phase s e e m e d ideal for this p u r p o s e , and p r e v i o u s investigations [13]provided

a basis for a s s u m i n g that sulfoximides XXIH a r e suitable for p y r o l y s i s . The oxidation of 2 - a m i n o i n d a z o l e s
(XVII, R =H, CH 3) with lead t e t r a a c e t a t e in the p r e s e n c e of dimethyl sulfoxide (DMSO) actually gave s u l -
foximldes XXIII. The tying up of the nitrene p r e v e n t e d c o m p e t i t i v e ring expansion to a t r i a z i n e . At 450~
(0.01 m m ) these sulfoximides, as a s s u m e d , w e r e p y r o l y t i c a l l y f r a g m e n t e d to DMSO, nitrogen, and c o n j e c -
t u r a l l y , to a c a r b e n o n i t r e n e , which underwent ring expansion to give a cyanoacetylene (XXIV, R =H, CH3).
However, t h e s e c y a n o a c e t y l e n e s a r e m o r e s i m i l a r to biscyanides VI than to bisacetylene VII and do not
undergo eyclization to benzazete d e r i v a t i v e s . The c y a n o a c e t y l e n e s w e r e subjected to t h e r m a l and photo-
c h e m i c a l action u n d e r v a r i o u s conditions in the p r e s e n c e of nucleophiles and dienes, which might have r e -
cated with the b e n z a z e t e s if they had f o r m e d .

631
 Attention was t h e r e f o r e d i r e c t e d to another s o u r c e of pyrolytic generation of c a r b e n e o n i t r e n e s - to
benzotriazines t h e m s e l v e s , f r o m which it was n e c e s s a r y to r e m o v e a nitrogen m o l e c u l e .
R

N

However, the f i r s t e x p e r i m e n t showed that t r i a z i n e s XIV a r e r e a d i l y cleaved at r e l a t i v e l y low t e r n -
p e r a t u r e s (450-500~ to give dehydrobenzene and, consequently, diphenylene in yields up to 60%, However,
when this r e a c t i o n was applied to pyridine in o r d e r to obtain the d i f f i c u l t - t o - p r e p a r e diazadiphenyIene it
was found that N 2 can be split out s e l e c t i v e l y , The p y r o l y s i s of p y r i d o t r i a z i n e XXV gave 2 - c y a n o - 6 - m e t h y l -
pyridine as a r e s u l t of splitting out of N 2 and m i g r a t i o n of a hydrogen a t o m , The f r a g m e n t a t i o n of b e n z o -

~N~NH, - - ~L~N, IN
_ _ H3CI ~ CN
XXV
triazine probably occurs by means of successive splitting out of N 2 and I~CN. We therefore made a p a r -
t i c u l a r l y thorough investigation [14] of the pyrolysis of benzotriazines, p a r t i c u l a r l y of 4-phenylbenzotriazine
.(XXVI), at 400-450 ~ At temperatures above 450 ~ the chief product was diphenylene, but at 420 ~ as a r e -
sult of the p y r o l y s i s we obtained a b r i g h t - r e d oil containing 20%dlphenylene, 15% 9-phenylacridine (XXIX),
5%unchanged benzotriazine XXVI, and 60%of a product that we c o n s i d e r e d to be the f i r s t t r u e azete d e r -
ivative - red 2-phenylbenzazete XXVII.
C6H5
I/~( C6H5 ~ ~N6~C6H5

XXV~

XXlX
Somewhat unexpectedly, the latter proved to be stable at - 80 ~ but was converted on heating to room
temperature to a pale-yellow dimer (XXV[I) of 2-phenylbenzazete (50%, based on the starting benzotria-
zine).
The quantitative c o n v e r s i o n of this d i m e r to 9-phenylacridine ( t h e r m a l l y o r by t r e a t m e n t with a hot
alcohol solution of hydrochloric acid} is in a g r e e m e n t with al~ of the four possible angular d i m e r i c s t r u c -
t u r e s of the XXVIII type, which a r e s i m i l a r to those f o r m e d f r o m benzocyclobutadiene. Two l i n e a r d i m e r i c
s t r u c t u r e s - d i b e n z o - l , 2 - and d i b e n z o - l , 5 - d i a z o e i n e - would also be possible, but the l a t t e r is excluded
by c o m p a r i s o n with a known s a m p l e [15], and the f i r s t is incompitable with the c o n v e r s i o n to 9 - p h e n y l a c r i d -
ineo The 9-phenylacridine f o r m e d as a r e s u l t of the p y r o l y s i s can also be obtained by reaction of the b e n z a -
zete with dehydrobenzene.
A f u r t h e r c o n f i r m a t i o n of the fact that the red compound in the p y r o l y z a t e is a z e t e XXVII is offered
by its e x t r e m e l y rapid r e a c t i o n (with decolorization) with nucleophilic r e a g e n t s and conjugated dienes when
they a r e introduced d i r e c t l y into the cold p y r o l y z a t e at - 4 0 ~ o r at lower t e m p e r a t u r e s ~ Thus XXVII r e -
acts instantaneously with dilute sulfuric acid in t e t r a h y d r o f u r a n (THF) to give o-amtnobenzophenone (50%}
o r with diphenylhydrazine in T H F to give o-aminobenzophenone phenylhydrazone (60%).o*
C6H5 C6H5

_XXVll HzX ~ N H TM ~N~ <

2
X=O~NNHC6H
5
* The yields a r e given for the s t a r t i n g t r i a z i n e , and, consequently, we a r e dealing h e r e with a l m o s t q u a n -
titative c o n v e r s i o n of azete XXVII.

632
 Like benzocyclobutadiene, azete i ~ I readily undergoes cyoloaddition with various dienes, and this
opens up broad possibilities for the synthesis of new heterocyclie systems. Thus it reacts with 1,3-diphenyl-
isobenzofuranto give adduct XXX (55%) with a four-membered azetine ring. However, the strained azetine
ring is relatively easily cleaved [16]. For example, reaction with cyclopentadiene leads to amino alcohol
XXXI (35%), which is formed by hydration of the D i e l s - A l d e r adduct during chromatographic treatment.

~ ~ XXVII
- - C6H5
X

Tetraphenylcyclopentadienone and 3,6-diaryltetrazines also give cycloadducts, which are converted

to benzazocine XXXII (50%) or benzetriazocine XXXIII (Ar =2-pyridyl) as a result of splitting out of CO and
N2, respectively.
HsCB C~H5 HsC~. /CB r"5

f I "CsH5
C6H5 XXXll C~H5
XXVII
~ H5C6~" ; HsC6 At"
N N

Ar XXX!lJ

Cycloaddition to benzazete XXVII was also observed with some 1,3-dipoles. Thus XXVII reacts with
diazomethane to give 3-phenylindole in ve r y low yield, possibly through splitting out of N 2 from the initial
adduct. However, the adduct formed with 4-methylbenzonitrile oxide, viz., oxadiazoline XXXIV, was ob-
tained in 50%yield. Adduct XXXIV underwent a new rearrangement to give benzimidazole XXXV in high
yield on heating in solution or during chromatography. The weakening of the strain of the azetine ring, the
weakness of the O - N bond, and the stability of the resulting benzophenone carbonyl group possibly promote
this rearrangement. An iminonitrene side chain, cyclization with the participation of which subsequently
gives benzimidazole XXXV, is formed simultaneously with this carbonyl group.
. ~ C6H5

H
XXVII J
H5C6 _ ~.~H5

I~3L--- N y

X215 AP N~ A r
k
Like benzocyclobutadiene, 2-phenylbenzazete XXVII is almost (or completely) unreactive with dieno-
philes such as alkenes, alkynes, and enamines. Dimerization and the possible reaction with dehydrobenzene
mentioned above constitute exceptions to this.
2-Phenylbenzazete proved to be relatively stable: it remained unchanged at - 5 0 ~ for a long time. We
decided to attempt to synthesize azetes with g r e a t e r stability by weakening the antiaromatic c h a r a c t e r of
the four-membered ring by increasing the electron density in the imine bond or by the introduction of an-
other condensed benzene ring. The f o r m e r was achieved as a r e s u l t o f p y r o l y s i s of 4-(p-methoxyphenyl)-
benzotriazine, which formed 2-(p-methoxyphenyl)azete. Mthough it underwent the same transformations
as the 2-phenyl derivative (XXVII), it was considerably more stable in solution and reacted appreciably
more slowly with tetraphenylcyclopentadiene and diphenylisobenzofuran.
Stabilization by condensation with a benzene ring was convincingly demonstrated during the flash pyro-
lysis of 4-phenyl-l,2,3-naphtho[2,3-b]triazine (XXXVIII). It gave 2-phenylnaphtho[2,3-b]azete (XXXVI) as

633
an o r a n g e - r e d c r y s t a l l i n e substance that was stable for s e v e r a l hours at r o o m t e m p e r a t u r e , e v e n when it
had a c c e s s to the a i r . Azete XXXVI v e r y readily d i m e r i z e s in solution, and, like the b e n z a z e t e s , r e a c t s
with nucleophilic r e a g e n t s and dienes. The yields of adducts d e c r e a s e as the length o f t i m e t h a t azeteXXXV1
is s t o r e d p r i o r to the r e a c t i o n is i n c r e a s e d . This azete can be c o m p a r e d with the analogous c a r b o c y c l i c
compound (XXXVII), which can also be isolated [17].
The facts set forth above constitute a l m o s t indisputable evidence that we have synthesized a z e t e s for
the f i r s t t i m e , and we hope that they will find sufficient application in the c h e m i s t r y of h e t e r o c y c l i c s y s -
tem.
The following portion of o u r p a p e r is devoted to r e s e a r c h with s e v e n - m e m b e r e d l , 2 , 3 - t r i a z e p i n e s .
T h e s e h e r e t o f o r e unknown h e t e r o c y c l e s w e r e r e q u i r e d for the synthesis of special dehydrogenated a r o m a t i c
compounds. V e r y little is p r e s e n t l y known about n o n - o r t h o - d e h y d r o g e n a t e d a r o m a t i c s y s t e m s . We have

XXXVI XXXVII
6H5 i~...~ H5 " C6H5
. " ?,
H XXXVIIi"

shown [18, 19] that o - d e h y d r o b e n z e n e d e r i v a t i v e s add s t e r o s p e c i f i c a l l y to dienes, while , m e t a " - d e h y d r o -

genated 1,8-dehydronaphthalene adds s t e r o s p e c i f i c a l l y to monoenes [20]. This difference was explained by
the fact that dehydrobenzene has a s y m m e t r i c a l higher filled MO (XXXIX), while 1,8-dehydronaphthalene
has an a n t i s y m m e t r i c a l MO (X-L) [21]. F u r t h e r m o r e , Hoffmann [21] has p r e d i c t e d that 4,5-dehydrophenan-
threne (XLI) and 2,2'-dehydrodiphenyl will have s y m m e t r i c a l higher filled MOs. Consequently, t h e s e c o m -
pounds will add to dienes in the 1, 4 position, which is c o n t r a r y to the conclusion that can be drawn f r o m
simple s t e r e o e h e m i c a l c o n s i d e r a t i o n s . To obtain t h e s e compounds by the chosen method, we needed a m i n o -
t r i a z e p i n e s XLII and XLIII. We decided to begin with the synthesis of the latter, i n a s m u c h as the s t a r t i n g

XXXIX XL
XL~

~NH2 ~ ~NH2
XL.J_._J XCtl_...J

compounds f o r its p r e p a r a t i o n were m o r e a c c e s s i b l e and, in addition, the probability of the f o r m a t i o n of a

s e v e n - m e m b e r e d ring in this m o r e flexible s y s t e m was higher. D i b e n z o [ d ~ f ] - l , 2 , 3 - t r i a z e p i n e (XLVII),
which, like acyclic d i a r y l t r i a z i n e s , might have p r o v e d to be unstable and p o s s i b l y nonplanar and n o n a r o -
m a t i c (or e v e n a n t i a r o m a t i c with an 8 v - e l e c t r o n s y s t e m ) , was n e c e s s a r y for the amination and oxidation.
The p r e c u r s o r of t r i a z e p i n e XLVII is 2,2'-diaminodiphenyl, which can be i n t r a m o l e c u l a r l y cyelized
to a t r i a z e p i n e on diazottzation [22, 23]. However, the diazotization p r o v e d to be e x t r e m e l y complex, and
we w e r e unable to isolate a t r i a z e p i n e , although it is p o s s i b l y an i n t e r m e d i a t e . (See s c h e m e on following
page .)

Diazotization in dilute HC1 gave all of the p r o d u c t s shown in the s c h e m e above. C a r b a z o l e was ob-
tained in high yield by diazotization in 5 N HC1 o r 50%acetic acid. Aprotic diazotization with pentyl nitrite
in refluxing benzene gave iminobenzocinnolininm ylld XLIV, which is an i s o m e r of t r i a z e p i n e XLVII. A
1 4 - m e m b e r e d cyclic b i s t r i a z i n e (XLV) was obtained in refluxing methylene chloride containing catalytic
amounts of hydrogen chloride.
A t t e m p t s to facilitate the f o r m a t i o n and i n c r e a s e the stability of the t r i a z e p i n e s t e r e o o h e m i c a U y by
m e a n s of r e m o v a l of the a r o m a t i c rings f r o m c o p l a n a r i t y by m e a n s of 6,6' substituents and also by m e a n s

634
 ~ NH

XLIV
N\ N.,.,-H

XLV
NaNO~2 C5HIIONOi -C6H6
- ./~C5H~10 NO --
AcOH h J CH2Ct2

//"-,.,...NH2

<~ NH2

NaNO21 dilute
HCt

XLIV --p NH2 -F -~-

NH2 H2N - ~

XLV/

of i n c r e a s i n g the angles between the bonds in the s e v e n - m e m b e r e d ring, linking the 6 and 6' positions through
the c a r b o n y l group, and a t t e m p t s to synthesize the m o r e stable N - s u b s t i t u t e d t r i a z e p i n e f r o m m o n o - N - s u b -
stituted dIaminodiphenyl w e r e u n s u c c e s s f u l . We then turned to the p r e p a r a t i o n of the t r i a z e p i n e by f o r m a -
tion of a C - N bond r a t h e r than an N - N bond, just as in all of the p r e c e d i n g r e a c t i o n s .
After s e v e r a l u n s u c c e s s f u l a t t e m p t s , we a r r i v e at the conclusion that this can be achieved by t e t r a -
azotization of diaminodiphenyl and subsequent t r e a t m e n t with a m m o n i a . This would lead to l i n e a r t r i a z i n e
XLVIII in which the nucleophilic side chain m a y r e p l a c e the diazonium group to give a t r i a z e p i n e ring. Of
c o u r s e , cyclization of the t r i a z i n e to give XLIX is also p o s s i b l e , but the l a t t e r will r e a d i l y split out n i t r o -
gen to give t r i a z e p i n e XLVII. This method p r o v e d to be e x t r e m e l y s u c c e s s f u l , t r i a z e p i n e XLVII (a stable
light-yellow c r y s t a l l i n e substance with mp 100 ~ was obtained in 75%yield by t e t r a a z o t i z a t i o n of d i a m i n o -
diphenyl in dilute HC1 at 0 ~ with subsequent c a r e f u l alkalization with a m m o n i a at 0% A t e t r a z o n i u m b o r o -

~ :~+ NH3 ~L~N=N__NH2

XLVIII
~N

XLVII

~ XLIX
N~--N=N--H
N#N

fluoride, which gave a t r i a z e p i n e on t r e a t m e n t with NH 3 [23], has also been isolated.

After isolation of the t r i a z e p i n e and investigation of its p r o p e r t i e s , it b e c a m e possible to explain the
complexity of the diazotization of 2,2'-diaminodiphenyl. On gentle heating in benzene, the t r i a z e p i n e was
c o n v e r t e d quantitatively to ylid XLIV, but in 5 N HC1 o r 50% acetic acid it gave a quantitative yield of c a r -
bazole. However, the t r i a z e p i n e can be obtained in m o r e acidic m e d i a (concentrated HC1 o r 50%H2SO4) , in
which it a p p a r e n t l y e x i s t s as a stable dication (LI). The f o r m a t i o n of all of the p r o d u c t s of diazotization
of diaminodiphenyl can be explained by r e a r r a n g e m e n t of t r i a z e p i n e XLVII to ylid XLIV o r by r e a c t i o n of
aminodiazonium salt L with the ylid to give aminoazide XLVI and benzocinnoline, and also by o t h e r r e -
actions indicated in the s c h e m e . (See s c h e m e on following page.) The IR s p e c t r u m of t r i a z e p i n e XLVII
does not contain the c h a r a c t e r i s t i c band of the diazonium g r o u p , although its c h e m i c a l p r o p e r t i e s , as in-

635
 XLW ~ XLV

~,~ ~ N H 2

dicated below in the scheme, are primarily properties of the diazo compound. It also couples with fl-naph-
thol to give an azo dye.

The triazepine ring was not disrupted during N-methylation of the lithium salt, but it cannot be p r e -
served when functional groups are introduced. Thus,for example, reaction with benzoyl chloride and ethyl
chloroformate gave ring-opening products of the LII type.

NHCO2R - - XLVII ~ N - - N H 2 -t-

LII LIII

In particular, we were unable to isolate N-amino compound LIII, although it is also formed during
amination. The triazepine does not react with chloramine or with O-(2,4-dinitrophenyl)hydroxylamine.
Hydroxylamine--O-sulfonic acid gives aminoazide XLVI in high yield, while aminoazide R'-LVI (30%) and
N-aminocarbazole LIII (40%) are formed on treatment of the lithium salt with O-(mesitylsulfonyl)hydro-
xylamine. Both of these products can be formed from N-aminotriazepine XLIII during ring opening to give
a diazonium-hydrazine ion pair, in which replacement of the nitrogen can lead to LIII, while intramole-
cular nitrogen t r a n s f e r can lead to XLVI (in analogy with the intermolecular reaction between diazonium
ions and hydrazines).
The r e s e a r c h on dibenzo[d~f]-l,2,3-triazepine (XLVII) also proved to be of value in another respect.
As already pointed out, when this triazepine is heated in benzene it rearranges to give N-iminobenzocin-
nolinium ylid XLIV. This ylid was also obtained directly by reaction of 2,2,-diaminodiphenyl with pentyl

636
nitrite in refluxing benzene and subsequent amination. The m e c h a n i s m of the X L V I I - X L I V t r a n s f o r m a t i o n
was p a r t i a l l y elucidated by m e a n s of l~N. The ylid and its N - s u b s t i t u t e d d e r i v a t i v e s (LV, R =Me, i t , MeCO,
PhCO, MeO2C , EtO2C , and ArSO2) constitute e x a m p l e s of the r a r e 47r - e l e c t r o n 1,3-dipolar s y s t e m s w i t h t h r e e n i -
trogen a t o m s (LIV). Huisgen [24] has p r o p o s e d t h a t they be called a z i m i n e s and has p r e d i c t e d 1 , 3 - d i p o l a r
cycloaddition r e a c t i o n s for them (see also 25]). A t t e m p t s to d e m o n s t r a t e this cycloaddition with a z i m i n e s
have as yet been u n s u c c e s s f u l [26, 27].
I
~N.~ --,,~
LIV

~'NR L-V
' ~ ~''N\~R
However, a z i m i n e s of the LVI type r e a c t e x o t h e r m a l l y with dimethyl and diethyl a c e t y l e n e d i c a r b o x y -
l a t e s i n b e n z e n e o r d i m e t h y l f o r m a m i d e (DMF) at r o o m t e m p e r a t u r e to give quantitative yields of 1 : 1 ad~lucts.
The g r e e n coloration of these compounds p r e s u p p o s e s that they a r e not the original 1 , 3 - d i p o l a r adducts
(LVH) but r a t h e r azomethine imines (LVIII). This s t r u c t u r e is c o m p l e t e l y c o n f i r m e d by the s p e c t r a l data,
which are s i m i l a r for the independently synthesized [28] s i m p l e r azomethine ylid (LIX).
i~ ~% co~c.~ ~ co~cH~
U /].
N CH302C-C.~C-CO2C3H~II-
H.._--
N
I
_1 ,~,
\\
I ")--cooc.o~
Y
I
~N~ Y
II. !1.
3
N" ,LN.~,./ - - ~ .N m

co~c~H5 Lf '. ~
T_ _
LV._.~ LVl._JI LVIII

The f o r m a t i o n of LVIII is weighty p r o o f in f a v o r of the initial 1 , 3 - d i p o l a r cycloaddition of azimine LIV

with subsequent ring opening of labile t r i a z o l i n e LVII to give the c o n s i d e r a b l y m o r e stable azomethine (LVIH).
This is a r a r e e x a m p l e of r e t r o - l , 5 - d i p o l a r cyclization.
We have p r e v i o u s l y o b s e r v e d a s i m i l a r chain of r e a c t i o n s with benzocinnoline N-oxide (LX), although
the reaction o c c u r r e d under c o n s i d e r a b l y m o r e s e v e r e conditions and gave p o o r e r yields. The products

U.o-
LX LXI

of the r e a c t i o n of LXI a r e also obtained as a r e s u l t of 1 , 3 - d i p o l a r cyeloaddition with subsequent r e t r o - l , 5 -

dipolar cycltzatlon. We feel that this reaction is the f i r s t e x a m p l e of the m a n i f e s t a t i o n of 1,3-dipole p r o -
p e r t i e s by an azoxy compound.
The azomethine [mines (LVIII) mentioned above m a y act as 1,3(47r)-, 1,~(67r)-, o r even 1,7(8~)-dipoles.
In actuality, they r e a c t with acetylenic e s t e r s to give s y m m e t r i c a l 1 : 2 adducts (LXII) [29]. Thus the r e -
action p r o c e e d s p r i m a r i l y in the direction of (67r+ 27r)-cycloaddition, which is not f o r m a l l y allowed, and the
next p r o c e s s is possibly:
CO2R

~CO2R
CO2CO2
LXII
R

637
 The formation of adducts LXII is an example of the extremely rare 1,5-dipolar cycloaddition r e a c -
tion. Their structures were confirmed by their spectroscopic properties. The symmetry of adducts LXII
follows from the identical char a c t e r of the products of the reaction of the starting azimine (LXI) initially
with one mole of dimethyl acetylenedicarboxylate and then with diethyl aeetylenedicarboxylate and vice
versa. Their structures were also confirmed by means of x - r a y crystallography.*
In contrast to the widely known and diverse 1,3-dlpolar cycloaddition reactions, reactions similar
to the 1,5-dipolar cycloaddition reaction described above have received practically no study. The factthat
these reactions may be extremely general in character is confirmed by the properties of 2-substituted
naphthotriazines of the LXIII type [30]. The slow addition of acetylenic e s t e r s to LXIII in refiuxing o-di-
chlorobenzene gave 2-methylacenaphthotriazines LXIV in 30-40%yields. 1 , i l - D t p o i a r (12~r+ 27r) cycload-
dttion apparently occurs initially and is followed by spontaneous dehydrogenation.
CH 3 ~Hs CHs
I+ I+
N~_.N'-.N- NIN'~.N N~'N"~N-

LXIII I..X IV

N~ "~N--

LXV LXVI

In conformity with this, the reactions proceeded better and gave higher yields in the presence of sul-
fur. Cyclic sulfodilmide LXV reacts similarly, although the dipolar C - S - C system (LXVI) acts only as
a 1,3-dipole [31, 32]. Cycloaddition processes of this sort open up wide synthetic possibilities with the
participation of vinylogs of dipolar systems containing more than four ~ electrons.
We thank all of our colleagues who participated in this research, particularly B. M. Adger, Dr. S.
Bradbury, Dr. S. F. Gait, Dr. M. Keatlng, M. E. Peek, Dr. M. J. Ranee, and R. W. Stephenson. We also
are grateful to the Council of Scientific Research for financial support.

LITERATURE CITED
1. S. Ballard and D. Melstrom, in: Heterocyclic Compounds, edited by R. C. Elderfield, Vol. 1, John
Wiley, New York.
2. L . A . Paquette, T. Kakihana, and J. F. Kelly, J. Org. Chem., 3__66,435 (1971).
3. K. Nakagawa and H. Onoue, Chem. Commun., 396 (1965).
4. K. Nakagawa and H. Onoue, Tetrahedron Lett., 1433 (1963).
5. C . D . Campbell and C. W. Rees, J. Chem. Sot., _C_C,742 (1969).
6. J . H . Hall and E. Patterson, J. Amer. Chem. Soc., 89, 5856 (1967).
7. G . H . Mitchell and F. Sondheimer, J. Amer. Chem. Sot., 9..~1,7520 (1969).
8. J . P . Horwitz, in: Heterocyclic Compounds, edited by R. C. E!derfield, Vol. 7, John Wiley, New York,
9. S. Bradbury, M. Keating, C. W. Rees, and R. C. Storr, Chem. Commun., 827 (1971).
10. D . J . C . Adams, S. Bradbury, D. C. Horwell, M. Keatlng, C. W. Rees, and R. C . S t o r r , Chem.Commun.,
828 (1971).
11. C.W. Rees and M. Yelland, J. Chem. Sot., Perkin I, 77 (1972).
12. B . M . Adger, C. W. Rees, A. A. Sale, and R. C. Storr, Chem. Commun., 695 (1971).
13. D . J . Anderson, T. L. Gtlchrist, D. C. Horwell, C. W. Rees, and E. Stanten, J. Chem. Soo., Perkin
I, 1317 (1972).
14. B . M . Adger, M. Keating, C. W. Rees, and R. C. Storr, Chem. Commun., 19 (1973).
15. A. Sondheimer, Ber., 2._99,1273 (1896).
16. E . M . Burgess and L. McCullagh, J. Amer. Chem. Sot., 8_.88,1580 (1966).
17. M . P . Cava, B. Hwang, and J. P. Van Meter, J. Amer. Chem. Sot., 8._55,4032 (1963).
*We thank Doctor A. Forbes Cameron for his x - r a y diffraction study of the preparation.

638
18. R.W. Atkin and C. Wo Rees, Chem Commun., 152 (1969).
19o Mo Jones and Ro H. Levin, J. Amer. Chem. Soc., 9._~.1,6411 (1969).
20. Co W. Rees and R~ C. Storr, J. Chem. Soc., C, 765 (1969).
21. R. Hoffmann, A. Imamura, and W. J. Hehre, J. Amer. Chem. Soe., 90, 1499 (1968).
22~ S . F . Gait, Co W. Rees, and R. C. Storr, Chem. Commun., 1545 (1971).
23. So F. Gait, M. E. Peek, C. W. Rees, and R. C. Storr, Chem. Commun., 982 (1972).
24. R. Huisgen, Angew. Chem., Inter. Ed., 2, 565, 633 (1963).
25. R. Co Kerber, Jo Org. Chem., 37, 1587 (1972).
26~ K.-H. Koch, Dissertation, Universit~t Wrzburg (1969).
27. R. Huisgen, H. Gotthardt, and R. Grashey, Ber., 101, 536 (1968).
28~ S. Fo Gait, M. J. Rance, C. W. Rees, and R. C. Storr, Chem. Commun., 688 (1972).
29. S. Fo Gait, M. J. Rance, C. W. Rees, and R. C. Storr, Chem. Commun., 806 (1972).
30. C .W . Rees, 1% W. Stephenson, and R. C. Storr, Chemo Commun., 1281 (1972)o
31. M . P . Cava, N. M. Pollack, and D. A. Repella, J. Amer~ Chem. Sot., 89, 3640 (1967).
32. R. Ho Schlessinger and I. S~ Ponticello, J. Amero Chem. Sot., 8__9.9, 3641 (1967).

639
POLAROGRAPHIC INVESTIGATION OF THE TAUTOMERIC
TRANSFORMATIONS OF ~-FORMYLACRYLIC ACID AND
OF THE HYDROLYSIS OF ITS ETHYL PSEUDOESTER. I

I. A. Kuzovnikova, L. A. Badovskaya, UDC ~43.2~3 : 547.724 : 541.634

Ya. I. TurTyan, and V. G. Kul'nevich

A p o l a r o g r a p h i c method was used to study the cis (HAt) , t r a n s (HAt) , and lactol (L) f o r m s of
f o r m y l a c r y l i c acid (FAA) and its ethyl p s e u d o e s t e r (E) and t h e i r i n t e r c o n v e r s i o n s . It is shown
that the slow step in the p r o c e s s E ~ L ~ - ~ H A c ~ A c - is hydrolysis of E. The pH of the solution
has a substantial effect on the state of the equilibrium in all of the steps because of the shift
in the equilibrium H A c ~ A c - . The equilibrium constants of all of the steps and the rate c o n -
stant of the hydrolysis of E as a function of the pH of the solution were found. The m o s t stable
of the t h r e e f o r m s of FAA is HAt. The cis f o r m e x i s t s only in solutions. The p o l a r o g r a p h i c
reduction of HA c and HAt at the ethylene bond p r o c e e d s at m o r e positive potentials than the
reduction of m a t e i e and f u m a r i e acids. In c o n t r a s t to HAc, HAt does not f o r m a p o l a r o g r a p h i c
dissociation curve; this is explained by the c l o s e n e s s of the potentials for the reduction of HAt
and At-.

A n u m b e r of studies of the synthesis of f o r m y l a c r y l i c acid (FAA) and its p s e u d o e s t e r (E) f r o m furan

compounds have been made in r e c e n t y e a r s [1, 2].
F o r m y l a c r y l i c acid in the lactol f o r m and its open cis and t r a n s i s o m e r s can be f o r m e d by h y d r o l y s i s
of the ethyl p s e u d o e s t e r o f / ~ - f o r m y l a c r y l i e acid (Scheme 1), but only the laetol and the t r a n s f o r m of FAA
could he isolated f r o m solution [1, 3].
. jCHO
O_/f~-~OC2H5 k,-~ H coo. c~io coo~i
--~O/\H
I II III
E L HA c ~At (1)
c,;5~ II ~/~/CHO
CO0/'~CHO
- COO-

In analogy with the p o l a r o g r a p h i c behavior of m aleic, f u m a r i c , and c i s - and t r a n s - a c e t y l a c r y l i c acids

[4, 5], one might expect that both HAt and HA c should be p o l a r o g r a p h i c a l l y active, and a p o l a r o g r a p h i c
method was t h e r e f o r e u s e d to study p r o c e s s e s (I).
The p o l a r o g r a p h i c c h a r a c t e r i s t i c s of the individually isolated t r a n s f o r m of FAA as a function of the
pH of the solution a r e p r e s e n t e d in Figs. 1 and 2. In this c a s e , as below, only the f i r s t wave, c o r r e s p o n d -
Lag to the reduction of the ethylene bond, is c o n s i d e r e d . The m o r e positive El/2 value of the t r a n s f o r m of
FAAas c o m p a r e d w i t h f u m a r i c acid is explained by the m o r e pronounced negative inductive effect of the c a r -
bonyl group. In c o n t r a s t to f u m a r i c acid, the s o - c a l l e d p o l a r o g r a p h i c dissociation c u r v e was not detected
in the case of the t r a n s f o r m of FAA (Fig. 1); this is a p p a r e n t l y due to the c l o s e n e s s of the potentials for
the reduction of HAt and its anion A t - . The t r a n s f o r m of the acid proved to be quite stable o v e r the entire
pH range, and a d e c r e a s e in the limiting c u r r e n t and a change in it with the pH of the solution could be o b -

K r a s n o d a r Polytechnical Institute. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 6,

737-742, June, 1974. Original a r t i c l e submitted June 28, 1973.

9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, N.Y. 10011. No part of tlns publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy o f this article is availablefrom the publisher for $15.00.

640
 & -Evz x/'-4
o o Oo
o t, c
x/~_~d'-3
o c o o

1,0

3~0-

0,8.
2
2,5.--

0,6!
2,0

0~4-
1,5

Fig. 1 Fig. 2
Fig. 1. Dependence of the limiting c u r r e n t on the pH of the t r a n s f o r m
of f i - f o r m y l a c r y l i c acid (CHAt =4.0~ 10 -4 M): 1) f r e s h l y p r e p a r e d s o l u -
tion; 2) the s a m e solution a f t e r 15 days.
Fig. 2. Dependence of the half-wave potentials on the pH: 1) cis f o r m
of FAA; 2) t r a n s f o r m of FAA; 3) m a l e i c acid; 4) f u m a r i c acid.

s e r v e d only a f t e r 10-15 days (Fig. 1). This m a y be explained by the

slow c o n v e r s i o n of the t r a n s f o r m to the cts f o r m and cyclization of
the l a t t e r .
We were able to investigate the p o l a r c g r a p h i e c h a r a c t e r i s t i c s
of the cis f o r m of FAA in solution, without isolation of HAc, by h y d r o -
l y s i s of the e s t e r o r t a u t o m e r i c c o n v e r s i o n of the lactol. This s o r t
of investigation was facilitated by the fact that the e s t e r and lactol,
like o t h e r s i m i l a r s u b s t a n c e s [6], a r e p o l a r . g r a p h i c a l l y inactive.
The p o l a r . g r a p h i c c h a r a c t e r i s t i c s of HA c (+Ac-) a f t e r r e a c h i n g
equilibrium in the steps involving h y d r o l y s i s of the e s t e r and t a u t -
o m e r i c c o n v e r s i o n of the lactol to HA c (the c o n v e r s i o n of HA c to
HAt can be d i s r e g a r d e d in m o d e r a t e l y acidic solutions and at r o o m
t e m p e r a t u r e ) a r e p r e s e n t e d in Figs. 2 and 3.
The El/2 value of the cis f o r m of FAA is m o r e positive than
2 4 pH
the El/2 value of m a l e t c acid (Fig. 2); as in the c a s e of the E1/2value
of t r a n s FAA as c o m p a r e d with the Eft2 value of f u m a r i e acid, this
Fig. 3 . Dependence of the
can be explained by the s t r o n g e r negative inductive effect of the c a r -
equilibrium limiting c u r r e n t of
bonyl group. Like the E1/2 values of m a l e i c and f u m a r i c acids, the
the cis f o r m of FAA on the pH
El/2 values of t r a n s - and c i s - F A A in the acidic pH range a r e close
(the s t a r t i n g solution was the
(Fig. 2). T h e ~ i m values for HA c a r e p r e s e n t e d tn Fig. 3. I n a s -
ethyl p s e u d o e s t e r of FAA; c ~ =
m u c h as the r a t e of c o n v e r s i o n of the e s t e r to HA c depended on the
4.0 9 104 M).
pH of the solution (see below), the ilem value was r e a c h e d at d i f f e r -
ent t i m e s that were longer, the higher the pH of the solution (Table 1).
The dependence of il~m on pH p a s s e s through a m a x i m u m (Fig. 3). F r o m the effect on the limiting c u r r e n t
of the height of the r e s e r v o i r containing the m e r c u r y it was e s t a b l i s h e d that the c u r r e n t at pH-< 4 (rising
branch of the curve) is by nature a diffusion c u r r e n t , while at pH > 5 the c u r r e n t is by nature a kinetic c u r -
rent. The i n c r e a s e in iliem as the pH i n c r e a s e s can be explained by a shift in the equilibrium to f a v o r the
f o r m a t i o n of the p o l a r . g r a p h i c a l l y active product (HAc+Ac-) due to dissociation of HAc, inasmuch as the
sum (HA c +Ac-) is p o l a r . g r a p h e d in this pH region (pH <4), and the c u r r e n t by nature is a diffusion c u r r e n t .
The descending branch of the i'l~m pH curve, in analogy with m a l e i c and f u m a r i c acids [4], is due to kinetic
inhibition in the step involving protonation of A c - . This anion is reduced d i r e c t l y at m o r e negative poten-
tials, and in the case of HAc, in c o n t r a s t to HAt, we o b s e r v e the usual p o l a r . g r a p h i c d i s s o c i a t i o n c u r v e s .
A c o m p a r i s o n of the i-liem value of the cis form of FAA with the limiting c u r r e n t of HAt o r m a l e i c acid
showed that complete c o n v e r s i o n of the e s t e r to the cis f o r m of FAA (89%) is not achieved even at the m a x -
i m u m limiting c u r r e n t (pH 4-5). This c o n v e r s i o n c o m e s to only 33%at pH 0-1. After the t a u t o m e r i c tra,{s-

641
 T A B L E 1. E q u i l i b r i u m and Kinetic P a r a m e t e r s of the C o n v e r s i o n
of the Ethyl P s e u d o e s t e r of q - F o r m y l a c r y l i c A c i d to Its Open cis
Form (CE~ -4 M, C L ~ 9 10 -4 M; 25~
Time required to
pH [reach equilibrium i (llim)L,
r eq 9A (il:q)E , gA k~+,min-*
ifor the ester
0,00 ~0,4 1,13 [ 87
1,00 ~0,5 1,2 1,18 [ 36
2,09 ~3 1,66 1,85 9.4
2,56 ~4 2,16 2,30 8,8
3,29 ~4,5 2,83 2,97 8,8
3,78 ~5 2,95 3.22 8,8

Ii4 f o r m a t i o n r e a c h e s e q u i l i b r i u m , the individually s y n -

t h e s i z e d l a c t o l showed the s a m e p o l a r o g r a p h i c c h a r a c t e r -
i s t i c s as in the c a s e of solutions of the e s t e r . The dif-
f e r e n c e here c o n s i s t e d only in the fact that the e q u i l -
i b r i u m in the c a s e of the lactol was r e a c h e d c o n s i d e r a b l y
m o r e r a p i d l y than in the c a s e o f the s t a r t i n g e s t e r .
The d i f f e r e n c e in the p o l a r o g r a p h i c c h a r a c t e r -
i s t i c s o f the p r o d u c t of the p r o c e s s E ~ L -~ and the in-
dividually i n v e s t i g a t e d HAt ( c o m p a r e F i g s . 1 and 3)
additionally indlc~tte that the h y d r o l y s i s of the e s t e r
t e r m i n a t e s with the f o r m a t i o n o f HA c ( + A t - ) u n d e r the
L . _ _ , ---- s e l e c t e d conditions (pH 0-8).
100 200 300 '[', r a i n

In the r e g i o n o f the l i m i t i n g diffusion c u r r e n t

Fig. 4. Change in the l i m i t i n g c u r r e n t of the
(pH < 5) we have
cis f o r m o f FAA with t i m e d u r i n g the h y d r o l -
y s i s of the e t h y l p s e u d o e s t e r o f FAA in s o l u - Lt i m~ -2 1~5 1'7 6 (2)
tions with the following pH v a l u e s : 1) 0.00;
at e q u i l i b r i u m :
2) 1.00; 3) 2.09; 4) 2.56; 5) 3.29; 6) 3.78.
iq: = (t"AcJe#Ae-lo ) (3)
and at a given t i m e :

ilim= n ([HAc] + [Ac-D, (4)

w h e r e the "0" p e r t a i n s to the starting_ c o n c e n t r a t i o n (CE ~ f o r the e s t e r and CL ~ f o r the lactol) and the l i m i t -
ing c u r r e n t c o r r e s p o n d i n g to it (lli m was found f r o m the wave of HAt); the s u p e r s c r i p t "e" e x p r e s s e s the
magnitude of the c o n c e n t r a t i o n and the c u r r e n t u n d e r e q u i l i b r i u m conditions; ~t is the I I ' k o v i c h constant,
and the r y m b o l s of the s u b s t a n c e s a r e indicated in S c h e m e (1).

Using (2) and (3) and the e x p r e s s i o n s at e q u i l i b r i u m in the c a s e of the s t a r t i n g lactol solutions:

K" [HAeleq (5)

~q [L]eq '
[H+][Ac-~q (6)
K_
[HAe]eq
CL~= [L]eq+ [HAc]eq-F[Ac].eq, (7)
we find:

i'-lime!H"~l (8)
K'~q= (~lio_~l~) " ([H+]+Ka)

Ka [H+T.
]{'umeq._Kli~('eq-'~2}____
- ::" o - (9)
K" /~ o 7eq~
eq ~ lira-- "Iim/
F r o m the s a m e e q u a t i o n s [(2) and (3)] and a l s o u s i n g (5) and (6) and the e x p r e s s i o n s at e q u i l i b r i u m in the
c a s e o f the s t a r t i n g e s t e r solutions

642
 K, ,[L]"eq[A1]eq
eq [E]eq ' (10)

C~o= [E ]e~[ L]e~-[HAcjhq+ [Ac-]eq ' (11)

[A1]eq7 [L}e~ [HAc]~q+[A"-] eq' (12)
we find
7,~q) ~ 9 9 ( I + f )
(Hm (13)
K q----- = 'Ii~} '
.: e q

where
f [H+] (14)
l! + _t_
Keq([H ], Ks)

In the acidic pH range (0-1) Eq. (8) is simplified ([H+] >> Ka), because i l i m e q i s p r a c t i c a l l y independent
of the pH (Fig. 3):

K" = i~ (15)
eq 7 o__~:eq "
lira qim
The K~q, value (0.55 =~0.05) was determined by means of (15) in the case of the starting lactol solu-
tion 0PH 1, ilim~176 #A, {limeq =1.20 pA). Using this value and the ilimeq values (pH 2.09-3.29) for the
starting lactol solution, on the basis of (9) we found Ka = (5.4 ~-1.0)'10 -3 (Table I).
The K'eq value was calculated from (13) and (14) for quite acidic solutions (pH 0-1) of the ester, in-
asmuch as in this case the accuracy in ffnding K'eq increased owing to the high equilibrium concentration
of the ester: Keq, = (1.8 ~-0.1) - 10-3.
It follows from a comparison of (Ka)HAc with (Ka)MA (MA is maleic acid) that (Ka)HAc < (Ka)MA;
this can be explained by reinforcement of the first-stage dissociation of maleic acid due to hydrogen bond-
ing and the opposing effect of the hydrogen bond in the case of the cis form of FAA. In the cis form of FAA
this effect apparently prevails over the negative inductive effect of the earbonyl group, which reinforces
dissociation.
Since the equilibrium was r e a c h e d rapidly in the c a s e of the s t a r t i n g lactol, it can be a s s u m e d that
the slow step in the c o n v e r s i o n of the e s t e r to (HA c +Ac-) (Scheme 1) is the r e v e r s i b l e h y d r o l y s i s step (I):
I h~
E~-L+A1
kl.

H~t m
HAc ~ A c +H+ (16)
Steps II and III a r e in e q u i l i b r i u m . Despite the p r e s e n c e of steps II and III, it can be shown that Scheme
(16) is d e s c r i b e d by the s e c o n d - o r d e r equation of a r e v e r s i b l e r e a c t i o n [7] u n d e r the condition of s u b s t i t u -
tion of the alcohol concentration (tAll) into this equation:

kl+= 2.3[A1 ]eq 9lg c~[A1eql+[al} (Q0_[A~l~q) (17)

t (2CE~ [A1 ]eq) CEO([Ateq]--[A1 ])

On the basis of (3)-(6), (10), and (12) and c o n s i d e r i n g that CE~ CE c - [A1]eq for the investigated
s y s t e m , we find f r o m (17) at constant pH [A1]eq = (3.5-3.8) 9 10 -4 M):

Veq "7 (2cEo- [all~q}k~+ {.

(18)
lg (~lim ~in~= const 2.3[A1 ]eq

Thus, the investigated p r o c e s s (16) is f o r m a l l y d e s c r i b e d by the f i r s t - o r d e r equation of a r e v e r s i b l e

r e a c t i o n . It should be noted that this conclusion r e m a i n s in force if one also t a k e s into account the p r e s -
ence of a c e r t a i n amount of ethyl alcohol (as well as L and HA +A-) in the s t a r t i n g e s t e r (Fig. 4). In this
case, because [A1]eq >> [A1]in ([A1]in=[0.8-1.9]" 10 -5 M) in o u r e x p e r i m e n t s , Eq. (18) r e m a i n s unchanged
[8]. The s u b s c r i p t "in" p e r t a i n s to t i m e t =0.
Equation (18) is c o n f i r m e d by the e x p e r i m e n t a l data (Fig. 5) - by the linear dependence of log (i L. .l lei q - .
ili m) on t at constant pH. The h y d r o l y s i s r a t e constant was found f r o m the slope of these lines (Table 1).

643
 The constancy of the r a t e constant at pH 2.1-3.8 indicates c o m -
0 ' 4 ~ 6 pensation f o r the effects of a change in the concentrations of
the basic and acidic c a t a l y s t s (the components of the buffer
0 , 2 ~ "'~.x~ x.~5.~ mixture) as the pH of the solution changes. At pH < 2, specific
~E acid c a t a l y s i s has a s t r o n g e r effect.

1.4-~ EXPERIMENTAL
\ -b.
The e s t e r was synthesized by the method in [9], and s a m -
ples f r o m the Institute of Organic Synthesis of the A c a d e m y
of Sciences of the Latvian SSR w e r e also used. The purity of
the e s t e r was m o n i t o r e d by m e a n s of IR s p e c t r o s c o p y . The
t r a n s f o r m of FAA and the lactol were obtained by the method
in [1].
The study of the p o l a r o g r a p h I e c h a r a c t e r i s t i c s of HA c
Fig. 5. Verification of Eq. (18) at the and HAt and the investigation of the kinetics (by r e c o r d i n g the
following pH values: 1) 0.00; 2) 1.00; p o l a r o g r a m s at different t i m e s ) and of the equilibrium of the
3) 2.09; 4) 2.56; 5) 3.29; 6) 3.78. r e a c t i o n (Scheme 1) w e r e p e r f o r m e d in 1 M HC1, 0.1 M HCI +
1 M KC1, and in u n i v e r s a l buffer solutions (+ 1 M KCI) with pH
2-10. An L P - 6 0 e l e c t r o n i c p o l a r o g r a p h (Czeckoslovakia) and a t h e r m o s t a t e d (at 25 O.2~ c e l l w i t h a c a p i l -
l a r y (m =3.03 m g / s e c and t = 2 . 7 8 s e c when E = - 1 . 0 V relative to an e x t e r n a l s a t u r a t e d c a l o m e l c o m p a r i s o n
electrode) were used. The oxygen was r e m o v e d by bubbling purified nitrogen through the solutions. The
concentrations of the compounds in the p o l a r o g r a p h i c cell were as follows: CE ~ and CHAt ~=4.0 9 10 -4 M,
and CL ~=3.76 910 -4 M. The ([lim~ value was 3.60 ~A.

LITERATURE CITED
1. S. H. S c h r o e t e r , R. Appel, R. B r a m m e r , and G. O. Schenk, Ann., 697, 42 (1966).
2. L. A. Badovskaya, V. G. Kul'nevich, G. F. Muzychenko, and L. V. Tsygankova, S u m m a r i e s of P a p e r s
P r e s e n t e d to the All-Union Council on the P r o b l e m of the Use of Pentosan-Containing Raw M a t e r i a l s
[in Russian], Riga (1969), p. 30.
3. V. G. Kul'nevich, G. F. Muzychenko, and L. A. Badovskaya, S u m m a r i e s of P a p e r s P r e s e n t e d at the
Jubilee I n t e r - V U Z Conference on C h e m i s t r y and C h e m i c a l Technology [in Russian], Ufa (1969), p. 40.
4. Ya. P. Stradyn,, V. V. T e r a u d , and M. V. Shimankskaya, Izv. Akad. Nauk L a t v . SSR, 5, 547 (1964).
5. J . H e y r o v s k y and J . Kuta, P r i n c i p l e s o f P o l a r o g r a p h y , A c a d e m i c P r e s s (1966).
6. E. V. Kirkland, C. A. Reynolds, and W. Wander, J. A m e r . Chem. Soc., 7__2, 1764 (1950).
7. K. J. L a i d l e r , Reaction Kinetics, P e r g a m o n .
8. N. M. ]~manu~l' and D. G. K n o r r e , Course in C h e m i c a l Kinetics [in Russian], Moscow (1969), p. 175.
9. A. Sch6nberg, P r e p a r a t i v e Organic P h o t o c h e m i s t r y [Russian translation], Moscow (1963), p. 91.

644
VINYLPYRYLATION OF AROMATIC COMPOUNDS

V~ V . M e z h e r i t s k i i , A. L. Vasserman, UDC 547.813

and G. N. Dorofeenko

The r e a c t i o n of f l - e t h o x y v i n y l p y r y l i u m s a l t s with a r o m a t i c compounds gives s t y r y l p y r y l i u m

salts, which a r e also f o r m e d f r o m m e t h y l p y r y l i u m salts, ethyl o r t h o f o r m a t e , and a r o m a t i c
compounds. The p r e v i o u s l y unknown phenomenon of attack by a c a r b o n i u m cation on the m e t a
position of a benzene ring p a s s i v a t e d by a nitro group (nitrobenzene) was detected.

It is known [1, 2] that the f i - c a r b o n atom in f i - e t h o x y v i n y l p y r y l i u m s a l t s is the active c e n t e r in r e -

actions with nucleophiles. It might have been expected that its high e l e c t r o p h i l i c i t y would p r o v e to be suf-
ficient for r e a c t i o n with a r o m a t i c compounds.
It was found t h a t / 3 - e t h o x y v i n y l p y r y l i u m and b e n z o p y r y l i u m s a l t s r e a c t with a r o m a t i c benzoid and
h e t e r o e y c l i c compounds on refluxing in acetic anhydride to give s t y r y l p y r y l i u m s a l t s II via the s c h e m e
CsH4R
()"~C--CH
"'. =CH--OC~H~
. , 0".." "/C=CH--CH--OC2H
o + C6HSR
. - -H+ O"'~C= C H-- ICH --OCzH,
I

-C2H5OH ., ..
II

The r e l a t i v e r e a c t i v i t I e s of f l - e t h o x y v i n y l p y r y l i u m s a l t s were studied in the c a s e of an active nucleo-

p h i l e - N,N-dimethylaniline~ 4 - f l - E t h o x y v i n y l b e n z o p y r y l i u m salt and monocyclic 4 - f l - e t h o x y v i n y l - and
4 - ~ - p h e n y l - o ~ e t h o x y v i n y l p y r y l i u m s a l t s undergo this r e a c t i o n . In the c a s e of m o n o c y c l i c 2 - f l - e t h o x y v i n y l -
p y r y l i u m salts, 2 - s t y r y l p y r y l i u m s a l t s could not be isolated u n d e r the s a m e conditions. Benzene itself and
substituted benzenes containing both e l e c t r o n - d o n o r and e l e e t r o n - a c c e p t o r substitutents can p a r t i c i p a t e in
this t r a n s f o r m a t i o n ; this was shown in the case of the r e a c t i o n of 2 , 6 - d i p h e n y l - 4 ( f l - e t h o x y v i n y l ) p y r y l i u m
p e r c h l o r a t e ~ In the c a s e of monosubstituted benzenes with e l e c t r o n - d o n o r groups ~ R 2 , OH, OR, and C1),
p a r a substitution o c c u r s to give products in yields close to quantitative; this was e s t a b l i s h e d by a l t e r n a t i v e
s y n t h e s i s of the s a m p l e s by condensation of m e t h y l p y r y l i u m s a l t s with the a p p r o p r i a t e aldehydes. The p a r a
c a r b o n atom with r e s p e c t to one of the methoxy groups is attacked in v e r a t r o l e , while 2 , 4 - d i h y d r o x y s t y r y l -
p y r y l i u m salts, w h i c h a r e u s e d for the synthesis of s p i r o p y r a n s [3], a r e f o r m e d in the c a s e of r e s o r c i n o l .
An i n t e r e s t i n g fact that indicates the exceptionally high e l e c t r o p h i l i c i t y of the f i - c a r b o n atom in fi-
e t h o x y v i n y l p y r y l i u m salts is the r e a c t i o n of t h e s e compounds with nitrobenzene. In this case the m e t a p o s i -
tion of the nitrobenzene molecule is attacked to give 4 - ( m - n i t r o s t y r y l ) - 2 , 6 - d i p h e n y l p y r y l i u m p e r c h l o r a t e ,
which is identical to a s a m p l e obtained by condensation of 2 , 6 - d i p h e n y l - 4 - m e t h y l p y r y l i u m p e r c h l o r a t e with
m - n i t r o - b e n z a l d e h y d e . This is a p p a r e n t l y the f i r s t noted instance of alkylation of a n i t r o - g r o u p - p a s s i v a t e d
benzene ring by a carbonium ion. The d i v e r s e alkylation, f o r m y l a t i o n , and acylation r e a c t i o n s of a r o m a t i c
compounds, the e s s e n c e of which c o n s i s t s in attack on the a r o m a t i c ring by a c a r b o n i u m cation, a r e not
r e a l i z e d in benzoid s y s t e m s with s t r o n g e l e c t r o n - a c c e p t e r substituents such as the nitro group.
The r e a c t i o n of s a l t s I with indole o c c u r s in the fi-position of the p y r r o l e ring and gives a quantitative
yield of ~-(3-indolyl)vinyl d e r i v a t i v e , which is identical to a s a m p l e obtained by condensation of 2,6-diphenyl-
4 - m e t h y l p y r y l i u m p e r c h l o r a t e with f i - f o r m y l i n d o l e .

Rostov State U n i v e r s i t y . S c i e n t i f i c - R e s e a r c h Institute of P h y s i c a l and Organic C h e m i s t r y , R o s t o v -

on-Don. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 6, pp. 743-745, June, 1974. Original
a r t i c l e submitted July 24, 1973.

9 19 75Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy of this article is availablefrom the publisher for $15.00.

645
 The p r e p a r a t i o n of the s t y r y l p y r y l i u m salts can be r e a l i z e d in
a single step by refluxing the methylpyrylium salts with ethyl o r t h o -
formate and the a r o m a t i c compound in acetic anhydride without iso-
lation of the intermediate fl-ethoxyvinyl derivatives. The reaction
probably p r o c e e d s through the intermediate formation of I. Another
possible path - through the intermediate formation of acetals of a r o -
matic aldehydes - should be excluded, inasmuch as we did not observe
t h e i r formation on refluxing the a r o m a t i c compounds with ethyl o r t h o -
formate under the reaction conditions. T h r e e - c o m p o n e n t condensa-
tions of heterocyclic s y s t e m s containing an active methyl group with
II II E ortho e s t e r s and a r o m a t i c compounds were unknown until the p r e s e n t
research.
The IR s p e c t r a of the compounds obtained have an intense band
at 1630-1650 cm -1, which is related to vibrations of C =C bonds con-
jugated with the pyrylium cation and bands c h a r a c t e r i s t i c for the v i b r a -
tions of the pyrylium ring, benzene rings, and functional substituents.

EXPERIMENTAL
The IR s p e c t r a of m i n e r a l oil suspensions of the compounds
o ll-Ilo o~ were r e c o r d e d with a UR-20 s p e c t r o m e t e r .
4 - f l - (N,N-dimethylamino) s t y r y l - 7 - h y d r o x y f l a v y l i u m Pe r c h l o r a t e .
A) A 0.4-g (1 mmole) sample of 4-/3-ethoxyvinyl-7-hydroxyflavylium
p e r c h l o r a t e and 0.42 ml (3 mmole) of N,N-dimethylaniline were r e -
fluxed in acetic anhydride for 1 h. The mixture was cooled and filt-
e r e d to give 0.46 g (100%) of the s t y r y l p y r y l i u m salt with mp 300 ~
(decomp.). IR spectrum: 3500, 1645, 1600, and 1100 cm - i . Found:
C 64.0; H 4.5; C1 7.6; N 2.8%. C25H22CINO6. Calculated: C 64.1; H 4.7;
C1 7.6; N 2.8%. A s i m i l a r p r o c e d u r e was used to obtain I I a - l , the
physical constants and yields of which are p r e s e n t e d in Table 1; 4 - f l -
(N,N-dimethylamino)strylflavylium p e r c h l o r a t e , with 300 ~(decomp.),
was obtained in 100%yield. IR spectrum: 1650, 1600, and 1100 cm -I.
~=========zZ Found: C 66.5; H 4.5; C1 8.0; N 3.1%. C25H22CINO5. Calculated:
C 66.4; H 4.9; C1 7.9; N 3.1%; 2,8,9-dibenzo-5-[fi-(N,N-dimethylamino)]
s t y r y l - 3 , 4 , 6 , 7 - t e t r a h y d r o x a n t h y l i u m pe r c h l o r a t e , with mp 26 8~ was
EE obtained in 94%yield. IR spectrum: 1645, 1590, and 1100 cm -1. Found:
C 70.5; H 5.4; C1 6.5; N 2.6%. C31H28CINO5. Calculated: C 70.2; H
5.3; C1 6.7; N 2.6%.
NN
B) A 0.3-g (1 mmole) sample of 4 - m e t h y l - 7 - h y d r o x y f l a v y l i u m
H
I
o o m m m m ~ --cn----~ p e r c h l o r a t e , 0.16 ml (1 mmole) of ethyl o r t h o f o r m a t e , and 0.14 ml
(1 mmole) of N,N-dimethylaniline were refluxed for 1.5 h in acetic
anhydride. The mixture was then cooled, and the r e s u l t i n g s h i n y - g r e e n
r~
plates were r e m o v e d by filtration to give 0.45 g (98%) of a product
with mp 300~ A s i m i l a r p r o c e d u r e was used to obtain s t y r -
ylpyrylium salts IIa-e,i,k.
Condensation of Methylpyrylium Salts with Aromatic Aldehydes.
A 1-mole sample of the methylpyryltum salt and 1.5 mole of aldehyde
were refluxed in acetic anhydride for 0.5-1.5 h. The s t y r y l p y r y l i u m
salts c r y s t a l l i z e d on cooling.
~ ~ z ~ ,~z~ 7 z
LITERATURE. CITED
1. H. K i r n e r and R. Wizinger, Helv. Chim. Acta, 4..~4,1766 (1961).
< 2. G . N . Dorofeenko, V. V. Mezheritskii, and A. L. V a s s e r m a n ,
Khim. G e t e r o t s i l d . Soedin., 570 (1974).
3. R. Dickinson, I. M. Heilbron, and F. O'Brien, J. Chem. Soc.,
9,077 (1928).
4. W. Dilthey and J. F i s c h e r , Chem. B e r . , 57, 1653 (1924).
646
REACTIONS OF 1,5-DIKETONES
X.* SYNTHESIS OF 4-KETOHYDROXANTHENES (NEW
FORM OF ISOMERIZATION OF 1,5-DIKETONES)

V~ I . V y s o t s k i i , N. V. Vershinina, UDC 547.815

and M. N. Tilichenko

The c o r r e s p o n d i n g 4 - k e t o h y d r o x a n t h e n e s , which undergo m e t h y l a t i o n and dehydration, a r e

f o r m e d in the condensation of e y c l o h e x a n e - l , 2 - d i o n e with 2 - d i m e t h y l a m i n o m e t h y l e y e l o h e x a -
none, 2 - b e n z y l i d e n e e y c l o - h e x a n o n e , and 2,6-dibenzylidenecyelohexanone. 1 0 a - H y d r o x y - l , 2 ,
3,4,5,6,7,8,Sa,10a-decahydro-4-xanthenone e x i s t s in t a u t o m e r i e relationships with 2,2v,3 -
triketoperhydrodiphenylmethane.

It was r e c e n t l y shown that the i n t e r m e d i a t e 1,5-diketone f o r m e d in the Michael condensation of e y c l o -

hexanone with 2,6-dibenzylidenecyclohexanone i s o m e r i z e s to hydroxydeeahydroxanthene during the s y n -
t h e s i s [1]. It s e e m e d of i n t e r e s t to examine o t h e r e x a m p l e s of this cyelization. F o r this, we s t u d i e d t h e
addition of c y c l o h e x a n e - l , 2 - d t o n e (I), which contains a conjugated c a r b o n y l group, to m e t h y l e n e c y c i o h e x a -
none (Ha) [this was obtained d i r e c t l y in the r e a c t i o n m i x t u r e f r o m the Mannich base (HI)I, 2 - b e n z y l i d e n e -
cyelohexanone (IIb), and ketone(IIc). I n t e r m e d i a t e IV, which is enolized to V, is a p p a r e n t l y obtained initially
during the reaction, and V then e y c l i z e s to xanthenone VI.
The s t r u c t u r e of VI was c o n f i r m e d by c h e m i c a l r e a c t i o n s and s p e c t r a l data.

O R O 0 X O X

I Ila-c IVa-c Va-c

i ,J
(CHal2NCH2 ~ u
0

VI a ' C VII a - c

R R
i. T s N H N H 2

2. N a B H 4
II II II
O X X
VIII b - c IXC

II.IV. V-Vii a R= H X=H.~. II, IV-Vlllib'R=CsH 5, X=H~; II,|V-IX C R=C6Hs, X=CHC6H 5

Absorption of a conjugated e a r b o n y l group a p p e a r s at 1680 c m - I in the IR s p e c t r a of the compounds. The

p r e s e n c e of an ethylene bond follows f r o m the a b s o r p t i o n at 1640 e m -1. A hydroxyl group band is o b s e r v e d

* See [1] f o r c o m m u n i c a t i o n I X .

F a r - E a s t e r n State U n i v e r s i t y , Vladivostok. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedin-

enii, No. 6, pp. 746-749, June, 1974. Original a r t i c l e submitted June 5, 1973.

9 19 75Plenum Publishing Corporation, 227 West 17th Street, New York, N.Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy of this article is availablefrom the publisher for $15.00.

647
 TABLE I. 4-Ketohydroxanthenes
rap, ~C (crystalliza- Empirical Found,% Calc.. %
Compound formula Yield, ~
tion solvent) c H c H
Vla a 114--114,5 C~3H,sO~ 70,0 8,2 70,2 72
(Deazcne)
VIb 202--203 ClgU72Oa 76,3 7,6 76,5 74
(Aqueous alcohol)
VI 205--206 C26HmO3 80,6 6,8 80,8 78
(Ethyl acetam)
VIlac 130--131 C)4H2oOs 71,0 8,6 71,2 77
(Ethyl acetate)
vlIb d 134--135 C~ol-I~4Os 76,9 8,2 76,9 78
(Alcohol)
VIIc 138--139 C27H2sO3 81,3 7,1 81.0 96
(Alcohol)
Vlll b |54--155 C,~H2oO2 81,3 7,5 81,4 54
(Alcohol)
VIII c 151--152 C~6H~402 84,6 7,3 84,8 96
(Alcohol)

aThe phenylhydrazone had mp 104-106~ (from alcohol). Found: N

9.3%. C19H24N202. Calculated: N 9.0%. The t r i t o s y l h y d r a z o n e had
mp 109-110~ (from methanol). Found: N 11.7%. C~4H42N6OsSa.
Calculated: N 11.6%. bThe t o s y l h y d r a z o n e had mp 172-173~ (de-
comp., f r o m aqueous dioxane). Found: N 6.4%. C26H31N203S. Cal-
culated: N 6.0%. CCH30: Found: 13.3%. Calculated 13.1%. dCH30:
Found: 10.0%. Calculated: 9.9%~ eThe t o s y l h y d r a z o n e had mp 201-
202~ (decomp., f r o m c h l o r o f o r m - m e t h a n o l ) . Found: N 5.7%.
C33H32N203S. Calculated: N 5.2%.

at 3400-3600 em-i. The benzyl proton in the PMR spectrum of product Vlb gives a doublet centered at 3.18
ppm ( J = l l IIz).
Compounds Vl readily undergo Helferich methylation to give methoxy derivatives VII. A band at 2845
cm-i, which can be assigned to the vibrations of C - H bonds of a methoxy group [2], appears in their IR
spectra in place of hydroxyl group absorption. The absorption of the carbonyl group and of the double bond
does not change in character. A singlet at 3.05 ppm, which corresponds to a CII30 group, appears in the
PMR spectra of VII.
The ease of dehydration increases in the order Vla-c. CompoundVie is converted almost quantitat-
ively to 9-phenyl-5-benzylidene-l,2,3,4,5,6,7,8-octahydro-4-xanthenone (VIIIc)on refluxing In benzene for
I h in the presence of catalytic amounts of p-toluenesulfonic acid. CompoundVlb is converted to 9-phenyl-
1,2,3,4,5,6,7,8-octahydro-4-xanthenone (VIIIb) (50%) in 4 h; water is not isolated from Via under similar
conditions.
Compounds Via and IVa are apparently tautomers. In fact, while the IR spectrum of a KBr pellet of
the compound corresponds to structure Via, an intense band at 1710 cm-i of an unconjugated carbonyl group
of open structure IVa appears in the spectrum of a solution in chloroform along with the frequencies enum-
erated above. The UV spectra of a eyclohexane solution has one maximum at 262 nm. This also corres-
ponds to structure IVa, inasmuch as the cyclic form should absorb like acetal ViIa, the UV spectrum of
which contains a single maximum at 217 nm. CompoundVia reacts with 3 mole of tosylhydrazlne and forms
a tritosylhydrazone. Although a few spots (in addition to the spots of the starting substances), which ap-
parently correspond to intermediate products, are detected during thin-layer chromatography (TLC) of
a mixture of Via with tosylhydrazine, only chromatographically individual tritosylhydrazone crystallizes
out from the mixture. This also indicates equilibrium Via ~-~IVa; several mono- and ditosylhydrazones
can be formed from the latter compound, but they are apparently quite soluble in methanol. The reaction
therefore goes to completion, and the insoluble tritosylhydrazone crystallizes out.
Ketol Vib forms the expected monotosylhydrazone. The reaction of Vie with tosylhydrazine is ac-
companied by dehydration to give the tosylhydrazone of VIIIc (confirmed by alternative synthesis from
VIIIc).

F o r p r o o f of the s t r u c t u r e of VIIIc, its t o s y l h y d r a z o n e was reduced with sodium borohydride to give

9 - p h e n y l - 4 - b e n z y l i d e n e - l , 2 , 3 , 4 , 5 , 6 , 7 , 8 - o c t a h y d r o x a n t h e n e {IXc) which was identical to a p r e v i o u s l y s y n -
t h e s i z e d sample [1].

648
 EXPERIMENTAL
The I1R s p e c t r a w e r e r e c o r d e d with a UR-20 s p e c t r o m e t e r , The PMR s p e c t r a of solutions of the c o m -
pounds in d e u t e r o c h l o r o f o r m w e r e r e c o r d e d with a ZKI~-60 s p e c t r o m e t e r (on the 5 scale with r e s p e c t to
t e t r a m e t h y l s i l a n e ) . The UV s p e c t r a of 0.001% solutions of the compounds in cyclohexane w e r e r e c o r d e d
with a Specord s p e c t r o p h o t o m e t e r (layer t h i c k n e s s 1 cm). The identical c h a r a c t e r of the compounds o b -
tained and of genuine s a m p l e s w e r e e s t a b l i s h e d f r o m the a b s e n c e of a d e p r e s s i o n during m e l t i n g of m i x t u r e s
of the s a m p l e s and f r o m the identical c h a r a c t e r of the IR s p e c t r a . Data on the s y n t h e s i z e d compounds a r e
p r e s e n t e d in Table 1.

. 1 0 a - H y d r o x y - l , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 8 a , 1 0 a - d e c a h y d r o - 4 - x a n t h e n o n e (Via). A 56-g (0.5 mole) s a m p l e of

ketone I was m i x e d with 40 m l of 6 N NaOH and with a heated (up to the boiling point) solution of 24 g (0.125
mole) of hydrochloride HI in 250 m l of alcohol, and the m i x t u r e was then refluxed f o r 20 min, cooled with
ice, and n e u t r a l i z e d to pH 7 with c o n c e n t r a t e d HCL The alcohol was r e m o v e d by distillation, and the r e s i -
due was diluted with 200 m l of w a t e r and acidified to pH 5 with HC1. The r e s u l t i n g oil was e x t r a c t e d with
benzene, and the e x t r a c t was washed with w a t e r , dried with D r i e r i t e , and e v a p o r a t e d to half its o r i g i n a l
v o l u m e . A total of 20 g of Via c r y s t a l l i z e d out f r o m the solution.
1 0 a - H y d r o x y - 9 - p h e n y l - l , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 8 a , 1 0 a - d e c a h y d r o - 4 - x a n t h e n o n e (VIb). A 3 . 4 - g (0.03 mole)
s a m p l e of ketone I and 5.6 g (0.03 mole) of IIIb w e r e refluxed in 30 m l of 0.15 N alcoholic KOH f o r 6 h.
The VIb that p r e c i p i t a t e d on cooling of the m i x t u r e was r e m o v e d by filtration. Compound Vib was s i m i l a r l y
obtained when the m i x t u r e was re fluxed for 45 rain.
1 0 a - M e t h o x y - l , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 8 a , 1 0 a - d e c a h y d r o - 4 - x a n t h e n o n e (VIIa). A 1.0-g s a m p l e of Via was m i x e d
with 10 m l of 0.25% HC1 in absolute methanol, and the m i x t u r e was re fluxed for 1.5 h. It was then cooled
and n e u t r a l i z e d (at 0 ~ with sodium b i c a r b o n a t e solution to p r e c i p i t a t e 0.35 g of a c e t a l VIIa. The f i l t r a t e
r e m a i n i n g a f t e r s e p a r a t i o n of the p r e c i p i t a t e was e x t r a c t e d with e t h e r , and the e x t r a c t was dried with
O r i e r i t e and e v a p o r a t e d to give an additional 0.5 g VIIa. Compounds VIIb, c w e r e s i m i l a r l y obtained.
9 - P h e n y l - l , 2 , 3 , 4 , 5 , 6 , 7 , 8 - o c t a h y d r o - 4 - x a n t h e n o n e (ViIIb). A m i x t u r e of 4.0 g of xanthene Vib, 100 m l
of benzene, and 70 m g of p - t o h e n e s u l f o n i c acid was refiuxed in a flask equipped with a D e a n - S t a r k t r a p
for 4 h, during which 0.18 m l of w a t e r (calculated value 0.24 ml) s e p a r a t e d . A t o t a l of 1.8 g of the s t a r t i n g
ketol c r y s t a l l i z e d out when the m i x t u r e was cooled. The filtrate was washed with sodium b i c a r b o n a t e s o l u -
tion and w a t e r , 85 m l of benzene was r e m o v e d by distillation, and 2.0 g of VIIIb c r y s t a l l i z e d out f r o m the
r e s i d u e . Compound VIIIc was s i m i l a r l y obtained.
T o s y l h y d r a z o n e s . The t o s y l h y d r a z o n e s w e r e obtained by m i x i n g m e t h a n o l solutions of the compounds
and t o s y l h y d r a z i n e . The r e a c t i o n products c r y s t a l l i z e d out while the m i x t u r e s were allowed to stand.
9- P h e n y l - 4 - b e n z y l i d e n e - 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 - o c t a h y d r o x a n t h e ne (IXc). A 1.0-g s a m p l e of to s y l h y d r a z o n e
of ViIIc and 2.0 g of sodium borohydride w e r e refluxed in 50 m l of m e t h a n o l f o r 15 h, a f t e r which the m i x -
t u r e was acidified with dilute HC1, and the p r e c i p i t a t e was r e m o v e d by filtration and washed with methanol.
The filtrate was e v a p o r a t e d , and the r e s i d u e (0.6 g) was purified by c h r o m a t o g r a p h y on a plate containing
A1203 (activity II) in p e t r o l e u m e t h e r - e t h y l acetate (7 : 1) to give 0.09 of IXc with mp 111-113 ~ (from alcohol)
(mp 111-113 ~ [11).
The authors thank the c o - w o r k e r s of the Pacific Institute of B i o o r g a n i c C h e m i s t r y L. I. Glebko, V.
A. Stonik, and V. V. I s a k o v for the analytical and s p e c t r a l me a s u r e m e n t s .

LITERATURE CITED
I. V. I. Vysotskii and M. N. Tilichenko, Khim. GeterotsiM. Soedin., 299 (1971).
2. L. Bellamy, Infrared Spectra of Complex Molecules, Methuen (1958).

649
SPIROPYRANS OF THE PHENANTHRIDINE SERIES

l~. R . Z a k h s , V. P. Martynova, UDC 547.814.5'836.3

a n d L . S. E f r o s

The r e l a t i v e stabilities of the cyclic and open f o r m s of s p i r o p y r a n s of the phenanthridine s e r i e s

depend on the c h a r a c t e r and position of the substituents in the c h r o m e n e ring and also on the
p o l a r i t y of the m e d i a . The s t r u c t u r e of the open f o r m s of the s p i r o p y r a n s is c l o s e r to the l i m i t -
ing dipolar s t r u c t u r e . The open f o r m s of the c a r b o x y d e r i v a t i v e s of the s p i r o p y r a n s a r e s t a b -
ilized in alcohol solutions due to proton t r a n s f e r to the phenoxide oxygen.

The e a s e of d a r k and photoinduced r e v e r s i b l e t r a n s f o r m a t i o n s of the open and s p i r a n f o r m s of s p i r o -

p y r a n s based on f i v e - m e m b e r e d nitrogen h e t e r o c y c l e s depends to a c o n s i d e r a b l e extent on the p r e s e n c e of
substituents and t h e i r c h a r a c t e r [1, 2]. We have p r e v i o u s l y e s t a b l i s h e d that 6 - ( o - o x i d o s t y r y l ) d e r i v a t i v e s
(i) of the N-methylphenanthridinium ion a r e capable of undergoing i n t r a m o l e c u l a r cyelization to give c o l o r -
l e s s s p i r o p y r a n s (II) [3].

~~ ~N/CH3
COO-

la-i W lla-I Ill

In o r d e r to a s c e r t a i n the effect of substituents on the p r o p e r t i e s o f s p i r o p y r a n s of the phenanthridine

s e r i e s , we synthesized a n u m b e r of compounds of this type with substituents in the c h r o m e n e ring (Table 1).
Like the p r e v i o u s l y d e s c r i b e d f i r s t r e p r e s e n t a t i v e s [3], they were obtained by condensation of 5 , 6 - d i m e t h y l -
phenanthridinium methosulfate with salicylaldehyde d e r i v a t i v e s in the p r e s e n c e of e x c e s s piperidine. The
condensation products w e r e isolated f r o m the r e a c t i o n m a s s in e i t h e r the s p i r a n ( I I a - e , k , / ) o r m e r o c y a n i n e
(If-j) f r o m , depending on the nature of R and R ' . The stability of the s p i r a n f o r m d e c r e a s e s as the e l e c t r o n -
a c c e p t o r p r o p e r t i e s of the substituents b e c o m e s t r o n g e r . The dibromo (If, R = R ' =Br) and n i t r o m e t h o x y
{Ig, R =NO2, R' =OCH 3) d e r i v a t i v e s , like the p r e v i o u s l y d e s c r i b e d nitro d e r i v a t i v e (R =NO2, R' =H) [3l, a r e
isolated as m e r o c y a n i n e s (I) in the condensation in alcohol. When they a r e heated in solvents of low p o l a r i t y
they a r e converted to the c o r r e s p o n d i n g s p i r o p y r a n s (i-If,g), which can be isolated in the c r y s t a l l i n e state.
A c o l o r l e s s s p i r o p y r a n f o r m (IIh) cannot be isolated for compounds with s t r o n g e r a c c e p t o r s u b s t i t u :
ents - the b r o m o n i t r o d e r i v a t i v e (Ih, R =NO 2, R, = B r ) . However, solutions of Ih in benzene and dioxane (two
a b s o r p t i o n m a x i m a of identical intensity at 395 and 590 nm a r e o b s e r v e d i m m e d i a t e l y a f t e r dissolving the
compound) a r e quite r a p i d l y d e e o l o r i z e d as a consequence of the f o r m a t i o n of s p i r o p y r a n IIh in solution,
as shown by the s i m i l a r i t y in the a b s o r p t i o n s p e c t r u m of the d e c o l o r i z e d solution (kmax 330 nm) and the
s p e c t r a of the r e m a i n i n g s p y r a n s (Tables 1 and 2). The d e c o l o r i z a t i o n is s h a r p l y a c c e l e r a t e d during i r r a d i a -
tion with sunlight. The r a t e of d a r k cyclization depends m a r k e d l y on the p o l a r i t y of the solvent. Thus the
t i m e r e q u i r e d f o r half c o n v e r s i o n of Ih to IIh at 20 ~ C in dioxane is ~30 min, a s c o m p a r e d with ~315 m i n
(at 30 ~ in a 5% solution of alcohol in benzene.
We w e r e a l s o unable to isolate s p i r o p y r a n s with NO 2 and COOH groups in the 8' position (Hi, j), a l -
though the i s o m e r i c 6' d e r i v a t i v e s a r e c o m p l e t e l y stable in the c r y s t a l l i n e state. It is, of c o u r s e , t r u e that

L e n s o v e t L e n i n g r a d Technological Institute. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedin-

enii, No. 6, pp. 750-754, June, 1974. Original a r t i c l e submitted July 13, 1973.

9 1975 PlenumPublishing Corporation, 227 West 17th Street, New York, 3s Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is availablefrom the publisher for $15.00.

650
 i
e~

o Q0 r--- t~ t"-,I

z." g~" ~o" ,,b~ ,'q ~" ~:~ ~" ~" @- ~" ,.b" ~o"
0

0
og

z ggd
!

g ~ g a ~ g s S g ~ g s
e~
!

,,.i

ID ,

2, o ~D LO ~1 0 ~ 0 r ea~ O~ 0 ~'q

~ gnu
oo o
U ~ Z Z Z ~ Z Z ~ Z Z Z Z

~ ~ ~ ~ - ~ ~ ~ - - ~ ~

!
o cO
u ,-a u 0 - ~ z z z L; L~

. . . . . . . . . -- o.~,~ ~ r~
g
~a

651
 TABLE 2. Absorption Spectra of I and II in Alcohol
Com-
~-m.=, nm(Ig s)*
pound

Ill 242, 270", 330, 384", 545 (4,73; 4.29; 3,98; 3.56; 3,42)
Ig qg 252, 327. 394. 420. 517 (4,59; 4,12; 4,19; 4,20; 4,14)
In 252, 270", 322, 395, 475 (4,62; 4,31; 4,21; 4,25; 4,16)
li 242, 251,270*, 322, 335", 360', 505 (4,61; 4,61; 4,28; 4,01; 3,95; 3,80; 3,78)
Jj 250, 317. 375, 412 (4,58; 3,87; 3,76; 3,81)
ltk 247, 265", 320, 405 (7,92; 3,59; 1,00; 0,45)
111 248, 265*, 290--300, 510 (6,45; 2,48; 1,00; 0,04)

* The intensities of the absorption relative to the absorption at 300-

320 nm are indicated instead of log ~ for IIk and IIZ. The shoulders
and inflection points are indicated by a s t e r i s k s .

8 .. ,7. ? 9 lo ~1 12 , 3 1 4 1 s ~ m
Ii, j exist p r i m a r i l y as s p i r o p y r a n s (Hi, j) in c h l o r o -
form solutions, but the a b s o r p t i o n in the visible region
90-
i
attests to the p r e s e n c e of appreciable amounts of the
80-
open f o r m s .
70 Considering the pronounced stabilization of the
open f o r m s in p o l a r media, it might be a s s u m e d that
90
the impossibility of isolating crystalline spiropyrans
,~0

/ IIh-j is due to strong polar interaction in the c r y s t a l

t
=- ~'o. lattices of these compounds. Molecules of such c o m -
0 pounds are stable in the cyclic form only when they
are shielded from one another by a solvate shell from
the molecules of the nonpolar solvent,
~ -
The s t r u c t u r e of the open f o r m s of the s p i r o -
83. pyrans is close to dipolar (I), inasmuch as pronounced
70. i negative s o l v a t o c h r o m i s m is p e c u l i a r to them [4]. The
long-wave maximum of Ih is shifted from 590 nm in
dioxane solution to 575 and 545 nm when ethanol is
SO.

i
addedj (up to 2 and 10% concentration), but it is found
z;O at 480 nm in alcohol; in the case of Ij', the long-wave
30- maximum is shifted from 530 nm in c h l o r o f o r m to 458
20, I
nm when ethanol is added (up to a 10% concentration).
These h y p s o c h r c m i c shifts a r e much g r e a t e r t h a n t h o s e
lO-
previously o b s e r v e d for the indoline analogs [5]. At
the same time, the absorptions of the s h o r t e r - w a v e
1700
,,,, , 1 5, 0 0 , 1300 , 1100
, , 9 ,,0 0 , 7< ~ o c m - Z
maximum of the open form and the long-wave maximum
Fig. 1. IR s p e c t r a (in KBr): 1) 5 - m e t h y l - of the closed form depend only slightly on the solvent.
spiro (5,6 -dihydrophenanthridine -6,2 ~- [2H]
The dipolar s t r u c t u r e of the open f o r m s is in
chromene); 2) 5 - m e t h y l - 6 t - n i t r o - 8 ~ - m e t h -
a g r e e m e n t with t h e i r IR s p e c t r a (Fig. 1), in which a
oxyspiro (5,6-dihydrophenanthridine-6,2-
carbonyl absorption band is absent. F o r the open f o r m s
[2I-I]chromene) (!Ig); 3) 5 - m e t h y l - 6 - ( 2 - o x i d o -
of the nitro derivative the absorption in the region of
3 - m e t h o x y - 5 - n i t r o s t y r y l ) phenathridinium
the stretching vibrations of the nitro group and the
salt fig).
a r o m a t i c ring is v e r y s i m i l a r to the absorption of s o -
diump-nitrophenoxide. The g r e a t e s t difference in the
IR s p e c t r a in these same regions is o b s e r v e d on p a s s -
ing to the c o r r e s p o n d i n g s p i r o p y r a n s .
The behavior of the 8'- and 6 t - c a r b o x y derivatives in alcohol solution is p e c u l i a r . In contrast to 6-
c a r b o m e t h o x y s p i r a n IIl, which is v e r y slightly colored with an absorption maximum in the usual region for
open f o r m s at ~510 nm, solutions of these compounds have intense absorption, but in the s h o r t e r - w a v e
region (~ 410 nm) c h a r a c t e r i s t i c for solutions in acidic media. M o r e o v e r , the relative intensity of the long-
wave absorption of Ij is approximately twice that of the 6 ' - i s o m e r . The r e a s o n f o r the difference in the
s p e c t r a of Ij, k and the s p e c t r a of the remaining spirans can only be proton t r a n s f e r f r o m the carboxyl
group to the phenoxide oxygen of the open form to give a s t r u c t u r e of the merocyanine salt type (HI), which

652
a p p a r e n t l y o c c u r s r e a d i l y i n t r a m o l e c u l a r l y . This s o r t of proton t r a n s f e r oil, at least, the f o r m a t i o n of a
hydrogen bond in Ij should t h e r e f o r e also o c c u r in the solid p h a s e . The p r e s e n c e of a s t r u c t u r e of the IH-
type is c o n f i r m e d by the fact that when e x c e s s a m m o n i a is added to an alcohol solution of Ik, the l a t t e r
initially b e c o m e s c r i m s o n - c o l o r e d as a consequence of the f o r m a t i o n of the open f o r m with R = C O 0 - and
is then d e c o l o r i z e d . The s p e c t r u m of the solution b e c o m e s p r a c t i c a l l y the s a m e as that of s p i r o p y r a n IIk in
dioxane. Thus when the c a r b o x y l group ionizes, the s p i r a n f o r m p r o v e s to be stable even in a l c o h o l s o l u -
tion; this is in a g r e e m e n t with the absence of e l e c t r o n - a c c e p t o r p r o p e r t i e s f o r this group.

EXPERIMENTAL
The aldehydes used in the synthesis and the s p i r o p y r a n s w e r e obtained by l i t e r a t u r e m e t h o d s .
5-Methyl-6 ' - R - 8 ' - R ' - s p i r o (5,6 - dihydrophenanthridine - 6 , 2 ' - [2H ]chromene s) (Ha-f ,k, l ) and 5 - M e t h y l -
6 - ( 2 - o x i d o - 3 - R ' - 5 - R - s t y r y l ) p h e n a n t h r i d i n i u m Salts fig-j). T h e s e compounds w e r e obtained by refiuxing an
alcohol solution (20 m l of alcohol p e r m i l l i m o l e ; 70%aqueous alcohol was u s e d in the p r e p a r a t i o n of If) of
e q u i m o l e c u l a r amounts of 5,6-dimethylphenathridinium methosulfate and the a p p r o p r i a t e aldehyde in the
p r e s e n c e of 2 equivalents of piperidine f o r 30 rain, Compounds I I a - e , k , / were isolated as the c o l o r l e s s
s p i r o p y r a n s , while If-j w e r e isolated in the open f o r m . Compound Ij was isolated f r o m the r e a c t i o n m i x -
t u r e by the addition of h y d r o c h l o r i c acid up to pH 6. The r e a c t i o n p r o d u c t s w e r e r e m o v e d by filtration,
and washed s u c c e s s i v e l y with alcohol and e t h e r . Compound IIf was obtained by the addition of an equal
volume of w a t e r to a hot solution of I f in alcohol (1 : 100). Heating of Ig in chlorobenzene (1 : 50) gave a
g r e e n solution, f r o m which IIg was isolated on cooling. All of the s p i r o p y r a n s except I I f w e r e only slightly
soluble in alcohol, hexane, and e t h e r , but m o r e soluble in a r o m a t i c o r chlorinated h y d r o c a r b o n s . C o m -
pounds IIa, c, e, l w e r e purified by c r y s t a l l i z a t i o n f r o m toluene (1 : 20; 1 : 60 f o r II1), while IIb was purified
by c r y s t a l l i z a t i o n f r o m benzene (1 : 30), Hd was purified by c r y s t a l l i z a t i o n f r o m m - x y l e n e (1 : 30), IIg was
purified by c r y s t a l l i z a t i o n f r o m chlorobenzene (1 : 50), and IIk was purified by c r y s t a l l i z a t i o n f r o m d i m e t h y l -
f o r m a m i d e (DMF) (1 : 20). Compound Ii was p r e c i p i t a t e d f r o m alcohol solution (1 : 120) by the addition of
a twofold quantity of water, while compounds Ih, j w e r e p r e c i p i t a t e d f r o m DMF solution (1 : 50) by the a d -
dition of a fourfold amount of e t h e r . All of the I compounds had intense c o l o r s in the c r y s t a l l i n e state: If
was d a r k blue, Ig and Ii were d a r k brown, Ih was o r a n g e - r e d , and Ij was o r a n g e - y e l l o w .

LITERATURE CITED
1. E. Berman, R. E. Fox, and F. D. Thomson, J. Amer. Chem. Sock, 81, 5605 (1959).
2. R. Gautron, Bull. S . c . Chim. F r a n c e , 3190 (1968).
3. V. P. Martynova, N. E. Shelepin, N. S. L o s e v a , l~. R. Zakhs, L. E. Nivorozhkin, V. I. Minktn, and
L. S. l~fros, Khim. G e t e r o t s i k l . Soedin., 167 (1971).
is A. I. Kiprianov, Usp. Khim., 2..99, 1336 (1960).
5. M. A. G a l ' b e r s h t a m , L. M. Mikheeva, and N. P. Samoilova, Khim. G e t e r o t s i k l . Soedin., 1534 (1972).

653
 CHARGE MIGRATION IN THE MOLECULAR IONS
OF ISOXAZOLE DERIVATIVES

K. K. Z h i g u l e v , S. D. 8 o k o l o v , UDC 547.786ol.717 : 543.51

and R. A. Khmel'nitskii

The effect of charge migration in the m o l e c u l a r ion on the dissociative ionization of isoxazole
derivatives was examined. It is shown that charge redistribution between the substituent in
the 3 position and the oxygen atom of the h e t e r o r i n g p r e c e d e s i s o m e r i z a t i o n of the m o l e c u l a r
ion and its disintegration. The intensity of the peaks of the RCO + ions in the m a s s s p e c t r a of
5 - R - 3 - a r y l i s o x a z o l e s i n c r e a s e s as the a c c e p t o r effect of the a r y l substituent becomes s t r o n g e r .
It is shown that the average internal e n e r g y with which the nitrobenzoyl ions are f o r m e d de-
c r e a s e s as the probability of t h e i r formation i n c r e a s e s , i.e., as the intensity of charge m i g r a -
tion from the a r y l substituent to the oxygen atom i n c r e a s e s .

The effect of charge migration in the m o l e c u l a r ion on the path of disintegration of a compound upon
e l e c t r o n impact has been noted by a number of investigators [1-4]. Continuing our r e s e a r c h on the m a s s
s p e c t r o m e t r y of isoxazoles (for example, see [5-7]), we have a r r i v e d at the conclusion that, owing to the
p r e s e n c e in molecules of these compounds of a labile N - O bond and s e v e r a l potential c h a r g e - l o c a l i z a t i o n
c e n t e r s , t h e i r dissociative ionization is controlled to a considerable extent by the charge distribution in
the m o l e c u l a r ion. In addition to the s y s t e m s considered previously, we have also obtained and investigated
the m a s s s p e c t r a of a n u m b e r of 3,5-diphenylisoxazole derivatives (I-XV).

I-XV

x Y x Y

I p-N02 H IX p-C'l p-NO2

II m-N02 H X p-Cl p-Cl
Ill p-Cl H XI p-NOa p-Cl
IV p-Br H XlI p-NO2 p-NO2
V H p-NO~ XIlI m-NO~ m-NO~
Vl H m-NO2 XIV m-NO~ p-N02
VII H p-CI XV p-NO2 m-NO2
VII1 H p-Br

Charge m i g r a t i o n in the m o l e c u l a r ion plays the decisive role u n d e r conditions of competitive d i s -

integrations of bonds of comparable e n e r g i e s . Thus a shift in the intensities in favor of the formation of
oxygen-containing ions is o b s e r v e d in the following o r d e r : isoxazole, 3,5-dimethylisoxazole, and 3,5-
diphenylisoxazole [6].

R--C~O+ 9 I ~ N '~ ~R
43,0 R= H 95.0
72,5 R=CHa 71,5
100.0 R=C6H5 6.7

Ko A. T i m i r y a z e v A g r i c u l t u r a l Academy, Moscow. T r a n s l a t e d from Khimiya Geterotsiklicheskikh

Soedinenii, No. 6, pp. 755-759, June, 1974. Original article submitted June 4, 1973.

9 19 75 Plenum Publishing Corporation, 22 7 West 17th Street, New York, _IV.Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

654
 TABLE 1. Effect of Substttuents on the Probability of
the Formation and Disintegration of Nitrobenzoyl Ions,
lqO2CsH4CO+, in the Mass Spectra of 5-1~itrophenyliso-
xaz 0 le s

NO2ceH4~S R3

Position of Intensity ratios

the NO z
group in the R3 Ilso+lt~o+llo~
NO2CsH4CO + ~.I ' % 1,5o ' %
ion
p H 7,2 146,6
p C~Hs 17,7 72,3
m CsHs 19,7 51,2
p p-CIC~H4 28,5 47,1
p p-O~,NCsH4 30,0 42,3
p . rn-O2NCsH4 30,7 33,9
m p-OzN'CsH~ 32,1 33,4
m rn-O2NCsH4 35,6 923,0

II~---&.+I'~ ~ This fact is not only a consequence of an increase in the

I ;so stability of the RCO + ions in the s e r i e s R =H, CH3, CsH 5 but is
15o also due to an increase in the fraction of RCO + ions due to charge
migration from group R in the 3 position to the oxygen atom. On
125 '*,
comparing the m a s s spectra of 3,5-diphenylisoxazole and 2-phenyl-
3 - b e n z o y l - l - a z i r i n e [8], one can see that the relative intensity
100
t of the peak of the benzoyl ion, CsHsCO +, is considerably higher
i
in the m a s s spectrum of the isoxazole derivative. On the other
75L[ hand, the intensity of the peak with m a s s 116 (M - CsHsCO)+is
F \ higher than the m a s s spectrum of the azirine derivative.
We investigated the m a s s spectra of the methyl e s t e r and
--h
the amide of 3 - ( o - c h l o r o p h e n y l ) - 5 - m e t h y l i s o x a z o l e - 4 - c a r b o x y l i c
acid. These compounds undergo thermal i s o m e r i z a t i o n to the
corresponding azirine derivatives. In comparing the dissociative
I
10 20 30 40
ionization of the i s o m e r s it was found that the intensity of the peaks
Imo+luo * I,o~ of CH3CO + ions is higher in the ease of the isoxazole derivatives.
zl~ ~~176 We a s s u m e d that redistribution of the charge in the m o l e c u l a r ion
Fig. 1~ Dependence between occurs during ionization and subsequent i s o m e r i z a t i o n prior to
the values that characterize the disintegration of the M + ion of the isoxazole derivative, during
probability of formation [(Iis0 + which the charge initially associated with ionization of the ~r-elec-
I120+Ii04)/ZIi, ~o ] and the prob- iron s y s t e m of the substituent in the 3 position then m i g r a t e s to
ability of disintegration [(Ii20 + the oxygen atom - the center of relative localization. Charge
I104)/Ii50, %] of nitrobenzoyl ions. migration to the oxygen atom in the azirine structure is relatively
hindered because of the energy barrier associated with the p r e s -
ence of a saturated carbon atom in the azirine ring. A result of this is the lower probabilityofthe formation
of RCO + ions in the case of the azirine derivative.

R~ ../"b -T~
/ R~ "

R~ R ~ / ~0 "N

IRsco + X R4 IR5 /~sCO+

57,0 o-C1 CONH2 CH3 44,3
42,4 o-C1 COOCH3 CH~ 31,8

It might be expected that the fraction of RSCO+ ions in the m a s s spectrum of the isoxazole derivative
would increase as the e l e c t r o n - a c c e p t e r character and relative ionization c r o s s section of the substituent
in the 3 position increase. The formation of RSCO+ ions is one of the m o s t important paths of dissociative
ionization of i s o x a z o l e derivatives. In [4] the p r e s e n c e of an inverse dependence between the intensities of
the peaks of the CH3CO + ions and M + ions in the m a s s spectra o f 3 - a r y l - 5 - m e t h y l i s o x a z o l e - 4 - c a r b o x y l i c
acids was shown. Thus the introduction of an lqO 2 group into the benzene ring promotes charge migration

655
 to the oxygen atom of the isoxazole ring and its disintegration to give CH3CO + ions. On the o t h e r hand, the
NH 2 group stabilizes the m o l e c u l a r ion. Thus charge distribution in M + m a y have a s t r o n g effect on its
stability.

....~X
f t+ I

~O ~ 6 sC~O ~ f f J ~ YCsH4C~-O

X=p-Br, p-Cl, p-NO2, m-NO2, H X=Y=p-C[, p-NO2,m-NO2

/C,,HsCO" =36,0; 32,8; 32,6; 29,2; 25,4 Iyc,H,CO~=38,0; 21.3; 28,9

.,O.,~ ~ u 9

Y=p-CI, p-N02, m-NO~

]'YC61LCO*=31,4;I0,3i9,1
In an investigation of the dissociative ionization of 3 , 5 - d i a r y l i s o x a z o l e s we established that the in-
tensity of the peak of the RSCO+ ions always i n c r e a s e s when an a c c e p t e r substituent is introduced into the
benzene ring attached to the C s atom. When Y =NO2, substituent X has an appreciable effect not only on
the probability of formation of O2NC~H4CO+ ions but also on the probability of t h e i r disintegration. These
ions disintegrate via two competitive paths:
NOn
-NO: "~/~ C~_0+ -NO C7H40~
C7H4O+
m, e 104 m/e 150 m/e 120

The sums of the Intensities of the ion peaks (Ii~o+It20+II04) and the (I120+Ito4)/I1so ratios, which c h a r a c t e r i z e
the efficiency of the formation and disintegration of the nttrobenzoyl ions, respectively, are presented in
Table 1. The introduction of substituent R3=YC6H4 (Y=H, p-C1, p-NO2, and m-NO 2) leads to an i n c r e a s e in
It50 and the sum Iis0+I120+I~04. The higher the sum, the lower the II~o+IloJIts0 ratio (Fig. 1). Consequently,
the probability of the disintegration of O2NC6H4CO+ ions d e c r e a s e s as the probability of t h e i r formation in-
c r e a s e s . In o t h e r words, the a v e r a g e internal e n e r g y of these ions b e c o m e s lower.

EXPERIMENTAL
The m a s s spectra of I-XV were obtained with a Varian MAT CH-6 s p e c t r o m e t e r (with a s y s t e m for
direct introduction of the sample into the ion source) at an ionizing voltage of 70 eV (50 eV in the c a s e of
I-IV). The ionization chamber temperature was 180". Peaks of ions with intensities greater than 5% of the
maximum peak are presented.

Mass spectra of a r y l i s o x a z o l e s I-XV

~/C6 H4X
YC6H4/'~o ~N

I (X=p-NO2,Y=H): 51 (6,3), 77 (33,3), 95,5 (5,2), 105 (100,0), 106 (8,9), 266 (66,6),
267 (9,3)
II (X=m-NO2,Y=H): 51 (5,0), 77 i31,6), 78 (9,3), 95,5 (5,9), 105 (100,0). 106 (9,3),
162 (5,5), 189 (5,3), 266 (56,3), 267 (13,2)
Ill (X=p-CI, Y=,H): 51 (6,5), 75 (5,0), 77 (34,4), I05 (I00,0), 106 (9,2), 178 (6,0},
227 (6,5), 255 (39,3), 256 (6,9), 257 (14,0)
IV (X=p-Br, Y=H): 77 (30,4), 105 (100,O), 106 (7,7), 299 (24,0), 301 (24,6)
V (X=H, Y=p-NO2): 50 (7,2), 51 (12,5), 63 (9,5), 76 (16,2), 77 (31,6), 89 (14.3),
104 (31,0), 105 (8,9), I16 (13,1), 120 (20,3), 144 (83,5), 14-5 (8,3), 150 (71,0), 151 (7,1),
165 (6,5), 191 (6,5), 192 (7,7), 219 (11,9), 220 (10,5), 265 (35,5), 266 (I00,0), "267 (16,7)
VI (X.=H, Y=rn-NO2): 39 (5,6), 43 (21,5), 50 (6,2), 51 (10,8), 63 (9,2), 75 (5,6),
76 (16,9), 77 (24,4), 89 (14,4), 92 (5,1), 103 (5,1), 104 (30.3), 105 (6,2), 116 (12,8). 121
(12,8), 133 (5,9), 144 (I00,0), 145 (10,8), 150 (62,1), 165 (5,1), 192 (5,6), 219 (6.2), 220
(5.6), 265 (12,3), 266 (I00,0), 267 (18,0)
VII (X=H, Y=p-CI): 51 (Z,5), 75 (6,8), 77 (9,9), 89 (7,9), 111 (26,5), 113 (10.4),

656
 139 (i00,0), 140 (7,7). 141 (34,4), 144 (17,4), 165 (5,0), 227. (6.8), 254 (14,9), 255 {59.4).
256 (15.4), 257 (19,6)
VIII (X=H, "/=p-t~r): 39 (5,0), 43 (7,3), 50-(7,3), 51 (12,3), 57 (5,9), 63 (6.91.
75 (ll,6), 76 (14,6), 77 (20,3), 89 (14,6), 94,5 (6,0), 105 (12,8). 116 (8,9), 144 (28.l}.
155 (27,4), 157 (30.,5), 165 (6,9), 183 (95,5), 184 (9,1), 185 (I0O,0}, 186 (8,2), 220 (5.0),
271 (7,t). 273 (6,4), 298 (15,1), 299 (53,9), 300 (22,4), 301 (57,5), 302 (8,7)
IX (X=p-CI, Y=p-NO~): 63 (5,5), 79 (13,7), 76 (17,6). 89 (6,3), 92 (10,1), Ill (6.3).
120 (21,1), 123 (6,l), 137 (25,6), 150 (100,0). 151 (9,8), 153 (8,6). 178 (32,7), 180 (11.7~.
219 (8,6), 300 (58,2), 301 (ll,5), 302 (19,3)
X (X=Y=p-CI): 75 (11,6), III (26,6), 113 (9,2), 139 (100,0). 140 (8,2), 141 (34,2).
219 (9,3), 289 (30,9), 290 (6,4), 291 (18,3)
XI (X=p-NO2, Y=p-CI): 75 (8,4), 95,5 (6,3), l l l (25,2), ll3 (8,8), 139 (100.0L
140 (8,9), 141 (32,2), 300 (46,0), 301 (8,7), 302 (16,7)
XII (X=Y=p-NO2): 43 (6,5), 50 (5,5), 57 (7,9), 59 (7,1), 63 (5.1), 75 (7,9), 76 (17,2},
89 (6,5), 92 (10,3), 104 (22,5). I17 (5.9). 120 (18,0), 143 (6.7), 150 (100,0), 151 (71),
189 (15,8), 190 (7,1), 311 (55,3), 312 (13,4)
XIII (X=Y=m-NO2): 76 (15,5), 89 (6,2), 104 (21,7), 143 (6,5), 150 (100.0), 151 (9.2).
189 (17,7), 190 (8,6), 191 (5,5), 311 (57,4), 312 (12,4)
X1V (X=m-NO~, Y=p-NO2): 39 (6,8), 50 (16,2), 62 (9,4), 63 (10,5), 64 (6.0). 75
(13,4). 76 (26,8), 88 (6,0), 89 (ll,0), 91 (7,1), 92 (18,3), 104 (24,4), 120 (9,9), 143 (71).
150 (100,0), 151 (10,4), 189 (15.7), 190 (8,6), 191 (6,3), 311 (66,0), 312 (13,4)
XV (X=p-N,O:, Y=m-NO~): 39 (5,3). 50 (12,7), 63 (9,0), 76 (12.0), 76 (29.4).
89 (12.7), 92 (7,4), 104 (29,4), 120 (4,0), 143 (7,8), 150 (100,0), 151 (9,0), 189 (16.1),
190 (8,0), 191 (6,0), 311 (62.0), 312 (ll,l).

LITERATURE CITED
1. F. W. McLafferty, J. Amer. Chem. S,c., 89, 5043 (1967).
2. H. Bruderer, W. Richter, and W. Vetter, Helv. Chim. Acta, 5_O0,1917 (1967).
3. A. Mandelbaum and K. Biemann, J. Amer. Chem. S,c., 90, 2975 (1968).
4o T. H. Kinstle and Wo R. Oliver, J. Amer. Chem. S.c., 91, 1864 (1969).
5. H. Nakata, H. Sakurai, H. Yoshirumi, and A. Tatematsu, Org. Mass Spectrom., I, 199 (1968).
6. K. K~ Zhigulev, R. A. Khmelvnitskii, M. A. Panina, I. I. Grandberg, and B. M. Zolotarev, Khim. Geter-
otsikl. Soedin., 889 (1972).
7. K. K. Zhigulev, R. A. Khmel~nitskii, S~ D. Sokolov, and N. M. Przheval' skii, Khirn. Geterotsiklo Soedino,
453 (1974).
8. K. Ko Zhigulev, R. A. Khmelvnitskii, and M. A. Panina, Khim. Geterotsikl. Soedin., 457 (1974).

657
2-ARYL-4H-3,1-BE N ZOXAZIN-4-ONE S
ALCOHOLYSIS

B. M. Bolotin, N . I. K u n a v i n , UDC 547.867.2 : 543.422

L . S. Z e r y u k i n a , a n d R . U. S a f i n a

The reaction of 2-(2-tosylaminophenyl)-4H-3,1-benzoxazine-4-one with alcohols in pyridine

gives tosylanthraniloylanthranilic acid e s t e r s . The synthesized compounds h m i n e s c e in the
crystalline state and in solutions at room t e m p e r a t u r e . The anomalously high Stokesian shift
characteristic for this s e r i es of compounds is due to intramoleeular hydrogen bonding with
the participation of the tosylamino group. Interaction of polar solvents and irradiation with
UV light lead to cleavage of the hydrogen bond, and as a consequence, to a decrease in the
Stokesian shift.

The literature contains many indications of unsuccessful attempts to alcoholize the most reactive
representatives of the 4H-3,1-benzoxazine-4-one class - its 2-methyl derivatives [1, 2]. We were able to
realize the alcoholysis of 2-(2-tosylaminophenyl)-4H-3,1-benzoxazine-4-one in pyridine [3] to give high
yields of tosylanthraniloylanthranilic acid e s t e r s . The reaction proceeds readily with normal aliphatic
alcohols and also with a l i p h a t i c - a r o m a t i c alcohols. However, the rate of alcoholysis decreases as the
length of the alkyl chain of the alcohol increases. Thus 91% aleoholysis occurs when 2-(2-tosylaminophenyl)-
4H-3,1-benzoxazin-4-one is refluxed in pyridine-butanol for 2 h, as compared with 76.7% alcoholysis in
the ease of decanol; in o r d e r to achieve complete reaction with methanol, it was necessary to reflux the
mixture for 36 h. Alcohols with iso structures and phenol do not react with 2-(2-tosylaminophenyl)-4H-
3,1-benzoxazine-4-one.
It might be assumed that the catalytic effect of pyridine consists in the formation of an extremely
active intermediate, which also reacts with the alcohol:

. ROH

TsHN

2-Phenyl-4H-3,1-benzoxazin-4-one does not react with alcohols even in the presence of pyridine.
The higher reactivity of the o-tosylamino-substituted compound becomes understandable if one compares
the magnitude of the half-wave potentials for polarographic reduction of 2-phenyl- and 2-(2-tosylamino-
phenyl)-4H-3,1-benzoxazin-4-ones. In the f o r m e r compound it is - 1 . 7 V, as compared with - 1 . 5 2 V in
the latter [4]. The high electrophilicity of the tosylamino-substituted compound is also responsible for
the ease of its reaction with pyridine and subsequent alcoholysls.
At first glance, the fact presented in [5] that 2-phenyl-4H-3,1-benzoxazin-4-one reacts readily with
phenol in the absence of pyridine seems to contradict the explanation proposed above. The apparent "con-
tradiction" is actually due to the fact that the reaction proceeds completely differently in the absence of
pyridine. F ir s t of all, the benzoxazinone is protonated by phenol. As a result, the electrophilicity of the

Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 760-763, June, 1974. Original
article submitted June 21, 1973.

9 19 75Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retn'eval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy of this article is availablefrom the publisher for $15.00.

658
 TABLE 1. Tosylanthraniloylanthranilic Acid E s t e r s
Com- I Crystal- Empirical Found, ~o
mp, ~ ,lization i Calc., ~o IYield.
pound
solvent
formula .%
c H N C ] H N
i
I CHs 164 AcOH C~H2oN2OsS 62,2 4,7 6,81 62,3] 4,7 6,6 94
II C2Hs 134 AcOH C~H~N2OsS 62,8 5,0 6,4 63,0[ 5,1 6,4 82
III CaH7 133 Phil C24H2~N2OsS 63,7 5,5 6,4 63,7[ 5,3 6,2 88
IV C4H9 113 Phil C25HzoN2OsS 64,4 5,7 6,2 64,4l 5,6 1 6,0 88
V CsHI7 100 Phil C=gH34N2OsS 66,5 6,6 5,3 66,61 6,6 5,3 84
VI C9HI9 91 Phil CsoH36N~OsS 67,2 6,8 5,4 67,1] 6,8 5,2 74
VH CioH21 99 Phil C31H~sN~OsS 67,7 7,2 5,0 67,6 7,0 5,1 87
"VIII CI6H33 I 87 PhH Ca7HsoN2OsS 69,4 7,8 4,8 69,41 8.1 4,5 99
IX CH2CsHs , 162 Phil C~sH24N2OsS 67,3 4,8 5,4 67,2 4,8 5,6 53
X CH2CHeC6H5 i 142 Phil C29H26N2OsS 6.7,7 5,1 5,6 67,7 5,1 5,4 89

m o l e c u l e i n c r e a s e s sharply, and this a l s o p r o m o t e s attack

I/tma ~ on it by phenol. This sort of protonation is p o s s i b l e only in
the c a s e of 2 - p h e n y l - 4 H - 3 , 1 - b e n z o x a z i n - 4 - o n e . The p r e s -
ence o f an i n t r a m o l e c u l a r hydrogen bond in the t o s y l a m i n o
derivative m a k e s it i m p o s s i b l e to protonate it with phenol.
It is p r e c i s e l y for this r e a s o n that 2 - p h e n y l - 4 H - 3 , 1 - b e n -
z o x a z i n - 4 - o n e r e a c t s with phenol in the absence of pyridine,
while its o - t o s y l a m i n o derivative does not.
Ayi].m
400 500 600 Electronic Spectra
Fig. 1. Dependence of the l u m i n e s - The tosylanthraniloylanthranilic acid e s t e r s absorb in
cence s p e c t r u m of an alcohol solution a s h o r t e r - w a v e region than b e n z o x a z i n o n e s . It is i n t e r e s t -
of tosylanthraniloylanthranilic acid ing that the c h a r a c t e r of the spectra and the position of the
e s t e r on the wavelength of the exciting m a x i m a are p r a c t i c a l l y independent of the length of the alkyl
light at 293 ~ K: 1) kex 313 nm; 2) kex chain of the alcohol r e s i d u e . This indicates that the e s t e r
365 nm. grouping does not e n t e r into the c o m p o s i t i o n of the c h r o m o -
p h o r e s r e s p o n s i b l e for the absorption at 267 and 319 rim.
As in the c a s e of b e n z o x a z i n o n e s , a capacity for f l u o r e s c e n c e is c h a r a c t e r i s t i c for t o s y l a n t h r a n i l o y l -
anthranilic acid e s t e r s . However, in contrast to the f o r m e r , they f l u o r e s c e intensely not only in the c r y s t a l -
line state but also in solution at r o o m t e m p e r a t u r e . Like the absorption s p e c t r u m , the f l u o r e s c e n c e s p e c t r u m
is independent of the length of the alkyl chain of the alcohol r e s i d u e . One's attention is directed to the
a n o m a l o u s l y high Stokesian shift, which, in analogy with b e n z o x a z i n o n e s [6], can be explained by strengthen-
ing of the i n t r a m o l e c u l a r hydrogen bond in the excited state.
The f o r m a t i o n of two types of i n t r a m o l e c u l a r hydrogen bonds is p o s s i b l e i n t h e t o s y l a n t h r a n i l o y l a n t h r a -
nilic acid e s t e r m o l e c u l e : t h o s e with the participation of the t o s y l a m i n o group and the amide carbonyI
group (form A) o r those with the participation of the amide hydrogen and the e s t e r carbonyl group (from B}.
o oR

t
Ts
B
A
It s e e m e d of interest to a s c e r t a i n which of t h e s e f o r m s is actually r e a l i z e d and how the f l u o r e s c e n c e p r o -
p e r t i e s depend on this. If the tosylanthraniloylanthranilic acid e s t e r s did e x i s t in form B, the f l u o r e s -
cence p r o p e r t i e s and, above all, the f l u o r e s c e n c e intensity should have been dependent on the length
of the alkyl chain, as in the e a s e of 2 - h y d r o x y - 4 - m e t h y l - 5 - c h l o r o a l k a n o p h e n o n e s [7]. However, this
is not actually observed~ For c o m p a r i s o n , we s y n t h e s i z e d m o d e l compounds in which only form A
or only form B can be r e a l i z e d . (See s c h e m e on the following page.)
It was found that 2 - ( N - t o s y l a n t h r a n i l o y l a m i n o ) b e n z y l alcohol, like tosylanthraniloylanthranilic a c i d .
e s t e r s , has an a n o m a l o u s l y high Stokesian shift and f l u o r e s c e s in the green region of the s p e c t r u m . 2 - ( 2 -

659
 CH

I
Ts
Tosylaminophenyl)benzoxazole and the o v e r w h e l m i n g m a j o r i t y of compounds in which the t o s y l a m i n o group
p a r t i c i p a t e s in the f o r m a t i o n of an i n t r a m o l e c u l a r hydrogen bond have the s a m e p r o p e r t i e s . At the s a m e
t i m e , m e t h y l benzoylanthrantlate, which does not contain a t o s y l a m i n o group, differs substantially f r o m
t h e m with r e s p e c t to its f l u o r e s c e n c e p r o p e r t i e s .
In studying the f l u o r e s c e n c e p r o p e r t i e s of the s y n t h e s i z e d e s t e r s , we noted that the c h a r a c t e r of the
s p e c t r u m depends m a r k e d l y on the solvent. Thus, while only one m a x i m u m (kma x 520 nm) is o b s e r v e d in
toluene at 77~ another m a x i m u m (kmax 418 rim) a p p e a r s in alcohol and d i m e t h y l f o r m a m i d e (DMF). The
r a t i o of the intensities of the nblue n and " g r e e n n f l u o r e s c e n c e m a x i m a depends on the wavelength of the
exciting light {Fig. 1). This indicates that in this case we a r e dealing with an equilibrium m i x t u r e r a t h e r
' than with an individual compound that has two f l u o r e s c e n c e m a x i m a . The a s s u m p t i o n of decomposition of
the substance as it d i s s o l v e s in alcohol is excluded, f o r the t o s y l a n t h r a n i l o y l a n t h r a n i l i e acid e s t e r is i s o -
lated unchanged when the alcohol solution is vacuum e v a p o r a t e d , It m u s t be a s s u m e d that we a r e dealing
in this case with an equilibrium m i x t u r e of two f o r m s , one of which has g r e e n f l u o r e s c e n c e , the o t h e r of
which has blue f l u o r e s c e n c e . The nbluen f o r m p r o b a b l y c o r r e s p o n d s to the c a s e in which the t o s y l a m i n o
group does not p a r t i c i p a t e in the f o r m a t i o n of an i n t r a m o l e c u l a r hydrogen bond. It Is p r e c i s e l y this fact
that m a y explain the e x i s t e n c e of the nblue n f o r m only in solutions in p o l a r solvents.
U l t r a v i o l e t - l i g h t i r r a d i a t i o n affects the e s t e r s in the s a m e way as a p o l a r solvent. In this c a s e , the
excitation e n e r g y in a portion of the m o l e c u l e s is expended in cleavage of the hydrogen bond, and one ob-
s e r v e s buildup of the "blue" f o r m , One of the a b o v e - m e n t i o n e d m o d e l c o m p o u n d s - 2 - ( N - t o s y l a n t h r a n i l o y l ~
amino)benzyl alcohol - behaves in t~recisely the s a m e way. At the s a m e t i m e , the s p e c t r u m of m e t h y l benzo-
ylanthranilate does not change e i t h e r in the p r e s e n c e of p o l a r solvents o r during UV i r r a d i a t i o n .
A change in the absorption s p e c t r a is o b s e r v e d s i m u l t a n e o u s l y with the change in the f l u o r e s c e n c e
s p e c t r a of t o s y l a n t h r a n i l o y l a n t h r a n i l i c acid e s t e r s . The intensity of the long-wave band falls. Absorption
at 350-420 nm a p p e a r s s i m u l t a n e o u s l y (Fig. 2). The a p p e a r a n c e in the a b s o r p t i o n s p e c t r u m of the e s t e r of
a long-wave ntail" as a r e s u l t of i r r a d i a t i o n m a y be a consequence of cleavage of the i n t r a m o l e c u l a r h y d r o -
gen bond and m o r e complete p a r t i c i p a t i o n of the t o s y l a m i n o group in conjugation. Thus both the h y p s o -
c h r o m i c shift of the f l u o r e s c e n c e s p e c t r u m and the b a t h o c h r o m i c shift of the a b s o r p t i o n s p e c t r u m attest to
disruption, during i r r a d i a t i o n , of the hydrogen bond in which the t o s y l a m i n o group p a r t i c i p a t e d ,

EXPERIMENTAL
The absorption s p e c t r a of solutions in alcohol and toluene (5 9 10-4-1 910 -5 M) w e r e r e c o r d e d at r o o m
t e m p e r a t u r e with a cuvette t h i c k n e s s of I era. The f l u o r e s c e n c e s p e c t r a o f the solutions w e r e r e c o r d e d with

I/Imax

~176176
~ ~ ~176176176
300 400 500 ~,nm
Fig. 2. Reduced a b s o r p t i o n and l u m i n e s c e n c e s p e c t r a
of an alcohol solution of t o s y l a n t h r a n i l o y l a n t h r a n i l i e
acid e s t e r at 293" K: 1) p r i o r to i r r a d i a t i o n with UV
light; 2) a f t e r i r r a d i a t i o n with UV light.

660
a device a s s e m b l e d f r o m an MDI~-3 m o n o e h r o m a t o r with a l i n e a r d i s p e r s i o n of 1.3 n m / m m . The s p e c t r a
w e r e r e c o r d e d at 77 and 293 ~ K and a r e p r e s e n t e d in this p a p e r with allowance for the quantum s e n s i t i v i t y
of the a p p a r a t u s .
A l c o h o l y s i s of 2 - ( 2 - T o s y l a m i n o p h e n y l ) - 4 H - 3 , 1 - b e n z o x a z i n - 4 - o n e . A solution of 1 g (2.5 m m o l e ) of
benzoxazinone and 0.01 m o l e of the a p p r o p r i a t e alcohol in 5 m l of pyridine was heated for 20 h with gentle
refluxing of the r e a c t i o n m i x t u r e , a f t e r which 1 m l of w a t e r was added to hydrolyze the unchanged b e n z o x -
azinone, and the m i x t u r e was heated f o r a n o t h e r hour. It was then cooled to r o o m t e m p e r a t u r e and poured
with s t i r r i n g into 100 m l of 5%aqueous sodium bicarbonate solution. The p r e c i p i t a t e d e s t e r was r e m o v e d
by filtration, washed with water, and c r y s t a l l i z e d f r o m a suitable solvent.

LITERATURE CITED
1. Ro Co B e r t e l s o n and W. J. B e c k e r , Jo H e t e r o c y c l . Chem., 3, 422 (1966)o
2. Wo Ried and B. P e t e r s , Ann., 729, 124 (1969).
3. B . M . Bolotin and V. G. Budz', USSR A u t h o r , s C e r t i f i c a t e No. 323,402 {1971); Byul. Izobr., No. 1
(1972).
4. Yu. A. Oavydovskaya and B. M. Bolotin, Zh. Vsesoyuzn. Khim. Obshchestva, 1_6.6,117 (1971).
5o A. Mustafa, A. H. E. K a r k a s h , and M. K a m e l , J. A m e r . C h e m . Soc., 77.7, 3860 (1955).
6. M . V . L o s e v a , Bo M. Bolotin, G. A. Ivanova, and R. N. N u r m u k h a m e t o v , Zh. F i z . K h i m . , 4_66,2195 (1972).
7. Bo N. T r i p a t h and C. L, G a r g , Indian J. Chem., 7, 778 (1969).

661
 SYNTHESIS OF SUBSTITUTED 2-AMINO-4H-1,3-OXAZINES

L. A. Ignatova, A. E. Gekhman, UDC 547.867.07

M. A. Spektor, P. L. Ovechkin,
and B. V. Unkovskii

4 , 4 , 6 - T r i m e t h y l - 2 - m e t h y l a r y l a m i n o - 4 H - 1 , 3 - o x a z i n e s w e r e synthesized by t n t r a m o l e c u l a r c y c l i -
zation of N - o x o a l k y l - S - m e t h y l t s o t h i o u r e a s .

The synthesis of a n u m b e r of 2 - a l k y l ( a r y l ) - 4 H - 1 , 3 - o x a z i n e s by r e a c t i o n of p - h a l o ketches w i t h n i t r i l e s

in the p r e s e n c e of Lewis acids has been d e s c r i b e d [1, 2], but 1,3-oxazines with functional groups attached
to the C 2 atom w e r e unknown up until now [3].
We undertook the synthesis of 4 , 4 , 6 - t r i m e t h y l - 2 - a m i n o - 4 H - 1 , 3 - o x a z i n e s (IVa-f), which a r e oxygen
analogs of 2 - a m i n o - 4 H - 1 , 3 - t h i a z i n e s [4], f r o m N - m e t h y l - N - a r y l - N ' - ( 2 - m e t h y l - 4 - o x o - 2 - a m y l ) t h i o u r e a s
(Ia-e), which w e r e c o n v e r t e d to N - m e t h y l - N - a r y l - N r- ( 2 - m e t h y l - 4 - o x o - 2 - a m y l ) - S - m e t h y l t s o t h i o u r e a h y d r i -
odldes (IIa-e). The l a t t e r a r e cyclized on t r e a t m e n t with alkali to aminooxazines I V a - e with methyl m e r -
captan evolution. The method is s i m i l a r to the method p r e v i o u s l y p r o p o s e d for the synthesis of 2 - a m i n o -
5 , 6 - d i h y d r o - 4 H - 1 , 3 - o x a z i n e s [5].
Aminooxazine IVf was s i m i l a r l y obtained f r o m N , N - d i m e t h y l - N ~ - ( 2 - m e t h y l - 4 - o x o - 2 - a m y l ) t h i o u r e a
(If). Compounds I V a - f can also be obtained in one step by methylation of I a - f with methyl iodide in an a l c o -
hol solution of p o t a s s i u m hydroxide. We also obtained IVf by cyelization of t h i o u r e a If in refluxing benzene
in the p r e s e n c e of red m e r c u r i c oxide. The f i r s t method was m o r e convenient f r o m a p r e p a r a t i v e point of
VieW.
CH31 OH-
[ .o~ u l
", H
CH3\ ,/__.C(~3 CH3~ ~ /CH3 CH 3 ~ , t / C H 3
CH3~"~/CH3 CH31-CH31..+.~
~":~C=O -OH-
~ CH3:I~. ~ -- CH3\~'~"
, CH3~. ~ T /~"
~1t3

S CH3/N\ R CH3/N\R CH3/i~\R

I II III IV
[--1Va R=p-CH3OC6H4; b R=m-CHsOCsH,; c R=p-CH3C6H4; dR=m-CH3C6H4;e R=CJ-I~;
f R=CH3
The cyclization of II a p p a r e n t l y p r o c e e d s through the enol f o r m of b a s e s III or, which is m o r e p r o b -
able, via a p u s h - p u l l m e c h a n i s m with synchronous cyclic t r a n s f e r of the p a i r of e l e c t r o n s along the s y s -
t e m of H - C H - C =O bonds, p r e c e d e d by s t r i p p i n g of a proton f r o m the Co~ atom in the oxoalkyl portion of
the m o l e c u l e , which o c c u r s in alkaline m e d i a . A consequence of this is an i n c r e a s e i n t h e e l e c t r o n density
on the oxygen a t o m , and this t e r m i n a t e s with i n t r a m o l e c u l a r nucleophilio attack of the c a r b o n atom of the
amidine f r a g m e n t of the m o l e c u l e .
In an attempt to synthesize 3 , 4 , 4 , 6 - t e t r a m e t h y l - 2 - p h e n y l i m i n o - 2 , 3 - d i h y d r o - 4 H - 1 , 3 - o x a z i n e (VI) via
a s i m i l a r path f r o m N - p h e n y l - N ' - m e t h y l - N , - ( 2 - m e t h y l - 4 - o x o - 2 - a m y l ) - S - m e t h y l i s o t h t o u r e a (V), we isolated
N - m e t h y l - N ' - p h e n y l - O - e t h y l t s o u r e a (in yields g r e a t e r than 80%), which is f o r m e d as a r e s u l t of d e s t r u c -
tion of the molecule at the N ' - C bond and nuoleophilic substitution of the methylthlo group by an ethoxy
group in the s t a r t i n g V o r in the initially f o r m e d N - m e t h y l - N ' - p h e n y l - S - m e t h y l i s o t h i o u r e a (VII), instead

M. V. L o m o n o s o v Moscow Institute of Fine C h e m i c a l Technology. T r a n s l a t e d f r o m Khimiya G e t e r -

otsiklicheskikh Soedinenii, No. 6, pp. 764-767, June, 1974. Original a r t i c l e submitted July 2, 1973.

9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy of this article is availablefrom the publisher for $15.00.

662
 TABLE 1. Substituted 2 - A m i n o - 4 H - 1 , 3 - o x a z i n e s ( I V a - f ) a n d T h e i r
Hcrates
I Iqo
Found, Calc.,
t% II IRspectra ~" ~
I ~ =~ I ~ {
>"
""~
e~
o J
no.~o :i ~
~em" [ a m " / ~ .-< ~1 ~ | ~ ' ~
I
a p-CI-I30--CsH~ 1,5381 C15t-I2oN20~ 68,6 7,7t 69,2 7,7 1712 1665 I 247 40' 182--182,5
b I--CHaOCaH4 1,5418 ClsH2oN20~ 69,7 7,7t 69,2 7,7 1715 1659 (4,02)
254 62 141--141,5
(4,01)
C Ip-CIta--C6H4 74,0 8,1[ 73,8 8,2 1720 1660 252 36 176--177
11',:3430:/~ ll[::~ (4,03)
d ~i--Ct[~--C6H4 74,0 8,3[ 73,8 8,2 1718 1658 251 60 158--158,5
[ (4,01)
e IC~H~ 1,5374]C14H~sN20 72,6 7,8[ 73,6 7,9 1720 1665 253 55 133--133,5
i
t (4,02)
f CHa 1,4688 CgHIsN20 64,5 9,6]64,3 9,6 172C 1665 205 60 134--135
(4,08)

* The c o m p o s i t i o n of the p i c r a t e s was c o n f i r m e d by d e t e r m i n a t i o n

of the p e r c e n t a g e of C, H, and N.

of the expected VI. Thus when a CH 3 group is attached to the N' nitrogen atom, the r a t e of cleavage of the
molecule a p p a r e n t l y e x c e e d s the r a t e of eyclization of V to VI; this m a y be a s s o c i a t e d with both the u n -
favorable configuration of imino s t r u c t u r e V as c o m p a r e d with II (as a consequence of s t e r i c i n t e r a c t i o n
of the m e t h y l groups attached to the N' atom and the adjacent c a r b o n atom) and with the different e l e c t r o n i c
s t a t e s of the N' nitrogen atom in III and V. As a consequence of p-~r i n t e r a c t i o n of the e l e c t r o n s of the
C =N bond and the N' nitrogen, the l a t t e r a c q u i r e s e x c e s s positive charge, and this p r o m o t e s cleavage of
the N ' - C bond.
The tendency for the V molecule to undergo c l e a v a g e is so g r e a t that S - m e t h y l i s o t h i o u r e a VII is f o r m e d
even on b r i e f heating in alcohol.

cH3~/"~c~3 on- CH3\~/~c'CH3

CH /N S\ / " N.~jO
3 ~1 Ctl3 " II
N\C6H 5 N'~'C6H5
v ~cz~ Vl

Vi| IX VIII

Compounds IV, VII, and VIII w e r e isolated and identified by m e a n s of t h e i r II1 and PMR s p e c t r a ; VII
was also identified by c o m p a r i s o n with a s a m p l e of known s t r u c t u r e .
The IR s p e c t r a of aminooxaztnes I V a - f contain the a b s o r p t i o n band of the s t r e t c h i n g v i b r a t i o n s of the
C =N bond at 1658-1665 cm-1; a s i m i l a r band is also p r e s e n t in the s p e c t r a of 2 - m e t h y l a r y l a m i n o - 5 , 6 -
d i h y d r o - g H - 1 , 3 - o x a z i n e s [51. In addition, the vC = C ring band is o b s e r v e d at 1712-1720 c m - l ; the unusually
high frequency for this band is a p p a r e n t l y a s s o c i a t e d with the p e c u l i a r i t i e s of the i n t e r a c t i o n of the ring
oxygen atom of IV with the 7r e l e c t r o n s of the C =C bond and the C =N bond of the amidtne s y s t e m . Thus,
for e x a m p l e , anomalously high vC =C values w e r e noted in the IIt s p e c t r a of vinyl fluorides [61, p y r i m i d i n e -
2-thiones [71, oxazolines [8], and 2 - a l k y l ( a r y l ) - 4 t t - l , 3 - o x a z i n e s a l t s [91, in which the e l e c t r o n s of the h e t e r o -
4-
atom in the ~ position r e l a t i v e to the C =C bond i n t e r a c t e f f e c t i v e l y with the C =O, C =S, o r H - - N = C
I

groups m e s o m e r i c a l l y , as a consequence of which t h e - I effect of the h e t e r o a t o m with r e s p e c t to the C =C

bond i n c r e a s e s . S i m i l a r r e a s o n s a p p a r e n t l y explain the vC =C frequency in the s p e c t r a of I V a - f .
The signal of six protons of geminal m e t h y l groups (1.05-1.13 ppm}, a broadened singlet of the p r o -
tons of a CH 3 group attached to a C =C bond (1.60-1.72), a weak r e s o l v e d q u a r t e t o f a n H - C = p r o t o n ( 4 . 5 ~ r
4.58), a singlet of C H 3 - N protons (3.08-3.10), and a multiplet of a r o m a t i c protons (6.70-6.90) a r e o b s e r v e d
in the PMR s p e c t r a of I V a - f .

663
 EXPERIMENTAL
The IR s p e c t r a of thin l a y e r s of the compounds w e r e r e c o r d e d with a UR-10 s p e c t r o m e t e r . The UV
s p e c t r a of ethanol solutions of the s u b s t a n c e s (1 9 10-5-5 9 10 -5 M) were r e c o r d e d with a Hitachi s p e c t r o -
p h o t o m e t e r . The PMR s p e c t r a w e r e m e a s u r e d with an RS-60 s p e c t r o m e t e r with hexamethyldisiloxane
(HMDS) as the internal s t a n d a r d .
N-Methyl-N-phenyl-NV- ( 2 - m e t h y l - 4 - o x o - 2 - a m y l ) - S - m e t h y l i s o t h i o u r e a Hydriodide (He). A m i x t u r e
of 2.2 g (8.0 m m o l e ) of Ie [4] and 1.3 g (9.0 m m o l e ) of m e t h y l iodide was allowed to stand at 25" for 10 h.
The acetone was vacuum e v a p o r a t e d to give 3.2 g (96%) of IIe with mp 1 2 1 . 5 - 1 2 2 . 5 ~ (purified by r e p r e c i p i t a -
tion f r o m methanol solution by the addition of ether). Found: N 6.7; S 8.1; I 31.5%. C15H23N2OS 9 HI. C a l -
culated: N 6.9; S 7.9; I 31.5%. A s i m i l a r p r o c e d u r e was used to obtain I I a - d , f, which were converted to
IVa-d, f without additional purification.
4 , 4 , 6 - T r i m e t h y l - 2 - m e t h y l p h e n y l a m i n o - 4 H - 1 , 3 - o x a z i n e (IVe). A 3 . 2 - g (7.9 m m o l e ) s a m p l e of h y d r i -
odide He was dissolved in 80 m l of a 3 N methanol solution of sodium hydroxide. The methanol was r e -
m o v e d by distillation a f t e r 24 h, and the residue was e x t r a c t e d with boiling hexane. The hexane wax r e -
m o v e d f r o m the e x t r a c t by distillation, and 30 m l of a s a t u r a t e d alcohol solution of p i c r i c acid was added
to the r e s i d u e . The p r e c i p i t a t e that f o r m e d a f t e r 4 h was r e m o v e d by filtration to give 2.0 g (57%) of the
p i c r a t e of oxazine IVe. The p i c r a t e was m i x e d with 10 g of activity lI aluminum oxide, and 10 m l of a 3 N
solution of p o t a s s i u m hydroxide in methanol was added. The methanol was vacuum e v a p o r a t e d , and the d r y
residue was c h r o m a t o g r a p h e d on aluminum oxide with elution b y h e x a n e - e t h e r (1 : 1) to give 0.98 g of oxazine
IVe. A s i m i l a r method was u s e d to obtain IVa-d, e as c o l o r l e s s oils that were stable on s t o r a g e and r e s i s -
tant to alkaline h y d r o l y s i s .
4 , 4 , 6 - T r i m e t h y l - 2 - m e t h y l ( p - t o l y l ) a m i n o - 4 H - 1 , 3 - o x a z i n e (IVc). A m i x t u r e of 1.0 g (3.4 m m o l e ) of
Ic and 0.6 g (4.1 m m o l e ) of m e t h y l iodide in 30 m l of a 3 N solution of p o t a s s i u m hydroxide in methanol was
allowed to stand at 25 ~ for 30 h. The methanol was then r e m o v e d by distillation, and the residue was e x -
t r a c t e d with boiling hexane. The hexane was r e m o v e d f r o m the e x t r a c t by distillation, 10 m l of a s a t u r a t e d
alcohol solution of p i c r i c acid was added to the r e s i d u e , and the r e s u l t i n g p r e c i p i t a t e was r e m o v e d by f i l -
t r a t i o n to give 0.80 g (38%) of the p i c r a t e of oxazine IV, f r o m which oxazine IVc was obtained as d e s c r i b e d
above.
4 , 4 , 6 - T r i m e t h y l - 2 - d i m e t h y l a m i n o - 4 H - 1 , 3 - o x a z i n e (IVf). A 5.5-g (1.4 m m o l e ) s a m p l e of I f and 2 2 . 1
g (3.3 mmole) of red m e r c u r i c oxide were refluxed in 20 m l of d r y benzene for 2 h, a f t e r which the m e r -
c u r i c sulfide and e x c e s s m e r c u r i c oxide w e r e r e m o v e d by filtration, the benzene was r e m o v e d by d i s t i l -
lation, and 20 m l of a s a t u r a t e d alcohol solution of p i c r i c acid was added to the r e s i d u e . The r e s u l t i n g p r e -
cipitate was r e m o v e d by filtration to give 6.8 g (62%) of the p i c r a t e of oxazine IVf, f r o m which oxazine IVf
was isolated.
N - M e t h y l - N - p h e n y l - S - m e t h y l i s o t h i o u r e a (VII). A solution of 3.0 g (9.2 m m o l e ) of V in 20 ml of
alcohol was heated at 78 ~ for 2 h, a f t e r which the alcohol was r e m o v e d by distillation. The residue was
c h r o m a t o g r a p h e d with a column filled with activity II aluminum oxide and elution by h e x a n e - e t h e r (2 : 1)
to give 1.2 g (71%) of i s o t h i o u r e a VII with mp 56-57 ~ (from hexane): Found: N 15.8%. CgHI2N2S. C a l c u -
lated: N 15.5%.

N - M e t h y l - N ' - p h e n y l - O - e t h y l i s o u r e a (VIII). A 2.0 g (6.1 m m o l e ) s a m p l e of V was added to 30 m l of a

3 N alcohol solution of sodium hydroxide, and the m i x t u r e was allowed to stand at 25" f o r 10h. The alcohol
was r e m o v e d by distillation, and the residue was e x t r a c t e d with hexane. The hexane was r e m o v e d by d i s -
tillation to give 0.9 g (82%) of t s o u r e a VIII as a c o l o r l e s s o i l PMR s p e c t r u m (in CC14): 1.18 (CH3-C , t),
2.25 (CH3-N , s), 3.73 (NH, s), 3.99 (CH2, q), and 6.85 (C6H5, m).

LITERATURE CITED
1. M. L o r a - T a m a y o , R. Madronero, J . Minor, and H. L e i p p r a n d , B e r . , 97, 2234 (19647.
2. R. Schmidt, B e r . , 98, 334 (1965).
3. R. Schmidt, Synthesis, 333 (19727.
4. P. L. Ovechkin, L. A. Ignatova, A. E. Gekhman, and B. V. Unkovskii, Khim. G e t e r o t s i k l . Soedin.,
937 (19727.
5. L. A. Ignatova, P. L. Ovechkin, M. Z. B r a n z b u r g , A. E. Gekhman, and B. V. Unkovskii, Khim. G e t e r -
otsikl. Soedin., 1037 (1972).
6. J . Miller, J. Org. Chem., 25, 1279 (1960).

664
7o B. V. Unkovskii, L. A. Ignatova, 1% L. Ovechkin, and A, I. Vinogradova, Khim. Geterotsikl. Soedin.,
1690 (1970).
8. R. Gompper and H. Herlinger, Ber., 89, 2825 (1956).
9. R. Schmidt, Ber., 98, 3892 (1965).

665
 UV SPECTRA OF SOME DERIVATIVES OF
5,10-DIHYDROPHENARSAZINE AND 5,10-
DIHYDRO PHENOXARSINE

R. R. Shagidullin, A. V. Chernova, UDC 543.42.6 : 547.864'867'242

B. D. Chernokal'skii, V. I. Gavrilov,
and G. R. Gavrilova

The l o n g - w a v e b a n d with a m a x i m u m a b o v e 300 n m in t h e UV s p e c t r a o f s u b s t i t u t e d 5 , 1 0 - d i h y -

d r o p h e n a r s a z i n e s i s i n t e r p r e t e d a s a t r a n s i t i o n w i t h i n t r a m o l e c u l a r c h a r g e t r a n s f e r in w h i c h
t h e t r i v a l e n t a r s e n i c a t o m a c t s a s an e l e c t r o n a c c e p t e r . T h e u n s h a r e d p a i r o f e l e c t r o n s o f
As(III) a p p a r e n t l y m a k e s i t s own c o n t r i b u t i o n to t h e z--Tr* t r a n s i t i o n s a t 240-280 n m .

T h e UV s p e c t r a o f a r y l a r s i n e s have b e e n i n t e r p r e t e d in a n u m b e r o f p a p e r s [1, 2]. H o w e v e r , t h e s p e c -

t r a and the d e t e r m i n a t i o n o f t h e n a t u r e o f t h e b a n d s b e c o m e m a r k e d l y c o m p l i c a t e d on p a s s i n g to 1 0 - s u b -
s t i t u t e d 5 , 1 0 - d i h y d r o p h e n a r s a z i n e s ( 5 , 1 0 - D H P A ) [3-5]. We have i n v e s t i g a t e d t h e UV s p e c t r a o f a n u m b e r
o f 5 , 1 0 - D H P A and t h e p r o d u c t s o f t h e i r o x i d a t i o n a n d m e t h y l a t i o n at t h e a r s e n i c a t o m ( T a b l e 1). T h e p r e s -
e n c e in t h e UV s p e c t r a o f 5 , 1 0 - D H P A d e r i v a t i v e s o f a b a n d at 3 0 0 - 3 5 0 n m i s c h a r a c t e r i s t i c ( F i g . 1).

T A B L E 1. UV S p e c t r a o f 1 0 - S u b s t i t u t e d 5 , 1 0 - D i h y d r o p h e n a r s a z i n e s
and 5,10-Dihydrophenoxarsines
kma x (log s ), nm (in ethanol)

As-C21t5 246(4,00) 293(4,11) 315(3,96)* 230 (4,14)* 288(3,58)

As (O) C2115 242 (4,03) 277 (3,59)
287 (3,68)
294(3,69)
As (CI%)C2H5I- 238(3,76)* 276(4,23) 316(4,04) 243(3,93) 280(3,53)
340(4,00) * 288(3,59)
295(3,60)
As-CH(CHa)2 246(3,97) 294(4,05)315(3,93)* 233 (4,12)* 289 (3,60)
As (O)-CH (CH~)2 238(3,75)* 276(4,26) 310(4,06)
325(3,87)*
336 (3,77)*
As+(CH3)CH(CH~)2I- 239(3,65)* 275(4,21) 312 (4,03)
336 (3,80)*
AsBr 225(4,54) 283 (4,21) 308(4,02) 246(4,13) 301(3,76)
353(3,75)
As-C6Hs 246(3,96)* 288 (4,06) 318(3,91) 236(4,36)* 289(3,68)
As(O)-C6Hs 221 (4,52)* 274 (4,19) 309(4,05) 244(4,17)* 280(3,52)
328 (3,88)* 288(3,59)
336 (3,85)* 297(3,55)
As+(CHs)C6H~I- 218 (4,69)* 273 (4,20) 318(4,06)
329 (3,99)*
339 (3,90)*
As-C6H4-CH3-n 235(4,40)* 292(4,07) 325(3,97) 238(4,37)* 289(3,67)
As-C~H4-CI-n 238(4,43)* 290(4,14) 328(3,99) 23O--
238(4,37)* 288(3,90
As-CeH~-OCH3-n 240(4,35) 291 (4,05) 326(3,95)* 230--
240(4,42)* 284(3,79)

* Shoulder.
A . E. A r b u z o v I n s t i t u t e o f O r g a n i c a n d P h y s i c a l C h e m i s t r y , A c a d e m y o f S c i e n c e s o f t h e USSR, K a z a n .
T r a n s l a t e d f r o m K h i m i y a G e t e r o t s i k l i c h e s k i k h S o e d i n e n i i , No. 6, p p . 7 6 8 - 7 7 0 , J u n e , 1974. O r i g i n a l a r t i b l e s u b -
m i t t e d J u n e 21, 1973.

9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, N.Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

666
 LgC Its appearance is a p p a r e n t l y a s s o c i a t e d with the p r e s e n c e
4,5 .. of two h e t e r o a t o m s - nitrogen and a r s e n i c - in the molecule
[ 5]. Absorption bands are not o b s e r v e d in the indicated
9..P :. ~,
region for model compounds with only one of them (see, for
example, the UV s p e c t r u m of 9 - c h l o r o - 9 - a r s a f l u o r e n e in
Fig. I).
3,5 ~ ,' "-. ~ The exposure of the nature of the long-wave transition
if -. ~\ in the s p e c t r a of 5,10-DHPA derivatives under d i s c u s s i o n
is facilitated by a c o m p a r i s o n of t h e i r s p e c t r a with the data
" /b for the oxides and methiodides (Table 1). If the unshared
p a i r of the e l e c t r o n s of the a r s e n i c atom did participate in
2,5 the transition, t h e i r bonding would lead to a d e c r e a s e in the
200 250 3 0 350 4 0 0 X, n-m
absorption at 315 nm. In fact, however, this is not o b s e r v e d
Fig. 1. UV s p e c t r a in ethanol: 1) 10- in the s p e c t r a of the methiodides and oxides of 1 0 - s u b s t i -
e t h y l - 5 , 1 0 - d i h y d r o p h e n a r s a z i n e ; 2) 10- tuted 5,10-DPHA, but, on the c o n t r a r y , one even notes a
ethyl- 5,10-dihydrophenarsazine 10- bathochromic shift of this band (Fig. 1). In view of the fact
methiodide; 3) 9 - c h l o r o - 9 - a r s a f l u o r e n e . that the a c c e p t o r p r o p e r t i e s of the a r s e n i c atom are in-
tensified when it p a s s e s to the t e t r a c o o r d i n a t e d state [6, 7],
it might have been a s s u m e d that the long-wave t r a n s i t i o n is a s s o c i a t e d with i n t r a m o l e c u l a r charge t r a n s -
fer to the a r s e n i c atom. There is no doubt that this sort of t r a n s i t i o n is facilitated to a considerable degree
by the p r e s e n c e in the molecule of a nitrogen atom that has e l e c t r o n - d o n o r p r o p e r t i e s . Replacement of the
nitrogen atom by oxygen, which is c h a r a c t e r i z e d by a higher ionization potential of the p e l e c t r o n s (I of
nitrogen is 9.47 eV, while I of oxygen is 12,81 eV [8]) leads to complete disappearance of the long-wave
bands in the s p e c t r a of the phenoxarsines (Table 1).
Three intense bands at 200, 240, and 290 nm are o b s e r v e d in addition to the region under c o n s i d e r a -
tion in the s p e c t r a of 5,10-DHPA derivatives. The p a r a m e t e r s of the last two bands are presented in Table
1 (the f i r s t band is situated on the boundary of the operating range of the s p e c t r o p h o t o m e t e r ) . The o b s e r v e d
t r a n s i t i o n s are probably t r a n s i t i o n s of the ~ * type, inasmuch as a bathochromic shift o c c u r s as the p o l a r -
ity of the solvent i n c r e a s e s . In addition, the unshared pair of e l e c t r o n of a r s e n i c apparently also participate
in the form ation of the bands, inasmuch as the indicated bands are shifted h y p s o c h r o m i c a l l y in the s p e c t r a
of the oxidized and methylated 5,10-DHPA derivatives.

EXPERIMENTAL
The UV s p e c t r a were r e c o r d e d with SF-8 and Specord UV-Vis s p e c t r o p h o t o m e t e r s . The solvents
were cyclohexane and ethanol. The investigated compounds were r e c r y s t a l l i z e d o r distilled directly p r i o r
to r e c o r d i n g of the s p e c t r a . The solution concentrations were 2 910-3-5 "10 -3 m o l e / l i t e r , and the l a y e r
t h i c k n e s s e s were 0.002-0.05 cm.

LITERATURE CITED
I. C.N. Rao, J. Ramachandran, and A. Balasubramanina, Can. J. Chem., 39, 171 (1961).
2o W . R . Cullen, B. R. Green, and R. M. H o c h s t r a s s e r , J. Inorg. Nucl. Chem., 2_!, 641 (1965).
3. C . S . Gibson, E. S. Hiseocks, J. O. A. Johnson, and J. L. Jones, J. Chem. Sot., 1622 (1930).
4. H. Moher and J. Sorge, Helv. Chim. Acta, 2_~2,235 (1939).
5. R . A . E a r l e y and M. J. Gallagher, J. Organomet. Chem., 2_~0,117 (1969).
6. E . N . Tsvetkov, A u t h o r ' s A b s t r a c t of Dissertation [in Russian], 18 (1970).
7. A . S . Gel'fond, V. I. Gavrilov, V. G. Mironova, and B. D. Chernokal'skii, Zh. Obshch. Khim., 4__22,
2462 (1972).
8. O . P . Charkin, G. V. Bobykina, and M. E. Dyatkina, Molecular Structure and Quantum C h e m i s t r y [in
Russian], Naukova Oumka, Kiev (1970), p. 155.

667
REACTIONS OF TRICHLOROMETHYLDIALKYLAMINFS
WITH 2-MFTHYLBENZOTHIAZOLE, 2-METHYLBENZOXAZOLE,
AND T H E I R SALTS*

L . A. L a z u k i n a a n d V. P . K u k h a r ' UDC 547 : 789.6

Trichloromethyldialkylamines react with nitrogen heterocyclie compounds containing an active

methyl group or with their salts to give 2-heteryl-l,l,3,3-tetrachloro-l,3-bis(dialkylamino)
propanes, which are hydrolyzed by water to heterylmalonamides. Cyanine dyes containing a
dimethylcarbamoyl group in the cv position relative to the polymethine chain were obtained.

Trichloromethyldialkylamines react relatively readily with various types of compounds containing

active methylene groups [2]. Ciernik [3] recently demonstrated that dichloromethyldimethylamine reacts
with nitrogen-containing heterocyclie bases with a methyl group in the 2 and 4 positions and that the final
products may be starting compounds for the synthesis of dyes.
We have found that trichloromethyldialkylamines also react with nitrogen heterocyclie bases contain-
ing active methyl groups - 2-methylbenzothiazole, 2-methylbenzoxazole, and t hei r h y d r o c h l o r i d e s - to give
I.
X ~ X , , /~CCINR2 f,/ c~-.r~.,\
" X /CONR2

I Ii

I, !1 X=S,O; R=CH3, C2H5

We were unable to isolate these compounds in the individual state, inasmuch as they hydrolyze in air,
and the reaction is accompanied by considerable resinification. Hydrolysis of I with aqueous potassium
carbonate solution gives N,N,N',N'-tetraalkylamides of heterylmalonic acids (II). (See scheme onthe following
page.)
2,3-Dimethylbenzothiazolium p-toluenesulfonate reacts with trichloromethyldimethylamine in a 1 : 2
ratio to give 2-(~-dimethylamino-~-chlorovinyl)-3-methylbenzcthiazolinm chloride (III). Treatment of III
with water and sodium perchlorate gives 2-(dimethylacetamido)-3-methyibenzcthiazolium perchlorate (IV).
Quaternary salt IV undergoes condensation with 1,3,3-trimethyl-2-formylmethyleneindoline to give
trimethylidynecyanine V (Xmax 537 nm), while styryl VI (Xmax 510 nm) is formed bythe actionofp-dimethyl-
aminobenzaldehyde.
As expected [4], the introduction of a dimethyloarbamoyl group into the ~ position of the polymethine
chain induces a small hypsochromic shift of the absorption maxima in the dyes (Xmax 842 and 530 nm [5, 6],
respectively, for dyes V and VI, which do not contain a dimethylcarbamoyl group).

EXPERIMENTAL
Benzothiazolylmalonic Acid N,N,N',N'-Tetramethyldiamideo A 0.05-mole sample of 2-methylbenzo-
thiazole was added to a solution of 0.1 mole of trichloromethyldimethylamine in 70 ml of dichloroethane,
* Communication VIII from the s er i e s N Polychloroalkylamines. See [1] for communication VII.

Institute of Organic Chemistry, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from
Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 771-773, June, 1974. Original article submitted May
29, 1973.

9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy of this article is availablefrom the publisher for $15.00.

668
 c"3 + 2cchN(c.92 ~ II .I +,F--cu=cct--"(CHgo "20
9 NaCIO4
I - I Cl
CH3 $Oa(;6H~.--CIt3-p CH 3
III

$\
~"d/(;-cu2-co-n(cM3)2
~ / ~ cLo;
(;fl a

~yCH3

N/ CH 3 CH~
CON(CH3) ~ ~
CH 3 S I 2 C

~ N ~ _ ~N ~ ~j'
"~/ ! CIO 4 i~
CH~ CH 3
V
lY

(;ON f(;H3)~
p -(CH3)2N=C6H4CHO s I "

i~Ha 4
V!

and the m i x t u r e was refluxed for 4 h (until hydrogen chloride evolution ceased). The dichloroethane was
r e m o v e d by v a c u u m distillation, and the residue (a v i s c o u s m a s s ) was added to 30 m l of a 3 0 % p o t a s s i u m
carbonate solution. The r e s u l t i n g oil was e x t r a c t e d with 30 m l of benzene, the benzene was r e m o v e d by
distillation, and the residue was vacuum distilled to give 2-me!:hylbenzothiazole (35%) with bp 90 ~ (10-12
m m ) . The r e s i d u e was a m i x t u r e of c r y s t a l s and oils. It was washed s u c c e s s i v e l y with acetone and w a t e r
and dried~ The yield of amide II, with mp 130-131 ~ (from ethanol), was 35%. Found: S 11.2%. C14H21N302S.
Calculated: S 11.0%.
Benzothtazolylmalonic Acid N,N,N ~ , N ' - T e t r a e t h y l d i a m i d e o This compound was s i m i l a r l y obtained
f r o m 0.05 mole of t r i c h l o r o m e t h y l d i e t h y l a m i n e and 0.02 mole of 2 - m e t h y l b e n z o t h i a z o l e h y d r o c h l o r i d e . The
yield of this amide, with m p 125-126 ~ (from ether), was 20%. Found: N 12.1%. C16H25N202S. Calculated:
12.1%.
2 - ( D i m e t h y l a c e t a m i d o ) - 3 - m e t h y l b e n z o t h i a z o l i u m P e r c h l o r a t e (IV). A 0.03-mole s a m p l e of 2 , 3 - d i -
methylbenzothiazolium p-toluenesulfonate was added with s t i r r i n g to a solution of 0.06 mole of t r i c h l o r o -
m e t h y l d i m e t h y l a m i n e in 50 m l of methylene chloride, a f t e r which the m i x t u r e was refluxed for 5 h. The
r e s u l t i n g p r e c i p i t a t e was s e p a r a t e d and m i x e d with 10 m l of a 3 0 % p o t a s s i u m c a r b o n a t e solution. The a q u e -
ous solution was e v a p o r a t e d on a w a t e r bath, and the p r e c i p i t a t e d c r y s t a l s w e r e r e m o v e d by f i l t r a t i o n and
dissolved in alcohol. A s a t u r a t e d aqueous solution of sodium p e r c h l o r a t e was added to the alcohol solution,
and the p r e c i p i t a t e d IV was s e p a r a t e d and dried to give 11%of a product with mp 190-191 ~ (from ethanol).
Found: S 9.5%. C12H14C1N205S. Calculated: S 9.3%. p - T o l u e n e s u l f o n y l chloride (25%) was obtained f r o m
the f i r s t filtrate a f t e r r e m o v a l of the methylene chloride by distillation.
B e n z o x a z o l y l m a l o n i c Acid N , N , N , , N , - T e t r a e t h y l d i a m i d e . A m i x t u r e of 0.03 mole of 2 - m e t h y l b e n z o x a -
zole h y d r o c h l o r i d e , 0.06 mole of t r i c h l o r o m e t h y l d i e t h y l a m i n e , and 50 m l of dichloroethane was refluxed
and s t i r r e d for 5 h. The dichloroethane was then r e m o v e d by v a c u u m distillation, and the residue was
m i x e d with 20 m l of a 3 0 % p o t a s s i u m carbonate solution. The organic l a y e r was s e p a r a t e d and mixed with
20 m l of e t h e r , and the e t h e r m i x t u r e was refiuxed for 30 min. The solution was cooled, and the p r e c i p i -
tated c r y s t a l s w e r e r e m o v e d by filtration to give 18%of the amide with mp 126 ~ (from e t h e r ) . Found: N
12.9%. CIsH25N30 3. Calculated: N 12.7%.
2- [ 1 - O i m e t h y l c a r b a m o y l - 3 - ( 1 , 3 , 3 - t r i m e t h y l - 2 - i n d o l i n y l i d e n e ) p r o p e n y l ] - 3 - m e t h y l b e n z o t h i a z o l i u m
P e r e h l o r a t e (V). A m i x t u r e of 0.2 m m o l e of p e r c h l o r a t e IV and 0.2 m m o l e of 1 , 3 , 3 - t r i m e t h y l - 2 - f o r m y l -
methyleneindoline was refluxed in 5 m l of acetic anhydride. The solution was cooled, and e t h e r was added
to p r e c i p i t a t e the dimethylidynecyanine (V). A product with mp 234 ~ (from ethanol) and k m a x 537 rim, was
obtained in 77%yield. Found: S 5.9%. C25H28C1N3OsS. Calculated: S 6.2%.
2- (1- D i m e t h y l c a r b a m o y l - 2- ( p - d i m e t h y l a m i n o p h e n y l ) - 2 - e t h e n y l ] - 3 - m e t h y l b e n z ~ 1 7 6 Perchlor~
ate (VI). A m i x t u r e of 0.3 m m o l e of IV and 0.3 m m o l e of p - d i m e t h y l - a m i n o b e n z a l d e h y d e was refluxed in

669
a solution of 5 ml of acetic anhydride for 1 h. The c r y s t a l s were r e m o v e d by filtration to give a product
with mp 189 ~ (from ethanol) and ~max 510 nm in 90%yield. Found: S 7.2%. C25H24C1N2OsS. Calculated:
s 7.1%.

LITERATURE CITED
1. V. P. Kukhar', V. I. Pasternak, M. I. Povolotskii, and N. G. Pavlenko, Zh. Organ. Khim., (1974, in
press).
V. P. Kukhar', V. I. Pasternak, and G. V. Pesotskaya, Zh. Organ. Khim., 9, 39 (1973).
3. J. Ciernik, Coll. Czech. Chem. Commun., 37, 2273 (1972).
4. A. I. Kiprianov and M. G. Suleimanova, Ukr. Khim. Zh., 33, 589 (1967).
5. L. W. B r o o k e r , R. H. Sprague, and H. W. C r e s s m a n , J. A m e r . Chem. S.c., 6~7, 1889 (1945).
6. A. I. Kiprianov, Introduction to the Electronic T h e o r y of Organic Compounds [in Russian], Kiev (1965),
p. 160.

670
 RESEARCH IN THE BENZAZOLE AND NAPHTHAZOLE SERIES
XXXVIII.* EFFECT OF AN o-NITRO GROUP ON THE STRUCTURE AND
PROPERTIES OF BENZOTHIAZOLYLFORMAZANS

N. N. Gulemina, L. F. Lipatova, UDC 547.556.9'789.6 : 5"43.422.4

G. N. Lipunova, and N. P. Bednyagina

The ortho effect of a nitro group in newly s y n t h e s i z e d 1 - b e n z o t h i a z o l y l - 5 - ( o - n i t r o p h e n y l )

f o r m a z a n s was investigated. It is shown that t h e s e compounds exist in solution as chelates
with the p a r t i c i p a t i o n of the nitro group. The a c i d - b a s e and t h e r m o c h r o m i e p r o p e r t i e s of
the f o r m a z a n s w e r e studied.

The effect of ortho substituents (CH3, OH, C O , H ) in the 5 position of the phenyl ring on the s t r u c t u r e
and p r o p e r t i e s of b e n z o t h i a z o l y l f o r m a z a n s was examined in [2, 3]. It was noted that in all c a s e s one ob-
s e r v e s a s t e r i c effect of the substituent that also affects the s t r u c t u r e of the f o r m a z a n s and t h e i r c o m p l e x -
ing p r o p e r t i e s . Our investigations have shown that the introduction of a nitro group into the ortho position
has a substantial effect on the state of the t a u t o m e r i c equilibria of the f o r m a z a n s .
The ortho effect of the nitro group was studied for a s e r i e s of benzothiazolyl f o r m a z a n s (Table 1) as
c o m p a r e d with the analogous p r e v i o u s l y d e s c r i b e d [1] compounds containing a nitro group in the p a r a p o s i -
tion r e l a t i v e to N(5)o A distinct band of VNH v i b r a t i o n s is o b s e r v e d in the IR s p e c t r a of I - V in CC14 at 3200-
3500 cm -1 (Table 1). The d e c r e a s e in the frequency of the s t r e t c h i n g v i b r a t i o n s by 40-60 cm -I as c o m p a r e d
with the VNH bands of f o r m a z a n s containing a p - n i t r o group [1] m a k e s it oossible to a s s u m e the p r e s e n c e
of an i n t r a m o l e c u l a r hydrogen bond of the type:
o
.O'-'N -

~%. J-~---s z H
N N
\El/ A
i
it

i.e~ the o - n i t r o group is included in the f o r m a t i o n of a chelate ring ( s t r u c t u r e A). This s o r t of i n t r a -

m o l e c u l a r hydrogen bond in m o l e c u l e s with rr conjugation should c a u s e a b a t h o c h r o m i c shift of the ab-
sorption band in the e l e c t r o n i c s p e c t r a s i m i l a r to that which was established in [4, 5] in a study of the
s t r u c t u r e and e I e c t r o n i c s p e c t r a of o - n i t r o a n i l i n e . In fact, the long-wave absorption band f o r I - V in n e u -
t r a l solvents (CC14 and benzene) is shifted b a t h o e h r o m i c a l l y by 20-30 n m as c o m p a r e d with the p a r a
analogs,
The ionization constants of I-VI w e r e m e a s u r e d (see Table 1 for the pK a values). The acid p r o p e r -
ties of f o r m a z a n s containing an o - n i t r o group a r e r e d u c e d as c o m p a r e d with p - n i t r o p h e n y l f o r m a z a n s . The
l i n e a r r e l a t i o n s h i p between AVNH and ApK a of the f o r m a z a n s (Fig. 1) is a c o n f i r m a t i o n that the d i f f e r e n c e s
between the compounds a r e due to i n t r a m o l e c u l a r hydrogen bonding. The deviation of point 4 f r o m this
line is a s s o c i a t e d with the fact that it is difficult to evaluate the AVNH and ApK a v a l u e s for IV, i n a s m u c h as
the p r e s e n c e of i n t e r m o l e c u l a r hydrogen bonds [1] that affect the magnitude of the pK a value of the f o r m a -
zan and the position of the VNH frequency is c h a r a c t e r i s t i c for 1 - b e n z o t h i a z o l y l - 3 - H - 5 - { p - n i t r o p h e n y l ) f o r m a -
zano

* See [1] for c o m m u n i c a t i o n XXXVII.

S. M. Kirov U r a l Polytechnic Institute, Sverdlovsk. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h
Soedinenii, No. 6, pp. 774-777, June, 1974. Original a r t i c l e submitted July 10, 1973.

9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy of this article is availablefrom the publisher for $15.00.

671
 AVNH J
C ~90"
100- o ~
25000

90- ~ 0~
20000
80,
15000
20~
70

sot
50 ~
2o
o
5
/ ,Y
10000

5000

t,O f j i 0
0,8 0,9 1,0 t,1 1,2 AOK"a 400 500 600 700 A,nm
Fig. 1 Fig. 2
Fig. 1. Dependence of ApK a on AVNH [ApKa = p K a of 1 - b e n z o t h i a z o l y l - 5 - ( o - n i t r o p h e n y l )
f o r m a z a n ( o ) - p K a of 1 - b e n z o t h i a z o l y l - 5 - ( p - n i t r o p h e n y l ) f o r m a z a n (p), A V N H = V N H ( p ) -
VNH(o)]: I) I; 2) II; 3) III; 4) IV; 5) V.
Fig. 2. Light-absorption curves of formazan I in a propanol-buffer solution (pH 8.6) at var-
ious temperatures.

The p r e s e n c e of a phenyl group attached to the m e s o c a r b o n atom in II and of an e l e c t r o n - a c c e p t o r

nitro group in benzothiazole V p r o m o t e s p a r t i a l opening of the chelate ring of s t r u c t u r e A and the a p p e a r -
ance of a t a u t o m e r i c f o r m with a free amino group [the IR s p e c t r a contain a second ~ H band at 3340 (V)
and 3335 (II) cm -1, Table 1].
The b e h a v i o r of 1 - b e n z o t h i a z o l y l - 3 - m e t h y l - 5 - ( 2 , 4 - d i n i t r o p h e n y l ) f o r m a z a n (VI), f o r which the o- o r
p - n i t r o group has the dominant effect on the s t r u c t u r e and p r o p e r t i e s , depending on the c h a r a c t e r of the
solvent, is p e c u l i a r . Only the PNH a b s o r p t i o n band at 3290 cm -1 c h a r a c t e r i s t i c for o - n i t r o p h e n y l f o r m a z a n s
I - V is o b s e r v e d in the IR s p e c t r u m of f o r m a z a n VI. The e l e c t r o n i c s p e c t r a of VI in nonpolar solvents a r e
also s i m i l a r to the s p e c t r a of f o r m a z a n I, while the nitro group in the p a r a position has the m a x i m u m e f -
fect on the acid p r o p e r t i e s and the c o l o r of the compounds in p o l a r solvents. The pK a values of VI and
1 - b e n z o t h i a z o l y l - 3 - m e t h y l - 5 - ( p - n i t r o p h e n y l ) f o r m a z a n (VII) a r e close (Table 1), and the e l e c t r o n i c s p e c t r a
of f o r m a z a n VI in alcohol and acetone contain the a b s o r p t i o n band of the anionic f o r m (kma x 644 nm).
All of the information stated above p r o v i d e s a b a s i s f o r a s s u m i n g that the p r e s e n c e of an i n t r a m o l e -
c u l a r hydrogen bond, the p o s s i b i l i t y of the f o r m a t i o n of which was p r e v i o u s l y a s s u m e d [6] f o r a r y l f o r m a z a n s
with an o - n i t r o group, is c h a r a c t e r i s t i c for f o r m a z a n s containing an o - n i t r o group.
It was of i n t e r e s t to investigate the t h e r m o c h r o m i e p r o p e r t i e s of I - V I in o r d e r to c o m p a r e t h e m with
the p r e v i o u s l y studied t h e r m o c h r o m i s m of 1 - b e n z o t h i a z o l y l - 5 - ( p - n i t r o p h e n y l ) f o r m a z a n s [1] in aqueous
alcohol solution. It was found that f o r m a z a n s I - V I do not undergo a change in c o l o r on heating in aqueous
alcohol solutions. T h e r m o c h r o m i c t r a n s i t i o n s ( r e d - v i o l e t ) w e r e o b s e r v e d when alcohol buffer solutions
with pH values close to the pK a values of the compounds were used, but the t r a n s i t i o n s w e r e l e s s distinct
than in the case of p - n i t r o p h e n y l f o r m a z a n s . Thus an i s o p i e s t i c point is absent in the s p e c t r u m of I, and
the b a t h o c h r o m i c shift between the t h e r m a l l y induced and s t a r t i n g f o r m s is 60 nm (Fig. 2), while it r e a c h e s
120 nm for 1 - b e n z o t h i a z o l y l - 3 - m e t h y l - 5 - ( p - n i t r o p h e n y l ) f o r m a z a n . The r e a s o n f o r the s m a l l e r t h e r m a l
induction effect of I - V is, on the one hand, the b l u e r c o l o r of the s t a r t i n g f o r m , which has a chelate s t r u c -
t u r e (kmaxVII 475, k m a x I 510 rim), and, on the o t h e r hand, the d e e p e r c o l o r of the t h e r m a l l y induced f o r m ,
which is an anion (XmaxVii 606 nm, )~maxI 568 a m ) . In c o n t r a s t to I-V, an isopiestic point is o b s e r v e d in
the s p e c t r u m when an alcohol buffer solution of f o r m a z a n VI (pit=8.2) is heated, and the b a t h o c h r o m i c shift
is 180 nm, i.e., it is close to VII with r e s p e c t to its t h e r m o c h r o m i c p r o p e r t i e s .
Thus the unique c h a r a c t e r of the o - n i t r o group is m a n i f e s t e d both in the s t r u c t u r e of the f o r m a z a n s
and in t h e i r p r o p e r t i e s .

EXPERIMENTAL
The IR s p e c t r a of s a t u r a t e d CC14 solutions w e r e r e c o r d e d with a UR-20 s p e c t r o m e t e r at 3200-3500
cm -I (LiF p r i s m ) . The e l e c t r o n i c s p e c t r a w e r e r e c o r d e d with an SF-4 s p e c t r o p h o t o m e t e r . The pK a values
of the compounds w e r e d e t e r m i n e d as in [1].

672
 TABLE 1

I )~max, nm I
i
R' R" benzene lac~. lal[ alcoa!
,
- - !c- ihol
pK~
Z~9 CC14
u I it. e lb. 1 !NaO_H,_
l I
I CH3 H ,o-NO~ .3o5 G
480 i470 1510, 565 ! 9,03-+0,05
560* 560*i !
I t i !
II C6H5 H !o-NO~ 3335 550 520--580 508 508 1580 , 993
3280 I, ',57o I58o] I
lII CH(CH3)2 H Io-NOo 3295 i546 548 154o 5601 558 10,69 I ' I

1V H H io-NO~ 3285 504 488 476 506 560 I ~,19

550" I ]
V Ct% XO..[o-NO[ 3340 5 0 486--510 '182 5641 564 7.75-0,05
3290 1564 1606 ]
V! CH~ IH o,p-Di-NO2 3290 480 480 1464 466! 644 8.35
562* 540~:: !640 644
VIP CH3 iH Ip'N02 3435 1458 480 i468 475i, 606 8,20
,3354 I
i
* Shoulder

T A B L E 2. C h a r a c t e r i s t i c s of the C o m p o u n d s O b t a i n e d
Com- Empirical Found.% ' Calc., %
pound mp, "C formula
H J N C I H
I 220a C.~}L2NGO~S 53,5 3,6 52,9 3,5
II 205 a I C20H,4N60~Sd 59,9 3.7 59,7 ' 3,5 m

111 198a ] C~7HITN60~S 55,7 4,4 2~,9 55,6 4,6 22,7

IV 235b C14HIoN602S 51,1 3,1 25.8 51,5 3,1 25,8
V 250c ! C,6H~2NvO4S 46,3 3,0 24,8 46,7 2,9 25,4
Vl 255C I CI6HI~N70~S 46,9 3,O 25,1 4,6,71 2,9 25,4

a From alcohol, b From nitromethane-alcohol (1:1). c From

n i t r o m e t h a n e , d Found: S 7~ C a l c u l a t e d : S 7.9%.

1 - B e n z o t h i a z o l y l - 3 - H - 5 - ( o - n i t r o p h e n y l ) f o r m a z a n (IV). This c o m p o u n d was o b t a i n e d by the m e t h o d

u s e d to p r e p a r e 1 - b e n z o t h i a z o l y l - 3 - H - 5 - ( p - n i t r o p h e n y l ) f o r m a z a n [1]. F o r m a z a n s I - H I , V, and VI weze
obtained by coupling of the a p p r o p r i a t e h y d r a z o n e s with a solution of the o - n i t r o b e n z e n e d i a z o n i u m salt.
The r e s u l t s of e l e m e n t a r y a n a l y s i s and the m e l t i n g points o f the c o m p o u n d s a r e p r e s e n t e d in T a b l e 2.

LITERATURE CITED
1. G. N. Lipunova, N. N. G u l e m i n a , A. P. Zeif, and N. P. B e d n y a g i n a , Khim. G e t e r o t s i l d . Soedin., 493
(1974).
N. P. Bednyagina, N. V. Serebryakova, R. I. Ogloblina, and I. I. Mudretsova, Khim.Geterotsikl.Soedin.t
541 (1968).
3~ G. M. P e t r o v a and N. P. B e d n y a g i n a , Zh. O b s h c h . K h i m . , 3_.99, 887 (1969).
4. A. M o r i t z , S p e c t r o c h l m . Acta, 18, 671 (1962).
5. W. Fo T o r b e s , Can. J . C h e m . , 3__6.,6 1350 (1958).
6. U. S~ Z e m p l e n , Z. M e s t a r , A. M i s s n u r , and A. M a j o r , A c t a C h e m . A c a d . Sci. Hung., 7_00,N o s . 3 - 4
(1955).

673
MASS SPECTRA OF DERIVATIVES OF IMIDAZO[2,1-b]
THIAZOLE AND THIAZOLO[3,2-a]BENZIMIDAZOLE

O. S. A n i s i m o v a , Yu. N. Sheinker, UDC 543.51 : 547.785.5'789.6

P. M. Kochergin, and A. N. Krasovskii

The m a s s s p e c t r a of 6-phenylimidazo[2,1-b]thiazole, thiazolo[3,2-a]benzimidazole, and a n u m -

b e r of t h i a z o l e - r i n g - s u b s t i t u t e d d e r i v a t i v e s w e r e investigated. The f r a g m e n t a t i o n of both groups
of compounds c o m m e n c e s with cleavage of the bonds in the thiazole ring and leads to the a p p e a r -
ance of n i t r o g e n - and s u l f u r - c o n t a i n i n g f r a g m e n t s in the s p e c t r a . The c o m m o n c h a r a c t e r of the
m a s s s p e c t r o m e t r i c disintegration of the investigated compounds indicates that they have s i m -
i l a r e l e c t r o n i c s t r u c t u r e s . The m a s s n u m b e r and position of a substituent in the thiazole ring
can be d e t e r m i n e d on the b a s i s of the m a s s n u m b e r s of a s e r i e s of f r a g m e n t s .

The m a s s s p e c t r a of the s i m p l e s t h e t e r o a r o m a t i c compounds have been studied quite adequately [1],

but the fragmentation of complex polyeyclic s t r u c t u r e s , p a r t i c u l a r l y condensed s y s t e m s with a c o m m o n
nitrogen atom containing different h e t e r o a t o m s , has been studied to a c o n s i d e r a b l y l e s s e r extent. T h e s e
groups of s u b s t a n c e s include d e r i v a t i v e s of imidazo[2,1-b]thiazole and t h i a z o l o ] 3 , 2 - a ] b e n z i m i d a z o l e . The
m a s s s p e c t r a of only a few thiazolobenzimidazole d e r i v a t i v e s have been d e s c r i b e d in the l i t e r a t u r e [2].
We have investigated the m a s s s p e c t r a of v a r i o u s t h i a z o l e - r i n g - s u b s t i t u t e d t h i a z o l o b e n z i m i d a z o l e s
(I-XIV) and 6 - p h e n y l i m i d a z o t h i a z o l e s (XV-XVIII), the s y n t h e s i s of which was d e s c r i b e d in [3, 4]. In o r d e r

I-XIV XV-XVIII
I R = R ' = R " = H ; II R=CH3, R'=R"=H; III R=R"=H, R'=CH3; IV R=R'=CH~, R"=tt;
V R=CH3, R'=C2Hs, R"=H; VI R=C2Hs, R'=CHz, R"=H; VII R=C6Hs, R'=R"=I-h
\'Ill R=R"=H, R'=C6Hs: IX R=R'=C~H~, R"=H; X R=CHs, R'=C_~Hs, R"=H; XI
I~=COCH3. R'=CH3, R"=H; XII R=H, R'=C6Hs, R"=CHz; XIII R=R'=C6H~, R"=CHs;
XIV R=COC6H~, R'=H, R"=CHs; XV R = R ' = H ; XVI R=H. R'=CH~; XVII R=R'=CH3;
XVIII R=COCH3, R ' = t t
to m o r e a c c u r a t e l y d e t e r m i n e the f r a g m e n t a t i o n of the investigated compounds, we also r e c o r d e d the s p e c -
t r a of a n u m b e r of s i m i l a r substituted 6 , 7 - d i m e t h y l t h i a z o l o b e n z i m i d a z o l e s (XII-XIV).
The c o r r e s p o n d i n g t h i a z o l e - r i n g - s u b s t i t u t e d t h i a z o l o b e n z i m i d a z o l e s and 6-phenylimidazothiazoles
have a p p r o x i m a t e l y identical stabilities with r e s p e c t to e l e c t r o n i m p a c t (Wm v a r i e s f r o m 20 to 30%as a
function of the substituent). In addition, it is c h a r a c t e r i s t i c that both c l a s s e s of compounds w e r e found to
have common paths of m a s s - s p e c t r o m e t r i c disintegration. T h e s e facts can be c o n s i d e r e d as an indication
of the c l o s e n e s s of the e l e c t r o n i c s t r u c t u r e s of the condensed thiazolobenzimidazole s y s t e m and the 6 - p h e n y l -
imidazothiazole s y s t e m , in which the phenyl ring is in conjugation with the imidazothiazole ring.
Ions due to cleavage of the thiazole ring bonds a r e c h a r a c t e r i s t i c for both the t h i a z o l o b e n z i m i d a z o l e s
+
and the 6 - p h e n y l i m i d a z o t h i a z o l e s , Peaks of S~_CI~, the r e l a t i v e intensity of which r e a c h e s ~10%, and low-
intensity peaks of the ions depicted below a r e o b s e r v e d in the s p e c t r a of unsubstituted I and XV and t h e i r
d e r i v a t i v e s (H-VII, XVI-XVHI):
S. Ordzhonikidze All-Union S c i e n t i f i c - R e s e a r c h P h a r m a c e u t i c a l C h e m i s t r y Institute, Moscow. T r a n s -
lated f r o m Khimiya G e t e r o t s i k U c h e s k i k h Soedinenii, No. 6, pp. 778-783, 3une, 1974. Original a r t i c l e s u b -
mitted D e c e m b e r 14, 1972; r e v i s i o n submitted O c t o b e r 31, 1973.

9 1975Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy of this article is availablefrom the publisher for $15.00.

674
 C--~ r

C--R

A c o m p a r i s o n of the m a s s n u m b e r s of t h e s e ions m a k e s it possible to d e t e r m i n e a substituent and its

+
position in the thiazole ring. Thus S~C--CH3 ions with m / e 59 a r e o b s e r v e d in the s p e c t r a of 2 - m e t h y l

d e r i v a t i v e s (II, IV, V, X, and XVII), while S~-~CH ions with m / e 45 o b s e r v e d in the s p e c t r a of the 2 - u n -
substituted compounds (see Table 1).
+
The S~C--C6H~ ion p e a k in the s p e c t r u m of 2-phenylthiazolobenzimidazole is the m o s t intense of
A-
all the f r a g m e n t a r y ions, while the intensity of the analogous S ~ C H ( m / e 45) in the s p e c t r u m of the 3-
phenyl i s o m e r (VIII) is v e r y low, and the m o s t intense p e a k is that f r o m the [ M - S C H . ] + ion. This is e v i -
dence that the position of the phenyl group in the thiazole ring e s s e n t i a l l y d e t e r m i n e s the site of c h a r g e
localization, and, in the case of VII, the charge is a p p a r e n t l y localized on the sulfur a t o m .
4-
The p r e s e n c e of CH~--C-~CR f r a g m e n t s (R =H, CH3) , which a r e produced by disintegration of the
thiazole ring at the 1-2 and 3-4 bonds with m i g r a t i o n of a hydrogen atom, p r o v e d to be typical for the s p e c t r a
of H-IV, XVI, and ~ which have m e t h y l substituents in the thiazole ring. Hydrogen m i g r a t i o n o c c u r s in
this c a s e a p p a r e n t l y f r o m the CH 3 group, inasmuch as this ion is absent in the s p e c t r a of I and XV, which
do not have CH 3 groups, and in the s p e c t r a of the diphenyl and monophenyl d e r i v a t i v e s (VII-X, XII-XIII).
Cleavage of the C - N and C - S bonds without m i g r a t i o n of a hydrogen a t o m t o give C s H s - C - CR+ions (R =H,
C6H 5) is c h a r a c t e r i s t i e for V I I - X and XII-XIII.
A distinctive feature of the disintegration of diphenyl d e r i v a t i v e s IX and XIII is also the p r e s e n c e in
the s p e c t r u m of an ion p e a k with m a s s n u m b e r m / e 165, the intensity of which is second only to that of the
m o l e c u l a r ion. In analogy with the disintegration of the diphenyl d e r i v a t i v e s of imidzole, thiazole, and o x a -
zole [5], s t r u c t u r e A can be a s s i g n e d to this ion.

I
H
A

The [M-SI-I.] + ion is o b s e r v e d in the s p e c t r a of II-VI, X, XVI, and XVIII. The e o m p o s i t i o n of this ion
was e s t a b l i s h e d by an analysis of the h i g h - r e s o l u t i o n s p e c t r u m of XVI and on the b a s i s of l i t e r a t u r e data
[2]. A hydrogen a t o m is a p p a r e n t l y s t r i p p e d f r o m the CH 3 group during this disintegration. This i s a t t e s t e d
to be the absence of the [ M - S H . ] + ion in the s p e c t r a of diphenyl-substituted compounds (IX and XIII). E l i m -
ination of S r a t h e r than SH. f r o m the m o l e c u l a r ion b e c o m e s m o r e advantageous in the ease of m e n o p h e n y l -
substituted VII, VIII, and XII, i n a s m u o h as m i g r a t i o n of a hydrogen atom to the sulfur atom is unlikely d u r -
ing the disintegration of t h e s e compounds.
P e a k s of [ M - I I ' ] + ions a r e c h a r a c t e r i s t i c for the s p e c t r a of II-IV and XVI. This ion p e a k is m o s t
intense (36%) f o r II; this is explained by the f o r m a t i o n of stable f r a g m e n t Bo Stripping of a hydrogen atom
in 3 - m e t h y l d e r i v a t i v e s III and XVI gives stable s t r u c t u r e C with charge localization on the sulfur a t o m , as
in alkyl d e r i v a t i v e s of thiophene [1].

B C

The low intensity of the [ M - H . ] + ion in the s p e c t r a of III (13.8%) and XVI (9.1%) as. c o m p a r e d with the
intensity of [ M - H ' ] + in H (36%) is a p p a r e n t l y evidence that stabilization of the C type is l e s s advantageous
for imidazothiazole d e r i v a t i v e s .
The e a s e of f o r m a t i o n of ions B and C leads to the a p p e a r a n c e of v e r y intense [M-CH3"] + p e a k s in
the s p e c t r a of ethyl d e r i v a t i v e s V and VI. As a consequence of the high a d v a n t a g e o u s n e s s of stabilization
with c h a r g e localization on the nitrogen a t o m (structure B), the intensity of the [M-CH3"] + p e a k in VI is
2.5 t i m e s that of V.

675
 TABLE 1. M a s s Spectra of Derivatives of 6 - P h e n y l i m i d a z o [ 2 , 1 - b ] -
t h i a z o l e and T h i a z o l o [ 3 , 2 - a ] b e n z i m i d a z o l e
I 39 (6,5), 45 (6,8), 46 (2,6), 50 (6,7), 51 (7,1), 52 (2,3), 57 (3,3), 58 (7,3), 62 (2,7),
63 (7,6), 64 (5,6). 69 (2.3). 70 (3,8), 74 (2,7), 75 (9), 76 (8), 77 (2,3). 90 (6,81,
102 (21,2), 103 (6,1). 129 (24,2), 130 (2,4), 134 (3), 173 (2), 174 (100), 175 (13.7),
176 (5,6). W.~.r~34,7~
11 39 (9,4), 45 (4), 50 (5,7),.51 (6), 52 (2,3). 58 (2,1), 59 (9,1), 60 (2,8), 63 (6). 64
(4,5), 69 (2,1), 70 (2,1), 71 .(3,6), 72 (2,8), 74 (2,3), 75 (7,2), 76 (7,6), 77 (3,8L
90 (8,1), 102 (15,3), 103 (3,8), 108 (2,3), 129 (14,5), 130 (4,7), 134 (6), 144 (2.t).
155(5), 160:(3), 161 (3,8). 187 (36,2), 1,88 (lO0), 189 (14,2), 190 (5,7). WM=26,5%
I11 39 (10,5), 40 (5,7), 44 (3),'45 (9), 50 (5,4), 51 (7), 52 (2,7), 63 (6), 64 (4,5), 69
(2,8), 70 (2,8), 71 (4,7). 73 (6,8), 74 (2), 75 (8,5), 76 (7,6), 77 (4,2), 90 (7), 102
(19), 103 (4,6), 116 (2,6), 117 (3), 118 (2,7), 134 (2,7), 143 (21,6), 155 (4,2). 160
(2), 187 (13,8), 188 (100), 189 (14). 190 (5,9). W:~=30,4%
IV 38 (7,4), 40 (7,7). 41 (4). 42 (3,1)., 44 (3,4), 45 (3,4), 50 (4,3), 51 (6,8). 52 (2,5).
53 (6,3), 58 (2), 59 (6,3), 63 (4,9). 64 (3,4), 69 (2), 71 (2), 75 (6,3), 76 (4,9), 77
(3,1), 90 (7,7), 102 (13,5), 103 (2,3), 116 (2,3), 129 (2), 134 (7,4), 143 (13,7), 144
(3,4), 161 (2), 168 (3,7), 169 (5,7), 175 (4,9), 167 (19,7), 188 (2,8), 200 (2,5), 201
(27), 202 (lO0), 203 (9,7). W~[=27,5%
V 41 (2,5), 59 (2,8), 90 (3,8), 102 (4,3), 122 (2), 129 (3,3), 134 (4,1), 142 (2,1), 143
(13,2), 156 (2,1), 161 (2,1), 168 (2,3), 187 (6,1), 188 (2), 200 (4,5), 201 (54,5), 202
(9,9), 215 (5,6), 2]6 (lO0), 217 (13.9), 218 (5,1). W.,~ =34,5%
VI 39 (3,7), 41 (3,6), 45 (2,1), 51 (2,3), 53 (2), 63 (2,1), 69 (2), 75 (3), 76 (2,6), 77
(2), 90 (7,4), 101 (2), 102 (13,1), 103 (2,3), 107 (2,1), 108 (3,8), 115 (3,1), 116
(3,1), 129 (3), 131 (3), 134 (ll,5), 142 (3,2), 143 (21,3), 144 (2,6), 156 (2), 161 (2).
168 (3), 175 (2,5). 187 (3,1), 199 (2,5), 200 (5,7), 201 (10O), 202 (16,4), 203 (5.7),
215 (4,9), 216 (80,3), 217 (13,9), 218 (5,1). W.~=21%
VII 41 (2), 58 (2,1), 86 (10), 89 (2,9), 90 (3,6), 101 (2), 102 (4,4), 116 (3,6), 121 (14,4).
122 (3,2), 129 (4,1). 134 (1), 190 (2), 217 (2), 218 (4), 248 (3,2), 249 (5,1). 250
(100), 251 (20,5), 252 (6,5).
VIII 45 (1,5), 77 (3,6). 90 (2,1), 102 (3,9), 116 (1,3), 121 (1,7), 190 (1), 205 (5,8), 212
(2), 217 (1), 218 (2). 248 (7,3), 249 (5,5), 250 (lO0), 251 (22,3), 252 (7,4),
IX 42 (2), 43 (2,2). 44 (2,2), 53 (2), 58 (3), 77 (5,5), 86 (12,2), 91 (2,9), 101 (2.8),
102 (4,4), 103 (2,5), 121 (2,7). 149 (2,7), 163 (4,2), 165 (15,3), 166 (2,8), 177 (2).
178 (8,9), 179 (2), 190 (2), 205 (6,3), 250 (2,7), 266 (2), 325 (2,7), 326 (100), 327
(27,1), 328 (8,1).
X 45 (2,1), 77 (2,6), 90 (1), 102 (2), I03 (3), I04 (2), 116 (2), 115 (5,4), 134 (2},
187 (2,6), 204 (3,4), 205 (3,5), 212 (2), 231 (2,7), 237 (5,2), 261 (2), 262 (4,8), 263
(16,1), 264 (100), 265 (21,4), 266 (6,3).
XI 39 ( l l ) , 42 (2,2), 43 (2,8), 45 (7), 50 (5,1), 51 (8), 52 (2,9), 58 (3,7), 63 (6,6), 61
(4,9), 69 (4,8), 70 (5,1), 71 (3,6), 75 (9,5), 76 (8,6), 77 (3,6), 89 (2,7), 90 (IOA).
(2).1
(5).9-1,8(2'2)3410-],2(2'2)' 102 (31,3), 103 (4,8), 107 (2), 116 (3,5), 118 (2,2), 128 (2,, 129
142 (2,4), 143 (65,1), 144 (9,4), 155 (2,4), 188 (14,6), 189 (13), 190
(2,7), 201 (3,6), 202 (1,4), 215 (67,5), 216 (10), 230 (100), 236 (19). W..,~=17,8
Xll 45 (2), 77 (2,8), 91 (2,4), 102 (2), 103 (2,2), 116 (2), 117 (2), 134 (2,2), 139 (3,7),
176 (2), 261 (2,2), 262 (2,1), 263 (14,9), 264 (3), 277 (27,9), 278 (I00}, 279 (3,1),
280 (6,9).
XIII 77 (1,5), 165 (3,8), 177 (3,4), 178 (4,4), 340 (7,2), 341 (2,1), 352 (4,41, 353 (21,2),
354 (100), 355 (29), 356 (6,1).
XIV 44 (2,4), 77 (18), 78 (2), 105 (27), I06 (2,5), 157 (4), 201 (3,9), 229 (2.2), 277 (2).
291 (8,8), 292 (2,1), 304 (3,6), 305 (20), 306 (100), 307 (20), 308 (7,3),
XV 39 (4), 40 (2,8), 44 (5,1), 45 (3,8), 50 (3), 51 (5,5), 52 (2,8), 57 (1,9), 58 (4,2), 59
(2,1), 63 (4,4), 64 (2,5), 70 (3,2), 75 (2,8), 76 (4,9), 77 f5,1), 87 (2,5), 88 (2,1), 89
(5,8), 90 (3,6), 1OI (2,6), 102 (6,2), 103 (8,1), I15 (4.4). ll6 (9,5), 128 (4,7), 129
(2,3), 142 (2,6), 147 (2,8), 155 (2), 173 (2), 174 (3), 175 (3), 198 (3), 199 (10,), 200
(100), 201 (14,5), 202 (5,8). W~I =30,3%
XVI 39 (9,3), 45 (5,7), 50 (2,6),,51 (6), 52 (2,4), 63 (4,3), 71 (5,4), 72 (2), 75 (2,3), 75
{5,4), 77 (7,7), 89 (5,9), 90 (3,1), 101 (2,6), 102 (7,7), 103 (12,6}, 104 (2,6), 115
(2,7), I16 (8,1), ll7 (5,7), 128 (6), 142 (3.4), 146 (2), 147 (5,4), 148 (2), 159 (3,2),
i
174 (2), 175 (2), 212 (2,3), 213 (9,1), 214 (100), 215 (14,3). W.~ =31,7%
XVII 39 (7,1), 40 (2,1), 41 (2,1), 45 (3), 51 (5,1), 52 (2), 53 (6,9), 59 (4,6), 63 (3), 71
(3,4), 76 (4,2), 77 (6,3), 89 (4,6), 90 (2), 101 (2,2), 102 (6,7), 103 (10), 104 (3,1),
ll5 (2,6), 116 (6,4), 117 (5), 127 (2), 128 (6,8), 129 (2). 147 (2,9), 148 (2), 154
(2,6), 166 (2), 169 (3), 170 (2), 175 (2), 195 (2), 213 (2,5), 226 (3,7), 227 (17,6),
228 (150), 229 (19,2), 230 (6,6). W.~z=30,4%
XVII1 39 (12,4), 40 (7,1), 41 (2,6), 42 (3,5), 43 (23,2), 44 (8,4), 51 (5,8), 52 (3,5). 59
(8,9), 63 (3,5), 71 (2,6), 76 (4,9), 77 (8,4), 89 (7,6), 90 (2,6), 91 (2,6), 10l (3,1),
102 (6,9), 103 (9,8), 104 (4), 114 (2,6), 115 (3,5), 116 (8,4), ll7 (7.1), 119 (2.2),
130 (7), 132 (4), 134 (4), 147 (2,6), 154 (2,6), 155 (2,5), 169 (9,8), 170 (2,5), 183
(5), 213 (12,9), 214 (6,2), 241 (3,2), 242 (5,5), 243 (2,7), 255 (8,9), 256 (100), 257
(21), 258 (6). Wr,i=22,10[o

An intense [ M - H ' ] + ion, to which s t r u c t u r e s B and C should be assigned, is a l s o o b s e r v e d in the s p e c -

tra of 2,3-dimethyl derivatives IV and XVII. However, [M-CH3"] + ion peaks are o b s e r v e d in addition to
[ M - H ' ] + ion peaks ih the spectra of IV and XVII. It might be a s s u m e d that this ion is f o r m e d via the d i s -
integration m e c h a n i s m peculiar to dimethyl derivatives of thiazole [6]. In the s y s t e m s that we examined,
the charge may be l o c a l i z e d both on the sulfur atom and on the nitrogen atom. Stripping o f a CH 3 group

676
f r o m both the 2 position and the 3 position of the thiazole ring is t h e r e f o r e p o s s i b l e , as a consequence of
which the [M-CH3"] + ion m a y have s t r u c t u r e s B and C.
It should be noted that while the intensity of the [M-CH3"] + ion is only 2.5%for XVII and a p p r o a c h e s
the intensity of the analogous ion in the s p e c t r a of thiazole d e r i v a t i v e s , s t r i p p i n g of a m e t h y l group in IV
is a v e r y advantageous p r o c e s s , and the intensity of the [M-CH3"] + ion r e a c h e s 19.7%.
Ions obtained by s t r i p p i n g of s u l f u r - c o n t a i n i n g n e u t r a l f r a g m e n t s a r e o b s e r v e d in addition to the a b o v e -
examined f r a g m e n t s in the s p e c t r a of t h i a z o l o b e n z i m i d a z o l e s .
Ion D, which is f o r m e d by the elimination of SCR" f r o m the m o l e c u l a r ion, and ion E, which is p r o -
duced during its disintegration, have the g r e a t e s t intensities of all the f r a g m e n t a r y ions. M o r e o v e r , the
intensity of D is substantially higher than the intensity of the SCR ion. This once again indicates the a d -
v a n t a g e o u s n e s s of charge localization on the nitrogen atom and r e m o v a l of SCR" as a neutral f r a g m e n t .
,'-i /CR' ~..~N
{N=(R' +"

m/~ 14a m=c. 3 ' " ~

E m/e 102 role 134 role 90

/ \ /',,,
tale 75 role 76 role 64 m/e 63

The magnitude of the m a s s n u m b e r of ion D and of ion ~CR" m a k e s it p o s s i b l e to d e t e r m i n e the p o s i -

tion of a substituent in the thiazole ring of the investigated h e t e r o c y e l e s .
S i m i l a r f r a g m e n t a t i o n of phenylimidazothiazole d e r i v a t i v e s is p r e s e n t e d below. The c o m p o s i t i o n s
of the f r a g m e n t s w e r e e s t a b l i s h e d by investigation of the h i g h - r e s o l u t i o n s p e c t r u m of XVI.
7 +" / C R ' 7""
Itt~
-":~' * I E
.,_~(R'i
,, II
s~ ~
// /\
,, ~ ..
I c~
__-~__~
A
// x.+
C~flst' ',~=' ~' ~ - - ;" -~,~= c~ ,H : ~ N y ' - , S j \ R . . . C+',
. 5 -------n--u~n C6tl ~j - - - n
~x~. role 142 role 116
m/e 155 R'=H R'
It +
rn/e 169 R'=CH 3 C6Hs--C--N~C '
+~x.__ -R'C--CR + .
[.+~ N7+" E m/e ma +-
I-NC"
C6Hs--(~:N
"S"
R .~ - C6Hs--C-=-N--C: s

role 147
Ca Hs--C~ "1
C6 H 5 - C ~ C HI
m/e Io3
role ;02

It can be s e e n f r o m a c o m p a r i s o n of the s p e c t r a of 6 - p h e n y l i m i d a z o t h i a z o l e s and t h i a z o l o b e n z i m i d a -

zoles that the p r i n c i p a l paths of t h e i r d i s i n t e g r a t i o n a r e identical and a r e due to cleavage of the thiazole
ring bonds. At the s a m e t i m e , the change in the mode of a t t a c h m e n t of the phenyl group to the thiazole ring
in the case of 6 - p h e n y l - s u b s t i t u t e d i m i d a z o t h i a z o l e s leads to a d e c r e a s e in the r e l a t i v e intensities of the
D and E ions and to the a p p e a r a n c e of low-intensity [ M - H C N ] +" ions, which can be explained by e l i m i n a -
tion of HCN f r o m the imidazole r i n g s .
The [ C 6 H 5 - C - N] +" ion, with an intensity of 13%, is also o b s e r v e d in the s p e c t r a of 6 - p h e n y l i m i d a z o t h i a -
zole. Its production f r o m ion E, as a t t e s t e d to by the p r e s e n c e of the c o r r e s p o n d i n g m e t a s t a b l e peak, can
be explained by s k e l e t a l r e a r r a n g e m e n t of ion E p r i o r to disintegration.

A c h a r a c t e r i s t i c p e c u l i a r i t y of the f r a g m e n t a t i o n of 6 - p h e n y l i m i d a z o t h i a z o l e d e r i v a t i v e is the a b -
sence of [M-C~Hs"] + ions and the low intensity of the ion with m / e 77; this p r o v e s the high d e g r e e of c o n -
jugation of the phenyl group with the imidazole ring in the i n v e s t i g a t e d s y s t e m .
The introduction of an acetyl group into the 2 position (XI, XVIII) brings about only slight changes in
the b a s i c p r i n c i p l e s of the d i s i n t e g r a t i o n of compounds of t h e s e c l a s s e s . In addition to the COCH3+ ion,
intense [M-CH3"] + and [M-COCH3"] + ion p e a k s a p p e a r in the s p e c t r a . Subsequent elimination of CS f r o m

677
the [M--COCH~'] + ion leads to the known D ion. The r e l a t i v e l y low stability of the [M-COCH3"] + ion as
c o m p a r e d with the m o l e c u l a r ions of the compounds e x a m i n e d above i n c r e a s e s the probability of the f o r m a -
tion of ion D, as a consequence of which its intensity r e a c h e s 65%, and the intensity of the f r a g m e n t p r o -
duced during its disintegration i n c r e a s e s c o r r e s p o n d i n g l y . It should be noted that the f o r m a t i o n of [ M - C O ] +-
ions, which a r e so typical f o r the s p e c t r a of C - a c e t y l and benzoyl d e r i v a t i v e s of benzimidazole [7], is not
c h a r a c t e r i s t i c for any of the examined acetyl d e r i v a t i v e s of 6-phenylimidazothiazole and t h i a z o l y l b e n z i m i -
dazole.
Thus an examination of the m a s s s p e c t r a showed that the f r a g m e n t a t i o n of the imidazothiazole s y s -
t e m c o m m e n c e s p r i m a r i l y through cleavage of the thiazole ring bonds, r e g a r d l e s s of whether this s y s t e m
is condensed with a benzene ring o r is in the 6 position. This s o r t of c h a r a c t e r of the disintegration is a p -
p a r e n t l y explained by the fact that the weakest link in the d e s c r i b e d s y s t e m s is the thiazole ring. This also
leads to the mort.typic c h a r a c t e r of the m a s s - s p e c t r o m e t r i c f r a g m e n t a t i o n of the two groups of compounds
examined in this p a p e r .

EXPERIMENTAL
The m a s s s p e c t r a w e r e obtained with an MKh-1303 s p e c t r o m e t e r with d i r e c t introduction of the s a m p l e
into the s o u r c e . The ionizing voltage was 50 eV. The h i g h - r e s o l u t i o n s p e c t r a w e r e r e c o r d e d at o u r r e -
quest with a JMS-01 (sG-2) s p e c t r o m e t e r in the m a s s s p e c t r o m e t r i c c e n t e r of J E O L (Japan), f o r which the
authors a r e s i n c e r e l y grateful.

LITERATURE CITED
1. G. Budzikiewicz, C. D j e r a s s i , and D. Williams, I n t e r p r e t a t i o n of the Mass Spectra of Organic C o m -
pounds [Russian t r a n s l a t i o n ] , Mir, Moscow (1966).
2. H. Ogura, T. Ltoh, and K. Kikuchi, J . t t e t e r o c y c l . Chem., 6, 797 (1969).
3. P. M. Kochergin and M. N. Shchukina, Zh. Obshch. Khim., 26, 458 (1956).
4. A. N. K r a s o v s k i i and P. M. Koehergin, Khim. G e t e r o t s i k l . Soedin., 899, 321 (1967).
5. I. H. Bowie, P. F. Donaghue, H. I. Rodda, and B. K. Simons, T e t r a h e d r o n , 2_~4,3965 (1968).
6. R. A. K h m e l ' n i t s k i i , E. A. Kunina, S. L. Gusinskaya, and V. Yu. Telly, Khim. G e t e r o t s i k l . Soedin.,
1372 (1971).
7. I. H. Bowie and J . R. Cooks, T e t r a h e d r o n , 24, 1875 (1968).

678
SYNTHESIS AND P R O P E R T I E S OF
1,2-DIHYDROPYRIDA ZINC [4,5-b]INDOLE
II.*

M. I . V l a s o v a a n d N. A. K o g a n UDC 547.757'852.3 : 542.941'943'951

The possibility of the synthesis of substituted 1,2-dihydropyridazino[4,5-b]indoles by the r e a c -

tion of 1-methyl-2-carbomethoxy-3-(a-halobenzyl)indole or 1 - m e t h y l - 2 - c a r b o m e t h o x y - 3 - ( ~ -
acetoxybenzyl)indole with hydrazines was demonstrated. The oxidation, reduction, and acyla-
tion reactions of the resulting 1,2-dihydropyridazino[4,5-b]indoles were studied.

The preparation of 1,2-dihydropyridazino[4,5-b]indoles by cyolization of 2-indolylmethylhydrazines

[1] and 3-indolylmethylhydrazines [2] with aromatic aldehydes is well known. We have previously described
the synthesis of 1,2-dihydropyridazino[4,5-b]indol-4-ones by intramolecular cyclization of 2-indolylhy-
drazones of aromatic aldehydes [3].
In the present communication we report the preparation of 1,2-dihydropyridazino[4,5-b]indol-4-ones
(HI-VIII) in high yields by reaction of 1-methyl-2-carbomethoxy-3-(a-acetoxybenzyl)indole (I) or 1-methyl-
2-carbomethoxy-3-(~-halobenzyl)indole (II) with hydrazines. Compounds III-V (but not VI-VIII) dissolve
on heating in strongly alkaline solutions and are recovered by acidification of the solutions; this is evidence
in favor of the existence of the O-sodium salt of the lactim structure in alkaline solutions as an anion with
the charge on the oxygen.
R R
{

~ CH--X

~--OCH3
CHa 0
{
CH3 0
IL
CH3 O
N\CoH2

1-11 ""~\d/
I CH3\N NH. " ~ "
C6Hs/'
I R
.2 - -

I -CH3
,~ /CH--NH--N~
[~ ~ - ' - ~ CG.~
~n.>~-c-oca3 ~--OCHa , N\R'
I II
CH3 0 CH3 0 CH3 O
XII-XIV Ill-VIII
A ~ J NilH2

CBH
{ 5 ~O
Ni ~ N/COCH3 o

~.~ ~ ~.~L o" ~,,~ o

XVll XVl XV

I X=--O--C(O- ; R=CcH5, o-CIC6H4, p-NO2C6H4; II X=CI, Br; R=C6H5, 0-CLC6H4, p-NO2C6H4

CH3
* See [3] for communication I.

Leningrad Pharmaceutical Chemistry Institute. Translated from Khimiya Geterotsiklicheskikh

Soedinenii, No. 6, pp. 784-787, June, 1974. Original article submitted June 14, 1973.

9 1975Plenum Publishing Corporation, 227 West 17th Street, New York, N.Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy of this article is availablefrom the publisher for $15.00.

679
 Compounds I I I - V e x i s t in the c r y s t a l l i n e state in the l a c t a m f o r m ,
inasmuch as the IR s p e c t r a contain the absorption band of a c a r -
bonyl group at 1650-1660 cm - l . The ability of VI-VIII to undergo
oxidation to give pyridazino [4,5-b]indol-4-ones and t h e i r insolu-
bility in alkaline solutions indicates that the phenyl group is a t -
tached to N(3). Alkylation of the NH 2 group of the hydrazine to give
substituted hydrazine A, which then u n d e r g o e s acylation and c y c -
lizes, a p p a r e n t l y o c c u r s initially during the s y n t h e s i s . Consequently,
~ v
if the hydrogen atom in the NH group of the phenylhydrazine is
aN~y~ aNce~ aNaN aN~,~ aN~e~ ~I~'~
alkylated, only h y d r a z i n e s XII-XIV, which a r e not cyclized on h e a t -
ing, a r e obtained.
The synthesis of a substance with mp 156 ~ to which the IX
s t r u c t u r e , obtained by heating 1 - m e t h y l - 2 - c a r b o x y - 3 - b e n z o y l i n d o l e
with phenylhydrazine in ethanol [4], was a s s i g n e d has been r e p o r t e d .
~0+ ~p" ~ ~ ~
However, it was l a t e r shown that cyclization does not o c c u r u n d e r
t h e s e conditions and that the c o r r e s p o n d i n g noncyclic h y d r a z o n e s
a r e obtained [5].
The IX that we synthesized m e l t e d at 353 ~ and had p h y s i c o -
c h e m i c a l c h a r a c t e r i s t i c s p e c u l i a r to compounds of this s e r i e s
[5-8].
Identical s u b s t a n c e s (XV), the e l e m e n t a r y composition of
which c o r r e s p o n d s to the loss of one nitrogen atom, w e r e obtained
I _-+ I I ++ I
by catalytic reduction of III, VI, and VII on Raney nickel in dioxane.
9+P u3 ~ -mW ~D u+~ It has been p r e v i o u s l y e s t a b l i s h e d [9] that reductive dehalogenation
~d 4 4 ~d ~
o c c u r s u n d e r the conditions of this reaction; this explains the iden-
o t i c a l c h a r a c t e r of the hydrogenated d e r i v a t i v e s of VI and VII. C o m -
I
I
pound XV has the c h a r a c t e r i s t i c (for p r i m a r y amides) s t r o n g band
of c a r b o n y l a b s o r p t i o n at 1642 cm -1 and an amide II band at 1618
cm -1. The bands at 3200 and 3395 cm - t c o r r e s p o n d to the s t r e t c h -
ing v i b r a t i o n s of the NH 2 group. The deamination that is o b s e r v e d
9 9 during the reduction is hindered if t h e r e is a deficit of e l e c t r o n
o ~ G Q ~
density on the nitrogen atom; this is c o n f i r m e d by hydrogenation
of acylated d e r i v a t i v e XVI, in which only N - N bond cleavage o c c u r s .
N3

The f o r m a t i o n of amide XV f r o m VII instead of the expected

anilide is a p p a r e n t l y explained by p a r t i c i p a t i o n of the adjacent
phenyl group and m i g r a t i o n of it f r o m the N (3) to N (2)

r r ~ aN EXPERIMENTAL
!
The UV s p e c t r a of alcohol solutions of the compounds w e r e
! r e c o r d e d with an SF-16 s p e c t r o p h o t o m e t e r ; the IR s p e c t r a of m i n -
e r a l oil s u s p e n s i o n s w e r e r e c o r d e d with a UR-20 s p e c t r o m e t e r .
4~

N! 1- P h e n y l - 5 - m e t h y l - l , 2 - d i h y d r o p y r i d a z i n o [4,5-b]indol-4-one
(III). A 3 . 4 - g (0.01 mole) s a m p l e of I (R --C6H5) was heated with
ea !
10 m l of h y d r a z i n e h y d r a t e in 20 m l of ethylene glycol at 125-130 ~
!
f o r 40 min. The cooled m i x t u r e was diluted with 10 m l of water,
!
~ and the r e s u l t i n g p r e c i p i t a t e was r e m o v e d by filtration and c r y s t a l -
r 9 lized f r o m dioxane to give 2.3 g (83%) of HI (see Table 1).
! d S ~ d ;
Compound IV was s y n t h e s i z e d by a s i m i l a r method. C o m -
pound V was also obtained f r o m II (R =p-NOzC6II~), but the r e a c t i o n
m i x t u r e was heated at 100 ~ for 3 min until a copious p r e c i p i t a t e
gl had f o r m e d .
_ l , 3 - D i p h e n y l - 5 - m e t h y l - 1 , 2 - d i h y d r o p y r i d a z i n o [4,5-b]indol-4-
one (VI). A 3 . 4 - g (0.01 mole) s a m p l e of I (R =C6H 5) was heated
with 16 m l of phenylhydrazine in 25 m l of ethylene glycol at 125-

680
 TABLE 2. 1 - R - 3 - P h e n y l - 5 - m e t h y l p y r i d a z i n o [ 4 , 5 - ] i n d o l - 4 - o n e s
(IX-X~)
i
Empirical i Found, % Calc., % [. @"
rap, Y: :formula L,,,. ~.,rim -~"
C H CI N C H CI
i r
i24o (4.44)i
IX C6H5 353 C2,H~7.N'30 ] 78,-/ 12,0 272 (4A8}]90
11,9i 78,6
345 (4.12)]
X ~-NO2C6H4 408 C~3Ht6N40 69,8 4,0 14,I 272 (4,56) 60
14,2 69,7 4,9
330 (4.13)
245 (4A5)
XI o-C1C6H4 262--265 IC23H~6ClN30] 71,6 4,1 9,2 10,9 71,6 4,2 9.~ 10,9 ~7~ (4,48)90.
I ! (4,12)

TABLE 3. N l - M e t h y l - N l - p h e n y l - N 2- ( 1 - m e t h y l - 2 - c a r b o m e t h o x y - 3 -
indolyl-R-phenylmethyl)hydrazine s (XII-XIV)

P Empirical Found, % Calc., o]~ )~max"

nm
~o formula (Ig E)
c Htcl N C [H iCI N

XII C6Hs [12~22

-- C25t{3~N30~ 75,2 6,3J-- 10,5 235(4,49) 80
298(4,26)
XI]I o-C!CeH4 180-- C2sH24CIN~Oz 69,3 9,7 235(4,46) 83
298(4,22)
Xl\q p-NOzC6H4 778:0 C25H24N404 ,67'5 5,4 -- 12,5k67,6 5,4 -- 12,6 232(4,47) 82
295(4,35)

130 ~ for 40 min. W a t e r (20 ml) was added to the cooled m a s s , and VI s e p a r a t e d as an oil, which c r y s t a l -
lized on heating in ethanol. The c r y s t a l s were r e m o v e d by filtration and c r y s t a l l i z e d from ethanol to give
2.8 g (79%) of VI.
Compounds VII and VIII were synthesized by a s i m i l a r p r o c e d u r e , but IX and XI were obtained from
the appropriate 1 , 2 - d i h y d r o p y r i d a z i n o [ 4 , 5 - b ] i n d o l - 4 - o n e s by the method described in [3]. Compounds IX
and X were oxidized in dioxane with aqueous KMNO 4 for 40 rain at 80 ~ (XI was heated at 100 ~ for 50 min).
The c h a r a c t e r i s t i c s of the compounds are p r e s e n t e d in Table 2.
N(~)-Methy~-N(~pheny~-N~2~(~-methy~2~carb~meth~xy-3~ind~ly~pheEy~methy~)hydrazine (XII). A
3 . 4 - g (0.01 mole) sample of I (R =CGH5) was heated with 18 ml of methylphenylhydrazine in 25 ml of ethylene
glycol at 125-130 ~ for 40 rain. The cooled mixture was diluted with 20 m l of water, and XH s e p a r a t e d as
an oil, which c r y s t a l l i z e d on heating in ethanol. The c r y s t a l s were r e m o v e d by filtration and c r y s t a l l i z e d
from ethanol to give 3.2 g (80%) of XII.
Compounds XIII-XIV were synthesized by a s i m i l a r method. The c h a r a c t e r i s t i c s of the compounds
are p r e s e n t e d in Table 3.
1 - M e t h y l - 2 - c a r b o x a m i d o - 3 - b e n z y l i n d o l e (XV). This compound, with mp 188 ~ (from benzene), was
obtained in 80-83%yield by the method in [3] by catalytic reduction of III, VI, and VII on Raney nickel. UV
s p e c t r u m , Xmax, nm (log e): 223 (4.50), 292 (4.12)o Found: C 77.4; H 6.1; N 10.6% CITHIsN20. Calcu-
lated: C 77.3; H 6.1; N 10.6%
1 - P h e n y l - 2 - a c e t y l - l , 2 - d i h y d r o p y r i d a z i n o - 5 - m e t h y l [ 4 , 5 - b ] i n d o l - 4 - o n e (XVI). A 2.77-g (0.01 mole)
sample of III was heated with 5.4 g (0.05 mole) of acetic anhydride in 30 m l of benzene for 30 min. The
solution was vacuum evaporated, and the residue was t r i t u r a t e d in e t h e r . The mLxture was filtered, and
the solid was c r y s t a l l i z e d from benzene to give 1.6 g (50%) of XVI with mp 197 ~ Found: C 71.7; H 5.4;
N 13.1%. C19HITN302. Calculated: C 71.5; H 5.3; N 13.2%.
1-Methyl-2-carboxamido-3-((~-acetamidobenzyl)indole (XVII). This compound, with mp 290-292 ~
(dioxane), was obtained in 84%yield by catalytic reduction of XVI on Raney nickel by the method in [3]. UV
s p e c t r u m , kmax, nm {log e ): 290 (4.13). Found: C 70.8; H 5.9; N 13.0%. C19H19N302. Calculated: C 71.0;
H 5.9; N 13.1%.

LITERATURE CITED

1Q H. Keberle and K. Hoffmann, Gazz. Chim. Ital., 93, 238 (1963).

2. I. Thesing and C. H. Willersinn, Chem. B e r . , 89, 1195 (1956).

681
 3e N. A. Kogan and M. I. Vlasova, Khim. G e t e r o t s i k l . Soedin., 1654 (1973).
4. R. Staunton and A. Topham, J. Chem. Soc., 1889 (1953).
5. N. N. Suvorov, Zh. D. Ovchinnikova, and Yu. N. Sheinker, Zh. Obshch. Khim., 31, 2333 (1961).
6. T. Nogrady and L. M o r r i s , Can. J. Chem., 4_~7,No. 11, 1999-2002 (1969).
7. H. King and E. Stiller, J. Chem. Sot., 466 (1937).
8. P. Nantka-Namirski and Z. Ozdowska, Acta Pol. P h a r m . , 2_~9,No. 1, 7-12 (1972).
9. N. A. Kogan and M. I. Vlasova, K h i m . - F a r m a t s . Zh., No. 7, 21 (1971).

682
SYNTHESIS OF SUBSTITUTED INDOLIZINES FROM
1-PHENACYL-5-METHYL-4-PHENYL-2-PHENACYLIDENE-
I, 2- DIHYDRO PYRIDINE

N. S. Prostakov and O. B. Baktibaev UDC 547.822.1W59.4.07

1 - P h e n a c y l - 5 - m e t h y l - 4 - p h e n y l - 2 - p h e n a c y l t d e n e - l , 2 - d i h y d r o p y r t d i n e was obtained, and its

cyclization to substituted indolizines was e x a m i n e d .

We have p r e v i o u s l y d e s c r i b e d [1] the t r a n s f o r m a t i o n s of l - p h e n a c y l - 2 , 5 - d i m e t h y l - 4 - p h e n y l p y r i d i n i u m

b r o m i d e (I) to substituted indolizines by the Chichibabin method [2]. New indolizines w e r e s y n t h e s i z e d in
the p r e s e n t study f r o m the s a m e q u a t e r n a r y salt (1) with the isolation of the i n t e r m e d i a t e 1 - p h e n a c y c l - 5 -
me t h y l - 4 - p h e n y l - 2 - p h e n a c y l i d e n e - l , 2 - d i h y d r o p y r i d i n e (If), which is f o r m e d by s u c c e s s i v e t r e a t m e n t of
salt I with benzoyl chloride and sodium hydroxide~ If one t a k e s into account the v a r i o u s concepts r e g a r d i n g
the s t r u c t u r e of analogous compounds, the p r o b l e m of the s t r u c t u r e of dihydropyridine IT cannot be c o n s i d -
e r e d to be definitely r e s o l v e d . In c o n f o r m i t y with [3], its s t r u c t u r e can be dipicted by two limiting s t r u c -
t u r e s . According to the data in [4], IT should have an ylid-like s t r u c t u r e .

+ ' ~ !!
. ~ -o_c// ~:OCsN s
c+Hs~

We have obtained c e r t a i n i n f o r m a t i o n r e g a r d i n g the s t r u c t u r e of ]I f r o m its s p e c t r a l c h a r a c t e r i s t i c s .

The bands at 700-740 c m -1 in its IR s p e c t r u m a r e r e l a t e d to the o u t - o f - p l a n e d e f o r m a t i o n v i b r a t i o n s of the
a r o m a t i c C - H bonds. We a s s i g n e d the band at 1636 cm - I to the s t r e t c h i n g v i b r a t i o n of the a r o m a t i c C - C
bonds, i n a s m u c h as the i n t e g r a l intensity of this band is 1.2 9 10 + m o l e - t - l i t e r 9 cm -2. The a b s o r p t i o n band
of the c a r b o n y l group a p p a r e n t l y is at 1500-1510 cm - t and is o v e r l a p p e d by the bands of a r o m a t i c C =C
bonds; this brings about a c o n s i d e r a b l e i n c r e a s e in the intensity and b r o a d e n i n g of the bands in this region.
The a s s i g n m e n t of the weak bands at 3080, 3060, and 3030 c m -1 r a i s e s s o m e difficulty. They m a y be due
to a r o m a t i c C - H bonds [1] and also to an enol hydroxyl group with a s t r o n g O - H . . . N i n t r a m o l e c u l a r bond.
O t h e r hydroxy d e r i v a t i v e s of nitrogen h e t e r o c y c l e s also have s i m i l a r s p e c t r a l c h a r a c t e r i s t i c s in the bonded
h y d r o x y l - g r o u p region [5]. Taking this into account, one m a y a s s u m e the p r e s e n c e of a c a r b o n y l group
(benzoyl group} and a hydroxyl group with a s t r o n g hydrogen bond (the enol f o r m of the second b e n z o y l group}
in II.
The PMR s p e c t r u m of II does not contain the signals of a methylene group o r a second m e t h y l group.
The o b s e r v e d signals c o r r e s p o n d to the protons of a m e t h y l group (5 2.18 ppm), the ~ p r o t o n of the h e t e r o -
ring (~ 8.06 ppm), and the methlyidyne proton of the enol (5 7.85 ppm). Two signals at 7.57 and 7.50 ppm,
which are split weakly as a consequence of aUylic coupling, a r e o b s e r v e d at s t r o n g e r field; this m a k e s it
p o s s i b l e to a s s i g n t h e m to the fl proton of the h e t e r o r i n g and to the methylidyne p r o t o n of the phenacylidene
grouping. The r e m a i n i n g f i v e - p r o t o n signals a r e due to t h r e e phenyl groups (singlets at ~ 7.35 and 7.22 ppm
and a multiplet at 6.95-7.16 ppm}. Thus s t r u c t u r e II, which c o r r e s p o n d s to the data in [4], is a p p a r e n t l y not
c o n f i r m e d by the PMR s p e c t r u m . The s p e c t r a l data obtained also somewhat c o n t r a d i c t the concepts in [3].
Taking the above information into account we suppose that the m o s t p r o b a b l e s t r u c t u r e m a y be depicted by
the enol f o r m of methylidyne d e r i v a t i v e II.
- - P+ L u m u m b a I n t e r n a t i o n a l - F r i e n d s h i p U n i v e r s i t y , Moscow. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k -
licheskikh Soedinenii, No. 6, pp. 788-791, June, 1974. Original a r t i c l e s u b m i t t e d April 18, 1972; r e v i s i o n
submitted N o v e m b e r 11, 1973.

9 1975PlenumPublishing Corporation, 227 West 17th Street, New York, N.Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy of this article is available from the publisher for $15.00.

683
 It has been established [3, 4] that the cyclization of analogous methylidyne derivatives when they are
heated with acetic anhydride gives i s o m e r i c indolizines with substituents in v a r i o u s positions of the five-
m e m b e r e d ring. Of compounds of the II type, we obtained 6 - m e t h y l - 2 , 7 - d i p h e n y l - 3 - b e n z o y l i n d o l i z i n e (iII),
6 - m e t h y l - 2 , 7 - d i p h e n y l - l - b e n z o y l i n d o l i z i n e (IV), and 6 - m e t h y l - 2 , 7 - d i p h e n y l - l - a c e t y l - 3 - b e n z o y l i n d o l i z i n e
iV).
t- -- COC(~Ms

CH, ~/;~.'N":'C H2C? CH : ~ / ~ . . / ~ - - ~ " C H a / ~ - / . N ' - - ~ . . tt CH ")'~" / :~""C ,.t//~\

8r- c0Hs M,,,o/C"c0xs : " * ~" 9I c0H5
I / II -._ I-/~ !*-]i20

1 I "-z. oc. , ~oc~

c~ c~ co.~~c o . c~.~~

COCoHs COCoHs COCoH s 9 COC~H~

Ill v

The initial step is deprotonation of II, which is p r o m o t e d by the basic nitrogen atom in its s t r u c t u r e .
I f one takes into account the fact that indolizines III and IV are f o r m e d in a ratio of 3 : 1, while V is the p r o -
duct of acetylation of 3-benzoylindoltzine lII, it can be concluded that the dominant reaction path is d e p r o -
tonation of the enol hydroxyl group r a t h e r than deprotonation of the phenacylidene group of dihydropyridine
II.
Indolizine HI was also obtained by benzoylation of 6-methyl-2,7-diphenylindolizine ivI) [1], while IV
was obtained by heating II with f o r m a m i d e . In the latter case, Ill is also f o r m e d in s m a l l amounts.
The IR s p e c t r a of indolizines IlI and IV are s i m i l a r but not identical. The weak bands at 3030-3120
cm -1 are related to the vibrations of the a r o m a t i c C - H bonds, while those at 2860-2980 cm -1 are related
to the stretching vibrations of the CH 3 group. T h e r e are bands of deformation vibrations of this group for
HI (IV) at 1460 (1470) and 1340 (1360) cm -1 and intense bands in the l o w - f r e q u e n c y region at 742 (748) and
707 (702) cm -1, which are related to the vibrations of monosubstituted phenyl rings. As expected, the g r e a t -
est difference is o b s e r v e d at 1500-1600 cm - l . The bands at 1610 and 1597 cm -1 were well r e s o l v e d for IV;
the f i r s t apparently is related to the s t r e t c h i n g vibration of the c a r b o n y l group, inasmuch as its integral
intensity is 2.9-104 m o l e - l ' l i t e r - cm -2. The bands at 1597, 1575, and 1505 cm -1 are related to the s t r e t c h -
ing vibrations of a r o m a t i c C =C bonds. The s p e c t r u m of indolizine HI contains a single band at 1600 cm -1.
This band is possibly the band of a carbonyl group, inasmuch as its integral intensity is 3 9104 mole -1 9l i t e r -
cm -2. The bands at 1574 and 1507 cm -1 are due to the vibrations of a r o m a t i c C =C bonds. The band at
1600 cm -1 in the IR s p e c t r u m of indolizine V is apparently related to the vibrations of carbonyl groups;
bands s i m i l a r to those in the s p e c t r u m of HI are also observed.
The UV s p e c t r a of indolizines III and IV are in s a t i s f a c t o r y a g r e e m e n t with the UV s p e c t r a r e p o r t e d
in [6, 7], and t h e i r m a s s s p e c t r a are identical.

EXPERIMENTAL
The IR s p e c t r a of KBr pellets and CHC13 solutions of the compounds were r e c o r d e d with a UR-20
s p e c t r o m e t e r . The integral intensities of the IR absorption bands were m e a s u r e d at 1300-1700 cm -~.
C h l o r o f o r m solutions (0.005 M) were usod for the m e a s u r e m e n t s , and the l a y e r thickness was 0.5 cm. The
integral intensities were calculated by the method in [8]. The UV s p e c t r a of ethanol Solutions were ob-
tained with an EPS-3 s p e c t r o p h o t o m e t e r . The PMR s p e c t r a of d e u t e r o c h l o r o f o r m solutions were obtained
with a JNM-4H-100 s p e c t r o m e t e r with t e t r a m e t h y l s i l a n e as the internal standard. The m o l e c u l a r weights
were determined with an MKh-1303 m a s s s p e c t r o m e t e r .
1 - P h e n a c y l - 2 , 5 - d i m e t h y l - 4 - p h e n y l p y r i d i n i u m Bromide (I). A mixture of 5.5 g (0.03 mole) of 2,5-
dimethyl-4-phenylpyridine and 6 g (0.03 mole) of bromoacetophenone in 20 ml of dry acetone was refluxed
for 3 h and allowed to stand for 12 h. The precipitate was r e m o v e d by filtration and washed once with 5 ml

684
of cold d r y acetone and s e v e r a l t i m e s with absolute e t h e r to give 11.2 g (97%) of salt I as a white powder.
Two p r e c i p i t a t i o n s of 0.4 g of the product f r o m a c e t o n e - a l c o h o l (3: 1) by the addition of absolute e t h e r
gave 0.34 g of p u r e salt I with mp 195-197 ~ Found: B r 20.8; N 3.6%. C21H20BrNO. Calculated: B r 20.8,
N 3.7%.
1- P h e n a c y l - 5 - m e t h y l - 4 - p h e n y l - 2 - p h e n a c y l i d e n e - l , 2 - d i h y d r o p y r i d i n e (II). A 2 . 8 - m l (27 m m o l e )
s a m p l e of f r e s h l y distilled benzoyl chloride was added in the c o u r s e of 5 min with v i g o r o u s s t i r r i n g u n d e r
nitrogen to a solution of 9 g (23 m m o l e ) of salt I in a m i x t u r e of 25 m l of w a t e r and 50 m l of methylene
chloride. The solution was s t i r r e d for 15 min, a f t e r which 52.5 m l of 6 N sodium hydroxide was added
in the c o u r s e of 10 min, and the m i x t u r e was s t i r r e d f o r a n o t h e r 30 min. The methylene chloride l a y e r
was washed s e v e r a l t i m e s with cold w a t e r and dried with m a g n e s i u m sulfate. The solvent was r e m o v e d
by distillation to give 9.1 g (95%) of crude II as reddish c r i m s o n - t i n t e d plates with m p 199-200.5" (twice
f r o m alcohol) and Rf 0.26 (KSK silica gel, benzene). Heating with a c t i v a t e d c h a r c o a l and subsequent c r y s -
tallization f r o m alcohol did not change the c o l o r of the c r y s t a l s . However, f i n e - g r a i n e d yellow c r y s t a l s
with the s a m e m e l t i n g point w e r e f o r m e d by r e c r y s t a l l i z a t i o n f r o m benzene (heating with activated c h a r -
coal). UV s p e c t r u m , Xmax, nm (log e): 255 (4.65), 390 (4.27). Found: C 83.1; H 5.7; N 3.5%. C28H23NO2.
Calculated: C 82.9; H 5.7; N 3.5%.
Indolizines III-V. A) A m i x t u r e of 0.5 g (1.2 m m o l e ) of II and 3.5 m l of f r e s h l y distilled a c e t i c a n -
hydride was heated at 120 ~ until II d i s s o l v e d (with shaking), and the m i x t u r e was held at 120 ~ for 1 h. It
was then cooled and poured into 50 m l of ice w a t e r . The aqueous m i x t u r e was m a d e alkaline with sodium
bicarbonate and e x t r a c t e d with c h l o r o f o r m . The p r o d u c t s were s e p a r a t e d by m e a n s of column c h r o m a t o -
graphy (activity II aluminum oxide, e t h e r ) . F r a c t i o n s with the following Rf v a l u e s w e r e isolated s u c c e s -
sively: 0.86 (0.27 g), 0.77 (0.09 g), and 0.46 (0.05 g). The f i r s t f r a c t i o n was r e c r y s t a U i z e d f r o m hexane
to give b r i g h t - y e l l o w s t a r - s h a p e d c r y s t a l s of indolizine III with mp 135-137 ~ UV s p e c t r u m , Xmax, nm
(log e): 256 (4.48), 310 shoulder, 400 (4.21). Found: C 86.5; H 5.8; N 3.4%; M 387 C28H21NO. Calculated:
C 86.8; H 5.5; N 3.6%; M 387. The second f r a c t i o n was r e c r y s t a l l i z e d f r o m h e x a n e - e t h e r t o give b r i g h t
yellow p l a t e s of indolizine IV with mp 192.5-193.5 ~ UV s p e c t r u m , Xmax, nm ( l o g e ) : 255 (4.60), 2 8 6 s h o u l d e r ,
390 (4.22). Found: C 86.7; H5.9; N3.4%; m o l . w t . 3 8 7 . C28H21NO. Calculated: C 86.8; H5.5; N3.6%; m o l . w t . 3 8 7 .
R e c r y s t a l l i z a t i o n of the t h i r d f r a c t i o n f r o m h e x a n e - e t h e r gave 0.02 g of V as b r o w n i s h g r a i n s with m p 121.5-
123 ~ Found: C 83.7; H 5.7; N 3.4%. C30H23NO2. Calculated: C 83.9; H 5.4; iN 3.3%.
B) A m i x t u r e of 1.2 g (4.2 m m o l e ) of indolizine VI and 0.7 m l (5.9 m m o l e ) of f r e s h l y distilled benzoyl
chloride in 15 m l of d r y benzene was held at r o o m t e m p e r a t u r e for 24 h and at 50-60 ~ for 3 h. It was then
cooled to r o o m t e m p e r a t u r e , t r e a t e d with 5 m l of water, m a d e alkaline with sodium hydroxide, and e x t r a c t e d
with c h l o r o f o r m . The e x t r a c t was dried with m a g n e s i u m sulfate, and the solvent was r e m o v e d by d i s t i l l a -
tion. The d a r k residue was p a s s e d through a s h o r t column filled with aluminum oxide with elution with
c h l o r o f o r m . R e c r y s t a l l i z a t i o n of the isolated r e s i d u e f r o m hexane gave 1.13 g (69%) of III as l a r g e , yellow,
s t a r - s h a p e d c r y s t a l s (Rf 0.86, the s a m e s y s t e m as above) with m p 135-137 ~ No m e l t i n g - p o i n t d e p r e s s i o n
was o b s e r v e d for a m i x t u r e of this product with a s a m p l e of the m a t e r i a l d e s c r i b e d above.
C) A s u s p e n s i o n of 1.22 g (3 m m o l e ) of dihydropyridine II in 2 m l of f r e s h l y distilled f o r m a m i d e was
heated to 200 ~ with shaking and held at that t e m p e r a t u r e for 1 min. It was then cooled to r o o m t e m p e r a t u r e
and t r e a t e d with 2 m l of w a t e r . The aqueous m i x t u r e was cooled to - 5 ~ and the d a r k - b r o w n p r e c i p i t a t e
was washed s e v e r a l t i m e s with cold w a t e r and once with 1 m l of cold acetone. The m a t e r i a l was v a c u u m
dried to give 0.8 g of a yellow powder, which, a c c o r d i n g to the r e s u l t s of t h i n - l a y e r c h r o m a t o g r a p h y on
aluminum oxide, was a m i x t u r e of indolizines III and IV (Rf 0.86 and 0.78). The m i x t u r e was s e p a r a t e d by
c h r o m a t o g r a p h y to give 0.06 g of III (rap 135-137 ~ and 0.51 g of IV. Two c r y s t a l l i z a t i o n s f r o m h e x a n e -
e t h e r gave IV as b r i g h t - y e l l o w plates with m p 192.5-193.5 ~ No m e l t i n g - p o i n t d e p r e s s i o n was o b s e r v e d for
a m i x t u r e of this product with a s a m p l e of IV f r o m e x p e r i m e n t A.

LITERATURE CITED

li N. S. P r o s t a k o v and O. B. Baktibaev, Khim. G e t e r o t s i k l . Soedin., 1395 (1971).

2. A. E. Chichibabin, Zh. Russk. Khim. O b s h c h e s t v a , 59, 477 (1927).
3. T. Melton and D. G. W i b b e r l e y , J. Chem. Sot., C, 983 (1967).
4. F. W. K r 6 e k and F. Krb~nke, B e r . , 102, 669 (1969).
5. N. S. P r o s t a k o v , L. A. G a i v o r o n s k a y a , and G. A l v a r a d o - U r b i n a , Khim. G e t e r o t s i k l . Soedin., 1087
(1971).
6. V. Bockelheideand R. S. Windgassen, J. Amer. Chem. Soc., 8_~1,1456 (1959).

685
7o T. Sasaki, K. Kanematsu, and Y. Yakimoto, J. Chem. Sot., C, 481 (1970).
8. D. A. Ramsay, J. Amer. Chem. Sot., 72, 74 (1952).

686
NUCLEOPHILIC SUBSTITUTION IN 2-NITRO-3-
HA LO P Y R I D I N E S

Yu. A. Azev, G. A . M o k r u s h i n a , UDC 547.822.5.7' 867.4

and I. Ya. Postovskii

Nucleophilic substitution o c c u r s in the 2 o r 3 position in 2 - n i t r o - 3 - h a l o p y r i d i n e s depending

on the nature of the halogen and the substituting agent. A s e r i e s of new 2 , 3 - s u b s t i t u t e d
p y r i d i n e s w e r e obtained as a r e s u l t of the r e a c t i o n s .

It is known that the nitro group in 2 - n i t r o p y r i d i n e and its d e r i v a t i v e s can be r e a d i l y r e p l a c e d by h y -

d r a z i n e [1], halogen [2], and hydroxy groups [1, 3]. 2 - N i t r o p y r i d i n e does not r e a c t with a m m o n i a [3]. The
ethoxy group in 2 - n i t r o - 3 - e t h o x y p y r i d i n e is r e p l a c e d on reaction with a m m o n i a , and 2 - a m i n o - 3 - e t h o x y -
pyridine is obtained in 8% yield as a side product [4]~ A halogen in the 3 position of pyridine r e a c t s with
nucleophiles only under s e v e r e conditions [5, 6].
No study of nucleophilic substitution of nitro groups and halogens in the 2 and 3 positions of the p y r i d -
ine ring, r e s p e c t i v e l y , has been m a d e . In o r d e r to a c c o m p l i s h this, we synthesized a n u m b e r of p r e v i o u s l y
u n d e s c r i b e d 2 - n i t r o - 3 - h a l o p y r i d i n e s (IIa-c and VIII). 2 - N i t r o - 3 - c h l o r o ( b r o m o , iodo)pyridines (IIIa, b, c)
w e r e obtained b y the S a n d m e y e r r e a c t i o n f r o m the p r e v i o u s l y d e s c r i b e d [7] 2 - n i t r o - 3 - a m i n o p y r i d i n e (i}. It
was found that diazotization of pyridine I in the p r e s e n c e of h y d r o c h l o r i c acid brings about not only s u b s t i -
tution of the amino group by a chlorine a t o m but a l s o simultaneous nucleophilic a t t a c k at the nitro group,
which is r e p l a c e d by chlorine to give 2 , 3 - d i c h l o r o p y r i d i n e (IIIa). 2 , 3 - D i b r o m o p y r i d i n e (IIIb} and 2 - n i t r o - 3 -
b r o m o p y r i d i n e (IIb} a r e obtained in a ratio of 1 : 2 by diazotization of I in h y d r o b r o m i c acid. If dilute s u l -
f u r i c acid is introduced into the diazotization reaction, only 2 - n i t r o - 3 - h a l o p y r i d i n e s (IIa-c} a r e isolated in
the p r e s e n c e of the c o r r e s p o n d i n g s a l t s . 2 - N i t r o - 3 - f l u o r o p y r i d i n e (VIII} was obtained by the Schiemann r e -
action. In c o n t r a s t to p y r i d i n e - 3 - d i a z o n i u m t e t r a f l u o r o b o r a t e [8], 2 - n i t r o p y r i d i n e - 3 - d i a z o n i u m t e t r a f l u o r o -
b o r a t e is stable but d e c o m p o s e s at 140~ to give VIII.
Nucleophilic substitution in 2 - n i t r o - 3 - h a l o p y r i d i n e s (IIa-c and VIII) has been investigated in r e a c t i o n s
with a m m o n i a , morpholine, hydrazine, aniline, and h y d r o c h l o r i c and h y d r o b r o m i c acids.
It has been e s t a b l i s h e d that the labilities of the nitro group and the halogens a r e c o m m e n s u r a b l e in
the r e a c t i o n of I I a - c with a m m o n i a and m o r p h o l i n e . P r o d u c t s of substitution of both the nitro group and the
halogens w e r e obtained f o r each nucleophile. Thus 2 - n i t r o - 3 - a m i n o p y r i d i n e (V) and 2 - a m i n o - 3 - c h l o r o -
(bromo, iodo)pyridines (VIIa-c) w e r e i s o l a t e d in the r e a c t i o n of p y r i d i n e s I I a - c with a m m o n i a , while 2 - n i t r o -
3 - m o r p h o l i n o p y r i d i n e (V) and 2 - m o r p h o l i n o - 3 - c h l o r o ( b r o m o ) p y r i d i n e s (VIIa, b) a r e f o r m e d f r o m IIa, b and
m o r p h o l i n e . In the c a s e of pyridine IIc, only 2 - n i t r o - 3 - m o r p h o l i n o p y r i d i n e (V) was obtained on r e a c t i o n
with mo rpholine.
Compounds Ha, b r e a c t differently with b e n z y l a m i n e . Two p r o d u c t s - 2 - n i t r o - 3 - b e n z y l a m i n o p y r i d i n e
(V) and 2 , 3 - d i b e n z y l a m i n o p y r i d i n e (IV) - w e r e also isolated in this c a s e . Compound V (R =benzylamino)
was the only compound obtained f r o m IIc in this reaction.(See s c h e m e on following page.}
P r o d u c t s of substitution of only the nitro group w e r e isolated in the r e a c t i o n of I I a - c with h y d r a z i n e .
The 2 - h y d r a z i n o - 3 - h a l o p y r i d i n e s (Xa-c) obtained give the c h a r a c t e r i s t i c (for 2-hydrazinopyridine) c y c l i z a -
tion r e a c t i o n with nitrous acid and acetic acid to give the c o r r e s p o n d i n g t e t r a z o l o [ 1 , 5 - a ] p y r i d i n e s (XI} and

S. M. K i r o v U r a l Polytechnic Institute, Sverdlovsk. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h

Soedinenii, No. 6, pp. 792-795, June, 1974. Original a r t i c l e s u b m i t t e d July 31, 1973.

9 1975Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy o f this article is availablefrom the publisher for $15.00.

687
 X

VI V Vii Xl

VIII I / II X

I' \ / I l
~N~NHC6Hs X

~l |If IV Xil
X a=Cl,b =Br, c=I; II X=a,b,c; Ill X~a,b; IV R=,NHCH~C6Hs;V R~morpholino, NHz,
NHCH2CsHs; VI X=a, b, R=morpholino;VIIX=a, b,c; R=NH~,morpholino;X X=a,b,c ;
XI X=a,b,c ; XII X~c; R=CHs, Cells

s y m - t r i a z o l o [ 4 , 3 - a ] p y r i d i n e s (XII). Compounds X a - c readily give hydrazones, which a r e converted to t r i -

a z o l c s XII on oxidation with b r o m i n e .
The nitro group in pyridines I I a - c and V (R =morpholino) is readily replaced by halogen when the c o m -
pounds a r e refluxed in h y d r o c h l o r i c o r h y d r o b r o m i c acid. In this case, 2,3-dihalopyridines Ha, b a r e f o r m e d
f r o m IIa, b, while products Via, b - i s o m e r s of VIIa, b - a r e obtained f r o m V (R =morpholino).
2 - N i t r o - 3 - f l u o r o p y r i d i n e (VIII) r e a c t s with morpholines, benzylamine, and a m m o n i a at room t e m p e r a -
t u r e to give fluorine-substitution products (V). In contrast to the chloro, bromo, and iodo derivatives (IIa-c),
which do not r e a c t with aniline even on refluxing in excess aniline, fluoro derivative VIII readily r e a c t s with
aniline even at room t e m p e r a t u r e to give 2 - n i t r o - 3 - p h e n y l a m i n o p y r i d i n e (IX).
Thus a p r e p a r a t i v e method for the synthesis of a s e r i e s of new or p r e v i o u s l y difficult-to-obtain 2,3-
substituted pyridine derivatives, which a r e of independent interest o r a r e starting m a t e r i a l s for s u b s e -
quent syntheses, was developed by means of nucleophilic substitution in 2 - n i t r o - 3 - h a l o p y r i d i n e s (IIa-c and
VIII).

EXPERIMENTAL

2 - N i t r o - 3 - e h l o r o ( b r o m o , iodo)pyridines (Ha-e). These compounds were obtained as follows: a ) f r o m

pyridine I via the Sandmeyer r e a c t i o n in sulfuric acid with c r y s t a l l i z a t i o n of the resulting nitrohalo d e r i v a -
t i v e s f r o m 50% aqueous alcohol (Table 1),* b) (for pyridine IIb) by diazotization of I in 20% I-IBr. T h e y i e l d
was 65%.
2,3-Dichloro(dibromo)pyridines (IIIa, b). Compound IIIa was obtained by the Sandmeyer reaction in
25% HC1 and was isolated by alkylation of the r e a c t i o n mixture to pH 7-8 and s t e a m distillation of the r e a c -
tion product. The yield of product with mp 66-67 ~ (mp 66.5-67.5 ~ [9]) was 65%. Compound IIIb was obtained
by the Sandmeyer reaction in 40% HBr. The precipitated IIb was r e m o v e d by filtration (45% yield). Product
IIIb was isolated by dilution of the m o t h e r liquor with w a t e r (25% yield). The product had mp 58-59 ~ (mp
58.5-59.6 ~ [10]).
2 - N i t r o - 3 - f l u o r o p y r i d i n e (VIII). This compound was obtained by the method in [8]. The diazonium
t e t r a f l u o r o b o r a t e was decomposed at 140 ~ Product VIII was extracted f r o m the reaction mixture by means
of c h l o r o f o r m . The solvent was evaporated, and the r e s i d u e was purified by vacuum sublimation at 80-90 ~.
A solution of VIII in c h l o r o f o r m was used without additional purification f o r the r e a c t i o n s with a m i n e s .
Reaction of IIa, b, c with Ammonia. A 1-g (6.0 mmole) sample of pyridine IIa was heated at 150 ~ in
10 ml of 28% ammonium hydroxide f o r 3 h. The solution was cooled, and the resulting precipitate was r e -
c r y s t a l l i z e d from petroleum ether to separate 2 - a m i n o - 3 - c h l o r o p y r i d i n e VIIa f r o m undissolved 2 - n i t r o - 3 -
aminopyridine (V). The yield of VIIa with mp 60-61 b imp 61.5-62 ~ [9]) was 60%. The yield of V was 15%.

*See Table 1 for the data for the undescribed substances.

688
 T A B L E 1. 2,3-Substiturted P y r i d i n e s

U: i

Com- Empirical Found, % . Calc.," % ~.

pound i~ R" mp, "c formula

IIa NO2 CI 90--91 CsHaCINuO2 37.8, ,.9,1.155

IIb NO2 Br 100--101 CsI-IzBrN~Oz 39.7! ~.bJ 13,61 29,61 1,51 13,81 65
IIc NO2 1 98--99 CsH3IN202 24.1) .... 11,1 24,0 1,2 11,2170
IV NHCH2C6Hs NHCH2C6Hs 166--167 C,gHI~N3H~O 74.21 7.21 13,0[ 74,3[ 6,8[ 13,7125
V NO2 Morpholino 62--63 CgHIINa03 51.51 5.2] 2o,11 51,71 5~3] 2o,11 40
V NO~ NHCrt2C6Hs llO--ltl CI2HuN302 62.51 4,91 18,51 62,71 4,81 18,31 15
Via C Morpholino 100--101 CgHnCIN20 55.11 5.61 14,1[ 54,4[ 5,6] 14,1[ 95
VIb Br Morpholino 89--90 CgHHBrNgO 44.31 4.71 11,9[ 44,5[ 4,6[ 11,5[ 95
V I I a Morpholino CI 94--95 CgHIICIN20 54.91 5.81 13,6[ 54,4[ 5,6] 14,1[ 40
VIIb Morpholino Br 92--93 CgHHBrN20 44.bl 4.{5111,5[ 44,5[ 4,6[ 11,5] 30
VIle NH~ I 87--88 C~HsIN2 27.61 2.41 13,0/27,3 2,3| 12,7 50
VIII NO~ F 38--39 CsH3FN202 41_71 2.41 19,91 42,21 2,1 / 19,7[ 25
IX NO2 NHC6Hs 85--86 CItHgN30~ (~1.41 4.41 19,1 61,4 4,2[ 19,6[ 55
Xb NHNH2 '147--148 CsH6BrN~ 32,21 8.41 22,1 31,9 3,2[ 22,3 55
Xc NHNH~ 96--97 CsH~IN3 25.7! 2.7:17,4 25.5 2.6/ 17,9 35

Compounds I17o, c r e a c t s i m i l a r l y with a m m o n i a to give V (R =NI,I2) and VIIb, c (R = NH2). The yields of V
and VIIb w e r e 15 and 50%, r e s p e c t i v e l y . Compound ViIb had mp 64-65 ~ (mp 64.5-65.5 ~ [10]).
Reaction of P y r i d i n e s IIa, b, c with Morpholine. A 1 - g (6.0 mmole) s a m p l e of IIa was refluxed f o r 3
h in 10 m l of 50% solution of morpholine in methanol. W a t e r was added to the r e a c t i o n m i x t u r e to precipi'-
t a t e 2 - m o r p h o l i n o - 3 - c h l o r o p y r i d i n e (VIIa), which was c r y s t a l l i z e d f r o m 50% aqueous alcohol. The m o t h e r
liquor was e v a p o r a t e d to d r y n e s s , and the r e s i d u e was r e c r y s t a l l i z e d f r o m 30% aqueous alcohol to give 2-
n i t r o - 3 - m o r p h o l i n o p y r i d i n e (V). The r e a c t i o n with pyridine IIb was c a r r i e d out s i m i l a r l y . In the c a s e of
IIc, the r e a c t i o n m i x t u r e was e v a p o r a t e d to dryness, and product V (R =morpholino) was c r y s t a l l i z e d f r o m
30% aqueous alcohol. The yield was 40%.
Reaction of I I a - c w i t h B e n z y l a m i n e . A 1 - g (6.0 mmole) s a m p l e of IIa was refluxed f o r 1 h in 10 m l of
a 50% methanol solution of b e n z y l a m i n e . The solvent was evaporated, and the r e s i d u e was diluted w i t h w a t e r
and e x t r a c t e d with c h l o r o f o r m . The e x t r a c t was dried with Na2SO4, filtered, and e v a p o r a t e d . The p r e c i p -
itated 2 , 3 - d i b e n z y l a m i n o p y r i d i n e (IV) was r e m o v e d by filtration and c r y s t a l l i z e d f r o m 50% aqueous a l -
cohol. The reaction was c a r r i e d out s i m i l a r l y with pyridine IIb. In the c a s e of IIc, a solution in c h l o r o -
f o r m was e v a p o r a t e d until an off formed, a f t e r which the m i x t u r e was t r e a t e d with e t h e r to give V (R =
NHCH2C6I-I5) in 15% yield.
Reaction of P y r i d i n e s IIa, b, c with H y d r a z i n e . A 1 - g (6.0 mmole) s a m p l e of pyridine IIa was refluxed
in 10 m l of a 50% solution of h y d r a z i n e hyctrate in methanol for 1 h or the m i x t u r e was allowed to stand at
r o o m t e m p e r a t u r e for 3 h. E v a p o r a t i o n of the r e a c t i o n m i x t u r e p r e c i p i t a t e d 2 h y d r a z i n o - 3 - c h l o r o p y r i d i n e
(Xa), with mp 160-161 ~ ( f r o m water) (rap 160-161 ~ [11]), in 55% yield. Compounds lib, c w e r e s i m i l a r l y ob-
tained.
Substitution of the Nitro Group in IIa, b and V (R =Morpholino) by Halogen. A 6.0-mmole s a m p l e of
IIa, b or V (R =morpholine) was refluxed in 10 m l of c o n c e n t r a t e d HC1 o r H B r . The r e a c t i o n p r o d u c t s w e r e
p r e c i p i t a t e d with w a t e r . P r o d u c t s IIa, b w e r e obtained f r o m IIIa, b, while Via, b w e r e obtained f r o m V (R =
morpholino). Compounds Via, b w e r e c r y s t a l l i z e d f r o m 50% aqueous alcohol.
8 - C h l o r o t e t r a z o l o [ 1 , 5 - a ] p y r i d i n e (XIa). A 0.5-g (3.5 mmole) s a m p l e of pyridine Xa was d i s s o l v e d in
8 ml of 10% H2SO4 and diazotized with 0.8 g (1.1 mmole) of NaNO 2 in 2 m l of w a t e r . The p r e c i p i t a t e was
r e m o v e d by f i l t r a t i o n to give 0.48 g (90%) of XIa with mp 182-183 ~ (from w a t e r ) . Found: C 38.9; H 2.0;
N 36.0%. CsH3C1N4. Calculated: C 38.7; H 1.9; N 36.1%. Compounds XIb, c w e r e s i m i l a r l y obtained. C o m -
pound XIb had mp 208-209 ~ (from water). Found: C 29.9; H 1.4; N 27.9%. CsH3BrN 4. Calculated: C 30.4;
H 1.5; N 28.1%. Compound XIc had mp 224-225 ~ {from water). Found: C 24.6; H 1.1; N 22.4%. C5H3IN4.
Calculated: C 24.4; H 1.2; N 22.8%. Compound XIa in t r i f l u o r o a c e t i c acid solution did not give an a b s o r p -
tion band c o r r e s p o n d i n g to the frequency of the s t r e t c h i n g v i b r a t i o n s of the azide group at 2100-2200 e m -1.

8 - B r o m o - 3 - m e t h y l - s y m - t r i a z o l o [ 4 , 3 - a ] p y r i d i n e (XIIb). A 0.7-g (4.0 mmole) s a m p l e of Xb was r e -

fluxed in 20 m l of a c e t i c acid f o r 9 h. The acetic acid was then r e m o v e d by distillation to give 0.68 g (95%)
of XIIb with mp 161-162 ~ ( f r o m benzene). Found: C 39.8; H 3.1; N 19.2%. CTHI6BrN3. Calculated: C 39.6~
H 2.8; N 19.8%.

689
 8 - B r o m o - 3 - p h e n y l - s y m - t r i a z o l o [ 4 , 3 - a ] p y r i d i n e (XIIb). A solution of 0.75 g (4.0 mmole) of Xb in 10
m l of alcohol was heated for 5 min with 0.7 g (6.6 mmole) of benzaldehyde in 10 m l of alcohol. The m i x t u r e
was t r e a t e d with w a t e r , and the p r e c i p i t a t e was r e m o v e d by filtration to give 1 g (90%) of benzaldehyde 3-
b r o m o - 2 - p y r i d y l h y d r a z o n e with mp 137-138 ~ (from 50% aqueous alcohol). Found: C 52.3; H 3.7; N 15.1%.
CI2H10BrN3. Calculated: C 52.2; H 3.6; N 15.2%. A 1 - g (3.6 m m o l e ) s a m p l e of the hydrazone was dissolved
in 6 m l of acetic acid, and 1 g (1.5 mmole) of sodium a c e t a t e and 0.8 m l of b r o m i n e in 2 ml of acetic acid
w e r e a d d e d . T h e m i x t u r e was refluxed f o r 5 rain, a f t e r which it was poured into 10 m l of w a t e r . The r e -
sulting oil c r y s t a l l i z e d on standing. T h e c r y s t a l s w e r e r e m o v e d by f i l t r a t i o n to give 0.9 g (90%) of XIIbwith
m p 175-176 ~ ( f r o m water). Found: C 52.6; tt 2.9; N 14.9%. C12HsBrN 3. Calculated: C 52.6; H 2.9; N 15.3%.
Reaction of VIII with Amines. A twofold e x c e s s of the a p p r o p r i a t e a m i n e was added to a solution
of VIII in c h l o r o f o r m , and the p r e c i p i t a t e d a m i n e salt was r e m o v e d by filtration. The solvent was r e m o v e d
by distillation, and product V was c r y s t a l l i z e d f r o m an a p p r o p r i a t e solvent; IX was c r y s t a l l i z e d f r o m 50%
aqueous alcohol.

LITERATURE CITED
1. W. Czuba and E.Plazek, Rec. T r a y . Chim., 77, 92 (1958); Chem. Abstr., 52, 17,263 (1958).
2. H. J. H e r t o g and B. Mulder, Rec. T r a y . Chim., 67, 957 (1948); Chem. A b s t r . , 43, 3824 (1949).
3. M a s a Katada, J. P h a r m . Soc. Japan, 67, 51 (1947); Chem. Abstr,, 45, 9537 (1951).
4. H. J. H e r t o g and C. J o u w e r s m a , R e c . T r a y . Chim., 72, 125 (1953); Chem. A b s t r . , 48, 1936 (1954).
5. H. J. Hertog and J. P. Wibaut, Rec. T r a y . Chim., 55, 122 (1936); Chem. Abstr., 30, 4860 (1936).
6. S. M. MeElvain and M. A, Goese, J. A m e r . Chem. Soc., 63, 2283 (1941).
7. J. W. K l a r k - L e w i s and M. J. Thompson, J. A m e r . Chem. Soc., 444 (1954).
8. A. Roc and G. F. Hawkins, J. A m e r . Chem. Soc., 69, 2443 (1947).
9. H. J. Hertog, J. C. M. Schogt, J. de Bruyn, and A. de Klerk, Rec. T r a y . Chim., 69, 673 (1950); Chem.
Abstr., 44, 8919 (1950).
10. H. J. Hertog, Rec. T r a y . Chim., 64, 85 (1945); Chem. Abstr., 40, 3449 (1946).
11. K. T. Ports and S. Husain, J. Org. Chem., 35, No. 3 , 808 (1970).

690
SYNTHESIS OF METHYL-SUBSTITUTED BENZOFURO-,
BENZOTHIENO-, AND BENZOSELENOPHENO]2,3-b]PYRIDINES

P. I. Abramenko, V. G. Zhiryakov, UDC 547.836.07

L. A. Balykova, and T. K. Ponomareva

T h r e e - r i n g benzo [b]furan, benzo [b]selenophene, and benzo [b]thiophene s y s t e m s condensed

with a pyridine r i n g and having a m e t h y l group in the ~ position of the p y r i d i n e ring w e r e
synthesized.

In the p r e s e n t communication we d e s c r i b e the s y n t h e s i s of t r i n u c l e a r h e t e r o e y c l e s containing a p y r i d -

ine ring s t a r t i n g f r o m 2 - h y d r o x y - 3 - n i t r o - 4 - m e t h y l p y r i d i n e (D via the s c h e m e :

~ NO 2

OH
CH3

PCI5 -- ~ N O '
~-Nf "~Ci
C6HsXNa ~
?lls
NO2 -~SnClz
XCGH5
HCl

I II Ill

IV V
lll-Va X=O; b X=Se; c X=S

B a s e s V a - c f o r m q u a t e r n a r y s a l t s when they a r e heated with alkylating r e a g e n t s . The IR s p e c t r a of

V contain c h a r a c t e r i s t i c f r e q u e n c i e s of the s t r e t c h i n g v i b r a t i o n s of the pyridine ring, r e s p e c t i v e l y , at 3000-
3100 and 1555-1580 cm -1.

EXPERIMENTAL
The UV s p e c t r a of 0.0001 M alcohol solutions w e r e r e c o r d e d with an S F - 4 s p e e t r o p h o t o m e t e r . The
IR s p e c t r a of m i n e r a l oil suspensions w e r e obtained with a UR-10 s p e c t r o m e t e r (NaCI prism}.
2 - H y d r o x y - 3 - n i t r o - 4 - m e t h y l p y r i d i n e (I}. A 2.6-g (0.017 mole} s a m p l e of 2 - a m i n o - 3 - n i t r o - 4 - m e t h y l -
pyridine [1] was dissolved in a m i x t u r e of 36 m l of w a t e r and 2.5 m l of c o n c e n t r a t e d sulfuric acid, a f t e r
which 10 g of ice and a solution of 1.38 g (0.02 mole} of sodium nitrite in 4.72 m l of w a t e r w e r e added while
the m i x t u r e was cooled with ice. The m i x t u r e was s t i r r e d for 20 min, a f t e r which it was refluxed for 10
rain and cooled. The r e s u l t i n g p r e c i p i t a t e w a s r e m o v e d by filtration and r e e r y s t a l l i z e d f r o m w a t e r to give
200 g (77%} of light-brown needles with mp 223-224 ~ UV s p e c t r u m : h m a x 308 nm, log e 4.20. Found: N
18.0%. C6H6N203. Calculated: N 18.2%.
2 - C h l o r o - 3 - n i t r o - 4 - m e t h y l p y r i d i n e (II). In analogy with [2], a m i x t u r e of 2.7 g (17.5 mmole} of I, 0.98
g (4.7 mmole) of phosphorus pentachloride, and 0.49 g (3.2 mmole} of phosphorus oxychloride was heated at
110-120 ~ for 4 h, a f t e r which 0.46 g (2.2 mmole) of p h o s p h o r u s pentachloride was added, and the m i x t u r e
was heated for 2 h. The m i x t u r e was then cooled and washed with water, and the r e s i n o u s product was
s t e a m distilled. The solid m a t e r i a l was r e m o v e d by filtration, washed with water, and dried to give 2.3 g
(76.6%) of c o l o r l e s s needles ( f r o m p e t r o l e u m ether} with mp 47.5-48 ~ Found: C1 20.5%. C~HsC1N202.
Calculated: C1 20.6%.
All-Union State S c i e n t i f i c - R e s e a r c h and Design Institute, Photographic C h e m i c a l Industry, Moscow.
T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 6, pp. 796-797, June, 1974. Original a r t i c l e
s u b m i t t e d May 18, 1973.

9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

691
 2 - P h e n o x y - 3 - n i t r o - 4 - m e t h y l p y r i d i n e (IIIa). A 2.3-g (0.1 g - a t o m ) s a m p l e of sodium was dissolved in
40 m l of anhydrous ethanol, and 9.4 g (0.1 mole) of phenol and 17.2 g (0.1 mole) of II (in portions) w e r e added
s u c c e s s i v e l y with s t i r r i n g under nitrogen. The m i x t u r e was refluxed f o r 10-12 h, a f t e r which it was e v a p -
o r a t e d in vacuo, and the r e s i d u e was t r e a t e d with w a t e r . The m i x t u r e was m a d e alkaline with 5% sodium
hydroxide solution and e x t r a c t e d with e t h e r . The e x t r a c t was washed s u c c e s s i v e l y with 5% sodium hydroxide
solution and w a t e r and d r i e d with m a g n e s i u m sulfate. The e t h e r w a s r e m o v e d by distillation, and the r e s i -
due was v a c u u m distilled to give 13.4 g (58%) of a f r a c t i o n with bp 173-177 ~ (7 ram). The c o l o r l e s s p r i s m
( f r o m p e t r o l e u m ether) had mp 56-57 ~ UV s p e c t r u m : }'max 269 nm, log e 4.15. Found: N 12.0%.
CI2HIoN203. Calculated: N 12.1%.
2 - P h e n y l s e l e n o - 3 - n i t r o - 4 - m e t h y l p y r i d i n e (IIIb) [in 38% yield as a light-yellow oil, with mp 170-175 ~
(5 mm), that began to c r y s t a l l i z e on standing. Found: N 9.4%. C12HIoN202Se. Calculated: N 9.6%] and
2 - p h e n y l t h i o - 3 - n i t r o - 4 - m e t h y l p y r i d i n e (IIIc) [in 46% yield as a light-yellow oil, with bp 178-181 ~ (7 ram),
that began to c r y s t a l l i z e on standing. Found: N 11.1%. CI2I-IIoN202S. Calculated: N 11.3%] w e r e s i m i l a r l y
obtained.
2 - P h e n o x y - 3 - a m i n o - 4 - m e t h y l p y r i d i n e (IVa). A 60-g s a m p l e of stannous chloride was added with v i g -
orous s t i r r i n g at 45-47 ~ to a solution of 11.5 g (0.05 mole) of Ilia in 180 m l of c o n c e n t r a t e d h y d r o c h l o r i c
acid, a f t e r which the m i x t u r e was s t i r r e d at 45-47 ~ f o r 3 h. It w a s then cooled, m a d e alkaline with sodium
hydroxide solution while cooling with ice w a t e r , and e x t r a c t e d with c h l o r o f o r m . The e x t r a c t was washed
with 5% sodium hydroxide solution and w a t e r and dried with p o t a s s i u m c a r b o n a t e . The c h l o r o f o r m was r e -
m o v e d by distillation to give 9 g (90%) of c o l o r l e s s p r i s m s ( f r o m p e t r o l e u m ether) with mp 64-65 ~ UV
s p e c t r u m : )~max 244, 292 nm, log ~ 4.27, 4.22. Found: C 71.8; H 5.9; N 13.8%. Cl2I-Ii2N20. Calculated:
C 72.0; H 6.0; N 14.0%.
A s i m i l a r p r o c e d u r e was u s e d to obtain 2 - p h e n y l s e l e n o - 3 - a m i n o - 4 - m e t h y l p y r i d i n e (IVb) [in 86% yield
as light-yellow needles with mp 47-48 ~ Found: C 54.7; H 4.4; N 10.5%. C12H12N2Se. Calculated: C 54.9;
H 4.6; N 10.7%] and 2 - p h e n y l t h i o - 3 - a m i n o - 4 - m e t h y l p y r i d i n e (IVc) [in 88% yield as l i g h t - r o s e - c o l o r e d n e e d l e s
with mp 61-62 ~ Found: C 66.4; H 4.3; N 12.7%. C12H12N2S. Calculated: C 66.6; H 4.4; N 12.9%].
4-Methylbenzofuro[2,3-b]pyridine (Va). A solution of 4.6 g (0.066 mole) of sodium n i t r i t e in 20 ml of
w a t e r was added with s t i r r i n g in the c o u r s e of 10 min at 0-5 ~ to a solution of 6.0 g (0.03 mole) of IVa in 120
m l of 25% sulfuric acid. The m i x t u r e was held at 0-5 ~ f o r 1 h, a f t e r which it was filtered, and u r e a and 6 g
of copper powder w e r e added to the f i l t r a t e with s t i r r i n g u n d e r nitrogen in the c o u r s e of 3-5 rain. The m i x -
t u r e was s t i r r e d at r o o m t e m p e r a t u r e f o r 4 h, heated to the boiling point, cooled, and m a d e slightly alkaline
with dilute sodium hydroxide solution while cooling with ice w a t e r . The r e a c t i o n product was e x t r a c t e d
with ether, and the e x t r a c t was washed with 5% sodium hydroxide solution and w a t e r . It was then dried with
p o t a s s i u m carbonate, and the e t h e r was r e m o v e d b y d i s t i l l a t i o n . The residue was vacuum distilled to give
2.2 g (40%) of a product with bp 155-157 ~ (12 m m ) . The c o l o r l e s s p r i s m s ( f r o m p e t r o l e u m ether) had mp
82-83 ~ UV s p e c t r u m : k m a x 281 nm, log ~ 4.20. Found: C 78.5; H 4.8; N 7.4%. C~2H~NO. Calculated:
C 78.7; H 4.9; N 7.6%. The ethiodide was obtained as l i g h t - b r o w n p r i s m s ( f r o m anhydrous ethanol) with
m p 208-209 ~ Found: I 37.3%. C14H14INO. Calculated: I 37.5%.
A s i m i l a r p r o c e d u r e was u s e d to obtain 4 - m e t h y l b e n z o s e l e n o p h e n o [ 2 , 3 - b ] p y r i d i n e (Vb) [in 22% yield
as a light-yellow oil with bp 158-162 ~ (4-5 m m ) . Found: C 58.3; H 3.5; N 5.5%. C12HgNSe. Calculated:
C 58.5; H 3.6; N 5.7%] and 4-methylbenzothieno[2,3-b]pyridine (Vc) [in 31% yield as c o l o r l e s s plates with
rap 101-102 ~ UV s p e c t r u m : Xma x 231, 294 nm, log ~ 4.71, 4.47. Found: N 6.9%. C~2H~NS. Calculated:
N 7.0%]. The ethiodide was obtained as g r a y i s h p r i s m s with m p 216-217 ~ ( f r o m anhydrous ethanol, m p
216-217 ~ [3]).

LITERATURE CITED
Io O. Seide, Ber., _57, 791 (1924).
2. H. E. Baumgarten and H. Chien-Fan Su, J. Amer. Chem. Soc., 7__44,3828 (1952).
3. V. G. Zhiryakov and P. I. Abramenko, Khim. Geterotsikl. Soedin., 227 (1965).

692
INVESTIGATION OF NITROGEN- AND SULFUR-CONTAINING
HETEROCYCLES
XXX.* REACTION OF 2-MERCAPTO-3-UREIDO-6-CHLOROPYRIDINE
WITH PHENACYL HALIDES

L. G. Levkovskaya, V. V. Makeeva, UDC 547.822.5.7' 864

and T. S. Safonova

2 - M e r c a p t o - 3 - u r e i d o - 6 - c h l o r o p y r i d i n e r e a c t s with the ortho, m e t a , and p a r a d e r i v a t i v e s

of phenacyl halides to give 2 - p h e n a c y l t h i o - 3 - u r e i d o - 6 - c h l o r o p y r i d i n e s , which a r e r e a d i l y
c y c l i z e d to 6 - a r y l p y r i d o [ 2 , 3 - b ] [ 1 , 4 ] t h i a z i n e s r e g a r d l e s s of the p r e s e n c e o r a b s e n c e of a
substituent in the m e t a and p a r a positions of the benzene r i n g .

In o r d e r to s y n t h e s i z e 6 - a r y l p y r i d o [ 2 , 3 - b ] [1,4]thiazines f r o m 2 - m e r c a p t o - 3 - u r e i d o - 6 - c h l o r o p y r i d i n e
(I}, we investigated the r e a c t i o n of I with the ortho, m e t a , and p a r a d e r i v a t i v e s of phenacyl h a l i d e s . C o m -
pound I r e a c t s with o - e h l o r o - , o - b o r o m o - , o - i o d o - , o - m e t h y l - , o-, m - , and p - f l u o r o , and o , p - d i m e t h o x y -
phenacyl halides and b r o m o p h e n y l i s o p r o p y l ketone to give 2 - p h e n a c y l t h i o - 3 - u r e i d o - 6 - c h l o r o p y r i d i n e s (III-
XI, Table 1). In the p r e p a r a t i o n of IV and V, we a l s o isolated 6 - a r y l p y r i d o [ 2 , 3 - b ] [ 1 , 4 ] t h i a z i n e s (XII and
XIII}. Compounds HI and VI-X, which have a substituent in the ortho position of the benzene r i n g of the
c a r b o n y l f r a g m e n t of the molecule, do not change on standing in a i r and in solution and during r e c r y s t a l -
lization f r o m p o l a r solvents and f o r m h y d r a z o n e s XV and XVI. On the o t h e r hand, r e g a r d l e s s of the p r e s -
ence or a b s e n c e of a substituent in the m e t a and p a r a positions, IV, V and XI a r e unstable, and a r e cyclized
to 6 - a r y l p y r i d o t h i a z i n e s (XII-XIV} on standing in alcoholic alkali solutions or on heating with d i m e t h y l -
f o r m a m i d e (DMF). This p r o c e s s is a c c o m p a n i e d by facile splitting out of a u r e a r e s i d u e . Compounds III
and VI-X, in which the ortho substituent s t e r i c a l l y hinders the f o r m a t i o n of an N s - C 6 bond, a r e not c y c l i z e d
to 6 - a r y l p y r i d o t h i a z i n e s . A u r e a r e s i d u e is not split out in this c a s e even under m o r e s e v e r e conditions.

~ N HCONH2_...~ ~ N HCONH2 ~ ~f'NHCONH2

CI/ ~':NI ~SH CI/ ~<N/ ~'S--C(R)2COCsH4R' CI/ "~N/ ~'S--C(R)2--~--CsH4R,

N--N HC~H3(NO:~)2
I A III-XI XV-XVI
KOH

R
11 B XII-XIV

iII R=H, RI=o-F; IV R=H, R~=m-F; V R=H, R~=P=F; VI R=H, R1=o-Br; VII R=H,
RL=o-C1; VIII R=H, RI=o-CH3; IX R=H, R~=op-(CH30)2; X R=H, R~=o-I; XI R=CHa,
R~=H; XII R=H, Rl=rn-F; XIII R=H, R~=p-F; XIV R=CH3, R~=H; XV R=H, R~=o-F;
XVI R=H, Rl=o-Br
6 - A r y l p y r i d o t h i a z i n e s XIII and XIV w e r e a l s o s y n t h e s i z e d by r e a c t i o n of 2 - m e r c a p t o - 3 - a m i n o - 6 -
c h l o r o p y r i d i n e (II) with p - f l u o r o p h e n a c y l halide and b r o m o p h e n y l i s o p r o p y l ketone, r e s p e c t i v e l y .

*See [1] f o r communication XXIX.

S. Ordzhonikidze All-Union S c i e n t i f i c - R e s e a r c h P h a r m a c e u t i c a l C h e m i s t r y Institute, Moscow. T r a n s -

lated f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 6, pp. 798-800, June, 1974. Original a r t i c l e s u b -
m i t t e d D e c e m b e r 14, 1972; r e v i s i o n s u b m i t t e d D e c e m b e r 7, 1973.

9 1975Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, wl'thout written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

693
 T A B L E 1. C h a r a c t e r i s t i c s of the C o m p o u n d s Obtained

Corn- mp, ~ a
pound
Empirical
formula
I Found, %
f talc., qo

I ci N S '/ C H I C1 N
[
Ill 195--197 C~4HnCIFNsO~S 49,63,0 10,5 12,2 9,6 49,5 3,2 10,4 12,41 9,4 99
IV Z17--219 CI4HnCII~NaOzS 49,813,1 10,2 12,2 9,2 49,5 3,2 10,4 12,4 9,4 53
V 205--207 C,4HnCI~N30~S 49,8 2,9 10,4 12,4 9,7 49,5 3.2 110,4 12,4i 9,4 59
VI 205--207 C,4HnBrCINsOeS 42,0 3,0 28,7' 10,5 8,3 41,9 2,7 '28,8* 10,~ 8,0 88
VII 184--185 C,4HuCI~NaO2S 47,2 3,3 19,6 12,1 9,4 47,3 3,1 '19,7 11,8 9,0 75
VIII 190--192 C,sH,4CIN~O~S 53,8 4,2 10,4 12,3 9,6 53,6 4,2 10,6 12,5 9,5 85
IX 175--177 C,GH,sCINaO4S, 50,2 4,4 9,1 11,2 8,5 50,3 4,2 9,3 11,0 8,4 77
X 187--189 C14HnCIINsO2S~ 37,3 2,2 9,3 7,1 37,5 2,4 - - 9,4 7.1 84
XI 170--172 CIsHI6CIN,~O2S 54,7 4,4 1~ 11,8 9,4 54,9 4,6 I0,I 12,0 9,1 57
XII 152--154 C~3HsCIFN~S 56,4 3,0 - - 10,3 11,9 56,0 2,9 - - 10,C 1 1 , 5 34
XIII 142--144 C~aHsCIFN2S 55,8 3,1 - - 10,4 11,5 56,0 2,9 - - ]10,0 I 1 , 5 75
XIV 95--96 CIsHIaCIN2S 62,3 4,6 12,5 I0,0 11,3 62,4 4,5 12,3 I 9,7 I1,1 66
XV 225--227 C2oHIsCIFNTOs.S~46,3 3,2 6,7 18,8 6,8 46,2 2,9 6,8 [8,9 6,2 88
XVI 188--190 C2oH~sBrCIN~OsSL 4t,3 2,4i .~0,2 -- 5,9 41,3 2,6 19,9 -- 5,5 82

a C o m p o u n d s III, X-XIII, and XVI w e r e c r y s t a l l i z e d f r o m ethanol,

I V - I X and X V w e r e c r y s t a l l i z e d f r o m d i m e t h y l f o r m a m i d e - w a t e r
(1 : 2), and XIV was c r y s t a l l i z e d f r o m b e n z e n e , bFound: I 28.9%.
Calculated: I 2 8 . 4 % . CFound: B r + C 1 1 6 . 6 % . Calculated: B r + C 1
16.9%.

The s t r u c t u r e s of 2 - p h e n a c y l t h i o - 3 - u r e i d o p y r i d i n e s I I I - X I and 6 - a r y l p y r i d o t h i a z i n e s X I I - X I V w e r e
c o n f i r m e d by m e a n s of IR and P M R s p e c t r o s c o p y . T h e IR s p e c t r a of I I I - X I contain the a b s o r p t i o n bands
of ketone and a m i d e CO g r o u p s (1650-1690 c m -~) and NH and NH 2 g r o u p s (3450-3480, 3340-3360, and 3250-
3290 cm-1), which a r e a b s e n t in the s p e c t r a of X I I - X I V . A s i n g l e t f r o m the p r o t o n s of the CI] 2 group is o b -
s e r v e d in the PMR s p e c t r a of XII and XIII; this is in a g r e e m e n t with t h e i r 7H s t r u c t u r e .

EXPERIMENTAL
The IR s p e c t r a of m i n e r a l oil s u s p e n s i o n s of the c o m p o u n d s w e r e r e c o r d e d with a P e r k i n - E l m e r
s p e c t r o m e t e r . The UV s p e c t r a of a l c o h o l solutions w e r e r e c o r d e d with an E P S - 3 s p e c t r o p h o t o m e t e r . The
P M R s p e c t r a w e r e r e c o r d e d with a JNM 4H s p e c t r o m e t e r (100 MHz) with t e t r a m e t h y l s i l a n e as the i n t e r n a l
s t a n d a r d . The c o m p o u n d s w e r e c h r o m a t o g r a p h e d on Silufol UV-254 in b e n z e n e - n - h e p t a n e - e t h y l a c e t a t e -
ethanol ( 1 9 : 1 : 2 : 2 ) . T h e c h r o m a t o g r a m s w e r e d e v e l o p e d with c o n c e n t r a t e d H2SO4 and e x a m i n e d in U V l i g h t .
D a t a on I I I - X I V a r e p r e s e n t e d in T a b l e 1.
2 - F l u o r o p h e n a c y l t h i o - 3 - u r e i d o - 6 - c h l o r o p y r i d i n e (III). A solution of 0.8 g (4.8 m m o l e ) of a o - f l u o r o -
p h e n a c y l c h l o r i d e in 5 m l of ethanol w a s added at 1 8 - 2 0 ~ to a s o l u t i o n of 1.0 g (4.8 m m o l e ) of I in 15 ml of
ethanol c o n t a i n i n g 0.3 g (4.9 m m o l e ) of KOH, and the m i x t u r e w a s s t i r r e d f o r 3 h. The r e s u l t i n g p r e c i p i t a t e
w a s r e m o v e d by filtration, w a s h e d s u c c e s s i v e l y with w a t e r and p e t r o l e u m e t h e r , and d r i e d to give 1.44 g
of c o l o r l e s s c r y s t a l s . P M R s p e c t r u m in CsDsN: 4.71 p p m (2H, CH2).
C o m p o u n d s X and XI w e r e s i m i l a r l y obtained. P M R s p e c t r u m of XI in C D C 1 3 : 1 . 5 8 p p m (6H, two CH 3
groups).

4 - F l u o r o p h e n a c y l t h i o - 3 - u r e i d o - 6 - c h l o r o p y r i d i n e (V) and 2 - C h l o r o - 6 - ( 4 - f l u o r o p h e n y l ) - 7 H - p y r i d o - [ 2 , 3 -
b][1,4]thiazine (XIID. The m e t h o d u s e d to p r e p a r e c o m p o u n d III w a s u s e d to obtain t h e s e c o m p o u n d s f r o m
1.5 g (7.3 m m o l e ) of I and 1.2 g (6.8 m m o l e ) of 4 - f l u o r o p h e n a c y l c h l o r i d e . The r e a c t i o n w a s c a r r i e d out at
- 5 to - 1 0 ~ and t h e y i e l d of c o l o r l e s s c r y s t a l s of V with R f 0.09 w a s 1.47 g (59%). The f i l t r a t e r e m a i n i n g
a f t e r s e p a r a t i o n of V was p o u r e d into w a t e r , and t h e r e s u k m g p r e c i p i t a t e w a s r e m o v e d b y filtration, w a s h e d
s u c c e s s i v e l y with w a t e r and p e t r o l e u m e t h e r , and d r i e d to give 0.51 g of l i g h t - y e l l o w n e e d l e s of XIII (25%).
PMR s p e c t r u m in C D C 1 3 : 4 . 0 2 p p m (2H, 7-CH2).
The method u s e d to p r e p a r e V w a s u s e d to s y n t h e s i z e IV and VI-IX. In the p r e p a r a t i o n of IV, p y r i d o -
t h i a z i n e XII was additionally i s o l a t e d f r o m t h e f i l t r a t e . P M R s p e c t r a : 3.18 p p m (2H, CI-I2) f o r VI in CDC13,
2.43 p p m (3H, CH3) f o r VIII in CsDsN , and 4.65 p p m (2H, CIt2).
2 7 C h l o r o - 6 - ( 4 - f l u o r o p h e n y l ) - 7 H - p y r i d o [ 2 , 3 - b ] [1,4]thiazine ( x n I ) , A) A m i x t u r e of 0.3 g (0.88 m m o l e )
of V in 6 m l of d i m e t h y l f o r m a m i d e and 1.5 m l of w a t e r was r e f l u x e d f o r 3 - 5 h, a f t e r which 10-15 m l of w a t e r
w a s added, and the r e s u l t i n g p r e c i p i t a t e was r e m o v e d b y f i l t r a t i o n , w a s h e d with w a t e r , and d r i e d to give
0.18 g (75%) of light-yellow n e e d l e s of XIII with m p 142-144 ~

694
 B) A solutiDn of 1.0 g (5.9 mmole) of 4-fluorophenacyl chloride in 10 ml of methanol was added to a
solution of 1.0 g (6 mmole) of 1I in 15 ml of methanol containing 0.36 g (6 mmole) of KOH, and the mixture
was s t i r r e d at 18-20 ~ for 3-5 h and then allowed to stand for 12 h. The resulting p r e c i p i t a t e was r e m o v e d
by filtration, washed s u c c e s s i v e l y with w a t e r and p e t r o l e u m ether, and dried to give 1.1 g (63%) of XIII with
mp 142-144 ~and Rf 0.55 (yellow spot). The IR s p e c t r a and c h r o m a t o g r a m s of the substances obtained by
methods A and B w e r e identical.
2 - C h l o r o - 6 - p h e n y l - 7 , 7 - d i m c t h y l p y r i d o [ 2 , 3 - b ] [ 1 , 4 ] t h i a z i n e (XIV). A) The method used to p r e p a r e XIII
(method A) was used to obtain 0.47 g of light-yellow c r y s t a l s of this compound.
B) A solution of 0.5 g (3 mmole) of II containing 0.18 g (3 mmole) of KOH was added to a solution of
0.6 g (2.6 mmole) of bromophenyl isopropyl ketone in 10 ml of methanol, and the solution was then s t i r r e d
at 60 ~ for 3 h, cooled, and filtered. The filtrate was vacuum evaporated to one t h i r d of its original volume,
and 15-20 ml of w a t e r was added. The resulting p r e c i p i t a t e was r e m o v e d by filtration and worked up as in-
dicated for XIII (method B) to give 0.59 g (66%) of a product with Rf 0.88. PMR s p e c t r u m in CDC13:1.52
ppm (6H, two CH 3 groups).
2,4-Dinitrophenylhydrazones XV and XVI. T h e s e compounds were obtained as yellow c r y s t a l s . IR
s p e c t r u m of XV: 3500, 3240-3340 cm -1 (NH, NI-I2), 1650 cm - I (amide CO). IR s p e c t r u m of XVI: 3460, 3280-
3350 cm -1 (NH, NH2), 1680 cm -1 (amide CO); UV spectrum, Xmax, nm (log e): 260 (4:18), 361 (4.16).

LITERATURE CITED
1. N. V. Sazonov andToSo Safouova, Khimo Geterotsikl. Soedin., 1694 (1973).

695
OPTICAL AND PHOTOCHEMICAL PROPERTIES
OF N-BENZALAMINOPHENYLP YRIDINIU M
PERCHLORATES

Yu. P. Andreichikov, M. I . K n y a z h a n s k i i , UDC 547.828 : 535.37 : 543.422.6

Ya. R. Tymyanskli, G. E. Trukhan,
and G. N. Dorofeenko

The e l e c t r o n i c s p e c t r a of a n u m b e r of benzylidene d e r i v a t i v e s of N - a m i n o a r y l p y r i d i n i u m
p e r c h l o r a t e s a r e a s s o c i a t e d with a b s o r p t i o n l o c a l i z e d on the individual p y r i d i n i u m a n d a z o -
methine f r a g m e n t s and with intramolecala~- c h a r g e t r a n s f e r (ICT) f r o m the azomethine f r a g -
ment to the p y r i d i n i u m ring. The l u m i n e s c e n c e is a s s o c i a t e d with the l a t t e r p r o c e s s . The
p h o t o c h r o m i s m is due to proton t r a n s f e r in the excited s t a t e of the azomethine f r a g m e n t ,
which c o m p e t e s with ICT, and is also due to s t r u c t u r a l f a c t o r s .

It has been d e m o n s t r a t e d [1] that the p h o t o c h r o m i s m and l u m i n e s c e n c e p r o p e r t i e s of o - h y d r o x y a z o -

methines a r e a s s o c i a t e d with s p e c i f i c r e d i s t r i b u t i o n of the e l e c t r o n dens[ty in the excited s t a t e of the m o l -
ecule, which leads to the f o r m a t i o n of an i n t e r m e d i a t e ionic f o r m . An investigation of s y s t e m s in which
c h a r g e t r a n s f e r is r e g u l a t e d by both e l e c t r o n i c and s t e r i c f a c t o r s t h e r e f o r e s e e m s of interest.

600 ~oo~o ~o ~ o , 30o. . . . ~,o ~,.%.~o-~

T;' i
-45

-4O

-35
I 30
9 I -

25

,,//',/! \ \ / 2O
5
4~ , ' , ,.J ~//"
, _._Y! \ '.-<.
l ". /
.4
, [~/ ~. /" 9 15
i

-I0
/ 2~1i x x . . /
i 5
/
I I p ( i i , i ~ 9 i
t6 18 20 22 24 26 28 3 0 32 3 4 36 38 4 0 v - t 0 - ' 31:c!-1

Fig. 1. S p e c t r a of III: 1 and 4) a b s o r p t i o n and l u m i n -

e s c e n c e (300~ 2) a b s o r p t i o n of the model compound,
2 , 4 , 6 - t r i p h e n y l p y r i d i n i u m p e r c h l o r a t e ; 3) f l u o r e s c e n c e
excitation (300~ 5 and 6) l u m i n e s c e n c e and f l u o r e s -
cence (77~

Rostov State University. S c i e n t i f i c - R e s e a r c h Institute of P h y s i c a l and Organic C h e m i s t r y , R o s t o v -

on-Don. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 6, pp. 801-804, June, 1974. O r i g -
inal a r t i c l e s u b m i t t e d July 2, 1973.

9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication nuzy be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is availablefrom the publisher for $15.00.

696
 500 450 400 350 300 250 ~,,nm
, i : : ~ 8 . 1~0-

40

35

,,/I y \// 1
~i o,,
\ 125
,20,
I .Vi 'q '~,
915.

-.10

s -~.,o-

Fig. 2. Spectra of VI: 1 and 3)~bsorptiun and

luminescence (300~ 2) fluorescence excita-
tion (300~ 4 and 5) luminescence and phos-
phorescence (77~

~J

[-.
.~44 44~r4u'~

.~. .9
Fig. 3. Kinetics of the photochromic
o zzs s163163163163 process in acetone solution (c 1.6-
g(s gs163163163 10 -4 mole/liter at 77~K); decrease in
o c~c 6#88C~ .m the integral intensity of the l u m i n e s -
# cence in: 1) 111, 2) I, and 3) II.
9 0
r~
r
0 In our preceding communications [2, 3] we described the
synthesis of N-aminoarylpyridiaium perchlorates and their p - n i -
r~ ~m trobenzylidene derivatives. The electron-aeeeptor properties of
2 the pyridinium ring [3] and the three-dimensional structure [4, 5]
r~ ~mm ~m~mzz
of similar compounds make it possible to use them as models for
the above-indicated purposes.
g ooo ~moomo
A s e r i e s of new azomethines - N-am[nophenylpyridinium
0
r.) perchlorates (see Table 1) - w e r e synthesized, and their e l e c -
j~,=z ,-,,
tronic absorption and luminescence spectra and photochemical
properties were investigated.
M
Ri

C~H
,o s,.//
~ - - ~',.~v'~ / ~
N=c"~/ \>

C6Hs~C6HS

697
 On the b a s i s of the r e s u l t s of an investigation of the a b s o r p t i o n s p e c t r a of a model compound (2,4,6-
t r t p h e n y l p y r i d t n i u m p e r c h l o r a t e ) and the available data on the s p e c t r a of a z o m e t h i n e s [6], we e s t a b l i s h e d
that the band at 310-320 a m in the UV s p e c t r a of the i n v e s t i g a t e d compounds is an a p p r o x i m a t e s u p e r i m p o -
sition of the a b s o r p t i o n bands that a r e p r i m a r i l y l o c a l i z e d on the p y r i d t n t u m and azomethine f r a g m e n t s .
However, the excitation s p e c t r a indicate that the o b s e r v e d l u m i n e s c e n c e (Table 1) is a s s o c i a t e d with
the long-wave a b s o r p t i o n band at 400-440 n m (Fig. 2). This band is the m o s t intense when R I = O H and R 2 =
H, while for the r e s t of the compounds it has low extinction but is displayed distinctly in the f l u o r e s c e n c e
excitation s p e c t r a (Fig. 2). When the ~ - p h e n y l substituents in the pyrtdine r i n g a r e r e p l a c e d b y methyl
groups, this a b s o r p t i o n band and the c o r r e s p o n d i n g f l u o r e s c e n c e d i s a p p e a r . At the s a m e t i m e , the introduc-
tion of an N(CH3) 2 group into the a r o m a t i c r i n g c a u s e s a substantial b a t h o c h r o m i c shift of the a b s o r p t i o n
band and the c o r r e s p o n d i n g f l u o r e s c e n c e (Table 1).
The compounds that we investigated, which a r e models of the individual p y r t d i n t u m and azomethine
f r a g m e n t s of the molecule, do not display long-wave a b s o r p t i o n and the c o r r e s p o n d i n g f l u o r e s c e n c e . On the
b a s i s of the r e s u l t s obtained, we r e l a t e d the indicated a b s o r p t i o n and l u m i n e s c e n c e to i n t r a m o l e c u l a r c h a r g e
t r a n s f e r (ICT) with s u b s t a n t i a l p a r t i c i p a t i o n of the i n t e r a c t i o n of the N-phenyl and ~ - p h e n y l groups, a p p a r -
ently as a r e s u l t of twisting v i b r a t i o n s . The p h o s p h o r e s c e n c e (v 19,000 c m -I) o b s e r v e d at 77~ is a p p a r -
ently a s s o c i a t e d with both the t r i p l e t state of the ICT and with the t r i p l e t of the azomethine f r a g m e n t [7].
P h o t o c h r o m i s m a s s o c i a t e d with p h o t o t r a n s f e r of a p r o t o n f r o m oxygen to nitrogen and a c c o m p a n i e d
by a d e c r e a s e in the integral intensity of the l u m i n e s c e n c e (Fig. 3} and the a p p e a r a n c e of a v i s u a l l y o b s e r v -
able color is o b s e r v e d for all of the a z o m e t h t n e s with R I = O H at 77~ in solution. Competition between ICT
and s t e r t c f a c t o r s , on the one hand, and competition between the f o r m a t i o n of an i n t e r m e d i a t e anionic f o r m
of the azomethine f r a g m e n t with subsequent addition of a proton to nitrogen, on the other, play a substantial
r o l e in this phenomenon. In fact, the r a t e of the p h o t o r e a c t i o n d e c r e a s e s in the s e r i e s of m e t a - , o r t h o - , and
p a r a - s u b s t i t u t e d p y r t d t n t u m p e r c h l o r a t e s (RI=OH).
The r e s u l t s of a m o r e detailed study of the s p e c t r a l and p h o t o c h e m i c a l p r o p e r t i e s of the azomethine
d e r i v a t i v e s of p y r i d i n i u m s a l t s will be p r e s e n t e d in our next communication.

EXPERIMENTAL
The UV s p e c t r a of methylene chloride solutions (~ 10 -5 m o l e / l i t e r ) was r e c o r d e d with an S F - 4 a s p e c -
t r o p h o t o m e t e r . The absorption, l u m i n e s c e n c e (fluorescence and p h o s p h o r e s c e n c e ) , and l u m i n e s c e n c e e x -
citation s p e c t r a w e r e r e c o r d e d with an ISP-51 s p e c t r o g r a p h with an FI~P-1 e l e c t r o n i c a d a p t e r and an S F - 4
s p e c t r o p h o t o m e t e r with special a d a p t e r s f r o m methylene chloride solutions at 293 and 77~ The IR s p e c -
t r a of m i n e r a l - o i l s u s p e n s i o n s w e r e r e c o r d e d with a UR-20 s p e c t r o m e t e r .
The N - b e n z a l s m i n o p h e n y l p y r i d i n i u m p e r c h l o r a t e s w e r e obtained by refluxing e q u i m o l a r m i x t u r e s
of the amine and the a p p r o p r i a t e benzaldehyde in ethanol for 1 ho Cooling of these solutions p r e c i p -
itated yellow p r i s m s , which w e r e c r y s t a l l i z e d f r o m ethanol. The physical constants of the compounds ob-
tained a r e p r e s e n t e d in Table 1. IR s p e c t r a : 1570, 1640 c m - I (pyrtdinium ring}; the a b s o r p t i o n band of the
N =CH group is o b s e r v e d as an inflection on the a b s o r p t i o n band o f the p y r i d i n t u m ring.

LITERATURE CITED
1. M. I. Knyazhanskii, M. B. Stryukov, V. I. Mtnkin, A. E. L y u b a r s k a y a , and L. P. Olekhnovich, Izv.
Akad. Nauk SSSR, Set. F i z . , No. 5, 1102 (1972).
2. G. N. D o r o f e e n k o , Y u . P. Andreichtkov, and G. E. Trukhan, Khim. G e t e r o t s t k l . Soedin. (1974, in
press}.
3. G. N. Dorofeenko, Yu. P. Andretchikov, E. A. Zvezedina, V. A. B r e n ' , G. E. Trukhan, V. V. Derbenev,
and L. N. Popova, Khtm. G e t e r o t s t k l . Soedin. (1974, in press}.
4. A. C a m e r m a n , L. H. Jensen, and A. T. Balaban, A c t a C r y s t . , 25, 2623 (1969}.
5. C. T o m a and A. T. Balabaa, T e t r a h e d r o n , 22, Suppl. 7, 9 (1966).
6. B. M. K r a s o v i t s k i i , N. F. Levchenko, N. N. M a l ' t s e v a , A. N. N a z a r e n k o , V. B. Smelyakova, and L. Sh.
Afanasiadi, in: A z o m e t h i n e s [in R u s s i a n ] , Izd. Rostovsk. Univ. (1967), p. 21.
7. M. I. Kuyazhanskii, M. B. Stryukov, and V. I. Mink[n, Opttka i Spektroskopiya, 3.3 , 879 (1972}.

698
NITRO DERIVATIVES OF 3-HYDROXYQUINOLINE

K. M. D y u m a e v , E. P. Popova, UDC 547.831.7 : 542.958.1

I. F. Mikhailova, L. I. Shibaeva,
a n d L . D. S m i r n o v

The nitration of 3-hydroxyquinoline with c o n c e n t r a t e d nitric acid in sulfuric acid at - 3 0 to

+30~ gives 5 - n i t r o - 3 - h y d r o x y q u i n o l i n e (85-92%) and 7 - n i t r o - 3 - h y d r o x y q u i n o l i n e (7-12%).
4 - N i t r o - 3 - h y d r o x y q u i n o l i n e is f o r m e d in 70% yield b y nitration in a c e t i c acid. 4 , 5 - D i n i t r o -
3-hydroxyquinoline is f o r m e d by f u r t h e r nitration of 4- and 5 - n i t r o - 3 - h y d r o x y q u i n o l i n e s .

It is known that a mixture of 5- and 8-nitroquinolines is f o r m e d by nitration of quinoline in sulfuric

acid [1]. The introduction of a hydroxyl group into the pyridine r i n g in the 2 or 4 position leads to nitration
in the 6 and 8 positions under the s a m e conditions, while the f o r m a t i o n of 3 - n i t r o - 2 - ( o r 4)hydroxyquinoline
is o b s e r v e d in nitration with c o n c e n t r a t e d nitric acid [2].
The nitration of 3-hydroxyqulnoline fI) has not been studied. Only 6- and 8 - n i t r o - 3 - h y d r o x y q u i n o l i n e s ,
which w e r e obtained as side products in low yields b y oxidation of the c o r r e s p o n d i n g nitroquinolines with
hydrogen peroxide, have been d e s c r i b e d in the l i t e r a t u r e [3-5].
We have studied the nitration of I under v a r i o u s conditions. When the nitration was c a r r i e d out with
an e q u i m o l e c u l a r amount of c o n c e n t r a t e d nitric acid in sulfuric acid at 0~ 5 - n i t r o - 3 - h y d r o x y q u i n o l i n e (II)
(85-92%), 7 - n i t r o - 3 - h y d r o x y q u i n o l i n e (III) (7-12%), and t r a c e s of 4 - n i t r o - 3 - h y d r o x y q u i n o l i n e (IV) a r e
formed.
NO2 NO;

~ OH a. H2SO4; HNO3; 0c

b.CH3COOH;tiNO3; 50 ~
11 III IV

a. 85-920/0 a. 7 - 1 2 % a.traces

b. 0% b. traces b. ~ 70%

Changing the nitration t e m p e r a t u r e f r o m - 3 0 to +30 ~ does not substantially change the r a t i o of the n i t r o
i s o m e r s and does not lead to the f o r m a t i o n of new compounds.
The s t r u c t u r e s of nitro d e r i v a t i v e s II and IlI w e r e p r o v e d by oxidative cleavage and w e r e c o n f i r m e d
by the PIVIR s p e c t r a , m - N i t r o a n i l i n e , the product of the decomposition of the r e s u l t i n g 6 - n i t r o a n t b r a n i l i c
acid [6], was isolated in the oxidation of nitro d e r i v a t i v e II with p o t a s s i u m p e r m a n g a n a t e in alkaline media.
The oxidation of i s o m e r s HI under s i m i l a r conditions gave 4 - n i t r o a n t h r a n i l i e acid.
In the nitration of I with c o n c e n t r a t e d nitric acid in acetic acid we isolated only 4 - n i t r o d e r i v a t i v e IV.
The b e s t r e s u l t s (70% yield) w e r e obtained by heating nitrate I in acetic acid at 50-60 ~ The s t r u c t u r e of IV
was p r o v e d by reduction to amino d e r i v a t i v e V and subsequent diazotization and r e p l a c e m e n t of the diazo
group by chlorine to give the known 4 - c M o r o - 3 - h y d r o x y q u i n o l i n e (VI).
4 , 5 - D i n i t r o - 3 - h y d r o x y q u i n o l i n e (VII) is f o r m e d by further nitration of i s o m e r II in acetic acid or by
nitration of IV in sulfuric acid. The r e s u l t s d e m o n s t r a t e that the position of the e n t e r i n g nitro group is
d e t e r m i n e d mainly by the orientation of the hydroxyl group. According to the data in [7-9], in sulfuric acid

S c i e n t i f i c - R e s e a r c h Institute of Organic I n t e r m e d i a t e s and Dyes, Moscow. T r a n s l a t e d f r o m Khimiya

G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 6, pp. 805-808, June, 1974. Original a r t i c l e s u b m i t t e d March 15, 1973.

9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, N.Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy of this article is availablefrom the publisher for $15.00.

699
 B
A , - -
c D

%~oH

~4D H ~

HB i< 1179~ 2~O2~ 2~38g ;ZSOHZ

Fig. I. P M R spectra of 5-nitro-3-hydroxyquinoline (If)and

7-nitro-3-hydroxyquinoline (Ill) (with hexamethyldis[loxane as
the internal standard).

quinoline is n i t r a t e d as the quinolinium ion. It m a y be a s s u m e d that this is also valid for 3 - h y d r o x y q u i n -

oltne I: the nitration is r e a l i z e d e x c l u s i v e l y in the benzene r i n g in Conformity with the directing effect of
the hydroxyl goup. In acetic acid, at l e a s t a portion of 3-hydroxyquinoline I m a y be p r e s e n t in the m o l e c -
ular f o r m and m a y be n i t r a t e d in the m o s t active (4) position [10].
The PMR s p e c t r a of II and III a r e p r e s e n t e d in Fig. 1. Signal A in the s p e c t r u m of II is affiliated
with H2, while signal C is affiliated with H 4 [5]. The additional doublet splitting of signal C m a y be due to
coupling of H 4 and H 8 [11]. Signal D is affiliated with H 7 and shows that the nitro group is in the 5 position
when the 8 position is free. The l e f t - h a n d portion of signal B c o r r e s p o n d s to proton H6, and the r i g h t - h a n d
portion of signal B (B') is affiliated with H s.
An investigation of the s p e c t r u m of III d e m o n s t r a t e d that two i s o m e r s with a nitro group in the 6 or 7
position may c o r r e s p o n d to this s p e c t r u m . The p r e s e n c e of s p i n - s p i n coupling between the B and E p r o -
tons makes it possible to favor the 7-nitro i s o m e r .

EXPERIMENTAL
The UV s p e c t r a of solution of the compounds in a l c o h o l - a m m o n i a (49 : 1) w e r e r e c o r d e d with an S F - 8
s p e c t r o p h o t o m e t e r . The PMR s p e c t r a of d e u t e r a t e d dimethyl salfoxide solutions w e r e r e c o r d e d w i t h a V a r -
ianHA-100 s p e c t r o m e t e r at 250 Hz. The c h r o m a t o g r a p h s w e r e obtained on S[lufol UV-254 plates (dioxane,
a m m o n i a vapors).
5 - N i t r o - 3 - h y d r o x y q u i n o l i n e (II) and 7-Nitro-3-hydroxyquinolhue (III). A 3 . 3 6 - m l (0.04 mole) s a m p l e
of HNO 3 (sp. gr. 1.35) was added to 5.8 g (0.04 mole) of I in 40 ml of c o n c e n t r a t e d H2SO4, and the m i x t u r e
was s t i r r e d at 0~ for 1 h, a f t e r which it was poured o v e r ice. Four compounds in the following o r d e r of de-
c r e a s i n g Rff. values on the c h r o m a t o g r a m w e r e detected in the r e a c t i o n mixture- t r a c e s of I (blue l u m i n e s -
cence in u v light), II and III (yellow l u m i n e s c e n c e ) , and t r a c e s of IV. The p r e c i p i t a t e was r e m o v e d by fil-
t r a t i o n and washed to n e u t r a l i t y with ice w a t e r to give 5.8 g (76.3%) of ]I with mp 230.5 ~ ( f r o m 50% C2H5OH).
Alkylation of the acidic f i l t r a t e to pH 2-3 with c o n c e n t r a t e d a m m o n i u m hydroxide yielded 1.63 g (21.4%) of
a m i x t u r e of II and III with t r a c e s of IV. Another 0.13 g (1.7%) of the s a m e mixture of i s o m e r s was e x t r a c -
ted f r o m the f i l t r a t e with butanol. A 1.76-g s a m p l e of the m i x t u r e was t r e a t e d with dioxane and filtered to
give 0.54 g (7.170) of III with mp 249.7 ~ ( f r o m aqueous alcohol). The f i l t r a t e was e v a p o r a t e d to d r y n e s s , and
c h r o m a t o g r a p h i c c o m p a r i s o n e s t a b l i s h e d that the r e s i d u e contained 0.9 g of II (overall yield 88.2%) and 0,3
g of III (overall yield 11.2%). UV s p e c t r u m , Amax, n m (log e) II. 240 (4.40), 435 (3.75); III: 230 (4.44),
295 (3.73), 410 (4.21). Found for II: C 56.5; H 3.2; N 14.9%. F o r III-. C 56.8; H 3.2; N 14.7%. CgHGN203.
Calculated. C 56.8; H 3.2; N 14.7%.
The oxidation of 0.57 g (0.003 mole) of II in a solution of 0.2 g of KOH and 1 . 2 6 g ( 0 . 0 0 8 m o l e ) ofKMnO 4
in 130 m l of w a t e r at 0 ~ gave 0.17 g of m - n i t r o a n i l i n e .

700
 4 - N i t r o a n t h r a n i l i c acid [12] was isolated f r o m the oxidation of HI under s i m i l a r conditions with sub-
sequent alkaline h y d r o l y s i s of the r e s u l t i n g oxalylanthranilic acid.
4 - N i t r o - 3 - h y d r o x y q u i n o l i n e (IV). A 1.4-ml (0.03 mole) s a m p l e of c o n c e n t r a t e d HNO 3 was added to
4.35 g (0.03 mole) of I in 110 ml of glacial CH3COOH, and the p r e c i p i t a t e d I was r e m o v e d by filtration and
dried to give 6.14 g (98%) of product. All of this product was dissolved in 100 ml of CH3COOH, and the s o l u -
tion was held at 50-60 ~ for 10-15 rain. Yellow c r y s t a l s of IV [2.96 g (52%)] p r e c i p i t a t e d f r o m the cooled s o -
lution. A total of 1.18 g of unchanged I was isolated f r o m the filtrate by c h r o m a t o g r a p h y with a column filled
with silica gel (elution with a m m o n i a c a l dioxane). The yield of IV, with mp 187.5-187.9 ~ (from aqueous
C2H~OH) , b a s e d on the c o n v e r t e d I was 69.8%. UV s p e c t r u m , ~ m a x , n m (log s 235 (4.43), 345 (3.48), 420
(3.55). Found: C 57.0; H 3.2; N 14.7%. C9H6N203. Calculated: C 56.8; H 3.2; N 14.7%.
4 - A m i n o - 3 - h y d r o x y q u i n o l i n e (V). A 0.6-ml (78 mmole) s a m p l e of h y d r a z i n e hydrate and 0.02 g of
Raney nickel in d i m e t h y l f o r m a m i d e (DMF) w e r e added to a solution of 0.5 g (0.026 mole) of IV In DMF. A f -
t e r 15-20 min the r e a c t i o n mixture was f i l t e r e d , the solvent was e v a p o r a t e d to d r y n e s s , and the r e s i d u e was
r e c r y s t a l l i z e d f r o m w a t e r to give 0.35 g (85.3%) of V with mp 119.7 ~ Found: N 14.7%. CgHsN20. Calculated:
N 14.7%. The N,O-dibenzoyl d e r i v a t i v e of V had mp 197.4-197.8 ~ ( f r o m methanol). Found: C 75.1; H 4.3;
N 7.7%. C23HI6N203. Calculated: C 75.0; H 4.4; N 7.6%.
4-Chloro-3-hydroxyquinoline (VI). A 0.1-g (1.5 mmole) sample of NaNO2 was added to 0.22 g (1.5
mmole) of V in 1.5 ml of concentrated HC1, after which the mixture was held at 20~ for 1 h and then stirred
at 60-70~for 2 h. The solution was neutralized with 2 N NaOH, and the precipitate was removed by filtra-
tion, dried, and suspended in dioxane. The insoluble portion was removed by filtration and reerystallized
from water to give 0.1 g (40%) of VI with mp 202.4~ No melting-point depression was observed for a mix-
tare of this product with a known sample obtained by the method in [13].
4,5-Dinitro-3-hydroxyquinoline (VII). A) A 0.38-g (2 mmole) sample of II was dissolved in 15 ml of
CH3COOH, and the solution was cooled and treated with 0.1 ml (2 mmole) of concentrated HNO3. The pre-
cipitated II was removed by filtration, dried, and heated with stirring in 20 ml of CH3COOH for 15-20 rain.
Cooling gave 0.13 g (26%) of crystals of VII with mp 190~ (from alcohol).
B) A 2-ml sample of HNO3 (sp. gr. 1.5) was added a t - 15~to 0.38 g (2 mmole) of IV in 3 .ml of concen-
trated H2SO4. After 1 h, the m i x t u r e was poured o v e r ice, and the r e s u l t i n g p r e c i p i t a t e was r e m o v e d by fil-
tration, washed to n e u t r a l i t y , and dried to give 0.17 g (38%) of VII with mp 189.3 ~ (from alcohol). No m e l t -
ing-point d e p r e s s i o n was o b s e r v e d for a mixture of s a m p l e s of compounds obtained by methods A and B.
Found: C 46.2; H 2.2; N 17.8%. CgHsN3Os. Calculated: C 46.0; H 2.2; N 17.9%.

LITERATURE CITED
1. J . S . Dewar and P. M. Maltlis, J. Chem. Soc., 2521 (1957).
2. K. Schofield and T. Swain, J. Chem. Soc., 1367 (1949).
3. E. Ochial, C. Kaneko, T. Kosuge, S. Migashita, and C. Kawasaki, Chem. P h a r m . Bull., Tokyo, 8, 24
(1960).
4. H. yon Euler, H. Hasselquist, and D. Nomura, Ark. Kem[, 1._55,283 (1960).
5. T. NakasMma and J. Suzuki, Chem. Pharm. Bull., Tokyo, 1.~7, 2293 (1969).
6. R. Kahn, B e r . , 3863 (1903).
7. K. Schofield, D. M. G. Crout, and J. R. Penton, J. Chem. Soc., B, 1254 (1971).
8. M . W . Austin, M. B r i c k m a n , J. H. Ridd, and B. V. Smith, Chem. Ind., London, 1057 (1962).
9. M . W . Austin and J. H. Ridd, J. Chem. Soe., 4204 (1963).
10. I. Gyenes, T i t r a t i o n s in Nonaqueous Media, Van N o s t r a n d - R e i n h o l d (1968).
11. J. E m s l e y , J. Finuey, and L. Sutcliffe, High-Resolution Nuclear Magnetic R e s o n a n c e S p e c t r o s c o p y ,
P e r g a m o n (1966).
12. P. G r a m m a t i c a k i s , Compt. Rend., 1585 (1961).
13. L . L . Smirnov, N. A. Andronova, V. P. Lezina, V. E. L a t y s h e v , and K. M. Dyumaev, Izv. Akad. Nauk
SSSR, Ser. Khim., 456 (1971).

701
HYDROACRIDINES AND RELATED COMPOUNDS
XIV.* REDUCTIVE P R O P E R T I E S
OF SOME N-ARYLDECAHYDROACRIDINES

A . N. S a v e r c h e n k o , V. A . Kaminskii, UDC 547.835.2

a n d M. N . T i l i e h e n k o

S o m e N - a ~ y l d e c a h y d r o a c r i d i n e s reduce N = N, C = N, C =O, NO2, and acridine groups in

acidic media. In n e u t r a l media, N - a r y l d e c a h y d r o a c r i d i n e s a r e oxidized by chloranil and
polyhaloalkaneso

1,4-Dihydropyridine d e r i v a t i v e s with e l e c t r o n - a c c e p t o r substituents display r e d u c t i v e ability with

r e s p e c t to a n u m b e r of organic compounds [2, 3]. I n a s m u c h as s o m e N - s u b s t i t u t e d d e c a h y d r o a c r i d i n e s a r e
r e a d i l y a c c e s s i b l e [4] and contain a 1,4-dihydropyridine f r a g m e n t that does not have e l e c t r o n - a c c e p t o r s u b -
stituents, it s e e m e d of i n t e r e s t to d e t e r m i n e t h e i r r e d u c t i v e c a p a c i t i e s .
We used the following compounds as oxidizing agents; 1) compounds containing N =N, C =N, C =O, and
NO 2 groups, as well as acridine; 2) polyhaloalkanes and chloranil. A s t r o n g l y acidic m e d i u m (HC1) is n e c e s -
s a r y for the reduction of s u b s t a n c e s in the f i r s t group. The reduction h e r e p r o b a b l y p r o c e e d s via an "ionic
hydrogenation" s c h e m e [5], during which the d e c a h y d r o a c r i d i n e acts as a h y d r i d e - i o n donor. Two v a r i a n t s
of the r e a c t i o n w e r e investigated: a) with a twofold m o l a r e x c e s s of the oxidizing agent; the oxidation p r o d -
uct - N - a r y l - s y m - o c t a h y d r o a c r i d i n i u m ion - was isolated as the p e r c h l o r a t e ; b) with a twofold e x c e s s of the
d e c a h y d r o a c r i d i n e with identification of the p r o d u c t s of c o n v e r s i o n of the oxidizing agents.
Using azobenzene as the oxidizing agent, we c o m p a r e d the r e d u e t i v e c a p a c i t i e s of 9, 10-diphenyl-,
1 0 - ~ - n a p h t h y l - , 1 0 - ( p - c a r b o m e t h o x y p h e n y I ) - , and 9-phenyl- 10- ( p - c a r b o m e t h o x y p h e n y l ) d e c a h y d r o a c r idines
(Ia-d). Variant (a) was used for this r e a c t i o n . The yield of N - a r y l - s y m - o c t a h y d r o a c r i d i n i u m p e r c b l o r a t e s
(IIa-d) w e r e 91, 63, 35, and 74%, r e s p e c t i v e l y . Dihydropyridine Ia was the m o s t active and a c c e s s i b l e of the
compounds, and the r e s t of the oxidizing agents of the f i r s t group w e r e t h e r e f o r e r e d u c e d only with this r e -
agent.
I n a s m u c h as d i s p r o p o r t i o n a t i o n to d o d e c a h y d r e a e r i d i n e and s y m - o e t a h y d r o a c r i d i n i u m ion d e r i v a t i v e s
[6] m a y compete with the reduction, we set up blank e x p e r i m e n t s in the absence of the oxidizing agent. The
yield of p e r c h l o r a t e IIa in this case was 28-40%. Consequently, in c a r r y i n g out the r e a c t i o n via v a r i a n t a,
the r e s u l t s w e r e c o n s i d e r e d to be positive if the yield of Ha exceeded 50%. The r e s u l t s a r e p r e s e n t e d in
Table 1. F r o m the data in Table 1 it can be concluded that conditions C a r e m o r e f a v o r a b l e for the r e d u c -
tion.
R' RI

Ox ( " f " ~ II a-d X=CIO,I ; a R=R'=C6115;

L~/L~.I~I+[~,,.
~ + Red b R=c(-naphfllylR'=H;
l
R R X- C R= p-C6H4COOCH,~, R' = H;
I n d R=p-C6H4COOCH$, R,=C~Hs;
0 X~I, R=R'=C6H 5

*See [1] for c o m m u n i c a t i o n XIII.

F a x - E a s t e r n State University. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 6, pp.

809-811, June, 1974. Original a r t i c l e s u b m i t t e d April 5, 1973.

9 1975 PlenumPublishing Corporation, 227 West 17th Street, New York, N.Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy of this article is availablefrom the publisher for $13.00.

702
 TABLE 1. Yields of IIa, %
Oxidizing agent
Condi-
tions nitro- I m-nitro- p-nitro- azo- p-di- } ' I
benz- aniline aniline benz- merhyl- acridirle ~7nitroso benzal-
ene
_ , 1 ene ~amm~ ~
Den~- ~
].ald.eh~de~
~almethyl~
~nmne_ !
aniline

* Conditions A indicate r e a c t i o n in e t h a n o l - d i m e t h y l f o r m a m i d e
(DMF), conditions B indicate r e a c t i o n in absolute benzene, and
conditions C indicate r e a c t i o n in absolute DMF.

TABLE 2. Yields of P e r e h l o r a t e IIe, 70

Temp., *C Oxidizing agent
CHBrs CH~Br2 CH~I CH~Qh CHCI3 C2CI~

20 55 0 0
10O 28 60

TABLE 3. Hydroacridine Derivatives

Com- mp, ~ Empiri&l Yield,
pound formula %
C H N C H

lb 120--121 C~H2~N 87,3 8,3 4,6 ~ 7,9 4,4 70

Ic 118--I 19 C21H2sNO2 78,1 7,9 4,5 78,0 7,7 4,4 22
ld 103--104 C27H29NO~ 81,2 7,3 3,6 81,2 7,3 3,5 55
Ill 152--155 C2oHz~I4N 30.8 3,3 1,9 30,6 2,9 1,8 60
IV 162--164 IC21H2~I4NO~ 30,0 3,4 1,8 30,4 2,8 1,7 65

The r e a c t i o n via variant b was c a r r i e d out with benzalanfline under conditions B and with n i t r o b e n -
zene, azobenzene, and acridine under conditions C. The product of the reduction of azobenzene is benzidine
(60%), the product of the reduction of benzalaniline is benzylaniline (7670), and the product of the reduction
of acridine is a c r i d a n (8070); aniline was o b s e r v e d among the products of reduction of nitrobenzene.
The r e a c t i o n with oxidizing agents of the second group p r o c e e d s without the addition of acids. Thus,
chloranil intwofold excess amounts converts Ia to IIa in 9670 yield. It has been d e m o n s t r a t e d [7] that
N - a r y l d e c a h y d r o a c r i d i n e s are oxidized by carbon t e t r a c h l o r i d e . We examined the applicability of this r e -
action to other polyhaloalkanes and accomplished the r e a c t i o n of 2,2'-methylenedicyclohexanone with aniline
(which leads to Ie) in the p r e s e n c e of a number of polyhaloalkanes. The r e a c t i o n was c a r r i e d out in ether
at r o o m t e m p e r a t u r e or in refluxing benzene. Twofold e x c e s s quantities of the polyhaloalkanes w e r e used.
The oxidation product was isolated as p e r c b l o r a t e lie. The r e s u l t s are p r e s e n t e d in Table 2. The activity
i n c r e a s e s as the degree of halogenation i n c r e a s e s and also in the o r d e r C1 < Br < I. Iodoform, with which
the r e a c t i o n p r o c e e d s r a p i d l y even at r o o m t e m p e r a t u r e to give good yields of a 1 : 1 complex - N - p h e n y l -
s y m - o c t a h y d r o a c r i d i n i u m iodide (lie, X = I ) - i o d o f o r m 0II) - displays the g r e a t e s t activity. A s i m i l a r c o m -
plex (IV) was obtained by r e p l a c e m e n t of aniline by p - a m i n o b e n z o i c acid. Complex III decomposes into its
components on passage through A1203; complex III is f o r m e d again when the components a r e mixed.

III ~ I I d +CHI3

EXPERIMENTAL
Decahydroacridines I a - d w e r e obtained by the method in [4]. Compound Ia was p r e v i o u s l y d e s c r i b e d
in [4]. See Table 3 for data on Ib-d.
Oxidation of I by Reagents of the F i r s t Group. A) A 0.5-ml sample of c o n c e n t r a t e d HC1 (conditions A)
was added to a mixture of 1 mmole of I and 2 mmole of oxidizing agent in 10 ml of the solvent, or the s o l -
vent was s a t u r a t e d with HC1 in an argon a t m o s p h e r e (conditions B and C). The mixture was heated under
argon on a boilhng-water bath for 1.5-2 h, after which it was cooled, diluted with water, made alkaline to pH

703
9 with Na2CO3, and e x t r a c t e d with ether. A s a t u r a t e d NH4C104 solution was added to the aqueous l a y e r , and
p e r c h l o r a t e s I I a - d w e r e r e m o v e d by filtration.
B) A m i x t u r e of 2 m m o l e of Ia and 1 m m o l e of oxidizing agent in 10 ml of H C l - s a t u r a t e d solvent (ben-
zene for benzalaniline and DMF for the other oxidizing agents) was heated under a r g o n on a b o i l i n g - w a t e r
bath for 2 h, after which it was cooled. In the c a s e of a c r i d i n e , the c r y s t a l l i n e product that p r e c i p i t a t e d was
r e m o v e d by filtration, dried, and identified as a c r t d a n ( m i x e d - m e l t i n g - p o i n t d e t e r m i n a t i o n and IR s p e c t r a ) .
In the e a s e of azobenzene, the r e s u l t i n g p r e c i p i t a t e was r e m o v e d b y filtration, d i s s o l v e d in w a t e r , and made
alkaline with Na2CO 3. The benzidine c r y s t a l s w e r e r e m o v e d by filtration, r e c r y s t a l l i z e d f r o m w a t e r , and
identified by a m i x e d - m e l t i n g - p o i n t d e t e r m i n a t i o n and IR s p e c t r a . In the c a s e of benzalaniline, w a t e r was
added to the r e a c t i o n m i x t u r e , and the benzene l a y e r was s e p a r a t e d , e v a p o r a t e d to half its original volume,
and p a s s e d through a column filled with A1203 with elution initially with p e t r o l e u m e t h e r and then with ethyl
acetate. The ethyl acetate eluate was e v a p o r a t e d , the r e s i d u e was dissolved in e t h e r , and HC1 was p a s s e d
through the solution to give benzylaniline hydrochloride, which was identical to an authentic s a m p l e (accord-
ing to a m i x e d - m e l t i n g - p o i n t d e t e r m i n a t i o n and the IR s p e c t r a ) . In the c a s e of nitrobenzene, w a t e r was
added to the r e a c t i o n m i x t u r e , and the aqueous mixture was made alkaline to pH 9 with Na2CO 3 and e x t r a c t e d
with ether. Aniline was detected in the e x t r a c t by means of t h i n - l a y e r c h r o m a t o g r a p h y (TLC) [A1203, p e t r o l -
e u m e t h e r - e t h y l a c e t a t e (3 : 1), Rf 0.3] and by a qualitative r e a c t i o n (furfural +CtI3COOH).
Oxidation of Ia with Chloranil. The oxidation was c a r r i e d out as in method A in ethanol - DMF without
the addition of HC1.
Reaction of 2,2'-Methylenedicyclohexanone with Aniline in the P r e s e n c e of Polyhaloalkanes. A m i x -
t u r e of 10 m m o l e of the diketone, 10 m m o l e of aniline, and 20 m m o l e of polyhaloalkane in 30 ml of e t h e r was
held at r o o m t e m p e r a t u r e for 2 h or heated in 30 ml of benzene for 2 h on a b o i l i n g - w a t e r bath. The m i x -
t u r e was diluted with w a t e r , and the organic l a y e r was s e p a r a t e d . The aqueous l a y e r was e x t r a c t e d with
e t h e r , and the e x t r a c t was t r e a t e d with s a t u r a t e d NI-I4C104 solution. Salt IIe was r e m o v e d by filtration.
Reaction of 2,2'-Methylenedicyclohexanone with A m i n e s in the P r e s e n c e of Iodoform. A solution of
20 m m o l e of i o d o f o r m in 50 ml of ether was added to a solution of 10 m m o l e of diketone and 10 m m o l e of
aniline or p - a m i n o b e n z o i c acid in 50 ml of ether. A copious p r e c i p i t a t e f o r m e d i m m e d i a t e l y . The m i x t u r e
was then allowed to stand at r o o m t e m p e r a t u r e for 2 h, a f t e r which c o m p l e x HI o r IV was r e m o v e d by ill-
tration, washed with e t h e r , and r e c r y s t a l l i z e d f r o m methanol (Table 3).

LITERATURE CITED
1. G. A. Klimov, A. V. Krivenk0va, T. N. M a k a r ' e v a , and M. N. Tilichenko, Khim. G e t e r o t s i k l . Soedin.,
824 (1973).
2, E. A. Braude, I. Hannah, and S. R. Linstead, J. Chem. Soc., 3251 (1960).
3. I. L. Kurz, R. F. Hutton, and F. H. W e s t h e i m e r , J. A m e r . Chem. Soc., 83, 584 (1961).
4. A. N. Saverchenko, V. A. K a m i n s k i i , and 1V[. N. Tiliehenko, Khim. G e t e r o t s i k l . Soedin., 384 (1973).
5. D. N. Kursanov and Z. I. P a r n e s , Usp. Khim., 38, 1783 (1969).
6. V. A. Kaminskii, A. N. Saverchenko, and M. N. Tilichenko~ Khim. G e t e r o t s i k l . Soedin., 1538 (1970).
7. V. A. K a m i n s k i i , A. N. Saverchenko, and M. N. Tilichenko, Zh. Organ. Khim., 6, 404 (1970).

704
~r-ELECTRON STRUCTURE, REACTIVITY,
AND ABSORPTION SPECTRA OF ANTHRAPYRIDONE*

B. E. Zaitsev and T. A. Mikhailova UDC 541.67 : 543.422.6:547.837.6

The 7r-electronic s p e c t r a , heats of atomization, and e l e c t r o n i c indexes of the l a c t a m and l a c -

t i m f o r m s of anthrapyridone w e r e calculated by the P a r t s e r - P a r r - P o p l e method with allow-
ance for 25 o n e - e l e c t r o n configurations. An examination of the 7r-bond o r d e r s and the
c h a r g e s on the a t o m s showed that a s y s t e m with a r - e l e c t r o n distribution close to the d i s -
tribution in anthraquinone and in a - p y r i d o n e f o r the l a c t a m t a u t o m e t e r and in ~ - h y d r o x y -
pyridine and anthraquinone for the l a c t i m f o r m is f o r m e d in the l a c t a m and l a c t i m of a n -
thrapyridone. The e l e c t r o n i c a b s o r p t i o n bands w e r e assigned. An a n a l y s i s of the c a l c u l a -
ted values d e m o n s t r a t e d that the long-wave band in the s p e c t r u m of the a n t h r a p y r t d o n e is
due to c h a r g e t r a n s f e r f r o m the amide group to the ketone group. The r e a c t i v i t y and l o c a l -
ization e n e r g y indexes of a r o m a t i c substitution r e a c t i o n s calculated by the Hiickel MO method
a r e in s a t i s f a c t o r y a g r e e m e n t with the e x p e r i m e n t a l data.
It has been shown [1] that, of the two possible f o r m s - l a c t a m and i a c t i m - anthrapyridone exists p r i -
m a r i l y in the l a c t a m f o r m in solution. The e l e c t r o n i c s t r u c t u r e and the a b o s r p t i o n s p e c t r a of t h e s e t a u t o -
m e r s have not been studied. Some bands of t h e s e f o r m s w e r e p r e s e n t e d in [1]. 2 - M e t h o x y a n t h r a p y r i d i n e
was s e l e c t e d as a model of the l a c t i m f o r m . This was done b e c a u s e the p e r c e n t a g e of the l a e t t m f o r m in
solution is so low that one cannot r e c o r d its e l e c t r o n i c s p e c t r u m . R e p l a c e m e n t of the hydroxyl group by a
methoxy group does not lead to substantial changes in the e l e c t r o n i c s p e c t r a . The p r e s e n t p a p e r is devoted
to a study of the e l e c t r o n i c s t r u c t u r e s and a b s o r p t i o n s p e c t r a .of the t a u t o m e r s of the l a c t a m and l a c t i m
f o r m s by the P a r i s e r - P a r r - P o p l e (PPP) method. The calculation was made with allowance for the i n t e r -
action of 25 o n e - e l e c t r o n configurations b y the method in [2]. The r e a c t i v i t y indexes w e r e calculated by the
H~tckel MO method. The heats of atomization w e r e calculated with a p r o g r a m that we worked out with r e a l -
ization of the Dewar a l g o r i t h m .

r-Electronic Structures
The r e l a t i v e stabilities of the l a e t a m and l a c t i m f o r m s can be e s t i m a t e d f r o m the heats of atomization
(AH) and, in s p e c i a l c a s e s , f r o m the E ~ b - andE~rb-bond e n e r g i e s . It is s e e n f r o m Table 1 that the lactim,
f o r m is somewhat m o r e f a v o r a b l e than the l a c t a m f o r m with r e s p e c t to the a t o m i z a t i o n e n e r g i e s . On the
other hand, according to the e x p e r i m e n t a l data, the l a c t a m f o r m is m o r e f a v o r a b l e [1]. The bond e n e r g i e s
of the two t a u t o m e r s a r e a p p r o x i m a t e l y identical. The c o n t r a d i c t o r y conclusions r e g a r d i n g the stabilities
of the t a u t o m e r s with r e s p e c t to the e x p e r i m e n t a l and calculated values can be explained as follows. The
calculations w e r e made for the gas p h a s e without allowance for
TABLE 1. E n e r g y C h a r a c t e r i s t i c s the i n t e r m o l e c u l a r interactions. The e x p e r i m e n t a l data w e r e
of Anthrapyridone T a u t o m e r s obtained f r o m solutions or f r o m c r y s t a l s , in which hydrogen
bonds and the other i n t e r m o l e e u l a r interactions m a y lead to a
Molecule E~x~ ,eV Zob e V , AH,
eV
shift in the e q u i l i b r i u m [3]. The e x p e r i m e n t a l data on r
done, a c c o r d i n g to which ~ - p y r i d o n e exists in the l a c t i m f o r m
l 28,55 81,25 149,50 in the gas p h a s e but in the l a c t a m f o r m in the c r y s t a l l i n e s t a t e
I! 28.49 81,26 149,68
and in solution [4], constitute a c o n f i r m a t i o n of this explanation.

* Communication V f r o m the s e r i e s ~Synthesis and P r o p e r t i e s

of D y e s . " See [1] for c o m m u n i c a t i o n IV.
S c i e n t i f i c - R e s e a r c h Institute of Organic I n t e r m e d i a t e s and Dyes, Moscow. T r a n s l a t e d f r o m Khimiya
G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 6, pp. 812-817, June, 1974. Original a r t i c l e s u b m i t t e d June 17, 1973.

9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy of this article is availablefrom the publisher for $15.00.

705
 TABLE 2. v-Electron Characteristics and Bond Lengths
Charge (Qi) B Ground
" ]state ]'~
Compound ond - - - -- '~

"~ ~ ~ bond

1 -- 0,406 --0,500 I--2 0,834 1,257 0.741

0,284 0,205 2--3 0,303 1,459 0,354
4 --0,017 --0,04t 2--15 0,299 t ,460 0,387
0.046 0,040 3--4 0,643 1,400 0,626
0,010 --0,009 3--8 0,599 1,408 0,574
g ' 0,022 0,010 4--5 0,664 1,396 0,678
II 19
0,010 --0,006 5--6 0,661 1,397 0,645
0,007 -0,024 6--7 0,666 1,396 0,682
0,042 --0,051 7--8 0,638 1,401 0.616
1 -0,027 0,033 8--9 0,323 1,456 0,371
11 0,014 0,033 9--10 0,368 1,448 0.495
12 --0,097 --0,067 9--16 0,823 1,369 0,660
4 ~1 t4 13 0,018 0,006 0--11 0,615 1,405 0,446
14 0,040 0,125 0--15 0,573 1,411 0,520
I5 --0,012 -- 0,075 1--12 0,617 1,405 0,540
16 0,002 --0,076 1--19 0,303 1,394 0,545
17 --0,476 --0,340 2--13 0,688 1,392 0,660
18 0,25l 0,152 3--14 0,640 1,401 0,579
19 0,200 0,590 4--15 0,662 1,397 0,599
6--18 0,357 1,450 0,418
i 7--18 0,789 1,265 0,121
8--19 0,382 1,380 0,466
1 -0,4t3 --0,485 1--2 0,827 1,258 0,745
2 0,282 0,200 2--3 0,302 1,459 0,356
3 -0,014 --0.041 2--15 0,312 1,458 0,374
0,044 0,050 3--4 0,639 1,401 0,632
17 5 0,005 i 0,021 3--8 0,602 1,407 0,544
OH 0,017 --0,006 ] 4--5 0,668 1.396 0,657
i 19 7 0,001 0,017 [ 5--6 0,658 11397 0,625
16~N 0,007 --0,002 } 6--7 0,671 t,395 0,692
* 7 $ I0 II 12 0,044 --0,012 7--8 I 0,635 1,401 0,582
I0 --0,016 0,017 8--9 0,322 1,456 0,412
:. ~ 1 3 11 0,069 0,142 9--10 0,499 1,425 0,451
12 0,021 I -0,034 9 - - 6 0,721 1,386 0,638
0~ 13 0,007 I -0,009 ~lO--II] 0,569 1,413 0,420
14 0.052 0,131 10--15 0,515 1,422 0,555
15 -0,024 --0,054 111--t2 0,521 1,421 0,498
16 --0,028 --0,147 1--19 0,514 1,356 0,574
17 0,061 0,195 2--I3 0,750 1,381 0,701
18 0,151 0,191 3--14 0,579 1,411 0,564
19 --0,270 --0,272 4--15 0,707 1,389 0,687
6--18 0,547 1,417 0,525
7--18 0,263 1,351 0,452
8--19 0,708 1,322 0,547
2 0,387 0,424 1--2 0,476 0,427
0,005 --0,148 1--6 0,460 0,399
-- 0,063 0,096 2--3 0,797 0,562
2 60 0,044 --0,174 3--4 0,499 0,632
6 --0,020 --0,127 4--5 0,817 0,496
0,183 0,151 5--6 0,412 0,466
7 I -0,535 --0,221 6--7 0,730 0,717
-- 0,408 -- 0,533 1--2 0,834 0,707
O 0,293 0,165 2--3 0,298 0,384
- 0,009 0,055
0,045 0,027
0,021 0,099
0,02 ! 0,099
0,045 0,027
i - 0,009 0,058

I t i s s e e n f r o m t h e P r s a n d Qi v a l u e s t h a t t h e d i s t r i b u t i o n o f t h e e l e c t r o n d e n s i t y in t h e k e t o n e a n d
amide groups and in the adjacent C =C bonds in the anthrapyridone molecule is close to the r distribution
in the corresponding bonds of anthraquinone and a-pyridone ( T a b l e 2). T h e d i s t r i b u t i o n o f t h e e l e c t r o n d e n -
sity and of the charges in the heteroring of the molecule of the lactim form is close to that in pyridine.

Pronounced redistribution of the electron density occurs in the first excited state. The 7r-dipole mo-
m e n t o f t h e m o l e c u l e i n t h e e x c i t e d s t a t e ( p = 9 . 8 8 ) i s a l m o s t d o u b l e t h e d i p o l e m o m e n t (p = 5 . 6 1 ) i n t h e
g r o u n d s t a t e . T h e b o n d o r d e r s in t h e r i n g s a r e e q u a l i z e d t o a c o n s i d e r a b l e d e g r e e d u e t o a s h i f t i n t h e
electron density from the pyridone or pyridol rings towards the ketone group. A large Positive charge
( + 0 . 1 2 5 , T a b l e 2) a p p e a r s o n t h e c a r b o n a t o m i n t h e 6 p o s i t i o n ( T a b l e 3). C o n s e q u e n t l y , t h i s p o s i t i o n s h o u l d
undergo nucleophilic attack.

706
 TABLE 3. Reactivity Indexes
Posi-
Compound tion of z~ L N Lre fE
................... a t o _m............

Anthrapyridone 1 1,8161 1,900 1,858 0,162 0,159 0,543

4 2,281 2,295 2,288 0.025 0,086 0,449
It 3 5 2.343 2.515 2,464 0,034 0.037 0.401
I~"N H 2,328 2,343 2,335 0,079 0,052 0,436
2,361 2.541 2,451 0.007 0,016 0,226
2,386 2,483 2,435 0.013 0,029 0,2O5
1 2,408 2,587 2,497 I 0,002 0,034 0,404
11 2,330 21415 2,3701 0,007 0,010 0,425,
O
2-Hydroxyanthrapyridtne 4 1,968 2,137 2,052 0,023 0,109 I 0.481
2,110 I 2,355 2,232 0,150 0,102 i 0.460
g. 2,445 I 2,543 2,494 0,011 0,027 [ 0,402
2,173 I 2,483 2,328 0.118 0,082 i 0,386
8 2,340 I 2,55O 2,446 0,013 0,011 0,423
[ 9 2,383 I 2,467 2,425 0,049 0,037 t 0.405
10 2,410 ] 2,587 2,498 0,002 0,035 0,403
11 I 2,320 2,405 2,363 0.013 0,013 0.425
I
I
O

TABLE 4. Calculated and Experimental E l e c t r o n i c Spectra of the

L a c t i m F o r m of Anthrapyridone
! F
I I ,
W e i g h t s o f the
e x c i t e d con-
figurations

i
I 397,3 390 i 0211 3,742 13~~ 81.0 (10--li); 6,2 (9--11)
II 347,1 347 i 0,341 , 4,122 68,8 (9--11); 10,2 (8--11);
i
4,8 (10--11)
III 315,4 -- I 0,100 ! 168 42,4 (8--I1); 10,2 (7--1t);
I 8,4 (9--11); 4.8 (9--12)
IV 308,3 308,3 i 0,553 ! 3,989 224 68,9 (7--11); 10,2 (t0--12);
6,8 (9--11); 4,0 (9--12)
V 265,3 0,708 l 6 32,4 (10--13); 22,9 (I0--12);
8,4 (9--13); 7,3 (lO--ll)
VI 261,0 261,0 0,586 I 4,062 79 17,7 (10--13); 16,6 (9--12);
16,6 (9--13); 15,0 (8--11);
13,8 00--14)
VII 252,9 252,9 0,045 L 4,057 24 33,6 (10--13); 21,2 (9--12);
! 11,8 (10--12); 6.80 (9--13)
r
VII I 246,9 246,9 0,145 i 4,136 352 31,2 (10--14); 22,2 (9--12);
15,2 (9--i2); 13,9 (9--14)
IX 239,7 0,I04 312 28,1 (9--14); 29.6 00--14);
6,1 (8--12)
X 230,9; 0,642 122 5,8 (7--12); 5.6 00--14)
4,5 (8--12); 4.5 (8--13)
45,0 (6--1t); 8.9 (9--12)
10,5 (9--13t
XI 221,9 0,165 24 25,0 (9--14); 15,3 (7--12);
27,0 (8--12); 10,0 (9--13)
XII 2t4,8 ] 0,162 i 56 I1,0 (7--12); 5,5 (9--13);
7,4 (7---13); 58.8 (10--15)
XIII 212,0] 0,677 . 115 6,6 (9--14); 5,9 (7--13);
F I 13,6 (7--9); 11,0 00--15);
11,5 (8--13); 28,8 (8--14)

Aromatic Substitution Reactions

A c c o r d i n g to the e x p e r i m e n t a l data, anthrapyridone r e a d i l y undergoes nucleophilic substitution r e -
actions (1 position > 6 position > 4 position) and e l e c t r o p h i l i c substitutions (1 position > 6 position) [5, 6].
In examining the r e a c t i v i t i e s by the MO method within the 7r-electron approximation, one usually p r o -
ceeds f r o m r e a c t i o n s o c c u r r i n g through the f o r m a t i o n of intermediate rr and o- c o m p l e x e s . In t h e f i r s t e a s e ,
it is a s s u m e d that electrophilic (fE) attack is directed to the a t o m with the m a x i m u m ~r-electron density,
while nucleophilic (fN) attack is directed to the a t o m with the m i n i m u m 7r-electron density. H o w e v e r a
m o r e c o r r e c t approach is a d i s c u s s i o n of the principles of the orientations of a r o m a t i c substitution p r o -
ceeding f r o m the limiting e l e c t r o n densities [7]. It is s e e n f r o m an examination of the e l e c t r o n densities
in the 1, 4, 5, and 6 p o s i t i o n s (Table 3) that their values a r e not in a g r e e m e n t with the experimental order
of a r o m a t i c substitution. It follows f r o m the calculated values of the limiting d e n s i t i e s (rE a n d f N ) for the

707
 t9
a
5to

4~5 - b
\
4~0- \
3p5 3,.5.

3~,0-
3'0i
2,5L ~ I I ' I ' ' 2t5
220 260 300 340 380 .~, n l ' n 24O 280 320 360 400 440

Fig. 1. E x p e r i m e n t a l and calculated e l e c t r o n i c s p e c t r a of 50% e t h -

anol solutions: a) l a c t i m f o r m of a n t h r a p y r i d o n e ( 2 - m e t h o x y a n t h r a -
pyridine); b) l a c t a m f o r m of a n t h r a p y r i d o n e (anthrapyridone).

TABLE 5. Calculated and E x p e r i m e n t a l E l e c t r o n i c S p e c t r u m of the

L a c t i m F o r m of Anthrapyridone
t~ Weight of the
-4
exceed con-
figuration
r ~ ~'max, FIITI 5=
I 368,6 1 351 0,290 4,47 268~ 68,0 10--11); 6,0 (8--11);
4 10--14);23,0 (9--11)
tl339,2 l -- 0,399 33 30,0 10--11); 8,1 (10--14);
49,8 (9--11)
III 307,4 { 311 0,05I 4,28 341 7,0 10--12); 62,2 (8---11);
13,3 (7--11)
IV 305,0 I -- 0,031 49 8,8 10--12);23,8 (8--1l);
8,0 (8--12);42,0 (7--11)
V 256,5 i 0,245 108 57,1 10--12); 6,0 (9--12);
10,0 7--11)
VI 248,4 0,080 192 13,0 (10--12); 35,0 (10--13) ;
25,0 (9--12)
VII 246,1 I 0,629 325 19,0 (10--13); 31,0 00--14);
18,0 (9--11);18,0 (9--12)
VIII 240,8] 0,095 331 6,0 (7--12); 5,0 (9--15);
I I 12,0 00--13); 9,0 (10--14);
i 9,0 (8--12);21,0 (6--11)
IX 233,0 -- 0,627 229 20,0 (9--14); 8,0 (10--13);
16,0 (10--14); 28,0 (8--12);
i
9,0 (10--15)
I

l a c t a m f o r m that the m o s t r e a c t i v e site for electrophilic and nucleophiltc substitution r e a c t i o n s is the 1 p o -

sition [1], followed by the 6 position for e l e c t r o p h i l i c substitution and the 4 position for nucleophilic s u b -
stitut[on; this is in a g r e e m e n t with the e x p e r i m e n t a l data.
In the c a s e of the ~ c o m p l e x , the r e a c t i v i t y is c h a r a c t e r i z e d b y the l o c a l i z a t i o n e n e r g i e s , which u s u -
ally give a b e t t e r d e s c r i p t i o n of a r o m a t i c substitution than the r e a c t i v i t y indexes of the isolated molecule
[81.
It is s e e n f r o m Table 3 that, a c c o r d i n g to the magnitudes of the l o c a l i z a t i o n e n e r g i e s of electrophtltc
(L E) and nucleophilic (LN) substitution, the m o s t r e a c t i v e s i t e for both eleetrophUic and nucleophilic attack
of the l a c t i m and l a c t a m f o r m s in neutral m e d i a ts the c a r b o n a t o m in the 1 position. This is in good a g r e e -
ment with the e x p e r i m e n t a l data. According to the L E and L R values (Table 3), attack then p r o c e e d s at the
4 and 6 positions. I n a s m u c h as the L E and L R values axe c l o s e , one should a s s u m e that the r e a c t i v i t i e s in
t h e s e positions a r e a p p r o x i m a t e l y identical.

Absorption Spectra of the Lactam and Lactim Forms

It is apparent f r o m the data in Table 4 that the calculated and e x p e r i m e n t a l ), max values a r e in s a t i s -
f a c t o r y a g r e e m e n t (Fig. 1). This a t t e s t s to the c o r r e c t s e l e c t i o n of the computational p a r a m e t e r s . A c c o r d -
ing to the weights of the excited configurations, 81% of the l o n g - w a v e I band (Table 4) p e r t a i n s to t r a n s i t i o n

708
f r o m the upper occupied MO (UOMO) or @10 to the l o w e r vacant MO (LVMO) or r F r o m an examination
of the coefficients of r e s o l u t i o n of the UOMO and LVMO with r e s p e c t to the a t o m i c o r b i t a l s , this transitEon
p e r t a i n s to an S ~ * t r a n s i t i o n p o l a r i z e d at 134 ~ r e l a t i v e to the y axis. According to the change in the e l e c -
i r o n distribution of the ehaxges in the m o l e c u l a r d i a g r a m s in the ground and excited s t a t e s , the t r a n s i t i o n
is r e a l i z e d through c h a r g e t r a n s f e r f r o m the a m i d e group to the keto group. This band can t h e r e f o r e be
called an i n t r a m o l e e u l a r c h a r g e t r a n s f e r band. The o s c i l l a t o r f o r c e (f) is 0.21. According to C I , 69%
of the II band (347 rim) is due to the r 9-~r 11 t r a n s i t i o n . The a s s i g n m e n t of the other bands is p r e s e n t e d in
Table 4.
The long-wave band of the l a c t i m f o r m is due p r i m a r i l y (68%) to t r a n s i t i o n between the r 0-*r 11 MO
and (23%) the r 1 6 2 11 t r a n s i t i o n and is p o l a r i z e d at 268 ~ r e l a t i v e to the y axis (Table 5). According to the
m a t r i x of the coefficients of expansion in the f o r m a t i o n of the r I0--~r 11 M e , the p a r t i c i p a t i o n of the MO of
the carbon a t o m s and the MO of the h e t e r o a t o m s is a l m o s t identical. The hydroxyl oxygen a t o m m a k e s the
g r e a t e s t contribution to the r 9 Me. It is a p p a r e n t f r o m a c o n s i d e r a t i o n of the change tu the c h a r g e s in the
m o l e c u l a r d i a g r a m s on p a s s i n g f r o m the ground s t a t e to the excited s t a t e that the e l e c t r o n c h a r g e s m i g r a t e
f r o m the l a c t i m r i n g to the anthraquinone s y s t e m during the l o n g - w a v e transition. The second band (339
nm) is p o l a r i z e d at 33 ~ r e l a t i v e to the y axis and is 1.5 t i m e s m o r e intense than the l o n g - w a v e band; this is
good a g r e e m e n t with the e x p e r i m e n t a l r e s u l t s . According to the CI, it is due p r i m a r i l y to t r a n s i t i o n
between r lo and r 11 (30%) and t r a n s i t i o n between r B and r tl (50%). The r e s t of the bands a r e p r e s e n t e d in
Table 5.

LITERATURE CITED
1, B. E. Zaitsev, T. A. Mikhailova, G. P. R odionova, and M. V. Kazankov, Zh. FEz. Khim., 47, 1095
(1973).
2. G. I. Kagan, V. A. Kosobutskii, V. K. Belyakov, and O. G. T a r a k a n o v , Khim. G e t e r o t s i k l . SoedEn., 794
(1972).
3. M. Dewar, Molecular Orbital T e h r o y of Organic C h e m i s t r y , M c G r a w Hill (1969).
4. l~. S. Levin and G. N. Rodionova, S p e c t r o s c o p y - Methods and ApplEcations [in Russian], Nauka, Mos-
cow (1969), p. 146.
5. S. I. Popov, M a s t e r ' s D i s s e r t a t i o n [in Russian], Moscow (1967).
6. R. A. Dupont, BUll. Soc. Chim. Belge, 5_22, 7 (1943).
7. W. K l e m p e r e r , W. Cronyn, H. Maki, and G. P i m e n t e l , J. A m e r . Chem. See., 76, 5846 (1954).
8. A. R. K a t r i t z k y (editor) , Advances in H e t e r o c y e l i c C h e m i s t r y , A c a d e m i c P r e s s .

709
PROOF OF THE STRUCTURE
OF 1 - T O S Y L - 5 - (2 V-NI T R O V I N Y L ) I iV[IDA Z O L E

A . M. R o z h k o v , A. I. Rezvukhin, UI)C 541.61 : 543.422.25 : 547.781

M. I . K o l l e g o v a , U. G . K o l m a k o v a ,
a n d V. P . M a m a e v

The s t r u c t u r e of 1 - t o s y l - 5 - ( 2 ' - n i t r o v i n y l ) i m i d a z o l e was established on the b a s i s of its NM_R

s p e c t r u m [by means of t r i s {dipivaloylmethanato)europium as the "shift r e a g e n t " ] and f r o m
the magnitude of the dipole moment,

1 - T o s y l f o r m y l i m i d a z o l e and the products of its condensation with nitroparaffins a r e well known [1],
but the position of the f o r m y l group and, consequently, the nitroalkenyl groups has not been established. In
this connection, we investigated the s t r u c t u r e of 1-tosylnitrovinylimidazole.
In addition to signals that c o n f i r m the p r e s e n c e of tosyl and fl-nitrovinyl groups, the PMR s p e c t r u m
of the compound (Table 1) contains two signals that can be a s s i g n e d to the H 2 and H 4 atoms of s t r u c t u r e I or
to the H 2 and H 5 atoms of s t r u c t u r e II.
H
I

HB O~S~O O~S=O
H('~D~/H c Ht\~--'~ Hc
H Ho H~" V \I-l~
~H 3 ~H3
I II

I n a s m u c h as the chemical shifts of H2, H4, and H~ a r e close [3], while it is difficult to predict the effect of
adjacent groups on them, it is impossible to choose between s t r u c t u r e s I and II on the basis of this s p e c -
~TUm.

Using i r i s (dipivaloylmethanato)europium, [Eu(DPM)3] ,

TABLE I. PMR Spectra
as a "shift r e a g e n t , " we followed the appreciable weak-field
r, ppm ISubstrate/ shift of the signals (At) at 2.0-2.7 ppm.
Protons tnd6-acetoneI inCDC13 IEu(DPM)3=
1.1
I n a s m u c h as the nitrogen a t o m in the 3 position is more
CH3 basic, the protons in the 2 and 4 positions should experience
Ha* 2,13 2,41 3,21
HB 2,21
7,61 2,02 2,50
-- I,65 a g r e a t e r shift (it is a s s u m e d [4] that the effect of the c o o r -
Hc'l" 2,02 2,27 1,30
HD 2,51 2,65 0,44 dinated Eu ion is t r a n s m i t t e d via a pseudocontact m e c h a n i s m ,
H2 and H4 1,71and 1,88 and 2,14 328 and 3,06 the determining f a c t o r s of which a r e the distance to the p r o -
ton and the angle between the major axis of the molecule and
* J A B = 1 3 . 2 Hz, t r a n s protons [2]. the line connecting it with the lanthanide ion). Thus the shift
~ J C D = 8 . 5 Hz. of the H2 signal is 28.3 ppm for 1-methylimidazone [5] for an
equimoleculax s u b s t r a t e - t o - E u ( D P M ) 3 r a t i o (as c o m p a r e d
with 25 ppm for H 4 and 10 ppm for Hs).
Novosibirsk Institute of Organic C h e m i s t r y , Siberian Branch, A c a d e m y of Sciences of the USSR. Nov-
o s i b i r s k Institute of R a i l r o a d T r a n s p o r t a t i o n Engineers. T r a n s l a t e d f r o m Khimiya Geterotsiklicheskikh
Soedinenii, No. 6, pp. 818-819, Jane, 1974. Original a r t i c l e submitted June 21, 1973.

9 1975Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy of this article is availablefrom the publisher for $15.00.

710
 I n a s m u c h as the signals at 2.02 and 2.14 p p m a r e shifted to an a p p r o x i m a t e l y equal extent, it can be
a s s u m e d that we a r e dealing with s t r u c t u r e I, in which the H 2 and H4 protons a r e at about the s a m e distances
f r o m N 3. The signal of the proton in the 5 position of s t r u c t u r e II should e x p e r i e n c e c o n s i d e r a b l y l e s s of a
shift as c o m p a r e d with the signal of the proton in the 2 position. The s m a l l shift in the H 2 and H4 signals
as c o m p a r e d with 1 - m e t h y l i m i d a z o l e [5] is explained b y weakening of the b a s i c i t y and, consequently, b y a
reduction in the capacity for complexing of the nitrogen a t o m in the 3 position through the two e l e c t r o n - a c -
c e p t e r substituents - the nitrovinyl group and the tosyl group. The r e a s o n s for the r e l a t i v e l y l a r g e shift of
the HA signal a r e unclear.
The magnitude of the dipole moment (Pexp 6.7 D, as c o m p a r e d with Pcalc 7.07 D for s t r u c t u r e I and
5.89 D for s t r u c t u r e II) also c o r r e s p o n d s to s t r u c t u r e I.
The e s t a b l i s h m e n t of the s t r u c t u r e of 1 - t o s y l n i t r o v i n y l i m i d a z o l e p r o v e s that 1 - t o s y l - 5 - f o r m y l i m i d a -
zole is f o r m e d b y tosylation of 4(5)formylimidazole and that the n i t r o p r o p e n y l d e r i v a t i v e obtained f r o m it
has the s a m e orientation of the substituents.

EXPERIMENTAL
The PMR spectra were recorded with a Varian HA-100 spectrometer relative to hexamethyldisiloxane
(HMDS). The spectra with Eu(DPM) 3 [6, 7] (10g0 solution in CDCI3) were obtained with a Brueher-Fizik AG
HX-90/8-15 spectrometer with homostabUization of the resonance conditions.
The following moments of the individual bonds and groups were used in the calculation of the dipole
moments via a vector-additive scheme." Csp3-H 0.28, Csp2-H 0.70, Csp3-Csp 2 0.78 [8], NO 2 3.31 (calcu-
lated from the experimental dipole moment of nitrobenzene [9]), C =N 0.56, C =N 1.8 [i0], S =O 3.76, C =S
0.44 [11], and C =O 2.3 D [12]. The geometrical parameters of pyrazole [13] were used.
The dielectric permeabUities of benzene solutions were determined at 25 ~ by the heterodyne method
with a Tangens apparatus. The orientation polarization was calculated by the Guggeneheim-Smith method
[14] with ~ 16.44, T 0, and Pexp co 917.19.

LITERATURE CITED
i. A.M. Rozhkov, U. G. Kolmakova, and V. P. Mamaev, Izv. Sibirsk. Otd. Akad. Nauk SSSR, Set. Khim.,
1, No. 2, 144 (1972).
2. W. Brfigel, Nuclear Magnetic R e s o n a n c e S p e c t r a and Chemical S t r u c t u r e , Vol. 1, A c a d e m i c P r e s s
(1967), p. 97.
3. Catalog of I n f r a r e d Spectra, Sadtler R e s e a r c h L a b o r a t o r y , No. 7848 (1970).
4. P. K r i s t i a n s e n and I. Ledeal, T e t r a h e d r o n Lett., 2817 (1971).
5. R . M . C l a r a m u n t , I. Elguero, and R. J a e q u i e r , OIVIR, 3 , 5 9 5 (1971).
6. K . R . Kopeeky, D. Nonhebel, G. M o r r i s , and G. S. Hammond, J. Org. C h e m . , 27, 1036 (1962).
7. K . I . E i s e n t r a u t and R. E. S i e v e r s , J. A m e r . Chem. See., 87, 5254 (1965).
8. L . A . Gr[bov and E. M. Popov, Dokl. Akad. Nauk SSSR, 145, 761 (1962).
9. O . A . Osipov and V. I. Minkin, Handbook of Dipole Moments [in Russian], V y s s h a y a Shkola, Moscow
(1965), p. 102.
10. K.B. Everard and L. E. Sutton, J. Amer. Chem. See., 71, 2318 (1949).
11. L.K. Yuldasheva, R. P. Arshinova, and S. G. Vul'fson, Izv. Akad. Nauk SSSR, Otd. Khim. Nauk, 555
(1969).
12. O. Exner and V. Jehli~ka, Coll. Czech. Chem. Commun.,30, 639 (1965).
13. S.A. GLller, I. B. Mazheika, and I. I. Grandberg, Khim. Geterotsikl. Soedin., 103 (1965).
14. A. Guggenheimand J. Prue, Physieochemical Calculations [Russiantranslation], Inostr. Lit., Moscow
(1958), p. 100.

711
SYNTHESIS AND PROPERTIES OF AZOLES
AND THEIR DERIVATIVES
XXI.* 1,5-BISHETERYL-3,3-DINITROPENTANES

G. A. Shvekhgeimer and G. A. Mikheichev UDC 547.785.5'787.3.07 : 543.422.4.6

Dihydrochlortdes of diimino e s t e r s of 4 , 4 - d i n i t r o p i m e l i c acid a r e f o r m e d f r o m 4 , 4 - d i n i t r o p i -

melic acid dinitrile and alcohols in the p r e s e n c e of hydrogen chloride. The dihydrochloride
of the methyl diimino e s t e r condenses with e t h y l e n e d i a m i n e , o - p h e n y l e n e d i a m i n e , and o - a m i -
nophenol to give the c o r r e s p o n d i n g 1 , 5 - b i s h e t e r y l - 3 , 3 - d i n i t r o p e n t a n e s .

Diimino e s t e r dihydrochlorides II-V a r e obtained in 84-100% yields when d r y hydrogen chloride is

bubbled through a solution of 4 , 4 - d i n i t r o p i m e l t e acid dinitrile (I) and the a p p r o p r i a t e alcohol (moIar r a t i o
1 : 2) in absolute dioxane:
/2N H'BCI
/CH2CH2C~,oR
(O2N)2C H2CH2CN/C + 2ROH + 2 HCI ~ (O,N)2C
CH2CH2CN - ~ //N H, I~[C|
CH2CH2C\o R

II-V

R------"~a; IH I~---C2HS: IV R=HC=CH2; V R=CH2CH2NO2

Reactions c h a r a c t e r i s t i c for imino e s t e r s a l t s w e r e r e a l i z e d for the dihydrochlorides obtained in this

study: II and III w e r e hydrolyzed to dimethyl and diethyl 4 , 4 - d i n i t r o p i m e l a t e s , r e s p e c t i v e l y , and salt II was
c o n v e r t e d to the diamide by heating and to the dimethyl diimino e s t e r of 4 . 4 - d i n i t r o p i m e l t c acid (VI) by
t r e a t m e n t with aqueous p o t a s s i u m c a r b o n a t e solution. Reaction of VI with a m m o n i u m chloride gave 4,4-
d i n i t r o p i m e l i c acid diamidine dihydrochloride.
Salt II r e a d i l y condenses with ethylenediamine to give 1,5-bis ( l ' , 3 ' - i m i d a z o l i n - 2 ' - y l ) 3 , 3 - d i n i t r o p e n -
tane (VII):

[ N-c. I

L "
VII,

Salt II r e a c t s s m o o t h l y with o - p h e n y l e n e d i a m i n e and o-amtnophenol to give high yields of the c o r r e -

sponding 3,3-dinitropentanes containing benzimidazolyl or benzoxazolyl groupings in the 1 and 5 positions
(VIII and IX):

il + 2 [ ~ INH2
(02N)~C CI12Cli z
~"~/'~"X H
L J2

VIII X=NIt: IX X=O

*See [1] for c o m m u n i c a t i o n XX.

I. M. Gubkin Moscow Institute of the P e t r o c h e m i c a l and Gas Industry. T r a n s l a t e d f r o m Khimiya G e t -
e r o t s i k l i c h e s k i k h Soedinenii, No. 6, pp. 820-822, June, 1974. Original a r t i c l e s u b m i t t e d June 10, 1972.

9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, hr..Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

712
 EXPERIMENTAL
The LR spectra were recorded with a UR-10 spectrometer. The UV spectra of n-heptane solutions
were recorded with a Unicam SPS00A speetrophotometer. The individuality of the products was monitored
by thin-layer chromatography (TLC) on activity I aluminum oxide [benzene-methanol (12 : i) for VIII, and
benzene-methanol (9:1) for IX; the ehromatograms were developed with iodine vapors].
4,4-Dinitropimelic Acid Diimino Ester Dihydrochlorides (II-V). The reaction was carried out without
access to moisture. Dry hydrogen chloride was bubbled with stirring at 0-5 ~ through a solution of 0.05 mole
of nitrile I and 0.i mole of the appropriate alcohol in 60 ml of absolute dioxane until the solution became
saturated, after which the mixture was allowed to stand overnight at 0-5 ~. It was then held under vacuum
to remove the dissolved hydrogen chloride, after which 150 ml of absolute ether was added. The resulting
precipitate was removed by filtration and washed with absolute ether until the excess hydrogen chloride had
been completely removed. The product was precipitated from glacial acetic acid solution by the addition of
absolute ether to give II with mp 102-103 ~ in 100% yield. Found: Cl 20.0%. CgHIsN406CI ~. Calculated:
C1 20.3%.
Compound HI, with mp 99-100 ~ was obtained in 99.5% yield. Found: Cl 18.7%. CIIH~.2N406CI 2. Cal-
culated~ Cl 18.8~0.
Product HI, with mp 109-110 ~ was obtained in 84% yield. Found: C1 17.7%. CI~HIsN40~CI 2. Calctt-
fated: C1 17.9%.
Compound V, with mp 93-95 ~ was obtained in 93% yield. Found: C1 15.2%. CIIH20N6OIoCI 2. Calcu-
lated: Cl 15.2%.
4,4-Dinitropimelic Acid D[methyl Diimino Ester (VI). A total of 7 ml of 33% aqueous potassium car-
bonate solution was added rapidly with vigorous stirring at 0-5 ~ to a suspension of 6.98 g (20 mmole} of salt
II in 80 ml of ether, after which the ether layer was immediately separated, and the aqueous layer was ex-
tracted with three 25-mi portions of ether. The ether layer and the extracts were combined and dried with
magnesium sulfate at 0~ The ether was removed by distillation to give 5.2 g (94%) of VI as a colorless
tmdistillable oil. IR spectrum: 1620 (C =N), 3330 (N-H), 1320 and 1590 em -I [C(NO2}2].
Starting salt II was recovered in quantitative yield when dry hydrogen chloride was bubbled through
a solution of VI in absolute ether at 0~
Diethyl 4,4-Dinitropimelate. Water (5 Inl) was added to a suspension of 7.54 g (20 mmole) of salt III
in 50 ml of ether, and the mixture was stirred at room temperature for 3 h. The aqueous layer was ex-
tracted with three 25-mlportions of ether, and the ether layer and extracts were combined and dried with
magnesium sulfate. The ether was removed by distillation, and the residue was fractionated in a stream of
nitrogen to give 3.86 g (63%) of diethyl 4,4-dinitropimelate with bp 174-175 ~ (2 mm), nD 2~ 1.4604,and d42~
1.2695. Found: C 43.4; H 5.9; N 9.4%. CIIHIsN208. Calculated: C 43.1; H 5.9; N 9.1%. IR spectrum: 1740
(C =O), 1310 and 1575 em -I [C(NO2}2].
Dimethyl 4,4-Dinitropimelate. This compound, with mp 44 ~ (from methanol) [2], was obtained in 90%
yield from salt II by the method used to prepare the diethyl ester.
4,4-Dinitropimelic Acid Diamide. A 0.87-g (2.5 mmole) sample of salt II was heated at 85-90 ~ until
methyl chloride evolution ceased. The reaction mixture was cooled, washed with ether, and dried to give
6.1 g (98%) of 4,4-dlnitropimelic acid diamide with mp 97.5-98 ~ (from propanol). Found: C 33.6; H 4.9;
N 22.2%. CITHI2N406. Calculated: C 33.9; H 4.8; N 22.6%. IR spectrum: 1690 (C =O}, 1330 and 1585 cm -I
[c (NO2)2].
4,4-Dinitropimelic Acid Diamidine Dihydroehloride. A 1.07-g (20 mmole) sample of a m m o n i u m chlo-
ride was added to a solution of 2.76 g (10 mmole) of e s t e r VI in 30 ml of absolute methanol, and the mixture
was s t i r r e d at r o o m t e m p e r a t u r e until it b e c a m e homogeneous, after which it was s t i r r e d for another 2 h.
It was then evaporated in vaeuo to d r y n e s s , and the r e s i d u e was extracted with ether. The ether e x t r a c t s
were discarded. The solid phase was then extracted with glacial acetic acid, and the e x t r a c t was diluted
with three volumes of absolute ether and worked up to give 2.97 g (93%) of 4,4-dinitropimelic acid diamidine
dihydrochloride with mp 94-95 ~ Found: C 26.1; H 5.1; C1 21.9; N 19.9%. CTHiGC12N60: Calculated:
C 26.3; H 5.0; C1 22.2; N 20.0%.
1,5_Bis(l~,3V-imidazolin-2T-yl)-3,3-dinitropentane (VII). A 3.49-g (10 mmole) sample of salt II was
added with s t i r r i n g at 0~ in the c o u r s e of 30 min to a solution of 1.2 g (20 mmole) of ethylenediamine in 50

713
ral of absolute methanol, after which the mixture was s t i r r e d at 40-50 ~ for 2 h. It was then cooled, and 0.73
g (20 mmole) of hydrogen chloride in 50 ml of absolute methanol was added dropwise. The solution was then
e v a p o r a t e d to 50 ml and filtered, and the filtrate was evaporated to d r y n e s s to give 3.62 g (97%) of VII with
mp 58-60 ~ (from alcohol). Found: C 35.5; H 5.5; N 22.8%. ClIH20C12N604. Calculated. C 35.6; H 5.4; N
22.6%. IR s p e c t r u m : 1300 and 1610 c m -1 [C (NO2)2].
1,5-Bis (2'-benzimidazolyl)-3,3-d[uitropentane (VIII). A mixture of 3.49 g (10 mmole) of salt II and
2.16 g (20 mmole) of o-phenylenediamine in 60 ml of absolute methanol was s t i r r e d in 200 ml of cold w a t e r
containing 1.38 g (10 mmole) of p o t a s s i u m carbonate. The mixture was extracted with five 50-ml portions
of ether, and the ether extracts were washed with water and dried with m a g n e s i u m sulfate. The ether was
r e m o v e d by distillation to give 3.35 g (85%) of VIII with mp 125 ~ (from propyl alcohol). Found: C 57.5; H
4.8; N 20.9%. C19H18N604. Calculated: C 57.8; H 4.6; N 21.3%. IR s p e c t r u m : 755, 870, 940, 1030, 1475
(benzimidazole ring); 1325 and 1605 c m -1 [C(NO2)2]. Several n a r r o w bands that a r e c h a r a c t e r i s t i c for sub-
stituted benzenes are o b s e r v e d in the UV s p e c t r a at ~275 nm, and t h e r e is a b r o a d band at 250 nm.
1 , 5 - B i s ( 2 ' - b e n z o x a z o l y l ) - 3 , 3 - d i n i t r o p e n e t a n c (IX). A mixture of 6.98 g (20 mmole) of salt II and 4.36 g
(40 mmole) of o-aminophenol in 120 ml of absolute methanol was s t i r r e d at 50 ~ for 1 h, after which the
cooled r e a c t i o n mixture was poured with s t i r r i n g into 300 ml of cold water. The r e s u l t i n g precipitate was
r e m o v e d by filtration, washed with water, and dried to give 7.44 g (94%) of IX with mp 108-109 ~ (from ben-
z e n e - p e t r o l e u m ether). Found: C 57.3; H 4.8; N 14.0%. CigHlGNtO 6. Calculated: C 57.6; H 4.0; N 14.1%.
IR s p e c t r u m : 760, 805, 845, 945, 1000, 1150, 1300, 1465 (benzoxazole ring); 1330 and 1575 c m -1 [C(NO2)2].
Several n a r r o w bands that a r e c h a r a c t e r i s t i c for substituted benzenes a r e o b s e r v e d in the UV s p e c t r u m at
max 275, and there is also a more intense and b r o a d e r band with a m a x i m u m at 233 nm.

LITERATURE CITED
1. G. A. Mikheichev, P e t r o l e u m and Gas and Their P r o d u c t s [in Russian], Moscow (1971), p. 168.
2. Z. Herzog, M. H. Gold, and R. D. Geckler, J. A m e r . Chem. Soc., 7.33, 749 (1951).

714
P YRIMIDINES
XL.* REACTION OF BISUREAS WITH ISOMERIC
HYDROXYAMINOP YRAZOLES

M. A. M i k h a l e v a , L . N. I I ' c h e n k o , UDC 542.953:547.836'859'775

a n d V. P . M a m a e v

It is shown that the r e a c t i o n of b e n z a l b i s u r e a with 3 - a m i n o - 5 - h y d r o x y - l - R - p y r a z o l e s gives

1-R-dipyrazolo[3,4-b : 4 ' , 3 ' - e ] p y r l d i n e (R =CH3) or a s p i r o ( p y r a z o l e - 4 , 5 ' - p y r i m i d i n e ) d e r i v a -
tive (R =C6H5). Similar r e a c t i o n s of b e n z a l b i s u r e a with 3 - h y d r o x y - 5 - a m i n o - l - m e t h y l p y r a z o l e
give 2-methyldipyrazole[3,4-b : 4 ' , 3 ' - e ] p y r i d i n e o r substituted t e t r a h y d r o p y r a z o l o [ 3 , 4 - d ] pc_
rimidine. Only the corresponding dipyrazolo[3,4-b : 4 ' , 3 ' - e ] p y r i d i n e s are f o r m e d in the r e a c -
tion of 1-methylhydroxyaminopyrazoles with methylenebisurea.

It has been shown that p y r a z o l e s containing hydroxyl or amino groups in the 3 or 5 position condense
with a r y l i d e n e b i s u r e a s to give, depending on the s t r u c t u r e of the starting p y r a z o l e , s p i r o p y r a z o l e p y r i m i -
dines [2], pyrazolooxazines [3], p y r a z e l o p y r i m i d i n e s [4], or products with m o r e complex s t r u c t u r e s [5]. In
the presen~ r e s e a r c h we have investigated the behavior of p y r a z o l e s simultaneously containing hydroxyl and
amino groups in the 3 and 5 positions of the pyrazole ring in s i m i l a r condensations. Two i s o m e r s - I and
I I - are possible for 3,5-disubstituted p y r a z o l e s when t h e r e is a substltuent in the 1 position.

NH2-~__ ~ HO .
N-.N/'~O ~'-N g2
I I
R R
I I!

On the basis of the results obtained in [2], it was nataral to assume that one should most likely ex-
pect the formation of a spiro(p~azole-4,5'-pyrimidine) derivative in the reaction of isomer I, which is a
compound of the p ~ o l o n e class [6],on reaction with aryltdenebtsureas. In fact, HI, to which the 3-amino-
1 , 4 ' , 6 ' - t r i p h e n y l s p i r o ( p y r a z o l e - 4 , 5 ' - h e x a h y d r o p y r i m i d i n e ) - 2 , 5 ' - d i o n e s t r u c t u r e (HI) was assigned on the
basis of the r e s u l t s of e l e m e n t a r y analysis and the s p e c t r a l c h a r a c t e r i s t i c s , was isolated in the condensa- '
tion of 1 - p h e n y l - 3 - a m i n o - 5 - p y r a z o l o n e (Ia) with b e n z a l b i s u r e a (the r e a g e n t molar r a t i o was 1 : 2).
However, the chief product of the r e a c t i o n was IVa, which p r e s u m a b l y had e m p i r i c a l f o r m u l a
C39H3~N602 on the basis of the analytical data and the e x p e r i m e n t a l l y d e t e r m i n e d molecular weight. This
made it possible to suppose that IVa is f o r m e d f r o m two molecules of p y r a z o l e Ia (C18H1~1602) and t h r e e
molecules of benzaldehyde (C21H1803) with splitting out of t h r e e molecules of water. The formation of IVa
in the r e a c t i o n of Ia with benzaldehyde confirmed this assumption. Considering the IR s p e c t r o s c o p i c da~a -
the p r e s e n c e of absorption bands at 1720 c m -1 (C =O in 4,4-disubstituted 5-pyrazolones [7]) and at 3380 c m -1
(NH) - the formula of one of the t h r e e s t r u c t u r a l i s o m e r s in Scheme 1 could be proposed for IVa.

*See [li for communication XXXIX.

Novosibirsk Institute of Organic C h e m i s t r y , Siberian Branch, Academy of Sciences of the USSR,

T r a n s l a t e d f r o m Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 823-827, June, 1974. Original a r t i -
cle submitted F e b r u a r y 8, 1973.

9 1975Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

715
 Scheme 1

C6HsCH IN. N./~ O i

I
NH-~O C6H5
C6H~--~ Nil
NH2~. . N H 2 ~
[! ~x +C,slIsCH(NHCONH ) - - il l "q"~ +
""N i'~O ~2 ~,...N./~O
i I C6H5
C6H5 C6H5 N'~CHC6H5/
I a III

NHi~-~ _CH2(NHCONH~)20~ ~0 CsHs

]2
N-~NZ'~O CH3IN "-.N/J~.N~"-N/N "~CH3 IVa
~H3 H H
Ib \ Vii
\C6HsCH(NHCONH2)1

HN.-.. CHC~H5 O /~O (CH3CO)20 O~ i~ ~---7//0

CeH5CHi ""N'~Ni~O / CH /N'~N/X~-N~'~"N/N'~CH3 CH /~4~.N./~-N.~,'~-N/ ~CH~
\ CH, /2 COCIt3 COCH,
Ivb v Vl

The choice made between t h e m was made on the basis of the PlV~ s p e c t r a l data. The PM:R s p e c t r u m of IVa
contains signals at 4.30 6 (s,* - - C H < ) , 4.95 5 (s, C = C H - ) , and 7.26 6 (m, Harom) with an intensity r a t i o
of 1 : 2 : 2 5 . i n a s m u c h as the signal of a proton of the - N = C H C 6 H 5 group (8-8.5 5 [8]) is absent in the s p e c -
t r u m , one can r e j e c t s t r u c t u r e 3. The proton signal of the > C H - - group appears as a r a t h e r n a r r o w sin-
glet, while splitting (or at l e a s t broadening) of the signal due to coupling of the protons I n t h e - N H - C H ~ - N H -
grouping should have o c c u r r e d for s t r u c t u r e 2; on the basis of this, we propose s t r u c t u r e 1 as most p r o b -
able for IVa.
Condensation of Ia with an equimolecular amount of b e n z a l b t s u r e a gives only IVa. A compound of a
s i m i l a r s t r u c t u r e (IVb) was obtained by r e a c t i o n of 1 - m e t h y l - 3 - a m i n o - 5 - p y r a z o l o n e (Ib) with a twofold
amount of b e n z a l b i s u r e a , but s p i r o ( p y r a z o l e - 4 , 5 ' - p y r i m i d i n e ) was not detected in the r e a c t i o n mixture in
this case.
A bright-yellow high-melting product that was p r a c t i c a l l y insoluble in the usual organic solvents was
isolated in the condensation of equimolecular amounts of Ib and benzalbisurea. The determination of the
molecular weight and the IR s p e c t r a l data (broad band of the absorption of a C =O group at 1640 c m -1) en-
abled us to p r o p o s e a substituted dipyrazolo[3,4-b : 4 ' , 3 ' - e ] p y ~ [ d i n e s t r u c t u r e (V) for it. The formation of
condensed pyridines of this kind is known for the r e a c t i o n of aldehydes with both a r o m a t i c amines and a m i -
n o p y r a z o l e s [9, 10]. An additional p r o o f of the s t r u c t u r e of V was the formation of diacetyl derivative VI
by refluxing dipyrazolopyridine V with acetic anhydride; this was evidenced by the appearance of new bands
in the IR s p e c t r u m of VI in the r e g i o n of absorption of the C =O group and also by the disappearance of the
bands of the NH s t r e t c h i n g vibration, as c o m p a r e d with the IR s p e c t r u m of starting V.
Condensation of pyrazolone Ib with m e t h y l e n e b i s a r e a [11] gave dipyrazolopyridine VT_I, the s t r u c t u r e
of which was established as d e s c r i b e d above on the basis of analytical and s p e c t r a l data.
The r e a c t i o n of h y d r o x y a m i n o p y r a z o l e II (an i s o m e r of the compound under cons i d e r a t i o n ) w i t h b t s u r e a
most likely should have given condensation s y s t e m s containing either an oxazine [3] or a pyrimidine [4]
r ing.

A malticomponent mixture with predominance of two compounds, for the first of which, with e m p i r i c a l
f o r m u l a C18H14N20,the s t r u c t u r e was not unambiguously established, was obtained when i s o m e r II was con-
densed with b e n z a l b i s u r e a (in a r a t i o of 1 : 2). The IR s p e c t r u m of the second compound contained a b s o r p -

*Here and subsequently, s is singlet and m is multiplet.

716
 tg~
4,5 i

,.~. i ~' ~\'! ", i-~

4,0
/-/ t k "\ / /~

/ \// \
3,5
~:..i / .'?-~-.""-'7 "-. t\

3,0
;,../' ',. i " '..'--... ",\
X / "~4 3 2 #
t /
~'-.~ / X I 11112
250 300 350 400

Fig. 1. UV s p e c t r a of d i p y r a z o l o p y r i d i n e s :
1) V; 2) VIII; 3) X; 4) XI.

Scheme 2

I 1 tl I it
Eli 3 CH~ CH a

II ~ VIII

~N 3 I I
clt~ (~Ha CH 3

XI X

tion bands at 1690 c m -1 (C =O) and at 3396 c m - I (NH) and the compound gave a qualitative r e a c t i o n for a
phenolic OH group and, with r e s p e c t to its m o l e c u l a r weight and e m p i r i c a l f o r m u l a , c o r r e s p o n d to the e x -
pected t e t r a h y d r o p y r a z o l o p y r i m i d i n e (VIII). We w e r e unable to dehydrogenate it by the b r o m i n a t i o n - d e h y -
d r o b r o m i n a t i o n method. The c o r r e s p o n d i n g p y r a z o l o p y r i m i d i n e (IX) was obtained by dehydrogenation of
t e t r a h y d r o compound VIII with chloranil.
The condensation of e q u l m o l e c u l a r amounts of h y d r o x y p y r a z o n e II and b e n z a l b i s u r e a gave, in addition
to VIII, a compound with an IR s p e c t r u m that did not contain absorption bands of C =O and NH groups; m o r e -
o v e r , it gave a qualitative r e a c t i o n for a phenolic hydroxyl group with FeC13. T h e s e data, the r e s u l t s of
e l e m e n t a r y a n a l y s i s , and the m o l e c u l a r weight d e t e r m i n a t i o n enabled as, in analogy with the p r e c e d i n g
c a s e , to a s s i g n the 1 , 7 - d i m e t h y l - 4 - p h e n y l - 3 , 5 - d i h y d r o x y d i p y r a z o l o [ 3 , 4 - b : 4 ' , 3 ' - e ] p y r i d i n e s t r u c t u r e (X) to
the isolated compound.
In the r e a c t i o n of II with m e t h y l e n e b i s u r e a in v a r i o u s m o l a r r a t i o s , we w e r e able to isolate only
1 , 7 - d i m e t h y l - 3 , 5 - d i h y d r o x y d i p y r a z o t o [3,4-b : 4' , 3 ' - e ] p y r i d i n e (XI), the s t r u c t u r e of which was e s t a b l i s h e d
on the b a s i s of analytical and s p e c t r a l data.
The r e g u l a r i t y in the change in the UV s p e c t r a of condensed p y r a z o l e s y s t e m s as a function of which
edge of the p y r a z o l e ring undergoes fusion (as we noted in [3, 4]) is o b s e r v e d for the i s o m e r i c d i p y r a z o l o -
pyridines obtained by the r e a c t i o n of h y d r o x y a m i n o p y r a z o l e s I and II with b i s u r e a s . In the c a s e of V and
VII, for which r i n g fusion o c c u r s at the 3 - 4 edge of p y r a z o l e , the UV s p e c t r a a r e c h a r a c t e r i z e d by the p r e s -
ence of an intense l o n g - w a v e m a x i m u m , as c o m p a r e d with the UV s p e c t r a of X and XI, which a r e fused at
the 4-5 edge of p y r a z o l e (Fig. 1).

EXPERIMENTAL
The IR s p e c t r a of KBr pellets (c--0.25%) w e r e r e c o r d e d with UR-10 and UR-20 s p e c t r o m e t e r s . The
UV s p e c t r a of alcohol solutions w e r e r e c o r d e d with a U n i c a m SP-700C s p e c t r o p h o t o m e t e r . The PMR s p e c -
t r a of deuterod[methyl sulfoxs solutions w e r e r e c o r d e d with a Vat[an A56/60A s p e c t r o m e t e r with h e x a -
methyldisiloxane (HMDS) as the internal standard. The m o l e c u l a r weights w e r e d e t e r m i n e d with an MS-902
mass spectrometer.

717
 2 , 2 V - B e n z a l b i s ( 1 - p h e n y l - 4 - b e n z a l - 3 - i m i n o - 5 - p y r a z o l o n e ) (IVa). A m i x t u r e of 1.75 g (0.01 mole) of
Ia and 2.12 g (0.02 m o l e ) o f benzaldehyde in 10 ml of glacial CH3COOH was r e f l u x e d for 1 h, a f t e r which it
was cooled and poure d into 250 ml of water. The aqueous m i x t u r e was n e u t r a l i z e d with d r y NattCO3, and
the r e s u l t i n g p r e c i p i t a t e was r e m o v e d by filtration and w a s h e d with alcohol to give 2.46 g (80%) of IVa with
mp 258-260 ~ ( f r o m alcohol). Found: C 75.1; H 5.2; N 13.2%; tool. wt. 671,659o* C3sH30N602 0.5C2H5OH.
Calculated: C 75.2; H 5.2; N 13.2%; tool. wt. 637. UV s p e c t r u m , k m a x , n m (log s 207 (4.68), 259 (4.45).
3 - A m i n o - l , 4 v,6T-triphenylspiro(pyrazole-4,Sw-hexahydropyrimidine)2,5T-dione (III). /k m i x t u r e of 1.75
g (0.01 mole) of Ia and 4.16 g (0.02 mole) of b e n z a l b i s u r e a was refluxed for 1.5 h in 10 ml of glacial
CH3COOH , a f t e r which it was cooled and poured into w a t e r . The aqueous m i x t u r e was n e u t r a l i z e d with d r y
NaHCO3, and the r e s u l t i n g p r e c i p i t a t e was r e m o v e d b y filtration, dried, and w a s h e d throughouly with e t h e r
to give 1.03 g (24%) of HI with mp 270-273 ~ ( f r o m alcohol). Found: C 69.7; H 5.0; N 16.6%. C24H21N502.
Calculated: C 70.2; H 5.1; N 17.0%. IR s p e c t r u m , c m - l : 1680, 1700 (C =O); 3410 ( N - H ) . UV s p e c t r u m ,
k m a x , n m (log s 202 (4.55), 252 (4.35).
E v a p o r a t i o n of the e t h e r f i l t r a t e gave 1.85 g (60%) of IVa.
2 , 2 ' - B e n z a l b i s ( 1 - m e t h y l - 4 - b e n z a l - 3 - i m i n o - 5 - p y r a z o l o n e ) (IVb). A m i x t u r e of 2.0 (17.7 mmole) of Ib
and 7.36 g (3.54 mmole) of b e n z a l b i s u r e a in 20 ml of glacial CH3COOH was r e f l u x e d for 1.5 h, a f t e r which
it was cooled and p o u r e d into 200 ml of w a t e r . The r e s u l t i n g p r e c i p i t a t e was r e m o v e d by filtration, w a s h e d
s u c c e s s i v e l y with w a t e r , 10% NaHCO 3 solution, and w a t e r , and dried to give 8.5 g (97%) of IVb with mp 283-
284 ~ (from n-propanol). Found: C 70.9;H 5.5; N 17.3%; mol. wt.490. C29H26N602. Calculated: C 71.0;
H 5.3; N 17.1%; m o l . wt. 490. IR s p e c t r u m (CHC13) , c m - l : 1710-1720 (C =O); 3210, 3270, and 3380 ( N - H ) .
UV s p e c t r u m , k m a x , n m (log ~): 208 (4.40), 294 (3.76). PMR s p e c t r u m , 5 , ppm: 2.3 '(s, CH3); 3.9
(s, - C H < ) ; 4.7 (s, > C H = C H - ) , and 7.4 (m, C6H5) with an intensity r a t i o of 6 : 1 : 2 : 15.

2 , 6 - D i m e t h y l - 4 - p h e n y l - 3 , 5 - d i o x o d i p y r a z o l o [ 3 , 4 - b :4T,3v-e]pyr[dine (V). A 2 . 0 - g (17.7 mmole) s a m p l e

of Ib was refluxed with 3.7 g (17.7 mmole) of b e n z a l b [ s u r e a in 25 ml of glacial CH3COOH for 6 h, a f t e r which
the m i x t u r e was cooled, and the r e s u l t i n g b r i g h t - y e l l o w p r e c i p i t a t e was r e m o v e d by filtration, w a s h e d with
a c e t i c acid, and dried o v e r NaOH in a d e s i c c a t o r to give 0.27 g (10%) of V with mp > 360 ~ Found: C 60.8;
H 4.5%; m o l . wt. 295. C15H13N~O2. Calculated: C 61.0; H 4.4%; tool. wt. 295.
The acetic acid f i l t r a t e yielded 1.45 g (33%) of IVb.
1 , 7 - D i a c e t y l - 2 , 6 - d i m e t h y l - 4 - p h e n y l - 3 , 5 - d i o x o d i p y r a z o l o [3,4-b : 4 T,3t-e]pyr idine (VI). A solution of
0.29 g (1 mmole) of V in 20 ml of a c e t i c anhydride was r e f l u x e d for 1 h, a f t e r which the hot m i x t u r e was fil-
t e r e d and cooled. The p r e c i p i t a t e d c r y s t a l s w e r e r e m o v e d by filtration to give 0.12 g of VI with mp 245-
250 ~ (from dioxane). Found: N 18.5; COCH 3 22.7%. C19H1yN504. Calculated-. N 18.5; COCH 3 22.7%. IR
s p e c t r u m , c m - l : 1700, 1720, and 1730 (C =O). UV s p e c t r u m , ~'max, n m (log e): 278 (4.28).
2 , 6 - D i m e t h y l - 3 , 5 - d i o x o d i p y r a z o l o [ 3 , 4 - b . 4 ' , 3 ' - e ] p y r i d i n e (VII). A m i x t u r e of 1.0 g (8.85 mmole) of Ib
and 1.2 g (8.85 mmole) of m e t h y l e n e b [ s u r e a in 20 ml of glacial CH3COOH was r e f l u x e d for 2 h, a f t e r which
it was allowed to stand overnight. The r e s u l t i n g yellow p r e c i p i t a t e was then r e m o v e d by filtration, washed
s u c c e s s i v e l y with acetic acid and w a t e r , and dried thoroughly o v e r NaOH in a d e s i c c a t o r to give 0.15 g (15%)
of VII with m p > 3 6 0 ~ ( f r o m acetic acid). Found: C 49.3; H 4.3; N 31.7%; tool. wt.219. CgHgNsO 2. C a l c u -
lated: C 49.3; H 4.1; N 31.9%; m o l . wt. 219. IR s p e c t r u m , c m - 1 : 1 6 5 0 b r o a d (C =O).
1 - M e t h y l - 4 - p h e n y l - 3 - h y d r o x y - 6 - o x o - 4 , 5 , 6 , 7 - t e t r a h y d r o p y r a z o l e [3,4-d]pyrimidine (VIII). A 4.0-g
(35.4 mmole) s a m p l e of II was refluxed for 2 h with 14.7 g (70.8 mmole) of b e n z a l b i s u r e a in 70 ml of g l a -
cial CH3COOH , a f t e r which the m i x t u r e was cooled and p o u r e d into 700 ml of w a t e r . The aqueous mixture
was filtered, and the f i l t r a t e was n e u t r a l i z e d with d r y NaHCO 3. The r e s u l t i n g o r a n g e - y e l l o w ( s o m e t i m e s
containing r e s i n ) p r e c i p i t a t e of A was r e m o v e d by filtration, washed with e t h e r , and r e c r y s t a l l i z e d f r o m a l -
cohol to give 1 g of a compound with a m o l e c u l a r weight of 302 and mp 265-270 ~ (decomp.).
The f i l t r a t e f r o m the s e p a r a t i o n of p r e c i p i t a t e A was allowed to stand f o r 3 days at r o o m t e m p e r a -
t u r e , as a r e s u l t of which a white p r e c i p i t a t e w a s obtained. It was r e m o v e d b y filtration and washed with
w a t e r to give 1.2 g (15%) of VIII with mp 290 ~ (decomp. f r o m alcohol). Found: C 58.9; H 5.7; N 18.4%; m o l .
wt. 244. C12H12N402.0.5C2H5OH. Calculated.. C 58.5; H 5.6; N 18.0%; tool. wt. 244. UV s p e c t r u m , ~ m a x ,
n m (log e). 209 (4.14), 252 (3.80).

* D e t e r m i n e d by i s o t h e r m a l distillation.

718
 1-Methyl-4-phenyl-3-hydroxy-6-oxo-6,7-dihyc~ropyrazolo[3,4-d]pyrimidine (IX). A mixture of 0.53 g
(2.18 mmole) of VIII and 0.64 g (2.61 mmole) of chloranil was refluxed for 5.5 h in 9 ml of absolute xylene,
after which the mixture was cooled, and the r e s u l t i n g precipitate was r e m o v e d by filtration and washed suc-
c e s s i v e l y with methanol and e t h e r to give 0.38 g (89%) of IX with mp > 345 ~ (deeomp. f r o m n-propanol).
Found: C 60.0; H 4.3; N 22.5%; tool. wt. 242. CI2HIoNaO2. Calculated: C 59.5; H 4.1; N 23.1%; mol. wt.242.
IR s p e c t r u m , c m - l : 1620-1640 (C =O). UV s p e c t r u m , ~'max, n m (log e): 204 (4.50), 256 (4.28), 314 (3.95).
1,7-Dimethyl-4-phenyl-3,5-d[hYdroxydipyrazolo [3,4-b : 4 ' , 3 ' - e ]pyridine (X). The p r o c e d u r e used to
obtain pyridine V was used to obtain this compound, with m p > 360 ~ in 10% yield f r o m II and benzalbisurea.
Found: C 61.4; H 4.5; N 23.4%; tool. wt. 295. C15H13N502. Calculated: C 61.0; H 4.4; N 23.7%; mol. wt. 295.
IR s p e c t r u m , c m - l : 1600, 1660 w.
1,7-Dimethyl-3,5-dihydroxydipyrazolo[3,4-b : 4 ' , 3 ' - e ] p y r i d i n e (XI). The p r o c e d u r e used to p r e p a r e
pyridine X was used to obtain this compound, with mp > 340 ~ (decomp.), in 7% yield f r o m II and methylene-
bisurea. Found: C 49.3; H 4.2; N 31.8%; tool. wt. 219. CgHgNsO2. Calculated: C 49.3; H 4.1; N 31.9%; mol.
wt. 219. IR s p e c t r u m , c m - l : 1620, 1680 w.

LITERATURE CITED
1. M . A . Mikhaleva, S. A. Romanovskaya, N. M. Belova, V. F. Sedova, and V. P. Mamaev, Zh. Organ.
K~him., 100, 859 (1974).
2. V . P . Mamaev and M. A. Mikhaleva, Kh[m. Geterotsikl. Soedin., 1083 (1967).
3. M.A. Mikhaleva and V. P. Mamaev, Izv. Sibirsk. Otd. Akad. Nauk SSSR, Ser. Khim., No. 14, 93 (1969).
4. V . P . Mamaev and M. A. Mikhaleva, Khira. Geterotsikl. Soedin., 535 (1971).
5. M . A . Mikhaleva, L. N. ]:l'chenko, and V. P. Mamaev, Khim. Geterotsild. Soedin., 233 (1974).
6. J. Feeney, G. A. Newman, and P. J. Pauwels, J. Chem. Soc., C, 1842 (1970).
7. M. St. Flett, C h a r a c t e r i s t i c Frequencies of Chemical Groups in the I n f r a r e d (1963), p. 72.
8. J. Emsley, J. Finney, and L. Sutcliffe, High-Resolution Nuclear Magnetic Resonance Spectroscopy,
P e r g a m o n (1966).
9. A. Brack, Belgian Patent No. 616,472 (1962); Chem. Abstr., 5_~8,P12,572c (1963).
10. H. B r e d e r e c k , F. E f f e n b e r g e r , and W. Rosemann, Chem. B e r . , 95, 2796 (1962).
11. Hirvaki Kadowaki, Bull. Chem. Soc. Japan, 1 1 , 2 4 8 (1936); Chem. Abstr., 30, 5944 (1936).

719
PARAMAGNETIC' RING CURRENT IN THE DIAZEPINE
RING OF THE 1H-BENZO-1,5-DIAZEPINIUM
MONOCATION

K. F. Turchin UDC 541.67 : 543.422.25 : 547.892

The signals of all of the protons in the PMR s p e c t r u m of 2 , 4 - d i m e t h y l - l H - b e n z o - l , 5 - d i a z e p i n e

h y d r o c h l o r i d e axe shifted to s t r o n g e r fields by 0.5-1.0 p p m r e l a t i v e to the signals of the a n a l -
ogous protons in model compounds. This shift is explained by the c o n s i d e r a b l e p a r a m a g n e t i e
contribution of the eight 7r e l e c t r o n s of the diazepine r i n g of the 1 H - b e n z o - l , 5 - d i a z e p i n i u m
monocation to the magnetic s u s c e p t i b i l i t y of the molecule. Calculations of the I t - e l e c t r o n
r i n g c u r r e n t and the 7r-electron component of the magnetic s u s c e p t i b i l i t y of this monoeation
by the MO LCAO method showed that the r i n g c u r r e n t in the s e v e n - m e m b e r e d rizig is p a r a -
magnetic and depends m a r k e d l y on the magnitude of the coulombie integral for nitrogen.

During a study of the PIVIR s p e c t r a of 2 , 4 - d i m e t h y l - l H - b e n z o - l , 5 - d i a z e p i n e (I), its hydrochloride

(I+C1-), and a solution of I in H2SO 4 (I++ 92HSO4-) , our attention was drawn to the unusual r e l a t i o n s h i p b e -
tween the magnitudes of the c h e m i c a l shifts of the phenyl and methyl protons in b a s e I and ionic f o r m s I +
and I ++.

.N "CH3 ~ . ~./CH 3
.N .%. a

n Lk.JA +~/\n
H3 3 ~J "~-"~c.~
il I+ I ++

In the s p e c t r u m of monocation I +, the signals of t h e s e protons a r e found at s t r o n g e r fields than in the

e a s e of b a s e I, while in the c a s e of dication I + + t h e y a r e found at w e a k e r fields (Table 1). The signal of
H " H

II II + Ill Ill +

the methylene protons in the 3 position, with an intensity of 2 proton units (p.u.), which is c h a r a c t e r i s t i c
for b a s e I and dieation I ++, is absent in the s p e c t r u m of monocation I+, in which the singlet with an inten-
s i t y of 1 p.u. at 4.0-4.2 p p m is affiliated with the 3-H proton.
It should be noted that B a r r y and c o - w o r k e r s , who studied the PM:R s p e c t r a of 1 H - b e n z o - l , 5 - d i z e -
pines [1], assigned the signal in the r e g i o n of the r e s o n a n c e of a r o m a t i c protons to the 3 - H proton of mono-
cation I +. This a s s i g n m e n t r a i s e s s o m e doubt. It might be a s s u m e d that exchange of the 3 - H p r o t o n of
monocation I + with the protons of the COOH groups of the solvent o c c u r s in the solvents used b y B a r r y and
c o - w o r k e r s [1]-CF3COOH and CI)C13 +CH3COOtt- and the signal at 4.0-4.2 p p m is v e r y m a r k e d l y
broadened.
The unusual s t r o n g - f i e l d position of the signals of all of the protons of monocation I + is p a r t i c u l a r l y
noticeable on c o m p a r i n g the c h e m i c a l shifts of the protons of I + with those of model compounds containing

S. Ordzhonikidze All-Union S c i e n t i f i c - R e s e a r c h P h a r m a c e u t i c a l C h e m i s t r y Institute, Moscow.

T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 6, pp. 828-832, June, 1974. Original a r t i c l e
s u b m i t t e d F e b r u a r y 8, 1973.

9 19 75Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is availablefrom the publisher for $15.00.

720
 T A B L E 1. C h e m i c a l Shifts of t h e P r o t o n s of t h e B a s e s and C a t i o n s
o f I, II, and III*

Formula Solvent ~, ppm

CHa 3-H 6-H, 9-H 7-H, 8-H

It CDC[a 2,32 2,80"t 7,3
1 CDaOD 2,38 2,901" 7,3
1 (CD3)2SO 2,29 2,80~" 7,22
1+CI- CDaOD 1,82 4,19 6,48 6,87
I-"CI- (CDa)2SO 1,80 4,08 6,65 6,85
I CDaOD+ DeSO4 1,82 4.20 6,47 6,87
12 H2SO4 3,6 - 4,70 ~" 8,4
11 CFaCOOII 1.87 6,1 7,1
CHa 6-H CH~
I1e CDCIa 1,88 4,40 3,42
II+C1- CDaOD 2,21 5,01 3,63
II+CI- (CDa)2SO 2,17 4,87 3,52
II+CI- 1 N DCI 2,I7 5,00 3,60
4-H, 7-H 5-H,6-H 2-H
Ill CDaOD 7,61 7,24 8,12
IIl (CDa)2SO 7,60 7,19 8,21
III+CI- CDaOD 7,88 7,66 9,50
IlI+CI- (CDa)~SO 7,80 7,61 9,69

* The P M R s p e c t r a w e r e o b t a i n e d w i t h a J N M - 4 H - 1 0 0 s p e c t r o m e t e r .
~"T h e s e a r e t h e p r o t o n s o f t h e CH 2 g r o u p .

i n d i v i d u a l f r a g m e n t s of t h e I + m o l e c u l e (Table' 1). 5 , 7 - D t m e t h y l - 2 , 3 - d i h y d r o - l H - 1 , 4 - d i a z e p i n e (II) and i t s

h y d r o c h l o r i d e (II+C1-), in w h i c h t h e 6 - H p r o t o n and t h e CH 3 g r o u p in t h e 5 and 7 p o s i t i o n s a r e a n a l o g o u s ,
r e s p e c t i v e l y , to the 3 - H p r o t o n and CH 3 g r o u p in t h e 2 and 4 p o s i t i o n s o f I+C1 - , a n d b e n z i m i d a z o l e (III) and
its h y d r o c b l o r i d e (III+CI-), t h e 4 - and 5-H p r o t o n s of w h i c h a r e a n a l o g o u s to 6- and 7 - H o f I+C1 - , r e s p e c -
t i v e l y , w e r e u s e d a s m o d e l c o m p o u n d s of t h i s kind.

The s i g n a l of t h e 3 - H p r o t o n of I+C1 - is found at s t r o n g e r f i e l d s (0.8 p p m s t r o n g e r ) t h a n t h e s i g n a l of

t h e c o r r e s p o n d i n g 6 - H p r o t o n in II+C1 - ( T a b l e 1). The s i g n a l of t h e p r o t o n s o f t h e m e t h y l s u b s t i t u e n t s o f
t h e s e v e n - m e m b e r e d r i n g in I+C1 - is s h i f t e d to s t r o n g e r f i e l d s b y 0.38 p p m r e l a t i v e to II+C1 - . T h e v a l u e s
found s h o u l d be c o r r e c t e d for the e f f e c t of t h e d i a m a g n e t i c r i n g c u r r e n t o f t h e b e n z e n e r i n g * in I+CIS. T h i s
e f f e c t w a s e v a l u a t e d f r o m t h e t a b l e s in [3] a s b e i n g 0.18 and 0.14 p p m f o r 3 - H and CH3, r e s p e c t i v e l y . C o n -
s e q u e n t l y , t h e e x c e s s s h i f t to s t r o n g f i e l d of the s i g n a l s of t h e 3 - H and CH 3 s i g n a l s in I+C1 - r e l a t i v e to t h e
p o s i t i o n s e x p e c t e d on t h e b a s i s o f a n e x a m i n a t i o n o f m o d e l c o m p o u n d II+C1 - a r e ~ 1 and 0.5 p p m , r e s p e c -
tively.

A c o m p a r i s o n of t h e c h e m i c a l s h i f t s of t h e p r o t o n s of t h e b e n z e n e r i n g o f I+C1 - w i t h t h e c o r r e s p o n d -
ing v a l u e s f o r III+C1 - s h e w s t h a t t h e s h i f t to s t r o n g f i e l d is 1.3 p p m f o r the 6 - H p r o t o n in I+C1 - r e l a t i v e to
4 - H in III+CI - a n d 0.78 p p m f o r 7 - H in I+C1 - r e l a t i v e to 5 - H in III+C1 - . T h e d i a m a g n e t i c r i n g c u r r e n t in
t h e f i v e - m e m b e r e d r i n g o f b e n z i m i d a z o l e p r o b a b l y m a k e s a c e r t a i n c o n t r i b u t i o n to t h e a b o v e d i f f e r e n c e s in
t h e c h e m i c a l s h i f t s . W h e n t h i s e f f e c t is t a k e n into a c c o u n t , t h e e x c e s s s h i f t to s t r o n g f i e l d o f t h e s i g n a l s
of the p r o t o n s of t h e b e n z e n e r i n g o f I+C1 - r e l a t i v e to t h e v a l u e s e x p e c t e d on the b a s i s of a s t u d y of m o d e l
c o m p o u n d III+C1 - w a s ~ 0.8 p p m f o r 6 - H and ~ 0.6 p p m f o r 7-H.-~
It i s i n t e r e s t i n g to n o t e t h e r e v e r s e e f f e c t of p r o t o n a t i o n of t h e n i t r o g e n a t o m on t h e c h e m i c a l s h i f t s
o f t h e p r o t o n s of I, on t h e one hand, and o f II a n d I l l , on t h e o t h e r . It f o l l o w s f r o m T a b l e 1 t h a t on p a s s i n g
f r o m b a s e s 1I a n d III to t h e c o r r e s p o n d i n g m o n o c a t i o n s II + a n d I l l + t h e s i g n a l s o f a l l o f t h e p r o t o n s a r e
s h i f t e d to w e a k e r f i e l d ; t h i s is a l s o c h a r a c t e r i s t i c f o r o t h e r n i t r o g e n h e t e r o c y c l i c c o m p o u n d s .
The e x c e s s s h i f t s to s t r o n g f i e l d ( A S ) o f t h e s i g n a l s of t h e p r o t o n s o f I+C1 - a r e p r e s e n t e d in T a b l e 2.
L e t us e x a m i n e t h e p o s s i b l e r e a s o n s f o r t h i s e f f e c t . One of t h e f a c t o r s t h a t a f f e c t t h e c h e m i c a l s h i f t s
o f p r o t o n s in c o n j u g a t e d s y s t e m s is the d e n s i t y of the 7 r - e l e c t r o n c h a r g e on t h e c a r b o n a t o m to w h i c h a p r o -
ton is c o n n e c t e d [4]. The d i f f e r e n c e s in t h e ~ r - e l e c t r o n d e n s i t i e s (Aq ~r) on t h e c a r b o n a t o m s in I + and t h e

*It w a s a s s u m e d t h a t t h e i n d i c a t e d e f f e c t is d e t e r m i n e d o n l y b y t h e d i s t a n c e b e t w e e n t h e p r o t o n a n d t h e c e n -
t e r of the b e n z e n e r i n g .
Ia t h e c a l c u l a t i o n o f the c o r r e c t i o n for t h e rhag c u r r e n t of t h e f i v e - m e m b e r e d r i n g in III+C1 - it w a s a s -
s u m e d t h a t t h i s c u r r e n t is of t h e s a m e m a g n i t u d e a s t h a t of t h e b e n z e n e r i n g .

721
 TABLE 2. A6 and R Values for the P r o t o n s and Aq ~r Values for the
Carbon A t o m s of Monocation I +
I
Parameter i 3-H ~1 2-CH~ 6-H 7-If
t

AS,ppm I - 1,0 ] -0,5 -0,8 -0,6

Aq~ ] ~-0,030 t -- 0,073 +0.030 +0,008
R, s l 2,7 3,7 3,7 5,0

TABLE 3. r - E l e c t r o n Ring C u r r e n t s 16 and 17 in the S i x - M e m b e r e d

and S e v e n - M e m b e r e d Rings of Monocation I +, Contributions of X 6Z,
X 677r, and X777r to the ~ - E l e e t r o n Component of the Magnetic Suscep-
tibility of the Two-Ring System, and Their Summation (ZX ~) for Var-
ious Values of Coulombic P a r a m e t e r h N (IC6H6 and XvC6Hs were a s -
sumed to be unity)

0 - 0,285 -- 2,473 1,37 -- 3,32 -- 1,80 -- 3,75

0,5 0,323 -- 1,638 1,23 -- 1,80 -- 1,40 -- 1,97
1.0 0.592 -- 1,097 1,135 -- 1,08 -- 1,00 -- 0,944
1,5 0.730 --0,753 1,08 -- 0,703 --0,701 --0,324
2,0 0.810 --0,532 1,055 --0,486 --0,503 0,066

c o r r e s p o n d i n g model compounds (II+ for C 3 and C2, 4, and HI + for C 6 and C7) are indicated in Table 2.* The
r e l a t i v e l y small differences in the r - e l e c t r o n densities and the constancy of the sign of differences A6 v i s -
h-ViS the difference in the sign of differences ~,qTr attest that it is not this effect that determines the shift
in the signals of the protons of I+C1 - to strong field.
Another factor that affects the magnitudes of the chemical shifts of the protons in conjugated cyclic
s y s t e m s is the induced ring c u r r e n t . The effect of the r i n g c u r r e n t should be identical in sign for all of the
protons situated in the plane of the ring and should d e c r e a s e as the distance f r o m the center of the r i n g in-
c r e a s e s . A c o m p a r i s o n of the A6 values found with the distances of the c o r r e s p o n d i n g protons f r o m the
center of the s e v e n - m e m b e r e d ring in I + (R, Table 2) shows that these conditions are basically satisfied,
and the sign of the effect of the r i n g c u r r e n t turns out to be the opposite of the sign of this effect in a r o m a t i c
systems.
Thus the data obtained in this study make it possible to conclude that the magnetic field in the s e v e n -
m e m b e r e d r i n g of the 1 H - b e n z o - l , 5 - d i a z e p i n i u m monocation induces a p a r a m a g n e t i e ring c u r r e n t , in con-
t r a s t to the diamagnetic ring c u r r e n t in a r o m a t i c s y s t e m s .
This conclusion is confirmed by calculation of the magnitudes of the ~r-electron ring c u r r e n t s and the
~r-electron component of the magnetic susceptibility of the 1 H - b e n z o - l , 5 - d i a z e p i n i u m monocation within the
f r a m e w o r k of the MO LCAO method by the p r o c e d u r e in [5] (Table 3). The calculation was made for dif-
ferent values of the coulombic integral for nitrogen, during which it was a s s u m e d that by virtue of the s y m -
m e t r y of the I + monocation the coulombic integrals for N 1 and N~ are equal, i.e., a N l = a N s = a C +hNfl. It
was further a s s u m e d that all of the r e s o n a n c e integrals are equal to fl and that both of the r i n g s of the two-
r i n g s y s t e m are r e g u l a r polyhedra.
According to Table 3, the calculation predicts the existence of a p a r a m a g n e t i e r i n g c u r r e n t in the
s e v e n - m e m b e r e d ring, the magnitude of which d e c r e a s e s as coulombic p a r a m e t e r h N for the nitrogen atom
i n c r e a s e s . The r i n g c u r r e n t for the s i x - m e m b e r e d ring is p a r a m a g n e t i e for v e r y low hN values and dia-
magnetic for v e r y high h N values and approaches the magnitude of the ring c u r r e n t in benzene as hN in-
c r e a s e s . The contributions of the s i x - and s e v e n - m e m b e r e d rings to the r - e l e c t r o n component of the m a g -
netic susceptibility of the t w o - r i n g s y s t e m change c o r r e s p o n d i n g l y : the p a r a m a g n e t i s m d e c r e a s e s as h N
i n c r e a s e s . However, the contributions of X 67r and X 77~r a r e p a r a m a g n e t i c and considerable with r e s p e c t
to their absolute value o v e r the entire r a n g e of h N values used in the l i t e r a t u r e [6]. The a n i s o t r o p y of the

~'The ~r-electron densities were calculated by the simple Hfiekel method (Hiickel MO) with h N = l and
k e n =1.

722
magnetic susceptibility of the iH-benzo~ 1,5-diazepinium monocation (A i +) should t h e r e f o r e be markedly
d e p r e s s e d o r even have a sign that is the opposite of the sign of A)~C6H6; this is in a g r e e m e n t with the ex-
p e r i m e n t a l data f r o m the PMR s p e c t r u m of I+C1 -.
In a number of studies it has been shown that the c h a r a c t e r of the ring c u r r e n t in a conjugated c a r b o -
cyclic s y s t e m (or of individual rings of a polycyclic ring) is d e t e r m i n e d by the number of ~r-electrons: the
c u r r e n t is diamagnetic for 4n +2 ~ - e l e c t r o n s and paramagnetic for 4n 7r - e l e c t r o n s (n is the whole number)
[7-10]. Cyclic s y s t e m s with 4n 7r-electrons have been singled out f r o m conjugated molecules with r e s p e c t
to a number of p r o p e r t i e s and have been called antiaromatic s y s t e m s [11, 12].
The existence of a paramagnetic ring c u r r e n t has been r e l i a b l y established in a study of the PMR
s p e c t r a of annulenes [10, 13, 14] and condensed conjugated c a r b o c y c l e s (three- and f o u r - r i n g systems) [15,
16]. The influence of this effect on the chemical shifts of the protons in some h e t e r o c y c l i c compounds has
also been contemplated [17, 18].
The conjugated s y s t e m of the 1 H - b e n z o - l , 5 - d i a z e p i n i u m monocation is f o r m e d by 12 7r-electrons, of
which eight belong to the s y s t e m of the s e v e n - m e m b e r e d diazepine ring. Consequently, this ring in I + is
lsoelectronic with r e s p e c t to the antiaromatic s y s t e m of the t r o p y l i u m anion, for which, in accordance with
the Hfickel MO method, two 7r-electrons a r e found in a doubly degenerate antibonding orbital, and the ring
c u r r e n t is paramagnetie and infinite in magnitude [10]. The introduction of h e t e r o a t o m s into the t r o p y l i u m
s y s t e m and condensation with a benzene r i n g lower the e n e r g y and r e m o v e the d e g e n e r a c y of the upper oc-
cupied level. However, the tmfilled c h a r a c t e r of the e l e c t r o n shell is r e t a i n e d [7, 19] as, for example, in
the antiaromatic penta]ene s y s t e m (eight 7r-electrons), for which calculations give a magnetic susceptibility
(of opposite sign) that is g r e a t e r than that of benzene by a factor of 2.5 [8, 9].
Thus all of the data obtained in this study indicate the existence of a paramagnetic ring c u r r e n t in the
conjugated h e t e r o c y e l i c 1 H - b e n z o - l , 5 - d i a z e p i n i u m monocation as one of the manifestations of the antiaro-
marie c h a r a c t e r of the diazepine ring in this s y s t e m .
The author thanks T. S. Safonov and Yu. N. Sheinker for t h e i r discussion of this r e s e a r c h and K. V.
Levshin for supplying the compounds.

LITERATURE CITED
1. W . J . B a r r y , I. L. Finar, and E. F. Mooney, Spectrochim. Acta, 21, 1095 (1965).
2. H. Staab and F. VSgtle, B e r . , 98, 2701 (1965).
3. C . E . Johnson and F. A. J. Bovey, J. Chem. P h y s . , 2_9.9, 1012 (1958).
4. B. P, Dayley, A. Gawer, and W. C. Neikam, Disc. F a r a d a y Soc., 34, 18 (1962).
5. J . A . Pople, Mol. P h y s . , 1, 175 (1958).
6. A. S t r e i t w i e s e r , Molecular Orbital T h e o r y for Organic C h e m i s t s , W i l e y (1961).
7. Ya. G. Dorfman, Diamagnetism and the Chemical Bond [in Russian], Gos. Izd. Fiz.-Mat. Lit., Moscow
(1961), p. 26.
8. G. B e r t h i e r , M. Ma.vot, and B. Pullman, J. Phys. et le Radium, 12, 717 (1951).
9. . T . K . Rebane, Dokl. Akad~ Nauk SSSR, 114., 70 (1957).
10. J . A . Pople and K. G. Untch, J. Amer. Chem. Soc., 88, 4811 (1966).
11. R. Breslow, Chem. Eng. News, 43, No. 26, 90 (1965).
12. I. F i s e h e r - H j a l m a r s , in: Aromatieity, P s e u d o - A r o m a t i c i t y , and Anti-Aromaticity, J e r u s a l e m Sym-
posia on Quantum C h e m i s t r y and B i o c h e m i s t r y , edited by E. D. Bergmaml and B. Pullman, J e r u s a l e m
(1971), p. 375.
13. K.G. Untch and D. C. Wysoeky, J. Amer. Chem. Soc., 89, 6386 (1967).
14. H. Ogawa, M. Kubo, and H. Saikaehi, Tetrahedron Left., 4859 (1971).
15. B.M. Trost and G. M. Bright, J. Amer. Chem. See., 89, 4244 (1967).
16. D.E. Jtmg, Tetrahedron, 2_5.5, 129 (1969).
17. R.H. Schlessinger, (in the references to Literature Cited No. 12), p. 258.
18. A.F. Pozharskii, I. S. Kashparov, P. J. Holls, and V. G. Zaletov, Khim. Geterotsikl. Soedin., 543
(1971).
19. M.E. Vol~pin, Usp. Khim., 2-9, 298 (1960).

723
SYNTHESIS OF NITRO-SUBSTITUTED 4-METHYL-
2,3-DIHYDI~O- AND 2,3,4,5-TETRAHYDI~O-
1H- 1,5-BENZO-2- DIA Z EPINONES

B. A. Puodzhyunaite and Z. A. Talaikite UDC 547.892.07 : 542.941.7T958.1

The nitration of 4 - m e t h y l - 2 , 3 - d i h y d r o - l H - 1 , 5 - b e n z o - 2 - d i a z e p i n o n e gives the 7 n i t r o d e r i v a -

tive. The 8-nitro i s o m e r was obtained f r o m 4 - n i t r o - l , 2 - p h e n y l e n e d i a m i n e . The catalytic
hydrogenation of the nitrobenzodiazepinones gives the 7- and 8-amino d e r i v a t i v e s . The n i t r o -
benzodiazepinones e x i s t in the enol f o r m in alkaline media.

We have e s t a b l i s h e d t h a t a m o n o n i t r o d e r i v a t i v e (II) is f o r m e d in the nitration of 4 - m e t h y l - 2 , 3 - d i h y d r o -

1H-1,5-benzodiazepinone (I) with a m i x t u r e of p o t a s s i u m n i t r a t e and s u l f u r i c acid at low t e m p e r a t u r e s * ;
r a i s i n g the r e a c t i o n t e m p e r a t u r e leads to r e s i n i f i c a t i o n . The s t r u c t u r e of II was c o n f i r m e d by a l t e r n a t i v e
s y n t h e s i s and t h e r m a l r e a r r a n g e m e n t of it to 6 - n i t r o - l - i s o p r o p e n y l - 2 - b e n z i m i d a z o l o n e (IV) [1, 2].
In the r e a c t i o n of a c e t o a c e t i c e s t e r with 4 - n i t r o - l , 2 - p h e n y l e n e d i a m i n e the m o r e b a s i c amino g r o u p
undergoes r e a c t i o n to give ethyl 3 - ( 2 - a m i n o p h e n y l - a m i n o ) c r o t o n a t e {III) [1, 2], which c y c l i z e s to 7 - n i t r o -
4 - m e t h y l - 2 , 3 - d i h y d r o - l H - 1 , 5 - b e n z o - 2 - d i a z e p i n o n e (II) on heating in the p r e s e n c e of s o d i u m methoxide. A c -
cording to the UV and IR s p e c t r a l data, product II is identical to the s u b s t a n c e obtained by d i r e c t n i t r a t i o n
of I. The PMR s p e c t r a c o n f i r m s t r u c t u r e II. Compound H d e c o m p o s e s to acetone and 4 - n i t r o - l , 2 - p h e n y l -
enediamine on refluxing with 5 N h y d r o c h l o r i c acid. A s i m i l a r decomposition was d e s c r i b e d in [3].

\ ~ (r , n.o

Ell a
I il Ill

g||

The product of t h e r m a l i s o m e r i z a t i o n - i s o p r o p e n y l b e n z i m i d a z o l o n e IV - is also f o r m e d b y heating

nitrobenzodiazepinone II or c r o t o n a t e IH in the p r e s e n c e of the s o d i u m alkoxide of ethylene glycol monoethyl
ether. The acid h y d r o l y s i s of IV gives the p r e v i o u s l y d e s c r i b e d 5 - n i t r o - b e n z i m i d a z o l o n e (V) [4].
8 - N i t r o - 4 - m e t h y l - 2 , 3 , 4 , 5 - t e t r a h y d r o - l H - 1 , 5 - b e n z o - 2 - d i a z e p i n o n e (VII) was s y n t h e s i z e d by fusing
4 - n i t r o - l , 2 - p h e n y l e n e d i a m i n e with crotonic acid. According to the data in [5], 4 - s u b s t i t u t e d o - p h e n y l e n e -
diamines r e a c t with a , f l - u n s a t u r a t e d acids to give 8 - s u b s t i t u t e d t e t r a h y d r o - l , 5 - b e n z o - 2 - d i a z e p i n o n e s .
Acylation of VII with acetyl chloride gave the c o r r e s p o n d i n g 5 - a c e t y l d e r i v a t i v e (IX).

*An attempt to n i t r a t e 2 , 3 , 4 , 5 - t e t r a h y d r o - l H - 1 , 5 - b e n z o - 2 - d i a z e p i n o n e under the s a m e conditions was tin-

successful.

Institute of B i o c h e m i s t r y , A c a d e m y of Sciences of the Lithuanian SSR, VUnius. T r a n s l a t e d f r o m

Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 6, pp. 833-837, June, 1974. Original a r t i c l e s u b m i t t e d June
26, 1973.

9 19 75Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retn'eval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is availablefrom the publisher for $15.00.

724
 C .10-3

~.I0-3
20
12.
I \ / ',
/b
10. 16
I~Ir
I'.: r"
\ I
I 9
I
Itf', \ ,' 9 12 ///" '~'i
\,; .
6" \,r ',. \ / ',
4,
l",i ;\ ' ',

2'

220 260 300 340 380 420 As nm

I
220 260 300 340 380 420 2v, nffl

Fig. 1 Fig. 2
Fig. 1. UV s p e c t r a of X (1 and 2) and VII (3 and 4) in acidic (1 and 3) and alkaline
(2 and 4) media.
Fig. 2. UV s p e c t r a of I (1 and 2) and II (3 and 4) in acidic (1 and 3) and alkaline
(2 and 4) media.

Catalytic hydrogenation of nitrobenzodiazepinones II and VII gave 7- and 8 - a m i n o - 4 - m e t h y l - 2 , 3 , 4 , 5 -

t e t r a h y d r o - l H - 1 , 5 - b e n z o - 2 - d i a z e p i n o n e s (VI and VIII), the s t r u c t u r e s of which w e r e c o n f i r m e d by the PMR
spectra.
The UV s p e c t r a of 4 - m e t h y l - 2 , 3 , 4 , 5 - t e t r a h y d r o - l H - 1 , 5 - b e n z o - 2 - d i a z e p i n o n e (X), VII, and dihydro-
benzodiazepinones I and II depend on the pH of the m e d i a (Figs. 1 and 2). The changes in the s p e c t r a in
acidic media a r e a s s o c i a t e d with salt f o r m a t i o n ; this is r e f l e c t e d in the s p e c t r u m of X and, to a l e s s e r e x -
tent, in the s p e c t r a of d i h y d r o b e n z o d i a z e p i n o n e s I and II. The changes in the s p e c t r a in alkaline m e d i a of
I, II, and VII a r e a s s o c i a t e d with the i n c r e a s e in conjugation due to the f o r m a t i o n of the enol f o r m ; this is
p a r t i c u l a r l y c h a r a c t e r i s t i c a l l y pronounced in the s p e c t r a of nitro d e r i v a t i v e s II and VII.

EXPERIMENTAL
The IR s p e c t r a of K-Br pellets of the compounds w e r e r e c o r d e d with a UR-10 s p e c t r o m e t e r . The UV
s p e c t r a of solutions of the compounds in alcohol and in 75% alcohol containing 5% H2SO4 or KOH w e r e r e -
corded with an SF-4A s p e e t r o p h o t o m e t e r . The PMR s p e c t r a w e r e r e c o r d e d with Vaxian HA-100 (100 MHz)
and P e r k i n E l m e r R-12 (60 MHz) s p e c t r o m e t e r s with h e x a m e t h y l d i s i l o x a n e (HMDS) and t e t r a m e t h y l s i l a n e
(TMS) as the internal s t a n d a r d s . The solvents for the PMR s p e c t r o s c o p y w e r e CF3CO2H (II, IV, and VII)
and acetone (III, VI, and VIII). The melting points w e r e c o r r e c t e d and w e r e obtained with a Boetius m i c r o -
heating stage.
i

4 - M e t h y l - 2 , 3 , 4 , 5 - t e t z ' a h y d r o - l H - 1 , 5 - b e n z o - 2 - d i a z e p i n o n e ( X ) . This compound, with mp 184-185 ~

(from alcohol) (mp 184-185 ~ [6]), was obtained in 87% yield by catalytic hydrogenation of I b y the method in
[6].
Ethyl 3 - ( 2 - A m i n o p h e n y l a m i n o ) c r o t o n a t e . This compound was obtained by r e a c t i o n of 0.1 mole of
o - p h e n y l e n e d i a m i n e with 0.3 mole of a c e t o a e e t i c e s t e r in neutral m e d i a in a s t r e a m of nitrogen at r o o m
t e m p e r a t u r e (63% yield) or by r e a c t i o n of the s a m e components in acidic media b y the method in [7] (75%
yield). The product had mp 80-82 ~ (from aqueous alcohol (rap 59-62 and 85 ~ [7]).
4 - M e t h y l - 2 , 3 - d i h y d r o - l H - 1 , 5 - b e n z o - 2 - d i a z e p i n o n e (I). This compound, with mp 146-148.5 ~ ( f r o m
water) (mp 147-149 ~ [6]), was obtained in 65% yield f r o m ethyl 3 - ( 2 - a m i n o p h e n y l a m i n o ) e r o t o n a t e by the
method in [6]. UV s p e c t r u m : Area x 290 nm, log e 3.62. UV s p e c t r u m : X m a x 290 nm, log e 3.53 (in a l c o -
hod [8].
Ethyl 3 - ( 2 - A m i n o - 5 - n i t r o p h e n y l a m i n o ) c r o t o n a t e (III). Six drops of c o n c e n t r a t e d h y d r o c h l o r i c acid
w e r e added to a mixture of 3.1 g (20 mmole) of 4 - n i t r o - l , 2 - p h e n y l e n e d i a m i n e [9] and 3.8 ml (30 mmole) of
a c e t o a c e t i c e s t e r , and the m i x t u r e was s t i r r e d for 20 rain. The solidified m a s s was washed with a m i x t u r e

725
 TABLE 1. P h y s i c a l Constants of the Compounds Obtained
Com- Empirical Found, % ! Calc., %
pound rap, ~ formula Yield, %
G ' H N I G ,' H N
I
II 242--243~a C:oHgN303 54,614,2 19,2177 (method)
tlI I35--138~ CI~HIsN304 54,515.9 -- 75
IV 228--230 CmHgNsOa 54,9] 3,9 19,2166 (method)
VI 156--158 C~oH~N30.0,5H~O 59,9 6,8 21,Ol --
Dihydro-
chloride
Picrate
243--245c CmHI~N30.2HCI
261 -t- 26,8 85
154--15~d CIoHlzNsO'C~H3NaO7 20,0 --
VIi 247--248e CmHHN~O3 18,9!72
VIII 175,5--176 f CtoHI~NsO 62,716,7 21,9170
Pierate 174--176,5 CmH13N30-C6H3NzO7 45,913,9 i200 --
1,X 218--219 CI2H~3N304 55.0[4,9 I5, 154; t 4,9 11519 70

aA change in the f o r m of the c r y s t a l s was o b s e r v e d at "~220 ~ (mp

227-228 ~ [1]). bAn unstable modification (rap 90-92~ changes
on s t o r a g e , is c h a r a c t e r i s t i c for the crude product (mp 138-139 ~ [1]).
cWith decomposition. Found; C1 15.9%. Calculated.. C1 16.1%.
d F r o m ethyl acetate, eThe f o r m of the c r y s t a l s changes at 210 ~
f F r o m ethyl a c e t a t e - p e t r o l e u m ether.

of p e t r o l e u m ether and ether (1 : 1) and r e m o v e d by filtration to give III. A sample was purified for analysis
by c h r o m a t o g r a p h y with a column filled with A1203. IR s p e c t r u m , u, cm-~: 1370, 1520 (NO2); 1620 (C =C);
1645 (NH2); 1655 (C =O); 3220-3430 (three bands, NH). PMR s p e c t r u m , 8, ppm: 1.17 (t,* g = 8 , CH3CH2),
4.20 (q, J = 7 , CH2CH3), 1.85 (s, 3-CH3) , 4.82 (s, 2-H), 6.98-7.16 (m, 3H).
7 - N i t r o - 4 - m e t h y l - 2 , 3 - d i h y d r o - l H - 1 , 5 - b e n z o - 2 - d t a z e p i n o n e (II). A ) A 10.4-g (0.06 mole} sample of
compound I was dissolved at r o o m t e m p e r a t u r e in 60 ml of concentrated H2SO4, and the solution was cooled
to - 4 0 ~ after which a mixture of 6.06 g (0.06 mole) of p o t a s s i u m nitrate and 40 ml of a concentrated H2SO4
were added gradually. The mixture was held a t - 1 0 to - 5 ~ for 3 h, after which it was poured over ice. The
aqueous mixture was cooled and neutralized to pH 4 with s a t u r a t e d sodium hydroxide solution. The r e s u l t -
ing precipitate was r e m o v e d by filtration, washed s u c c e s s i v e l y with water and acetone, and r e c r y s t a l l i z e d
f r o m dimethylformamide (DMF). UV s p e c t r u m , ),max, n m (log e): 275 (4.04), 305 (4.02). IR s p e c t r u m , v,
c m - l : 1340, 1540 (NO2); 1630 (C =N); 1665 (C =O); 3160-3355 (three bands, NH). PMR s p e c t r u m , 8, ppm:
2.97 (s, 4-CH3) , 3.96 (s, 3-H), 7.53 and 8.35-8.53 (m, 3-H).
B} A 7.9-g (0.03 mole} s a m p l e of crotonate HI was heated with sodium methoxide, obtained f r o m 0.7 g
(0.03 g-atom} of sodium in 100 ml of absolute methanol, on a water bath for 3 h. -The solvent was then
evaporated in vacuo to one third of the original volume, 60 ml of water was added, and the mixture was neu-
t r a l i z e d with acetic acid. The resulting precipitate was r e m o v e d by filtration to give II in 8(if0 yield. The
product did not depress the melting point of II obtained f r o m e x p e r i m e n t A. Their UV, IR, and PMR s p e c t r a
were identical.
6 - N i t r o - l - i s o p r o p e n y l - 2 - b e n z i m i d a z o l o n e (IV). A) A 0.3-g (1.3 mmole) sample of II (from method A)
was heated while gradually r a i s i n g the t e m p e r a t u r e to 245-250 ~ Heatingwas discontinued after 5 min, and
the solid was dissolved in acetonitrile. Compound IV was obtained by cooling the solution (mp 229-239 ~ [1]).
A s i m i l a r r e a c t i o n was c a r r i e d out with a sample of II obtained by method B. No melting-point de-
p r e s s i o n was o b s e r v e d for a mixture of s a m p l e s obtained by the two m e t h o d s , and their IR and PMR s p e c -
t r a were identical. IR s p e c t r u m , v, c m - l : 1335, 1520 (NO2); 1680-1705 (C =O), 3150 (NH). PMR s p e c t r u m ,
, ppm: 2.32 (d, J = 8 , 1-CH3); 5.40, 5.66 (1-CH2); 7.49, 8.18-8.33 (m, 3H).
B) A 0.44-g (2 mmole) s a m p l e of II was added to a solution obtained f r o m 0.046 g (0.002 g-atom) of
sodium in 10 ml of 2-ethoxyethanol, and the mixture was heated at a bath t e m p e r a t u r e of 130 ~ for 17 h. The
solvent was then vacuum evaporated, and 10 ml of water was added to the residue. The aqueous mixture
was neutralized to pH 7 with acetic acid to give 0.24 g (55%) of IV with mp 228-230 ~
C) Compound IV was s i m i l a r l y obtained f r o m crotonate III. The mixture was heated at 110 ~ for 12 h
and worked up to give a product with mp 227-229 ~ in 65% yield. No melting-point d e p r e s s i o n was o b s e r v e d
for mixtures of samples obtained by the various methods.

*The following abbreviations are used h e r e and subsequently: s is singlet, d is doublet, t is triplet, q is
quartet, and m is multiplet.

726
 5 - N i t r o - 2 - b e n z i m i d a z o l o n e (V)..A mixture of'0.54 g (2.5 mmole) of IV, 6 ml of alcohol, and 0.5 ml of
20 N H2SO4 was held at r o o m t e m p e r a t u r e for 24 h, a f t e r which it was poured o v e r ice, and the aqueous m i x -
t u r e was n e u t r a l i z e d with a m m o n i u m hydroxide to give 0.28 g (67%) of V with nap 305-306 ~ (from alcohol).
No melting-point d e p r e s s i o n was o b s e r v e d for a mixture of this product with a s a m p l e obtained b y the
method in [4] f r o m 4 - n i t r o - l , 2 - p h e n y l e n e d i a m i n e and urea.
H y d r o l y s i s of 7 - N i t r o - 4 - m e t h y l - 2 , 3 - d i h y d r o - l H - 1 , 5 - b e n z o - 2 - d i a z e p i n o n e . A m i x t u r e of 0.5 g {2.2
mmole) of II, 10 ml of 5 N HC1, and 10 ml of alcohol was heated on a w a t e r bath for 4 h. The solvent and the
acetone f o r m e d in the r e a c t i o n w e r e r e m o v e d by distillation into a r e c e i v e r containing a solution of 2 , 4 - d i -
nitrophenylhydrazine. An orange p r e c i p i t a t e , which had mp 125-127 ~ (from alcohol) a f t e r r e c r y s t a l l i z a t i o n
and did not d e p r e s s the melting point of a s a m p l e obtained f r o m acetone and 2,4-dinitrophenylhydrazine, was
isolated f r o m the f i r s t drops of the distillate.
The volatile components w e r e r e m o v e d by distillation, and 10 ml of w a t e r was added to the r e s i d u e .
The aqueous mixture was n e u t r a l i z e d with a m m o n i u m hydroxide to give a d a r k - o r a n g e p r e c i p i t a t e , the iden-
tity of which as 4 - n i t r o - l , 2 - p h e n y l e n e d i a m i n e was c o n f i r m e d b y t h i n - l a y e r c h r o m a t o g r a p h y (TLC) on A1203
and silica gel [ c h l o r o f o r m - e t h y l a c e t a t e (1: 1)].
7 - A m i n o - 4 - m e t h y l - 2 , 3 , 4 , 5 - t e t r a h y d r o - l H - 1 , 5 - b e n z o - 2 - d i a z e p i n o n e (VI). A solution of 1.5 g (6.8
mmole) of II in 150 ml of glacial acetic acid was hydrogenated o v e r p a l l a d i u m black. After the calculated
amount of hydrogen had been a b s o r b e d the color of the solution changed. The c a t a l y s t was then s e p a r a t e d
and excess hydrogen chloride in e t h e r was added to the filtrate. The bright p r e c i p i t a t e of the dihydrochlo-
r i d e of amine VI p r e c i p i t a t e d , and the b a s e was obtained by the addition of a c h l o r o f o r m solution of a m m o n i a
to a s u s p e n s i o n of the dihydrochloride in t e t r a h y d r o f u r a n (THF). P r o d u c t VI was purified by r e c r y s t a l l i z a -
tion f r o m T H F - p e t r o l e u m ether. IR s p e c t r u m , v, c m - i : 1650 (C =O), 3200-3430 (three bands, NH). PMR
s p e c t r u m , 6, ppm: 1.20, 1.27 (two d, J =3, and J = 6 , 4-CH3; in the p r e s e n c e of CF3CO2H, d, J = 6 ) ; 2.33 (m,
3-H); 3.88 (m, 4-H); 6.06 (s, 5-H; in the p r e s e n c e of CF3CO2H the signal vanished); 6.60-6.88 (m, 3H).
8 - N i t r o - 4 - m e t h y l - 2 , 3 , 4 , 5 - t e t r a h y d r o - l H - 1 , 5 - b e n z o - 2 - d i a z e p i n o n e (VII). A m i x t u r e of 8 g (0.051
mole) of 4 - n i t r o - l , 2 - p h e n y l e n e d i a m i n e and 15.1 g (0.18 mole) of crotonic acid was heated at a bath t e m p e r -
a t u r e of 110 ~ for 20 h. The viscous m a s s was then suspended in 60 ml of w a r m methanol, the s u s p e n s i o n
was filtered, and the solid was r e c r y s t a l l i z e d f r o m dioxane. UV s p e c t r u m , k m a x , n m (log ~): 266 (4.23),
310 (3.86), 380 (3.58). IR s p e c t r u m , v, c m - l : 1330, 1540 (NO2), 1660 (C =O), 3195-3360 (three bands, NH).
PM_R s p e c t r u m , 8, ppm: 1.71 (d, J = 7 , 4-CH3) , 2.90 (m, 3-H), 4.90 (m, 4-H), 7.60 and 8.34-8.68 (m, 3H).
8 - N i t r o - 4 - m e t h y l - 5 - a c e t y l - 2 , 3 , 4 , 5 - t e t r a h y d r o - l H - 1 , 5 - b e n z o - 2 - d i a z e p i n o n e (IX). A 0.4-ml (50 mmole)
s a m p l e of d r y pyridine and 0.4 g (5 mmole) of acetyl chloride w e r e added to a solution of 1.1 g (5 mmole) of
of VII in 90 ml of d r y dioxane, and the mixture was s t i r r e d at r o o m t e m p e r a t u r e for 30 min, a f t e r which it
was heated on a bath at 50 ~ for 3 h. The solvent was e v a p o r a t e d , and the r e s i d u e was dissolved in c h l o r o -
form. The solution was t r e a t e d s e v e r a l t i m e s with dilute h y d r o c h l o r i c acid and dried. A portion of the s o l -
vent was r e m o v e d by distillation, and product IX was p r e c i p i t a t e d with ether and r e c r y s t a l l i z e d f r o m a c e -
t o n e - p e t r o l e u m ether.
8 _ A m i n o _ 4 - m e t h y l - 2 , 3 , 4 , 5 - t e t r a h y d r o - l H - 1 , 5 - b e n z o - 2 - d i a z ~ p i a o n e (VIII). A solution of 1.2 g (5.5
mmole) of VII in 75 ml of THF was hydrogenated o v e r p a l l a d i u m black. A f t e r the calculated amount of h y -
drogen had been a b s o r b e d , the mixture was f i l t e r e d , and the f i l t r a t e was c o n c e n t r a t e d in vacuo to one t h i r d
of its original volume, and the b a s e was isolated b y p r e c i p i t a t i o n with e t h e r - p e t r o l e u m ether. The p r e c i p -
itate was r e c r y s t a l l i z e d f r o m ethyl acetate. The IR and PM:R s p e c t r a w e r e s i m i l a r to the s p e c t r a of VI.
The physical constants and yields of all of the compounds obtained in this investigation a r e p r e s e n t e d
in Table 1.

LITERATURE CITED

1. A. N. Kost, Z. F. Solomko, V. A. Budylin, and T. S. Semenova, Khim. G e t e r o t s i k l . Soedin., 696 (1972).

2. M. I s r a e l and L. C. J o n e s , J. G e t e r o c y c l . Chem., 8, 797 (1971).
3. E. Mueller, R. H a i l e r , and K. W. Merz, Ann., 697, 193 (1966).
4. O. Kym and L. R a t n e r , B e t . , 45, 3238 (1912).
5. R. M. Acheson a n d W , R. Tully, J. Chem. Soc., C, 1117 (1970).
6. J. Davoll, J. Chem. Soc., 308 (1960).
7. W. A. Sexton, J. Chem. Soc., 303 (1942).
8. A. R o s s i , A. Hunger, J. Kebrle, and K. Hoffmann, Helv. Chim. Acta, 43, 1298 (1960).
9. Organic Synthesis [Russian t r a n s l a t i o n ] , Vol. 3, Inostr. Lit., Moscow (1959), p. 162.

727
1,4-BENZODIAZEPINES AND T H E I R CYCLIC
H O M O L O G S AND A N A L O G S
XIV.* IR AND PMR SPECTRA OF SOME
1,2- DIHYDRO-3H- 1,4-BENZODIAZEPINES

A. V. B o g a t - s k i i , S. A . A n d r o n a t i , UDC 547.892 : 543.422.25.4

Yu. Yu. S a m i t o v , A. I. G a l a t i n a ,
E. V. K o n o v a l o v , E . P . S a e n k o ,
a n d S. G. S o b o l e v a

The dependence of the IR and PMR spectral characteristics of 12 compounds of the 1,2-di-
hydro-3H-1,4-benzodiazepine s e r i es on structural and steroehemieal factors was studied.
Information in favor of concepts regarding the pseudoboat conformation as the p r i m a r y one
for this type of 1,4-benzodiazepine derivative was obtained.

The l i t e r a t u r e contains only episodic and nonsystematized information on the IR spect ra of 1,2-di-
hydro-3H-1,4-benzo-2-diazepinones [2-4] and only a few papers devoted to the PMI~ spect ra of these sub-
stances. We have investigated the IR and PMR spectra of 1,4-benzodiazepines of the A type and their
N4-oxides.
L
*See [1] for communication XIII.

f ~ . . r . NH-- C / / 0
9 /CH z
Br ~--~'C i = N
C6Hs

~ H

Fig. 1. PMR spectrum of 7-bromo-5-

phenyl- 1,2-dihydro-3H- 1,4-benz6-2-
diazepinone.

Institute of Organic Chemistry, Academy of Sciences of the Ukrainian SSR, Kiev. I. I. Mechnikov
Odessa State University. Translated f r om Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 838-842,
June, 1974. Original article submitted April 16, 1973.

9 1975PlenumPublishing Corporation, 227 West 17th Street, New York, iV..Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is availablefrom the publisher for $15.00.

728
 RI
I v

RA~'~N / ~\R:
f
C6Hs
{h A
R=INO2, Br, CI, H, CH~;RI=H, CH3; R:=H, CH3, C2H~,i-C~H?;X=O, S, H2.

The synthesis and p h y s i c a l , c h e m i c a l , and p h a r m a c o l o g i c a l p r o p -

e r t i e s of t h e s e s u b s t a n c e s w e r e d e s c r i b e d in [2-4]. 7 - C h l o r o - l - m e t h y l -
5 - p h e n y l - l , 2 - d i h y d r o - 3 I - I - 1 , 4 - b e n z o d i a z e p i n e (compound No. 4, m e d a z -
apam) was obtained b y the action of u r o t r o p i n on 5 - c h l o r o - 2 - ( 2 - b r o m o -
ethylmethyl)aminobenzophenone in absolute e t h a n o l [5].
The p r e s e n c e of a b s o r p t i o n bands of a C 5 =N 4 double bond at 1590-
1610 c m - i in t h e i r IR s p e c t r a (Table 1) is c h a r a c t e r i s t i c for 1 , 2 - d i h y d r o -
g ~ g 3 H - 1 , 4 - b e n z o d i a z e p i n e s . The a s s i g n m e n t of this band is c o n f i r m e d by its
.I I absence in the s p e c t r u m o f 7 - c h l o r o - 5 - p h e n y l - l , 2 , 3 , 4 - t e t r a h y d r o - 5 H -
1 , 4 - b e n z o - 2 - d i a z e p i n o n e . The LR s p e c t r a of 1 , 2 - d i h y d r o - 3 H , - 1 , 4 - b e n z o -
2 - d i a z e p i n o n e s , as a l r e a d y noted in [2-4], contain the a b s o r p t i o n bands
of a carbonyl group and f r e e and a s s o c i a t e d NH groups. The m o s t intense
(at 3180 c m -I) of the bands that a r e r e l a t e d to the vibrations of the NH
...1|!1 group c o r r e s p o n d s to the v i b r a t i o n s of the N - H bond of an amide group with
a cis config .uration [6]. The integral intensity of this band r e m a i n s p r a c -
t i c a l l y the s a m e on dilution [4], which m a y attest to the p r e s e n c e of an
i n t r a m o l e c u l a r hydrogen bond between the NH group and the carbonyl
group or to the f o r m a t i o n of d i m e r i c a s s o c i a t e s due to hydrogen bonds of
the a m i d e groups. In addition, the cis configuration of the amide group
is evidence in f a v o r of the boat c o n f o r m a t i o n of the 1 , 2 - d i h y d r o - 3 H - 1 , 4 -
b e n z o - 2 - d i a z e p i n o n e molecttles.

c~./~. N 'h
)~.~..o
C61-1~

R
q.a
r
Bands of the s t r e t c h i n g v i b r a t i o n s of the c a r b o n - c a r b o n s e s q u i -
O00~OOm bonds of benzene r i n g s a r e p r e s e n t e d at 1450-1550 c m -1 in the IR s p e c -
t r a of 1 , 2 - d i h y d r o - 3 H - 1 , 4 - b e n z o d i a z e p i n e s . The C - H s t r e t c h i n g v i b r a -
O
r~
I011111 tions of the benzene r i n g s of compounds A lead to the a p p e a r a n c e of a b -
s o r p t i o n bands at 3030-3100 c m -1. The C - H s t r e t c h i n g v i b r a t i o n of the
methylene group in the 3 position of the benzodiazepine s y s t e m in the a b -
eg s e n c e of aliphatic substituents give two bands of a s y m m e t r i c a l and s y m -
m e t r i c a l v i b r a t i o n s at 2850-2940 c m -1. When aliphatic groups a r e p r e s -
ent in the 1, 3, or 7 positions, the c o r r e s p o n d i n g additional bands a p p e a r
.2
in the s p e c t r a . In addition to this, a shift in the a b s o r p t i o n bands of the
methylene group is noted (in the c a s e of 3-unsubstituted compounds).

OU~UUU~ The PMR s p e c t r a contain a multiplet signal of a r o m a t i c protons at

7.45-8.00 p p m (for solutions in d6-dimethyl sulfoxide). The intense p e a k
.4
of this multiplet in the s p e c t r u m of 7 - b r o m o - 5 - p h e n y l - l , 2 - d i h y d r o - 3 H -
1 , 4 - b e n z o - 2 - d i a z e p i n o n e (compound No. 9, Fig. 1) at 7.70 p p m belongs
to the protons of the 5-phenyl substitutent, judging f r o m its c h e m i c a l
shift and integral intensity. The signal of the indicated protons a r e s i m -
i l a r l y displayed in the s p e c t r a of the other compounds (A).

729
 T A B L E 2. C h e m i c a l Shifts of t h e M e t h y l , M e t h y l e n e , a n d M e t h y l i d y n e
Protons of 1,2- Dihydro-3H- 1,4-benzodiazepines

~oncn! & ppm (_o,I)

RE R.o R3 Solvent (qo)
CH~ CH2 CH

1 C1 o
d6-DMSO 4,41 --
2 C1 o d6-DMSO 4,87 --
3 Cl CH8 d6-DMSO 3,55 4.41
4
5
C1
C1 CHa
L d6-DMSO
~-DMSO
2,95
1,76
3,80
--
--
6 CI CH~H~ d6-DMSO 2"~7 3,76
3,62
o 1,25
7 C1 d~-DMSO 4,83 --
8 H H o ds-DMSO 4,34 --
9 Br H ~-DMSO 4,40 --
10 H H O ~-DMSO 4,47 --
tl H ICsH7 O d~-DMSO 1,22
4~-31 3,70__
12 CH3 H 0 ds-DMSO
2 CI H o 0 CsDsN 4,65 --
2 C'I H O CD3COOD 4,65 --
4 C'I CH3 H H2 C~DsN 2,17 3,08 --
4 CI cH0 CD~COOD 3,03 3,97 --
9 Br CsDsN 4,05 --
7 cl H H S CsDsN 4,59 --

~ . N H _ C ~'~O
~
CIH3
N--C~
C6H5 C L . ~ C = N / CHz
R=i=C3H ? J
CBH5

J
R= C2H5

RC
:H3 ~
a

2 ~ ppm 4 3 .~ ppm

Fig. 2 Fig. 3
F i g . 2. P M R s p e c t r a of 3 - m e t h y l - (a), 3 - e t h y l - (b), and 3 - i s o p r o p y l -
7 - c h l o r o - 5 - p h e n y l - l , 2 - d i h y d r o - 3 H - 1 , 4 - b e n z o - 2 - d i a z e p i n o n e s (c),

F i g . 3. PAIR s p e c t r a o f m e d a z e p a m a t . a) 60 MtIz; b) 100 MHz.

The s i n g l e t (1H) a t 3 10.80 p p m in t h i s s p e c t r u m i s t h e s i g n a l of t h e p r o t o n o f an a m i d e g r o u p . W e

n o t e t h a t t h e i n t e n s i t y o f t h i s s i g n a l is c o n s i d e r a b l y l e s s w h e n t h e s p e c t r u m o f a s o l u t i o n of t h e c o m p o u n d in
ds-DMSO i s r e c o r d e d t h a n w h e n t h e s p e c t r u m i s r e c o r d e d w i t h u n d e u t e r a t e d DMSO a s t h e s o l v e n t . * T h i s
c a n b e e x p l a i n e d b y d e u t e r i u m e x c h a n g e , i . e . , b y d e u t e r a t i o n o f c o m p o u n d No. 9 at t h e N 1 a t o m .
The c h e m i c a l s h i f t s of t h e p r o t o n s a t t a c h e d t o t h e C 3 a t o m a n d t h e p r o t o n s o f t h e s u b s t i t u e n t s a t t a c h e d
to the N 1 and C 3 a t o m s a r e p r e s e n t e d in T a b l e 2. It is s e e n f r o m T a b l e 2 t h a t t h e c h e m i c a l s h i f t s o f t h e
m e t h y l e n e p r o t o n s o f c o m p o u n d s A d i f f e r a p p r e c i a b l y w h e n t h e s p e c t r a a r e r e c o r d e d in d i f f e r e n t s o l v e n t s
(ds-DMSO, C~DsN , a n d CD3COOD). A s in t h e c a s e o f o t h e r p r o p e r t i e s of c o m p o u n d s A , t h e c h a r a c t e r of s u b -
s t i t u e n t R h a s a r e g u l a r e f f e c t on t h e c h e m i c a l s h i f t s o f t h e p r o t o n s o f t h e m e t h y l e n e g r o u p . A n i n c r e a s e in
i t s e l e e t r o n e g a t i v i t y s h i f t s the s i g n a l o f t h e m e t h y l e n e p r o t o n s to l o w e r f i e l d ; t h i s i s a p p a r e n t l y a s s o c i a t e d
w i t h a d e c r e a s e in t h e e l e c t r o n d e n s i t y on t h e C =N b o n d u n d e r t h e i n f l u e n c e o f t h e s u b s t i t u e n t .
T h e u s u a l s i g n a l s o f a l k y l p r o t o n s a r e o b s e r v e d in t h e P M R s p e c t r a o f 3 - a l k y l - s u b s t i t u t e d d e r i v a t i v e s
o f t h e A t y p e ( F i g . 2), a n d d i a s t e r e o t o p i c i t y o f t h e m e t h y l g r o u p s is d i s t i n c t l y o b s e r v e d in t h e c a s e o f t h e
resonance band of the isopropyl group.

* T h e d6-DMSO c o n t a i n s up to 1% d e u t e r i u m o x i d e , a c c o r d i n g to t h e m a n u f a c t u r e r ' s l a b e l .

730
 Substitution of the C 3 a t o m or of adjacent a t o n ~ of the h e t e r o r i n g has the g r e a t e s t effect on the c h a r -
a c t e r of the r e s o n a n c e of the protons attached to C 3. Thus r e p l a c e m e n t of the oxygen a t o m attached to C 2 b y
sulfur and introduction of a s e m i p o l a r oxygen a t o m in the N 4 position lead to an i n c r e a s e of ~ 0.40 p p m in the
c h e m i c a l shift.
Substitution at the N 1 a t o m by a methyl group leads to splitting of the signal of the C 3 methylene group
into a quartet; this can be explained by the r e t a r d e d c h a r a c t e r of r i n g inversion.
The r e s o n a n c e signal of the protons of the r i n g methylene groups at 2.80-3.30 p p m g e n e r a t e s the
g r e a t e s t i n t e r e s t in the PMR s p e c t r u m of compound No. 4 (Fig. 3). As s e e n f r o m the s p e c t r u m , these p r o -
tons f o r m an A A ' B B ' spin s y s t e m and r e s o n a t e as two mult[plets, of which the signal of the 2-CH 2 protons
evidently a p p e a r at high field, and the protons of the 3 - C H 2 group a p p e a r at low field. This is a p p a r e n t l y in
good a g r e e m e n t with the concept of the higher b a s i c i t y of the N 4 ring a t o m as c o m p a r e d with N I. The c h a r -
a c t e r of the s p e c t r u m also a t t e s t s that the cyclic s y s t e m under c o n s i d e r a t i o n is quite r i g i d , and r i n g i n v e r -
sion is hindered at r o o m t e m p e r a t u r e .

EXPERIMENTAL
The IR s p e c t r a of solutions of the compounds (Nos. 1-7) in CC14 or CHC13 w e r e r e c o r d e d with an
IKS-14A s p e c t r o m e t e r . The solution concentration was 0.01 mole and the l a y e r th[clmess was 5.006 m m .
The PMR s p e c t r a w e r e r e c o r d e d with a T e s l a $9 487B NMR s p e c t r o m e t e r at 80 MHz with h e x a m e t h y l d i s i l -
oxane as the external s t a n d a r d for 5-10% solutions of compounds A in d6-dimethyl sulfoxide, p e r d e u t e r o p y -
ridine, and p e r d e u t e r o a c e t i c acid. The s p e c t r u m of compound No. 4 was also r e c o r d e d with a Varian HA-
100D s p e c t r o m e t e r at 100 MHz.
1 - M e t h y l - 5 - p h e n y l - 7 - c h l o r o - l , 2 - d i h y d r o - 3 H - 1 , 4 - b e n z o d i a z e p i n e . A 2.8-g (8 mmole) s a m p l e of
5 - c h l o r o - 2 - ( 2 - b r o m o e t h y t ) m e t h y l a m i n o b e n z o p h e n o n e and 2.8 g (20 mmole) of urotropin w e r e refluxed in 50
ml of absolute ethanol for 10 h, a f t e r which the r e a c t i o n m i x t u r e was v a c u u m e v a p o r a t e d , and the r e s i d u e
was t r e a t e d with methylene chloride and w a t e r . The organic l a y e r was s e p a r a t e d , and the aqueous l a y e r
was made alkaline and e x t r a c t e d with methylene chloride. The e x t r a c t s w e r e combined and dried with c a l -
cined sodium sulfate, the methylene chloride was r e m o v e d b y distillation, and the r e s i d u e was c r y s t a l l i z e d
f r o m ether. The yield of product with mp 100-103 ~ (mp 102-103 ~ [5]) was 1.8 g (83%).

LITERATURE CITED

I. Yu. I. Vikhlyaev, A . V . B o g a t - s k i i , T. A. Klygul', S. A. Andronati, O. P. Rudenko, and P. B. Terent'ev,

in: P h y s i o l o g i c a l l y Active Substances [in Russian], No. 6, Naukova Dumka, Kiev (1974), p. 94.
2. L. H. Sternbach, R. I. F r y e r , W. M e t l e s i c s , E. R e e d e r , G. Sach, G. Saucy, and A. Stempel, J. Org.
Chem., 27, 3788 (1962).
3. A . V . B o g a t - s k i i a n d S. A. Andronati, Zh. Obshch. K_hlm., 39, 443 (1969).
4. S. A. Andronati, A. V. Bogatskii, Yu. I. Vikhlyaev, Z. I. ZhUina, B. M. Kats, T. A. Klygul', V. N.
Khudyakova, T. K. Chumachenko, and A. A. t~nnaa, Zh. Obshch. Khim., 40, 1881 (1970).
5. N. B l a z e v m and F. Kajfe~, J. H e t e r o c y c l . Chem., 8, 845 (1971).
6. L. B e l l a m y , I n f r a r e d S p e c t r a of Complex Molecules, Methuen (1958).

731
NEW H E T E R O C Y C L I C sym-TRIAZOLOPYRIMIDINIUM
SYSTEMS - QUINOLINE, PYRIDAZINE,
AND P H T t I A L A Z I N E DERIVATIVES

G. M. G o l u b u s h i n a , O. G. P o n o m a r e n k o , UDC 547.792.9'831.6'852.7'852.9'859
G. N. P o s h t a r u k , a n d V. A. C h u i g u k

Pyrimido [1' ,2' : 1,5]-sym-triazolo [4,3-b]pyridazinium, pyrimido [1' ,2' : 1,5]-sym-triazolo-

[4,3-b]phthalazinium, and pyrimido [1' ,2 ' : 1,5]-sym-triazolo [4,3-a]quinolinium salt deriva-
tives were obtained by condensation of 3-amino-sym-triazolo [4,3-b]pyridazinium, 3-amino-
sym-triazolo [3,4-a]phthalazinium, and 1-amino-sym-triazolo [4,3-a]quinolinium salts with
fl-diketones and 1,1,3 ,3-tetraethoxypropane. The structures of the reaction products were
confirmed by the PMR spectra.

Salts of amino derivatives of sym-triazolo [4,3-a]pyridine [1] and sym-triazolo[1,5-a]pyrtmidine [2]

react with fl-diketones and their analogs with ring closure to pyrimidine rings to give the corresponding
sym-triazlopyrimtdinium salts. In the present r e s e a r c h we have examined the condensation of fl-diketones
with salts of 3-amino-sym-triazolo [4,3-b]pyridazine (I), its benzo analog 3-amino-sym-triazolo [3,4-a]-
phthalazine (II), and 1-amino-sym-triazolo [4,3-a]quinoline (III).
R2 N--N NH2\ N

i a-d II Ill

I a RI=R~=H: b R~=f~|, R2=H; C R'=CI, R'~=CH3; d R'=NHNH2, R~-=H

The perchlorates or hyd_vobromides of II and III were heated with fl-diketones without a solvent, while
I (as the free base or as the hydrochloride) was heated with the fl-diketone in trifluoroacetic acid solution.
A pyrimidinium ring was formed from the amino group and the adjacent nonbridging nitrogen atom in all
cases. The reaction products are pyrimido[l',2' : 1,5]-sym-triazolo[4,3-b]pyridazinium salts (IV), pyrim-
ido [1' ,2' : 1,5]-sym-triazolo [3,4-a]phthalazinium salts (V), and pyrimido [1' ,2' : 1,5]-sym-triazolo [4,3-a]-
quinolinium salts (VI) (Table 1).

clo; ao; e~ x-
IVa-g Ya-d Vl a - c

All of the salts that contain methyl groups in the ~ and (or) ~/positions with respect to the bridge
nitrogen atom in the pyrimtdine ring give polymethine dyes in the usual manner. The PM_R spectra (Table
2) of the products of the reaction with acetylaeetone contain signals of the proton of the pyrimidine ring
(7.5 ppm) and the associated methyl groups, and the signal of the a-methyl group is found at weaker field

T. G. Shevchenko Ktev State University. Translated from Khimiya Geterotsiklicheskikh Soedinenii,

No. 6, pp. 843-845, June, 1974. Original article submitted November 9, 1972; revision submitted Novem-
ber 11, 1973.

9 1975Plenum Publishing Corporation, 227 ICest 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy of this article is availablefrom the publisher for $15.00.

732
 TABLE 1. Compounds IV-VI
Com- Empirical Found, Ca: } ,~-
R' % ~176c " g' ! o
pound* Ra I Ra formula
c, _N c1 -N--
IVa H I CH ICI-I3 90 i 263--2651 C mH mC'INsO4 12,1123,1 11,8 23,41100
IVb u t cHi IC6H~ 90 265--267 ClsHi2CI'NsO4 9,5119,0 9,8 19.4] 62
IV c C[ H iCH~ CHs 30 245--2471 CIoH9CI~NsO4 21,5121,t]21,3 20,9 75
IVd CI H ~CH~ C~Hs 90 ] 267--268 C15H.CIzNsQ 18,2J 17,5j 17.9 17,7 100
1Ve CI CHa{ H H 10 I >340 CgH7ClzNsO4 22,1] 122,2 [ 39
[vf CI CH~ CHa CH~ I >340 t CnHllCl~,NsO4 20,3 20,1 / 20,4 20,1 ] 89
IVg CsHrN~ H I CH3 CH~ [147--150 Cs9HIzFsN7O4 / lg,0/ 18,81 82
Va CH~ H I CH~ 120 296---298 CI4HmC|NsO4 9,9l /10,1 I I00
Vb Gila CHd, CH~ 240 301--303 1 CIsHI4C1N504 9,9 / [ 9,8
Vc co~ H I CH3 30 299--303 CmHI4CINsO4 89j /86
Vd H H 30 324--325 C~2HsCINb-O4 11,1[ Jll,O I 79
Via CH~ H CHa 120 266--267 i CIsHI3C1N~O4 10,1 t ~10,2 " 85
Vlb CH~ CHa [ CHa 180 285--286 CmHIslN4
VfC C~H~ H ( CHa 180 >330 C2oHlsBrN4"f

*Compound VIb w a s obtained as the iodide, VIc w a s obtained as the

b r o m i d e , mad the r e m a i n i n g compounds w e r e obtained as the p e r -
chlorates.
"]'Found: Br 19.9%. Calculated. Br 19.9%.

TABLE 2. Chemical Shifts of the P r o t o n s of IV-VI (8 ppm)*

Compound 3-H . R-" Ra B-H R4

IVa 7.5--7.6~" 8,09 (9,5; l) 2,80 7.55 2.70

IVb 2,71 7,81 and 7,35
IVc 7,8 (1o) 7,55 (10) 2.70 7.55 2,65
ivd 2,78 7,85 and 7.35
tv~ 7,87 2.37 2,77 7.49 2,68
IVg. 7,86 (I0) 8.28 (10) 2,75 7,50 2.63

I-H 5-H R3 R~ R'

Va 8,375 8,77 2.58 7,37 2.73

VC 8,36~ 8.77 2.77 7,65
Via 2,73 2,67
VIc 2.85 8,1--7,7

* The J values in hertz are indicated in p a r e n t h e s e s .

~Quartet: 5 (2-H) 8.62 ppm (J2,a=4 Hz, 32,4=1 Hz).
$ Multiplet.

(2.7-2.8 ppm) as c o m p a r e d with the signal of the T - m e t h y l group (2.6-2.7 ppm). The signal of the ~ - m e t h y l
group is always l o w e r and broader than that of the T - m e t h y l group as a c o n s e q u e n c e of coupling with the
adjacent proton. I n a s m u c h as the difference in the c h e m i c a l shifts of the a - and T - m e t h y l groups is s m a l l
(-~ 0.1 ppm), the s t r u c t u r e s of the products of condensation with b e n z o y l a c e t o n e w e r e d e t e r m i n e d mainly
f r o m the character of the signal of the phenyl group, which in all c a s e s w a s split into two groups of bands
with an i n t e n s i t y ratio of 2 : 3 (lower at w e a k field) and a difference of 0.4 ppm or m o r e b e t w e e n the c e n -
t e r s of t h e s e bands; this constitutes evidence that the phenyl group is in the T position [3].
Compound Id r e a c t s w i t h 2 m o l e s of a c e t y l a c e t o n e in t r i f l u o r o a c e t i c acid to give IYg, the PMR s p e c -
t r u m o f w h i e h contains three singlets f r o m the proton and methyl groups of the p y r a z o l e ring at 6.38, 2.47,
and 2.29 ppm, r e s p e c t i v e l y .
1,1,3,3-Tetraethoxypropane r e a c t s with salts of I and lI to give IVe and Vd with unsubstituted p y r i m i -
dine rings.
N--___y-c~3
c.~N.~_~_,v.N~% ~ .~,~oo.

I
CH3 CF3GO0-
wg

733
 EXPERIMENTAL
Condensed a m i n o t r i a z o l e s I - I I I w e r e obtained b y r e a c t i o n of ~ - h y d r a z i n o d e r i v a t i v e s of the a p p r o p r i -
ate h e t e r o e y c l e s w i t h c y a n o g e n b r o m i d e [4-6]. The PM:R s p e c t r a of solutions in t r i f l u o r o a e e t i c acid w e r e
r e c o r d e d with a ZKR-60 s p e c t r o m e t e r . The c h e m i c a l shifts a r e on the 6 s c a l e with r e s p e c t to h e x a m e t h y l -
disiloxane (internal standard).
P e r c h l o r a t e s of P y r i m i d o [1',2' : 1 , 5 ] - s y m - t r i a z o l o [4,3-b]pyridazinium D e r i v a t i v e s (IV, Table 1). A
mixture of I or its hydrochloride with a fl-diketone (molar r a t i o 1 : 1.3) was d i s s o l v e d in the m i n i m u m
amount of t r i f l u o r o a c e t i e acid, and the solution was heated on a w a t e r bath. The m i x t u r e was then cooled,
and the solid was t r i t u r a t e d with ether. The r e s u l t i n g s a l t (except for IVg) was c o n v e r t e d to the p e r c h l o r a t e
and c r y s t a l l i z e d f r o m ethanol (IVb was c r y s t a l l i z e d f r o m acetic acid, IVe was c r y s t a l l i z e d f r o m n - p r o p y l
alcohol, and IVg was r e c r y s t a l l i z e d f r o m o-xylene).
P y r i m i d o [1' ,2' : 1 , 5 ] - s y m - t r i a z o l o [3,4-a]phthalaz inium and P y r i m i d o [1' ,2 ' : 1 , 5 ] - s y m - t r i a z o l o [4,3-a]-
quinolinium D e r i v a t i v e s (V and VI, Table 1). A m i x t u r e of the p e r e h l o r a t e of II or the h y d r o b r o m i d e of 11I
with the fl-diketone (molar r a t i o 1 : 1 . 3 ) w a s heated at 130-140 ~ (Via) 150-160 ~ ( V a ) , o r 160-170 ~ (Vb, Ve, VIb,
and Vie). The r e a c t i o n product was t r i t u r a t e d with e t h e r and c r y s t a l l i z e d f r o m w a t e r (Vc was c r y s t a l l i z e d
f r o m acetic acid).
T e t r a e t h o x y p r o p a n e was condensed with the p e r c h l o r a t e s of Ic and ]I by r e f l u x i n g a m i x t u r e of the
components (molar r a t i o 1 : 1.3) in alcohol. C o m p o u n d Vd was c r y s t a l l i z e d f r o m ethanol, while Ve was
c r y s t a l l i z e d f r o m n - p r o p y l alcohol.

LITERATURE CITED
1. G. M. Golubushina and V. A. Chuiguk, Khim. G e t e r o t s i k l . Soedin., 1433 (1971).
2. G. M. Golubushina, L. S. Gutenko, and V. A. Chuiguk, Ukr. Khim. Zh., 3_~7, 1044 (1971).
3. J. A. Bee and F. L. R o s e , J. Chem. Soc., 2031 (1966).
4. K. T. Ports and C. L o v e l e t t e , J. Org. Chem., 3_44, 3221 (1969).
5. Methods for the Synthesis of Chemical Reagents and P r e p a r a t i o n s [in Russian], Vol. 12, IREA, Mos-
cow (1965), p. 50.
6. A. Le B e r r e and C. Renault, Bull. Soe. Chim. F r a n c e , 3139 (1969).

734
REACTION OF 1-AMINO-, 2-AMINO-,
AND 1,2-DIAMINOIMIDAZOLES WITH fl-DIKETONES

G . M. G o l u b u s h i n a , G. N. Poshtaruk, UDC 547.781.5'785.1'852.9'859

a n d V. A. C h u i g u k

1 , 2 - D i a m i n o - 4 - p h e n y l i m i d a z o l i u m p e r c h l o r a t e condenses with 2 mole of fl-diketones to give

pyri mido [2',1' : 2,3 ]imidazo [1,5-b]pyridazintum d e r i v a t i v e s , while, 1ike 1 - a m i n o - 2 - m e r c a p t o -
4-phenyltmidazole, to give imidazo[1,5-b]pyridazine d e r i v a t i v e s . Salts of 1-benzylidene-
a m i n o - and 1 - ( 2 - t h i a z o l y l ) - 2 - a m i n o i m i d a z o l e s r e a c t with fl-diketones to give substituted
imidazo [1,2-a]pyrimtdinium d e r i v a t i v e s .

A t h r e e - r i n g p y r i m i d o i m t d a z o p y r i d a z i n i u m p e r e h l o r a t e (IIa) was unexpectedly obtained in the r e a c t i o n

of 1 , 2 - d t a m i n o - 4 - p h e n y l i m i d a z o l i u m p e r c h l o r a t e [1] with acetylacetone. Compound IIa is f o r m e d v e r y r e a d -
ily even in the cold in alcohol solution. Both methyl groups of the p y r i m i d i n e r i n g of IIa axe active and
f o r m a b i s s t y r y l with p-dimethylaminobenzaldehyde.

CIO~ C6Hs CsH5 R" C61t~

II a-c I IV a-i III
1Va--d X=INH~; IVe, g; X=SH; IVf X=SCHa; IVh X=NHC(CHa)CHCOCH3; IVi X=
=N(COCH3)2; IVa,c--g, lIa (R'=R) R=H; IIb (W=R), Ilc 1Vb R=C2Hs; llc R':!I;
IVa,b,e,f,h,i, ,x"'-,.. =CH.~, IVC,g R'=R"=C6Hs," IVd R'=CH3, R"=CeH5

The methyl groups in the 4 and 7 positions have the l o w e s t c h e m i c a l shifts in the PM1R s p e c t r u m of
IIa (2.00 and 1.65 ppm) b e c a u s e of shielding b y the phenyl group (7.26 ppm). The signals of these groups
a r e split (J=0.7 and 1.2 Hz) due to coupling with the 3-H protons (6.99 ppm) and 8-H (6.52 ppm) p r o t o n s ,
r e s p e c t i v e l y , in c o n t r a s t to the methyl groups in the 2 and 9 positions (2.48 and 2.22 ppm). The coupling of
the 7-CH 3 protons with 8-H and of the 4-CH 3 protons with 3 - H is c o n f i r m e d not only by the mutual splitting
with identical constants but also by the double-proton r e s o n a n c e when, for e x a m p l e , the peak at 2.00 p p m
is n a r r o w e d as the signal at 6.99 p p m is s a t u r a t e d . Other fl-diketones also give s a l t s of the II type.
1 , 2 - D i a m i n o - 2 - p h e n y l i m i d a z o l e (I) r e a c t s with fl-diketones in acetic acid to give t m i d a z o p y r i d a z t n e s
(IVa-d), which give II on r e a c t i o n with fl-diketones in the p r e s e n c e of m i n e r a l acids. Thus IVb, which r e -
acts with acetylacetone in the p r e s e n c e of HC104 to give IIc, is obtained by condensation of I with 3 - e t h y l -
2,4-pentanedione. Compound IVa r e a c t s with acetic anhydride to give a dtace~yl d e r i v a t i v e at the amino
group (IVi); this was also o b s e r v e d for s t a r t i n g amine I [1].
As in the s p e c t r a of II, the 5-phenyl signal in the PMR s p e c t r a of i m i d a z o p y r i d a z i n e s (IV) is not split,
and 4-CH 3 is shielded by the phenyl group and is split by coupling with 3-H. However, all of the signals in
the s p e c t r u m of IVa axe shifted d i a m a g n e t i c a l l y as c o m p a r e d with the c o r r e s p o n d i n g signals of cation II,
except for the 4-CH 3 signal, which is shifted to weak field by 0.1 ppm. This can be explained b y the l o w e r
shielding of the methyl group b y the phenyl group in IV as c o m p a r e d with II, in which the phenyl group is
m o r e noncoplanar b e c a u s e of additional coupling with 4-CH 3. When R" = P h in IV, the phenyl groups in the
4 and 5 positions shield one another and give one o v e r a l l signal at 6.5 ppm, while when R" =CH 3, the phenyl
group in the 5 position gives a signal at 7.12 ppm.
T. G. Shevchenko Kiev State University. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii,
No. 6, pp. 846-850, J u n e , 1974. Original a r t i c l e s u b m i t t e d N o v e m b e r 9, 1972; r e v i s i o n submitted N o v e m b e r
11, 1973.

I
9 19 75 Plenum Publishing Corporation, 227 West 17th Street, New York, N.Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

735
 The condensation with fl-diketones to give imtdazo [1,5-b]pyridazines is a p p a r e n t l y c h a r a c t e r i s t i c for
1 - a m i n o i m i d a z o l e s . Thus 1 - a m i n o - 2 - m e r c a p t o - 4 - p h e n y l i m i d a z o l e [2] r e a c t s with fl-dtketones in the p r e s -
ence of m i n e r a l acids to give IVe, g; when the components a r e heated in the a b s e n c e of acid they give a n o n -
cyclic a z o m e t h i n e , which is cyclized by the action of acids. Of the p o s s i b l e s t r u c t u r e s of the 7 - m e r c a p t o
d e r i v a t i v e s (IVe,g), the m o s t significant ones, at l e a s t in the solid state, a r e p r o b a b l y the ~ and ft. s t r u c -
t u r e s , i n a s m u c h as a n u m b e r of intense bands at 2600-3050 c m -1, which a r e c h a r a c t e r i s t i c for v ~ - H , a r e
o b s e r v e d in the IR s p e c t r u m (in KBr).

-s I.)T__~."
H
% -s~___."~'~
I! .

A m i x t u r e of i s o m e r s is f o r m e d in the r e a c t i o n of benzoylacetone with I. The PMR s p e c t r u m of the

crude product contains the signals of two methyl groups, the intensity r a t i o of which gives a r a t i o of 5 : 1
for i s o m e r s IVd and IV (X =NH2, R =H, R' =C6H5, R" =CH3). The f i r s t i s o m e r (IVd) was obtained a f t e r r e -
crystallization.
Compound IVe r e a c t s with dimethyl sulfate in alkaline m e d i a to give a methylthio, d e r i v a t i v e (IVf),
which is subsequently methylated at N(6) to give a q u a t e r n a r y salt. The 2 - C H 3 and 3-H signals in the PMR
s p e c t r u m of the q u a t e r n a r y salt a r e shifted by 0.1-0.15 p p m to w e a k field as c o m p a r e d with the analogous
signals of IV, while the phenyl signal was v i r t u a l l y unchanged, and the 4 - C H 3 signal is shifted to strong field
by ~ 0.1 ppm. If the methylation had o c c u r r e d at N(1), all of the signals should have been shifted to w e a k
field. The methyl group attached to N(6) r e m o v e s the phenyl group even m o r e f r o m the plane of the t w o - r i n g
s y s t e m , and its signal t h e r e f o r e does not change, despite c o n v e r s i o n of the s y s t e m to a cation, while the
chemical shift of 4-CH 3 b e c o m e s even s m a l l e r b e c a u s e of an i n c r e a s e in the shielding of this group b y the
phenyl group.
A product of the r e a c t i o n with two molecules of a c e t y l a c e t o n e , to which we a s s i g n e d anil s t r u c t u r e
IVh, was also obtained in the r e a c t i o n of I with acetylacetone in the a b s e n c e of m i n e r a l acids or in acetic
acid or t r i f l u o r o a c e t i c acid.
To c o n f i r m the s t r u c t u r e of II we used 2 - a m i n o - l - b e n z y l i d e n e a m i n o - 4 - p h e n y l i m i d a z o l e p e r e h l o r a t e
(V) [1], which gives s a l t s Via, b on condensation with a c e t y l a c e t o n e and 3 - c h l o r o - 2 - m e t h y l - 2 - b u t e n a l .

N~CHC6H5 Z N~CHCsH5 S~N

"CaHs R" ~.. + ~,~- C6H5 I~"

.HCIO4 CH3 "~~',t R, X-
V Vl a - b vH a -d
Via R=I'-i. R'=CHa, Z=OH; VIb R=CHa, R ' = H , Z=C1; VlIa--C X=CIO4; v I I d X =
=CF3COO; VIla R = R ' = C H a , R"=C6Hs; vIIb.R=R"=C6Hs, R'=CHa; VIIc R = R ' = R " =
=C6Hs; VIId R=R"=p-BrC6H4, R'=CI-I3

The f o r m a t i o n of a p y r i m i d i n e r i n g is c o n f i r m e d by the fact that s a l t s Via, b give polymethine dyes

and t h e i r PMR s p e c t r a c o r r e s p o n d to the s p e c t r a of II. As with other h e t e r o c y c l e s [3], 3 - c h l o r o - 2 - m e t h y l -
2-butenal in this c a s e gives one i s o m e r (VIb) with an unsubstituted 7 postton of the p y r i m i d t n e r i n g with
r e s p e c t to the bridge nitrogen atom. However, we w e r e unable to h y d r o l y z e the a z o m e t h i n e s and obtain
1-amino d e r i v a t i v e s by means of 2 - a m t n o - l - ( a - m e t h y l b e n z y l i d e n e a m t n o ) - 4 - p h e n y l i m i d a z o l e , i n a s m u c h as
this compound is h y d r o l y z e d so r e a d i l y that t h r e e - r i n g s y s t e m s II a r e f o r m e d i m m e d i a t e l y .
Imidazo [1,2-a]pyrimidinium s a l t s with alkyl substttuents attached to N(t) can be obtained by a l k y l a -
tion of imtdazo [1,2-a]pyrimtdines [4, 5], but compounds with m o r e c o m p l e x substituents attached to N(t)
cannot be obtained by this method. The l a t t e r a r e r e a d i l y a c c e s s i b l e v i a the a b o v e - d e s c r i b e d condensation.
Thus s a l t s of 1 - ( 2 - t h i a z o l y l ) - 2 - a m t n o - 4 - a r y l i m i d a z o l e s r e a c t with f i - d i k e t o n e s to give i m i d a z o [ 1 , 2 - a ] p y -
r t m i d i n i u m s a l t s (VII) with 2-thiazolyl substituents attached to N(1). Salts VII give polymethine dyes, and
t h e i r s t r u c t u r e s w e r e c o n f i r m e d by t h e i r PMR s p e c t r a . The methyl group in the 5 position is shielded by
the phenyl group in the 3 position, and its c h e m i c a l shift is 2.07 p p m , which is c h a r a c t e r i s t i c for a f r a g -
ment of this type [7]. The s t r u c t u r e of VIIc, obtained by condensation with benzoylacetone, was p r o v e d by
the fact that the signal of one methyl group (2.70 ppm), which d e t e r m i n e s its position as 7-CH3, is o b s e r v e d

736
in its PMR s p e c t r u m . In addition, a convincing p r o o f of the position of the phenyl group (5-C~Hs) is its
coupling with 3-CGHs, as a r e s u l t of which (mutual shielding) the signals of both phenyl groups a r e shifted
to strong field (6.72 and 6.78 p p m as against 7.31 for 3-C6H 5 in VIIa).

EXPERIMENTAL
The PMR s p e c t r a of t r i f l u o r o a c e t i c acid solutions of the compounds r e l a t i v e to hexamethyldisiloxane
(HMDS) as the internal s t a n d a r d w e r e r e c o r d e d with a ZKR-60 s p e c t r o m e t e r .
2 , 4 , 7 , 9 - T e t r a m e t h y l - 6 - p h e n y l p y r l m i d o [2' ,1' : 2,3]imidazo [1,5-b]pyridaztnium p e r c h l o r a t e (IIa). A)
A solution of 0.69 g (2.5 mmole) of the p e r c h l o r a t e of I and 1.5 ml (15 mmole) of acetylacetone in 3 ml of
alcohol was r e f l u x e d for 2 h, a f t e r which it was w o r k e d up to give 0.57 g (57%) of a light-yellow c r y s t a l l i n e
p r e c i p i t a t e of IIa, which was c r y s t a l l i z e d f r o m methanol. It exploded on heating above 330 ~ without melting.
Found: C1 8.9; N 14.3%. C19H19C1N404. Calculated: C1 8.8; N 14.0%.
B) When 0.69 g of the p e r c h l o r a t e of I and 2 ml of a c e t y l a c e t o n e w e r e heated on a w a t e r bath, 0.74 g
(74%) of Ha p r e c i p i t a t e d f r o m the hot r e a c t i o n m i x t u r e a f t e r 5-7 min.
7,_._99-Dimethyl-6-phenyl-2,4-bis ( p - d i m e t h y l a m i n o s t y r y l ) p y r i m i d o [2' ,1' : 2,3]imidazo [ 1 , 5 - b ] p y ~ d a z i n -
ium P e r c h l o r a t e . A 0.1-g (0.25 mmole) s a m p l e of Ha was dissolved by heating in 2 ml of acetic anhydride,
after which 0,15 g (1 mmole) of p - d i m e t h y l a m i n o b e n z a l d e h y d e and two drops of t r i e t h y l a m i n e w e r e added,
and the mixture was heated at 170-175 ~ for 3 h. The m i x t u r e was cooled, and the r e s u l t i n g precipita,te was
washed with boiling alcohol to give 0.05 g (30%) of a b l s s t y r y l with mp 283-285% Found: Ct 5.5; N 12.6%.
C37H37C1N604. Calculated: C1 5.5; N 12.8%.
2 , 4 , 7 , 9 - T e t r a m e t h y l - 3 , 8 - d i e t h y l - 6-phen:~lpyri mido [2', 1' : 2,3]imidazo [1,5-b]pyridazinium P e r c h l o r a t e
(lib). A mixture of 0.69 g (2.5 mmole) of the p e r c h l o r a t e of I and 0.9 ml (7 mmole) of 3 - e t h y l - 2 , 4 - p e n t a n e -
dione was heated at 150-160 ~ for 3 h. The r e s u l t i n g d a r k m a s s was t r i t u r a t e d with acetone to give 0.37 g
(32%) of a brown powder. The product was c r y s t a l l i z e d f r o m ethanol to give yellow c r y s t a l s of p e r c h l o r a t e
IIt) with mp 244-246 ~ PMR s p e c t r u m , 5 , ppm: 0.83 (CH2CH3) , 1.60 (7-CH3), 2.03 (4-CH3) , 2.30 (9-CH3) ,
2.53 (2-CH3) , 2.2-2.5 (CH2CH3) , 7.27 (C6H5). Found: C1 8.0; N 12.2%. C23H27C1N404. Calculated: C1 7.7,
N 12.2%.
2 , 4 , 7 , 9 - T e t r a m e t h y l - 8 - e t h y l - 6-phenylpyrimido [2', 1' : 2,3 ]imidazo [1,5-b]pyridazinium P e r c h l o r a t e
('fie). A mixture of 0.27 g (1 mmole) of IVb, 0.5 g (5 mmole) of a c e t y l a c e t o n e , and a few drops of 57% p e r -
chloric acid was heated at 160-170 ~ for 2 h, and the r e s u l t i n g d a r k m a s s was t r i t u r a t e d with ether and c r y s -
tallized f r o m alcohol to give 0.15 g (35%) of yellow c r y s t a l s of IIc with mp 256-257 ~ (from ethanol); PMR
s p e c t r u m , ~, ppm: 0.78 (CH2CH3), 1.66 (7-CH3) , 1.97 (4-CH3), 2.24 (CH2CH3) , 2.32 (9-CH3) , 2.49 (2-CH3) ,
7.01 (3-H), 7.31 (6-C6H5). Found: C1 8.2; N 13.2%. C21H23C1N404. Calculated: C1 8.2; N 13.0%.
7 - A m i n o - 2 , 4 - d i m e t h y l - 5 - p h e n y l i m i d a z o [ 1 , 5 - b ] p y r i d a z i n e (IVa). A solution of 0.52 g (3 mmole) of
diamine I in 1 ml of acetic acid and 0.4 ml (4 mmole) of a c e t y l a c e t o n e was heated on a w a t e r bath for 2 h,
a f t e r which the m i x t u r e was cooled and p o u r e d into w a t e r . The aqueous mixture was made alkaline with
a m m o n i a and worked up to give 0.46 g (65%) of o r a n g e c r y s t a l s of IVa with mp 213 ~ (from ethanol). PMR
s p e c t r u m , 6, ppm: 1.75 (4-CH3), 2.03 (2-CH3) , 6.05 (3-H), 7.15 (5-C~H5). Found: C 70.7; H 5.8; N 23.5%.
C14H14N4. Calculated: C 70.5; H 5.9; N 23.6%. T r e a t m e n t of the f i l t r a t e with a 20% NaOH solution gave 0.2
g (28%) of yellow c r y s t a l s of 7- ( 4 - o x o - 2 - p e n t e n - 2 - y l a m i n o ) - 2 , 4 - d i m e t h y l - 5 - p h e n y l i m i d a z o [1,5-b]pyridazine
(IVh) with mp 217-219 ~ (from ethanol). Found: C 69.9; H 6.0; N 17.6%. C19H2~N402. Calculated: 71.3;
H 6.2; N 17.5%. T r e a t m e n t of IVh with p e r c h l o r i c acid gave a p e r e h l o r a t e that was identical to lIa.
7 - ( D i a c e t y l a m i n o ) - 2 , 4 - d i m e t h y l - 5 - p h e n y l i m i d a z o [ 1 , 5 - b ] p y r i d a z i n e (IVi). A mixture of 0.12 g (5
mmole) of IVa and 0.3 ml (3 mmole) of acetic anhydride was heated on a w a t e r bath for 30 min, a f t e r which
0.12 g of the diacetyl d e r i v a t i v e was r e m o v e d by filtration. W a t e r was added to the f i l t r a t e to give another
0.03 g of the diacetyl derivative. The o v e r a l l yield of IVi with mp 162-163 ~ ( f r o m ethanol) was 94%. Found:
C 67.1; H 5.8; N 17.3%. C18Hl~N402. Calculated: C 67.4; H 5.6; N 17.4%.
7 - A m i n o - 2 , 4 - d i m e t h y l - 3 - e t h y l - 5 - p h e n y l i m i d a z o [1,5-b]pyridazine (IVb). This compound was obtained
f r o m I and 3 - e t h y l - 2 , 4 - p e n t a n e d i o n e by refluxing in acetic acid at 150-160 ~ for 2 h. The yield of product
with mp 215-216 ~ ( f r o m ethanol) was 40%. Found: C 71.6; H 6.2; N21.2%. C16H18N4. Calculated: C 72.2; H 6.8;
N 21.0%.
7 - A m i n o - 2 , 4 , 5 - t r i p h e n y l i m i d a z o [ 1 , 5 - b ] p y r i d a z i n e (IVc). A mixture of 0.7 g (4 mmole) of I and 1.56
g (7 mmole) of dibenzoylmethane in 1 ml of acetic acid was heated at 200 ~ for 4 h, a f t e r which it was cooled,

737
t r i t u r a t e d with e t h e r , and washed s e v e r a l t i m e s with boiling methanol to give 0.16 g (12%) of a r e d s u b s t a n c e
with mp 252-255 ~ (from propanol). PMR s p e c t r u m , 6 , ppm: 6.77 (4- and 5-C6H5), 7.18 and 7.57 (three and
two protons of 2-C6H5, r e s p e c t i v e l y ) . Found: C 79.3; H 5.2; N 15.7%. C24Hl~N4. Calculated: C 79.5; H 5.0;
N 15.5%.
7 - A m i n o - 2 - m e t h y l - 4 , 5 - d i p h e n y l i m i d a z o [1,5-b]pyridazine (IVd). This compound was obtained by h e a t -
ing I and benzoylacetone in acetic acid at 175-180 ~ for 2 h. The m i x t u r e was t r i t u r a t e d with e t h e r and m e t h -
anol to give a r u b y - r e d c r y s t a l l i n e substance with mp 275 ~ (from propanol) in 76% yield. PMR s p e c t r u m ,
6, ppm: 2.17 (2-CH3), 6.20 (3-H), 6.66 (4- and 5-C6H~). Found: C 76.1; H5.7; N 18.6%. C19H16N4. Calcu-
lated: C 76.0; H 5.4; N 18.7%.
7 - M e r c a p t o - 2 , 4 - d i m e t h y l - 5 - p h e n y l i m i d a z o [ 1 , 5 - b ] p y r i d a z i n e (IVe). A 0.47-g (2.5 m m o l e ) s a m p l e of
III was heated at 135-140 ~ for s e v e r a l minutes with 2 ml of acetylacetone in the p r e s e n c e of a few drops of
57% p e r c h l o r i c acid. The r e s u l t i n g p r e c i p i t a t e was s e p a r a t e d and washed with e t h e r to give 0.54 g (83%) of
yellow c r y s t a l s of IVe with mp 309-311 ~ ( f r o m ethanol). PIVIR s p e c t r u m , 8, ppm: 1.87 (4-CH3), 2.20
(2-CH3) , 6.34 (3-H), 7.14 (5-C6H5). Found: N 16.4; S 12.5%. C14H~3N3S. Calculated: N 16.5; S 12.6%.
1 - ( 4 - O x o - 2 - p e n t e n - 2 - y l a m i n o ) - 2 - m e r c a p t o - 4 - p h e n y l i m i d a z o l e . A m i x t u r e of 0.95 g (5 mmole) of III
and 2 ml (20 mmole) of a e e t y l a c e t o n e was heated at 150 ~ The m i x t u r e began to solidify a f t e r 10 min, and
it was then t r i t u r a t e d with e t h e r to give 1.31 g (95%) of a white c r y s t a l l i n e s u b s t a n c e with mp 223-224 ~
(from ethanol). Found: N 15.6; S 11.4%. C14H15N3OS. Calculated. N 15.4; S 11.7%.
7 - M e t h y l t h i o - 2 , 4 - d i m e t h y l - 5 - p h e n y l i m i d a z o [ 1 , 5 - b ] p y r i d a z i n e (IVf). A 0 ~ (0.9 m m o l e ) s a m p l e of
dimethyl sulfate was added to a solution of 0.1 g (0.4 mmole) of IVe in 15 ml of 2% NaOH, and the mixture
was worked up to give 0.08 g (75%) of a yellow p r e c i p i t a t e of IVf with mp 169-170 ~ (from ethanol). Found:
N 15.6; S 11.9%. C15H15N3S. Calculated: N 15.6; S 11.9%.
7 - M e t h y l t h i o - 2 , 4 , 6 - t r i m e t h y l - 5 - p h e n y l i m i d a z o [ 1 , 5 - b ] p y r i d a z i n i u m P e r c h l o r a t e . A solution of 0.4 g
(1.5 mmole) of IVf in 2 ml of d i m e t h y l f o r m a m i d e (DMF) was heated with 0.6 ml (5.4 mmole) of dimethyl s u l -
fate on a w a t e r bath for 2.5 h. The r e s u l t i n g s a l t was p r e c i p i t a t e d with e t h e r , dissolved in w a t e r , and i s o -
lated as the p e r c h l o r a t e . The shiny white plates [0.54 g (96%)] had mp 225-226 ~ (from methanol). PMR
s p e c t r u m , 6, ppm: 1.75 (4-CH3), 2.30 and 2.43 (2-CH 3 and S-CH3) , 3.60 (6-CH3), 6.47 (3-H), 7.17 (5-C~H5).
Found: C19.2; S 8.3%. C16HIsC1N304S. Calculated: C1 9.4; S 8.4%.
7 - M e r c a p t o - 2 , 4 , 5 - t r i p h e n y l i m i d a z o [ 1 , 5 - b ] p y r i d a z i n e (IVg). A mixture of 0.38 g (2 mmole) of HI, 0.66
g (3 mmole) of dibenzoylmethane, a few drops of 57% p e r c h l o r i c acid, and 1 ml of acetic acid was heated at
120 ~ for 2-3 min. Shiny r u b y - r e d plates [0.67 g (88%)] with mp 315-317 ~ (from diethylene glycol) p r e c i p -
itated f r o m the r e s u l t i n g solution. PM:R s p e c t r u m , 6, ppm: 6.83 (4- and 5-C6H5, b r o a d peak), 8.43 (3-H),
7.17 and 7.70 (three and two protons of 2-C6H5, r e s p e c t i v e l y ) . Found: N 11.2; S 8.7%. C24Hl~N3S. Calcu-
lated: N 11.1; S 8.4%.
1 - B e n z y l i d e n e a m i n o - 5 , 7 - d i m e t h y l - 3 - p h e n y l [ m i d a z o [ 1 , 2 - a ] p y r i m i d i n i u m P e r c h l o r a t e (Via). A solution
of 1.81 g (5 mmole) of V in 1 ml of acetylacetone was heated at 190-200 ~ for 7 h, and the r e a c t i o n product
was t r i t u r a t e d with e t h e r to give 1.83 g (86%) of yellowish c r y s t a l s of Via with mp 267-268 ~ (from m e t h -
anol). PMR s p e c t r u m , 6, ppm: 1.99 (5-CH3), 2.46 (7-CH3) , 6.90 (6-H), 7.20 (3-C6H5), 7.92 (2-H), 8.57
(N-CHC~Hs), 7.55 and 7.18 (two and t h r e e protons of the benzylidene phenyl group). Found: C1 8.4; N 13.2%.
C21HI9CIN404. Calculated: C1 8.3; N 13.1%.
1-Benzylideneamino-5,6-dimethyl-3-phenylimidazo[1,2-a]pyrimidiniumPerchlorate (Vlb). A 0.6 ml
s a m p l e of 3 - c h l o r o - 2 - m e t h y l - 3 - b a t e n a l was added to a s u s p e n s i o n of 0.72 g (2 mmole) of V in 10 ml of
methanol in the cold, a f t e r which the m i x t u r e was allowed to stand for 3 days and was then f i l t e r e d to give
0.37 g (43%) of yellowish c r y s t a l s of VIb with mp 267-268 ~ (from methanol). PMR s p e c t r u m , 6 , p p m : 2.03
(5-CH3) , 2.13 (6-CH3) , 7.20 (3-C6H5) , 8.04 (2-H), 8.55 and 8.63 (7-H and N-CHCGHs) , 7.62 and 7.19 (two and
t h r e e protons of the benzylidene phenyl group). Found: C1 8.3; N 13.2%. C21H19C1N404. Calculated: C1 8.3;
N 13.1%.
5 , 7 - D i m e t h y l - 3 - p h e n y l - l - ( 4 - m e t h y l - 2 - t h i a z o l y l ) i m i d a z o [ 1 , 2 - a ] p y r i m i d i n i u m P e r c h l o r a t e (VIIa). A
0.36-g (1 mmole) s a m p l e of 1 - ( 4 - m e t h y l - 2 - t h i a z o l y l ) - 2 - a m i n o - 4 - p h e n y l i m i d a z o l i u m p e r c h l o r a t e was heated
with 0.3 g (3 mmole) of a c e t y l a c e t o n e at 145 ~ for 1 h, a f t e r which the m i x t u r e was cooled, and the r e a c t i o n
m a s s was t r i t u r a t e d with ether and f i l t e r e d to give 0.38 g (80%) of VIIa with mp 253-254 ~ ( f r o m ethanol).
Found: C1 8.5; N 13.4%. C18tI17C1N404S. Calculated: C1 8.4; N 13.2%.

738
 5 , 7 - D i m e t h y l - 3 - p h e n y l - l - ( 4 - p h e n y l - 2 - t h i a z o l y l ) i m i d a z o [ 1 , 2 - a ] p y r i m i d i n i u m P e r c h l o r a t e (VIIb). This
compound was s i m i l a r l y obtained f r o m 1 - ( 4 - p h e n y l - 2 - t h i a z o l y l ) - 2 - a m i n o - 4 - p h e n y l i m i d a z o l e p e r e h l o r a t e and
acetylacetone. The yield of product with mp 280 ~ (from nitromethane) was 91%. PMR s p e c t r u m , ~, ppm:
2.07 (5-CH3) , 2.61 (7-CH3), 7.20-7.42 (protons of the phenyl group of the thiazole ring), 7.31 (3-C6H5) , 7.52
(6-H and thiazole ring proton), 8.22 (2-H). Found: C1 7.5; N 12.2%. C23HIgC1N404S. Calculated: C1 7.4;
N 11.6%.
7- NIethyl-3,5-diphenyl- 1- (4-phenyl-2-thiazolyl) imidazo [1,2-a]pyri midinium P e r c b l o r a t e (VIIc). This
compound was obtained f r o m 1 - ( 4 - p h e n y l - 2 - t h i a z o l y l ) - 2 - a m i n o - 4 - p h e n y l i m i d a z o l i u m p e r c h l o r a t e and b e n -
zoylacetone by heating at 145 ~ for 3 h. The yield of yellow c r y s t a l s with mp 247-248 ~ (from nitromethane)
was 82%. PMR s p e c t r u m , 5, ppm: 2.70 (7-CH3) , 6.72 and 6.78 (3- and 5-C6H~) , 7.24 and 7.45 (6H and t h i a -
zole r i n g proton), 7.08-7.31 (protons of the phenyl group of the thiazole ring), 8.19 (2-H). Found: C1 6.7;
N 10.5%. C28H21C1N404S. Calculated: C1 6.5; N 10.3%.
5,7-Dimethyl-3-(p-bromophenyl)-l- [4-(p-bromophenyl)-2-thiazolyl]imidazo[1,2-a]pyrimidinium Tri-
fluoroacetate (VIId). A 0.47-g (1 mmole) s a m p l e of 1- [4- (p-bro mophenyl)-2-thiazolyl ] - 2 - a m i n o - 4- ( p - b r o -
mophenyl)imidazole was dissolved in 0.4 ml of t r i f l u o r o a c e t i e acid, a f t e r which 0.2 g (2 mmole) of a c e t y l -
acetone was added, and the mixture was heated at 145-150 ~ for 1.5 h. It was then cooled, and the r e a c t i o n
product was t r i t u r a t e d with e t h e r to give 0.49 g (79%) of VHd with mp 310 ~ (from ethanol). Found: Br 24.5;
N 8.6%. C25HITBr2F3N402. Calculated: Br 24.5; N 8.6%.

LITERATURE CITED
Io H. B e y e r , A. Hetzheim, H. Honeck, D. Ling, and T. Pyl, B e r . , 101, 3151 (1968).
2. T. Pyl, F. Washchk, and H. Beyer, Ann., 663 , 113 (1963).
3. G. M. Golubushina and V. A. Chuiguk, Khim. Geterotsikl. Soedin., 1035 (1971).
4. G. M. Golubushina and V. A. Chuiguk, Ukr. I~im. Zh., 37,799, 1133 (1971).
5. W. Paudler and J. Kuder, J. Org. Chem., 31, 809 (1966).
6. S. I. Shul'ga and V. A. Chuiguk, Ukr. Khim. Zh., 37,257 (1971).
7. H. Beyer and S. Schmidt, Ann., 748, 109 (1971).

739
ACYLATION OF SOME SUBSTITUTED
1,2,4-TRIA ZOLE-3- THIONES

M. M. Tsitsika, S. M. Khripak, UDC 547.792.5 : 542.951.1

a n d I. V. S m o l a n k a

Acylation of s o m e substituted 1 , 2 , 4 - t r i a z o l e - 3 - t h i o n e s in the p r e s e n c e of t r i e t h y l a m i n e gives

N - s u b s t i t u t e d d e r i v a t i v e s . S-Substituted d e r i v a t i v e s , which a r e r e a d i l y t r a n s a c y l a t e d to the
N - s u b s t i t u t e d d e r i v a t i v e s on heating, a r e f o r m e d in the c a s e of 4 - p h e n y l t r i a z o l e t h i o n e s in
alkaline media. In the c a s e of 4 - a l l y l t r i a z o l e t h t o n e s acylation in alkaline m e d i a gives only
the N - s u b s t i t u t e d d e r i v a t i v e s . B r o m i n a t i o n of the acyl d e r i v a t i v e s gives the disulfides.

It is known [1] that acylation of t h i o u r e a with acid c h l o r i d e s depends on the conditions used to c a r r y
out the r e a c t i o n . The r e a c t i o n s p r o c e e d by means of S , N - t r a n s a c y l a t i o n . It was of i n t e r e s t to investigate
the acylation of 4,5-substituted 1 , 2 , 4 - t r i a z o l e - 3 - t h i o n e s (In, b) with acid chlorides.
We w e r e unable to acylate In, b with acid c h l o r i d e s (benzoyl chloride and cinnamoyl chloride) in b e n -
zene solution on prolonged heating- the s t a r t i n g In, b w e r e isolated f r o m the m i x t u r e s .
However, N - a c y l d e r i v a t i v e s (IVa~ a ' , b, b') a r e f o r m e d in the p r e s e n c e of t r i e t h y l a m i n e . The action
of an aqueous alcohol solution of s o d i u m hydroxide on Ia, b gives s o d i u m s a l t s Ha, b. Reaction of IIa with
acid chlorides (benzoyl and cinnamoyl chlorides) in benzene at r o o m t e m p e r a t u r e gave the S - d e r i v a t i v e s
(IIIa, a'), which w e r e not identical to the s u b s t a n c e s obtained by r e a c t i o n of Ia with acid chlorides in the
p r e s e n c e of t r i e t h y l a m i n e . Heating S - d e r i v a t i v e s IIIa, a ' in benzene solution for 30 min gives N - d e r i v a t i v e s
(IVa, a').

When the S - d e r i v a t i v e s 0IIa, a') a r e melted, they undergo t r a n s a c y l a t i o n to N - d e r i v a t i v e s (IVa, aD.

It is noteworthy that I l i a ' undergoes p a r t i a l melting at 152-154 ~, t u r n s yellow (the N - d e r i v a t i v e s axe yellow),
N--N
C6 HS-~N ~/L-sco R'
I

II[:,a'

N--N Br~ N--N ~--N"

C6HS--J~NI/J-- SNa CHCI3
t I I
R R R
tlajb

N--NH ..coo, N--N--co.'

Cr,Hs'-J~N,~ S
I I
R R
la,b IV a,a',b,b'
Ia, IIa, Ilia, IVa, Va R=C6Hs; R'=C6Hs; Ilia', IVa' R=C6Hs; R'=CH~=CH--C6Hs;
Ib, Ilb, IVb R=CH2--CH=CH2; R'=C~Hs; Ivb',R=CH2--CH=CH2; R/=CH~=CH--C~H5

again solidifies, and melts at 205-206 ~ (like N - d e r i v a t i v e IVa).

Uzhgorod State University. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i e h e s k i k h Soedinenii, No. 6, pp. 851-

853, June, 1975. Original article s u b m i t t e d April 13, 1973.

9 1975Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

740
 ,g e /h :"".
:.,. ..,... tgC

/~"\ r. . . . . 9

r ! ,.

, II~'\ /

,:::\!
a" t "i \/ "'}, 319
[~ !\
\ \ ,-5
=,'i
I.
i,, % .,
ai
3p7 ',"% \ ~i ' "%
"
! % t )
\ /\
\./ ~z i2
3t5 , , ,

22.0 240 260 280 300 320 A,~,[lrrl 220 240 a6o 2so 3oo 32o'

Fig. 1 Fig. 2
Fig. 1. UV s p e c t r a of: 1) Ilia'; 2) IVa'; 3) IVa; 4) Ilia.
Fig. 2. UV s p e c t r a of: 1) IVb'; 2) IVb; 3) Va.

TABLE 1. C h a r a c t e r i s t i c s of the Compotmds Obtained

N,% Yield, a]o
Compound I mp, "C i Empirteal formula
found calc. (method)

lIIa 204--205 CalHtsNaOS 11,9 11,8 68

Ilia' 206--207 C2aHITNaOS 11,0 11,0 70
IVa 204--205 CmHlsNaOS 11,8 11,8 51 (A)
91 (B)
IVa' 206--207 C2aH~7N30S 10,9 11,0 42 (A)
90 (c)
IVb 82--83 C18HIsNaOS 13,0 t3,1 47
1Vb' 122--123 C2oHI7NaOS 12,0 12,1 61

Hydrolysis of S - d e r i v a t i v e s Ilia, a' and N - d e r i v a t i v e s IVa, a', b, b' at r o o m t e m p e r a t u r e with a 2 N

aqueous alcohol solution of alkali gives the starting IIa, b, which give t r i a z o l e t h i o n e s Ia, b on acidification
with h y d r o c h l o r i c acid.
When there is an allyl substituent in the 4 position, acylation of s o d i u m salt lib with acid c h l o r i d e s hi
b e n z e n e gives only N - a c y l derivatives IVb, b', w h i c h are identical to the compounds obtaind by acylation of
Ib in the p r e s e n c e of triethylamine.
B r o m i n a t i o n of Ha, Ilia, a', and IVa, a' gives only one disulfide - Va. Brominatton of Hb and IVb, b'
gave oily substances that could not be purified.
The UV s p e c t r a of N - d e r i v a t i v e s IVa, a' are s i m i l a r to one another but differ f r o m the UV s p e c t r a
of S - d e r i v a t i v e s Ilia, a' (Fig. 1). The UV s p e c t r a of the s u b s t a n c e s obtained by acylation of Ib and IIb are
s i m i l a r (Fig. 2).

EXPERIMENTAL
The UV s p e c t r a of ethanol solution of the compounds w e r e r e c o r d e d with an S F - 4 s p e c t r o p h o t o m e t e r .
Soditlm Salt of 4 , 5 - D i p h e n y l - l , 2 , 4 - t r i a z o l e - 3 - t h i o n e (IIa). A 2 . 5 3 - g (0.01 mole) s a m p l e of Ia w a s
added to an alcohol solution of 0.4 g (0.01 mole) of s o d i u m hydroxide, and the mixture w a s heated on a w a t e r
bath until the s o l i d had d i s s o l v e d c o m p l e t e l y . It w a s then cooled, and the r e s u l t i n g precipitate w a s r e m o v e d
by filtration and washed with cold ethanol to give 2.6 g (95%) of product.
Sodium Salt of 4 - A l l y l - 5 - p h e n y l - l , 2 , 4 - t r i a z o l e - 3 - t h i o n e (IIb). A 2 . 1 7 - g (0.01 mole) s a m p l e of Ib w a s
added to an alcohol solution of 0.4 g (0.01 mole) of s o d i u m hydroxide, and the mixture w a s heated until all
of the solid had dissolved. The solution w a s cooled, and ether w a s added to precipitate 2.2 g (92%) of a
c r y s t a l l i n e substance.

741
 4 , 5 - D i p h e n y l - 3 - c i n n a m o y l t h i o - l , 2 , 4 - t r i a z o l e (IIIa'). A s u s p e n s i o n of 0.66 g (2.4 mmole} of IIa and
0.38 g (2.4 mmole) of cinnamoyl chloride in benzene w a s s t i r r e d at r o o m t e m p e r a t u r e for 20 min. The p r e -
cipitated sodium chloride was r e m o v e d by filtration, and a c r y s t a l l i n e s u b s t a n c e was p r e c i p i t a t e d f r o m the
filtrate by the addition of ether.
A s i m i l a r p r o c e d u r e was used to obtain IIIa, IVb, b ' (see Table 1).
4 , 5 - D i p h e n y l - 2 - c i n n a m o y l - l , 2 , 4 - t r i a z o l e - 3 - t h i o n e (IVa'). A) A m i x t u r e of 0.5 g (0.2 mmole) of Ia,
0.31 g (0.2 mmole) of cirmamoyl chloride, and 1 g of t r i e t h y l a m i n e in benzene was r e f l u x e d for 30 min. It
was then cooled, and the r e s u l t i n g c r y s t a l s w e r e r e m o v e d b y filtration and w a s h e d with ether. Compounds
IVa, b, b ' w e r e s i m i l a r l y obtained (see Table 1}.
B) A 0.3 g (0.8 mmole) of H I a ' was r e f l u x e d for 30 min to give IVa'. Compound IVa was s i m i l a r l y ob-
tained (see Table 1).
No melting-point d e p r e s s i o n s w e r e o b s e r v e d for m i x t u r e s of the s u b s t a n c e s obtained by the v a r i o u s
methods.
B i s ( 4 , 5 - D i p h e n y l - l , 2 , 4 - t r i a z o l - 3 - y l ) Disulfide (Va). C) A solution of 0.13 g (0.75 mmole) of b r o m i n e
in carbon t e t r a e h l o r i d e was added dropwise with cooling and s t i r r i n g to 0.44 g (1.5 mmole) of IIa in c h l o r o -
f o r m , and the r e s u l t i n g p r e c i p i t a t e was r e m o v e d b y filtration and washed with ether to give 0.35 g (71%) of
Va with mp 221-222 ~ ( f r o m alcohol). Found: N 16.8%. C28H20~6S2. Calculated: N 16.7%.
D) A m i x t u r e of 0.26 g (0.7 mmole) of IVa' and 0.11 g (0.35 mmole) of b r o m i n e in c h l o r o f o r m was
s t i r r e d at r o o m t e m p e r a t u r e for 30 rain, and the r e s u l t i n g p r e c i p i t a t e was r e m o v e d b y filtration and washed
with e t h e r to give 0.15 g (86%) of Va with mp 221-222 ~ (from alcohol). Found." N 16.8. C28H2oN6S2. C a l -
culated: N 16.7%.
Compound Va was obtained by method D b y b r o m i n a t i o n of Ilia, a ' and IVa. No melting -point d e p r e s -
sion was o b s e r v e d for m i x t u r e s of s u b s t a n c e s obtained by the different methods.

LITERATURE CITED
1. T. Wieland and H. Hornig, Ann., 600, 12 (1956).

742
LETTERS TO THE EDITOR

SYNTHESIS OF TRIMETHYLETHYLENE SULFIDE

Zh. Zh. Zhumabaev, A. D. A l l e y , UDC 547.717 : 543.544

and B. A. K r e n t s e l '

The widely accepted data on the p r o p e r t i e s of t r i m e t h y l e t h y l e n e sulfide (I) (bp 145-150~ d4 ~ 0.927;
for example, see [1]), which is obtained in 60% yield by thiocyanation of 2 , 3 - d i b r o m o - 2 - m e t h y l b u t a n e by
means of NH4CNS and subsequent t r e a t m e n t with Na~S~., r a i s e doubts in connection with the anomalously
high boiling point of I in the homologous s e r i e s of methyl-substituted episulfides, Our attempts to obtain
episulfide I by the method in [2] (even when the r e a c t i o n conditions w e r e changed) were unsuccessful be-
cause of side r e a c t i o n s that occur even during the thiocyanation of 2,3-dihaloalkanes [3].
We w e r e able to obtain I [bp 106-108, 53 ~ (100 mm), d425 0.8842] only by r e a c t i o n of t r i m e t h y l e t h y l e n e
oxide with KCNS via a modified method [4].
Episulfide I p o l y m e r i z e s via an ionic m e c h a n i s m to give s t e r e o r e g u l a r p o l y m e r s only on anionic catal-
ysis.

EXPERIMENTAL
Trimethylethyleue Sulfide (I). A 24.1-g i0.28 mole) sample of t r i m e t h y l e t h y l e n e oxide [5] (bp 75 ~ d42~
0.8204, n 2 ~ 1.3834) and a solution of 27.2 g (0.28 mole) of KCNS in 40 ml of 50% ethanol w e r e maintained
in a sealed ampoule at constant rotation in the vertical position for 50 h. The upper l a y e r was s e p a r a t e d , the
same amount of the KCNS solutions was added, and the mixture was s t i r r e d for 24 h. The upper l a y e r was
then s e p a r a t e d and dried with calcium chloride in a r e f r i g e r a t o r . Vacuum distillation with a fractionating
column (normal distillation is accompanied by decomposition of D gave 14.6 g (51%) of c o l o r l e s s episulfide
I (91% pure according to gas - liquid c h r o m a t o g r a p h y with bp 53 ~ (100 mm), nD 25 1.4644, and d42~ 0.8842. UV
s p e c t r u m (in heptane): )~max 263 nm, e 32.3 IR s p e c t r u m (thin l a y e r ) : 2980, 2995 c m - t (vC-H of the
methylidyne group of the episalfide ring), 950, 972 c m - I (eptsulfide ring bands). The splitting of the band
at 1375 c m - I indicates the p r e s e n c e of a gem-dimethyl group. PMR s p e c t r u m (of the pure substance): 8
1.50 (doublet, J = 5 Hz), 1.54 and 1.56 (singlets), 2.76 (quartet). Found: C 58.8; H 9.8; S 31.4%. C5HI~S.
Calculated: C 58.8; H 9.8; S 31.4%.

LITERATURE CITED
1. E. E. Reid, Organic C h e m i s t r y of Bivalent Sulfur, Vol. 3, New York (1960), p. 89.
2. C. Galtngaert, Bull. Soc. Chim. Belge, 31, 109 (1922).
3. N. N. Mel'nikov and N. D. Sukhareva, Reactions and Methods for the Investigation of Organic Com-
pounds [in Russian], Vol. 8, Moscow (1959), p. 16.
4. H. R. Snyder and I. M. Stewart, J. Amer. Chem. Soc., 69, 2674 (1947).
5. M. M. Movsumzade, Izv. Az. Fil. Akad. Nauk SSSR, 5, 61 (1942).
6. E. Vandenberg, J. Pol. Sci., 5, 61 (1972).

A. V. Topchiev Institute of P e t r o c h e m i c a l Synthesis, Academy of Sciences of the USSR, Moscow.

T r a n s l a t e d f r o m Khimiya Geterotsiklicheskikh Soedinenii, No. 6, p. 854, June, 1974. Original article sub-
mitted March 26, 1973; r e v i s i o n submitted September 10, 1973.

9 19 75 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N.Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is availablefrom the publisher for $15.00.

743
DIRECT REPLACEMENT OF A NITRO GROUP
BY A HALOGEN IN A NUMBER
OF IMIDAZO[4,5-c]PYRIDINE DERIVATIVES

Yu. M. Yuttlov and I. A. Svertilova UDC 547.783v822.5.7

The c o r r e s p o n d i n g 4 - h a l o - 1 , 3 - d i h y d r o - 2 H - t m i d a z o [ 4 , 5 - c ] - 2 - p y r i d o n e s (II, III) a r e obtained by heating

4 - n i t r o - 1 , 3 - d i h y d r o - 2 H - i midazo [4,5-c ] - 2 - p y r [done (I) with c o n c e n t r a t e d h y d r o c h l o r [ c or h y d r o b r o mic acid.
Compound II was also obtaIned b y fusing 2 - c h l o r o - 3 , 4 - d i a m i n o p y r t d i n e with urea. R e p l a c e m e n t of the nitro
group by a halogen o c c u r s p a r t i c u l a r l y r e a d i l y in the e a s e of 4 - n i t r o - l , 3 - d t h y d r o - l , 3 - d i m e t h y l - 2 H - i m i d a z o -
[ 4 , 5 - c ] - 2 - p y r i d o n e (IV). 4 - C h l o r o - and 4 - b r o m o - l , 3 - d i h y d r o - l , 3 - d i m e t h y l - 2 H - i m i d a z o [ 4 , 5 - c ] - 2 - p y r i d o n e s
(V and VI) a r e obtained in high yields even when a solution of IV in the c o r r e s p o n d i n g acid is e v a p o r a t e d on
a w a t e r bath.
R e p l a c e m e n t of the nitro group by a halogen could not be r e a l i z e d for the c o r r e s p o n d i n g i m i d a z o -
[4,5-b]pyridine d e r i v a t i v e s even under m o r e s e v e r e conditions than those d e s c r i b e d above. Thus 5 - n i t r o -
1 , 3 - d i h y d r o - l , 3 - d i m e t h y l - 2 H - i m i d a z o [ 4 , 5 - b ] - 2 - p y r i d o n e r e m a i n s unchanged when it is heated with h y d r o -
chloric acid up to 190 + for 16 h.

NO 2 CI (;1

I 11

EXPERIMENTAL
4 - C b l o r o - l , 3 - d i h y d r o - 2 H - i m i d a z o [ 4 , 5 - c ] - 2 - p y r i d o n e (II). A mixture of 2 g (11 mmole) of I and 40 ml
of c o n c e n t r a t e d HC1 was heated at 150-160 ~ for 15 h, a f t e r which the solution was e v a p o r a t e d and n e u t r a l -
ized with a m m o n i a to give 1.33 g (70%) of c o l o r l e s s p r i s m s with mp 342 ~ (after r e p r e c i p i t a t i o n f r o m h y d r o -
c h l o r i c acid solution by the addition of a m m o n i a ) ,
4 - B r o m o - l , 3 - d t h y d r o - 2 H - i m t d a z o [ 4 , 5 - c ] - 2 - p y r i d o n e (HI). This compound was s i m i l a r l y obtained in
507o yield as p r i s m s with mp 335-336 ~ (the product was r e p r e c i p i t a t e d f r o m weakly alkaline solution by the
addition of h y d r o c h l o r i c acid).
4 - C b l o r o - l , 3 - d i h y d r o - l , 3 - d i m e t h y l - 2 H - i m i d a z o [ 4 , 5 - c ] - 2 - p y r i d o n e (V). A 2.08-g (10 mmole) s a m p l e
of IV was refluxed with 50 ml of c o n c e n t r a t e d HC1 for 3 h, a f t e r which the solution was e v a p o r a t e d and n e u -
t r a l i z e d with a m m o n i a to give 1.9 g (96%) of c o l o r l e s s p r i s m s of V with mp 199-200 ~ ( f r o m isopropyl a l c o -
hol}.
4 - B r o m o - l , 3 - d i h y d r o - l , 3 - d i m e t h y l - 2 H - t m i d a z o [ 4 , 5 - c ] - 2 - p y r i d o n e (VI). This compound was s i m i l a r l y
obtained in 87% yield as c o l o r l e s s r o d s with mp 194 ~ (from a l c o h o l ) .
4 - N i t r o - l , 3 - d i h y d r o - l , 3 - d i m e t h y l - 2 H - t m i d a z o [ 4 , 5 - c ] - p y r i d o n e (IV). A 26-rnl s a m p l e of dimethyl sul-
fate was added at 25-30 ~ to a solution of 20 g (111 mmole) of I in 260 ml of a 5% solution of KOH, a f t e r

Donetsk P h y s i c a l Organic C h e m i s t r y Branch, L. V. P i s a r z h e v s M i Institute of P h y s i c a l C h e m i s t r y ,

A c a d e m y of Sciences of the Ukrainian SSR. T r a n s l a t e d f r o m K h i m i y a G e t e r o t s i k l i c h e s k i k h Soedinenii, No.
6, pp. 854-855, June, 1974. Original a r t i c l e s u b m i t t e d July 16, 1973; r e v i s i o n s u b m i t t e d October 31, 1973.

9 19 75PlenumPublishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy of this article is availablefrom the publisher for $15. 00.

744
which the mixture was held at this t e m p e r a t u r e for 3 h, and the precipitate was r e m o v e d by filtration to
give 20.8 g (90%) of light-yellow p r i s m s with mp 225 ~ (from alcohol).
All of the compounds obtained were c h a r a c t e r i z e d by analysis for C, H, Br, and C1.

745
ANTHRAQUINONEISOIMIDA ZOLES

M. V. G o r e l i k and Khan Ir Gvon UDC 547.673'785.5

Heterocyclic anthraquinone derivatives of the I type r e a d i l y undergo nucleophilic addition r e a c t i o n s

that axe not c h a r a c t e r i s t i c for compounds of the anthraquinone s e r i e s owing to partial localization of the
diene s y s t e m in the ring adjoining the h e t e r o r i n g [1]. The s a m e effect might have been expected in the case
of the p r e v i o u s l y unknown anthraquinoneisoimidazoles (II), b e a r i n g in mind that the r e c e n t l y synthesized
2,2-pentamethylenebenzisoimidazole has c l e a r l y e x p r e s s e d unsaturated c h a r a c t e r [2].

EXPERIMENTAL
2,2-Dialkylanthra[1,2-d]imidazoline-6,11-diones (HI). T h e s e compounds w e r e obtained by heating 10
mmole of 1 , 2 - d i a m i n o a n t h r a q u i n o u e (IV) with 20 mmole of cyclohexanone o r acetone and 0.2 g of sulfuric

R
O N--X ,3 N--C--R" O HN--C--R'}

il il II
0 0 0
I I| Ill
1

iHY ]RCOR'
O NH 2 ~ HN--C--R' O NH.

~ I[ /

O
N
yH2 RCOR"
~ I

O
H
~ "
II

O
I " NH:

VIII V-Vll IV
I X=O,S, Se, NAt;a RR'=(Cft2)5,b R-R'=CH3; V Y=CI ;VIY=-Br;
VII Y= C~H~SO2

acid in 10 ml of dimethylformamtde at 50~ for 2 h. The yields r a n g e d f r o m 85 to 92%. Compound IIIa had
mp 190-190.5~ h m a x , a m (log e): 268 (4.66), 567 (4.21); VCO 1629, 1650 c m -1. Compound IIIb had mp 229-
230~ h m a x , n m (log ~): 268 (4.63), 570 (4.16); vCO 1630, 1648 c m -1. Lead dioxide or manganese dioxide
was added to a solution of 10 mmole of imidazoline HI in 100 ml of dioxane at r o o m t e m p e r a t u r e until the
color changed f r o m r e d - v i o l e t to b r o w n - y e l l o w (5-10 rain) to give 2 , 2 - d i a l k y l a n t h r a ] l , 2 - d ] i s o i m i d a z o l e -
6,11-diones (II) in 70-75% yields. Compound IIa had mp 190 ~ (decomp.), X m a x 4 0 5 u m (loge 3.36), a n d v c o
1670 c m -~. Compound Hb had mp 195 ~ ( d e c o m p J , k m a x , nm ( l o g e ) : 315 {3.76, shoulder), 405 (3.36); VCO 1679
c m -1.

Anthraquinone[somidazoles II are distinguished by t h e i r high r e a c t i v i t i e s and they actively add various

nucleophilic agents to give 4-substituted anthraquinoneimidazolines. Thus when a solution of 2 mmole of
hydrochloric, h y d r o b r o m i c , or benzenesulfonic acid in 3 ml of dioxane was added to a solution of 1 mmole
of II in 10 ml of dioxane at r o o m t e m p e r a t u r e , the r e d - v i o l e t coloration of imidazolines V-VII, r e s p e c t i v e
tively, appeared immediately. The yields of V-VII r a n g e d f r o m 88 to 93%. Compound Va had mp 193.5-

S c i e n t i f i c - R e s e a r c h Institute of Organic I n t e r m e d i a t e s and Dyes, Moscow. T r a n s l a t e d f r o m Khimiya

Geterotsiklicheskikh Soedinenii, No. 6, pp. 855-856, June, 1974. Original article submitted July 25, 1973;
r e v i s i o n submitted October 26, 1973.

9 1975Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retn'eval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is availablefrom the publisher for $15.00.

746
194~ ).max, n m (log e): 270 (4.67), 552 (4.15); vCO 1640, 1659 c m -1. Compound Via had mp 199-199.5~
) ' m a x , n m (log e): 271 (4.63), 550 (4.11); vCO 1635, 1659 c m -I. Compound VIIa had mp 231-232~ Amax,
n m (log ~): 273 (4.68), 523 (4.15); VCO 1640, 1661 c m -1. The s t r u c t u r e of 4 - s u b s t i t u t e d imidazolines V-VII
was c o n f i r m e d by a l t e r n a t i v e s y n t h e s i s f r o m the c o r r e s p o n d i n g 3 - s u b s t i t u t e d 1,2-diaminoanthraquinones
(VIII).
The products w e r e isolated by dilution of the solutions with w a t e r and w e r e purified by c h r o m a t o g -
r a p h y of c h l o r o f o r m solutions on a l u m i n u m oxide with subsequent c r y s t a l l i z a t i o n f r o m alcohol (imidazol-
ines) or b e n z e n e - h e x a n e (isoimidazoles); the r e s u l t s of e l e m e n t a r y analysis w e r e in s a t i s f a c t o r y a g r e e -
ment with the calculated values. The e l e c t r o n i c a b s o r p t i o n s p e c t r a w e r e obtained f r o m alcohol solutions of
the imidazolines and f r o m dioxaae solutions of the i s o i m i d a z o l e s . The IR s p e c t r a w e r e obtained f r o m KBr
pellets of the compounds.

LITERATURE CITED
I~ M. V. Gorelik, in: Chemistry of Anthraquinone [in Russian], Khimiya, Moscow (1969), p. 5.
2. D. W. S. Latham, O. Meth-Cohn, and H. Suchitzky, Chem. Commun., 1040 (1972).

747
SYNTHESIS OF iSOFLAVONES THAT HAVE
HYPOCHOLESTERINEMIC ACTIVITY

G . N. D o r o f e e n k o , A. L. Shinkarenko, UDC 547.814.5.07 : 541.69

L. I. Lisevitskaya, A. L. Kazakov,
A. I. Pyshchev, a n d V. V. M e z h e r i t s k i i

A modification of a method for the s y n t h e s i s of isoflavones [1] was developed that m a k e s it p o s s i b l e

to r a p i d l y synthesize natural isoflavones - c l a d r i n (Ic), c a b r e u v i n lid), and t h e i r analogs (Ia, b) - in high
yields:

o
[~ C'~'CHzAr I. DMF., POCl3 ~
R/~-,.,~/~0 H 2. H20 R
A r

! a-d
a R=OH, Ar=C6Hs;b R=OCHa, Ar=C6H~;c R=OH, Ar=3,4-(CH30)2C6H3;d R=OCIi3,
Ar = 3,4- (CH~O)~C~H3

A solution of 0.01 mole of o - h y d r o x y a r y l benzyl ketone in 10 ml of d i m e t h y l f o r m a m i d e was added to

6 ml of phosphorus at such a r a t e that the t e m p e r a t u r e of the m i x t u r e did not exceed 90-100 ~ After 30 min,
the mixture was p o u r e d into w a t e r , and the p r e c i p i t a t e d isoflavone was r e m o v e d b y filtration. The p h y s i c a l
constants of the s y n t h e s i z e d compounds w e r e in a g r e e m e n t with the l i t e r a t u r e data.
In e x p e r i m e n t s with r a b b i t s (with e x p e r i m e n t a l l y induced a t h e r o s c l e r o s i s on a background of a c h o l e s -
t e r o l load) isoflavones Ic and Id showed the c a p a c i t y to n o r m a l i z e lipid m e t a b o l i s m . They r e d u c e the l e v e l
of c h o l e s t e r o l , 13-1ipoproteids, and the c h o l e s t e r o l / p h o s p h o l i p i d coefficient in blood s e r u m .
The p e r c e n t a g e of c h o l e s t e r o l in the a o r t a of r a b b i t s who have r e c e i v e d Ia mad Ib was l o w e r by f a c t o r s
of 1.46 and 2.11, r e s p e c t i v e l y , than in a control group of a n i m a l s . The investigated s u b s t a n c e s r e d u c e the
p e r c e n t a g e of c h o l e s t e r o l in the l i v e r . Thus the isoflavones have a pronounced a n t i s c l e r o t i c effect.

LITERATURE CITED
1. S. A. Kagal, P. M. N a i r , and K. V e n k a t a r a m a n , T e t r a h e d r o n Lett., 592 (1962).

Rostov State University. S c i e n t i f i c - R e s e a r c h InstLtute of P h y s i c a l and Organic C h e m i s t r y , R o s t o v -

on-Don. P y a t i g o r s k P h a r m a c e u t i c a l Institute. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii,
No. 6, p. 857, June, 1974. Original a r t i c l e s u b m i t t e d July 6, 1973; r e v i s i o n s u b m i t t e d D e c e m b e r 7, 1973.

9 19 75Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of tins publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy of this article is availablefrom the publisher for $15.00.

748
SYNTHESIS OF THE 1-(5-TETRAZOLYL)-
3,5-DIPHENYLVERDAZYL RADICAL

V. P . Shchipanov and A. A. Skachilova UDC 547.796.1'883

We have o b s e r v e d that 1 - ( 5 - t e t r a z o l y l ) - 3 , 5 - d i p h e n y l f o r m a z a n (I) r e a c t s with f o r m a l d e h y d e in alkaline

media to give the leuco b a s e (II) of the l - ( 5 - t e t r a ~ o l y l ) - 3 , 5 - d i p h e n y l v e r d a z y l r a d i c a l (Ii).

N--N~
{I
N
"~.C--N H N~-C,6H s CH~O ~-"%c_NC~-r
/..H2
PbO~ li "c-N/ \~N-c~.~
N--N.,,

~-~v
H
II
N
,
N ~ - ~ / ; . N N~.~ - ~ N-~
H
)
N N"
I ~
\c// "~c/ ~,c/
~6"~ 16Ha ~"s
I II Ill

In c o n t r a s t to the leuco b a s e s of t r i a r y l v e r d a z y l r a d i c a l s , II is stable with r e s p e c t to a i r oxygen in

the c r y s t a l l i n e state and in solution but f o r m s v e r d a z y l r a d i c a l III, which is p a r a m a g n e t i c in the c r y s t a l l i n e
s t a t e and in solution (according to ESR data), on oxidation with lead dioxide in ether.

EXPERIMENTAL
Leuco Base II of the 1 - ( 5 - T e t r a z o l y l ) - 3 , 5 - d i p h e n y l v e r d a z y l Radical (ID. A 2 . 1 - m l s a m p l e of a 37%
solution of f o r m a l d e h y d e was added to a solution of 2.92 g (0.01 mole) of I in 90 ml of 1% sodium hydroxide,
and the mixture was maintained for 3 h without a c c e s s to the a i r , a f t e r which it was filtered. The f i l t r a t e
was acidified with acetic acid to give 1.75 g (57%) of II with mp 180.5-182.5 ~ (deeomp., c o l o r l e s s needles
f r o m c h l o r o f o r m ) and R f 0.21 in a thin l a y e r of activity IV A1203 [ a c e t o n e - c h l o r o f o r m - a c e t i c acid
( 7 6 : 2 2 : 2 ) ] . The c b r o m a t o g r a m was developed with iodine v a p o r s . UV s p e c t r u m (in alcohol), k m a x , n m
(log ~): 230 (4.27), 305 (4.03). IR s p e c t r u m : 3321 (NH) e m -1. Found: 59.0; H 4.2; N 37.0%. C15HI4N8.
Calculated: C 58.8; H 4.6; N 36.6%.
1 - ( 5 - T e t r a z o l y l ) - 3 , 5 - d i p h e n y l v e r d a z y l Radical (Ill). A solution of 0.3 g of II in 200 ml of diethyl ether
was shaken with 3 g of brown PbO 2 and 3 g of anhydrous Na2SO a for 30 min, a f t e r which the g r e e n solution
was filtered and c o n c e n t r a t e d in vacuo to 20 ml. The addition of heptane p r e c i p i t a t e d 0.2 g (66%) of III as a
d a r k - b l u e powder with mp 104.5 ~ (decomp., r e c p r e e i p i t a t i o n f r o m e t h e r solution by the addition of heptane):
The product was r e a d i l y soluble in m o s t organic solvents and in aqueous alkali solution but insoluble in
w a t e r and aliphatic h y d r o c a r b o n s . Application of a c h l o r o f o r m solution of Ill to A1203 of any d e g r e e of a c -
tivity led to r a p i d decolorization of the s a m p l e b e c a u s e of r e d u c t i o n of III to II (Rf 0.21). UV s p e c t r u m (in
benzene), k m a x , n m (log e): 380(3.97),690 (3.64). Found: C 59.0; H 4.5; N 36.6%. C15H13N8. Calculated:
C 59.0; H 4.3; N 36.7%.

Tyumen Industrial Institute. T r a n s l a t e d f r o m Khimiya GeterotsiklicheSkikh Soedinenii, No. 6, pp.

857-858, June, 1974. Original a r t i c l e submitted F e b r u a r y 26, 1973; r e v i s i o n s u b m i t t e d D e c e m b e r 5, 1973.

9 19 75Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy of this article is available from the publisher for $15.00.

749
5- FLUO1ROSULFONYLC YTOSINE

L . S. G e r m a n , V. R . P o l i s h c h u k , UDC 547.854.81'221
M. N. P r e o b r a z h e n s k a y a a n d S. Ya. Mel'nik

We have found that refluxing of uracil (I) with e x c e s s fluorosulfonic acid gives 5 - f l u o r o s u l f o n y l u r a c i l
(ll), which f o r m s 5-fluorosulfonylcytosine (llI) r a t h e r than a sulfamide on t r e a t m e n t with a m m o n i u m h y d r o x -
ide; this is the f i r s t instance of the direct synthesis of cytosines f r o m the c o r r e s p o n d i n g u r a c i l s .

EXPERIMENTAL
A solution of 20 g of I in 200 ml of fluorosulfonic acid was heated at 160-180~ for 5 h, a f t e r which the
fluorosulfonic acid was r e m o v e d by v a c u u m distillation, and the r e s i d u e was t r e a t e d with ice to give 30.2 g
(91.8%) of II with mp 255-256 ~ (decomp., f r o m water). UV s p e c t r u m (in w a t e r ) , ?~max, n m (e): 262 (7730).
P1V[R s p e c t r u m (6, ~ acetone): singlet at 7.96 and b r o a d singlet (center at 11.2 ppm). 19F NMR s p e c t r u m
(in acetone with CF3COOH as the external standard): singlet a t - 1 3 7 . 7 ppm. Found: C 24.5; H 1.8; F 9.8%.
C4H~FN204S. Calculated: C 24.8; H 1.6; F 9.8%.
A total of 7 ml of 6% a m m o n i u m hydroxide solution was added to a solution of 1.84 g of II in 12 ml of
w a t e r , After 10 rain, the m i x t u r e was cooled, and the p r e c i p i t a t e d c r y s t a l s w e r e s e p a r a t e d to give 1.15 g
(55%) of the hydrate of Ill with mp 209-210 ~ ( f r o m water); ~ max, n m (e): 278 (13,900). PMR s p e c t r u m (di-
methyl sulfoxide, t e t r a m e t h y l s i l a n e as the external standard): singlet at 8.15 ppm. 19F NM:R s p e c t r u m
(DMSO, CF3COOH as the e x t e r n a l standard): singlet a t - 1 4 3 . 5 ppm. Found: C 22.8; H 2.9; N 20.2%.
C4HTFN304S. Calculated-. C 22.7; H 3.3; N 19.9%.

Institute of H e t e r o o r g a n i c Compounds, A c a d e m y of Sciences of the USSR. Institute of E x p e r i m e n t a l

and Clinical Oncology, A c a d e m y of Medical Sciences of the USSR, Moscow. T r a n s l a t e d f r o m Khimiya G e t -
e r o t s i k l i c h e s k i k h Soedinenii, No. 6, p. 858, June, 1974. Original a r t i c l e s u b m i t t e d D e c e m b e r 17, 1973.

9 1975 Plenum Publishing Corporation, 227 West 17th Street, New York, N.Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy of this article is availablefrom the publisher for $15.00.

750
5-POLYFLUOROALKYLURACILS

L. S. German, V. R. Polishchuk, UDC 547.854.4'221

M. N. Preobrazhenskaya, S. Ya. Mel'nik,
and L. M. Kirshchenya

We have a c c o m p l i s h e d the synthesis of 5 - p o l y f l u o r o a l k y l u r a c i l s by condensation of 5 - h y d r o x y m e t h y l -

uracil (I) with fluoro olefins in anhydrous HF.
X2 xI
O O I
HN'~'~./CH: CH X~ /X' II 1

H H
I I1

a X'=X2=X3='H; b XI=F, X2=X3=H;C XI~:(2=F, X3=lt;d XI=X2=X3=F

The r e a c t i o n o c c u r s via a s c h e m e involving c o n c e r t e d e l e e t r o p h i l i c addition, in which the driving force is

a p p a r e n t l y the f o r m a t i o n of a stable r e s o n a n c e - s t a b i l i z e d cation f r o m I in acidic media:

0 0 0

o.-A.Y _,,o - oA. -J

H H H

EXP ERIMENTAL
Dry vinyl fluoride was bubbled through a stirred solution of 6.7 g of I in i00 ml of anhydrous HF at
0 ~ at a rate sufficient to insure complete absorption, after which the HF was evaporated, and the residue
was treated with water and neutralized with ammonium bicarbonate to give 3.9 g (44%) of Ha with mp 256-
258 ~ (from 50% ethanol). UV spectrum, )`max (50% ethanol), nm (e): 264 (8100). 19F NIVIR spectrum (here
and subsequently, relative to the CF3COOH solvent): doublet of triplets (42 ppm), JCHF=56.4 Hz, JCFCH =
17.7 Hz. Found: C 44.3; H 4.5; F 19.4%. CTHsF2N202. Calculated: C 44.2; H 4.2; F 20.0%. The following
compounds were similarly obtained: rib (from I and vinylidene fluoride, 43% yield) with mp 266-269 ~ (from
50% ethanol). UV spectrum, )`max (50% ethanol), nm (e): 263 (7800). IOF NMR spectrum: triplet (-9.55
ppm), JCFCH=9.7 Hz. Found: C 40.5; H 3.5; F 27.0%. CTH7F3N202. Calculated: C 40.4; H 3.4; F 26.4%.
Compound lic, with nap 261-263 ~ (from 50% ethanol), was obtained in38.4% yieldfroml an~trifluoro-
ethylene. UV spectrum, )`max (50% ethanol), nm (~): 261 (7400). 19F NMR spectrum: doublet of doublets
(4.29 ppm), JCFaCF=II~ Hz, JCF3CH=6.4 Hz; multiplet (124.3 ppm), JCHF=46.7 Hz (from PMR data)~
Found: C 37.2; H 2.9; F 33.0%. CTH6F4N202. Calculated: C 37.2; H 2.7; F 33.6%.

A mixture of 7 g of I, 8 g of tetrafluoroethylene and I00 g of HF was stirred at 20 ~ for 4 h in an auto-

clave. The usual workup gave 2 g of lid with mp 260-262 ~ [purified by adsorption chromatography on silica
gel in chloroform-methanol (5 :i)]. UV spectrum, ),max (50% ethanol), nm (e): 262 (7800). 19F NMR spec-
trum: singlet (9.2 ppm), triplet (41.7 ppm), JCF2CH2=I8.5 Hz. Found: C 34.7; H 2.9%. CTHsFsN202. Cal-
culated: C 34.4; H 2.0%.
Institute of H e t e r o a r o m a t i c Compounds, A c a d e m y of Sciences of the USSR. Institute of E x p e r i m e n t a l
and Clinical Oncology, A c a d e m y of Medical Sciences of the USSR, Moscow. T r a n s l a t e d f r o m Khimiya G e t -
e r o t s i l d i e h e s k i k h Soedinenii, No. 6, p. 859, June, 1974. Original a r t i c l e s u b m i t t e d D e c e m b e r 17, 1973.

9 19 75Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy of this article is availablefrom the publisher for $15.00.

751
ELIMINATION OF BROMINE DURING THE REACTION
OF 2,8-DIBROMO-7-E THOX Y-3-PHENOXA ZINONE
WITH MORPHOLINE*

I. Ya. Postovskii, G. B. A f a n a s ' e v a , UDC 547.867.6.7 : 542.944

a n d T . S. V i k t o r o v a

We have established that the r e a c t i o n of 2 , 8 - d i b r o m o - 7 - e t h o x y - 3 - p h e n o x a z i n o n e (I) with morpholine

without a solvent leads not only to r e p l a c e m e n t of the b r o m i n e in the quinoid ring but also to simultaneous
elimination of the second b r o m i n e atom in the 8 position to give 2 - m o r p h o l i n o - 7 - e t h o x y - 3 - p h e n o x a z i n o n e
0I). The s t r u c t u r e of the l a t t e r was proved by synthesis f r o m 7-ethoxy-3-phenoxazinone and conversion of
II to the known [2] 2-(p-tolylthio) derivative (IV).
]~ /--k

I V Yi

. , +, t + t..a +

II i~ III

The r e a c t i o n of I with morpholine and morpholine hydrochlortde in alcohol does not lead to elimina-
tion but r a t h e r to nucleophilic substitution of the bromine atom in the quinotd ring to give 2 - m o r p h o l i n o - 8 -
b r o m o - 7 - e t h o x y - 3 - p h e n o x a z i n o n e (V) and also to r e p l a c e m e n t of the ethoxy group by a morpholtne r e s i d u e
to give small amounts of 2 , 7 - d i m o r p h o t i n o - 8 - b r o m o - 3 - p h e n o x a z i n o n e (VI).
N-Methylmorpholine also r e a c t s with I to give V. P i p e r i d l n e and aniline r e a c t like morpholine. The
mechanism of the r e a c t i o n is being studied.

EXPERIMENTAL
2 - M o r p h o l i n o - 7 - e t h o x y - 3 - p h e n o x a z i n o n e (I1). A 15-ml sample of morpholine was added to 1 g (2.5
mmole) of I, and the mixture was reflaxed for 3 h. It was then cooled, and the resulting precipitate was r e -
moved by filtration, washed with alcohol, dried, and c h r o m a t o g r a p h e d with a column filled with activity HI
aluminum oxide (elution with chloroform) to give 0.45 g (55%) of orange needles with mp 223-225 ~ (from
butanol). Found: C 66.1; H 5.6; N 8.970. ClsH18zN204. Calculated: C 66.3; H 5.6; N 8.670.
2 - M o r p h o l i n o - 8 - b r o m o - 7 - e t h o x y - 3 - p h e n o x a z i n o n e (V) and 2 , 7 - D i m o r p h o l i n o - 8 - b r o m o - 3 - p h e n o x a -
zinone (VI). A 1-g (2.5 mmole) sample of I, 1.9 g (14.4 mmole) of morpholine hydrochloride, and 15 ml of
morpholine w e r e suspended in 50 ml of ethanol, and the mixture was refluxed for 3 h. It was then cooled

*Communication X f r o m the s e r i e s " R e s e a r c h on the C h e m i s t r y of Phenoxazines." See [1] for c o m m u n i -

cation IX.

S. M. Kirov Ural Polytechnic Institute, Sverdlovsk. T r a n s l a t e d f r o m Khimiya Geterotsikl|chesMkh

Soedineni[, No. 6, pp. 860-861, June, 1974. Original a r t i c l e submitted December 26, 1973.

9 19 75Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy o f this article is availablefrom the publisher for $15.00.

752
and the r e s u l t i n g p r e c i p i t a t e was r e m o v e d by filtratibn, washed with alcohol, and c h r o m a t o g r a p h e d with a
column filled with activity III aluminum oxide (elution with c h l o r o f o r m ) . E v a p o r a t i o n of the f i r s t (yellow)
fraction gave 0.6 g (60%) of V w i t h mp 240-242 ~ (from butanol). Found: C 53.5; H 4.3; Br 19.7; N 7.1%.
C18HTBrN204. Calculated: C 53.4; H 4.2; Br 19.7; N 6.9%.
Evaporation of the second (brown) fraction gave 0.15 g (15%) of VI. Found: C 53.8; H 4.3; N 9.3%.
C20H10N304. Calculated: C 53.8; H 4.5; N 9.5%.

LITERATURE CITED
1. I. Ya. P o s t o v s k i i , K. I. P a s h k e v i c h , and G. B. A f a n a s ' e v a , Khim. G e t e r o t s i l d . Soedin., 464 (1974).
2. G. B. A f a n a s ' e v a , T. S. Viktorova, K. I. P a s h k e v i c h , and I. Ya. P o s t o v s k i i , Khtm. Geterosikl. Soedin.,
348 (1974).

753
MECHANISM OF THE PHOTOCHEMICAL ADDITION-
SUBSTITUTION REACTIONS OF SIX-MEMBERED
AZA AROMATIC COMPOUNDS IN H Y D R O G E N -
CONTAINING SOLVENTS (REVIEW)

A. C a s t e l l a n o , J. P. Catteau, UDC 541.14:547.821.831.833.

A. L a b l a c h e - C o m b i e r , B. P l a n c k a e r t , 861.853~176
a n d G. A l l a n

The c o r r e s p o n d i n g semiquinone radicals are formed via a one-photon reaction during the i r -
radiation of pyridine, quinoline, isoquinoline, pyrazine, pyrimidine, quinoxaline, and acridine
in neutral hydrogen-containing solvents such as ether, methanol, or ethanol. In all c a s e s , the
dissolved substance in the n r * - e x c i t e d (usually singlet) state splits out a hydrogen atom from
the solvent. Six-membered monoaza a r o m a t i c compounds on irradiation in methanol acidified
with HC1 are converted to the same semiquinone radicals as in neutral media, but via a two-
photon p r o c e s s consisting of electron t r a n s f e r from an alcohol molecule to the higher excited
triplet state of the protonated monoaza a r o m a t i c compound. The corresponding cation radi-
cals are f o r m e d by UV irradiation of pyrazine, quinoxaline, and phenazine in methanol acid-
idified with HClo Six-membered o - d i a z a compounds of the phthalazine and cinnoline type do
not r e a c t with ether in the absence of a ketone, which acts as a chemical s e n s i t i z e r . How-
ever, they r e a c t with methanol via a two-photon mechanism in which the f i r s t step is proton-
ation of the dissolved substance, which is followed by e l e c t r o n t r a n s f e r .

Many papers devoted to photochemical substitution reactions of aza a r o m a t i c compounds with h y d r o -

gen-containing solvents have been published in the last decade [11o P r i m a r y reaction products - photoaddi-
tion products that are usually unstable under the experimental conditions - were isolated in some cases [11.
The photochemical reaction with acridine has received the most study [1]. Acridan, diacridanyl, and
9-substituted 9, 10-dihydroacridan (scheme 1) a r e formed in different ratios as a function of the solvent when
acridine is i r r a d i a t e d in ether, alcohol, or h y d r o c a r b o n s .

Scheme 1

RH R
-b

H
H

We have studied photosubstitution in the case of the following reactions. 1) Photosubstitution of pyri-
dine by cyclohexane [2] yielded 2-and 4-cyclohexylpyridines and dicyclohexyl (scheme 2):

This paper was p r e s e n t e d by A. L a b l a c h e - C o m b i e r at the Euehem conference on the c h e m i s t r y of hetero-

cyclic compounds (Grande Motte, F r a n c e , April 24-27, 1973).

Scientific-Technical u n i v e r s i t y , Lille. T r a n s l a t e d from Khimiya Geterotsiklicheskikh Soedinenii, No.

7, pp. 867-884, July, 1974o

9 76 Plenum Pt~blishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the pttblisher for $15. 00.

755
 '~
= i

Fig. 1 Fig. 2 Fig. 3

Fig. 1. ESR s p e c t r a : a) 0.1 M solution of quinoline in methanol; b) the s a m e solution 20 rain a f t e r i r r a d i a -
tion; c) 0ol M solution of quinoline in ether; d) 0.4 M solution of quinoline in ether.
Fig. 2. Kinetics of the f o r m a t i o n of r a d i c a l s f r o m various aza a r o m a t i c compounds in 0.5 M methanol so-
lution at 113~ (the concentration units w e r e selected a r b i t r a r i l y ) : a) 0~ M quinoxaline; b) 0.4 M quinoline;
c) 0.6 M isoquinoline; d) 1.4 M pyrazine; e) > 1o5 M pyridine; f) > 1.5 M pyrimidine,
Fig. 3. ESR spectra: a) solution of quinoline in CH3OH; b) solution of quinoline in CD3OD; c) solution of
2-methylquinoline in CH3OH; d) solution of 2-methylquinoline in CD3OD~

2a

, ,

lb

Fig. 4 Fig. 5 Fig. 6

Fig. 4. ESR s p e c t r a : 1) 9-phenylacridine in CH3OH; 2) 9-phenylacridine in CD3OD; a) e x p e r i m e n t a l s p e c t r a ;
b) t h e o r e t i c a l s p e c t r a (0.4 M at 193~176
Fig. 5. ESR s p e c t r a : 1) 9-phenylacridine in CH3OH; b) 9-phenylacridine in CD3OD (0.2 M, l13~
Fig. 6. ESR s p e c t r a of r a d i c a l s f o r m e d during UV i r r a d i a t i o n of 0~ M solutions of 9--phenylacridine: a)
r a d i c a l X-H (CH~OH solvent); b) r a d i c a l X-D (CD3OD solvent) c) mixture of radicals X - H and X-D [CH3OH +
CD30D solvent (i:I)].

Scheme 2

hv
C6H12

lO1= 1o/=, 2"h,

2) The photochemical substitution of quinoline by cyclohexane and of quinoline and s o m e of its methyl-
substituted d e r i v a t i v e s by e t h e r [3] gave 2- and 4 - s u b s t i t u t e d compounds when methyl groups w e r e absent
in these positions. The photochemical reaction of 8-methylquinoline with neutral ethanol gave equal amounts

756
of the 2-(a Zayd roxyethyl) de rivative and 1,2,3,4- tetrahydroquinoline. Only aromatic compounds are formed
in the case of quinoline [41 (scheme 3):

Scheme 3 ~C2H5
(C2H5)2O
C4R 9 - s

2 O <'/o 10 ~

C2HsOH~.,-. [ ~ C
C
(H3
O
)C2H5 + ~ H CH(OH)CH3
1.5~ 20 ~

3) In the photochemical substitution of isoquinoline by ether [31, substitution o c c u r s only in the 1 pos-
ition (scheme 4), and 1-methylisoquinoline does not react:

Scheme4
(C2H5) z O

CH3CHOC2H5
5~

4) In the photochemical substitution of pyrazine by cyclohexane, the products are 1-cyclohexylpyrazine

and dicyclohexyl (scheme 5 ) :

Scheme 5
h'q % _p + Polymers
C6H12

8o/o 70~

5) In the photochemical substitution of quinoxaline by ether, the reaction products [61 are 2-(1-ethoxy-
ethyl)quinoxaline and 2-ethylquinoxaline (scheme 6):

Scheme6
(C2Hfi)20
C H (O C2H~,) C H3 C2H5

21 ~ 2~

The s t r u c t u r e s of the compounds obtained suggest a radical mechanism for the o c c u r r e n c e of these
photochemical reactions. F r o m the numerous studies devoted to the flash photolysis of acridine, it was
concluded that radicals of the I type are intermediates in these reactions [1]. However, 4 y e a r s ago, when
we began our studies, there had been p r a c t i c a l l y no ESR studies of these photochemical reactions nor spec-

t r a l studies of the one- and two-ring compounds, and the m e c h a n i s m s of the photochemical substitution-ad-
dition reactions were interpreted in analogy with the photochemical reactions of acridine. Our goal was to
confirm that radicals a r e the intermediate p a r t i c l e s in these reactions, to c h a r a c t e r i z e them, and to estab-
lish the m e c h a n i s m of their formation and, consequently, the mechanism of the photochemical substitution-
addition r e a c t i o n s .

STRUCTURE OF THE RADICALS FORMED IN NEUTRAL MEDIA

Electron-spin-resonance signals are observed when pyridine, quinoline, isoquinoline, acridine, pyra T
zinc, pyrimidine, quinoxaline and s o m e of t h e i r m e t a y l - s u b s t i t u t e d derivatives in ether, methanol, o r ethanol are

757
 T A B L E 1. E x p e r i m e n t a l S e c o n d a r y M o m e n t s of H a d i c a t s F o r m e d
d u r i n g UV I r r a d i a t i o n of A z a C o m p o u n d s in CHaOH and CD3OD at
l13~

Compound Solvent M 2 AM 2

Quinoline CHaOH 88 12
CD3OD 76
2 -Methylquinoline CHaOH 95 13
CD~OD 82
4-Methytqninoline CHaOH 127 13
CDaOD 114
2,4-Dimethylquinoline CHaOH 134 13
CDaOD 121
Isoquinoltne CHaOH 81 8
CDaOD 73
3 -Methylisoquinoline CHaOH 82 7
CD3OD 75

T A B L E 2. E x p e r i m e n t a l S e c o n d a r y M o m e n t s T A B L E 3. T h e o r e t i c a l and E x p e r i m e n t a l
(G 2) of R a d i c a l s F o r m e d d u r i n g UV I r r a d i a - S e c o n d a r y M o m e n t s of t h e R a d i c a l s F o r m e d
tion of Q u i n o l i n e and I s o q u i n o l i n e in V a r i o u s b y I r r a d i a t i o n of Some Azo C o m p o u n d s
S o l v e n t s at l 1 3 ~ * (CD3OD, 113~

Secondary moment
Solvent Quinoline Isoquinoline Compound
theoretical ] exptt.

Methanol 100 92 Quinoline 72 76

Ethanol 102 95 2 -Methylquinoline 75 82
Ether 112 --T 4-Methylquinoline 114 I14
2,4-Dimethylqulnoline 116 12[
Isoquinoline 68 73
#
3 - Methylisoquinoline 70 75
C a l c u l a t e d with a l l o w a n c e f o r the f a c t t h a t
g = 2.0023 at 113~
tThe secondary moment cannot be measured
a c c u r a t e l y b e c a u s e of the low i n t e n s i t y of the
signal.

T A B L E 4. S e c o n d a r y M o m e n t s of the R a d - i r r a d i a t e d , but only in g l a s s m a t r i c e s . T h e ESR s i g n a l s

i c a l F o r m e d d u r i n g UV I r r a d i a t i o n of 9- t h e r e f o r e do not h a v e h y p e r f i n e s p l i t t i n g and c a n n o t b e
P h e n y l a c r i d i n e (l13~ a n a l y z e d b y the u s u a l m e t h o d . L e t us c o n s i d e r the
rl i p r o b l e m of the i d e n t i f i c a t i o n of the s t r u c t u r e in the
Secondar moment c a s e of q u i n o l i n e . T h i s m e t h o d w a s a l s o u s e d f o r the
Solvent exptl, theoretical
r e s t of the i n v e s t i g a t e d c o m p o u n d s . T h e b r o a d b a n d
Methanol 42 of the ESR s p e c t r a o b t a i n e d at 77~ b y UV i r r a d i a t i o n
d4-Methanol 38 31 with a P h i l i p s Sp 500 l a m p of a v e r a g e p r e s s u r e of 0.1
Ethanol 41
Ether 45 M s o l u t i o n s of q u i n o l i n e in m e t h a n o l , e t h a n o l , o r e t h e r
is due to the s u p e r i m p o s i t i o n of the s i g n a l s of r a d i c a l s
of the d i s s o l v e d s u b s t a n c e and the s o l v e n t [7]~
W h e n m e t h a n o l is u s e d a s the s o l v e n t , a m e t h y l r a d i c a l is f o r m e d , w h e r e a s when e t h e r is u s e d a s the
s o l v e n t , a n e t h y l r a d i c a l i s f o r m e d ( F i g . 1, s p e c t r a a and C)o I f the i r r a d i a t e d s o l u t i o n is a l l o w e d to s t a n d
in the d a r k , the m e t h y l r a d i c a l s v a n i s h a f t e r 20 m i n , and o n l y the s i g n a l of the r a d i c a l of the d i s s o l v e d s u b -
s t a n c e , w h i c h d o e s not h a v e h y p e r f i n e s p l i t t i n g ( F i g . l b ) , r e m a i n s . T h e c o n c e n t r a t i o n of e t h y l r a d i c a l s d e -
c r e a s e s when a 0.4 M q u i n o l i n e s o l u t i o n r a t h e r than a 0.1 M s o l u t i o n is u s e d . T h i s is a g e n e r a l p r o p e r t y .
A l i m i t i n g c o n c e n t r a t i o n , a b o v e w h i c h one c a n n o t d e t e c t s o l v e n t r a d i c a l s , e x i s t s f o r e a c h of the i n v e s t i g a t e d
c o m p o u n d s . A s shown in F i g . 2, one o b s e r v e s a d e p e n d e n c e b e t w e e n the k i n e t i c s of f o r m a t i o n of r a d i c a l s of
the d i s s o l v e d s u b s t a n c e and t h i s l i m i t i n g c o n c e n t r a t i o n . W e e x p l a i n the a b s e n c e of s o l v e n t r a d i c a l s a t high
c o n c e n t r a t i o n s of the d i s s o l v e d s u b s t a n c e b y t h e i r r a p i d r e c o m b i n a t i o n . T h i s r e c o m b i n a t i o n p r o c e e d s m o r e
r e a d i l y when l a r g e a m o u n t s of r a d i c a l s a r e f o r m e d (for high c o n c e n t r a t i o n s of the d i s s o l v e d s u b s t a n c e ) than
when s m a l l a m o u n t s a r e f o r m e d (for low c o n c e n t r a t i o n s of the d i s s o l v e d s u b s t a n c e ) [6]. (We a s s u m e t h a t
the s o l v e n t r a d i c a l s a r e f o r m e d a s a r e s u l t of p h o t o c h e m i c a l r e a c t i o n of the d i s s o l v e d s u b s t a n c e . )

758
 The solvent radicals are not stable enough at II3~ to be detectable by means of ESR spectroscopy,
and only the signals of the dissolved substance remain~ We carried out all of our subsequent ESR experi-
ments at this temperature. From the structures of the products of the reactions of quinoline with ether [3]
and alcohol (scheme 3), two types of radicals - radical 17 or radicals Ilia, b [7] - can be formed as inter-
mediates in the investigated photosubstitution reactions. The formation of an anion radical is excluded:

R N H H

H 9 H 9 H

As shown in Fig. 3, the ESR signals obtained during UV i r r a d i a t i o n of quinoline or 2-methyl quinoline in
CH3OH do not coincide with the signals obtained when CD3OD is used as the solvent. This is evidence that
a portion of the solvent is included in the radical of the dissolved substance~
To confirm the s t r u c t u r e s of these radicals, we had to use the method of secondary moments. The
experimental s e c o n d a r y moment of the ESR signal, M2, is
c~
M2=~AH~G(H) dH,
0

where G(H) is the absorption curve, and H is the magnetic field,

It is shown in Table 1 that the difference between the s e c o n d a r y moments in CH3OH and CD~OD is al-
most constant in a single s e r i e s of quinoline and isoquinoline derivatives. The experimental s e c o n d a r y mo-
ments for quinoline and isoquinoline in methanol and ethanol are a l m o s t identical (broadening of the s p e c -
t r u m bee.ause of the effects of the m a t r i x and saturation of the signal [81 is observed in ether) (Table 2).
F r o m the data in these two tables, one can exclude radicals IIIa and IIIb (Tr or o'), inasmuch as in radical III
0r), the constant of the interaction of the hydrogen atoms with the sp3-hybridized carbon atom should have a
high value~ F o r IV [91 it is 61.6 G and, consequently, the experimental secondary moment should be higher
than the observed value. F u r t h e r m o r e , when R = CH2-OH, the methylene protons a r e found in the Y posi-
tion, and their interaction constant is less than 1 G [10]; in this case, the difference between the e x p e r i m e n -
tal s e c o n d a r y m o m e n t s in CH3OH and CD3OD should be considerably less than the observed 13 G2 (Table 1).
In radicals III (o'), the hyperfine interaction constant of the nitrogen atom should have a value on the
o r d e r of 50 G - it is 52.5 G [11] for the pyridine cation radical - and the ESR s p e c t r u m consequently should
be considerably b r o a d e r than the s p e c t r u m observed.
The data in Table 1 and 2 c o r r e s p o n d to radical IIo To confirm this hypothesis, we calculated the
theoretical s e c o n d a r y moment of this radical, in which the nitrogen atom is in the sp2-hybridized state.
According to [12], the s e c o n d a r y moment of radicals of the II type is
(y2
M~=M2H+M~,r ~ q-M2N+M2NH,

where M2H and M~g, r e s p e c t i v e l y , are the contributions of the hyperfine interaction of hydrogen and anisot-
ropy g, 0- i's the width of the band of a single c r y s t a l , and M2N and M2NH pertain to the hyperfine interaction
of the nitrogen atom and the hydrogen atom bonded to it.
In analogy with previous ESR studies, we have a s s u m e d that [7]

~/I2N _ D ~,'~--"0 ,
M2H=Eni174pi,
i

where Pi is the spin density on the carbon atom bonded to the hydrogen atom, n i is the number of hydrogen
atoms bonded to carbon atom i, M2N = 914pzN (PN is the spin density on nitrogen), ~2/4 = 6 G 2, and M2g =
4 G 2.

F o r the methyl derivatives we assumed that M2CHo = 495Pt2, where Pt is the total spin density a s s o -
ciated withthe methyl groupo The spin densities were calculated by the method in [13], during which we a s -
sumed that [71

759
 T A B L E 5. Spin D e n s i t i e s of S e m i q u i n o n e R a d i c a l s F o r m e d f r o m
Q u i n o l i n e s and I s o q u i n o l i n e s

9 ,. i 2-Methyl- 4-Methyl- 2,4-

Dimethyl- Isoquinoline 3-Methyliso-
Position [ Qumoune i quinoline quinoline quinoline :quinolifie
............ ,. . . . . . . . . . . .
1 ] 0,1566 0,1320 0,1345 0,1130 0,4042 0,4084
2 I 0,2109 0,1833 0,2135 0,1825 0,1007 0,1095
3 I --0,0250 0,0101 --0,0443 --0,0130 -0,0510 -0,0495
4 I 0,3634 0,3568 0,3726 0,3658 0,1507 0,1396
5 0,1837 0,1966 0,1996 0,2132 0.t178 0,1124
6 i -0,0065 --0,0151 --0,0119 --0,0209 0,1216 0,1247
7 [ 0,0791 0,0931 0,0880 0,1036 -0,0295 --0,0334
8 i 0,1037 0,1001 0,1115 0,1088 0.2476 0,2486

T A B L E 6. R a d i c a l s F o r m e d d u r i n g UV I r r a d i a t i o n of 9 - P h e n y l -
a c r i d i n e (233~ l i q u i d phase), and Q u i n o x a l i n e (l13~ glass)

Solvent 9-Phenylacridine Quinoxaline

CHaOH X-H VIII-H

CH3OD X-D VIII-D
CDaOD X-H
CD3OD X-D
CH~OH (50)-CHsOD (50) X-H (50)--X-D (50)
CH~OH (80)-CH3OD (20) X-H (80)-X-D (20)

,aN=,~C+0.9~C-C; ~C--N=~C--C; ~=1,2,

a

w h e r e a N is the c o u l o m b i c i n t e g r a l of the n i t r o g e n a t o m , o~C

i s the c o u l o m b i c i n t e g r a l of the c a r b o n a t o m , fi C-C is the r e s -
o n a n c e i n t e g r a l of t h e C - C bond, fiC-N is the r e s o n a n c e i n t e g -
r a l of t h e C - N b o n d , and ~ is the p a r a m e t e r of the i n t e r a t o m i c
G exchange integral.

To c a l c u l a t e the s p i n d e n s i t y a s s o c i a t e d with the m e t h y l

g r o u p we u s e d a h y p e r c o n j u g a t i o n m o d e l with an i n d u c t i v e e f -
f e c t [7].
The e x p e r i m e n t a l and t h e o r e t i c a l s e c o n d a r y m o m e n t s
f o r the II r a d i c a l o r i t s m e t h y l d e r i v a t i v e s c o i n c i d e s a t i s f a c t o r -
F i g . 7. ESR s p e c t r a o b t a i n e d b y i r r a -
i l y in the c a s e of q u i n o l i n e s , and the e x p e r i m e n t a l and t h e o r e t -
d i a t i o n of a 0.4 M s o l u t i o n of 4 - m e t h -
i c a l s e c o n d a r y m o m e n t s f o r the V r a d i c a l o r i t s 3 - m e t h y l d e -
y l q u i n o l i n e : a) in n e u t r a l CD3OD; b) in
r i v a t i v e c o i n c i d e s a t i s f a c t o r i l y in the c a s e of i s o q u i n o l i n e s
a 0~ M s o l u t i o n of DC1 in CD3OD; c)
( T a b l e 3)~
in twofold d i l u t e d (CD3OD) s o l u t i o n b .
On the b a s i s of s i m i l a r e x p e r i m e n t s and c a l c u l a t i o n s f o r
o t h e r c o m p o u n d s we a r r i v e d a t the c o n c l u s i o n t h a t on i r r a d i a -
tion in e t h e r , n e u t r a l m e t h a n o l , o r e t h a n o l , p y r i d i n e f o r m s r a d i c a l VI [2], p y r a z i n e f o r m s r a d i c a l VII [6],
q u i n o x a l i n e f o r m s r a d i c a l V I I I - H [6], p y r i m i d i n e f o r m s r a d i c a l IX [14], and a c r i d i n e f o r m s r a d i c a l I [15], a s
p o s t u l a t e d b y f l a s h - . p h o t o l y s i s e x p e r i m e n t s [1]. In a l l of t h e s e r a d i c a l s the n i t r o g e n a t o m b o n d e d to the h y -
d r o g e n a t o m is sp2--hybridizedo

C6H 5

H ,ep
I H I
H H A A
V__ ~ Vl._~ Vl,--i-HA=H ~ ~-a A=H
VII---~- D A= D ~- D A= D

In the c a s e of 9 - - p h e n y l a c r i d i n e [15], we w e r e a b l e to v e r i f y the v a l i d i t y of m a n y of the p a r a m e t e r s u s e d in

the c a l c u l a t i o n s , i n a s m u c h a s t h i s c o m p o u n d f o r m s r a d i c a l s that a r e s t a b l e in the l i q u i d p h a s e on i r r a d i a -
tion in e t h e r , m e t h a n o l , o r e t h a n o l . T h e e x p e r i m e n t a l s p e c t r a of CH3OH and CD3OD s o l u t i o n s and the c a l c u -
l a t e d s p e c t r a c o i n c i d e ( F i g . 4). T h e r a d i c a l o b s e r v e d in CH3OH is u n d o u b t e d l y X-H, w h i l e t h a t o b s e r v e d in

760
CD3OD is undoubtedly X-D. When the e x p e r i m e n t is c a r r i e d out in a glass m a t r i x at 113~ (the conditions
under which the s p e c t r a of all of the compounds that we studied were recorded), the hyperfine splitting of
the signals of the 9-phenylacridinyl radicals X-D and X-H vanishes (Fig~ 5), and they take on the f o r m of
the signals c h a r a c t e r i s t i c for the r a d i c a l s of other compounds. The experimental s e c o n d a r y moment and
the theoretical moment of the X-D radical calculated with the same p a r a m e t e r s as those used for quinoline
and other investigated compounds a r e in good a g r e e m e n t [151 (Table 4).
F r o m the results of these e x p e r i m e n t s we concluded that the p a r a m e t e r s used for the calculation of
the theoretical s e c o n d a r y moments of the radicals formed from quinoline and other compounds were a c c u -
r a t e l y chosen and, consequently, that the s t r u c t u r e s postulated by us a r e c o r r e c t .

MECHANISM OF THE PHOTOCHEMICAL REACTIONS IN NEUTRAL MEDIA

Nonpolar Aprotic Hydrogen-Containing
Solvents
It is well known that the m e c h a n i s m of photochemical substitution of s i x - m e m b e r e d aza a r o m a t i c c o m -
pounds by ether implies splitting out of a hydrogen of the solvent by the n r * - e x c i t e d state of the dissolved
substance [1, 16]. All of these reactions a r e one-photon reactions [81, and their m e c h a n i s m is s i m i l a r to
the m e c h a n i s m of the photochemical reaction of quinoline, which is depicted in scheme 7. A dependence
exists between the s t r u c t u r e of the isolated products

Scheme 7
ether + CH3--~H-- OC2H5
H
-}- ~ Oc2H5

[~H \CH(OC2Hs)CH3 H
Jr- ~ Oc2H5

~\CH(Or CH3
(schemes 1-6) and the spin density calculated for semiquinoline radicals I, II, and IV-X: as shown in Table
5, recombination between the semiquinone radical and the solvent radical for quinoline and isoquinoline
occurs at the carbon atoms with the highest spin density (C-2 and C-4 of quinoline, and C-1 of isoquinoline)
[7]~ Similar dependences were obtained for pyridine [2], pyrazine [5], pyrimidine [14], quinoxaline [6], acri-
dine, and 9-phenylacridine [15]o
In the case of 4-methylquinoline [3] and quinoxaline [6], primarily 2-(1-ethoxyethyl) derivatives are
obtained in addition to 2-ethyl-substituted compounds (their ratio in the first case is 5 and 40%)~ It is pos-
sible that they are formed not by recombination of the semiquinone and ethyl radicals, which is observed
at 77~ by ESR spectroscopy, but rather are the photochemical products of a Norrish reaction of the II type,
which takes place with the primary products [3, 4] (scheme 8). If recombination were to occur, ethyl-sub-
stituted compounds would be obtained in all cases and one should expect the formation of 4-substituted de-
rivatives.
CH3 Scheme 8 CH3
/ell 3
v "N- -c-H ~'~N/.~c'--H
H. /0 I H
.f6
I

CH
I
CH
I
CH3 CH3

--CH3CHO
[~~HCHCH3 C2H5

761
Methanol and Ethanol
In p o l a r solvents the n~* transitions are shifted to lower wavelengths, while the ~r* transitions are
shifted to higher wavelengths [17], and formation of semiquinone radicals via the same mechanism as in
ether or cyclohexane is therefore not apparent. The radicals formed during irradiation of 9-phenylacridine
in the liquid phase at 233~ and during irradiation of quinoxaline in a glass matrix at l13~ are shown in
Table 6. These compounds were selected because radicals VIII-H and VIII-D, X-H and X-D, or mixtures
of them are readily distinguished in them (Fig. 6). In methanol or in deuteromethanol the hydroxyl hydrogen
of the alcohol is linked with the nitrogen of the semiquinone radical [18]. Rapid exchange o c c u r s between
this hydrogen and the hydroxyl hydrogen of methanol: radical X-D is formed during irradiation of 0.2 M
solutions of 9~phenylacridine in a mixture of CH3CH2OCH2CH3 and CH3OD even when the methanol c o n c e n t r a -
tion is 1%. Similar results were obtained for a 0.4 M solution of quinoxaline at l13~ When the methanol
concentration in ether is 1%, it is absolutely obvious that the first step is photochemical reactions with
ether 181.
This sort of rapid exchange, even in a glass matrix at l13~ seems strange a p r i o r i . Kellog has
reported that 1-hydro~-deutero-3,5-diearbethoxypyridine is formed in the irradiation of XI in CH3CH2OD
(scheme 9)~ RadicalXIH is possibly an intermediate in this reaction and d~)es not exchange the nitrogen-
bonded hydrogen for deuterium f r o m the hydroxyl group of the solvent [19, 20].

Scheme 9
D H H

C H ~j -N': "CH.~ . o CH~ "N" "CH, C H 3" N "CH 3

H ~ ~ H ~ H

Because of the rapid exchange, one cannot establish which of the hydrogen atoms of methanol is ini-
tially bonded to the nitrogen atom of the semiquinone radical. Consequently, one cannot determine whether
the mechanism of the photochemical reactions of s i x - m e m b e r e d a r o m a t i c compounds with methanol is the
same as that in the reaction with ether or another solvent. This p r o b l e m will be solved in the future.

MECHANISM OF PHOTOCHEMICAL REACTIONS IN HCI-ACIDIFIED ALCOHOL

Six-Membered Monoaza Aromatic Compounds.
Structures of the Radicals Formed in
Acidified Methanol
It is considerably more difficult to determine the structures of radicals formed during UV irradiation
of six-membered monoaza aromatic compounds in acidified CH3OH than the structures of radicals formed
in neutral solution. The signal for pyridine is small as compared with the noise level. Nevertheless, when
the pyridine and HCI concentration is 1.5 M (in CH3OH), one can conclude that the ESR spectrum obtained
at II3~ does not correspond to radical XIV or to the cyclohexadienyl radical formed by the addition of a
hydrogen atom to the ring-carbon atom - in this case the signal would be greater than the observed signal
[8, 21]o The spectra obtained in neutral CH3OH and during irradiation of dFpyridine in CD3OD and DCI re-
call the spectra obtained by irradiation of ds-pyridine in CD3OD [2].

H H
x~__.2v

The ESR s p e c t r a observed during irradiation of a 0.4 M solution of quinoline in 0.4 M acidified
CH3OH at 113~ are b r o a d bands devoid of hyperfine splitting, but they a r e n a r r o w e r than those observed
in the s p e c t r a of solutions in neutral methanol. This cannot be the signal of a radical of the XV type that
was proposed by Stermitz and c o - w o r k e r s to explain the m e c h a n i s m of the photochemical reaction of quin-
oline with HCl-acidified ethanol (scheme 10) (other reactions of this type have also been described I1, 4, 8,
211). The signal of this radical

762
 H
SchemeI 0 ~
CH3CH2OH
[ ~ + H CL- H / \CL-
H H X.._~. . H H
+ ClinCH--OH

[ H

l - H20
~CH(OM)CH3

\eL-

CHCH3

CHCH3 / \CL ~
H H ~ H H
l
(~C2H 5 -{- ~ H5
7~ ~10~

would be b r o a d e r than that of r a d i c a l lI and, c o n s e q u e n t l y , that of the o b s e r v e d s i g n a l . The ESR s p e c t r u m

o b s e r v e d d u r i n g UV i r r a d i a t i o n of 0.4 M solutions of 4 - m e t h y l q u i n o l i n e in a 0.4 M solution of DC1 and
CD3OD d i f f e r s f r o m the s p e c t r u m of a solution in n e u t r a l CD3OD, but the r e c o r d e d s p e c t r u m is v e r y c l o s e
to the s p e c t r u m of a solution in n e u t r a l CD3OD (Fig, 7) upon twofold dilution of the solution with CD3OD [8,
21]. S i m i l a r l y , the s p e c t r a of quinoline, i s o q u i n o l i n e , and 9 - p h e n y l a c r i d i n e in H C l - a c i d i f i e d methanol at
low acid and solution c o n c e n t r a t i o n s coincide with the s p e c t r a in n e u t r a l m e t h a n o l . This p r o v e s that iden-
t i c a l s e m i q u i n o n e r a d i c a l s a r e f o r m e d during i r r a d i a t i o n of s i x - m e m b e r e d a r o m a t i c compounds in n e u t r a l
and a c i d i f i e d methanol~ The n a r r o w i n g of the s i g n a l at high c o n c e n t r a t i o n s is a s s o c i a t e d with e l e c t r o n -
exchange p r o c e s s e s , as shown in s c h e m e 11 for auinoline, r a t h e r than with exchange of the h y d r o g e n atom
a t t a c h e d to the n i t r o g e n atom with the s o l v e n t . If this s o r t of exchange o c c u r s s u f f i c i e n t l y r a p i d l y , this hy-
d r o g e n a t o m will not p a i r up with the e l e c t r o n . In the c a s e of the d e u t e r i u m atom, the d i s a p p e a r a n c e of
this p a i r i n g will have a v e r y s l i g h t effect on the f o r m of the s p e c t r u m ; this does not a c t u a l l y o c c u r (Fig. 7)
[8, 211o

Scheme II

H H H H

We have p r e v i o u s l y shown that this s o r t of e l e c t r o n exchang e o c c u r s in the c a s e of anion r a d i c a l s [23] and

c a t i o n r a d i c a l s [24], for e x a m p l e , c a t i o n r a d i c a l XVI [25].

CH300C- - ~ 1 - - CH2CH2CH 2 - - ~ I ~ ' ~ COOCH3

XVI

Mechanism of P h o t o c h e m i c a l Reactions
in HC1-Aeidified Alcohol
The UV i r r a d i a t i o n of s i x - m e m b e r e d m o n o a z a a r o m a t i c compounds in n e u t r a l and H C l - a c i d i f i e d m e t h -
anol l e a d s to i d e n t i c a l r a d i c a l s , but t h e i r f o r m a t i o n in the f i r s t c a s e is the r e s u l t of a one-photon r e a c t i o n
[2, 6-8, 14, 15], w h e r e a s in the second c a s e it is the r e s u l t of a two-photon r e a c t i o n [8, 211. N e i t h e r s e m i -
quinone r a d i c a l s n o r the t r i p l e t of the d i s s o l v e d s u b s t a n c e s that a r e o b s e r v e d when HC1 is used a r e o b s e r v e d
when h y d r i o d i c acid is u s e d . The p r e s e n c e of HI c o n s i d e r a b l y r e d u c e s the l i f e t i m e of the t r i p l e t but h a s
l i t t l e effect on the Quantum y i e l d [26]. This c o n f i r m s the a s s u m p t i o n that in H C l - a c i d i f i e d methanol s e m i -
quinone r a d i c a l s a r e f o r m e d only as a r e s u l t of two-photon p r o c e s s e s and not as a r e s u l t of s i m u l t a n e o u s l y
o c c u r r i n g one- and two--photon p r o c e s s e s . C o n s i d e r i n g the p h o t o c h e m i c a l r e a c t i v i t i e s of a z a compounds -
only the n~r* s t a t e can r e a d i l y s p l i t out h y d r o g e n [1, 16, 27] - and the fact that semiquinone r a d i c a l s a r e

763
formed in HCl-acldified methanol, it can be concluded that the mechanism of the photochemical reaction of
s i x - m e m b e r e d monoaza aromatic compounds with HCl-acidified ethanol differs from the mechanism pro-
posed by Stermitz in the case of quinoline [221 (scheme 10). The reaction might have occurred through en-
ergy transfer from the molecules of the dissolved substance (XVII) to the solvent m o l e c u l e s with subsequent
dissociation of the excited state of the solvent molecule and addition of the resulting H" radicalto the unpro-
tonated molecule, as shown in s c h e m e 12 in the ease of the reaction with quinoline~ Similar p r o c e s s e s in-
volving energy transfer and ethanol dissociation were noted in the irradiation of ethanol solutions of naph-
thalene [28]. The same mechanism was proposed to explain the photochemical reactions of p y r a z o l o p y r i m i -
dines with HCl-acidified methanol [29]~

Scheme 12

CL-H

(CHBOH) + CH3OH

Q
"k EL- H
CH20H ~- H XVH

In our case, a mechanism similar to that indicated in scheme 12 is unlikely, inasmuch as v e r y small
amounts of the unprotonated aza aromatic compounds remain in the s y s t e m , and radicals of the XVIII and
XIX type were never detected. We will subsequently present a rigorous proof that this sort of energy-trans-
fer p r o c e s s is not realized in the case of phthalazine.

~x v Lj
L.___
H20 H H~

Xj_~X

The mechanism presented in s c h e m e 13 for the photochemical reaction of quinoline with HCl-acidified
methanol is the most probable m e c h a n i s m . Electron transfer is realized in this case between methanol
and the higher excited triplet state of the protonated form of quinoline. This sort of electron transfer was
also previously reported (see review [301)o It takes place, for example, between the s~nglet excited state of
paraquat dichloride and methanol [31] (scheme 14),

XVT______+~ CH3OH ~ CH ~ + CH3OH 9

Electron transfer does not occur from the chloride ion, inasmuch as chlorine radicals were not de-
tected, and chlorination products were not isolated. This sort of electron-transfer process occurs only
from the iodide ion [30, 321.

Scheme 14 pQ-~
C H3-~-~N~N+-- C H3
2CL
2CL-
PQ* "~ hv (P(~4-"I-~SHCH2
OH HOOCH 3
2CL-- 2CL-- ]
j/~CH3OH
4-
PQ 4- CH3O~ 4- CH3OH 2

764
Mechanism of Photochemical Reactions

in Neutral Alcohol
On the b a s i s o f t h e f a c t s t h a t rapid exchange o c c u r s between semiquinone radicals and the hydroxyl hy-
drogen of alcohol, that the reaction of monoaza a r o m a t i c compounds in neutral methanol is a one-photon r e -
action whereas it is a two-photon reaction in HCl-acidified methanol, and that C1- does not t r a n s f e r an e l e c -
tron in HC1 media, it can be concluded that the reaction does not o c c u r with e l e c t r o n t r a n s f e r f r o m CH30-
or from CHaOH to the excited protonated aza a r o m a t i c compound. It is more likely that the photochemical
reactions in methanol or ethanol p r o c e e d in the same way as in ether, i.e., as a result of splitting out of a
hydrogen atom of the methyl group by the nr* -excited state of the dissolved substance in the case of meth-
anol and of a hydrogen atom of the methylene group in the case of ethanol [17]. This sort of equilibrium
has already been proven in the case of acridine [1, 16, 331.
Six-Membered p-Diaza Aromatic Compounds
P y r a z i n e , quinoxaline, and phenazine are converted to cation radicals XX-H, XXI-H, and XXII-H, r e -
spectively, on i r r a d i a t i o n in HCl-acidified methanol at 293~ (liquid phase). If the solvent is CD3OD acidi-
fied with DC1, cation radicals XX-D, XXI-D, and XXII-D are f o r m e d [18]. The signals of these radicals have
good hyperfine splittings, and their ESR s p e c t r a have a l r e a d y been studied by Barton and Fraenkel [34].

A A A
i [ I

I f [
A A A

X XX-H A=H XXI-H A=H I.___~I

/,X - H A=H
xx-O A: 0 xxI-o A=D XXII-D A: O

Scheme 15
., N ~"
CH3OH ~ HCL .- or .
. (o'l CH3OH

H H
. . ,KI
'4- f ". N ~"
H

Nj_
H'

TO explain the formation of these radicals we have proposed a mechanism (scheme 15) that is s i m i l a r
to the m e c h a n i s m presented in scheme 13. It consists in electron t r a n s f e r from methanol molecules to
photoexeited diprotonated molecules of the diaza a r o m a t i c compounds. Inasmuch as this reaction occurs
v e r y rapidly, it was not possible to conclude whether it is a one-photon or two-photon reaction. However,
it is logical to suppose that electron t r a n s f e r to diprotonated excited compounds will proceed m o r e readily
than to monoprotonated compounds~ This m e c h a n i s m is more likely than the m e c h a n i s m proposed by Bailey
and c o - w o r k e r s for the photochemical reaction of phenazine (P) in strongly acidified methanol [35]:

hv

pH+-+IpH**,
IpH+* + H+~.<.~_ipH2++*,
IPH=+ +* + CHaOH~ PH2 + CHaOH +*,
PH2+ PH+--~ (PH) 2+ H +,
(PH) m-~-2PH,
PH. +H+-+P,H2 +' (XXI-H).

T r a n s f e r of two electrons of the methanol molecule is a s s u m e d in the third step of this m e c h a n i s m , and
this is v e r y unlikely. Bailey and c o - w o r k e r s were unable to c h a r a c t e r i z e the PH~ radical by e i t h e r ESR
s p e c t r o s c o p y or flash photolysis~

765
 We feel that the p h o t o c h e m i c a l r e a c t i o n s of s i x - m e m b e r e d d i a z a a r o m a t i c compounds with n e u t r a l
methanol a r e one--photon p r o c e s s e s [6] that take p l a c e due to s p l i t t i n g out of one of the h y d r o g e n a t o m s of
methanol by the n r * - e x c i t e d state of the d i s s o l v e d s u b s t a n c e . T h e s e r e a c t i o n s p r o c e e d in the s a m e way as
the r e a c t i o n s of s i x - m e m b e r e d m o n o a z a a r o m a t i c compounds.

PHOTOCHEMICAL ACTIVITY OF SIX-MEMBERED o-DIAZA AROMATIC

COMPOUNDS IN HYDROGEN-CONTAINING SOLVENTS [27]

The b e h a v i o r of one-ring and t w o - r i n g s i x - m e m b e r e d o - d i a z a a r o m a t i c compounds d i f f e r s f r o m the

b e h a v i o r of o t h e r d i a z a a r o m a t i c s u b s t a n c e s .
N e i t h e r p y r i d a z i n e , p h t h a l a z i n e , cinnoline, n o r any of t h e i r m e t h y l - , p h e n y l - , and d i p h e n y l - s u b s t i t u t e d
d e r i v a t i v e s r e a c t with e t h e r : the f o r m a t i o n of p r o d u c t s was not o b s e r v e d , and ESR s i g n a l s w e r e not d e t e c t e d .
In the c a s e of p h t h a l a z i n e , XXIII is f o r m e d when a ketone is added to a p h o t o l y z e d solution, and an ESR s i g -
nal a p p e a r s . The ketone does not act as a t r i p l e t - t r i p l e t e n e r g y c a r r i e r , inasmuch as the quantum yield for
p h t h a l a z i n e is one [36], but r a t h e r as a " c h e m i c a l s e n s i t i z e r " I3710 P r e c i s e l y this method was used to ob-
tain d i a d d u c t s of e t h e r s with quinoxaline [6]. The r e a c t i o n m e c h a n i s m in the c a s e of p h t h a l a z i n e is d e p i c t e d
in s c h e m e 16~ The p h t h a l a z i n y l r a d i c a l (XXIV) and its homologs w e r e c h a r a c t e r i z e d by m e a n s of the meth-
od of s e c o n d a r y m o m e n t s .
When methanol is u s e d as the solvent, semiquinone r a d i c a l s a r e f o r m e d as a r e s u l t of a t w o - p h o t o n
p r o c e s s even in the a b s e n c e of ketone.

The fact that an ESR s i g n a l is not d e t e c t e d when e t h e r is used as the solvent p r o v e s that the two-pho-
ton r e a c t i o n with methanol is not a c h a r g e - t r a n s f e r r e a c t i o n with subsequent s p l i t t i n g of methanol into

Scheme 16 CH3
CsH5COCH3h--~ (C6H5COCH3)T+ CH3CH2OC2H5~ C6H~'-C--OH -.p CH~.-~H--OC2H5

C6H5~Co
I
-I- ,, ~ y
N-..H
--F C6HsCOCH3
OH
XX
I._.~V
l c.~.-oc2, s

C2HsOCHCH3 C2HsOCHCH3
XXlII

"CH2OH and H" r a d i c a l s in analogy with s c h e m e 12. Thus, in c o n t r a s t to naphthalene [28], e n e r g y t r a n s f e r

f r o m the e x c i t e d t r i p l e t s t a t e to the solvent is i m p o s s i b l e f o r unprotonated o - d i a z a a r o m a t i c compounds.
The f i r s t step in the p h o t o c h e m i c a l r e a c t i o n with methanol should be p r o t o n a t i o n of the o - d i a z a c o m -
pound with subsequent e l e c t r o n t r a n s f e r f r o m methanol o r f r o m CH30- to the t r i p l e t e x c i t e d state of the
m o n o p r o t o n a t e d a r o m a t i c compound. This m e c h a n i s m in the c a s e of p h t h a l a z i n e is p r e s e n t e d

CH3OH

T~
...N +" ]
+ CH3OH

+ CH3OH
- ~ + ~.,OH

766
in s c h e m e 17. A triplet state can be detected by ESR s p e c t r o s c o p y only in methanol solution and not in e t h e r
solution~ This p r o v e s that in this case a triplet compound different from phthalazine is observed and is in
a g r e e m e n t with the p r o p o s e d m e c h a n i s m . The fact that the photochemical reaction is not a one-photon r e -
action in the p r e s e n c e of CH30- is yet another p r o o f that s i x - m e m b e r e d monoaza compounds do not r e a c t
with methanol with e l e c t r o n t r a n s f e r f r o m the CH3OH and CH30- molecules to a molecule of the protonated
monoaza compound.

CONCLUSIONS
As a result of this research, it has been established that if the aza aromatic compound has an n~r*
state, it is precisely this state that is active, and a one-photon reaction occurs. For quinoline and quinoxa-
line this is undoubtedly a singlet state, inasmuch as the r~r* * state is a triplet state [I, 3, 38]. In the case
of isoquinoline, this is also possibly a singlet state, inasmuch as the S I and T I states are 7rr*-excited
states~ The difference in energies between the S1(~r* ) and S2(nTr* ) levels is less than between the T2(n~* )
and Tl(~t~r* ) states [1]. For acridine it has been provefi by numerous studies that the photochemical reac-
tion proceeds at least partially with the Sl(nr*) excited state [I, 16]. Inasmuch as the spectroscopic state
of pyridine is unknown, the nature of the n~r* active excited state cannot be proved.
If an nr* state is not formed during excitation, the photochemical reaction should proceed via a differ-
ent path~ This explains the unusual behavior of phthalazine and other o - d i a z a a r o m a t i c compounds [27], in-
a s m u c h as it is known that the singlet states of phthalazine have a v e r y b r i e f lifetime [39] and that a v~r*
triplet is formed quantitatively during excitation [40]. The reaction p r o c e e d s via a two-photon m e c h a n i s m
concluding with protonation, if it is not a l r e a d y realized by an acid of the HC1 type, and electron t r a n s f e r
f r o m the oxygen-containing so lvent to the higher excited triplet state of the dis solved substance.
This r e s e a r c h also opens up the possibility of the use of ESR s p e c t r o s c o p y in the study of s e v e r a l
aspects of photochemical reactions in those c a s e s in which flash photolysis and e m i s s i o n s p e c t r o s c o p y do
not give information.

The experimental conditions have a l r e a d y been described by us in [2, 3, 5, 8, 15],

LITERATURE CITED
io A. Lablache-Combier, in: Elements de Photochimie Avane~e, edited by P~ Courtot, Hermann, Paris
(1972), p. 289.
2o S. Caplain, Ao Castellano, J. P. Catteau, and A. Lablache-Combier, Tetrahedron, 27, 3541 (1971)o
3. A. Castellano and A. Lablache-Combier, Tetrahedron, 27, 2303 (1971)o
4. F. Ro Stermitz, C. C, Wei, and C. M~ O'Donnel, J. Amer. Chem. Soc., 92, 2745 (1970)o
5. B~ Planckaert, Th~se de 3-eme Cycle, Lille (1972).
6~ A. Castellano, J. Po Catteau, A. Lablache-Combier, B. Planckaert, and G. Allan, Tetrahedron, 28,
3511 (1972).
7~ G. Allan, Ao Castellano, J. P. Catteau, and A. Lablaehe-Combier, Tetrahedron, 27, 4687 (1971}.
8. Jo Po Catteau, Th~se de Doctorat des Sciences, Universit~ des Sciences et Techniques de Lille (1973).
9~ H.J. Bower, J. A. MacRae, and M. C~ R. Symons, Jo Chem, Soc., A, 1918 (1968).
i0. D~ H. Levy and R. J~ Myers, J. Chemo Phys., 43, 3063 (1965}.
11. R.E. Cramer and R. S. Drago, Jo Amer~ Chem. SOCo, 90, 4790 (1968),
12. Go Vincow and P~ M. Johnson, J. Chem. Phys., 39, 1143 (1963}.
13. Ao Do McLachlan, Mol. Phys., 3, 233 (1960)o
14. A~ Castellano, J~ P. Catteau, A~ Lablache-Combier, and G. Allan, Unpublished Data.
15o A. Castellano, J~ P. Catteau, A. Lablache-Combier, and Go Allan, Can. J. Chem. (in press).
16. D.G. Whitten and Y. J. Lee, J~ Amer. Chem~ Soc., 93, 961 (1971)o
17. No J, Turro, Molecular Photochemistry, W. A. Benjamin Inco, New York (1965), po 59~
18~ A. Castellano, J. P. Catteau, and A. Lablache-Combier, Chem. Commun~ 1207 (1972)o
19. Ro M. Kellog, T. J. Van Bergen~ and H. Wynberg, Tetrahedron Lett,, 5211 (1969)~
20. To Jo Van Bergen and R. Mo Kellog, J. Amero Chemo Soc., 94, 8451 (1972).
21o A. Castellano, J. P. Catteau, and Ao Lablaehe-Combier (in press).
22. F.R. Stermitz, C. Co Wei, and W. H. Huang, Chem. Commun., 482 (1968)o
23. G.L. Malinovski and W. H. Bruning, J. Amer. Chem. Soc~ 89, 5063 (1967}.
24. S.P. Sorensen and W. H. Bruning, J. Amer. Chem. Soc., 94, 6352 (1972).
25. Mo Itoh, J. Amer. Chem~ Soc~ 93, 4750 (1971).

767
26~ So Siegel and H. S~ Judeikis, J. Chemo Phys., 4_~2,3060 (1965)o
27~ A. Castellano, J. P. Catteau, A. Lablache-Combier, and B. Planckaert, Tetrahedron Lett. (in press).
28 S. Siegel and K. Eisenthal, Jo Chem. Phys., 42, 2494 (1965)o
29 M. Ochiai, E. Mizata, Yo Asaki, and K, Morita, Tetrahedron, 2..44,5861 (1968)o
30 A. Lablache-Combier, Bull. Soco Chim. France, 4791 (1972).
31 A. S. Hopkins, A. Ledwith, and M. F. Stam, Chem. Commun., 494 (1970).
32 E. M. Kosower and L. Lindquist, Tetrahedron Lett~ 4481 (1965).
33 V. Zanker and G. Prell, Bo Bunsenges, Phys. Chem,, 73, 791 (1969)o
34 B~ L. Barton and G~ K. Fraenkel, Jo Chemo Phys., 4_11,1455 (1964).
35 D. N. Bailey, D. K. Roe, and D. M. Hercules, J. Amero Chemo Soc., 90. 6291 (1968).
36 V. L. Alvarez and S. G. Hadley, J. Phys. Chem., 7__6.6, 3937 (1972).
37 P. S. Engel and B. N. Monroe, in: Advances in Photochemistry, edited by J. N~ Pitts, Jr., G. S.
Hammond, and W. A. Noyes, Jr., VOlo 8, Wiley-Interscience (1971), p. 265.
38. J. G. Calvert and J. N. Pitts (editors), Photochemistry, Wiley (1966), p. 297.
39. Y. H. Li and E. C. Lira, J. Chem. Phys., 5_66,1004 (1972).
40. E. C. Lim and J. Stanislaus, J. Chem. Phys~ 5__33,2096 (1970)o

768
REACTION OF 2-ACYLOXIRANES WITH CYCLIC
KETONES

I . G. T i s h c h e n k o , O. N. Bubel', UDC 547.729

a n d Go Z . S t a s e v i c h

Acyloxiranes r e a c t with cyclopentanone and cyclohexanone in the p r e s e n c e of catalytic

amounts of boron trifluoride etherate to give the c o r r e s p o n d i n g 2-acyl-l,4-dioxaspiro[4,41-
nonanes and 2-acyl-l,4-dioxaspiro[4,5ldecanes. The c o r r e s p o n d i n g cis-2,3-dimethyl-2 acetyl-
1,4-dioxaspiroalkanes are f o r m e d f r o m t r a n s - 2 , 3 - d i m e t h y l - 2 - a c e t y l o x i r a n e .

Up until now the reaction of a c y l o x i r a n e s with ketones has not been investigated. We have studied the
reaction of 2-acyloxiranes (Ia-e) with cyclopentanone and cyclohexanone in the p r e s e n c e of catalytic amounts
of boron trifluoride ethe rate; the reaction gives the c o r r e s p o n d i n g 2- acyl- 1,4-dioxaspiro[4,41nonanes (II- V)
and 2-acyl-l,4-dioxaspiro[4,51decanes (VI-X).

R~,, .R I

~"
"O'
, " c :l "~' . o = ~ ;H~)n o~. j o !,
O
0 [(clt2)!
i a-e ,(/~/o/, ll-X

li,, ,,,,CH a "

C H 3~" l i"~c/CH3
Oil OH II
O
Xlll
Ia, II, VI RZ=R2=R3=H; R4=CH3; lb, III, VII RI=R2=H; R3=R4=CHs; IC, IV, Vlll
Rt=R2=R4=CH3; R3=H; ld, V, IX RZ=R3=R4=CH3; R~=H; Ie, X RI=R2=R3=H;
R4=Ph; I1--V n=0; VI--X n= 1
Aeyloxirane Ib r e a c t s readily with cyclopentanone, and acyloxiranes Ia, c r e a c t readily with cyclo-
pentanone and cyclohexanone even at room t e m p e r a t u r e , while heating to 80~ is required in the remaining
c a s e s . The s t r u c t u r e s of II-X were established by hydrolysis in acetic acid to the c o r r e s p o n d i n g ketoglycols
and cyclic ketones, which were identified from t h e i r p h y s i c o c h e m i c a l constants and the melting points of
their 2,4-dinitrophenylhydrazones; the s t r u c t u r e s were also confirmed by their IR and PMR speetrao
Absorption bands at 1090, 1115, 1150, and 1200 cm -1, which are c h a r a c t e r i s t i c for theCOCOC fragment of
the 1,3-dioxolane ring [11 are observed in the IR s p e c t r a of II-X~ The stretching vibrations of the earbonyl
group in II-IX appear at 1710-1720 cm -1, while the stretching vibrations of the carbonyl group in X appear
at 1690 cm-~.
Ring expansion of 2-'acyloxiranes I a - e p r o c e e d s via a known mechanism [2, 31 with inversion of the
configuration of one of the r i n g - c a r b o n atoms; this is confirmed oy the eis s t r u c t u r e of spirans V and IX.
The configurations of spirans V and IX were established by c o m p a r i s o n of their PMR spectra with the spectra
of authentic trans-2,3-dimethyl-2-acetyl-l,4- dioxaspiro[4,4]nonane (XI) and its cis i s o m e r . The PMR s p e c t r a
of the cis i s o m e r and of s p i r a n V are identical and differ from the PMR s p e c t r u m of XI (Fig. 1) with r e -
spect to the position of the signals of the CH 3 groups.

Vo I. Lenin B e l o r u s s i a n State University, Minsk. T r a n s l a t e d from Khimiya Geterotsiklicheskikh

Soedinenii, No. 7, pp. 885-888, July, 1974. Original a r t i c l e submitted D e c e m b e r 7, 1972; revision submitted
J a n u a r y 10, 1974o

9 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

769
 TABLE I. Ketoglycols Obtained by Hydrolysis of II-X
J
Ketoglycol I Bp, ~ (ram) nD~
. . . . . . . . . . . . . . . . . . . . . . . . . !. . . . . . . . . . . .
3 , 4 - D i h y d r o x y - 2 - b u t a n o n e [7] 60--68 (0,2) 1,4505
3 - M e t h v l - 3 , 4 - d i h y d r o x y - 2 - b u t a n o n e [61 101--102 (1t) i !,4490
Erythro-3 -Methyl-3,4-dihydroxy - 2 - p e n t anone 102--103 (10) ! 1,4520
4-Mettayl-3,4-dihydroxy-2-pentanone [5] 100--102 (12) i 1,4524
1-phenyl-2,3-dihydroxy-l-propanone* mp 78--79~ Ii --

Found: C 64~ H 6~ CgH1003. Calculated: C 65~ H 6o1%o

t r a n s - S p i r a n XI was synthesized f r o m cyclopentanone and t h r e o - 3 - m e t h y l -

3,4-dihydroxy-2-pentanone (XII), which was obtained by hydroxylation of t r a n s -
3-methyl-3-penten-2-one with potassium permanganate.

CH3xx /CH3
H/C=C.,.c..CH3
K h~nO 4
CH3,,
",__ ,
H""I ]'~,c.-Ci%
..CH3 ~=0
.
" tl o. 6.~
O

XII

CH3, 9 /
CH3

OvO

XI

Cis i s o m e r V was s i m i l a r l y obtained from eyclopentanone and e r y t h r o - 3 -

'2 ~ ~,'ppm methyl-3,4-dihydroxy-2-pentanone (XIII). The latter was synthesized by acid
h y d r o l y s i s of oxirane Id~
Fig. 1. PMR sp.eetra
of cis- and trans-2,3- The p r a c t i c a l l y complete coincidence of the chemical shifts of the signals
dimethyl-3-acetyl-l~- of the 2- and 3-CH 3 groups in the PMR spectra of V and IX makes it possible to
4-dioxaspiro[4,4lno- conclude that spiran IX also has the cis configuration.
nanes (V, X-I): I) cis
isomer (V); 2) trans EXPERIMENTAL
i s o m e r (XI)~
The IR spectra of thin layers of the eompounds were recorded with a UR-
20 spectrometer. The PMR spectra of CCI 4 solutions were recorded with a
Varian HA-100-15D s p e c t r o m e t e r with tetramethylsilane as the internal standard. T h i n - l a y e r c h r o m a t o g r a -
phy (TLC) on a loose l a y e r of activity II aluminum oxide [elution with e t h e r - p e t r o l e u m ether (1:1); the
c h r o m a t o g r a m s were developed in iodine vapors] was used to evaluate the individuality of the compounds
obtained. The starting acyloxiranes (Ia-e) were obtained by the methods described in [4-6].
2-Acetyl-l,4-dioxaspiro[4,4lnonane (II)o A solution of 10 g (0.12 mole) of oxirane Ia in 25 g (0.3 mole)
of cyclopentanone was added dropwise at 5 ~ to a mixture of 25 g (0~ mole) of cyclopentanone and 0~ ml of
boron trifluoride etherate~ Ten minutes after the addition of the oxirane solution the reaction mixture was
neutralized with methanolic potassium hydroxide and washed with water. The organic l a y e r was dried with
potassium carbonate and fractionated with a Vigreux column at reduced p r e s s u r e to give 8.2 g (43%) of II
with bp 109-110 ~ (12 mm), nD 2~ 1.4571, and d420 1.0942. Found: C 63.4; H 8.3%; MRD 42.48. C9H1403. Cal-
culated: C 63.5; H 8.2%; MR D 42.66. PMR spectrum* : 5 2.16 (s, CH3) , 3.82-4.30 (m, 2~ 1.71-1.86
ppm [(CH2)41.
3,3-Dimethyl-2--acetyl-l,4-dioxaspiro[4,4lnonane (IV). A solution of 10 g (0.09 mole) of oxirane Ic in
15 g (0.18 mole) of cyclopentanone was added dropwise at 20 ~ to a mixture of 20 g (0.24 mole) of cyclopen-
tanone and 1 ml of boron trifluoride etherate. After 1.5 h, the reaction mixture was worked up as in the
preceding experiment to give 11.2 g (55%) of IV with bp 97-98 ~ (12 mm), nD 2~ 1.4490, and d42~ 1.0301.
Found: C 66.7; H 9.2%; MR D 51.61. CilHi803o Calculated: C 66.7; H 9.1%; MRD 51.89. PMR spectrum: 6

The following abbreviations are used here and subsequently: s is singlet, d is doublet, q is quartet, and
m is multiplet.

770
1.04 (s, CH3), 1.36 (s, CH3) , 2.19 (s, COCH3), 3.85 (s, 2-H, and 1.68-1.89 ppm [(CH2)4].
2-Acetyl-l,4--dioxaspiro[4,5]deeane (VI). A solution of 10 g (0.12 mole) of oxirane Ia in 30 g (0.3 mole)
of cyclohexanone was added dropwise to a mixture of 50 g (0.5 mole) of eyclohexanone and 1.5 ml of boron
trifluoride etherate, after which the t e m p e r a t u r e of the mixture was raised to 35 ~ It was then cooled to
20 ~ and allowed to stand for 12 h. Workup gave 19.3 g (90%7 of VI with bp 114-115 ~ (11 ram), nD 2~ 1.4660,
and d42~ 1.0798. Found: C 65.5; H 8.8%; MR D 47.26. C~0H1603. Calculated: C 65.2; H 8.7%; MRD 47.26.
PMR s p e c t r u m : 5 2.23 (s, COCH3), 3.80--4.28 (m, 2,3-H3), and 1.25-1.75 ppm [(CH2)~].
3,3-Dimethyl-2--acetyl-l,4-dioxaspiro[4,5]decane (VIII). The p r o c e d u r e used to obtain VI was used to
p r e p a r e this compound from 2 mole of cyclohexanone and 0.4 mole of oxirane Ic in the p r e s e n c e of 1.5 ml
of boron trifluoride etherate. The yield of product with bp 108-109 ~ (12 mm), nD 2~ 1.4540, and d420 1.0260
was28%. Found: C67o9;H9.3%;MRD56.04. C12H2003. Calculated: C 67.9; H 9.4%; MR D 56.49. PMR spec-
t r u m : 5 1.04 (s, CH3), 1.36 (s, CH3), 2.20 (s, COCH3) , 3.97 (s, 2-II), and 1.48-1.56 ppm [(Ci'12)5].
2-Methyl-2--acetyl-l,4--dioxaspiro[4,5]decane (VII). A solution of 10 g (0.1 mole) of oxirane Ib in 35 g
(0.35 mole) of cyclohexanone was added with s t i r r i n g to a mixture of 15 g (0.15 mole) of cyclohexanone and
1 ml of b o r o n trifluoride etherate heated to 60 ~ a f t e r which the mixture was heated to 80 ~ for 30 rain.
Workup of the mixture gave 9.6 g (48%) of VII with bp 109-110 ~ (11 mm), nD 2~ 1.4584, and d42~ 1.0474.
Found: C 66.8; H 9.2%; MR D 51.68. C11H1803. Calculated: C 66~ H 9.1%; MRD 51.88. PMR spectrum: 5
1.32 (s, CH3), 2.19 (s, COCH3), 3.60 (d, 3-H, J = 8.5 Hz), 4.15 (d, 3-H, J = 8.5 Hz), and 1.30-180 ppm I(CH2)5].
c i s - 2 , 3 - D i m e t h y l - 2 - a c e t y l - l , 4 - d i o x a s p i r o [ 4 , 5 ] d e c a n e (IX). The p r o c e d u r e used to synthesize VII was
used to p r e p a r e this compound. Workup gave 61% of a product with bp 116-117 ~ (12 mm), nD 2~ 1.4620, and
d42~ 1.0383. Found: C 68.0; H 9.5%; MR D 56.21. C12H2003. Calculated: C 67.9; H 9.4%; MRD 56.49. PMR
s p e c t r u m : 5 1.09 (d, 3-CH3, J = 6.5 Hz), 1.28 (s, 2-CH3) , 2.16 (s, COCH3), 3.99 (q, 3-H, J = 6.5 Hz), and 1.30-
1.80 ppm [(CH2)5].
2 - B e n z o y l - l , 4 - d i o x a s p i r o I 4 , 5 ] d e c a n e (X). The p r o c e d u r e used to synthesize VII was used to obtain
this compound f r o m oxirane Ie and cyclohexanone by heating at 80 ~ for 3 h. Workup gave 69% of a product
with bp 126-127 ~ (0.4 mm), nD 2~ 1.5362, and d42~ 1.1201. Found: C 73.4; H 7.4%; MR D 68.52. C15H1803. Cal-
culated: C 73.1; H 7.4%; MR D 67.77.
2-Methyl-2-acetyl-l,4-dioxaspiro[4,4lnonane (III). The p r o c e d u r e used to synthesize IV was used to
obtain this compound from 0.5 mole of cyclopentanone and 0.1 mole of oxirane Ib. The mixture was heated
at 20 ~ for 2 h. Workup gave 59% of a compound with bp 97-98 ~ (12 mm), nD 2~ 1.4490, and d42~ 1.0527. Found:
C 65~ H 8.8%; MRD 46.99. Ci0HI603. Calculated: C 65.2; H 8.7%; MR D 47.26. PMR s p e c t r u m : 5 1.33 (s,
CH3), 2.19 (s, COCH3), 3.59 (d, 3-H, J = 8.5 Hz), 4.16 (d, 3-H, J = 8.5 Hz), and 1.30-1.80 ppm [(CH2)41o
cis-2,3-Dimethyl-2--acetyl-l,4-dioxaspiro[4,4]nonane (V). The p r o c e d u r e used to synthesize III was
used to obtain this compound. Workup gave 57% of a product with bp 102-103 ~ (11 mm), nD 2~ 1.4522, and
d42~ 1.0375. Found: C 66.4; H 9.2%; MR D 51.58. CIlHi803o Calculated: C 66.7; H 9.1%; MRD 51.89. PMR
spectrum: 5 1.12 (d, 3-CH3, J =6.4 Hz), 1.28 (s, 2-CH3), 2.16 (s, COCH3), 3.82 (q, 3-H, J = 6.4 Hz), and
1.72-2o05 ppm I (CHH2)4].
Hydrolysis of II-X. Acetic acid was added to a mixture of 0.03 mole of the spiran and 2.5 ml of water
until the spiran had dissolved completely, a f t e r which the solution was refluxed for 3--5 h and fractionated
with a Vigreux column at reduced p r e s s u r e . The p h y s i c o c h e m i c a l constants of the ketoglycols obtained a r e
presented in Table 1. The 2,4-dinitrophenylhydrazones of the isolated cyclopentanone and cyclohexanone
melted at 145 and 161 ~ (from methanol), respectively. No melting-point d e p r e s s i o n was observed for mix-
tures of these h y d r a z o n e s with genuine samples.
threo-3-Methyl-3,4-dihydroxy-2-pentanone {XII). A solution of 43 g (0.27 mole) of p o t a s s i u m p e r m a n -
ganate in 1500 ml of acetone and 80 ml of w a t e r was added dropwise with s t i r r i n g to a cooled (to - t 0 ~ mix-
ture of 20 g (0.2 mole) of t r a n s - 3 - m e t h y l - 3 - p e n t e n - 2 - o n e [41 in 40 ml of acetone, after which the mixture
was filtered, and the acetone was removed f r o m the filtrate at reduced p r e s s u r e . The residue was satu-
r a t e d w i t h p o t a s s i u m carbonate and extracted repeatedly with ether. The ether e x t r a c t s were dried with
p o t a s s i u m carbonate, the ether was removed, and the residue was distilled at reduced p r e s s u r e to give 24%
of the ketodiol with bp 78-80 ~ (1 mm), nD2~ 1.4515, and d420 1.0901. Found: C 54.7; H 9.0%; MR D 32.69.
C6H1203. Calculated: C 54.5; H 9.1%; MR D 32.97.
E r y t h r o - 3 - M e t h y l - 3 , 4 - d i h y d r o x y - 2 - p e n t a n o n e (XIII).A mixture of 29 g (0.25 mole) of oxirane Id and
200 ml of 5% p e r c h l o r i c acid was s t i r r e d at 60 ~ for 5 h. The mixture was then cooled, neutralized with

771
potassium carbonate, and vacuum evaporated to 50 ml. This material was extracted with ether, and the ex-
t r a c t s were dried with potassium carbonate. The ether was removed, and the residue was distilled at r e -
duced p r e s s u r e to give 31% of the ketodiol with bp 77-79 ~ (1 mm), nD 2~ 1.4520, and d42~ 1.0912. Found: C
54.6; H 9.0%; MR D 32.65. C6H1203o Calculated: C 54.5; H 9,1%; MR D 32.97.
t r a n s - 2 , 3 - D i m e t h y l - 2 - a c e t y l - l , 4 - d i o x a s p i r o [ 4 , 4 ] n o n a n e (XI). A 1-ml sample of boron trifluoride eth-
c r a t e was added to a mixture of 13.2 g (0.1 mole) of ketodiol XII, 63 g (0.75 mole) of cyelopentanone, and 2
g of anhydrous copper sulfate, after which the mixture was allowed to stand at room t e m p e r a t u r e for 3 days.
It was then filtered, and the filtrate was neutralized with methanolie potassium hydroxide, diluted with ether,
washed with water, and dried with sodium sulfate~ The solvent was removed, and the residue was distilled
at reduced p r e s s u r e . The product was dissolved in e t h e r - h e x a n e (1:3), and the solution was filtered through
a l a y e r of aluminum oxide to give XI with bp 62-63 ~ (0.3 mm), nD 2~ 1.4515, and d42~ 1.0316 in 30-35% yield~
Found: C 66.6; H 8~ MR D 51o79o C/iH/803o Calculated: C 66~ H 9o1%; MR D 51.89. PMR spectrum: 5
1.12 (s, 2--CH3), 1.20 (d, 3-CH3, J = 6~ Hz), 2o18 (s, COCH3), 3~ (q, 3-H, J = 6~ Hz), and 1.60-1o95 ppm
[(C H2)4]o
The cis i s o m e r , with bp 103-104 ~ (12 mm) and nD 2~ 1.4520, which was identical to spiran V, was s i m -
ilarly obtained from ketodiol XIII.

LITERATURE CITED
Io Eo Do Bergmann and So Pinchas, Rec. Tray. Chimo, 7._.!I,161 (1952).
2~ Vo No Yandovskii and To Io Temnikova, Zho Organ. Khim,, 4~ 1758 (1968).
3. Bo N. Blackett, Jo M. Coxon, M. P~ Hartshorn, A. Io Lewis, G. R. Little, and Go Io Wright, Tetrahedron,
2_66,1311 (1970)o
4. H.O. House and Ro Ro, J. Amero Chemo Soc., 80, 2428 (1958).
5. I. No Nazarov and A. A. Akhrem, Zho Obshch. Khimo, 20, 2189 (1950).
6. I.G. Tishchenko, in: Liquid-Phase Oxidation of Unsaturated Organic Compounds [in Russian], Minsk
(1961), po 73.
7. H.O. Lo Fisher, Eo Baer, H, Pollock, and Ho Nidecker, Helv. Chim. Acta, 20, 1213 (1937).

772
RESEARCH ON UNSATURATED LACTONES
XXIX.* SYNTHESIS OF 1,2,3-PHOSPHODIAZOLE DERIVATIVES
FROM SUBSTITUTED BUTENOLIDS

Ao Ao Avetisyan, A. N. Dzhandzhapanyan, UDC 547.722.3'724'778.07

G. G. Tokmadzhyan, and M. G. Dangyan

The phenylhydrazones of 2-acetyl-2-buten-4-olides react with phosphorus trichloride to give

1,2,3-phosphodiazole derivatives. The reaction proceeds similarly if the double bond in the
butenolide is hydrogenated. However, if there is a benzoyl group rather than an acetyl group
present, only N-dichlorophospho derivatives of the phenylhydrazones are formed.

We have studied the reaction of phenylhydrazones of 2-acetyl-2-buten-4-olides with phosphorus trichlo-

ride. 1,2,3-phosphodiazole d e r i v a t i v e s , which a r e c r y s t a l l i n e substances with unpleasant odors, are ob-
tained when the components (1:1.5) are heated in the p r e s e n c e of triethylamineo A s i m i l a r reaction o c c u r s
in the methyl ketone s e r i e s [2].

C.3-. /C--C"3 C H~-~U_.~__~ - - ~"2 H2 CH.- /C--CHo

R\I--J~--NH PCL~ " R'~I
~
L N PCI Pd/CaC03 P.~..~.
/f I"
.~ N PC[
,./'-o-" ~o ~ 0 , ~ ,.l'.o-~o'y" ~.,'-o-',o
C6H5 CGH5
I-III IV-VI Vlll

tPCI
I, IV, VII, VIII R=R'=CH~; ce~b.k___~-ce3
II, V R=CHs, R'=C2H~; R,,,,,J [ N--NH
III, VI RR'=(CH2)s R,/'~O/'~O ~1-16

The characteristic frequencies of the absorption of the carbonyl group of a five-membered lactone
ring (1755-1761 cm4), of the C = N group (1658-1666 cm-i), and of the phenyl ring (1580-1600 cm -I) are
found in the IR spectra of the compounds obtained.
Under similar conditions, the reaction of 2-acetyl-3,4,4-trimethylbutane-4-olide phenylhydrazone
(VII) with phosphorus trichloride gives a 1,2,3--phosphodiazole (VIII) that contains a saturated lactone ring
in the 5 position. This same compound (VIII) is formed by hydrogenation of the phosphodiazole over P d /
CaCO~ in ethanol.
2-Benzoyl-2--buten--4--olides (IX, X) that do not have CH groups in the c~ position relative to the h y d r a -
zone grouping undergo substitution of the hydrogen of the NH group of the phenylhydrazone to give dichloro-
phospho derivatives (XI, XII).
CH3\ ./~]--% H5 CH 3 C--C.H-
ii ~ o

R, 7-xo ..-'~o cl6us -Hcl Rff~.o/'~.o I "

C6H5
IX, X XI, XII

IX, XI R=R'=CH3; X, XI1 RR'=(CH2) 5

* See [1] for communication XXVIII.

E r e v a n State University. T r a n s l a t e d from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 889-
891, July, 1974. Original a r t i c l e submitted July 4, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

773
 The dichlorophospho derivatives of 2-benzoyl-2-buten-4-olide phenylhydrazones also a r e crystalline
substances with a d i s a g r e e a b l e odor.

EXPERIMENTAL
The IR s p e c t r a of m i n e r a l - o i l suspensions of the compounds were recorded with an IKS-14 s p e c t r o m -
eter. The 2 - a c e t y l - 3 , 4 , 4 - t r [ a l k y l - 2 - b u t e n - 4 - o l i d e phenythydrazones (I-III) were obtained by the method in
[31.
1- Chloro-2-phenyl-4-(3,4,4-trimethyl-2-buten-4- , l i d - 2-yl)- 5H- 1,2,3-phosphodiazole (IV), A mixture
of 3.9 (0.015 mole) of 2 - a c e t y l - 3 , 4 , 4 - t r i m e t h y l - 2 - b u t e n - 4 - o l i d e (1), 2.32 g (0.023 mole) of triethylamine,
and 16 ml of methylene chloride was added dropwise to a cooled mixture of 3.2 g (0.023 mole) of PC13
and 8 ml of methylene chloride, after which the mixture was heated at 35 ~ for 4 h and allowed to
stand at r o o m t e m p e r a t u r e until hydrogen chloride evolution ceased. The precipitate - triethylamine
hydrochloride - was r e m o v e d by filtration, the solvent was r e m o v e d f r o m the filtrate, and the r e s i -
due was r e c r y s t a l l i z e d to give 4.2 g (84%) and IV with mp 252 ~ (from dioxane). Found: C 55.5; H
5.2; C1 11.1; N 8.3%. C15H16C1N202P. Calculated: C 55.8; I-I 5.0; C1 11.0; N 8.7%.
1- Chloro-2-phenyl~-(3,4-dimethyl-4- ethyl- 2-buten- 4-olid-2- yl)- 5H- 1,2,3-phosphodiazole (V) o Simi-
larly, 4.1 g (0.015 mole) of phenylhydrazone II gave 5 g (50%) of V with mp 253-254 ~ (from dioxane). Found:
C 57.1; H 5.3; C1 10o9; N 8o1%. CI~HisC1N202P. Calculated: C 57.1; H 5.4; C1 10.6; N 8~
1- Chloro- 2-phenyl~-(3-methyl-4,4-pentamethylene- 2-buten- 4-.lid- 2- yl)- 5 H-l, 2,3-phosphodiazole (VI).
Similarly, 3.6 g (49~ of VI, with mp 260 ~ (from dioxane), was obtained by reaction of 6 g (0.025 mole) of
phenylhydrazone III and 3~ g (00038 mole) of triethylamine in 30 ml of methylene chloride with a mixture
of 5.23 g (00038 mole) of PC13 and 10 ml of methylene chloride. Found: C 59.4, H 5.9; C1 9.5; N 8.0%.
CisH20C1N202Po Calculated: C 59~ H 5.5; C1 9~ N 7.7%0
2-Acetyl-3,4,4-trimethylbutan-4-olide Phenylhydrazone (VII). A mixture of 13.6 g (0.08 mole) of 2-
acetyl-3,4,4-trimethylbutan-4-olide and 8.61 g (0008 mole) of phenylhydrazine was allowed to stand at room
t e m p e r a t u r e for 24 h. The precipitated c r y s t a l s were r e c r y s t a l l i z e d to give 13.8 g (68%) of VII with mp
102-104 ~ (from alcohol). Found: N 10o9%o CIsH20N2020 Calculated: N 10.8%.
1- C hlo ro- 2-phenyl~-(3,4,4-trimethylbutan- 4- . l i d - 2 - y l ) - 5 H- 1,2,3--phosphodiazole (VIII). A) As in the
m~hod described above, 2 g (40%) of VIII, with mp 244 ~ (from chloroform-hexane), was obtained from 4~ g
(0~ mole) of PC13 in 8 ml of CH2CI2, 3.9 g (0.015 mole) of phenylhydrazone VII, and 3.13 g (0.03 mole) of
triethylamine in 16 ml of CH2CI 2. Found: Cl 10.7%. CIsHIsCIN202P. Calculated: Cl 10.9%.
B) A solution of 0.5 g (0.0016 mole) of phosphodiazole IV in 20 ml of absolute ethanol was hydrogenated
over Pd/CaCO~ (5% Pd). The alcohol was removed by distillation at the end of the hydrogenation to give
0.4 g (80%) of VIII with mp 244-246 ~ (from ehloroform-hexane). No melting-point depression was observed
for a mixture of this product with the product described above. IR spectrum: 1765 em -i (laetone ring C ~ O).,
1658-1666 cm 4 (C ~ N), and 1603 cm -i (phenyl group),
2-Benzoyl-3,4,4-trialkyl-2-buten-4-olidePhenylhydrazones (IX, X)o These compounds were ob-
tained by the method in [I]o
Dichlorophospho Derivative (XI) of 2-Benzoyl-3,4,4-trimethyl-2-buten-4-olldeo A 2.5-g (0.008 mole)
sample of phenylhydrazone IX and 1.57 g (0.015 mole) of triethylamine in I0 ml of CH2CI 2 were heated with
2.36 g (0.016 mole) of PC13 at 40 '~ for 12 h. Workup gave 0.8 g (24.3%) of XI with mp 215-216 ~ (from toluene).
Found: C 57.3; H 5.2; C1 16.3; N 7.0%. C20HIgCI2N202P. Calculafed: C 57~ H 4.5; C1 16.9; N 6~
Diehlorophospho Derivative (XII) of 2-Benzoyl-3-methyl-4,4-pentamethylene-2-buten-4-olideo As in
the preceding experiment, 0.2 g (16.6%) of XII with mp 225 ~ (from toluene) was obtained f r o m a mixture of
1 g (2.7 mmole) of phenylhydrazone X, 0.6 g (6 mmole) of triethylamine, 5 ml of CH2C12, and 0.87 g (5.9
mmole) of PC13. Found: C1 16o0; N 6~176 C23H23C12N202P. Calculated: C1 15.4; N 6o1%o

LITERATURE CITED

Io A. A. Avetisyan, A. N. Dzhandzhapanyan, G. V. Simonyan, and M. T. Dangyan, Arm. Khim. Zh. (in

press).
2. N. I. Shvetsov-Shilovskii, N. P. Ignatova, and N. N. Mel'nikov, Khim. Geterotsikl. Soedin., 753 (1967).
3. A. A. Avetisyan, Ts. A. Mangasaryan, M. T. Dangyan, and S. G. Matsoyan, Zh. Organ. Ix'him., 7, 964
(1971)o

774
REACTIONS OF 2-AND 4-METHYLPYRYLIUM
SALTS WITH ETHYL ORTHOFORMATE

A . Lo V a s s e r m a n , V. V. Mezheritskii, UDC 547.813:814'831.2:668.8

a n d "Go N . D o r o f e e n k o

Under m i l d conditions 2- and 4 - m e t h y l p y r y l i u m s a l t s r e a c t with ethyl o r t h o f o r m a t e to give

t h e i r / 3 - e t h o x y v i n y l d e r i v a t i v e s . S y m m e t r i c a l and u n s y m m e t r i c a l cyanine dyes w e r e synthe-
sized by heating the l a t t e r with 2- and 4 - m e t h y l p y r y l i u m salts or N-methylquinaldinium p e r -
c h l o r a t e . The p y r y l o c y a n i n e s r e a c t with p e r c h l o r i c acid to give b i s p y r y l i u m salts, and they
a r e c o n v e r t e d to the c o r r e s p o n d i n g pyridine b a s e s by the action of a m m o n i u m a c e t a t e .

We recently began a systematic study of the reaction of pyrylium salts containing active methyl groups
with ortho esters [I]o
In the present study in the reactions of 2- and 4-methylpyrylium and benzopyrylium salts with ethyl
orthoformate we selected conditions that make it possible to obtain cyanine dyes or to stop the reaction at
the step involving the formation of 2- and 4-fl-ethoxyvinylpyrylium salts~ The transformations that occur
in this case can be represented by the following scheme:

6"~c-cR~
.. .--- o")c=cr~
.-, + .+

2. HC(OC2Hs)3 H ~ HC(OC2Hs)2 + C2HsOH

It

+ - 0 /C=CI~CH--OC.H~

III

,.. +

IV

The reaction with 4 - m e t h y l b e n z o p y r y l i u m s a l t s p r o c e e d s at 30-35~ 2 - M e t h y l b e n z o p y r y l i u m salts

f o r m 2-/~-ethoxyvinyl d e r i v a t i v e s at higher t e m p e r a t u r e s (80-90~ More s e v e r e conditions (100-110 ~ and
longer reaction t i m e s a r e r e q u i r e d for the r e a c t i o n of ethyl o r t h o f o r m a t e with monocyclic [1] 2- and 4-
m e t h y l p y r y l i u m s a l t s . 4 - B e n z y l p y r y l i u m salts occupy an i n t e r m e d i a t e position with r e s p e c t to the a c t i v -
ity of the methyl group in r e a c t i o n s with ethyl o r t h o f o r m a t e :

~"3 'I ~"2c6M~ ~H3

This o r d e r of r e a c t i v i t i e s is also c o n f i r m e d by the r e a c t i o n s of these m e t h y l p y r y l i u m salts with their fl-

ethoxyvinyl d e r i v a t i v e s .
The individuality of the compounds obtained and the c o m p l e t e n e s s of the reaction w e r e monitored f r o m
the d i s a p p e a r a n c e of the signal of the protons of the methyl group of the s t a r t i n g p y r y l i u m salt and also by

Rostov State U n i v e r s i t y . S c i e n t i f i c - R e s e a r c h Institute of P h y s i c a l and Organic C h e m i s t r y , Rostov-

on-Don. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 7, pp. 892-896, July, 1974. Original
a r t i c l e submitted July 10, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. 1I. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the pubOsher. A copy o f this article is available from the pub#sher for $15.00.

775
c h r o m a t o g r a p h y . Signals of the protons of the vinyl group and of the methyl and methylene groups of the
ethyl group are p r e s e n t in the PMR s p e c t r a of the P - e t h o x y v i n y l p y r y l i u m salts.
An absorption band at 1620-1635 em -t, which is c h a r a c t e r i s t i c for the stretching vibrations of the py-
rylium cation, and a band at 1250-1240 em 4, which is related to the stretching vibrations of an ether group,
were isolated in the IR s p e c t r a of the /3-ethoxyvinylpyrylium salts.
A new absorption at 500-400 nm as c o m p a r e d with the starting methylpyrylium salts appears in the
UV s p e c t r a of the synthesized compounds.
The p r e s e n c e of a vinyl group is also confirmed by bromination, which is easily realized by the addi-
tion of an equimolecular amount of b r o m i n e to a w a r m solution of the ~ - e t h o x y v i n y l p y r y l i u m salt in dioxane,
The yields of the dibromo derivatives were 70-40%~

clot ClO7

Cyanine dyes are formed by heating the 2- and 4-methylbenzopyrylium salts or 4-benzyl-2,6-diphenyl-
pyrylium salt with their P-ethoxyvinyl derivatives; any pair of these components undergoes this reaction.
The formulas of the synthesized pyrylocyanines are presented below.
OH

ltO~O//"'C H= CH--C H~k"-O"J'L"--~"O H HO CH=CH~--CH=

clo~- cm~-
V a, b VIII a, b .6H5

C6Hs--C=CH --R
I
~] ClO~ f ~ c6"5,---dc6"5
C6H5~'-0~ / \ C6H5 .. I
Vl a, b ClO~ IX ~C6H:

R C R ~ N / / ~ " C N=C~--CH=(L._~O
6 H4~ c l O
- ClO4" CIH3: -C6Hs
VII a, b x
--C--C6H5 --HC
il tl

V-Villa R=lt; vb, VIII b R=COOC21t5; Vl a R b ~ ; Vlb R = ~ ' J L

VII b R= OH CBH5 \C6H$ C6H5~ "O f ~ "OH

In the absence of bases, 2-methyl-4,6-diphenylpyrylium and 4-methyl-2,6-diphenylpyrylium perchlorates do

not form cyanines even on refluxing in acetic anhydride. Cyanine dyes cannot be obtained by heating these
salts with /3-ethoxyvinylflavylium perehlorate or with their p-ethoxyvinyl derivatives or by condensation of
the latter with 4-methylbenzopyrylium salts.
The pyryloeyanines react with perehloric acid to give bispyrylium salts. This sort of formation of
bispyrylium salts was previously described [2, 3] for monomethylidynepyrylocyanineo

IV
2filO~

Trimethylidynecyanines f r o m monocyclie p y r y l i u m salts a r e capable of exchanging a h e t e r o c y c l i c

oxygen for nitrogen~ Thus when cyanine VI is refluxed with ammonium acetate in acetic acid it is c o n v e r t -
ed to pyridinocyanine XI~

C~Hs--C~CH HC--C6H 5
CH~COONH4 ~ C ~
~H
VI - Cld3COO-------
~ C6H5 oH5 C 5 C6H5

XI

776
 TABLE i. Pyrylocyanines

Found, % Calc., %
O Empirical zi'5" o ,-d
forfiaula IR spectrum, cm- E ~ "
O C H CI C , H C1
, ] i

Va 282 C21H15C108 58,6 3,8 8,0 585 34!82[ 3500, 1640, 1620, r 87,5
745140,00
1590, 1100
Vb
Via
VIb
215
2953
30O
C2vHz3C1Ot2
C49H35C108 7 4, ii
--
6,3,:56,3,'4,016,2i
] -- __ __
3500, t725, 1700,
1620, 1590, 1100
1640, 1610, 1590,
1095
C41H29C107 173,7 4,5 5,4 73,5 4,31 5,3 3550, 1640, 1625,
700i53,84[100
75O ]56,00 6O
63O 14,55 6O
Dec. 1600, 1100
VIIa 2848 C33H~CIOs __ _ I --I 1650, 1620, 1600, 745 42,22 100
1100
Vllb 278 CzaH23C108 67,4 3,7 3550, 1645, 1625, 75O 53,84 73
1590, 1100
Villa 293 C37HIgCIOa 64,1 3,5 3500, 1640, 1615, 645 0,28 72
1590, 1100

vTi 285
300
Dec.
242
C3oH23CIO1o 62,4 4,0 6,3 62,21 4,016,I 3500, 1725, 1625,
C3~H25C107
1590, 1100
71,7 4,5 5,3 70,8 4,2 5,9 3500, 1650, 1620,
1590, I100
C33H2~NC106* 66,4 4,0 7,0 66,7 4,3 7,0/ 3500, 1645
650 2,31 86
1645 5,24 52
600 7,49 96

Found: N 3.0%. Calculated: N 2.8%.

The structure of XI was confirmed by chemical methods. It was shown that the condensation of 4-benzyl-2,
6-diphenyl-N-benzylpyridinium perchlorate with ethyl orthoformate and subsequent treatment w ith 70%
perchloric acid gives a compound identical to diperehlorate XII obtained from dipyridine XI and benzyl
chloride with subsequent treatment with 70% perchloric acid. The transformations presented above indi-
cate that both oxygen atoms in the pyrylocyanine undergo replacement by nitrogen.

~ H2%H5 C6H5--C~Clt -C--C6Hs

HC(O C._,Hs)3
C~H5J@\C6H 5 (CH3CO)20 C6H5{ / @ C 6 H 5 C6H5
I~C6H5
CFO~ CH~C6H5 CIO~- CHzCGH5 CH2CGHs ~6H~ ~6H5
.~ C---CH

I, C6HsCHoC[,toluene
XI
2. HCIO4 C~ H~/~"N~'c6 H 5 C Coli~
CH2C6H3 _ CH2C~H5
2CIO4
X|I

A bathochromic shift of 40-70 nm as compared with the fi-ethoxyvinylpyrylium salts is observed in

the UV spectra of the synthesized eyanines; an increase in the bathochromic effect is observed on passing
from monocyclic to condensed pyrylium salts.

EXPERIMENTAL
The IR spectra of mineral-oil suspensions of the compounds were recorded with a UR-20 spectrom-
eter. The UV spectra of acetic acid solutions were recorded with a Speeord UV-vis spectrophotometer.
The PMR spectra of trifluoroacetic acid solutions were recorded with an RYa-2305 spectrometer with
tetramethylsilane as the internal standard. Chromatography was carried out on Silufol in nitromethane-
chloroform-acetic acid (i 9 1 : 1).
Starting Methylpyrylium Salts. A Grignard reagent obtained from 3.7 ml of methyl iodide and 1.5 g of
magnesium in 45 ml of absolute ether was added to a suspension of 0.016 mole of Y-unsubstituted pyrylium
perchlorate in 60 ml of dry ether, and the resulting solution was stirred at room temperature for 20 min.
It was then cooled with ice and decomposed with ammonium chloride solution. The ether layer was sepa-
rated, washedwith I N sodium carbonate solution and water (three times), and dried with anhydrous sodium
sulfate. Acetic anhydride (I0 ml) and 1.6 ml of 70% perchlorie acid were added to the dried ether solution.
The resulting salt was removed by filtration and recrystallized from acetic acid. This method was used to
obtain 2,6-diphenyl-4-methylpyrylium perehlorate (nap 270* [4]) in 60% yield and 4-methylflavylium perchlo-
rate (rap 200 ~ 6]) in 40% yield.

777
 2,6-Diphenyl-4-/?-ethoxyvinylpyrylium P e r c h l o r a t e . A 0.3-g (1 mmole) s a m p l e of 2,6-diphenyl-4-
m e t h y l p y r y l i u m p e r c h l o r a t e was dissolved in glacial acetic acid, and 0.4 ml (2 mmole) of ethyl o r t h o f o r m a t e
was added to the hot solution. The solution was cooled to c r y s t a l l i z e out 0.32 g (80%) of a product with mp
194 ~ (from acetic acid). IR s p e c t r u m : 1630, . 1600, 1245, and 1100 cm -1. UV s p e c t r u m , Xmax, nm (a-10"~):
650 (27.03). PMR s p e c t r u m , 5, ppm: s of a r o m a t i c protons 7.75, 7.5, 7.25; d of vinyl protons 5.88 and
5.75; q 4.0 (Ctt2CH3); t 1.12 (CH2CtI3). R f 0o73. Found: C 62.3; H 4.9; C1 8.5%~ C21H19C106. Calculated: C
62.5; H 407; C1 8.8%. 2 , 6 - D i p h e n y l - 4 - o ~ - p h e n y l - f i - e t h o x y v i n y l p y r y I i u m p e r c h l o r a t e with mp 200 ~ and R f
0.75 was s i m i l a r l y obtained in 85% yield. Found: C 67.5; H 5.0; C1 7.4%. C2~H24C106, CaIculated: C 67.5; H
5.0; C1 7.4%. IR s p e c t r u m : 1635, 1590, 1250, and 1100 c m - i . UV s p e c t r u m , ~max, nm (a-10-~): 710 (29.68).
4 - P - E t h o x y v i n y l f l a v y l i u m P e r c h l o r a t e . A) A 0 . 4 - m l (2 mmole) s a m p l e of ethyl o r t h o f o r m a t e was added
to a w a r m solution of 0.3 g (1 mmole) of 4 - m e t h y l f l a v y I i u m p e r c h l o r a t e in n i t r o m e t h a n e (30-35~ After 1-
1.5 h, the m i x t u r e was diluted with e t h e r , and the p r e c i p i t a t e was r e m o v e d by filtration to give 0.32 g (90%)
of a product with mp 180-182 ~ and R f 0.70. IR s p e c t r u m : 1620, 1600, 1245, and 1110 cm -1. UV s p e c t r u m ,
Xmax, nm (~o10-3): 680 (25.79)0 PMR s p e c t r u m , 5, ppm: s of a r o m a t i c protons 7.62, 7.12, 6.88; d of vinyl
protons 6.32, 6.12; q 4.0 (CII2CH3); t 1.0 (CH2Ctt3). Found: C 6005; H 4.4; C1 9.6%. C19H17C10~. Calculated:
C 60.5; H 4.5; C1 9.4%. 4 - f i - E t h o x y v i n y l - 7 - h y d r o x y f l a v y I i u m p e r c h l o r a t e with mp 204 ~ was s i m i l a r l y ob-
tained in 90% yield. IR s p e c t r u m : 3550, 1620, 1600, 1250, and 1100 c m -1. UV s p e c t r u m , Xmax, nm (e.10-3):
700 (36.84)~ Found: C 57.5; H 4.4; C1 8.9%. Ci9HI?C107. Calculated: C 58.0; H 403; C1 9.0%.
B) A 1 . 6 - m l (0.01 mole) s a m p l e of ethyl o r t h o f o r m a t e was added to a solution of 0.3 g (1 mmole) of
4 - m e t h y l f l a v y l t u m p e r c h l o r a t e in acetic acid (100-105~ After 1-1~ h, the m i x t u r e was diluted with ether,
and the p r e c i p i t a t e d 4-fi-ethoxyflavylium p e r c h l o r a t e was r e m o v e d by filtration to give 0.31 g (89%) of p r o d -
uct. The s a m p l e s obtained by the two methods w e r e identical, as d e m o n s t r a t e d by a c o m p a r i s o n of the m e l t -
ing points of m i x t u r e s of the s a m p l e s and the IR s p e c t r a in the fingerprint region. A s i m i l a r p r o c e d u r e was
used to obtain 2 - / ? - e t h o x y v i n y l - 7 - h y d r o x y b e n z o p y r y l i u m p e r c h l o r a t e with mp 175 ~ in 66% yield. IR s p e c t r u m :
3500, 1630, 1590, 1245, and 1090 cm-4~ UV s p e c t r u m , ?~max, nm (~.10-~): 650 (23.42). Found: C 49.4; H 4.1;
C1 11.3%. C13H13C107. Calculated: C 49.2; H 401; C1 11.2%.
2,4-Diphenyl-6-(~, / ? - d i b r o m o - / ? - e t h o x y e t h y l ) p y r y l i u m P e r c h l o r a t e . A 0.05-ml s a m p l e of b r o m i n e was
added with s t i r r i n g to a solution of 0.4 g (1 mmole) of 2,4-diphenyl-6--fi-ethoxyvinylpyrylium p e r c h l o r a t e in
dioxane. After 12 h, the d i b r o m o d e r i v a t i v e was r e m o v e d by filtration to give 0.41 g (71%) of a product with
mp 269-270 ~ (from acetic acid). IR s p e c t r u m : 1620, 1590, 1520, and 580 cm -1. Found: C 45.0; H 3,8; C1, Br
34.4%. C21H19Br2C1060 Calculated: C 44.8; H 304; C1, B r 34.7%. A s i m i l a r p r o c e d u r e was used to obtain
the following compounds. 2 , 6 - D i p h e n y l - 4 - ( a , / ? - d i b r o m o - / ? - e t h o x y e t h y l ) p y r y l i u m p e r c h l o r a t e with mp 226 ~
was obtained in 75%yield, Found: C 44.6; H 3.3; C1, B r 3502%0 C21H19Br2CIO 6. Calculated: C 44.8; H 3.3;
C1, Br 34.8. 7-Hydroxy--4-(c~,fi-dibromo-fl-ethoxyethyl)flavylium p e r c h l o r a t e with mp 272 ~ was obtained in
74.5 yield. Found: C 41.6; H 3.0; C1, B r 35.7%0 C19H17Br2C1OT. Calculated: C 41.2; H 3.1; C1, B r 35~
B i s f l a v e n e t r i m e t h y l i d y n e P e r c h l o r a t e (VIIa). A) A 0 . 2 - m l (1 mmole) s a m p l e of ethyl o r t h o f o r m a t e
was added to 0.3 g (1 mmole) of 4 - m e t h y l f l a v y l i u m p e r c h l o r a t e in acetic a c i d - n i t r o m e t h a n e (9 0-95~ After 2-3
h, the solid was r e m o v e d by filtration to give 0.33 g (60%) of a product with mp 284-286 ~ (from acetic acid)
[61.
B) A 0.3-g (1 mmole) s a m p l e of 4 - m e t h y l f l a v y l i u m p e r c h l o r a t e was dissolved in a m i x t u r e of 2 ml of
acetic acid and 1 ml of acetic anhydride, and 0038 g (1 mmole) of 4 - f l - e t h o x y v i n y l f l a v y l i u m p e r c h l o r a t e was
added to the hot solution. The m i x t u r e was heated to c o m p l e t e l y dissolve the solids. It was then cooled,
and the resulting g r e e n plates w e r e r e m o v e d by filtration to give 0.55 g (100gO of product. The other c y a -
nine dyes w e r e s i m i l a r l y obtained (see Table 1).
1 , 3 - B i s ( 2 - p h e n y l - 4 - b e n z o p y r y l i u m ) p r o p e n e D i p e r c h l o r a t e ~ A 0.05-ml (0.5 mmole) s a m p l e of 70% p e r -
chloric acid w a s added to a solution of 0.3 g (0.5 mmole) of VIIa in acetic acid. A yellow substance c r y s t a l -
lized out when the m i x t u r e was cooled. Workup gave 0.65 g (100%) of a product with mp 300 ~ (dec.). IR
s p e c t r u m : 1650, 1625, 1600, and 1100 c m -1. Found: C 60.6; H 304; C1 10.5%o C33H24C12010o Calculated: C
60.8; H 3.7; C1 10.9%. A b i s p y r y l i u m salt with mp 300 ~ (dec.) was s i m i l a r l y obtained f r o m Vb. IR s p e c -
trum: 3500, 1725, 1645, 1620, 1590, and 1100 c m - t . Found: C 48.4; H 3.2; C1 10.8%. C27H24C12Oi6. Calcu-
lated: C 48.0; H 3.5; C1 10.5%.
1,3-Diphenyl-l,3-bis (2,6-diphenyl-4-pyridyl)propene (XI). A 0.76-g (1 mmole) s a m p I e of Via was r e -

Here and subsequently, s is singlet, d is doublet, t is triplet, and q is quartet.

778
fluxed in acetic acid with e x c e s s a m m o n i u m acetate for 2.5-3 h, a f t e r which the m i x t u r e was poured into
ice w a t e r . The c o l o r l e s s s u b s t a n c e that f o r m e d a f t e r a few hours was r e m o v e d by filtration to give 0.49 g
(75%) of a product with mp 90-92 ~ IR s p e c t r u m : 1610, 1590 c m -1. Found: C 89.8; H 5.0; N 4.3%. C49H36N2.
Calculated: C 90.2; H 5.5; N 4.3%.
1 , 3 - D i p h e n y l - l , 3 - ( 1 - b e n z y l - 2 , 6 - d i p h e n y l - 4 - p y r i d i n i u m ) p r o p e n e D i p e r c h l o r a t e (XII). A) A 0.65-g (1
mmole) s a m p l e of XI was refluxed in toluene with 0.3 ml (2 mmole) of benzyl chloride for 2-3 h. The m i x -
ture was cooled, and the p r e c i p i t a t e was r e m o v e d by filtration and converted to the d i p e r c h l o r a t e by the ac-
tion of 0.3 ml of 70% p e r c h l o r i c acid in acetic acid. The yield of product with mp 300 ~ (dec.) was 0.6 g (60%).
Found: C 73~ H 5.0; C1 7.1; N 2.5%. C63HsoN2Cl~O8. Calculated: C 73.2; H 4.8; C1 6.9; N 2.7%.
B) A 0.51-g (1 mmole) s a m p l e of 2 , 6 - d i p h e n y l - 4 - b e n z y l - N - b e n z y l p y r i d i n i u m p e r c h l o r a t e was refluxed
with 0ol ml (0.5 mmole) of ethyl o r t h o f o r m a t e in acetic anhydride for 8-10 h. The m i x t u r e was then cooled,
and the solid was r e m o v e d by filtration and converted to the d i p e r c h l o r a t e by the action of 70% p e r c h l o r i c
acid in acetic acid. The yield of product with mp 300 ~ (dec.) was 0.8 g (80%). The s u b s t a n c e s obtained by
methods A and B w e r e identical (according to the IR s p e c t r a at 600-1800 cm-1).

LITERATURE CITED

Io G. N. Dorofeenko, V. V. M e z h e r i t s k i i , and A. L. V a s s e r m a n , K-him. G e t e r o t s i k l . Soedin., 37 (1974).

2. M. Simalty, H. S t r z e l e c k a , and H. Khedija, T e t r a h e d r o n , 27, 3503 (1971).
3, H. Khedija, M. Simalty, and H. S t r z e l e c k a , Comptes Rend., 272, 1370 (1971).
4. A. T. Balaban and C. D. Nenitzescu, Ann., 625, 74 (1959).
5. H. S t r z e l e c k a , Ann. Chim., 1, 201 (1966).
6. R. Wizinger and H. Tobel, Helv. Chim. Aeta, 4_0.0, 1305 (1957).

779
REACTIONS OF fl-ETHOXYVINYLPYRYLIUM
SALTS WITH NUCLEOPHILES

V. V. M e z h e r i t s k i i , A. L. Vasserman, UDC 547. 813

a n d G. N. D o r o f e e n k o

N i t r f i e s , G r i g n a r d r e a g e n t s , and C H - a c i d compounds attack the f i - c a r b o n a t o m in fi-ethoxy-

v i n y l p y r y l i u m s a l t s to give, r e s p e c t i v e l y , n i t r i l i u m s a l t s , s t y r y l p y r y l i u m s a l t s , and p y r y l -
o merocyanines.

In the p r e s e n t study we have examined the r e a c t i o n s of the p r e v i o u s l y s y n t h e s i z e d [1, 2] f l - e t h o x y -

v i n y l p y r y l i u m s a l t s with some nucleophiles.

2- and 4 - E t h o x y v i n y l p y r y l i u m and b e n z o p y r y l i u m salts add aliphatic and a r o m a t i c n i t r i l e s at t h e / ~ -

carbon atom to give n i t r i l i u m salts:
OC2H5
... , - O,,/C=CH--CH--OC2H s

CIO~ CIO~ CIO~"

Acid hydrolysis of the n i t r i l i u m s a l t s gives f l - h y d r o x y v i n y l p y r y l i u m salts and carboxylic acids, as shown

in the c a s e of p e r c h l o r a t e I:

%|{: ~oH5

- + %HsCOOI!
C6Hs/~O/'~CH --CH--N~C--C6H 5 C6Hs CH=CH--OH
ClO~" ClO;
I II

The isolation of salt II and benzoic acid c o n f i r m s the p r o p o s e d s t r u c t u r e o f . p e r c b l o r a t e I. The IR s p e c t r u m

of I contains a band at 1640-1660 e m -1, which is c h a r a c t e r i s t i c for the C =i~ grouping, and bands r e l a t e d to
the vibrations of the p y r y l i u m ring, a r o m a t i c substituents, and functional groups.
It was shown that 2- and 4 - f i - e t h o x y v i n y l p y r y l i u m and b e n z o p y r y l i u m s a l t s r e a c t with p h e n y l m a g n e -
s i u m b r o m i d e and that the attack of the nucleophile is directed to the f l - c a r b o n a t o m of the fl-ethoxyvinyl-
p y r y l i u m salt. T r e a t m e n t of the r e a c t i o n products with p e r c h l o r i c acid in acetic anhydride gives s t y r y l p y -
r y l i u m salts.
...~ + %H~MgBr (~6Hs HCIO 4
0... / C = C H - - C H - - O C ~ H - - ~ " -, ...
clo: clo~

The s t r u c t u r e s of the products were c o n f i r m e d by c o m p a r i s o n (mixed-melting-point determinations

and IR s p e c t r a in the " f i n g e r p r i n t " region) with s a m p l e s obtained by condensation of m e t h y l p y r y l i u m s a l t s
with benzaldehyde. Alkyl- and b e n z y l m a g n e s i u m b r o m i d e s a p p a r e n t l y also undergo this r e a c t i o n , but the
r e a c t i o n products cannot be isolated b e c a u s e of t h e i r instability.
The possibility of the r e a c t i o n of 2 , 4 - d i p h e n y l - 8 - ( f l - a l k o x y c y c l o a l k y l i d e n e ) p y r y l i u m salts with c o m -
pounds containing an active methylene group was shown hi a special example by K i r n e r and Wizinger [3].
We have extended this r e a c t i o n to 2- and 4 - ( f l - a l k o x y v i n y l ) p y r y l i u m and b e n z o p y r y l i u m salts. To effect con-
densation we used malonic, cyanoacetic, and a c e t o a c e t i c e s t e r s , acetylacetone, dibenzoylmethane, and phen-
Rostov State University. S c i e n t i f i c - R e s e a r c h Institute of P h y s i c a l and Organic C h e m i s t r y , R o s t o v -
on-Don. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 7, pp. 897-900, July, 1974. O r i g -
inal a r t i c l e submitted August 8, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

780
ylacetie acid. The r e a c t i o n p r o c e e d s with the formation of substances to which we feel it is possible to
assign s t r u c t u r e s III a-l:
(~ CHaCOONa . X.
"" +
O'.../C=CH--CH--OC2H 8 + CH~. ",' _C2H50H o"' . .b/ c : c . - c u = c ( "Y"::
cio~- -tlctoa IIIa-I

/R /CN
C~Hs CH--CH =C\R CH--CH=C,

C6Hs/ d ~CH--C H= C/RI~, ,, \CGH~ " m.o

HOI \CoH s
III a - f Ill g, i III k

/r
CH--CH=C',.COO C2H5.

[ cs
.o~l~.ofl~cv-cK=C/coo%.s

IIIj Ill l

Ilia R=CN, R'=COOC2Hs; b R=R'=COOC2Hs; c R=R'=COCHa; d R=R'=COC6Hs:

e R=COCHa, R'=COOC2H~; f R=C6Hs, R'=COOH; g R=CN, R'~COOC2Hs; h R=
=COCHa, R'=COOC2H~; i R~R'=COCH~

The yields of products III are usually close to quantitative r e g a r d l e s s of the s t r u c t u r e s of the s t a r t i n g py-
r y l i u m salt and the methylene-active compounds. To c o n f i r m the s t r u c t u r e s of merocyanines III we a c -
complished the r e a c t i o n of 2 , 4 - d i p h e n y l - 6 - ( f l - e t h o x y v i n y l ) p y r y l i u m p e r c h l o r a t e with sodiomalonic e s t e r ,
as a r e s u l t of which a product identical to llIb is formed.
O'")C:Clt--(;tt--OC~H-...
- ~ + NaCH(COOCoH~,)~,_
- -NaCIO~- lllb
CIO~ -CtH~OH

The synthesized p y r y l o m e r o e y a n i n e s axe capable of exchanging a heterocyr oxygen atom for n i t r o -

gen on melting with a m m o n i u m acetate to give compounds of the pyridine s e r i e s :

CH3COONH4
III g, i
C6H5/ ~N ,/ ~CGH5

R,I~'=COCH3; R=COCIIa; l'=COOC:ll 5

P y r y l i u m salts containing an active methylene group, which undergoes quantitative condensation with
anisaldehyde, a r e obtained by the action of p e r c h l o r i c acid on the p y r y l o m e r o c y a n i n e s :

//COCH3 /COCH3
CH~C~
! COOC~H~ ~H=C\cooc2H 5
CH2 ~ C=CI|--C6H4--OCH 3

IIih
CsH5 C6H5 C6H5/"~O~ \C6H 5
clo7 cio7

The IR s p e c t r a of the p y r y l o m e r o c y a n i n e s contain c h a r a c t e r i s t i c absorption bands of the functional

groups of p y r y l o m e r o c y a n i n e s [4, 5].

EXPERIMENTAL
The IR s p e c t r a of m i n e r a l - o i l suspensions of the compounds were obtained with a UR-20 s p e c t r o m e t e r .
N - c ~ - E t h o x y - f i - [ 2 , 4 - d i p h e n y l - 2 - p y r a n y l i d e n e ] e t h y l a c e t o n i t r i l i u m P e r c h l o r a t e (I). A 0~ (1 mmole)
sample-of 2 , 4 - d i p h e n y l - 6 - ( f l - e t h o x y v i n y l ) p y r y l i u m p e r c h l o r a t e was refluxed for 20 rain with 0.08 ml (1.5
mmole) of acetonitrUe in glacial acetic acid. After 24 h, the nitrilium salt was r e m o v e d by filtration to
give 0.42 g (95%) of a product with mp 238 ~ (dec.). IR s p e c t r u m : 1640, 1600, and 1100 c m -1. Found: C 62.9;
H 4.6; C1 8.4; N 3.4%. C23H22NC10~. Calculated: C 62.2; H 4.9; C1 8.0; N 3.2%. P e r c h l o r a t e II (88%) and
benzoic acid (85%) were isolated by acidic h y d r o l y s i s of I.

781
 TABLE 1. Synthesized P y r y l o m e r o c y a n i n e s
]

I
Found, % I Calc.,~o I
E == ' Empirical IR spectrum, cm-1 ~2
~)~, ~ formula i
' C H N' C I:H~ N '
r L ~ i /
Ilia . 152 C24t'f19NOa 78.3 4,9 ~ 0 78,1 5,1; 3,9' 2210, 1720, 1665, 1600 80
IIIb ' 91; C2GH24Oa !75,5 5,6 - - 75,0 5,8 --i 1755, 1710, 1660, 1590 95
]llc !01 . C24H2oO3 J 79,3' 5,2. --i 80,9 5,6 1720, 1680, 1650, 1590 92
Illd !08 ! Ca4H2+Oa 84,9.5,11--i 85,0 5,0 1700, 1680, 1650, 1600 40
H i e 151 C2~Ho204 177,7 5,71 --! 77,8 57, --! 1760, 1665, 1640, 1600 98
Illf 176 C_*7H2oOa 83,2 5,0;--' 82,7 o,l~ 1700, 1650, 1600 96
llI g 162 C24H~gNO3 78,3 4,9 4,0 78,2 5, I' 3,9: 2200, i700, t680, 1610 80
Illh 164 C2sI-I2204 177,7 5,7--~ 77,8 5,7 --' 1755, 1660, 1645, 1590 98
I l l i I22 C241-t~0Oa 79,3' 5,2 - - 79,6, 5,8 --i 1725, 1680, 1655, 1600 I 82
llIj 134 CI9HIrNO6 164,414,4 i 3,8! 64,2 4,81 3,9 3500, 2210, 1725, 1700, ] 89
I 1680, 1610
111k 142 C2~H~TNO+ ,73,1 4,6! 3,6 73,51:4,71 3,9 3500, 2210, 1760, 1700, I 90
5,5 3,3 1640, 1600
11I l t53 C2sH2aNO3 i79,71[ 5,4 3,3 ~79,8 2210, 1700, 1665, 1595 87

The following compounds w e r e s i m i l a r l y obtained. N - a - E t h o x y - f i - [ 2 , 4 - d i p h e n y l - 2 - p y r a n y l i d e n e ] e t h y -

y l b e n z o n i t r i l i u m p e r c h l o r a t e with mp 289 ~ (dec.) was obtained in 88% yield. IH s p e c t r u m : 1645, 1600, and
1095 c m -I. Found: C 65.5; H 4.6; C1 7.2; N 2.6%. C28H24NC10 6. Calculated: C 66.4; H 4.7; C1 7.0; N 2.7%;
N - a - E t h o x y - f l - [ 2 , 6 - d i p h e n y l - 4 - p y r a n y l i d e n e ] e t h y l b e n z o n t t r i l i u m p e r c h l o r a t e with mp 300 ~ (dee.) was ob-
tained in 85% yield. IR s p e c t r u m [ 1645, 1600, and 1100 c m -1. Found: C 66.7; H 4.6; C1 8.0; N 2.6%.
C28H24NCIO~. Calculated: C 66.4; H 4.7; C1 7.0; N 2.7%; N - a - E t h o x y - f l - [ 7 - h y d r o x y - 4 - f l a v e n y l ] - e t h y l -
benzonitrilium p e r c h l o r a t e with mp 216 ~ was obtained in 82% yield. IR s p e c t r u m : 1660, 1610, and
1100 em -1. Found: C 63.0; H4o5; C17.0; N2.4%. C26H22NC10 7. Calculated: C 62.9; H4.4; C17.2; N2.8%.
2 , 4 - D i p h e n y l - 6 - s t y r y l p y r y l i u m P e r c h l o r a t e . A G r i g n a r d r e a g e n t obtained f r o m 0.83 ml of b r o m o b e n -
zene and 0.2 g of m a g n e s i u m in 10 ml of absolute ether was added r a p i d l y to a suspension of 0.8 g (2 mmole)
of 2 , 4 - d i p h e n y l - 6 - f i - e t h o x y v i n y l p y r y l i u m p e r c b l o r a t e in 30 ml of dry ether, and the r e s u l t i n g solution was
s t i r r e d for 20-30 min. The mixture was then d e c o m p o s e d with cold a m m o n i u m chloride solution, and the
e t h e r l a y e r was s e p a r a t e d , washed with 1 N sodium c a r b o n a t e solution and w a t e r , and dried with c a l c i u m
chloride. Acetic anhydride (2 ml) and 0.2 ml (2 mmole) of 70% p e r c b l o r i e acid w e r e added to the ether s o -
lution, and the mixture was worked up to give 0.65 g (75%) of a product with mp 233 ~ [6]. The following
compounds w e r e s i m i l a r l y obtained. 2 , 6 - D i p h e n y l - 4 - s t y r y l p y r y l t u m p e r c h l o r a t e with mp 252-253 ~ [6] was
obtained in 69% yield. 4 - S t y r y l f l a v y l i n m p e r e h l o r a t e with mp 240 ~ was obtained in 71% yield. Found:
C 67.4; H 4.6; C1 8.6. C23H17C105. Calculated: C 67.4; H 4.1; C1 8.7%.
Ethyl a - C a r b e t h o x y - T - p y r a n y l i d e n e - 4 - e r o t o n a t e . A 0.4-g (1 mmole) s a m p l e of 2 , 4 - d i p h e n y l - 6 - f i -
ethoxyvinylpyrylium p e r c h l o r a t e and 0.16 ml (1 mmole) of malonie e s t e r w e r e refluxed in acetic anhydride
for 10 min. Sodium acetate [0.08 g (1 mmole)] was added, and the mixture was refluxed for another 30 min.
It was then cooled and diluted with 10 ml of water. After 24 h, the mixture was filtered to give 0.4 g of IIIb.
A s i m i l a r p r o c e d u r e was used to obtain I l i a - / (see Table 1).
A 0.18-g (1 mmole) s a m p l e of sodiomalonie e s t e r was added to a s u s p e n s i o n of 0.4 g (1 mmole) of
2 , 4 - d i p h e n y l - 6 - f l - e t h o x y v i n y l p y r y l i u m p e r c h l o r a t e in d r y ether. After a few h o u r s , the s o d i u m p e r c h l o r a t e
was r e m o v e d by filtration, ether was r e m o v e d by distallatton, and the r e s i d u e was refluxed for 10-15 min
in acetic anhydride. The mixture was diluted with w a t e r and e x t r a c t e d with e t h e r , and the e x t r a c t was dried
with sodium sulfate. The e t h e r was r e m o v e d by distillation to give IIIb.
1 - A c e t y l - l - e a r b e t h o x y - 3 - [ 2 , 6 - d i p h e n y l - 4 - p y r i d y l ] - l - p r o p e n e . A 0.4-g (1 mmole) s a m p l e of IIIh was
fused with a m m o n i u m acetate, and the mixture was poured into the m i n i m u m amount of water. The mixture
was worked up to give 0.38 g (100%) of a product with mp 129-130 ~ (from tsopropyl alcohol). IR s p e c t r u m :
1750, 1665, 1640, and 1600 c m -1. Found: C 78.3; H 5.7; N 3.7%. C25H23NO3. Calculated: C 78.1; H 5.8;
N 3.6%. A s i m i l a r p r o c e d u r e was used to obtain 1 , 1 - d t a c e t y l - 3 - [ 2 , 6 - d i p h e n y l - 4 - p y r i d y l ] - l - p r o p e n e with
mp 144 ~ in 86% yield. IR s p e c t r u m : 1720, 1665, 1650, and 1600 c m -1. Found: C 81.7; H 5.8; N 3.2%.
C24H21NO2. Calculated: C 81.1; H 5.9; N 3.9%.
1 - A c e t y l - l - c a r b e t h o x y - 3 - [ 2 , 6 - d i p h e n y l - 4 - p y r y l i u m ] - l - p r o p e n e . A 0 . 1 - m l (1 mmole) s a m p l e of 70%
p e r c b l o r i c acid was added to 0.4-g (1 mmole) of IIIh in acetic anhydride, and the mixture was diluted with
d r y ether. The r e s u l t i n g p r e c i p i t a t e was r e m o v e d b y filtration to give 0.46 g (97%) of a product with mp
289 ~ (from acetic acid). IR s p e c t r u m : 1750, 1665, 1640, 1620, 1600, and 1100 c m -1. Found: C 61.6; H 5.2;
C1 7.8%. C25H23C10 8. Calculated: C 61.6; H 4.7; C1 7.3%.

782
 1 - A c e t y l - l - c a r b e t h o x y - 3 - [2,6-diphenyl-4-pyrylium]-4- (p-methoxyphenyl) 1,4-butene. A 0.1-ml
(i mmole) sample of 70% percklortc acid and 0.12 ml (I mmole) of anisaldehyde were added to a solution
of 0.4 g (i mmole) of IIIh in acetic anhydride, and the mixture was refluxed for ~ 1 h. It was then worked
up to give 0.6 g (100%) of a product with mp 300 ~ (dec.). IR spectrum: 1720, 1640, 1620, 1590, and ii00
cm -i. Found: C 65.7; H 4.8; CI 5.1%. C33H29CIO 9. Calculated: C 65.4; H 4.8; Cl 5.8%.

LITERATURE CITED
io G. N. Dorofeenko, V. V. Mezheritskii, and A. L. Vasserman, Khim. Geterotsikl. Soedin., 37 (1974).
2. A. L. Vasserman, V. V. Mezheritskii, and G. N. Dorofeenko, I/him. Geterotsild. Soedin., 892 (1974}.
3. H. Kirner and R. Wizinger, Helv. Chim. Aeta, 4_~4, 1778 (1961).
4. L. Bellamy, Infrared Spectra of Complex Molecules, Methuen (1958).
5. A. T. Balaban, G. D. IV[ateescu, and M. Elian, Tetrahedron, 188, 1083 (1962).
6. W. Dilthey and J. Tiseher, Chem. Ber., 5_/7, 1658 (1924).

783
REACTION OF SOME AROMATIC NITRILE
OXIDES WITH DIMEDONE

A. A. A k h r e m , V. A . Khripach, UDC 547.786.3 : 543.422.25.4'51

a n d F. A. L a k h v i c h

1,3-Dipolar cycloaddition of benzonitrile and m-nitrobenzonitrile oxides to the enol f o r m of

dimedone gives the c o r r e s p o n d i n g 4-oxotetrahydrobenzisoxazoles. A second r e a c t i o n path -
nucleophilic addition of the enol to the N-oxide to give a h y d r o x a m i c acid derivative - is ob-
s e r v e d in the case of m-nitrobenzonitrile oxide. The t e t r a h y d r o b e n z i s o x a z o l e s are converted
to enamine derivatives of benzoyldimedone under catalytic hydrogenation conditions.

It is known [1] that the r e a c t i o n of nitrile oxides with enolized aliphatic fi-diketones proceeds via
1,3-dipolar cycloaddition to the C =C bond of the enol forms to give 5-hydroxyisoxazolines, which are sub-
sequently stabilized to isoxazoles by splitting out of a water molecule. However, there is no information in
the l i t e r a t u r e r e g a r d i n g the r e a c t i o n of nitrile oxides with c y c l i c / 3 - d i k e t o n e s to give cycloalkanoisoxazoles.
The latter, being the "latent form" of 2 - a c y l c y c l o a l k a n e - l , 3 - d i o n e s , m a y find interesting synthetic ap-
plications.
The r e a c t i o n of a r o m a t i c nitrile oxides, p a r t i c u l a r l y benzonitrile oxide (II) and m-nitrobenzonitrile
oxide (III), with dimedone proceeded in situ under conditions that make it possible to maximally reduce
dimerization of the oxide [2].
As assumed, products of 1,3-dipolar cycloaddition - isoxazoles VII and VIII, r e s p e c t i v e l y - are ob-
tained ia the r e a c t i o n of nitrtle oxides II and III with dimedone (I); the intermediate isoxazolines (VI) w e r e
not isolated.
In the case of m - n i t r o b e n z o n i t r i l e oxide (III) a second reaction path - nucleophilic addition of the enol
of I to the nitrone to give hydroxamic acid derivative IV - is also realized. This s o r t of addition to stable
nitrile oxides was p r e v i o u s l y described [3] for amines, alcohols, carboxyltc acids, and some other r e -
agents.
The s t r u c t u r e of acid IV was confirmed by h y d r o l y s i s to hydroxamic acid V and dimedone (I) under
acidic conditions and also by the spectral data. Thus the PMR s p e c t r u m of acid IV contains, in addition to
signals of the a r o m a t i c protons and methyl and methylene protons of the dimedone fragment in the expected
regions, the r e s o n a n c e signal of a vinyl proton at 6.38 ppm. The mass s p e c t r u m contains a molecular ion
peak with m / e 304, the principal paths of disintegration of which under the influence of electron impact ap-
p a r e n t l y include cleavage of the e s t e r C - O bond. As a r e s u l t of this, the principal peaks in the mass s p e c -
t r u m of IV c o r r e s p o n d to m-NO2C6H4CO + and m-NO2C6H4CNO+ fragments with intensities of 100 and 99.96%,
respectively.
The [R s p e c t r u m of acid IV displays absorption bands of a s s o c i a t e d hydroxyl (2500-3200 c m -~) and
carbonyl (1615 c m -1) groups included in strong hydrogen bonds of the chelate type, which are c h a r a c t e r i s t i c
for dimedone and its derivatives [4].
The s t r u c t u r e of cyclohexanoisoxazoles VII and VIII follows f r o m the set of data f r o m p h y s i c o c h e m -
ical methods of analysis and also f r o m a c o m p a r i s o n of the p r o p e r t i e s with IX, which we synthesized by the

Institute of Physical Organic C h e m i s t r y , A c a d e m y of Sciences of the B e l o r u s s i a n SSR, Minsk. T r a n s -

lated f r o m Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 901-904, July, 1974. Original article sub-
mitted July 12, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 1 7th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored h7 a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

784
method in [5]. Thus, for example, the PM_R s p e c t r a of VII-IX have p r a c t i c a l l y identical patterns of r e s o n a n c e
signals f r o m the protons of identical s t r u c t u r a l fragments of the molecules under c o m p a r i s o n (see the ex-
p e r i m e n t a l section).
O

R/ ~ H+ />N0 It
O
~ON//CI0 - R--C~o H + I

IV Y
l i O / ~ + r --C+=N--O-
I II, Ill
m,
R\ -H~O R\Nii~-n.2,....,...~_

VI VII, VIII

II, Vll R=C6Hs; Ill,IV, VIII R=NO2C6H 4

In c o n f o r m i t y with the proposed s t r u c t u r e , the IR s p e c t r a of tsoxazoles VII and VIII contain the c h a r -
a c t e r i s t i c (for this sort of compound) absorption band of a conjugated caxbonyl group at 1685-1700 c m -~.
In addition, there are two bands of medium intensity, which are due to absorption of the a r o m a t i c and isox-
azele r i n g s , at 1600-1700 c m -1.
F r a g m e n t a t i o n of VII and VIH under electron impact is also c h a r a c t e r i s t i c . Thus, while the paths of
disintegration of the molecule in the case of acid IV are determined by the lability of the C - O bond and the
stability of the aromatic ion arising as a result of its cleavage, the fragmentation of VII and VIII is deter-
mined by the stability of the isoxazole rings (probably the rearranged isoxazole ring [7]) conjugated with
the aromatic ring. This sort of fragmentation is typical for cyclic ketones [8] and consists in cleavage of
the ~ bond with respect to the carbonyl group and subsequent hydrogen migration and homolytic cleavage
leading to the M + -98 ion (of maximum intensity in the spectrum) and elimination of a ketone homolog as a
neutral particle.
It is known [9] that 3-substituted isoxazoles undergo opening of the isoxazole ring at the N-O bond
under catalytic hydrogenation conditions to give enamlnoketones.
o ,nil2 0
R',I,~ ~2/PaR/~'~
~'-o>%..~ - - o ~ 4 -

VII-IX X-XII
VII, XI R=C6Hs; VIII, Xll R NH2C6tt,; IX, X R = C H 3

In our case, the hydrogenation of cyclohexanoisoxazole IX under the usual conditions gave a quantitative
yield of the known [5] enaminod[ketone X. It should be noted that the facile opening of the isoxazole ring
that we o b s e r v e d proceeds in the absence of a base, in c o n t r a s t to what usually o c c u r s in the case of other
[soxazoles (for example, see [9-11]).
Like IX examined above, VII and VIII also r e a d i l y undergo opening of the isoxazole ring to give ena-
mine derivatives XI and XII, r e s p e c t i v e l y , during hydrogenation in the p r e s e n c e of a Pd catalyst. A c c o r d -
ing to the l:R s p e c t r a , as in the case of X [12] and a number of other r e l a t e d enaminoketones [13, 14], the
latter contain a strong t n t r a m o l e c u l a r hydrogen bond of the chelate type.
The s t r u c t u r e of enamino derivatives of 2-benzoyldimedone (XI and X!I) is in good a g r e e m e n t with the
P~CR and m a s s - s p e c t r a l data p r e s e n t e d in the experimental section.

EXPERIMENTAL
The melting points were determined with a Kofler block. The IR spectra were obtained with a UR-20
spectrometer, and the PMR spectra were obtained with a JNM-PFT-100 spectrometer with tetramethyl-
s[lane as the internal standard. The mass-spectrometric data were obtained with a Varian MAT-311 spec-
trometer. Thin-layer chromatography (TLC) on microplates (7.6 by 2.5) with a fixed layer of Woelm silica
gel and Silufol UV-254 plates was used to monitor the course of the reactions. S[licie acid (100-150 mesh)
was used for column chromatography.
Reaction of BenzonEtrile Oxide (II) with Dimedone (I). A mixture of 2.8 g (0.02 mole) of I and 3.2 g
(0.02 mole) of b e n z o h y d r o x a m i c acid chloride tn 100 ml of absolute t e t r a h y d r o f u r a n (THF) was t r e a t e d with

785
 stirring and cooling (~ 0 deg) in the course of 2 h with a solution of 3 g (0.03 mole) of triethylamine in 50
rnl of THF, after which the mixture was stirred for another 30 min. After 3 h, the precipitated triethyl-
amine hydrochloride was separated, and the solvent was removed in vacuo. The oily residue (,~ 6 g) was
chromatographed with a column filled with silicic acid. Elution withhexane-ether (9 : 1) yielded 1.2 g (26%)
of 5,5-dimethyl-3-phenyl-4-oxo-4,5,6,7-tetrahydrobenz[1,2-d]isoxazole(VII)with mp 121-123~ (from hex-
ane). IR spectrum (KBr).~ 1580, 1595, 1700, 2965, 2880, and 3080 cm-I. PM:R spectrum* in CF3COOH, 6,
ppm: 1.47 (2CH3, s), 2.89 (CH2, s), 3.23 (CH2, s), and 7.80 (C6H5, m). Found: C 74.6; H 6.2; N 5.6%; IV[(mass
s p e c t r o m e t r i c a l l y ) 241. C15H15NO2. Calculated: C 74.7; H 6.2; N 5.87c; )~I 241.29.
Reaction of m - N i t r o b e n z o n i t r i l e Oxide (III) with Dimedone (I). A solution of 2 g (0.01 mole) of b e n z o -
h y d r o x a m i e acid chloride in 200 ml of c h l o r o f o r m was added in the c o u r s e of 5 h with vigorous s t i r r i n g at
r o o m t e m p e r a t u r e to a m i x t u r e of 2.8 g (0.02 mole) of I and 2 g (0.02 mole) of t r i e t h y l a m i n e in 50 ml of
c h l o r o f o r m , a f t e r which the r e a c t i o n mixture was allowed to stand overnight. The mixture was then t r e a t e d
with water, and the organic l a y e r was s e p a r a t e d and dried with MgSO 4. The solvent was r e m o v e d , and the
oily r e s i d u e (~ 4 g) was c h r o m a t o g r a p h e d with a column filled with silicic acid. Elution with h e x a n e - e t h e r
(9 ~.1) yielded 0.55 g (19.2%) of 5 , 5 - d i m e t h y l - 3 - ( m - n i t r o p h e n y l ) - 4 - o x o - 4 , 5 , 6 , 7 - t e t r a h y d r o b e n z [1,2-d]isoxa-
zole (VIII) with mp 112-113 ~ (from hexane). IR s p e c t r u m (KBr): 1580, 1595, 1620, 1685, 2880, and 2970
c m -i. PMR s p e c t r u m in CC14, 5, ppm: 1.20 (2CH3, s), 2.42 (CH2, s), 2.85 (CH2, s), and 8.20 (C~H4, m).
Found: C 63.0; H 4.8; N 9.7%; M (mass s p e c t r o m e t r i c a l l y ) 286. C15HuN204. Calculated: C 62.9; H 4.9;
N 9.8%; M 286.29.
Elution w i t h h e x a n e - e t h e r (6:4) yielded 1.08 g (36%) of d i m e d o n y l - ( m - n i t r o b e n z o h y d r o x a m i c acid) (IV)
with mp 172-174 ~ (from aqueous methanol). IR s p e c t r u m (KBr): 1565, 1590, 1615, 1640, and 2500-3200
(broad band) c m -I. P_MR s p e c t r u m in CF3COOH , 5, ppm: 1.26 (2CH3, s), 2.62 (CH2, s) 2.72 (CH2, s), 6.38
(=CH, s), and 8.30 (C~H4, m). Found~ C 59.1; H 5.3; N 9.2%; M (mass s p e c t r o m e t r i c a l l y ) 304. C15H16N205.
Calculated: C 59.2; H 5.3; N 9.2%; M 304.32.
H y d r o l y s i s of E s t e r IV. A solution of 0.2 g of IV in 20 ml of methanol was acidified with dilute (1 : 1)
H2SO4 to pH ,~ 1, and the mixture was allowed to stand overnight. It was then concentrated, diluted with w a -
t e r , and e x t r a c t e d with c h l o r o f o r m . The usual workup of the e x t r a c t and subsequent c r y s t a l l i z a t i o n f r o m
c h l o r o f o r m gave 0.06 g of dimedone (I) and 0.05 g of b e n z o h y d r o x a m i c acid (V).
Cyclohexanoisoxazole IX. This compound, with mp 56-57 ~ (from hexane), was obtained by the method
in [5]. IR s p e c t r u m (KBr): 1610, 1690, 2880, and 2970 c m -1. ])MR s p e c t r u m in CC14, ~, ppm: 1.13
2CH3, s), 2.28 (CH2, s), 2.36 (CH3, s), and 2.80 (CH2, s).
Hydrogenation of Isoxazole IX. A solution of 0.1 g of IX in 15 ml of ethanol was hydrogenated at r o o m
t e m p e r a t u r e and n o r m a l p r e s s u r e in the p r e s e n c e of 0.05 g of 5% Pd/BaSO 4. After an equivalent amount of
hydrogen had been absorbed, the c a t a l y s t was r e m o v e d by filtration, and the solvent was r e m o v e d in vacuo.
Enaminodiketone X, with mp 133-134 ~ (mp 133 ~ [5]) was obtained in quantitative yield.
5 , 5 - D i m e t h y l - 2 - ( a - a m i n o b e n z y l i d e n e ) c y c l o h e x a n e - l , 3 - d i o n e (XI). Enamino derivative XI, with mp
273-274 ~ (from c h l o r o f o r m ) , was obtained in quantitative yield f r o m VII by a method s i m i l a r to the p r e c e d -
9ing method. IR s p e c t r u m (KBr): 1590, 1655, 1695, 2880, 2970, 3110, and 3270 c m -1. ])MR s p e c t r u m in
CF3COOH , 6, ppm: 1.32 (2CH 3, s), 2.88 (2CH 2, s), and 7.72 (C6H5, m). Molecular weight found (mass s p e c -
t r o m e t r l c a l l y ) 243. CIsHITNO2. Calculated mol. wt. 243.22.
5 , 5 - D i m e t h y l - 2 - ( m , ~ - d i a m i n o b e n z y l i d e n e ) c y c l o h e x a n e - 1,3-dione (XII). S i m i l a r l y , isoxazole VIII was
c o n v e r t e d quantitatively to XII with mp 212-215 ~ (from chloroform). IR s p e c t r u m (KBr): 1590, 1630, 1650,
2880, 2970, 3150, 3290, 3380, and 3470 c m -1. ])MR s p e c t r u m in CF3COOH , 6, ppm." 0.96 (2CH3, s), 2.17
(2CH2, s), and 7.52 (CGH4, m). Molecular weight found (mass s p e c t r o m e t r i c a l l y ) 258. C15Hl~N202. Calcu-
lated mol. wt. 258.32.

LITERATURE CITED
1. A. Quilico and G. Speroni, Gazz. Chim. Ital., 76, i48 (1946).
2. R. Huisgen, Angew. Chem., 75, 613 (1963).
3. C. Grundmann and H. D. F r o m m e l d , J. Org. Chem., 31, 157 (1966).
4. K. Nakanishi, I n f r a r e d Spectroscopy, P r a c t i c a l , Holden-Day, San F r a n c i s c o (1962).
5. A . W . C r o s s l e y and N. Renouf, J. Chem. Soc., 101, 1524 (1912).

* H e r e and subsequently, s is singlet and m is multiplet.

786
 6. H. Smith, J. Chem. Soc., 803 (1953).
7. A.A. Polyakova and A. A. Khmel'n[tski[, Mass Spectrometry in Organic Chemistry [in Russian],
I<himiya, Leningrad (1972), p. 268.
8. H. Budzikiewicz, C. Djerass[, and D. Williams, Interpretation of the Mass Spectra of Organic Com-
pounds, Holden-Day (1964).
9. R. Barnes, in: Heterocyclic Compounds [Russian translation], Vol. 5, Inostr. Lit. Moscow (1961),
p. 377.
I0. J.W. Scott and G. Saucy, J. Org. Chem., 37, 1652 (1972).
ii. R.V. Stevens, C. G. Christensen, W. L. Edmonson, M. Kaplan, E. B. Reid, and M. P. Wentland, J.
Amer. Chem. Soc., 9.3, 6629 (1971).
12. G.O. Dudek and G. P. Volpp, J. Org. Chem., 30, 50 (1965).
13. V.S. Bogdanov, V. V. Negrebetskii, F. A. Lakhvich, A. M. Moiseenkov, and A. A. Akhrem, Izv. Akad.
Nauk SSSR, Ser. Khim., 1114 (1972).
14. V.S. Bogdanov, V. V. Negrebetski[, V. A. Korenevskii, A. M. Moiseenkov, F. A. Lakhvich, and A. A.
Akhrem, Izv. Akad. Nauk SSSR, Ser. Kh[m., 550 (1971).

787
SYNTHESIS OF 2-R-FLUORANTHENO[2,3-d]-
AND 2-R- FLUORANTHENO [3,2-d]OXA ZOLES

~. I. S h e n b o r and V. I. Tikhonov UDC 547.787.3.07 : 543.422.4.6

2 - R - F l u o r a n t h e n o [2,3-d]- and 2-R-fluorantheno [3,2-d]oxazoles were synthesized, and their

UV and IR s p e c t r a were studied. Ten new compounds a r e described.

We have p r e v i o u s l y described a new s e r i e s of 2-R-fluorantheno[8,9-d]oxazoles with a h e t e r o c y c l i c

s y s t e m in the phenylene portion of the fluoranthene molecule [1]. The p r e s e n t paper is devoted to a study
of the synthesis and spectral c h a r a c t e r i s t i c s of fluoranthenooxazoles with an oxazole residue on the naphtha-
lene portion of the molecule. Considering the available data (Table 1), the compounds obtained in this study
can be considered to be probable optical bleaches.
The essential s i m i l a r i t y between the reaetivities of the o-hydroxynitro derivatives of fluoranthene and
their analogs of the naphthalene s e r i e s has been demonstrated, and this is an additional confirmation of the
existence of an inhibiting interaction of the phenylene and naphthalene portions in the fluoranthene molecule
[2]. However, one should not understand this to mean a complete analogy between the reactivities of the
compounds being c o m p a r e d here; thus acylation of 2 - n i t r o - 3 - h y d r o x y f l u o r a n t h e n e (Ib), obtained by a known
method f r o m 2 - n i t r o - 3 - a m i n o f l u o r a n t h e n e (Ia) [3], proceeds most completely for its sodium salt (Ic), while
Ib itself is unstable under the conditions of the acylation of f i - n i t r o - a - n a p h t h o l [4]. The acylation of 2 - h y -
d r o x y - 3 - n i t r o f l u o r a n t h e n e (Ig) (the l a t t e r was obtained f r o m 2 - a c e t a m i d o - 3 - n i t r o f l u o r a n t h e n e (If) [5] under
conditions close to those in the synthesis of a - n i t r o - f l - n a p h t h o l [6])didnot r a i s e any special difficulties.
The different tendencies of Ib and Ig with r e s p e c t to acylation can probably be explained by s t e r i c shielding
of the hydroxyl group in Ig by the adjacent p e r i - o r i e n t e d 4-hydrogen atom and the nitro group.

! a-i Ila Ilia

I aRI=N02, R2=NH2; b RI=N02, R2=OH; cRI=NO2, R2=ONa; dR~=NO2, R~=OCOCHs;

e RI=NO2,R~=OCOC6Hs; f RI=NHCOCH3,R2=NQ; g RI=OH,R2=NO~;h RI=OCOCHa,
R2=NO2; i RI=OCOC~Hs,R2=NQ; II a Illa R3=CH3; II b, IIIbR3=C6Hs

2 - R - F l u o r a n t h e n o [ 2 , 3 - d ] - (IIa, b) and 2-R-fluorantheno[3,2-d]oxazoles (IIIa, b) were obtained in good

yields by prolonged refluxing of the appropriate acetates and benzoates (Ib and Ig) in acetic acid with zinc
according to the method in [7].
The IR s p e c t r a of Ha, b and Ilia, b contain c h a r a c t e r i s t i c absorption bands of the vibrations of the
benzoxazole ring and the stretching vibrations of the C - O - C bond in the benzoxazole ring at 1600-1610,
1550-1570, 1235, 1050-1060, and 925-930 c m -1 [8, 9]. The formation of an intramolecular hydrogen bond
of the chelate type between the hydroxyl group and the oxygen atom of the nitro group was noted in Ib and
Ig (a v e r y broad intense absorption band is found at 2500-3200 cm -1) [10].

Dnepropetrovsk Chemical Engineering Institute. Translated f r o m Khimiya Geterotsiklicheskikh

Soedinenii, No. 7, pp. 905-907, July, 1974. Original a r t i c l e submitted July 16, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher A copy o f this article is available from the publisher for $15.00.

788
 TABLE i. Data from UV Spectra
~'max,nm log s
Compound B' band s band p band B' band band p band

IIa 242 264, 274, 304", 314, 4,65 4,40, 4,48, 3,63, 3,65,
280, 292 320, 352, 4,47, 4,63 3,72, 3,86,
360 3,90
IIb 232 254, 268, 320, 338, 4,38 4,29. 4.18, 4,05, 4,03.
276, 304 344 4,23, 4,64 4,01
IIIa 240 258, 268, 306*, 312", 4.75 4,40, 4.41, 3,72, 3,82,
274, 284, 330, 356, 4,45, 4,56, 3,92, 3,92,
294 370 4,76 4,18
IIIb 234 270, 276, 326, 368, 4,57 4.10, 4,17, 4,42, 4,64.
310 385 4,62 4,40

* The noted ~ max values w e r e a s s i g n e d to the p bands a c c o r d i n g

to the magnitude of log ~.

T h r e e r e g i o n s of a b s o r p t i o n m a x i m a - 230-245, 250-310, and 315-390 n m (Table 1) - which, a c c o r d i n g

to the w e l l - k n o w n c l a s s i f i c a t i o n [11] for p o l y c y c l i c h y d r o c a r b o n s , p a r t i c u l a r l y for f l u o r a n t h e n e , should be
a s s i g n e d , r e s p e c t i v e l y , to the fi', fi, and p b a n d s , can be noted in the UV s p e c t r a of IIa, b and IIIa, b. The
UV s p e c t r a of IIa, b and IIIa, b r e t a i n the g e n e r a l f o r m of the UV s p e c t r u m of unsubstituted f l u o r a n t h e n e ;
in addition to this, one should note the b a t h o c h r o m i c shift of the m o s t intense fi bands in the s p e c t r a of IIb
and iIIb (304-310 nm) as c o m p a r e d with the s p e c t r a of Ita and IIIa (292 and 294 nm), w h i c h is c a u s e d by
l e n g t h e n i n g of the conjugation chain in IIb and IIIb; a s i m i l a r effect was noted for 2 - R - f l u o r a n t h e n o [8,9-d]-
o x a z o l e s [1].
In o r g a n i c s o l v e n t s ( c h l o r o f o r m , a c e t o n e , etc.) all of the f l u o r a n t h e n o o x a z o l e s obtained in this s t u d y
have blue f l u o r e s c e n c e in UV b e a m s , in c o n t r a s t to the s t a r t i n g c o m p o u n d s , which have g r e e n f l u o r e s c e n c e .

EXPERIMENTAL
The IR s p e c t r a of KBr p e l l e t s w e r e r e c o r d e d with a U R - 2 0 s p e c t r o m e t e r . The UV s p e c t r a of s o l u -
ttons in 95% ethanol (10 - t - 10 .5 m o l e / l i t e r ) w e r e r e c o r d e d with an S F - 4 s p e c t r o p h o t o m e t e r .
2 - N i t r o - 3 - h y d r o x y f l u o r a n t h e n e Sodium Salt (Ic). A m i x t u r e of a solution of 0.5 g (1.9 m m o l e ) of Ia
in 50 ml of ethanol and 42 ml (116 m m o l e ) of a 10% s o d i u m h y d r o x i d e solution was r e f l a x e d for 1 h, after
w h i c h the solution w a s f i l t e r e d , and the f i l t r a t e was c o o l e d to give 0.33 g (61%) of r e d n e e d l e s w t t h m p > 350 ~
Found: C 67.4; H 2.6; N 4.7%. C1GHsNaNO s. C a l c u l a t e d : C 67.3; H 2.8; N 4.9%.
2 - N t t r o - 3 - a c e t o x y f l u o r a n t h e n e (Id). A solution of 0.69 g (8.75 m m o l e ) of a c e t y l c h l o r i d e in 50 ml of
a c e t o n e was added with s t i r r i n g to a s u s p e n s i o n of 0.5 g (1.75 m m o l e ) of I c t n 75 ml of a c e t o n e , and the s o -
lution was s t i r r e d for 2 rain. It was then diluted with wa~/er and w o r k e d up to give 0.49 g (91%) of yellow
p l a t e s of Id with mp 170-171.5 ~ (dec., f r o m i s o p r o p y l alcohol). Found: C 71.0; H 3.5; N 4.4%. C/SH/tNO 4.
C a l c u l a t e d : C 70.8; H 3.6; N 4.6%.
2 - N t t r o - 3 - b e n z o x y f l u o r a n t h e n e (Ie). A 1.23-g (8.75 m m o l e ) s a m p l e of b e n z o y l c h l o r i d e was added
with s t i r r i n g to a s u s p e n s i o n of 0.5 g (1.75 m m o l e ) of Ic in 25 ml of p y r i d i n e , and the solution was heated
to 55-60 ~ It was then cooled, diluted with w a t e r , and w o r k e d up to give 0.58 g (91%) of long y e l l o w n e e d l e s
of Ie with mp 197-198 ~ (dec., f r o m n - b u t y l alcohol). Found: C 75.1; H 3.75; N 3.8%. C2sHlaNO 4. C a l c u -
lated, C 75.2; H 3.6; N 3.8%.
2 - H y d r o x y - 3 - n i t r o f l u o r a n t h e n e (Ig). A m i x t u r e of a solution of 1.22 g (4 m m o l e ) of If in 100 ml of
ethanol and 80 ml of a 10% s o d i u m h y d r o x i d e solution (220 m m o l e ) was r e f l a x e d for 6 h, a f t e r which the s o -
lution w a s f i l t e r e d , and the f i l t r a t e was n e u t r a l i z e d with c o n c e n t r a t e d h y d r o c h l o r i c acid to give 0.97 g (95%)
of fine y e l l o w n e e d l e s of Ig with mp 163-164 ~ (dec., f r o m a c e t i c acid). Found. C 73.2; H 3.55; N 5.2%.
C16HgNOa. C a l c u l a t e d : C 73.0; H 3.45; N 5.3%.
2 - A c e t o x y - 3 - n i t r o f l u o r a n t h e n e (Ih). A 3 . 0 6 - g (30 m m o l e ) s a m p l e of a c e t i c a n h y d r i d e was added with
s t i r r i n g to a solution of 1.3 g (5 m m o l e ) of Ig in 70 ml of p y r i d i n e , and the s o l u t i o n w a s heated to 55-60%
It w a s then cooled and diluted with w a t e r to give 1.42 g (94%) of long y e l l o w n e e d l e s of Ih with nap 173-174 ~
(from b e n z e n e - p e t r o l e u m ether). Found: C 70.9; H 3.55; N 4.45%. CI~-ItiNO 4. C a l c u l a t e d : C 70.8; H 3.6;
N 4.6%.

789
 2-Benzoxy-4-nitrofluoranthene (Ii). The procedure used to synthesize le was used to obtain this c o m -
pound in 92% yield from fg. The longyellow needles had m p 195-196 ~ (from aqueous acetic acid). Found: C 75.1;
H 3.8; N 3.75%. C2sHI3NO 4. Calculated: C 75.2; H 3.6; N 3.8%.
2-Methylfluorantheno[2,3-d]oxazole (IIa). A 0.8-g (12.3 mmole) sample of zinc dust was added to a
solution of 0.4 g (1.3 mmole) of Ig in 70 ml of acetic acid, and the mixture was reflaxed for 10 h. It was
then filtered, and the filtrate was cooled, diluted with water, and worked up to give a l i g h t - g r a y product,
which was chromatographed in c h l o r o f o r m on silica gel (5 g). Elution with c h l o r o f o r m gave a g r e e n band,
f r o m which 0.14 g (42%) of l i g h t - g r e e n fine needles of IIa, with mp "182.5-183.5 ~ (from aqueous ethanol), was
isolated. Found: C 84.15; H 4.2; N 5.5%. CisHllNO. Calculated: C 84.1; H 4.3; N 5.45%.
2-Phenylfluorantheno[2,3-d]oxazole (IIb). The p r o c e d u r e used to synthesize IIa was used to obtain
this compound f r o m Ie. Elution with c h l o r o f o r m gave a dark band, f r o m which IIb was isolated in 72% yield.
The l i g h t - g r a y fine needles had mp 192.5-193.5 ~ (from t o l u e n e - p e t r o l e u m ether), Found~ C 86.7; H 4.55;
N 4.27c. C23H13NO. Calculated: C 86.6; H 4.1; N 4.4%.
2- ~,~ethylfluorantheno [3,2-d]oxazole (IIIa). The p r o c e d u r e used to synthesize IIa was used to obtain
this compound f r o m lh in 60~ yield. The l i g h t - g r a y fine needles had mp 189-190 ~ (from carbon t e t r a c h l o -
ride). Found: C 84.0; H 4.4; N 5.6%. CIsHilNO. Calculated: C 84.1; H 4.3; N 5.45%.
2-Phenylfluorantheno[3,2-d]oxazole (IIIb). The p r o c e d u r e used to synthesize IIa was used to obtain
this compound f r o m Ii in 64% yield. The light r o s e - c o l o r e d fine needles had mp 206-207 ~ (from t o l u e n e -
p e t r o l e u m ether). Found: C 86.4; H 4.0; N 4.5%. C23H13NO. Calculated: C 86.6; H 4.1; N 4.4%.

LITERATURE CITED
1. M . I . Shenbor and V. I. Tikhonov, Khim. Geterotsikl. Soedin., 608 (1973).
2. G. Geuskens and I. Nasielski, Spectrochim. Acta, 166, 1416 (1960).
3. H . J . Andrew, N: Campbell, I. T. Graig, and K. I. Nichol, J. Chem. Soc., C14, 1761 (1968).
4. E. Grandmougin and O. Michel, B e r . , 25, 972 (1892).
5. E . H . Charlesworth and C. V. Lithown, Can. J. Chem., 47, 1595 (1969).
6. V. Hartmarm, Organic Synthesis, Vol. 13, (1933), p. 78.
7. W. BSttcher, B e r . , 16, 1933 (1883).
8. P. Bassignana, C. Cogrossi, and M. Gandino, Spectrochim. Acta, 19, 1885 (1963).
9. Y. Imai, I. Taoka, K. Uno, and Y. Iwakura, Macromol. Chem., 8__33,170 0965).
10. L. A. Kazitsyna and N, B. Kuplet-skaya, Applications of UV, IR, and NM:R Spectroscopy in Organic
C h e m i s t r y fin Russian], Vysshaya Shkola, Moscow (1971), p. 34.
11. E. Clar and I. F. Stephen. T e t r a h e d r o n , 200, 1559 (1964).

790
2 - A R Y L - 4 H - 3 , 1 - B E N Z O X A Z I N - 4 - O N ES

NITRATION

R. U. Safina and B. M. B o l o t i n UDC 547.867.2 : 542.958,1

2- (3-Nitrophenyl)-4H-3,1-benzoxaz in- 4-one is for med in the nitration of 2 - p h e n y l - 4 H - 3 , 1 -

b e n z o x a z i n - 4 - o n e , while 2 - ( 2 - t o s y l a m i n o - 5 - n i t r o p h e n y l ) - 4 H - 3 , 1 - b e n z o x a z i n - 4 - o n e is f o r m e d
in the nitration of 2 - ( 2 - t o s y l a m i n o p h e n y l ) - 4 H - 3 , 1 - b e n z o x a z i n - 4 - o n e .

No nitration products can be detected in the nitration of 2 - p h e n y l - 4 H - 3 , 1 - b e n z o x a z i n - 4 - o n e in dichlo-

roethane with a fourfold excess of fuming nitric acid. Only N-benzoylanthranilic acid, which is the product
of h y d r o l y s i s of the starting compound, is isolated f r o m the r e a c t i o n mixture. However, if the amount of
nitric acid is doubled, the chief r e a c t i o n product p r o v e s to be N - b e n z o y l - 5 - n i t r o a n t h r a n i l i c acid (path
a o r b):

.~CO0 H
o

b"~'--.. NOo 0

Path a s e e m s p r e f e r a b l e to us, for, as seen f r o m the fact p r e s e n t e d above, hydrolysis proceeds c o m -

pletely in those c a s e s where nitration does not occur. N - B e n z o y l - 5 - n i t r o a n t h r a n i l i c acid can be easily con-
v e r t e d to 6 - n i t r o - 2 - p h e n y l - 4 H - 3 . 1 - b e n z o x a z i n - 4 - o n e by heating with acetic anhydride.
The nitration p r o c e e d s completely differently in sulfuric acid. In this case, the chief r e a c t i o n p r o d -
uct is 2 - ( 3 - n i t r o p h e n y l ) - 4 H - 3 . 1 - b e n z o x a z i n - 4 - o n e . In addition, a small amount of N-(3-nitrobenzoyl)an-
thranilic acid is formed. The latter is probably obtained as a r e s u l t of h y d r o l y s i s of the a l r e a d y nitrated
benzoxazinone when the r e a c t i o n mixture is poured over ice. If in this case h y d r o l y s i s o c c u r r e d initially
followed by nitration, as in the nitration in dichloroethane, the final r e a c t i o n product should have been
N - b e n z o y l - 5 - n i t r o a n t h r a n i l i c acid r a t h e r than N-(3-nitrobenzoyl)anthranilic acid.
The e n t r y of the nitro group into the phenyl ring of 2 - p h e n y l - 4 H - 3 , 1 - b e n z o x a z i n - 4 - o n e indicates that
the electron density in the phenyl ring is higher than in the benzoxazinone portion of the molecule. In this
c a s e , the latter acts as an orienting group of the II type.
We accomplished the nitration of 2 - ( 2 - t o s y l a m i n o p h e n y l ) - 4 H - 3 , 1 - b e n z o x a z i n - 4 - o n e only in dichloro-
ethane, inasmuch as detosylation is possible in sulfuric acid [1]. 2 - ( 2 - T o s y l a m i n o - 5 - n i t r o p h e n y l ) - 4 H - 3 , 1 -
b e n z o x a z i n - 4 - o n e is f o r m e d in the nitration. In addition. N - ( 2 - t o s y l a m I n o - 5 - n i t r o b e n z o y l ) a n t h r a n i l i c acid
is detected in the r e a c t i o n mixture.
The p r e s e n c e of nitrated benzoxazinone in the r e a c t i o n products indicates that h y d r o l y s i s in the case
of o - t o s y l a m i n o - s u b s t i t u t e d 2 - p h e n y l - 4 H - 3 , 1 - b e n z o x a z i n - 4 - o n e is hindered and that there is time for n i t r a -
tion of the nonhydrolyzed benzoxazinone. In this case, the 5' position of the phenyl ring undergoes attack,
which is p r o m o t e d by the coordinated orientation of the t o s y l a m i n e group - an Orienting group of the I
type - and the benzoxazinone ring, which as we noted above is an orienting group of the II type.

All-Union S c i e n t i f i c - R e s e a r c h Institute of Chemical Reagents and E s p e c i a l l y P u r e Chemical Sub-

s t a n c e s , Moscow. T r a n s l a t e d f r o m Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 908-909, July, 1974.
Original article submitted June 21, 1973.

9 76 Plenum PublishhTg Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available front the publisher for $15.00.

791
 E X P E R I ME N T A L
2- ( 3 - N i t r o p h e n y l ) - 4 H - 3 , 1 - b e n z o x a z i n - 4 - o n e . A 0 . 5 - c m 3 (0.012 mole) s a m p l e of fuming nitric a c i d w a s
added at 15-20 ~ with vigorous s t i r r i n g in the c o u r s e of 15 min to a solution of 2.23 g (0.01 mole) of 2 - p h e n y l -
4 H - 3 , 1 - b e n z o x a z i n - 4 - o n e [2] in 7.5 c m 3 of c o n c e n t r a t e d sulfuric acid, a f t e r which the mixture was s t i r r e d
at the s a m e t e m p e r a t u r e for another hour. It was then poured into 150 g of c r u s h e d ice, and the r e s u l t i n g
p r e c i p i t a t e was r e m o v e d by filtration, washed to n e u t r a l i t y with w a t e r , dried, and r e c r y s t a l l i z e d f r o m acetic
anhydride (with decolorization by charcoal) to give 1.25 g (46%) of a product with mp 164.5-166 ~ The p r o d -
uct was identical to a s a m p l e of 2 - ( 3 - n i t r o p h e n y l ) - 4 H - 3 , 1 - b e n z o x a z i n - 4 - o n e s y n t h e s i z e d by the method in
[31.
2- ( 2 - T o s y l a m i n o - 5 - n i t r o p h e n y l ) - 4 H - 3 , 1 - b e n z o x a z i n - 4 - o n e . A 3 . 7 5 - c m 3 (0.09 mole) s a m p l e of fuming
nitric acid (sp. gr. 1.5) was added in the c o u r s e of an hour with vigorous s t i r r i n g at 70 ~ to a solution of 3.95
g (0.01 mole) of 2 - ( 2 - t o s y l a m i n o p h e n y l ) - 4 H - 3 , 1 - b e n z o x a z i n - 4 - o n e [4] in 50 c m 3 of dichloroethane, a f t e r
which the mixture was s t i r r e d for another 15 rain. It was then poured into 300 c m 3 of ice w a t e r , and the
organic l a y e r was s e p a r a t e d , washed with w a t e r , and dried o v e r c a l c i u m chloride. The dichloroethane was
r e m o v e d in vaeuo, and the r e s i d u a l solid product was c r y s t a l l i z e d f r o m acetic anhydride to give 1.5 g (34%)
of a product with mp 247-248 ~ The product was identical to a s a m p l e of 2 - ( 2 - t o s y l a m i n o - 5 - n i t r o p h e n y l -
4 H - 3 , 1 - b e n z o x a z i n - 4 - o n e s y n t h e s i z e d by the method in [5].

LITERATURE CITED

1. G. Schroeter and O. Eisleb, Ann., 367, 101 (1907).

2. B. I. Bain and R. K. Smalley, J. Chem. Soc., C, 1593 (1968).
3. M. T. Bogert, R. A. Gortl~er, and C. G. Amend, J. A m e r . Chem. Soc., 33, 951 (1911).
4. M. V. L o s e v a and B. M. Bolotin, Khim. G e t e r o t s i k l . Soedin., 1341 (1972).
5. M. V. L o s e v a , B. M. Bolotin, G. A. Bogdanova, and B. M. K r a s o v i t s k i i , Khim. Geterotsikl. Soedin.,
616 (1972).

792
MASS SPECTROMETRIC STUDY

OF 2- AND 4-SILALACTONES

V. N, Bochkarev, N. S. Fedotov, UDC 543.51 : 5 4 7 . 2 4 5 ' 8 ' 8 9 2 ' 8 9 6

I. G. Rybalka, and, Z. F. ?Jfironov

tn c o n t r a s t to the p r e v i o u s l y i n v e s t i g a t e d 1 - s i l a l a c t o n e s , e j e c t i o n of a CO 2 m o l e c u l e f r o m t h e
m o l e c u l a r ion is not c h a r a c t e r i s t i c in t h e d i s i n t e g r a t i o n of 2 - a n d 4 - s i l a l a e t o n e s u n d e r e l e c -
t r o n i m p a c t . M i g r a t i o n of t h e s i l i c o n a t o m to the o x y g e n a t o m d u r i n g f r a g m e n t a t i o n of t h e
2 - and 4 - s i l a l a c t o n e s w a s o b s e r v e d . The d e p e n d e n c e of t h e p a t h s of d i s i n t e g r a t i o n of the
s i l a l a e t o n e s on t h e r i n g s i z e a n d the n u m b e r of m e t h y l e n e l i n k s w a s e s t a b l i s h e d . The p o s -
s i b i l i t y of t h e i d e n t i f i c a t i o n o f i s o m e r i c 2 - s i l a l a c t o n e s on the b a s i s of t h e i r m a s s s p e c t r a
was observed.

We h a v e p r e v i o u s l y i n v e s t i g a t e d [1] the p a t h s of f r a g m e n t a t i o n of 1 - s i l a l a e t o n e s u n d e r e l e c t r o n i m -
p a c t . It s e e m e d of i n t e r e s t to a s c e r t a i n t h e e f f e c t of t h e i n t r o d u c t i o n of one o r s e v e r a l l i n k s b e t w e e n the
s i l i c o n a t o m a n d t h e e s t e r o x y g e n a t o m on the d i r e c t i o n of the m a s s - s p e c t r a l d i s i n t e g r a t i o n of s i l a l a c t o n e s
In o r d e r to a c h i e v e t h i s , w e i n v e s t i g a t e d the m a s s s p e c t r a of i s o m e r i c 2 - s i l a l a c t o n e s I a n d II, w h i c h d i f f e r
w i t h r e s p e c t to r i n g s i z e , and s i l a l a c t o n e HI.

CH2--O--CO CH2--O--CO (CH2) 3 O

l II Ill

The m o l e c u l a r ion p e a k s a r e p r a c t i c a l l y a b s e n t in the m a s s s p e c t r a of 1-Ili, but p e a k s of ( M - 1 ) + i o n s ,

t h e f o r m a t i o n of w h i c h is a s s o c i a t e d w i t h c~ c l e a v a g e w i t h r e s p e c t to the e s t e r o x y g e n a t o m , and p e a k s o f
(Td-CH3) + i o n s , w h i c h a r i s e a s a r e s u l t of e l i m i n a t i o n of a m e t h y l r a d i c a l f r o m t h e s i l i c o n a t o m , a r e o b -
s e r v e d in a l l c a s e s . The m a s s s p e c t r u m of s i x - m e m b e r e d 2 - s i l a l a c t o n e I d i f f e r s s h a r p l y f r o m t h e p r e -
v i o u s l y i n v e s t i g a t e d s p e c t r a of 1 - s i l a l a c t o n e s [1] w i t h r e s p e c t to the a b s e n c e of an ( M - C O 2 ) p e a k and the
p r e s e n c e of a m a x i m a l l y i n t e n s e p e a k of an ion w i t h m / e 88 ( s e e s c h e m e 1). The e j e c t i o n of a f o r m a l d e -
h y d e m o l e c u l e f r o m t h i s ion l e a d s to an ion w i t h a d i m e t h y l s i l e n e s t r u c t u r e w i t h m / e 58. The 88+--~58 +
t r a n s i t i o n is c o n f i r m e d b y t h e p r e s e n c e of a m e t a s t a b l e p e a k w i t h m* 38.8 ( c a l c u l a t e d v a l u e 38.2). A n ion
w i t h m / e 115, ( . ~ I - C H 3 - 2 8 ) +, is o b s e r v e d in the s p e c t r u m of I. I n a s m u c h a s it h a s b e e n s h o w n [1] t h a t the
e j e c t i o n of an e t h y l e n e m o l e c u l e is not c h a r a c t e r i s t i c for s i l a l a c t o n e s in w h i c h t h e s i l i c o n a t o m a n d the c a r -
b o n y l g r o u p a r e s e p a r a t e d b y two c a r b o n a t o m s , it c a n be a s s u m e d t h a t t h i s ion is f o r m e d a s a r e s u l t of

T A B L E 1. R e l a t i v e I n t e n s i t i e s (%) of the C h a r a c t e r i s t i c Ions in

the M a s s S p e c t r a of I s o m e r i c 2 - S i l a l a e t o n e s I and II

m/e 157 143 130 129 I I28 I15 113 100 88 85 75 72 58

7 ~ a7
74
15 5~ 100
36
22
32
27 lI
100
61
54

T r a n s l a t e d f r o m K h i m i y a G e t e r o t s i k l i c h e s k i k h S o e d i n e n i t , No. 7, pp. 910-912, J u l y , 1974. Original

a r t i c l e s u b m i t t e d J u n e 14, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

793
elimination of a CO molecule f r o m the (M-CH3) + ion (a p r o c e s s analogous to the ejection of SO during the
fragmentation of silasultines [2]).
Scheme 1

. . + . -H2CO (CHa):~ i +
(CH3)2SIOH
(CHs)~Si=Ctl~" (CH~)2SICII~O .~ --

role 72 mile 88 m/e 58 m/e 75

-cn3 (CHs)-"--]i--CrI-.--~H--CH3-tt" m/e 157 -CO

role 143 ~ CH2_O_C~ O ' ' " m/e 129

l-CO I, I~+"

m/el_H~CO
1'5 -CH2OCO ~

+ ! m/e 128
CUa--~--~CH 2 -OH; role 100
CH--CH2

The subsequent l o s s of a formaldehyde molecule leads to an ion with m / e 85. An ion with m / e 72 may a r i s e
as a r e s u l t of simple cleavage of two ring bonds in the molecular or fragment ions containir/g the
+
- (CH3)2SiCH2-group. The (Ctt3)2SiOH ion with m / e 75 is a r e a r r a n g e d ion. Migration of the distant silicon
atom to the oxygen atom was observed previously in the mass s p e c t r a of s[lacycloketones and in the mass
s p e c t r u m of methyl 4 - t r i m e t h y l s i l y l b u t y r a t e [4]. It is possible that s i m i l a r migration also o c c u r s during
the formation of the ion with m / e 128, (_~-H2CO) +. The paths of the formation and the m / e values of the
c h a r a c t e r i s t i c ions in the mass s p e c t r u m of I are p r e s e n t e d in scheme 1, while the relative intensities a r e
presented in Table 1.
The mass s p e c t r u m of II, which is an i s o m e r of silalactone I, contains peaks of two ions that are not
o b s e r v e d in the s p e c t r u m of I: the (M-CH3-H2CO) + ion with m / e 113, and an ion with m / e 130. The de-
velopment of the l a t t e r is due to the elimination of an ethylene molecule f r o m the molecular ion, which is
c h a r a c t e r i s t i c for compounds in which the carbonyl group and the silicon atom are separated by three meth-
ylene groups [1, 3]. It was shown that in this case the silicon atom m i g r a t e s to the carbonyl oxygen atom
(see scheme 2). The m / e values of the r e s t of the ions in the s p e c t r a of II and I are identical, but the r e l a -
tive intensities differ s h a r p l y (see Table 1).
The ion peak with m / e 72 in the s p e c t r u m of silalactone II is a maximum peak; this is explained by
the development of this ion f r o m the ion with m / e 130 as a r e s u l t of loss of the - C H 2 C O 2 - g r o u p.
Scheme 2
-H~CO
m,/e 113 role 88 ~ m/'~ 58 m/~ 75

_CH 3 9 _C.,H 4 /O~

m/e 1,13 ,.~-._ (CH3)o_Si(Ctl2)3~O -H., m/e 157 " ~ (CH3)2--S'i C-.=C||~
t I+
1 CIt~O

9 C2tt~ I_c2H. t

+/o\ "/O~--~H~ _ ". ml<, Ioo

('ltl~--O
:%_ i
CH:~--O
ni/C" tl5 I11,1~ 130 m/e 72

The s h a r p i n c r e a s e in the intensity of the ion with m / e 115 is a s s o c i a t e d with the possibility of ejection of
an ethylene molecule f r o m the (M-CH3) + ion with m / e 143. In this case, the silicon atom migrates to the
carbonyl oxygen [3]. The 130+--72 + and 143+--115 + transitions a r e confirmed by the p r e s e n c e of the c o r -
responding metastable peaks. The paths of formation and the m / e values of the c h a r a c t e r i s t i c ions in the
mass s p e c t r u m of II are presented in s c h e m e 2, while the relative intensities a r e presented in Table 1.
Ion peaks with m / e 185, 171, 158, 145, and 117 are o b s e r v e d in the mass s p e c t r u m of 4-silalactone
III. The s t r u c t u r e s of these ions and their relative intensities a r e p r e s e n t e d in s c h e m e 3.

794
 Scheme 3

~cuposi~cu.hcooH -c~"s ~.~-si(c,p~l zC~H~ j"-si-(cuao

nl/e 1.15 (16%) II
o o

c2H4 Ill, M +" IV, /~.t+" nl/e 144 17~)

c,o=c./~ \-cn~ "-..(

XO H nL/e 185 ll%~ \ x /C~2__
\ (CH3)~--Si ~H2
mid 117 121~ i--CHs ro/e 171 111%) +O CH~
'--~./o "--c. H6 li I -
o C;H,~--C--O
0 m/e 15S (14%)
rn/e 129

In addition, the spectrum of III contains peaks of all of the ions characteristic for the spectrum of l-silalac-
tone IV. These are the ion peaks with m/e 144 (7~), 143 (12%), 129 (36~), 116 (22%), i01 (100~c), I00 (5%),
75 (63~), 72 (19~). and 58 (3~), the structures and the paths of the formation of which were examined in [i].
We explain the similarity in the mass spectra of Ill and IV by the possibility of transannular interaction of
the ester oxygen atom with the silicon atom in the macrocyclie system of silalaetone Ill. Under the influ-
ence of electron impact, propylene is ejected from the molecular ion of Ill, and this leads to the develop-
ment of the molecular ion of l-sflalactone IV, as shown in scheme 3. Similar ejection from the (M-CH3) +
ion leads to an ion with m/e 129.
The mass spectra were recorded with an MKh-1303 spectrometer at 150 ~ and an ionizing voltage of
30V.

LITERATURE CITED
i. V. N. Bochkarev, N. S. Fedotov, I. G. Rybalka, and V. F. Mironov, Khim. Geterotsikl. Soedin. (in
press).
2. J. Dubac, P. Mazerolles, M. Joly, W. Kitching, C. W. Fong, and W. Atwele, J. Organomet. Chem.,
34. 17 (1972).
3. W. P. Weber, R. A. Felix, A. K. Wfllard, and H. G. Boettger, J. Org. Chem., 36, 4060 (1971).
4. W. P. Weber. R. A. Felix, and A. K. Willard, J. Amer. Chem. Soc., 92, 420 (1970).

795
STUDY OF THE FORMATION OF 2-SUBSTITUTED
3 a,4,6,6a-TETRAHYDROTHIENO [3,4-d]OXAZO LINES
FROM cis- AND trans-4-AMINO-3-
H YDROX YTHIOP HANS

S. D. Mikhno, T. M. Filippova, UDC 547.732.787

I. G. Razumova, N. S. Kulachkina,
I. K. S h m y r e v , a n d V. ~r B e r e z o v s k i i

The formation of 2-substituted 3a,4,6,6a-tetrahydrothieno [3,4-d]oxazolines f r o m N - a c y l -

substituted c i s - a n d t r a n s - 4 - a m i n o - 3 - h y d r o x y t h i o p h a n s in deuteroacetic acid and by the ac-
tion of thionyl chloride was studied. Only the derivatives of c i s - 4 - a m i n o - 3 - h y d r o x y t h i o -
phans are cyclized in deuteroacetic acid. The formation of an oxazoline ring f r o m 4 - a m i n o -
3-hydroxyth[ophan by the action of thionyl chloride depends both on the relative position of
the hydroxy and amino groups and on the c h a r a c t e r of the acyl substituent attached to the
amino group.

The inversion of t r a n s - 4 - b e n z a m i d o - 3 - h y d r o x y t h i o p h a n (Vb) to cis i s o m e r Va p r o c e e d s through the

for mat[on of 2 - p h e n y l - 3 a , 4 , 6 , 6 a - t e t r a h y d r o t h i e n o [3,4- d]oxazol ine (VI, R = C 6H5) [1].
It s e e m e d of interest to study the cyclization capacity of i s o m e r i c thiophanamino alcohols as a func-
tion of their cts and trans configuration and the c h a r a c t e r of the acyI substitnent attached to the amino
group. This was accomplished in the case of three i s o m e r i c p a i r s : 4 - a c e t a m i d o - (IIIa, b), 4 - u r e i d o -
(IVa, b) [1], and 4-benzamido-3-hydroxythiophans (Va, b) [1, 3].
The i s o m e r i c 4 - a c e t a m i d o - 3 - h y d r o x y t h i o p h a n s (Ilia, b) w e r e synthesized f r o m c i s - and t r a n s - 4 -
amino-3-hydroxythiophan hydrohalides (Ia, b) [1].
The action of acetyl chloride on hydrohalides Ia and l'b gave c i s - and t r a n s - 4 - a c e t a m i d o - 3 - a c e t o x y -
thiophans (IIa, b).

I a, b II a, b Ill a, b

|-III a eis isomers; b [tans isomers

These compounds w e r e hydrolyzed with 2 N sodium hydroxide solution to c [ s - and t r a n s - 4 - a e e t a m i d o -

3-hydroxythiophans (IIIa, b). Compound IIIa can be obtained directly f r o m h y d r o b r o m i d e Ia when the a c y l a -
tion time is reduced. The configuration of the substituent in Ha, b and IIIa, b was established, while the
configuration for IVa, b was confirmed f r o m the PM:R s p e c t r a (Tables 1 and 2) [3, 4].
The difference in the magnitudes of the chemical shifts between the geminal protons attached to C 5 is
substantially l a r g e r in the PMR s p e c t r a of lib-IVb than in the s p e c t r a of IIa-IVa (Table 1).

All-Union S c i e n t i f i c - R e s e a r c h Vitamin Institute, Moscow. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h -

eskikh Soedineni[, No. 7, pp. 913-917, July, 1974. Original a r t i c l e submitted November 22, 1972; r e v i s i o n
submitted October 25, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

796
 T A B L E 1. C h e m i c a l Shifts of t h e P r o t o n s of IIa, b - I V a , b *
Chemical shifts, 8, p p m

Isomer
o
type 2-H 2-H' 3-H 4-H 5-H 5-H' ~
~v NH COCH3 Solvent
o

cis (a) 3,21 3,00 5,66 4,92 3,19 3,04 0,15 1,93 2,02
II trans (b) 3,27[ 2,931 5,60 [ 4,89 13,3212,88~0,44 8,65 1,95 2,02 C~D~N
cis (a) 3,17 / 3,02 4,51--4,9914,51--4,99/3,1313,13 0 8,42 2,04
III trans (b) 3,201 3,99 4,63--5,I1 4,63--5,tl 3,45 2,8510,6218,50] 2,04 CsDsN
cis (a) 3,01 2,68 3,90 I 4,60 /2,98 2,71 0,271 I
IV ] trans (b) 3,06 2,76 4,00--4,50 3,20 2,62 0,58 CD3COOD

* The p a r a m e t e r s of the P M R s p e c t r a of IIa, b w e r e c a l c u l a t e d

w i t h a Y i n s k - 2 2 c o m p u t e r f r o m an i t e r a t i o n p r o g r a m .

T A B L E 2. S p i n - S p i n C o u p l i n g C o n s t a n t s of I I a , b - I V a , b
Corn- Spin-spin coupling constants, J, Hz

IIa 12,1 4,6 2,4 3,9 7,0 9,9 10,3 7,9

ilb 12,0 5,2 3,2 3,9 5,9 , 3,8 11,2 7,3
Ilia 11,4 3,8 2,3 3,7 E/4,s = 16,2 8.7
Illb 10,8 4,2 3,9 5,I I 4,0 10,8
IVa 12,0 5,2 2,6 6,7 9,0 10,6
IVb 11,6 4,2 3.6 5,1 3,8 11,3

T h e v i c i n a l s p i n - s p i n c o u p l i n g c o n s t a n t s f o r I I b - I V b a r e r e l a t i v e l y c l o s e in m a g n i t u d e ( 3 . 2 - 5 . 9 Hz,
T a b l e 2). w h i l e t h o s e f o r I I a - I V a a r e c h a r a c t e r i z e d b y a b r o a d r a n g e ( f r o m 2.3 to 9.9 I I z , T a b l e 2).
The a b o v e - d e s c r i b e d c h a r a c t e r i s t i c p e c u l i a r i t i e s of the PM:R s p e c t r a of the i n v e s t i g a t e d c o m p o u n d s
m a k e it p o s s i b l e to a s s i g n i s o m e r s I I b - I V b to t h e t r a n s s e r i e s and i s o m e r s I I a - I V a to the c i s s e r i e s .

The i n t r a m o l e c u l a r c y c l i z a t i o n of I l i a , b - V a , b w a s s t u d i e d in d e u t e r o a c e t i c a c i d a n d in t h e p r e s e n c e
of t h i o n y l c h l o r i d e , i . e . , u n d e r c o n d i t i o n s w h e r e i n v e r s i o n is p o s s i b l e d u r i n g t h e f o r m a t i o n of t h e o x a z o l i n e
r i n g s [5, 6]. The c o u r s e of the r e a c t i o n w a s m o n i t o r e d b y m e a n s of P_MR s p e c t r o s c o p y .
The p e r c e n t a g e s of t h e o x a z o l i n e s w e r e d e t e r m i n e d f r o m the r a t i o of t h e i n t e g r a l i n t e n s i t i e s of the
s i g n a l s of t h e p r o t o n s a t t a c h e d to C3a and C6a of t h e o x a z o l i n e d e r i v a t i v e s (Table 3) a n d the p r o t o n s a t t a c h e d
to C 3 and C t of the s t a r t i n g c o m p o u n d s (Table 1).
We h a v e s h o w n t h a t o n l y c i s - a m i n o a l c o h o l s I l I a - V a f o r m 2 - s u b s t i t u t e d 3 a , 4 , 6 , 6 a - t e t r a h y d r o t h i e n o -
[ 3 . 4 - d ] o x a z o l i n e s (VI-VIII) on h e a t i n g in d e u t e r o a c e t i c a c i d , w h i l e t r a n s - a m i n o a l c o h o l s I I I b - V b a r e a c e t y l -
a t e d a t the h y d r o x y l g r o u p u n d e r the s a m e c o n d i t i o n s to g i v e 3 - a c e t o x y t h i o p h a n s IIb, IXb, a n d Xb.
R
I
A
R CO N tl oH N/// 0 RCONH OH R.CONII OCOCH3

III-V a VI-VIII Ill-V b lib, I x b , x b

11,111, Vl R=Ctf3; IV, VII, IX R=NH2;V, VIII,X R=C~H 5

In the c a s e of I I I a - V a , s i g n a l s c h a r a c t e r i s t i c f o r p r o t o n s a t t a c h e d to C3a and C~a of the 2 - s u b s t i t u t e d

3 a , 4 , 6 , 6 a - t e t r a h y d r o t h i e n o [ 3 , 4 - d ] o x a z o l i n e s w e r e o b s e r v e d in the PlVIR s p e c t r a of the r e a c t i o n m i x t u r e s . It
s h o u l d be n o t e d t h a t a l l of the s u b s t i t u t e d o x a z o l i n e s f o r m e d in t h e s e r e a c t i o n s (VI-VIII) h a v e e i s f u s i o n of
t h e t h i o p h a n a n d o x a z o l i n e r i n g s , a s e v i d e n c e d b y t h e v i c i n a l s p i n - s p i n c o u p l i n g c o n s t a n t s [2, 3].
The d e p e n d e n c e of t h e a m o u n t of o x a z o l i n e d e r i v a t i v e VII f o r m e d on t h e r e a c t i o n t i m e in t h e e y c l i z a -
t i o n is shown in F i g . 1 ( c u r v e 1). The f i r s t o b s e r v a b l e c o n v e r s i o n p r o d u c t f o r s t a r t i n g a m i n o a l c o h o l s I I I a
a n d Va is a l s o a 2 - s u b s t i t u t e d o x a z o l i n e . H o w e v e r , s i g n a l s of the p r o t o n s o f the c i s - 4 - a e e t a m i d o - (IIa) and
c i s - 4 - b e n z a m i d o - 3 - a c e t o x y t h i o p h a n s u b s e q u e n t l y a p p e a r in the P M:R s p e c t r a of t h e r e a c t i o n m i x t u r e . In
the c a s e of I I I a , d i a c e t y l d e r i v a t i v e Ha r e m a i n s p r a c t i c a l l y t h e o n l y p r o d u c t of c o n v e r s i o n a f t e r r e f l u x i n g
f o r 16 h in d e u t e r o a c e t i c a c i d . Q u a n t i t a t i v e e v a l u a t i o n s of t h e p e r c e n t a g e of I I a a s a f u n c t i o h of t h e r e a c t i o n

797
 TABLE 3. P a r a m e t e r s of the PMR Spectra of VI-VIII
Spin-spin coupling
3a-HChemical4_H
4-H'shif' 6, ppm constants, J, HZ
Com-
pound
Solvent
6-H 6-H' 6a-H 4-H - ' 6a-6H

SOCI2 5,28 2,87--3,62 2,87--3,62 5,91 N1 ] 5,7 7,5 ] 4,4

VI CD3COOD 5,03 5,64 I EJ~a--4 6,3 7,5 5,4
VII CD3COOD 4,54 5,28 [ Y'/3a--, 8,4 6,9 5,6
CDCI3 5,58 3,53 3,22 3,29 3,29 6,21 0,5 " 5,0 7,5 5,0
VIII CD3COOD 5,16 2,73--3,40 2,78--3,40 5,52 Z/3a-4 7,3 7,5 5,1

C,%1
IOC~
I
90

/
0 2 4 6 8 10 12 14 16 18 20 22 24 26 "~ h

Fig. 1. Change in the concentration of the r e a c t i o n p r o d -

ucts f o r m e d f r o m amino alcohols IVa and Va (c i ~_,/[)as a
function of the refluxing time in deuteroacetic acid: 1)
change in the concentration of the oxazoline derivative VII
f o r m e d f r o m IVa; 2) change in the concentration of oxazoline
derivative VIII f o r m e d f r o m Va; 3) change in the c o n c e n t r a -
tion of the product of acetylation at the hydroxyl group ob-
tained f r o m VIII (the mean square deviations a r e shown by
the a r r o w s near each point).

time a r e impossible because of overlapping of the o b s e r v e d signals in the P_MR s p e c t r a of the r e a c t i o n mix-
tures, The curves showing the change in the concentration of the r e a c t i o n products as a function of time for
Va are p r e s e n t e d in Fig. 1 (curves 2 and 3).
Thus t r a n s - a m [ n o alcohols IIIb-Vb do not undergo inversion to the cis configuration on heating in deu-
t e r o a c e t i c acid, and oxazoline derivatives t h e r e f o r e cannot be formed. The substituent attached to the
amino group affects the o c c u r r e n c e of intramolecular cyclization r e a c t i o n s . We have p r e v i o u s l y shown that
VIII is f o r m e d f r o m Va, b by the action of thionyl chloride [2]. The r e a c t i o n for the t r a n s i s o m e r proceeds
with inversion to the cts configuration.
Under the same conditions we were able to o b s e r v e the formation of oxazoline derivative VI f r o m IIIb
in the PMR spectra. One hour after the s t a r t of the reaction, starting amino alcohol HIb was p r a c t i c a l l y
completely converted to oxazoline VI. Just as in the case of Vb, inversion to the cis configuration o c c u r s
in this case during the formation of oxazoline VI. However, we were unable to isolate this compound f r o m
solution, inasmuch as it is apparently unstable and undergoes ring opening and hydrolysis during isolation.
As a r e s u l t , we obtained the known c i s - 4 - a m i n o - 3 - h y d r o x y t h i o p h a n hydrochloride (Ia) [1].
Compounds Ilia and IVa, b proved to be incapable of undergoing i n t r a m o l e c u l a r cyclization under these
conditions.
Thus the formation of the oxazoline ring during the action of thtonyl chloride depends on the config-
uration of the substituents of the starting amino alcohol and on the c h a r a c t e r of the substituent attached to
the amino group. This s o r t of dependence can be explained if it is a s s u m e d that the intermediates in the
formation of oxazolines f r o m amino alcohols by the action of thionyl chlorode a r e the c i s - l - a m i n o - 2 - c h l o r o
derivatives [6], inasmuch as the relative position of the amino and hydroxyl group and the substituent at-
tached to the amino group determine the type of substitution of the hydroxyl group by halogen [7, 8].

798
 EXPERIMENTAL
The PM_R spectra were recorded with a Hitachi R-20A spectrometer (60 MHz). Tetramethylsilane
was used as the internal standard. The chemical shifts of the protons attached to C 3 and C 4 of the thiophan
ring in the spectra of the 3,4-substituted thiophans and the chemical shifts of the protons attached to C3a
and CGa in the spectra of the oxazoline derivatives were calculated as the centers of the corresponding mul-
tiplets. The corresponding AB systems were isolated and calculated in order to determine the chemical
shifts of the g~minal protons of the thiophan ring. Proton-magnetic double resonance was used in the anal-
ysis of the spectra.

cis-4-Acetamido-3-acetoxythiophan (iIa). A 6-ml sample of pyridine was added to 4 g (20 mmole) of

la [i], and the mixture was stirred at 50-60 ~ for 30 rain. It was then cooled, and i0 ml of chloroform was
added. A 4-ml (41 mmole) sample of aeetyl chloride was added at 0 ~ and the mixture was stirred ~t
18-20 ~ for 2 h. Water (20 rnl) was added, and the mixture was extracted with chloroform. The solvent was
removed in vacuo, 2 ml of alcohol was added to the residue, and the mixture was held at 0 ~ for 18-20 h.
The resulting precipitate was separated to give 2,4 g (59e/c) of colorless prisms with mp 131-132 ~ (from al-
cohol). Found: C 47.2; H 6.4; N 6.8~. ClsHI3NO3S. Calculated: C 47.2; H 6.4; N 6.9~c.
trans-4-Acetamido-3-aeetox3;thiophan (Hb) o Under conditions similar to those used to synthesize IIa
1.85 g (88%) of colorless needles of lib with mp 94.5-95 ~ was obtained from 3.2 g (19.6 mmole) of Ib [I] and
3.46 ml (20.2 mmole) of acetyl chloride. Found: C 47.2; H 6.4; N 6.4%. CIsHI~NO3S. Calculated: C 47.2;
H 6.4; N 6.8%.
eis-4-Acetamido-3-hydroxythiophan (IHa). A) A 5-ml sample of 2 N sodium hydroxide solution was
added to a solution of 1 g (4.9 mmole) of lla in 16 ml of alcohol, and the mixture was refluxed for 25 min.
It was then cooled and extracted with chloroform. The chloroform was removed to give 0.52 g (64%) of
colorless plates of Illa with mp 164-164.5 ~ (from alcohol). Found: C 44.6; H 6.6; N 8.5%. C~HIINO2S. Cal-
culated: C 44.7; H 6.9; N 8.7~.
B) A 6-ml sample of pyridine was added to 28 g (14 mmole) of I~, and the mixture was stirred at 50-
60 ~ for 30 min. It was then cooled,.and 15 ml of chloroform was added. A 3-ml (31 mmole) sample of
acetyl chloride was added at 0 deg. and the mixture was stirred at 18-20 ~ for 30 min. Water (I0 ml) was
added, and the mixture was extracted with chloroform. The chloroform extracts were washed with 2 N hy-
drochloric acid and water, the chloroform was removed, and 1 rnl of alcohol was added to the residue, The
resulting precipitate was separated to give 0.7 g (31c/c) of a product with mp 164-164.5 ~ (from alcohol). No
melting-point depression was observed for a mixture of this product with the compound obtained by method
A.
trans-4-Aeetamido-3-hydroxythiophan (IIlb). A 6.5-ml sample of 0.5 N sodium hydroxide solution was
added to a solution of 1.4 g (7 mmole) of Ilb in i0 ml of alcohol, and the mixture was refluxed for 20 min.
It was then cooled and extracted with chloroform. The chloroform was removed, 1 ml of alcohol was added
to the residue, and the mixture was held at 0 deg for 12-16 h. The resulting precipitate was separated to
give 0.84 g (76%) of colorless pris ms with mp 107.5-108 ~ (from alcohol). Found: C 4406;H 6.7; N 8.3%.
C~HIINO2S. Calculated: C 44.7; H 6.9; N 8.7%.
cis-4-Amino-3-hydroxythiophan Hydrochloride (In). A 0.4-ml (7 mmole) sample of thionyl chloride
was added at 0 deg to a solution of 1 g (6.2 mmole) of Illb in 5 ml of chloroform, and the mixture was
stirred at 18-20 ~ for 1 h. It was then concentrated in vacuo to dryness, and 1.5 rnl of alcohol was added to
the residue. The mixture was held at 0 deg for 12-16 h, and the resulting precipitate was removed by fil-
tration to give 0.76 g (79~) of a product with mp 206-207 ~ No melting-point depression was observed for
a mixture of this product with a known sample of la [1].

LITERATURE CITED

1, S. D. Mikhno, N. S. Kulachkina, T. N. P o l y a n s k a y a , L. B. Stepina, and V. M. B e r e z o v s k i i , Khim. G e t -

erotsikl. Soedin., 1609 (1970).
2. S. D. Mikhno, T. M. Filippova, N. S. Kulachkina, T. N. P o l y a n s k a y a , I. ~ . Kustanovich, and V. M.
B e r e z o v s k i i , Khim. G e t e r o t s i k l . Soedln., 1339 (1971).
3. S. D. Mikhno, T. M. Filippova, N. S. Kulachkina, T. N. P o l y a n s k a y a , V. V. Mishchenko, I. K~
I. M. Kustanovich, and V. M. B e r e z o v s k i i , Khim. G e t e r o t s i l d . Soedin., 760 (1972).
4. T. M. Filippova, S. D . . ~ i k h n o , N. S. Kulaehkina, I. M. Kustanovich, and V. M. B e r e z o v s k i i , Khim.
Geterotsild. Soedin., 316 (1971).

799
5. ]~. M. Bamdass, E. I. V[nogradov, D. P. V[tkovent, A. S. Khokhlov, Yu. B. Shvetsov, and L. A. Shchuk-
iaa, Dokl. Akad. Nauk SSSR, 79, 60 (195D.
6. T. A. Fogl[a and D. Swern, J. Org. Chem., 34, 1680 (1969).
7. S. H. Pines and M. A. Koslowski, J. Org. Chem., 37, 292 (1972).
8. S. H. Pines and ~. A. Koslowski, J. Org. Chem., 34, 1621 (1969).

800
TRANSMISSION OF THE ELECTRONIC EFFECTS
OF SUBSTITUENTS ]BY THE THIOPHENE RING

L. P. Pivovarevich, L. A. Kutulya, UDC 543.422.4 : 547.732.04

Yu. N. Surov, S. V. Tsukerman,
and V. F. Lavrushin

The shifts in the frequencies of the stretching vibrations of the hydroxyl group of phenol and
pentachlorophenol that a r i s e during the formation of hydrogen bonds with a number of sub-
stituted acetophenones and 2-acetylthiophenes, 2-acetylfuran, and 2-acetylselenophene and
the frequencies of the s t r e t c h i n g vibrations of the carbonyl group of the latter were subjected
to a c o r r e l a t i o n analysis (with the Hammett, Brown, Taft, Y u k a w a - T s u n o , and S w a i n - L u p t o n
equations), and it was shown that the thiophene r i n g in the investigated molecules in both the
static state and during the formation of H complexes t r a n s m i t s the conjugation effects better
than the benzene ring.

The p r o b l e m of the t r a n s m i s s i o n of electronic effects by f i v e - m e m b e r e d h e t e r o c y c l i c s y s t e m s - fu-

ran, thiophene, and selenophene - has r e c e n t l y been a t t r a c t i n g a g r e a t deal of attention [1, 4]. As far as
the thiophene ring is concerned, the information on its conductivity is quite contradictory. Thus, for ex-
ample, the investigators in [2-4] concluded that the latter t r a n s m i t s substttuent effects better than benzene,
whereas Marino [1] p r e s e n t s c o n t r a d i c t o r y data. We have p r e v i o u s l y investigated the p r o t o n - a c c e p t o r c a -
pacity of 2-acetylthiophene derivatives and s o m e of its analogs in aqueous sulfuric acid solution [5, 6] and
showed that the thiophene s y s t e m is a better conductor of electronic substituent effects, p a r t i c u l a r l y direct
polar conjugation, than the benzene ring. It was of interest to a s c e r t a i n whether this principle is c h a r a c -
t e r i s t i c only for protonation of h e t e t o a r o m a t i c methyl ketones in strongly acidic media o r whether it also holds
for other p r o c e s s e s in which they participate. This compelled us to investigate the p r o t o n - a c c e p t o r c a p a c -
ity of substituted acetophenones and 2-acetylthiophenes (see Table 1) during the formation of H complexes
with phenol and a more acidic proton donor - pentachlorophenol. For the c h a r a c t e r i s t i c s of the hydrogen
bond we used the shifts in the frequencies of the s t r e t c h i n g vibrations of the hydroxyl group of the indicated
p r o t o n - d o n o r compounds (A~OH) that o c c u r during interaction with the caxbonyl group of the methyl ke-
tches. In addition, we m e a s u r e d the frequencies of the stretching vibrations of the carbonyl group (vCO) of
the investigated compounds in carbon t e t r a c h l o r i d e solutions in o r d e r to obtain information r e g a r d i n g t r a n s -
missiou of the electronic subst[tuent effects in the benzene and thiophene s y s t e m s in the static state.
The experimental data are presented in Table 1. The AvOH values obtained for the H complexes of
ketones with pentachlorophenol a r e substantially l a r g e r than for the c o r r e s p o n d i n g complexes of phenol;
this is a consequence of the formation of a stronger bonds when a more acidic proton donor is used [I0].
It is apparent from Table 1 that when the benzene ring in acetophenone is replaced by a selenophene
or furan ring the AuOH values of the H complexes, which characterize their strengths, increase (compare I,
X-XII, and XXIH), while the AVOH values for 2-acetylthiophene (XI) differ only slightly from the values for
acetophenone (1). It follows from this that the electron-donor effect of the investigated hetaryl compounds
increases in the order: phenyl ~ thienyl < selenienyl < furyl. The same dependence was noted previously in
an investigation of the hydrogen bonds of c~,fi-unsaturated ketones containing these groupings [i0].

A. M. G o r ' k i i K h a r k o v State University. T r a n s l a t e d f r o m Khimiya Geterotsiklicheskikh Soedinenii,

No. 7, pp. 918-923, July 1974. Original a r t i c l e submitted July 10, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

801
 T A B L E 1. D a t a f r o m the IIR S p e c t r a of H e t e r o a r o m a t i c M e t h y l K e t o n e s
a n d T h e i r H C o m p l e x e s with P h e n o l a n d P e n t a c h l o r o p h e n o l
nhenol A. PCP*
No. Compound AV~H , vOH , Vco, cm -I
cm -1 0i22 "! =

I C6HsCOCH3 197 261 1691,1 T

II 4-CHaC~H4COCHa 207 279 1687,4 T
llI 4-C (CHa)~C~H4COCHa 214 283
IV
V
4-C~HsC6H4COCI-I~
4-CHaOC6H4COCH3
197
220
262
314
l~,a,
1683,1 T
VI 4-C2HsOCsH4COCHa 220 313
VII 4-CIC6H4COCHa 176 236 16~,81.
VIII 4-BrCsH4COCHa 177 249 1693,2 t"
IX 4-NO2CsH4COCt-I~ 138 1700,5I"
X 3-NO2C6H4COCHa 143 1700,71.
XI C4HaSCOCH~ 196 264 1672,2$
XII 5-CH~C4H~SCOCHa 208 27O 1668,0
XIII 5-C~HsC4H2SCOCHa 210 29t 1666,6
XIV 5-CH3OC4H~SCOCH3 232 337 1660,0
XV 5-C6HsC4H2SCOCHa 203 289 1669,0
XVI 5-CIC4H=SCOCH3 186 250 1683,0
XVII 5-BrC4H2SCOCHa 183 232 1675,0
XVIII 4-BrC4HeSCOCHa 174 236 1678,0
XlX 5-IC4HeSCOCHa 182 253 1675,0
XX 5-NO=C4H=SCOCHa 125 1688,0
XXI 4-NO=C4H~SCOCHa 114 1687,0
XXII C4HaOCOCHa 214 285 1687,5:[:
XXIII C~HaSeCOCHa 201 273 1666,0

* A v a l u e of 3592 c m -1 w a s a s s u m e d for v O H of t h e f r e e h y d r o x y l g r o u p
of p e n t a c h l o r o p h e n o l (PCP) in c o n f o r m i t y with [7].
* The v CO v a l u e s w e r e t a k e n f r o m [8].
$ The v CO v a l u e s w e r e t a k e n f r o m [9].

In an i n v e s t i g a t i o n of the f r e q u e n c i e s of t h e s t r e t c h i n g v i b r a t i o n s of the c a r b o n y l g r o u p s of m e t h y l k e -
t o n e s , the h e t e r o c y c l i c g r o u p i n g s a r e a r r a n g e d in a d i f f e r e n t s e q u e n c e w i t h r e s p e c t to t h e i r e f f e c t t h a n t h a t
n o t e d f o r the exvOH v a l u e s " p h e n y l < f u r y l < t h i e n y l < s e l e n i e n y l . H o w e v e r , t h i s is in a g r e e m e n t w i t h a n a l -
ogous d a t a for h e t e r o c y c l i c a n a l o g s of c h a l c o n e s [10]. This is a p p a r e n t l y a s s o c i a t e d w i t h the f a c t t h a t o t h e r
f a c t o r s , for e x a m p l e , the r e d u c e d m a s s , d i f f e r e n c e s in c o n f o r m a t i o n [11-14], e t c . , in a d d i t i o n to the e l e c -
t r o n i c e f f e c t s o f t h e g r o u p s a f f e c t t h e v C O v a l u e s of m e t h y l k e t o n e s ; a t t e n t i o n w a s d r a w n to t h i s in [15].
The e f f e c t of v a r i o u s s u b s t i t u e n t s in the a c e t o p h e n o n e s a n d 2 - a c e t y l t h i o p h e n e s on the s p e c t r o s c o p i c
c h a r a c t e r i s t i c s of t h e i n v e s t i g a t e d c o m p o u n d s and t h e H c o m p l e x e s c o r r e s p o n d s to t h e i r e l e c t r o n i c n a t u r e :
e l e c t r o n - d o n o r s u b s t i t u e n t s i n c r e a s e t h e p r o t o n - a c c e p t o r c a p a c i t y of k e t o n e s d u r i n g t h e f o r m a t i o n of h y d r o -
gen b o n d s and l o w e r the v CO v a l u e s , w h i l e e l e c t r o n - a c c e p t o r s u b s t i t u e n t s b r i n g a b o u t a n i n c r e a s e in the
v C O v a l u e s a n d a d e c r e a s e in the A v O H v a l u e s . The s o m e w h a t a n o m a l o u s b e h a v i o r of n i t r o d e r i v a t i v e s of
2 - a c e t y l t h i o p h e n e in the r e a c t i o n to f o r m H c o m p l e x e s w i t h p h e n o l w a s p r e v i o u s l y d i s c u s s e d in [16].
In o r d e r to e v a l u a t e the e f f e c t i v e n e s s of the t r a n s m i s s i o n of e l e c t r o n i c s u b s t i t u e n t e f f e c t s b y t h i o p h e n e
and b e n z e n e r i n g s , we p e r f o r m e d a c o r r e l a t i o n a n a l y s i s of the H a m m e t t , B r o w n , and T a f t e q u a t i o n s [17] and
a l s o of t h e t w o - p a r a m e t e r e q u a t i o n s o f t h e Y u k a w a - T s u n o [ 1 7 ] and S w a i n - L u p t e n [18] type. The r e s u l t s o b -
t a i n e d a r e p r e s e n t e d in T a b l e s 2 and 3.
It is a p p a r e n t f r o m T a b l e 2 t h a t the AVOH v a l u e s of p h e n o l in t h e s e r i e s of a c e t o p h e n o n e s c o r r e l a t e
b e s t of a l l w i t h the H a m m e t t o- c o n s t a n t s ( k = 0 . 9 9 5 ) . The s u b s t i t u e n t e f f e c t in t h i s s y s t e m is p r o b a b l y t r a n s -
m i t t e d p r i m a r i l y v i a an i n d u c t i o n m e c h a n i s m ; t h i s is c o n f i r m e d b y t h e g o o d c o r r e l a t i o n w i t h the cr ~ p a r a m -
e t e r s (k= 0.983). The c o r r e l a t i o n c o e f f i c i e n t w i t h the cr + p a r a m e t e r s is h i g h e s t for 2 - a c e t y l t h i o p h e n e s , and
e f f e c t s of d i r e c t p o l a r c o n j u g a t i o n of the s u b s t i t u e n t s with t h e r e a c t i o n c e n t e r c o n s e q u e n t l y p l a y a l a r g e r o l e
in t h i s c a s e , w h i l e the cr ~ v a l u e s p o o r l y c h a r a c t e r i z e the e f f e c t of s u b s t i t u e n t s on the r e a c t i v i t y of t h i o p h e n e
d e r i v a t i v e s (k = O. 909).
The r e a c t i o n c o n s t a n t s (m), w h i c h c h a r a c t e r i z e t h e s e n s i t i v i t y of the s y s t e m s to t h e e l e c t r o n i c e f f e c t s
of s u b s t i t u e n t s ( H a m m e t t a n d B r o w n e q u a t i o n s ) d u r i n g c o r r e l a t i o n of AVOH of p h e n o l a r e p r a c t i c a l l y i d e n -
t i c a l f o r a c e t o p h e n o n e and 2 - a c e t y l t h i o p h e n e d e r i v a t i v e s ; t h u s d i f f e r e n c e s in the t r a n s m i s s i o n of the e l e c -
t r o n i c e f f e c t s b y b e n z e n e a n d t h i o p h e n e r i n g s axe not m a n i f e s t e d in t h i s c a s e .
In t h e s e r i e s of H c o m p l e x e s w i t h p e n t a c h l o r o p h e n o l , t h e c o r r e l a t i o n c o e f f i c i e n t s axe l o w e r w i t h r e -
s p e c t to the o n e - p a r a m e t e r e q u a t i o n s t h a n in t h e p r e c e d i n g s e r i e s ; t h i s is a p p a r e n t l y a s s o c i a t e d w i t h t h e

802
 I "0

d
0
0

0
0 0
0
0"
0
g 0
0

r/2

0 o o o o o o

m
c~
o" ~2
0

++oNoN
x~ m%'7 I~ 1 m ~
1
-F 4 - ~ o~'~ ~
~c-n"l I I I

II tlli II II II [I I! II
0 11 II II II 11 II
m 0

ECD ~ o o o

E~
'~.~
c~

o
m e~
.,,,~

co

| =
o ~ 0 0 ~ 0 0 0
~ M M ~ M

I r.~ m
o~
.~ <

0 u.,
0 <
.o ~ g
d d d d d d d d d

~
o
r..)
m
~ ~m
o ~ ~ 2 4 7 o
4~
~247247 g~ .E

~ol I I I
[I II II II II II II II II
d I1 II I[ U II II

803
considerable effect of s t e r i c hindrance on the formation with it of a hydrogen bond because of the p r e s e n c e
in the ortho, ortho' positions relative to the hydroxyl group of bulky chlorine atoms. This effect is un-
doubtedly manifested more for 2-acetylthiophenes, which exist p r i m a r i l y as syn c o n f o r m e r s [11, 19] (the
carbonyl group and the ring h e t e r o a t o m a r e situated on one side of the bond connecting them). Moreover,
one cannot exclude the possibility that substituents of different electron nature have a certain effect on the
conformational state of the thiophene compounds and, consequently, on the degree of s t e r i c hindrance in
the H complexes. However, these c i r c u m s t a n c e s should not substantially interfere with the c h a r a c t e r i s t i c s
of the relative t r a n s m i s s i o n s of the benzene and thiophene s y s t e m s .
Judging f r o m the c o r r e l a t i o n coefficients, the undoubtedly great role of effects of direct polar conju-
gation is noticeable in the formation of the hydrogen bond of ketches with pentachlorophenol. In addition,
inasmuch as pentachlorophenol f o r m s s t r o n g e r hydrogen bonds than phenol, a difference is displayed in the
susceptibility to electronic effects in the benzene and thiophene r i n g s , and this difference is p a r t i c u l a r l y
distinct in the c o r r e l a t i o n with the cr+ p a r a m e t e r s (mT+> mB +) and the magnitude of the t r a n s m i s s i o n fac-
tor (~/= m T + / m B + = 1.17).
Correlation analyses with the use of the t w o - p a r a m e t e r equations of the Y u k a w a - Tsuno (1) [17] and
S w a i n - L u p t o n (2) [18] type give the best r e p r e s e n t a t i o n of the r o l e of the various components of the e l e c -
tronic substituent effects in the benzene and thiophene s y s t e m s :
ArCH= ArCHH+ m0a~+ rnR~R+, (17
ArCH=AvOHI~+ fF + rR, (2)

where (70 are constants that characterize the inductive effect of substituted phenyl, ffil+ characterize the
capacity of a substituent for direct polar conjugation with the reaction center, F and H are constants that
characterize the so-called field and resonance effects of a substituent, m0, mR, f , and r are coefficients of
the sensitivity to the above-indicated effects, respectively.
It is apparent from the data in Table 3 that in the series of H complexes of acetophenones with both
phenol arid pentachlorophenol these correlation ratios are observed quite satisfactorily, and higher corre-
lation coefficients are obtained when Eq. (2) is used. At the same time, the use of the F and H constants
for 2-acetylthiophenes gives poorer results as compared with Eq. (1). We calculated the corresponding
transmission factors for the thiophenc ring from the m0, mR, f , and r parameters obtained for the analo-
gous benzene and thiophene series: T0=0.93 TII =1.64, Tf =I.0, and Tr =1.28 for H complexes of phenol;
T0 = 1.07, TII = 1.33 for the H complexes of pentachloroph6nol.* These values indicate approximately iden-
tical transmission of inductive (field) effects in the benzene and thiophene systems, while conjugation effects
a r e t r a n s m i t t e d considerably better by the thiophene ring.
The c o r r e l a t i o n of the ~ CO values of 2-acetylthiophenes with r e s p e c t to the Hammett and Brown equa-
tions is s a t i s f a c t o r y , although the c o r r e l a t i o n coefficients a r e also lower than in the acetophenone s e r i e s .
The values c o r r e l a t e poorly with the r constants.
The application of t w o - p a r a m e t e r equations of the (1) and (2) type to the frequencies of the stretching
vibrations of the carbonyl group of acetophenones gives good results (k = 0.993 and 0.975), but the c o r r e l a -
tions with r e s p e c t to these equations are considerably w o r s e in the s e r i e s of substituted 2-acetylthiophenes.
The low c o r r e l a t i o n coefficients of the ~CO values of 2-acetylthiophenes as c o m p a r e d with the values for
acetophenones are probably due to the effect on the earbonyl frequencies of thiophene derivatives of possible
conformational changes when substituents are introduced. In addition, as noted in [16, 20], interaction of
the substituents not only with the r e a c t i o n center but also with the h e t e r o a t o m o c c u r s in the thiophene ring.
The low c o r r e l a t i o n coefficients obtained on application of equations of the (1) and (2) type to the vCO
values of 2-acetylthiophenes do not make it possible to f o r m a judgment r e g a r d i n g the t r a n s m i s s i o n of
various components of the electronic substituent effects in the static state by means of the thiophene ring.
However, a c o m p a r i s o n of the r e a c t i o n constants in the Hammett and Brown equations for acetophenones
and 2-acetylthiophenes undoubtedly indicates in this case also the considerably g r e a t e r effective t r a n s m i s -
sion of the e l e c t r o n effects of the substituents by the thiophene r i n g as c o m p a r e d with the benzene ring.

*The T f and ~/r values for the s e r i e s of H complexes of ketones with pentachlorophenol were not calculated
in view of the low magnitude of the c o r r e s p o n d i n g c o r r e l a t i o n coefficients.

804
 EXPERIMENTAL
The investigated methyl ketones w e r e obtained and purified as d e s c r i b e d in [5, 6]. The m e a s u r e m e n t s
of the A~OH and ~ CO values and the purification of c a r b o n t e t r a c h l o r i d e and phenol w e r e a c c o m p l i s h e d in
a c c o r d a n c e with [10]. T e c h n i c a l - g r a d e pentachlorophenol was purified by r e p r e c [ p i t a t i o n f r o m alkaline s o -
lution by the addition of dilute h y d r o c h l o r i c acid and two r e c r y s t a l l [ z a t i o n s f r o m carbon t e t r a c h l o r i d e to
give a product with mp 191 ~ in a g r e e m e n t with the l i t e r a t u r e value [7]. The c o r r e l a t i o n analysis was p e r -
f o r m e d by means of the method of l e a s t s q u a r e s .

LITERATURE CITED
i. G. Mar[no, Khim. Geterotsild. Soedin., 579 (1973).
2. F. Fr[nguelli, G. Mar[no, and A. Tat[cchi, J. Chem. Soc., Perk[n Trans., 2, 158 (1972).
3. D.A. Forsyth and D. S. Noyce, Tetrahedron Lett., 3893 (1972).
v.
4. A. Perj~ssy, P. HrcLar, R. Fr[mm, and Z. F[sera, Tetrahedron, 288, 3781 (1972).
5. S.V. Tsukerman, L. P. P[vovarevich, L. A. Kutttlya, N. S. Pivnenko, and V. F. Lavrushin, Reakts.
Sposobnost' Organ. Soed[n., 9, 119 (1972).
6. L.A. Kutulya, L. P. Pivovarevich, V. G. Gordienko, S. V. Tsukerman, and V. F. Lavrush[n, Reakts.
Sposobnost' Organ. Soed[n., 9, 1043 (1972).
7. S.M. Petrov and V. S. Pi1yugin. Zh. Prirodnykh. Soedin., I_55,555 (1971).
8. C. Laurence and B. Wojtkowiak, Bull. Soc. Chim. France, 3124 (1971).
9. T.G. Traylor and J. C. Ware, J. Amer. Chem. Soc., 89, 2304 (1967).
10. S.V. Tsukerman, Doctoral Dissertation [in Russian], Rostov-on-Don (1972).
II. H.J. Streurman and H. Schenk, Rec. Tray. Chim., 89, 392 (1970).
12. Z. Arl[nger, K. Dahlquist, and S. Jorsen, Acta Chem. Scand., 2_44, 662 (1970).
13. S.V. Tsukerman, V. D. Orlov, and V. F. Lavrushin, Zh. Strukt. Khim., i00, 263 (1969).
14. P.Z. Veracini, P. Z. Bar[l[, and Z. Lunazz[, Mol. Phys., 24, 673 (1972).
15. N.N. Zatsepina, Yu. L. Kam[nsk[i, and I. F. Tup[tsyn, Reakts. Sposobnost' Organ. Soed[n., 6, 778
(1969).
16. L.P. Pivovarevich, L. A. Kutulya, Yu. N. Surov, S. V. Tsukerman, and V. F. Lavrushin, Reakts.
Sposobnost' Organ. Soedin., i0, 119 (1973).
17. V.A. Palm, Fundamentals of the Quantitative Theory of Organic Reactions [in Russian], Khimiya,
Leningrad (1967).
18. C.G. Swain and E. C. Lupton, J. Amer. Chem. Soc., 90, 4323 (1968).
19. H. Lumbroso, D. M. Bertin, and P. Cagn[ant, Bull. Soe. Chim. France, 1720 (1970).
20. L.E. Kholodov, Reakts. Sposobnost' Organ. Soedin., 5, 246 (1968).

805
RESEARCH ON A NUMBER OF SUBSTITUTED
ARYLAMIDES OF DITHIOCARBOXYLIC ACIDS
XV. OXIDATION OF DITHIOMALONIC ACID ARYLAMIDES
TO SUBSTITUTED 1,2-DITHIOLS

A . D. G r a b e n k o , L. N.' K u l a e v a , UDC 547.738'772

a n d P . S. P e l ' k i s

Dithiomalontc acid d i a r y l a m [ d e s a r e cyclized to 3 , 5 - d i a r y l a m i n o - l , 2 - d i t h i o l i u m halides by

oxidation with an equivalent amount of b r o m i n e (iodine) in c h l o r o f o r m solution; the s a m e
amides a r e cyclized to 4 - b r o m o - 3 , 5 - d i a r y l a m i n o - l , 2 - d i t h i o l i u m b r o m i d e s with excess b r o -
mine and to 3 - a r y l a m i n o - 5 - a r y l i m i n o - l , 2 - d i t h i o l s in alkaline media with p o t a s s i u m l e f t [ c y -
anide. The behavior of the synthesized substituted 1,2-dithiols with r e s p e c t to various r e -
agents was studied.

In c o n t r a s t to d e r i v a t i v e s of other dithio acids, dtthiomalonic acid a m i d e s and N-substituted amides a r e

oxidized to 1,2-dithiol d e r i v a t i v e s [1-3] that have found b r o a d p r a c t i c a l application [4].
Schmidt [2] and Barnikow [5] obtained 3 , 5 - d i a r y l a m i n o - l , 2 - d i t h l o l t u m iodides by oxidation of dithio-
malonic acid d i a r y l a m i d e s with iodine in alcohol solution. In an attempt to oxidize dithiomalontc acid dian-
ilide with b r o m i n e in c h l o r o f o r m solution Barnikow and c o - w o r k e r s w e r e unable to isolate an oxidation
product and identified only e l e m e n t a r y sulfur [6].
We have obtained 3,5-diaryl~amino-l,2-d[thielium b r o m i d e s (Ia, b) by the action of a solution of b r o -
mine in c h l o r o f o r m on dithiomalonic acid d i a r y l a m i d e s and 3 , 5 - d i a n i l i n o - 1 , 2 - d i t h i o l i u m iodide, which is
identical to the product d e s c r i b e d in [5], by the action of iodine on dithiomalonic acid dtanilide under s i m -
ilar conditions.
In c o n t r a s t to the data in the l i t e r a t u r e r e g a r d i n g ring opening and isolation of e l e m e n t a r y sulfur [7,
11], ionic halogen is r e a d i l y split out by the action of b a s i c r e a g e n t s (NaOH, KSH, C6HsNH2, etc.) on b r o m i d e
I to give 3 - a r y l a m i n o - 5 - a r y l i m i n o - l , 2 - d i t h i o l s (IIa, b).
p-~c...N,~--c,.--cN,co..R-p

S--S NaO~l S----S Br2~.- S--S Br"

Br-
I a-b II a - b IV a - b

~ Br

Iil V a-b

I, II, IV, V a R=H; b R=CH~

Institute of Organic Chemistry, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from
Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 924-927, July, 1974. Original article submitted June
25, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
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806
 When Ia is refluxed with concentrated h y d r o c h l o r i c acid, b r o m i n e is r e p l a c e d by chlorine to give the
c o r r e s p o n d i n g 1,2-dithiolium chloride (IIIa). Compound IIIa was also obtained by refluxing IIa with h y d r o -
chloric acid. A dithiolium salt that is r e s i s t a n t to hydrolytic cleavage at the C =N bond is f o r m e d in this
reaction.
Like I, on t r e a t m e n t with b a s e s , 1,2-dithioHum chloride IIIa r e a d i l y splits out ionic halogen and is
converted to IIa. The r e s i s t a n c e of the t,2-dithiol[um hal[des that we obtained to basic r e a g e n t s is a p p a r -
ently explained by the p r e s e n c e of arylamino groups in the 3 and 5 positions, which are r e s p o n s i b l e for the
possibility of the formation of dipolar s t r u c t u r e s and stabilize the 1,2-dithiolium ring.
The oxidation of dithiomalonic acid diarylam[des with 2 or 3 moles of b r o m i n e in c h l o r o f o r m solution
gives 4 - b r o m o - 3 , 5 - d [ a r y l a m i n o - l , 2 - d [ t h i o l i u m b r o m i d e s (IVa, b). Compound IVa was also obtained by the
r e a c t i o n of Ha with a molar amount of bromine in c h l o r o f o r m .
On t r e a t m e n t with b a s e s , IV r e a d i l y splits out ionic halogen to give 4 - b r o m o - 3 - a r y l a m i n o - 5 - a r y l i m i n o -
1,2-dithiols (Va, b). The b r o m i n e in the 4 position of the 1,2-dithiol[um ring is inert with r e s p e c t to nucleo-
philic substitution r e a c t i o n s (except for the r e a c t i o n with hydrazine hydrate). The 1,2-dith[ol[um salts a r e
decomposed by the action of hydrazine hydrate and a r y l h y d r a z i n e s in aqueous solutions, and p y r a z o l e d e r i v -
atives are f o r m e d in anhydrous media [7].
3.5-Dianilinopyrazole, which is identical to the compound we p r e v i o u s l y obtained in [8], is obtained by
heating 3 , 5 - d i a n i l i n o - l , 2 - d i t h i o l i u m b r o m i d e in hydrazine hydrate or in an alcohol solution of hydrazine hy-
drate on a w a t e r bath for s e v e r a l hours. The r e a c t i o n proceeds with hydrogen sulfide evolution. 3,5-Dian-
ilinopyrazole was also obtained by heating Va with an alcohol solution of hydraz[ne hydrate. Splitting out of
halogen apparently o c c u r s during the step involving ring opening after the addition of hydrazine to the 1,2-
dith[oI [9].
The oxidation of diothiocarboxylic acid diarylamides with p o t a s s i u m ferrieyanide has not been de-
s c r i b e d in the l i t e r a t u r e . It is known only that dithiooxanilide is not oxidized by p o t a s s i u m f e r r i c y a n i d e to
the benzothiazol derivative [10]. We c a r r i e d out the oxidation of dithiomalonic acid dianilide with an equi-
molar amount of p o t a s s i u m f e r r i c y a n i d e in alkaline media and obtained 3 - a n i l i n o - 5 - p h e n y l i m i n o - l , 2 - d i t h i o l ,
which was identical to Ha.
On t r e a t m e n t with reducing agents, 1,2-dithiol derivatives a r e either desulfurized [4] or undergo
cleavage of the S - S bond [2]. We obtained dithiomalonic acid dianilide by reduction of 3 - a n i l i n o - 5 - p h e n y l -
i m i n o - l , 2 - d i t h i o l with zinc in acetic acid.

EXPERIMENTAL

3 , 5 - D i a n i l i n o - l , 2 - d i t h i o l i u m Bromide (In). A solution of 0.6 g (0.003 mole) of bromine in c h l o r o f o r m

was added with s t i r r i n g to a solution of 1 g (0.003 mole) of dithiomalonic acid dianilide in 40 ml of dry
c h l o r o f o r m , after which the mixture was allowed to stand at r o o m t e m p e r a t u r e for 2-3 h. The r e s u l t i n g
yellow precipitate was r e m o v e d by filtration, washed with c h l o r o f o r m , and air dried to give 1.2 g (94%) of
a product with mp 177 ~ (from alcohol). Found: Br 22.2%. CI~Hi3N2BrS 2. Calculated: Br 21.9%.
3 , 5 - D [ ( p - t o l u i d i n o ) - l , 2 - d i t h i e l i u m bromide (Ib), with mp 214-216 ~ (from alcohol), was s i m i l a r l y ob-
tained in 89~c yield. Found: Br 20.4%. CnHnN2BrS 2. Calculated: Br 20.4%.
3 - A n i l i n o - 5 - p h e n y l i m i n o - l , 2 - d i t h [ o l (IIa). A) A mixture of 1 g (0.003 mole) of 3 , 5 - d i a n i l i n o - l , 2 - d i -
thiolium b r o m i d e (or chloride) and 20 ml of 5% aqueous sodium hydroxide solution was s t i r r e d for 1-2 h.
The resulting precipitate was r e m o v e d by filtration, washed with w a t e r , and aLr dried to give 0.65 g (84%)
of a product with mp 161 ~ (from alcohol). Found: S 22.3%. CIsH12N2S2. Calculated: S 22.4%.
B) A solution of 0.2 g of sodium hydroxide in 30 ml of water was added to a solution of 1 g (0.003
mole) of dithiomalonic acid dian[lide in 25 ml of alcohol, after which the mixture was cooled to 7-8 ~ and a
solution of 1.2 g of p o t a s s i u m f e r r i c y a n i d e in 10 ml of water was added slowly with stirring. The mixture
was than allowed to stand at r o o m t e m p e r a t u r e for 1-2 h. The r e s u l t i n g yellow precipitate was r e m o v e d by
filtration, washed with w a t e r , and air dried to give 0.9 g (90%) of a product with mp 160~ (from alcohol).
3 - ( p - T o l u i d i n o ) - 5 - t o l y l i m i n o - l , 2 - d i t h i o l (IIb), with mp 160 ~ (from alcohol), was s i m i l a r l y obtained by
method A. Found: S 20.0%. CnH18N2S2. Calculated S 20.4%.
Compounds IIa and IIb were obtained as yellow c r y s t a l l i n e substances that were soluble in many o r -
ganic solvents and stable on heating.

807
 .3.~5-Dianilino-l,2-dithiolium Chloride (III). A) A mixture of 0.5 g of 3 , 5 - d i a n i l i n o - l , 2 - d R h [ o l i u m b r o -
mide and 10 ml of concentrated HC1 was heated on a water bath for 10 h, after which it was allowed to stand
at r o o m t e m p e r a t u r e for 48 h. The precipitate that f o r m e d on standing was r e m o v e d by filtration, washed
with water, and air dried to give 0.4 g (93%) of a product with mp 193-194 ~ (from alcohol). Found: C1 10.7%.
C15H13N2C1S2. Calculated: C1 11.1%.
B) A 0.5-g sample of 3 - a n i l i n o - 5 - p h e n y l i m i n o - l , 2 - d i t h i o l was heated on a water bath with an alcohol
solution of h y d r o c h l o r i c acid (1 ml of concentrated HC1 in 5 ml of alcohol} for 1-2 h. A portion of the s o l -
vent was r e m o v e d in vacuo, and the resulting light-brown precipitate was r e m o v e d by filtration, washed
with w a t e r , and air dried to give a product with mp 194 ~ (from alcohol}.
4 - B r o m o - 3 , 5 - d i a n i l i n o - l , 2 - d i t h i o l i u m Bromide (IV). A) A solution of 1.5 g of b r o m i n e in c h l o r o f o r m
was added slowly with s t i r r i n g to a solution of 1 g (0.003 mole) of dithiomalonie acid anilide in 10 ml of
chloroform. After 1-2 h, the resulting crystalline precipitate was r e m o v e d by filtration, washed with chlo-
r o f o r m , and air dried to give 1.5 g (91%) of a product with mp 142 ~ (from alcohol).
B) A solution of 0.5 g of bromine in 10 ml of c h l o r o f o r m was added with s t i r r i n g to a solution of 1 g
(0.003 mole) of 3 - a n i l i n o - 5 - p h e n y l i m i n o - l , 2 - d i t h i o l in 10 ml of c h l o r o f o r m ; the addition of the f i r s t portions
of the bromine solution was accompanied by the production of a viscous mass that c r y s t a l l i z e d on further
addition of bromine. The yellow precipitate was r e m o v e d by filtration, washed with c h o l o r o f o r m , and air
dried to give 1.5 g of a product with mp 141-142 ~ (from alcohol). Found-. Br 36.4%. C15HI2N2S2Br2. Cal-
culated: Br 36.0%.
4 - B r o m o - 3 , 5 - d i ( p - t o l u i d i n o ) - l , 2 - d i t h l o l [ u m bromide (IVb), with mp 155-156 ~ (from alcohol}, was ob-
tained by method A f r o m dithiomalonic acid di(p-toluldide). Found: Br 34.2%. C17HITN2S2Br2. Calculated:
Br 33.9%.
4 - B r o m o - 3 - a n i l i n o - 5 - p h e n y l i m i n o - l , 2 - d i t h i o l (Va). A 0.5-g sample of IVa was added to 5 ml of 5%
aqueous solution of sodium hydroxide, and the mixture was s t i r r e d vigorously at r o o m t e m p e r a t u r e for 2 h.
The precipitate was r e m o v e d by filtration, washed with water, and air dried to give 0.36 g (90%) of a p r o d -
uct with mp 133-134 ~ (from alcohol). Found: Br 20.0%. C17H17N2BrS2. Calculated: Br 20.4%.
4 - B r o m o - 3 - (p-toluidino)-5- (p-tolylimino)-l,2-dithiol (Vb), with mp 160 ~ (from alcohol}, was s i m i l a r l y
obtained. Found: S 20.3%. CI?H20N2S2. Calculated: S 20.0%.
3,5-Dianilinopyrazole. A) A 0.4-g (1.4 mmole) sample of 3 - a n i l i n o - 5 - p h e n y l i m i n o - l , 2 - d i t h i o l was
dissolved in 10 ml of alcohol, and 2 ml (60 mmole) of 50% hydrazine hydrate was added. The mixture was
heated at 60-70 ~ for 6-7 h until hydrogen sulfide evolution ceased completely. A portion of the solvent was
r e m o v e d in vacuo, and the precipitate was r e m o v e d by filtration, washed slightly with w a t e r , and air dried
to give a product with mp 199-200 ~ (from alcohol}.
B) A 0.5-g (1.3 mmole) sample of 4 - b r o m o - 3 - a n i l i n o - 5 - p h e n y l i m i n o - l , 2 - d i t h i o l was heated on a water
bath with 4 ml (0.12 mole) of 50% hydrazine hydrate in alcohol solution until hydrogen sulfide evolution
ceased. Water (3 re_l) was added, the mixture was cooled, and the resulting white crystalline product was
r e m o v e d by filtration, washed with cold w a t e r , and air dried to give a product with mp 199 ~ (from alcohol).
Reduction of 3 - A n i l i n o - 5 - p h e n y l i m i n o - l , 2 - d i t h i o l . A 0.5-g sample of zinc dust was added to a solu-
tion of 0.4 g (1.3 mmole) of IIa in 10 ml of acetic acid and 1 ml of h y d r o c h l o r i c acid, and the resulting light-
yellow precipitate was r e m o v e d by filtration and dissolved in methanol. The solvent was r e m o v e d in vacuo,
and the r e s i d u e was purified by p a s s i n g a c h l o r o f o r m solution of it through a column filled with A1203 and
subsequently r e m o v i n g the solvent in vacuo to give 0.12 g of a product with mp 147-148 ~ No melting-point
d e p r e s s i o n was o b s e r v e d for a mixture of this product with dithiomalonic acid dianilide.

LITERATURE CITED

1. W. Walter and J. Gurts, Ann., .649, 88 (1961).

2. U. Schmidt, Ber., 9._2_2, 1171 (1959).
3. K . A . Jensen, H. R. B a e c a r o , and O. Buchardt, Acta Chem. Scand., 17, 163 (1963).
4. N. Karasch, The C h e m i s t r y of Organic Sulfur Compounds, Vol. 2, P e r g a m o n P r e s s (1966), p. 268.
5. G. Barnikow, B e r . , 100, 1389 (1967).
6. G. Barnikow, V. Kath, and H. Conrad, J. prakt. Chem., 3 1 , 2 6 2 (1966).
7. E . J . Klingsberg, J. A m e r . Chem. Soc., 83, 2934 (1961}.

808
 8. A.D. Grabenko, L. N. Kulaeva, and P. S. Pel'kis, Author's Certificate No. 188978 (1967); Byul.
Izobr., No. 23, 20 (1966).
9. E.J. Kl[ngsberg, J. Org. Chem., 28, 529 (1963).
i0. A. Reissert, Ber., 37, 3708 (1904).
ii. D. Leaver, D. M. McKinnon, and W. A. H. Robertson, J. Chem. Soc., 32 (1965).

809
SOME CYCLIZATION REACTIONS
OF w-CHLORO-w-AC YLA MIDOAC ETOPHENONES

B . S. D r a c h , I. Yu. Dolgushina, UDC 547.789.1.5'781'822.7'869.2 : 542.953

a n d A . D. S i n i t s a

Substituted t h i a z o l e s , 1,4-benzothiazines, imidazo [2,1-b]thiazoles, and i midazo [1,2-a]pyridines

containing a c y l a m i d e r e s i d u e s as substituents w e r e obtained by r e a c t i o n of w - c h l o r o - w - a c y l -
aminoacetophenones with t h i o a m i d e s , o-aminothiophenol, 2 - a m i n o t h l a z o l e , and 2 - a m i n o p y r i -
dine. Some of t h e s e s u b s t a n c e s can be used for the synthesis of h e t e r o c y c l i c b a s e s with all
unsubstituted amino group.

The products of condensation of phenylglyoxal with acid a m i d e s [1, 2] r e a c t with thionyl chloride or
phosphorus pentachloride to give high yields of w - c h l o r o - t c - a c y l a m i d o a c e t o p h e n o n e s (I), which a r e e x t r e m e l y
r e a c t i v e and r e a d i l y r e a c t with d i v e r s e substances containing a labile hydrogen a t o m [1, 3, 4]. We r e c e n t l y
found that I condensed with t h i o a c e t a m i d e under v e r y mild conditions via the general s c h e m e of the s y n t h e -
sis o f t h i a z o l e s [2]. In a continuation of this r e s e a r c h we have investigated the condensations of I with thio-
for mamide, thiobenzamide, thtourea, methyl d i t h i o c a r b a m a t e , o-aminothiophenol, 2 - a m i n o t h t a z o l e , and
2 - a m i n o p y r i d i n e (see the s c h e m e below).

NH2~c_R,
S'/ C'Hs~"~T----~ I.CHaCOOH+ HBr C6ttsj ' ~
""~R CONH,~S ~,~L-R, 2. NH4OH
II I11 a, b

~.S , / ~NHCOR
W a-c
NH~ . S~.
y_~ C6Hs , N~/-S~,
9I a - d

it a-c

N 6H5

'- Vl ,a,c

I, IV--VI a R=CH3; b R=C6Hs; c I~=CH30; d R=C6HsCH~O; III a R'=CH3; b R'=C6H5

In all c a s e s , the r e a c t i o n of thioamides gave substituted thiazoles (II) containing a c y l a m i d e r e s i d u e s in the

5 position. T h e r e is no doubt about the s t r u c t u r e s of these compounds b e c a u s e s o m e of t h e m w e r e p r e -
viously synthesized by other methods. F o r e x a m p l e , the product of condensation of w - c h l o r o - w - a c e t a m i d o -
acetophenone ga) with t h i o f o r m a m i d e is undoubtedly 4 - p h e n y l - 5 - a c e t a m i d o t h i a z o l e (see Table 1), inasmuch

Institute of Organic C h e m i s t r y , A c a d e m y of Sciences of the Ukrainian SSR, Kiev. T r a n s l a t e d f r o m

Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 7, pp. 928-931, July, 1974. Original a r t i c l e submitted May
10, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

810
 T A B L E I. A e y l D e r i v a t i v e s of 2 - R ' - 4 - P h e n y l - 5 - a m i n o t h t a z o l e s (II)

I Found, % Calc., %
mp, ~ (crystal- Empirical
ula r
R R'
lizationsolvent) form s c H s

CHa IH i45--14,6 (benzene)* CIIHloN2OS ! 6 0 6 ! 4 6 i - i605 46 -- 70

CHa C6Hs I81--182 (benzene) C~vHI4N2OS "~' I " ! 1 0 9 ~ " 10,9177
CH~ CHaS 166---167 (benzene)T C~HI2N~OS2 -- ' -- '2 3' , 9' , - !- - 24,3 80
CHs NH2 217--220 (methanol)$ CuHuNaOS 56,6 4,8 -- 50,6!4,8 -- 160
CHsO C~Hs 163--164 (benzene) CIrH14N202S - - - - 1 0 , 6 - - - - I G 3 1 6 4
CHaO CHaS 78--80(benzene+hexane C12Hi2,N~OzS2 - - i - - 22,61 -- :-- j22,9' 65
C~Hs NH~ 175--176 (methanol)$ C~HtaNaOS 64,71 461 -- 651144 - - i71
CsH~CH~O[CHa 't07--108 (cycIohexane) CrsH~6N2OzS 668 50 --;66,6' 5 0 ; - i80
C6H~CH~OICaHs 134--135 (cyclohexane) C2aH18N202S 71,1'2'4'7'
I ' -- [ [715'4'7
, [ -- ~(94

*In c o n f o r m i t y w i t h the l i t e r a t u r e d a t a [5].

~ A c c o r d i n g to [6], t h i s c o m p o u n d h a s mp 168 ~
$ T h i s is the d e c o m p o s i t i o n t e m p e r a t u r e .

T A B L E 2. Heterocyclic Bases III-VI

COLT] -
rap, ~ (crystallization solvent) Empirical Found, % Cale.,
pound foffnula

IIla 122--124 (cyclohexane) C!oH~oN~S C 63,1 C63,1 90

H 5,3 5,3
Illb 107--110 (cyclohexane) C~sHI2N2S
T
C 71,6 HC71,4 87
H 5,0 4,8
iVa 142--145 (benzene) CI6H14NzOS S 11,2 S 11,4 60
IVb 143--144(benzene +cyclohexane) C2~H~6N2OS S 9,3 S 9,3 86
IVc i83--184(Senzene) C16HI4N202S S 10,7 S 10,7 67
Va 167--168 (benzene) C13HuN3OS S 12,4 S 12,5 55
Vc 175--180*(ethyl acetate) CI3HuN302S S 11,7 s 11,7 62
Via 208--209*(ethyl acetate) CI~H~3NaO N 16,6 N I6,7 60
VIc 177--178 (acetone) CIsHI3N~O2 N 15,5 N 15.7 68

* This is the decomposition temperature.

a s it is i d e n t i c a l to the p r o d u c t o f t h e r e a c t i o n o f a c e t i c a n h y d r i d e with 4 - p h e n y l - 5 - a m i n o t h i a z o l e [5].

2-Methylmercapto-4-phenyl-5-acetamidothiazole [6], w h i c h p r o v e d to b e i d e n t i c a l to t h e p r o d u c t of c o n d e n -
s a t i o n o f I a with m e t h y l d i t h i o c a r b a m a t e , w a s a l s o s i m i l a r l y s y n t h e s i z e d .
The d i r e c t i o n of the c o n d e n s a t i o n s of I w i t h a m i n o t h i o p h e n o l , 2 - a m i n o t h i o a z o l e , and 2 - a m i n o p y r i d i n e
d o e s not r a i s e a n y s p e c i a l doubts and w a s n o t s p e c i a l l y p r o v e d . E v i d e n t l y , t h e s e c o n d e n s a t i o n s , l i k e t h e r e -
a c t i o n s w i t h t h i o a m i d e s , p r o c e e d v i a a g e n e r a l s c h e m e t h a t is c h a r a c t e r i s t i c for m a n y a - h a l o c a r b o n y l c o m -
p o u n d s [7]. A s a r e s u l t , 2 - a c y l a m i d o - 3 - p h e n y l b e n z o - l , 4 - t h i a z i n e s (IV), 5 - a c y l a m i d o - 6 - p h e n y l i m i d a z o -
[ 2 , 1 - b ] t h i a z o l e s (V), and 2 - p h e n y l - 3 - a c y l a m i d o i m i d a z o [ 1 , 2 - a ] p y r i d i n e s (VI), r e s p e c t i v e l y , w e r e o b t a i n e d .
A simple synthesis of acyl derivatives of various heterocyclic amines from readily accessible I is of
preparative interest because the corresponding primary amines, from which stlch acyl derivatives might
have been obtained, are difficult to obtain or are unknown. The products of condensation of w-ehloro-w-
earbobenzoxyamidoacetophenone with thioamides are especially interesting, inasmuch as these substances
r e a d i l y s p l i t out the p r o t e c t i v e g r o u p f r o m the n i t r o g e n a t o m and g i v e 2 - a l k y l ( a r y l ) - 4 - p h e n y l - 5 - a m i n o t h i -
a z o l e s (Ill) in g o o d y i e l d s . T h i s m e t h o d f o r the p r e p a r a t i o n of 5 - a m i n o t h i a z o l e h o m o l o g s is m o r e c o n v e n i e n t
t h a n the l i t e r a t u r e m e t h o d for t h e i r s y n t h e s i s b y c o n d e n s a t i o n of a - a m i n o n i t r i l . e s w i t h e s t e r s o r s a l t s of
d i t h i o c a r b o x y l i c a c i d s [5, 6].

The p r e v i o u s l y unknown w - c h l o r o - w - c a r b o b e n z o x y a m i d o a c e t o p h e n o r t e (Id) is r e a d i l y o b t a i n e d f r o m t h e

p r o d u c t o f the c o n d e n s a t i o n of p h e n y l g l y o x a t w i t h b e n z y l u r e t h a n e ,
W e t h a n k A. V. K i r s a n o v f o r his a s s i s t a n c e a n d a d v i c e in t h i s r e s e a r c h .

E X P E R I M E N T A L

w - C h l o r o - w - a c y l a m i d o a c e t o p h e n o n e s ( I a - c ) . T h e s e c o m p o u n d s w e r e o b t a i n e d b y the a c t i o n o f t h i o n y l
ehlorid-"e on t h e p r o d u c t s of c o n d e n s a t i o n o f p h e n y l g l y o x a l w i t h a c i d a m i d e s a s p r e v i o u s l y d e s c r i b e d in [1-4].

811
For the preparation of Id, 0.03 mole of benzylurethane was added to a solution of 0.03 mole of freshly dis-
tilled phenylglyoxal in 20 ml of tetrahydrofuran (THF), and the mixture was refluxed for 4 h. The THF was
then vacuum evaporated, and the residual w-hydroxy-co-carbobenzoxyamidoacetophenone was washed with
ether and crystallized from acetone to give a product with mp 133-134 ~ in 77% yield. Found: C 67.5; H 5.3%.
CI6HIsNO4. Calculated: C 67.4; H 5.3%. Treatment of a suspension of 0.01 mole of this compound in 20 ml
of anhydrous THF with 2 ml of thionyl chloride for 24 h gave Id, with nap 91-92 ~ (from cyclohexane), in al-
most quantitative yield. Found: Cl 11.4%. CI6HI4CINO 3. Calculated: Cl 11.7%.
Acyl Derivatives of Heterocyclic Amines (II, IV-Vl). A saturated solution of 0.01 mole of the appro-
priate thioamide, o-aminothiophenol, 2-aminothiazole, or 2-aminopyridine in THF was added to a solution
of 0.01 mole of freshly prepared I in 10-15 ml of THF, and the mixture was allowed to stand for 24 h. The
THF was vacuum evaporated, and the residue was mixed with 20 ml of absolute methanol. The mixture was
refluxed for 1 h, the methanol was vacuum evaporated, and the residue was treated with 30 ml of a saturated
aqueous solution of sodium bicarbonate. The resulting precipitated bases eli, IV, or V) were removed by
filtration, dried in a vacuum desiccator over phosphorus pentoxide, and crystallized from a suitable sol-
vent. Ammonium hydroxide (10%) was used to isolate VI.
2-Amino-4-phenyl-5-benzamidothiazole, which was obtained from Ib and thiourea, was dried with
great difficulty, inasmuch as a hydrate is formed [8]. The anhydrous base was obtained after drying this
hydrate for a week in a vacuum desiccator over fresh portions of phosphorus pentoxide.
2-Alky1(aryl)-4-phenyl-5-aminothiazoles (III). A 0.003-mole sample of the product of condensation
of Id with the appropriate thioamide was mixed with 4 ml of a saturated solution of hydrogen bromide in
glacial acetic acid by the method in [9]. After 3-4 h, at which point carbon dioxide ~volution had ceased,
30 ml of absolute ether was added to the mixture, and the resulting precipitate was removed by filtration,
vacuum dried, and treated with 20 ml of 10% ammonium hydroxide. Bases III precipitated initially as oils
that gradually crystallized. The crystalline masses were removed by filtration, dried in a vacuum desic-
cator over alkali, and purified by recrystallization from cyclohexane.

LITERATURE CITED

1. B. S. Drach, I. Yu. Dolgushina, and A. V. Kirsanov, Zh. Organ. Khim., 8, 1224 (1972).
2. B. S. Drach, I. Yu. Dolgushina, andA. V. Kirsanov, Zh. Organ. Khim., 9, 414 (1973).
3. D. Matthies, Arch. Pharm., 301, 867 (1968).
4. D. Matthies, Synthesis (1972), p. 380.
5. A. H. Cook, S. I. Heilbron, and A. L. Levy, J. Chem. Soc., 1594 (1947).
6. A. H. Cook, S. I. Heilbron, and A. L. Levy, J. Chem. Soc., 1598 (1947).
7. W. L. Mosby, Heterocyclic Systems with Bridgehead Nitrogen Atoms, Part i, New York (1961), pp.
157, 460.
8. Yoshio Tashika and Yoshihiro Nitta, J. Pharm. Soc. Japan, 72, 1157 (1952); Chem. Abstr., 47, 6939
(1953).
9. D. Ben-Ishai and A. Berger, J. Org. Chem., 17, 1564 (1952).

812
ACTION OF PHOSPHORUS PENTASULFIDE
ON 5 - A C E T A M I D O T H I O H Y D A N T O I N S
AND 4-BROMO- 5 - A C E TA M I D O P Y R A Z O L ES

Z. I. Moskalenko and G. P . Shumelyak UDC 547.778.779'783'789

New condensed s y s t e m s - (5,4-thiazolo)imidazoline-2-thione and pyrazolo[5,4-d]thlazoles - a r e

f o r m e d by r e a c t i o n of phosphorus pentasulfide with 5-acetamidothiohydantotns and 4 - b r o m o - 5 -
acetamido derivatives of pyrazole.

Thiazoles condensed with pyrimidine [1], thionaphthene [2], thtazolinethione [3], and pyrazole [4]
rings were synthesized by r e a c t i o n of phosphorus pentasulfide with ~ - a c y l a m i n o c a r b o n y l derivatives o f h e t -
e r o c y c l i c compounds.
In the p r e s e n t paper it is shown in the case of 1,3-dimethyl-5-acetamidothiohydantoin that this r e a c -
tion gives a r e p r e s e n t a t i v e of yet another condensed s y s t e m - (5,4-thiazolo)imidazoline-2-thione (I).

N_._-rv.----N/CH3

CHs
[

It was of interest to extend the action of phosphorus pentasulfide also to 1 - b r o m o - 2 - a c e t a m i d o - s u b -

stituted h e t e r o c y c l i c compounds. As a r e s u l t of this r e a c t i o n with p y r a z o l e s II, derivatives of the p r e -
viously undescribed pyrazolo[5,4-d]thlazole condensed s y s t e m (III) a r e formed.

R' . $
R'~___~Br p2s5 . ~CH 3
N~N~N HCOCH3 { l
l I
R R
II a, b Ill a, b

II-III a R=C6Hs, R'=CH3; II-Ill b R=C4H 9, R'=C61t s

Bases I and III are quite soluble in most organic solvents, slightly soluble in p e t r o l e u m ether, in-
soluble in w a t e r , and r e a d i l y f o r m p i c r a t e s and q u a t e r n a r y salts.

EXPERIMENTAL
1,3-Dimethyl-5-nitrosothiohydantoin. A 2.8-g sample of NaNO 2 was added with s t i r r i n g to a solution
of 2.88 g (0.02 mole) of 1,3-dimethylthlohydantoin in 20 ml of CH3COOH. After 3 h, another 2.8 g of NaNO 2
was added, and the next day the resulting white-yellow precipitate was r e m o v e d by filtration and washed
with water to give 3 g (88%) of a product with mp 205 ~ (from 35% ethanol). Found: N 24.2; S 18.3%.
C5H7N302S. Calculated." N 24.4; S 18.5%.
1,3-Dimethyl-5-acetamidothiohydantoin. A thoroughly ground mixture of 3.4 g (0.02 mole) of 1,3-di-
methyl-5-nitrosothiohydantoin and 6.5 g (0.1 mole) of zinc dust was added in small portions to 60 inl of
CH3COOH and 30 ml of acetic anhydride heated to 60% and the mixture was held at this t e m p e r a t u r e for 2 h.

Shostkinskii Branch, State Scientific-Research and Design Institute of the Photographic-ChemicalIn-

dustry. Translated from KhimiyaGeterotsfldieheskikhSoedinenii, No. 7, pp. 932-934, July, 1974. Original
article submitted July 23, 1973.

9 76 Plenum Publishing Corporation, 227 West 17th Street, N e w York, N. Y. t 001 t. No part o f th& publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

813
The hot solution was filtered, and the filtrate was diluted with 15 ml of water and evaporated to dryness in
vacuo. Another 15 ml of water was added, and the mixture was again evaporated. The residue was c r y s t a l -
lized f r o m alcohol to give 2 g (50%) of colorless p r i s m s with mp 168 ~ The product was soluble in benzene,
alcohol, and ether. Found: N 20.6; S 15.7%. CTHi0N302S.Calculated: N 20~ S 15.9~b.
1 - P h e n y l - 3 - m e t h y l - 5 - a m i n o p y r a z o l e . This compound was synthesized by heating diaeetonitrile with
phenylhydrazine in hydrochloric acid by the method in [5].
. 1 - P h e n y l - 3 - m e t h y l - 5 - a c e t a m i d o p y r a z o l e . This compound was obtained by acetylation of 1-phenyl-3-
m e t h y l - 5 - a m i n o p y r a z o l e by the method in [6].
1 - B u t y l - 3 - p h e n y l - 5 - a m i n o p y r a z o l e . A mixture of 1.44 g (1 mmole) of w-cyanoacetophenone and 1.26
g (2 mmole) of butylhydrazine in 10 ml of ethanol was refluxed for 9 h, after which the ethanol and excess
butylhydrazine were r e m o v e d by vacuum distillation, and the residual oil was c r y s t a l l i z e d by trituration
with 10 ml of p e t r o l e u m ether to give 1.8 g (81%) of c o l o r l e s s needles with mp 81-82 ~ [from b e n z e n e - p e -
t r o l e u m ether (2 : 1)]. Found: N 19.4%. C13HiTN8. Calculated N 19.5%.
1 - B u t y l - 3 - p h e n y l - 5 - a c e t a m i d o p y r a z o l e . A mixture of 2.15 g (1 mmole) of 1 - b u t y l - 3 - p h e n y l - 5 - a m i n o -
pyrazole and 6.12 g (6 mmole) of acetic anhydride was heated at 100 ~ for 45 min. It was then diluted with
three volumes of water, and the contents were evaporated to dryness. This operation was repeated twice.
The resulting viscous oil c r y s t a l l i z e d on t r i t u r a t i o n with 10 ml of cold water to give 2.5 g (97%) of a product
with mp 90-91 ~ (from 50% ethanol). Found: N 16.2%. ClhH19N30. Calculated'. N 16.3%.
1 - P h e n y l - 3 - m e t h y l - 4 - b r o m o - 5 - a c e t a m i d o p y r a z o l e (IIa). A solution of 3.7 g (23 mmole) of bromine
in 6 ml of CH3COOH was added with s t i r r i n g to a solution of 4.2 g (20 mmole) of 1 - p h e n y l - 3 - m e t h y l - 5 -
a c e t a m i d o p y r a z o l e in 5 ml of 50% CH3COOH , after which 20 ml of water and 50 ml of 25% sodium carbonate
solution were added. The crystalline product was r e m o v e d by filtration, washed with water, and r e c r y s t a l -
lized f r o m benzene to give 5.2 g (90%) of a product with mp 162-163 ~ Found: B r 27.2; N 14.2%. C12HI2BrN30o
Calculated~ Br 27.2; N 14.2%.
1 - B u t y l - 3 - p h e n y l - 4 - b r o m o - 5 - a c e t a m i d o p y r a z o l e (IIb). A solution of 2.2 g (13 mmole) of bromine in
2 ml of CH3COOH was added to a solution of 2.6 g (10 mmole) of 1 - b u t y l - 3 - p h e n y l - 5 - a c e t a m i d o p y r a z o l e in
15 ml of CH3COOH. After 2 h, 200 ml of water and 20 ml of 25% sodium carbonate solution were added, and
the resulting precipitate was r e m o v e d by filtration, washed with water, and dried to give 2.8 g (82%) of a
product with mp 109-110 ~ (from benzene). Found: Br 23.6; N 12.6%. Cl~HIsBrN30. Calculated: Br 23.5;
N 12.5%.
1 , 3 - D i m e t h y l - 4 , 5 - ( 2 - m e t h y l - 5 , 4 - t h i a z o l o ) i m i d a z o l i n e - 2 - t h i o n e (I). A finely ground mixture of 2 g (10
mmole) of 1,3-dimethyl-5-acetamidothiohydantoin and 2.2 g of phosphorus pentasulfide was heated in 10 ml
of dry toluene and 110 ~ for 30 min. The toluene was decanted, 60 ml of toluene was added, and the mixture
was refluxed again for 30 min. This operation was r e p e a t e d twice. The toluene was r e m o v e d by vacuum
distillation, and the residue was t r i t u r a t e d with 15 ml of 5% NaOH. The solid was r e m o v e d by filtration,
washed with water, and dried to give 0.85 g (33%) of a product with mp 150 ~ Found: N 21.3; S 32.1%.
CTHgN3S2. Calculated: N 21.1; S 32.2%. The methosulfate was obtained f r o m equimolecular amounts of I
and dimethyl sulfate in benzene and had mp 140 ~ Found-" N 13.0; S 29.3. C9H15N304S3. Calculated: N 12.9;
S 29.6%.
2,6-Dimethyl-4-pheuylpyrazolo[5,4-d]thiazole (IIIa). A finely ground mixture of 2.95 g (10 mmole) of
IIa and 3 g (14 mmole) of phosphorus pentasulfide was heated at 145-150 ~ until hydrogen sulfide and h y d r o -
gen bromide evolution ceased (1 h), after which 20 ml of water and 5 ml of 25% NaOH were added, and the
mixture was s t e a m distilled to give 1.2 g (52%) of a product with mp 90-91 ~ (from petroleum ether). Found:
N 18.3; S 13.9%. C12HllN3S. Calculated: N 18.3; S 14.0%. The pierate had mp 96-97 ~ (from ethanol).
Found: N 18.4%. C12HllN3S.(NO2)3C6H2OH. Calculated: N 18.3%.
1 , 2 , 6 - T r i m e t h y l - 4 - p h e n y l p y r a z o l o [5,4-d]thiazolium P e r c h l o r a t e . An equimolecular mixture of IIIa
and dimethyl sulfate (0.5 mmole of each) was heated at 130 ~ for 3 h, after which it was t r i t u r a t e d with 1 ml
of water, heated with activated charcoal, and filtered. Sodium p e r c h l o r a t e (1 g) was added to the filtrate,
and the resulting precipitate was r e m o v e d by filtration, washed s u c c e s s i v e l y with 1 ml of water, 0.5 ml of
alcohol, and'2 ml of ether, and dried to give 0.15 g (86%) of a product with mp 179-180 ~ (from ethanol).
Found: C1 9.9; N 12.5; S 8.5%. C14H16C1N30r Calculated: C1 9.9; N 12.4; S 8.6%.
2 - M e t h y l - 4 - b u t y l - 6 - p h e n y l p y r a z o l o [5,4-d]thiazole (IIIb). A finely ground mixture of 1.68 g (5 mmole)
of pyrazole Hb and 1.5 g (7 mmole) of phosphorus pentasulfide was heated at 120 ~ for 2 h, after which the

814
melt was t r i t u r a t e d with 20 ml of water and made slightly alkaline with 10% NaOH. The l i b e r a t e d oil was
e x t r a c t e d with benzene and e h r o m a t o g r a p h e d on A1203. The benzene was r e m o v e d by distillation, and the
r e s i d u e was c r y s t a l l i z e d f r o m p e t r o l e u m ether to give 0.5 g (38%) of a product with mp 82-83 ~ Found:
N 15.6; S 11.7%. C15H17N3S. Calculated: N 15.5; S 11.8%. The p i c r a t e had mp 100-101 ~ (from ethanol).
Found: N 16.7%. Cl~H17N3S.(NO2)3C~H2OH. Calculated: N 16.7%.

LITERATURE CITED
I. E. A. Fallen and G. H. Hitchlngs, J. A m e r . Chem. Soc., 7_.22,3203 (1950).
2. Z. I. l~iroshnichenko and M. A. Al'perovich, Zh. Obsheh. Khim., 322, 612 (1962).
3. G. P. Shumelyak and M. A. Al'perovich, Zh. Obshch. Khim., 34, 251 (1964).
4. Z. I. Moskalenko and M. A. Al'perovich, Khim. Geterotsikl. Soedin., 254 (1965).
5. I. I. Grandberg, Ting Wei P ' i , a n d A . N. Kost, Zh. Obshch. Khim., 3_22,2 3 t l (1961).
6. A. IVlichaelis, Ann., 339, 141 (1905).

815
MASS SPECTRA OF IMIDAZO[2,1-b]THIAZOLE
AND THIAZOLO [3,2-f ]XANTHENE DERIVATIVES

O. S. A n i s i m o v a , Y u . N. S h e [ n k e r , UDC 543.51 : 547.781'789'857.4

P. M. K o c h e r g [ n , a n d I . A. M a z u r

The general p r i n c i p l e s of the m a s s - s p e c t r o m e t r i c disintegration of imidazo[2,1-b]thiazole

and thiazolo [3,2-f ]xanthene d e r i v a t i v e s w e r e established, and the c h a r a c t e r i s t i c f r a g m e n t s
w e r e identified. Disintegration proceeding with cleavage of the bonds in the thiazole r i n g of
the 2(3)-ring s y s t e m is c h a r a c t e r i s t i c of all of the investigated compounds. The cleavage of
the S - C bonds, which a r e the w e a k e s t in the investigated s y s t e m s , p r o c e e d s e s p e c i a l l y
readily. Intense peaks of ions due to stepwise disintegration of the p y r i m i d i n e ring a r e also
o b s e r v e d in the s p e c t r a of thiazoloxanthenes.

Up until now inadequate study has been devoted to the f r a g m e n t a t i o n of condensed h e t e r o a r o m a t i c s y s -

t e m s during dissociative ionization. In p a r t i c u l a r , of the c l a s s of i m i d a z o t h i a z o l e s , an interesting p e c u l i a r -
ity of which is the p r e s e n c e of a bridging nitrogen a t o m in the molecule, only s o m e d e r i v a t i v e s of 6-phen-
ylimidazo[2,1-b]thiazole and thiazole[3,2-a]benzimidaz~)le [1, 2] have been investigated.
We have investigated the disintegration of imidazo [2,1-b]thiazole (I) and its various substituted de-
r i v a t i v e s (II-V) and of thiazolo [3,2-f ]xanthene d e r i v a t i v e s (VI-IX) under e l e c t r o n impact. The synthesis
of I - V and VI-IX was p r e v i o u s l y d e s c r i b e d in [3-6].
O

Ctt s

I-V Yl-IX
I R=RI=R2=H; II R~CHa, RI=R2=H; III R=COCH3, RI=CHs, R2=H; IV R~RI=H,
R2=COOH; V R=R~=H, R2=COOCH3; VI R=R~=H; VII R=CH~, RI=H; VIII R=H,
RI~CH3; IX R=RI=CH3

The m a s s s p e c t r a of I-IX a r e p r e s e n t e d in Table 1.

The m o l e c u l a r ion of imidazothiazole I is c h a r a c t e r i z e d by high stability with r e s p e c t to e l e c t r o n i m -
pact (W M =41.8) and p r a c t i c a l l y only the m o l e c u l a r ton p e a k is p r e s e n t in the s p e c t r u m of I at an ionizing
e l e c t r o n e n e r g y of 12 eV. P e a k s of both nitrogen-containing and sulfur-containing f r a g m e n t s f o r m e d during
cleavage of various bonds in the imidazole and thiazole rings of the t w o - r i n g s y s t e m a p p e a r at 50 eV.
The principal paths of disintegration of imidazothiazole I a r e p r e s e n t e d in the s c h e m e below. The
ejection of an SH" group f r o m the m o l e c u l a r ion of [midazothiazole I is not o b s e r v e d in the s p e c t r u m . This
c o n f i r m e d our p r e v i o u s l y e x p r e s s e d a s s u m p t i o n [2] r e g a r d i n g the participation of hydrogen atoms f r o m the
alkyl group in the 2 or 3 position of the t w o - r i n g s y s t e m in the splitting out of an SH group. One might have
a s s u m e d s e v e r a l different s t r u c t u r e s for each of the ions with m a s s n u m b e r s m / e 84, 72, 71. However, a
c o m p a r i s o n of the s p e c t r a of imidazothiazole I and d e r i v a t i v e s II and HI showed that the m a s s n u m b e r s of
the indicated ions do not shift on introduction of substituents into the thtazole ring. This fact p r o v i d e s a

S. Ordzhonikidze All-Union S c i e n t i f i c - R e s e a r c h P h a r m a c e u t i c a l - C h e m i s t r y Institute, Moscow. Z a -

porozhe State Medical Institute. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soed[nenii, No. 7, pp. 935-
939, July, 1974. Original a r t i c l e submitted May 21, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

816
 T A B L E 1. M a s s S p e c t r a of Imidazo [2,1-b]thiazole and Thiazolo [3,2-f ]-
xanthene Derivatives

Corn-, Mass spectra

pound i

39 (3,6), 40(3,5), 41 (I,6), 44 (3,5), 45 (8,5), 46 (5,6), 52 (12,7), 53 (3,1), 57 (6,4),

58 (12,7), 59 (2,4), 62 (I,I), 69 (2,4), 70 (14,5), 71 (9,3), 72 (4,5), 79 (14,5), 80
(2,2), 84 (5,6), 97 (7,3), 98 (1,8), 124 (I00), 125 (7,3), 126 (4,7).Wm'~41,8%
39 (16,7), 40 (5,3), 41 (3,1), 42 (1,4), 43 (1,4), 44 (1t,4), 45 (7,2), 46 (1,4), 50
(2,6), 51 (3,8), 52 (ll,I), 53 (9,4), 54 (3,3), 56 (2), 57 (8,3), 58 (7,5), 59 (2),
60 (5,3), 66 (2,8), 67 (3,1), 69 (5,8), 70 (5,6), 71 {9,9), 72 (7,2), 78 (2), 79 {6,4).
8O (18,1), 81 (2,1), 83 (4,5), 84 (ll,1), 85 (2,2), 93 (3,9), 94 (2,2), 105 {2,6), ll0
(7,5), 111 (3,8), 137 (27,8), 138 (I00), 139 (9,7), 140 (55. Wrn=27,6%
III 39 (16,7), 40 (6,4), 41 (3,5), 42 (19,4), 43 (41,7), 44 (3,9), 45 (9,4), 51 (4,2), 52
(9,7), 53 (3,9). 57 (7,2). 58 (4.4), 59 (8,t), 66 (6.1), 68 (2.5), 69 (6.9), 70 (7,5).
71 (8,1), 72 (4,7), 80 (3.2), 83 (3,9), 84 (8,3), 93 (25), 94 (8,3), 96 (3,3), 105
(2,6), 110 (3,9), 111 (3,2), 137 (22.2), 138 (13,6), 15I (2,8), 165 (91,7). 166 (9,4),
167 (5,3), 180 (100), 181 (2,5), 182 (6,3).Wm=20,5%
IV 39 (3,8), 40 (5,4), 41 (2), 44 (13,7), 45 (28), 46 (8,2), 51 (5). 52 (13,5), 53 (7,4),
57 (9,3), 58 (38,2), 59 (6), 60 (2,8), 64 (2), 69 (4,3), 70 (17,6), 71 (7,7), 72 (8,1),
79 (20,6), 83 (4), 84 (4), 85 (2), 96 (2,8), 97 (5,5), 123 (9,6), 124 (44). 125 (3,8),
126 (2,4), 151 (33,8), 152 (2,9), 153 {2), 168 (100), 169 (8,5), 170 (5,4). Wm=
=21,15%
39 (2,6), 40 (2,7), 43 (2), 44 (7,9), 45 04,4), 46 (2,6), 51 (3,5), 52 (7,9), 53 (5,7),
57 (4,8), 58 (29,4), 59 (6,t), 69 (2,5), 70 (ll,t), 71 (3,5), 72 (3,2), 79 {23.5), 83
{4,4), 84 (2), 97 (2,7), 98 (3,8), 122 (14,4), 123 (75), 124 (6,4), 125 (4,1), 152
(100), 153 (12), 154 {5,5), 182 (70,55, 183 (7), 184 (3,8).Wm=21,2%
VI 40 (3), 41 (3,8), 42 (5,2), 44 (2,7), 45 (4,8), 52 (4,05, 53 (2), 54 (2), 56 (4,1), 57
(5,8), 58 (15,8), 59 (2,2), 66 (2,3), 67 (9,1), 70 (6,7), 72 (2,9), 77 (2), 79 (2,15,
80 (3,0), 81 (2,3), 84 (3,4), 98 (2,1), 99 (8,5), 100 (2,1), ll0 (10,3), Ill (2,6),
ll8 (2,4), 124 (12,6), 125 (8,2), 126 (2,6), 136 (2,0), 150 (12,6), 151 (47), 152
(15,9), 153 (3,8), 178 (7,2), 179 (18,2), 180 (3,5), 207 (4,8), 236 (100), 237 (13,2),
238 (6,5). Wm=24,3%
VII 39 (13,7), 40 (3,5), 41 (4,8), 42 (10), 43 (3,4), 44 (4,9), 45 (7,8), 52 (2,8), 53
(3,1). 54 (3,0), 55 (2,2), 56 (3,7), 57 (2,1), 58 (2,4), 66 (3,0), 67 (11,9), 68 (2,4),
69 (2,2), 70 (7,45), 71 (10,4), 79 (2,2), 80 (4,4), 81 (3,3), 82 (6,7), 83 (2,4), 93
(3,4), 94 (3,9), 96 (2,0), 97 (3,15, 98 (4,8), 99 (9,8), 124 (4,9), 125 (7,2), 126
(2,8), 138 (12,2), 139 (9,2), 163 (2,4), 164 (22,75, 165 (44,4), 166 (9,6), 167 (3,3),
192 (7,7), 193 (24,4), 194 (4,4), 221 (5,6), 250 (100), 251 (13,2), 252 (5,8).
Wrn=21,3%
VIII 39 (12,4), 40 (3,2), 41 (3,5), 42 {7,4), 44 (2,8), 45 (3,1), 53 (2,1), 54 (2,1), 56
(4,1), 58 (2,6), 59 (7,4), 66 (4,1), 67 (7,95), 70 (6,8), 71 (5,4), 72 (12,4), 80 (2,7),
81 (2,1), 98 (2,4), 99 (13,5), 122 (5,6), 123 (2,6), 124 (6,7), 125 (6,3), 126 (3,0),
138 (10,2), 139 (8,0), 163 (3,0), 164 (13,7), 165 (44,5), 166 (13,7), 167 (3,3). 192
(7,0), 193 (19,1), 194 (3,5), 221 (4,1), 250 (100}, 251 (14,3), 252 (6,7). Win=
=21,3%
IX 39 (3,2), 41 (3,2), 42 (7,6), 44 (2), 45 (2,8), 51 (2), 52 (3), 53 (17,2), 54 (3,2),
56 (2,4), 58 (2,4), 59 (6,8), 67 (8,4), 68 (2), 70 (4), 71 (3,6), 72 (3,6), 80 {3,2),
85 (3,6), 86 (3,6), 93 (2,4), 99 (13,2), 111 (2), 126 (2,0), 137 (2,4), 138 (3,2), 139
(2), 151 (2), 152 (9,2), 153 (9,6), 154 (2,6), 178 (22), 179 (32), 180 (7,6), 181
(2,4), 206 {7,6), 207 (19,6), 208 (4), 235 (5), 264 (100), 265 (6,4). Wm=24,4%

basis for assuming that the formation of ions with m/e 8 4 , 7 2 , a n d 71 o c c u r s exclusively during the cleavage
o f t h e SC b o n d i n t h e S i - C 2 p o s i t i o n .

~7"---N- - - ~ "]:+" +/C H

CH2=E=N--C~S + - - ]~N&Sg" ~ S ~ I ~ f m/e 58
a ?R/e 84
/ m/e 124 ~ -""~ ~
/ , ~."A, S~-Ci'-I ~ m/e 45
CH2= N--C---~-S+ ~ f %
b ~.,/~72 / - cZ~=e, d.=~F_c.
+ .

c ra/e "11 d m/e 79 +i

h m/e 97
*1 -HCN ~'~-HCN
+ +
GHm-C--N--~-CH CH=S--C__~--'~CH
C m/e 52 i m/e 70

The other possible paths of the formation of these ions, for example, by cleavage of C2-C 3 or C8-C 4
bonds, apparently are not realized. All of the information set forth above enabled us to assign structures
a, b, and c to the fragments under consideration.

On the basis of the intensity ratio of the peaks of the fragments, elimination of SCH" from the molec-
/ CH
ular ion to give d and formation of the + S x/ H i o n (f) s h o u l d b e c o n s i d e r e d to be the most favorable
CH

817
d i s i n t e g r a t i v e p r o c e s s e s . These ions, and the +S = CH ion (g) also o b s e r v e d in the s p e c t r u m , w e r e c h a r -
a c t e r i s t i c for all of the [midazothiazole d e r i v a t i v e s that we p r e v i o u s l y investigated [2].
Thus, as s e e n f r o m the s c h e m e p r e s e n t e d above, the m o l e c u l a r ion of imidazothiazole I d i s i n t e g r a t e s
due to cleavage of two or t h r e e bonds, one of which in m o s t c a s e s is the S - C (1-2 or 1-8) bond. One should
note the s u c c e s s i v e elimination of two HCN molecules leading to the a p p e a r a n c e in the s p e c t r u m of ions h
and i as the only exception to this. The data obtained attest to. the p r e f e r a b l e n e s s of cleavage of the S - C
bond during the disintegration of the m o l e c u l a r ion of imidazothiazole.
An e x a m i n a t i o n of the m a s s s p e c t r u m of 2 - m e t h y l i m i d a z o t h i a z o l e II showed that the introduction of a
methyl group l e a d s to a s u b s t a n t i a l d e c r e a s e in the stability of the m o l e c u l a r ion (see (Table 1}. An intense
( M - H ' ) + p e a k a p p e a r s in the s p e c t r u m of II; this is explained by the e a s e of stabilization of the r a d i c a l cen-
t e r in the ion f o r m e d in this c a s e [2]. The disintegration of 2 - m e t h y l i m i d a z o t h i a z o l e is b a s i c a l l y s i m i l a r to
the disintegration of imidazothiazole I. The only difference is the fact that HCN in II is eliminated f r o m the
( M - H ' } + ion r a t h e r than f r o m the m o l e c u l a r ion. As expected, the p e a k of the (M-SH3"} + ion is o b s e r v e d
in the s p e c t r u m of II, and the m a s s n u m b e r s of ions f, g, h, and t i n c r e a s e by 14 units. The m a s s n u m b e r s
of ions a, b, and c r e m a i n unchanged; this is in a g r e e m e n t with the s t r u c t u r e s p r o p o s e d for them.
The s t a b i l i t y of the m o l e c u l a r ions of 2 - a c e t y l - 3 - m e t h y l i m i d a z o t h i a z o l e (IlI) with r e s p e c t to e l e c t r o n
i m p a c t falls to 20.5% as a consequence of the a d v a n t a g e o u s n e s s of detachment of an acetyl group. The in-
t e n s e (42%) p e a k of the C~)CH 3 ion is o b s e r v e d in the s p e c t r u m of imidazothtazole III, and the most intense
p e a k (92%) a f t e r the m o l e c u l a r ion p e a k belongs to the (M-CH3.)+ f r a g m e n t . This is explained by the high
stability of ion j, which is f o r m e d during the elimination of a CH s group.
+--CH 3

The ejection of ketene f r o m the m o l e c u l a r ion of III, as in the c a s e of acetyl d e r i v a t i v e s of t h i a z o l o -

b e n z i m i d a z o l e s and 6-phenylimidazothtazole [2], is l e s s advantageous. The s u c c e s s i v e ejection of CO, CS,
and HCN groups o c c u r s during the subsequent disintegration of the(M-CH3") + ion. This f r a g m e n t a t i o n path
is the dominant one. P e a k s of the a, b, c ions that a r e typical for imidazothiazole compounds a r e also ob-
s e r v e d in the s p e c t r u m of IIL
The stability of the m o l e c u l a r tons with r e s p e c t to e l e c t r o n i m p a c t for c a r b o x y and c a r b o m e t h o x y de-
r i v a t i v e s IV and V is ~21%. The f i r s t act in the f r a g m e n t a t i o n of these compounds is elimination of OH.
(IV) and OCH 3" (V) groups. The high intensity of the p e a k of the ion with m / e 151 that is f o r m e d in this c a s e
is explained by the e a s e of stabilization of the r a d i c a l center in it. During the next act in the disintegration
of this ion, a CO molecule is ejected to give an ion with m / e 123. This f r a g m e n t a t i o n path is the p r i m a r y
path in the s p e c t r u m of V, and ions with m / e 151 and 123 have r e l a t i v e intensities of 100 and 76.5%, r e s p e c -
tively. The f u r t h e r disintegration of the ion with m / e 123 p r o c e e d s with s u c c e s s i v e ejection of CS and HCN
p a r t i c l e s , as evidenced by the c o r r e s p o n d i n g m e t a s t a b l e t r a n s i t i o n s . P e a k s of ions d and e that a r e typical
for imidazole [2,1-b]thiazole d e r i v a t i v e s a r e t h e r e f o r e o b s e r v e d in the s p e c t r urn. In addition, the s p e c t r u m
of V contains p e a k s of ions with m / e 58 and 45 (f and g) that a r e peculiar to imtdazothtazoles that do not
have substituents in the thiazole ring.
The m o r e advantageous p r o c e s s in the s p e c t r u m of acid IV is decarboxylation of the m o l e c u l a r ion.
The subsequent disintegration of the r e s u l t i n g ion with m / e 124 is s i m i l a r to the f r a g m e n t a t i o n of the m o l e c -
ular ion of imidazothiazole I. The only substantial difference in the s p e c t r a of I and IV below m / e 124
p r o v e s to be the r e l a t i v e l y higher intensity of the peaks of tons f and g. This is a p p a r e n t l y explained by the
fact that the ions of the indicated s t r u c t u r e s a r e f o r m e d not only during disintegration of the (M-CO2) +" ion
but also d i r e c t l y f r o m the m o l e c u l a r ion.
Thus disintegration with cleavage of the bonds in the thiazole r i n g , mainly with cleavage of the S - C
bonds, is c h a r a c t e r i s t i c for all of the investigated imidazo [2,1-b]thiazole d e r i v a t i v e s .
At p r e s e n t , the m a s s s p e c t r a of various xanthenes have been e x a m i n e d in detail [7], but t h e r e a r e no
data available in the l i t e r a t u r e for thiazoloxanthenes. An analysis of the m a s s s p e c t r a obtained in this
showed that the disintegration of t h i a z o l o [ 3 , 2 - f ]xanthenes (VI-IX) can be d e s c r i b e d by a general s c h e m e and
that the principal direction of f r a g m e n t a t i o n is stepwise disintegration of the p y r i m i d i n e r i n g of the t h r e e -
r i n g s y s t e m , which is r e p r e s e n t e d below:

818
 o ,]+. ~ R,]

c., -c.~ ,[.-co

m ~N~S/\ R -HCN ~'4.~N~/~..S~I~ -H

n l

According to the values of the metastable peaks, ion M in the spectra of all of the investigated th[azolo-
xanthenes may disintegratewith ejection of both a CH 3 group and an HCN group to give ions m and n, respec-
tively. The elimination of a methyl group is easily accepted if it is assumed that [on I has the structure
presented in this scheme. At the same time, splitting out of an HCN group from the ion of this structure is
unlikely. The observed increase in the mass number of ion n by 14 units in the spectra of 2- and 3-methyl
derivatives VII and VIII and by 28 units in the spectrum of 2,3-dimethyl derivative IX as compared with the
thiazole-ring-unsubstituted th[azoloxanthene VI proves that splitting out of HCN does not involve the thia-
zole portion of the molecule. It is therefore logical to assume that ion M may exist in the form of different
structures, for example, l I, /2, and/3, which are presented below.

R,] ~"

-'~..N//-..S.J--R -ell; m
Z1 .

n * N' + ,} II

Z2 Za

Elimination of an HCN group from ions with structures 12 and 13 will lead to fragment n. Similar
fragmentation was previously described for 3-methylxanthene. In addition to the fragments presented in
scheme 2, peaks of ions f and g that are typical for the imidazo[2,l-b]thiazole system are observed in the
spectra of VI-IX. The spectra of thiazoloxanthenes that have methyl substituents in the thiazole ring (VII-
IX) contain the peak of theCH2-C = CR ion that is characteristic for alkyl derivatives of [midazothiazole
[2]. The existence of the ions listed above provides evidence that, despite the peculiarities introduced into
the disintegration of molecules VI-IX by the presence of a dimethylhydroxypyrimidine ring, the fragmentation
directions that are common to [midazothiazoles are also peculiar to these compounds.
Thus a comparison of all of the spectra that we investigated shows that disintegration with cleavage
of the bonds in the th[azole ring of the two(three)-ring system is characteristic for [midazo[2,l-b]thiazole
and thiazole[3,2-f ]xanthene derivatives. Similar data were previously obtained for substituted thiazole-
[3,2-a]benzimidazoles [2]. As a rule, one of the S-bonds, which can apparently be considered to be the
weakest in the heterocycles under examination, is cleaved. These data are in agreement with the chemical
properties of the investigated compounds [5, 8, 9]. The introduction of a d[methyldihydroxypyrimidine ring
into the molecule leads to the appearance of fragments due to the characteristic stepwise disintegration of
the dihydroxypyrimidine ring in the spectrum, in addition to the ions that are usual for [midazoth[azole
systems.

EXPERIMENTAL
The mass spectra were recorded with an MKh-1303 spectrometer with direct introduction of the sub-
stances into the ion source at an ionizing voltage of 50 eV.

LITERATURE CITED
1. H. Ogura, T. Utoh, and K. Kikueh[, J. Heterocycl. Chem., _6, 797 (1969).
2. O. S. Anisimova, Yu. N. Sheinker, P. M. Koeherg[n, and A. N. Krasovskii, Khim. Geterotsikl. Soed[n.,
778 (1974).
3. P. M. Kochergin, Zh. Obshch. Khim., 30, 1529 (1960).
4. I. A. Mazur and P. M. Koehergin, Kh[m. Geterots[kl. Soedin., 508, 512 (1970).

819
5~ M. I. Yurchenko, B. V. Kurmaz, and P. M. Kochergin, Khtm. Geterotsikl. Soed[n., 996 (1972).
6. E. Och[ai, Bet., 69, 1650 (1936).
7. I. Hass, K. Zeller, andW. Voetter, Org. Mass Spectr., 3, 181 (1970).
8. E. G. Knysh, A. N. Krasovskii, and P. M. Kochergtn, Khim. Geterotsikl. Soed[n., 1128 (1971).
9. E. G. Kaysh, A. N. Krasovsk[[, and P. M. Kocherg[n, Kh[m. Geterots[kl. SoedirL., 25 (1972).

820
BENZINDOLES
VIII.* NITROSATION IN THE INDOLE AND ANGULAR
BENZINDOLE SERIES

L. B. Shagalov, T. A. Tkachenko, UDC 547.759.31 : 542.958.2

A. M. Vasil'ev, V. N. Eraksina,
T. A. Babushktna, and N. N. Suvorov

On the basis of the analogy in the PMR s p e c t r a of the products of nitrosation of indole and
benzindoles it was established that the nitrosation of [4,5]benzindole leads to 1 - n i t r o s o - 3 -
o x i m i d o - 2 - ([4,5]benzindol-3-yl)- [4,5]benzindoline, while nitrosation of [6,7]benzindoles
leads to 3 - o x i m i n o - 2 - ( [ 6 , 7 ] b e n z i n d o l - 3 - y l ) - [6,7]benzindolenine.

The nitrosation of indoles that have substituents in the p y r r o l e ring p r o c e e d s with the formation of
oximtdo or n i t r o s o compounds, depending on the position of the substituent [2]. In the case of unsubstituted
indole the r e a c t i o n proceeds in a more complex fashion to give two products - the s o - c a l l e d "indole r e d "
(I) and the c o l o r l e s s "dinitroso indole" (II) - the r a t i o of which depends on the r e a c t i o n t e m p e r a t u r e : I is
f o r m e d p r i m a r i l y at r o o m t e m p e r a t u r e , while II is f o r m e d p r i m a r i l y at 10~

sxoit ~ ~ o u

NO
H H
I II

In c o n t r a s t to indole, the r e a c t i o n of [4,5]- and [6,7]benzindoles with nitrous acid in acetic acid media
proceeds unambiguously and, in each c a s e , gives only one product. A c o l o r l e s s substance (III) with R f 0.67
[Silufol, b e n z e n e - e t h a n o l (6 : 1)] was isolated in the nitrosation of [4,5]benzindole; the d a r k - r e d product (IV)
of n i t r o s a t i o n of [6,7]benzindole has R f 0.34 (with the s a m e system).
The s t r u c t u r e s of I and II were p r e v i o u s l y established on the basis of UV s p e c t r o s c o p i c data [6] and
were confirmed by us by means of the PM:R s p e c t r a (Table 1). In fact, "dinitrosoindolenform II is c h a r a c -
t e r i z e d by the singlet of an indoline proton (6.42 ppm), and the signal of the indole 2-H proton (7.30 ppm)
appears as a doublet (J2,1=2.7 Hz). The a s s i g n m e n t of this signal was confirmed by double r e s o n a n c e on
the signal of the proton of the NH group. The J2,1 s p i n - s p i n coupling constants a r e identical for I and II.
The PM:R s p e c t r u m of III also contains the signal of an indoline proton (7.26 ppm), which is absent in the
s p e c t r a of I and IV. A shift in the signals of the protons of the OH, NH, and 2-H groups to weaker field is

*See [1] for communication VII.

D. I. Mendeleev Moscow Institute of Chemical Technology. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h -

eskikh Soedinenii, No. 7, pp. 940-942, July, 1974. Original article submitted September 24, 1973.

019 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

821
 TABLE 1. Chemical Shifts of the P r o t o n s of N i t r o -
soindoles and Nitrosobenzindoles (ppm)

Compound OH NH 2-H H

] 13,22 11,72 8,26

II 11,62 11,01 7,30 6,42
III 11,23 11,35 6,89 7,26
IV 12,69 12,69 8,37

o b s e r v e d for the l a t t e r as a consequence of an increase in the a r o m a t i c c h a r a c t e r of the entire s y s t e m , and

J2,1 =2.7 Hz for III, while J2,1 =3.2 Hz for IV. The chemical shifts of the protons of the OH and NH groups
of IV are identical (12.69 ppm), and the integral intensity of this signal c o r r e s p o n d s to two protons. These
data make it possible to a s s i g n a s t r u c t u r e s i m i l a r to II to III and a s t r u c t u r e s i m i l a r to I to IV.

III IV

The formation of I and II should p r o c e e d through an intermediate, which, on the one hand, is, in all likeli-
hood, oxidized by nitrogen oxide to I, and, on the other, is n i t r o s a t e d further to II. The absence of c o m -
pounds s i m i l a r to I in the products of nitrosation of [4,5]benzindole attests to the relative stability of the
intermediate with r e s p e c t to oxidation. In the case of [6,7]benzindole, the formation of IV proves to be
p r e f e r a b l e , apparently as a consequence of s t e r i c hindrance during nitrosation at nitrogen.

EXPERIMENTAL
The PMR spectra of dimethyl sulfoxide solutions were recorded with an HA-100 spectrometer with
hexamethyldisiloxane (HMDS) as the internal standard. The IR spectra of mineral-oil suspensions were
recorded with a UR-10 spectrometer.
l-Nitroso-3-oximido-2-([4,5]benzindol-3-yl)- [4,5]benzindoline (III). A 1.7-g sample of [4,5]benzin-
dole was suspended in 15 ml of glacial acetic acid, and a solution of 0.65 g of NaNO 2 in 1 ml of water was
added to it gradually. The mixture was stirred at room temperature for 4 h and poured into 200 ml of wa-
ter. The resulting precipitate was removed by filtration, washed with water, and dried in a vacuum desic-
cator over NaOH to give 1.9 g (quantitative) of Ill. The product was reerystallized from ethyl acetate to
give barely yellowish crystals (the melting point was not determined). Found. C 73.1; H 4.1; N 14.3~.
C2r162 2. Calculated-- C 73.5; H 4.1; N 14.3%. IR spectrum- 3410, 3335, and 1710 cm -i. UV spectrum
(in ethanol), Xmax ,nm (log e). 250 (4.42), 290 (4.10), 300 (4.10), 316 (3.98),and 330 (3.92).
3-Oximido-2-([6,7]benzindol-3-yl)- [6,7]benzindoline (IV). The nitrosation was carried out by the
method described for [4,5]benzindole to give 1.45 g (quantitative) of IV from 1.3 g of [6,7]benzindole and 0.5
g of NaNO 2. Recrystallization from alcohol gave a dark-red crystalline substance (the melting point was
not determined). Found. C 76.5; H 4.2; N 11.3%. C24HIsN30. Calculated. C 76.4; H 4.0; N 11.1%. IR spec-
trum: 3420, 1680, and 1630 cm -I. UV spectrum (in ethanol}, Amax, nm (log e). 268 (4.38) and 284 (4.31).

LITERATURE CITED

1. L. B. Shagalov, V. N. Eraksina, T. A. Tkachenko, and N. N. Suvorov, Trudy MKhTI im. D. I. Men-

deleeva, 80, 72 (1974).
2. R. P. E. Verkade, J. L i e s t e , and E. G. G. W e r n e r , Rec. Tray. Chim., 64, 289 (1945).
3. C. Zatti and A. F e r r a t i n i , Ber., 23, 2299 (1890).
4. P. Seidel, Ber., 77, 797 (1944).
5. C. Zatti and A. F e r r a t i n i , Gazz. Chim. Ital., 2_.11, 19 (1892).
6. H. F. Hodson and G. J. Smith, J. Chem. Soc., 3546 (1957).

822
SYNTHESIS AND SPECTRAL CHARACTERISTICS
OF PHOTOCHROMIC 6- AND 8-PHENYL- SUBSTITUTED
INDOLINE SPIROCHROMENES

E. V. ]3raude and M. A. Gal'bershtam UDC 541.145:547.752'814.1.07:543.422.6

Two photochromic tndoline s p t r o c h r o m e n e s were synthesized. The introduction of a phenyl

group into the 6 or 8 position causes a b a t h o c h r o m i c shift of the bands in the electronic ab-
sorption s p e c t r u m of the merocyanine form.

In a search for structural factors that affect the spectral characteristics of the colored form of spiro-
chromenes [I], we obtained the corresponding spirans (III) containing a phenyl substituent in the pyran por-
tion of the molecule from 3-phenyl-5-nitro- (Ha) and 5-phenyl-3-nitrosalicylaldehyde (lib) [2] by reaction
with 1,3,3-tr imethyl-2- methyleneindoline:

l
R R R -- --I~'
R/
Ia ~ Y II a, b

OH

9
I
R' R' CH 3
Ib III a, b

a R=CGH 5, R' =bJO2; b R=NO 2, R'=C6H 5

We were able to obtain 3-phenylsalicylaldehyde (Ia), which was previously synthesized by the Oatter-
mann reaction [3], by the Duff method by reaction in glacial acetic acid, despite the data of Ligett and Diehl
[4] indicating that o-hydroxyphenyl does not undergo this reaction.
Spirans IIIa, b have photochromic properties at room temperature: colorless solutions of them in
toluene and dioxane take on a blue-azure coloration on irradiation with UV light that gradually disappears
after irradiation is discontinued. Violet-colored alcohol solutions of the spiran sustain an increase in the
intensity of the coloration under the influence of UV irradiation and are decolorized on irradiation with an
incandescent lamp.
We used the method in [5] to determine the parameters of the absorption spectra of the merocyanine
forms of spirans Ilia, b and also, for comparison of l',3',3'-trimethyl-6-nitro-2H-chromene-2-spiro-2'-
indoline (IIIc, R =H, R' =NO2) and 1', 3',3'-trimethyl-8-nitro-2H-chromene-2-spiro-2'-tndoline (IIId, R =
5/02, R ~=H) (Table 1). The introduction of a phenyl group into the 6 or 8 position leads to a bathochromie
shift of ali of the absorption bands of the meroeyanine form, which may reach 30 nm for the first band and
15-20 nm for the second band; the oscillator force of the bands apparently does not change substantially.

S c i e n t i f i c - R e s e a r c h Institute of Organic I n t e r m e d i a t e s and Dyes, Moscow. Translated f r o m I ~ i m i y a

Geterotsiklieheskikh Soedinenii, No. 7, pp. 943-945, July, 1974. Original a r t i c l e submitted July 10, 1973.

9 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 1001 l. No part o f this pubfication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available front the publisher for $15.00.

823
 T A B L E 1. C h a r a c t e r i s t i c s of t h e E l e c t r o n i c A b s o r p t i o n S p e c t r a of
the M e r o c y a n i n e F o r m s of S p i r a n s
I
I band II band
Corn- Solvent t-
pound ~rnax, nm 8max ~,,n,~=,nrn I ~ax

Alcohol 554 40000 0,60 379 26000 0,59

IIIa Dioxane 592 53000 0,67 389 32000 0,59
Toluene 602 46000 0,65 389 29000 0,48
Alcohol 578 21000 0,31 368 10000 0,29
Illb Dioxane 622 41000 0,53 388 25000 0,41
Toluene 631 33000 0,47 393 19000 0,36
Alcohot 523 26000 0,42 358 17000 0,45
(532~)
IIIc Dioxane 582 49000 0,61 375 27000 0,55
Toluene 596 53000 0,75 373 20000 0,34
(6988)
Alcohol 542 34000 0,48 358 10000 0,31
(5446)
IIId Dioxane 596 70000 0,94 383 34000 0,47
Toluene 598 98000 1,26 389 29000 0,35
(6026)

A b a t h o c h r o m i c s h i f t is a l s o o b s e r v e d on p a s s i n g f r o m 6 - n i t r o - s u b s t i t u t e d c o m p o u n d s to 8 - n i t r o - s u b s t i t u t e d
c o m p o u n d s . T h e n e g a t i v e s o l v a t o c h r o m i s m c h a r a c t e r i s t i c f o r m o s t m e r o c y a n t n e f o r m s of s p t r o p y r a n s [5]
is observed for IIIa-d.

EXPERIMENTAL
T h e m e a s u r e m e n t of the a b s o r p t i o n s p e c t r a of t h e s t a r t i n g s o l u t i o n s of t h e s p i r o c h r o m e n e s in t h e
p h o t o s t e a d y s t a t e , t h e c a l c u l a t i o n of t h e e x t i n c t i o n c o e f f i c i e n t s of the c o l o r l e s s and c o l o r e d f o r m s of t h e
s p i r o c h r o m e n e s a t v a r i o u s w a v e l e n g t h s , a n d the a p p r o x i m a t i o n of t h e d a t a o b t a i n e d b y m e a n s of G a u s s i a n
c u r v e s w i t h an- M - 2 2 0 c o m p u t e r w e r e r e a l i z e d a s d e s c r i b e d in [5]. The IR s p e c t r a 0 f K B r p e l l e t s w e r e
m e a s u r e d w i t h a U R - 2 0 s p e c t r o m e t e r . A n a l y s i s of g a s - l i q u i d c h r o m a t o g r a p h y (GLC) w a s r e a l i z e d w i t h an
LKhM-TA chromatograph with a 2-m tong column filled with Chromosorb W impregnated with SE-30 sili-
cone r u b b e r (5%). The c o l u m n t e m p e r a t u r e w a s 200 ~ t h e c a r r i e r g a s w a s h e l i u m , a n d the d e t e c t o r w a s a
katharometer.
3 - P h e n y l s a l i c y l a l d e h y d e (In). G l a c i a l a c e t i c a c i d (200 ml) a n d 490 g (3.5 mole) of u r o t r o p i n w e r e
a d d e d to 70 g (0.41 mole) of o - h y d r o x y d i p h e n y l , a n d t h e m i x t u r e w a s h e a t e d f o r 7 h on a b o i l i n g - w a t e r b a t h .
It w a s t h e n d i l u t e d w i t h a hot m i x t u r e o f 0.5 l i t e r of w a t e r and 0.5 l i t e r of c o n c e n t r a t e d HC1. The m i x t u r e
w a s t h e n s t i r r e d f o r 1 h, c o o l e d , a n d a l l o w e d to s t a n d o v e r n i g h t . The r e s u l t i n g p r e c i p i t a t e w a s r e m o v e d b y
f i l t r a t i o n , a n d t h e f i l t r a t e w a s t h e n d i s t i l l e d . T h e d i s t i l l a t e w a s e x t r a c t e d w i t h c h l o r o f o r m , and the e x -
t r a c t w a s d r i e d w i t h m a g n e s i u m s u l f a t e . The s o l v e n t w a s r e m o v e d b y d i s t i l l a t i o n , and t h e r e s i d u e w a s
v a c u u m d i s t i l l e d t o g i v e a m i x t u r e of o - h y d r o x y d i p h e n y l and a l d e h y d e Ia (3 : 2 a c c o r d i n g to GLC data) w i t h
b p 140-143 ~ (10 m m ) . T h i s f r a c t i o n w a s s e p a r a t e d b y m e a n s of p r e p a r a t i v e GLC w i t h a K h r o m - 3 1 c h r o m a t -
o g r a p h [with a 5 - m l o n g c o l u m n f i l l e d w i t h C h r o m a t o n H i m p r e g n a t e d w i t h A p i e z o n L (15%) at 275 ~ to g i v e
4.08 g (5%) of a l d e h y d e Ia w i t h nap 6 8 - 6 9 ~ (mp 6 9 - 7 1 . 5 ~ [3]). IR s p e c t r u m : 1650 c m - i (C =O).
5 - P h e n y l s a l t c y l a l d e h y d e (rio). A m i x t u r e of 500 g of g l y c e r o l and 70 g of b o r i c a c i d w a s h e a t e d at 170 ~
f o r 2 h w i t h r e m o v a l of the w a t e r b y d i s t i l l a t i o n . The m i x t u r e w a s t h e n h e a t e d at t h e s a m e t e m p e r a t u r e in
v a c u o (at 20 ram) until w a t e r e v o l u t i o n c e a s e d c o m p l e t e l y , a f t e r w h i c h 50 g (0.36 mole) of u r o t r o p i n and 50
g (0.29 mole) of p - h y d r o x y d i p h e n y l w e r e a d d e d . At t h e e n d of the e x o t h e r m i c r e a c t i o n , the m i x t u r e w a s
h e a t e d at 160 ~ f o r 1 h. It w a s t h e n c o o l e d to 100 ~ 260 ml of 30% s u l f u r i c a c i d w a s a d d e d , and t h e m i x t u r e
w a s s t e a m d i s t i l l e d . The d i s t i l l a t e w a s e x t r a c t e d w i t h e t h e r , and the e x t r a c t w a s d r i e d w i t h m a g n e s i u m
s u l f a t e . T h e s o l v e n t w a s r e m o v e d b y v a c u u m d i s t i l l a t i o n to g i v e 3.49 g (6%) of a l d e h y d e rb w i t h bp 157-165 ~
(0.01 mm) a n d mp 107 ~ (mp 102 ~ [7]). IR s p e c t r u m : 1650 c m -1 (C =O).
5 - N i t r o - 3 - p h e n y l s a l t c y l a l d e h y d e (IIa). A s o l u t i o n of 0.3 ml (7 m m o l e ) of f u m i n g n i t r i c a c i d (sp. g r .
1.51) in 10 ml of a c e t i c a c i d w a s a d d e d in the c o u r s e of 30 min at 10-15 ~ to a m i x t u r e of 0.8 g (4 m m o l e )
of I a a n d 30 ml of g l a c i a l a c e t i c a c i d , a f t e r w h i c h t h e m i x t u r e w a s s t i r r e d f o r 2 h and p o u r e d o v e r a m i x -
t a r e o f 50 g of ice a n d 30 ml of w a t e r . The r e s u l t i n g y e l l o w p r e c i p i t a t e w a s r e m o v e d b y f i l t r a t i o n a n d
w a s h e d w i t h w a t e r to g i v e 0.67 g (68%) of a l d e h y d e Ha w i t h mp 139-140 ~ Two r e c r y s t a l l i z a t i o n s f r o m a l -
c o h o l g a v e 0.3 g (31%) of a l d e h y d e IIa [2] w i t h m p 144-145 ~ IR s p e c t r u m : 1640 c m - i (C =O).

824
 3 - N i t r o - 5 - p h e n y l s a l i c y l a l d e h y d e (IIb). This compound, with mp 115-116 ~ was obtained as d e s c r i b e d
above in 30% yield f r o m aldehyde lb. IR s p e c t r u m : 1660 c m - I (C =O) [2].
l ' , 3 ' , 3 ' - T r i m e t h y l - 6 - n i t r o - 8 - p h e n y l - 2 H - c h r o m e n e - 2 - s p i r o - 2 ' - i n d o l i n e (Ilia). A solution of 0.4 g (2.3
mmole) of f r e s h l y distilled 1 , 3 , 3 - t r i m e t h y l - 2 - m e t h y t e n e i n d o l i n e in 10 ml of alcohol was added in the c o u r s e
of 30 min to a solution of 0.47 g (2 mmole) of aldehyde Ha in 50 ml of ethanol, and'the mixture was refluxed
for 2 h. T h e r e s u l t i n g p r e c i p i t a t e was s e p a r a t e d and c r y s t a l l i z e d f r o m alcohol containing activated c h a r -
coal. The hot alcohol solution was f i l t e r e d through a 1 - c m thick l a y e r of bentonite, a f t e r which the product
was c r y s t a l l i z e d f r o m hexane to give 145 mg (19%) of s p i r o c h r o m e n e liIa as a light-yellow powder with mp
166-167 ~ UV s p e c t r u m in octane, Xmax, n m (e): 206 (42,000), 243 (44,000), and 315 (15,000). Found:
C 75.2; H 5.4; N 7.1%. C25H22N203. Calculated: C 75.4; H 5.6; N 7.0%.
1' ,3' , 3 ' - T r i m e t h y l - 6 - p h e n y l - 8 - n i t r o - 2 H - c h r o m e n e - 2 - s p i r o - 2 '-indoline (lIFo). This co mpound, with
mp 152-153 ~ (from alcohol), was s i m i l a r l y obtained in 15% yield f r o m aldehyde Irb. UV s p e c t r u m in octane,
~'max, n m (a): 207 (27,000) and 248 (30,000). Found: C 74.9; H 5.6; N 7.2%. C25H22N203. Calculated:
C 75.4; H 5.6; N 7.0%.

LITERATURE CITED
i~ V. I. P a n t s y r n y i and 1V[. A. G a l , b e r s h t a m , Khim. G e t e r o t s i k l . Soedin., 659 (1973).
2. M. C r a w f o r d and J. W. R a s b m ' n , J. Chem. Soc., 2155 (1956).
3. K. H. Slotta and A. E. Nold, B e r . , 6__88,2226 (1935).
4. L. M. Ligett and H. Diehl, P r o c . Iowa Acad. Sci., 52, 191 (1945).
5. M. A. G a l ' b e r s h t a m , N. P. Samoilova, and L. M. Mikheeva, Khim. G e t e r o t s i k l . Soedin., 1535 (1972).
6. R. C. B e r t e l s o n , Tech. Chem., Vol. 3, New York (1971), p. 73.
7. J. C. Duff, J. Chem. Soc., 547 (1941).

825
3-PHENOXY-1,2,3,4-TETRAHY DROBENZO [h]-
QUINOLINE *

S. I. K u t k e v i c h u s , K . S. S h e r e n a s ,
and R. I. Poshyunas UDC 547.836.3' 822.1 : 542.944~

Thionyl chloride c h l o r i n a t e s 3 - p h e n o x y - l , 2 , 3 , 4 - t e t r a h y d r o b e n z o [ h ] q u i n o l i n e s in the 6 p o s i -

tion at r o o m t e m p e r a t u r e , but at 75-80~ it also p a r t i a l l y c h l o r i n a t e s t h e s e compounds in
the 4 position, which is a c c o m p a n i e d by a r o m a t i z a t i o n of the t e t r a h y d r o p y r i d i n e ring. In[he
c a s e of 3 - ( 2 , 4 , 6 - t r i b r o m o p h e n o x y ) - l , 2 , 3 , 4 - t e t r a h y d r o b e n z o [h]quinoline, a t r i b r o m o p h e n o l
r e s i d u e is p a r t i a l l y split out to give 4,6-dichlorobenzo[h]qutnoltne.

It has been shown [2, 3] that thtonyl chloride c h l o r i n a t e s 3 - h y d r o x y - o r 3 - c h l o r o - l , 2 , 3 , 4 - t e t r a h y d r o -

benzo [h]quinoltne in the 6 position at r o o m t e m p e r a t u r e , while, in addition to chlorination, a substituent is
split out when the m i x t u r e is refluxed, and the t e t r a h y d r o p y r t d t n e r i n g is a r o m a t i z e d . In the p r e s e n t study
it is shown that chlorination in the 6 pos ition occur s s m o o t h l y when 3 - p h e n o x y - 1,2,3,4-tetr ahydrobenzo [h]-
quinoline (In) [4] is allowed to r e a c t with thtonyl chloride at r o o m t e m p e r a t u r e , and 3 - p h e n o x y - 6 - e b l o r o -
1,2,3,4-tetrahydrobenzo[h]quinoline (IIa) is f o r m e d . However, when Ia is r e f l u x e d with SOC12, a mixture of
3 - p h e n o x y - 4 , 6 - d i c h l o r o b e n z o [h]quinoltne (IVa) and 3 - p h e n o x y - 6 - c h l o r o b e n z o [h]quinoline (Va) is f o r m e d , Le.,
the t e t r a h y d r o p y r i d t n e r i n g is a r o m a t i z e d , and the s t a r t i n g compounds undergo p a r t i a l dichlorination.

HI~'/~ OR C6HsCO-..N,~"--.~OR

CI CI
I a-d II a - d III a

;o'o ,":ot-
CI CI CI
v a-c IV a - d v! a

Here and subsequently, a R=C6Ha, b R=o-C6H4CI, c R=p-C6H~C1, d R= sym-C6H2Br~.

It might have been a s s u m e d that the second chlorine a t o m e n t e r s the benzene ring of the phenoxy
group. We t h e r e f o r e c a r r i e d out the a l t e r n a t i v e synthesis of such compounds s t a r t i n g f r o m 7 a , 8 - d i h y d r o -
7H-azirino[1,2-a]benz[g]tndole (VII), which r e a c t s with o- or p - c h l o r o p h e n o l to give a mixture of 3 - c h l o r o -
phenoxy- 1 , 2 , 3 , 4 - t e t r a h y d r o b e n z o [h]qutnoline ([b, c) and 2 - c h l o r o p h e n o x y m e t h y l - 2 , 3 - d i h y d r o - l H - b e n z [g]-
indole (VIIIb, c). The l a t t e r a r e isolated as the acetyl d e r i v a t i v e s .

* Communication XIX f r o m the s e r i e s "Investigation of the P r o d u c t s of the Reaction of Eptchlorohydrin witt

A r o m a t i c A m i n e s . " See [1] for c o m m u n i c a t i o n XVIII.
Kaunas Polytechnic Institute. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 7, pp.
946-951, July, 1974. Original a r t i c l e submitted June 26, 1972; r e v i s i o n s u b m i t t e d F e b r u a r y 5, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

826
 HN~",( ~OR~ C H 2 O R
CIC6H4OH

Vll Ib, c ylll b,c

Compounds Ib, c r e a c t with thionyl chloride at r o o m t e m p e r a t u r e to give 3 - e h l o r o p h e n o x y - 6 - c h l o r o -

1,2,3,4-tetrahydrobenzo [h]quinolines (IIb, c), which are a r o m a t i z e d to 3 - c h l o r o p h e n o x y - 6 - c h l o r o b e n z o [h]-
quinolines (Vb, c) on refiuxing. Neither of these products a r e identical to IVa, and, in addition, substances
with three halogen atoms - 3 - c h l o r o p h e n o x y - 4 , 6 - d i c h l o r o b e n z o [h]quinolines (IVb, c) - are f o r m e d alongwith
thionyl chloride.
An attempt to h y d r o l y t i c a l l y cleave the ether bond of the phenoxy group in IVa by heating with h y d r o -
chloric or hydr[odic acids was unsuccessful. Replacement of one chlorine atom by a hydroxyl group o c -
c u r r e d on r e a c t i o n with h y d r o c h l o r i c acid under p r e s s u r e . It is known [5-7] that the halogen atoms in the
2 and 4 positions of quinoline compounds have i n c r e a s e d lability. In this case also, the 4-C1 atom a p p a r -
ently also undergoes h y d r o l y s i s to give 3-phenoxy-4-hydroxy-6-chlorobenzo[h]quinoline (Via). Compound
!Va is r e d u c e d to Va by the action of hydriodic acid. These t r a n s f o r m a t i o n s indicate that the second chlo-
rine atom is located in the pyridhae ring.
The action of thionyl chlor i de on 3- (2,4,6-tr ibromophenoxy)- 1,2,3,4-tetrahydrobenzo [h]quinoline [4]
(Id) at r o o m t e m p e r a t u r e gives 3 - ( 2 , 4 , 6 - t r i b r o m o p h e n o x y ) - 6 - c h l o r o - l , 2 , 3 , 4 - t e t r a h y d r o b e n z o [ h ] q u i n o l [ n e
(IId). 4,6-Dichlorobenzo[h]quinoline (IX) was isolated along with IVd and Vd by heating it with SOC12, and
t r a c e s of 6-chlorobenzo[h]quinoline were detected by c h r o m a t o g r a p h y , i.e., splitting out of a tribromophenol
r e s i d u e is o b s e r v e d in this case. Compound IX is identical to the compound synthesized by the method in
[8], and this confirms not only its s t r u c t u r e but also the assumption of the p r e s e n c e of halogen in the 4 p o s i -
tion r a t h e r than in the 2 position in IVa-d.

Id SOCI 2 1 POCI a OH Ni-I~e

or ~ vd+lvd+
IId
El El CI
IX Xl X

On passing f r o m the PM:R s p e c t r u m of Ia to the s p e c t r u m of Ha, the multiplet signal of the 7-H p r o -
ton at 7.86-8.20 ppm can be isolated f r o m the unresolved multiplet of a r o m a t i c protons due to the effect of
the magnetic a n i s o t r o p y of the 6-C1 atom. On examination of the PMR s p e c t r a of IVa, Va, c and IX it is
seen that the differences in the signals of the 7-H, 8-H, 9-H, and 10-H protons a r e insignificant. However,
the singlet of the 5-H proton is found at 7.4 ppm in the case of monochloro derivative Va, while the singlet
of the 5-H proton is found at 8.07-8.17 ppm in the case of dichloro derivatives IVa, c and IX. This shift in
the signal can be explained by the effect of 4-C1 and is incompatible with the assumption that the second
chlorine a t o m is in the 2 position. The doublet of the 2-H proton (8.65ppm), withJ2,4=2.7 Hz for Va, is con-
verted to a singlet in the case of IVa, c while in the case of IX it is e x p r e s s e d as a doublet with J2,3 =4.8
Hz, which is close to the o b s e r v e d J2,3 (and not J3,4) value for quinoline derivatives. As a r e s u l t of h y d r o l -
ysis of one of the chlorine a t o m s , a change in the position of the 2-H and 5-H singlets is o b s e r v e d in the
PMR s p e c t r a of hydroxy derivative Via and its benzoate, while the position of the 7-H signal r e m a i n s p r a c -
tically unchanged. This s e r v e s as a confirmation of the fact that 4-C1 r a t h e r than 6-C1 is hydrolyzed. It
is known [9] that 4-hydroxyquinoline derivatives exist in a t a u t o m e r i c qu[nolone f o r m , as a r e s u l t of which
a ~C =O band is o b s e r v e d in the IR s p e c t r a at 1610-1638 em -l. A vC =O band also appears in the 11~ s p e c -
t r u m of Via at 1624 c m -1. The certain shift to strong field of the 10-H signal in the PMR s p e c t r a of Via
and XI, as well as the i n c r e a s e in J2,3 in the case of XI, should apparently be explained by the contribution
of the quinolone s t r u c t u r e . However, the compounds apparently participate p r i m a r i l y in the hydroxy f o r m
in the benzoylation r e a c t i o n , inasmuch as products other than the O-benzoyl derivatives could not be de-
tected.
Thus, in addition to chlorination in the 6 position, chlorination in the 4 position and a r o m a t i z a t i o n of
the t e t r a h y d r o p y r i d i n e ring, p r i m a r i l y with retention of the substituent in the 3 position, are also o b s e r v e d
in the r e a c t i o n of thionyl chloride with 3 - a r y l o x y - l , 2 , 3 , 4 - t e t r a h y d r o b e n z o [h]quinolines. It should be noted
that chlorination in the 4 position and splitting out of a tribromophenol r e s i d u e , as well as the p r e v i o u s l y
investigated chlorination in the 6 position, p r o c e e d in the step involving the t e t r a h y d r o derivatives, i.e.,

827
p r i o r to a r o m a t i z a t i o n , i n a s m u c h as a r o m a t i z e d compounds Va, d do not r e a c t w i t h t h i o n y l c h l o r i d e . Chlo-
r i n a t i o n in the 4 position and a r o m a t i z a t i o n of 3 - a r y l o x y - l , 2 , 3 , 4 - t e t r a h y d r o b e n z o [h]quinolines also o c c u r
when a m i x t u r e of thionyl chloride and the s t a r t i n g m a t e r i a l s is allowed to stand for a long t i m e at r o o m
temperature.

EXP ERIMENTAL
The PM1R s p e c t r a w e r e r e c o r d e d with a P e r k i n - E l m e r R-12 s p e c t r o m e t e r at 60 MHz with t e t r a m e t h -
ylsilane as the internal standaxd. The IR s p e c t r a w e r e r e c o r d e d with an IKS-14 s p e c t r o m e t e r .
3 - P h e n o x y - 6 - c h l o r o - 1 , 2 , 3 , 4 - t e t r a h y d r o b e n z o [h]quinoline (lIa). A mixture of 2.8 g (0.01 mole) of 3-
p h e n o x y - l , 2 , 3 , 4 - t e t r a h y d r o b e n z o [ h ] q u i n o l i n e (la) and 10 ml of thionyl chloride was allowed to stand at r o o m
t e m p e r a t u r e for 15 min, a f t e r which it was d e c o m p o s e d with ice, and the r e s u l t i n g p r e c i p i t a t e was r e m o v e d
by filtration and shaken with 10% s o d i u m hydroxide solution in the p r e s e n c e of ether. The ether was r e -
moved, and the r e s i d u a l c r y s t a l s w e r e r e c r y s t a l l i z e d f r o m butyl a c e t a t e to give 2.4 g (78%) of a product with
mp 166.5-167.5 ~ Found: C1 11.3; N 4.5%. ClgH16C1NO. Calculated: C1 11.4; N 4.5%.
3- ( 2 - C h l o r o p h e n o x y ) - 6 - c h l o r o - l , 2 , 3 , 4 - t e t r a h y d r o b e n z o [h]quinoline (lib). This compound was s i m i -
l a r l y obtained and had mp 120.5-122 ~ (from alcohol). Found: C1 20.6; N 4.1%. C19H15C12NO. Calculated:
C1 20.6; N 4.1%.
3- ( 4 - C h l o r o p h e n o x y ) - 6 - c h l o r o - l , 2 , 3 , 4 - t e t r a h y d r o b e n z o [h]quinoline (lIc). This compound was s i m i -
l a r l y obtained and had mp 111.2-112.5 ~ (from alcohol). Found: C1 20.4; N 4.1%. C19HtsC12NO. Calculated:
C1 20.6; N 4.1%.
3- (2,4,6-Tr i b r o m o p h e n o x y ) - 6 - c h l o r o - 1,2 ,3 , 4 - t e t r a h y d r o b e n z o [h]quinoline (lid). This co mpo und was
s i m i l a r l y obtained in 80% yield and had mp 194.5-195.5 ~ (from chloroform). Found: halogens 50.2; N 2.5%.
CigH13BrC1NO. Calculated: halogens 50.4; N 2.6%.
1 - B e n z o y l - 3 - p h e n o x y - 6 - c h l o r e - 1 , 2 , 3 , 4 - t e t r a h y d r o b e n z o [h]quinoline (lEa). A m i x t u r e of 1.2 g (4
mmole) of I I a , 0.6 g (4 mmole) of benzoyl chloride, and 8 ml of pyridine was heated at 95 ~ for 5 h. The m i x -
t u r e was worked up to give 1.1 g (67%) of IHa with mp 171.5-172.5 ~ (from alcohol). Found: C1 8.6; N 3.5%.
C26H20C1NO2. Calculated: C1 8.6; N 3.4.
3-Phenoxy-4,6-dichlorobenzo[h]quinoline (IVa)and 3-Phenoxy-6-chlorobenzo[h]quinoline (Va). A
mixture of 5.5 g (0.02 mole) of Ia and 22 ml of thionyl chloride was refluxed for 2 h. The mixture was
t r e a t e d with ice, and the r e s u l t i n g p r e c i p i t a t e was r e m o v e d by filtration and dissolved in a c e t o n e - a l c o h o l
in the p r e s e n c e of s o d i u m acetate. The solvent was p a r t i a l l y r e m o v e d , and the r e s u l t i n g c r y s t a l s w e r e r e -
moved by filtration, washed with w a t e r , and r e c r y s t a l l i z e d f r o m acetone to give 2.3 g (34%) of IVa with mp
156-157 ~. Found: C 66.7; H 3.3; C1 21.0; N 4.1%. C19HllC12NO. Calculated: C 67.1; H 3.3; C1 20.8; N 4.1%.
The m o t h e r liquor r e m a i n i n g a f t e r the isolation of IVa was e v a p o r a t e d , and the oily r e s i d u e was ex-
t r a c t e d with p e t r o l e u m ether. T h e p e t r o l e u m ether was p a r t i a l l y r e m o v e d , arid the r e s u l t i n g c r y s t a l s w e r e
r e m o v e d by f i l t r a t i o n and r e c r y s t a l l i z e d f r o m p e t r o l e u m ether and alcohol to give 0.8 g (13%) of Va with mp
84-86 ~ In o r d e r to c o m p l e t e l y s e p a r a t e the IVa i m p u r i t y , the isolated substance was heated under p r e s s u r e
with h y d r o c h l o r i c acid, and the mixture was made alkaline with s o d i u m hydroxide and e x t r a c t e d with ether
to give a product with mp 87.3-88.3 ~ (from alcohol). Found: C 74.9; H 4.1; C1 11.6; N 4.5%. CtgH12C1NO.
Calculated: C 74.7; H 4.0; C1 11.6; N 4.6%.
Similar r e s u l t s w e r e obtained under the s a m e conditions when Ha was used.
Reaction of Ia with thionyl chloride at r o o m t e m p e r a t u r e for 70 h gave Va with mp 86.2-87.2 ~ (from
alcohol) in 7% yield.
3- (2-Chlorophenoxy)-4,6-dichlorobenzo [h]quinoline (IVb) and 3- (2-Chlorophenoxy)-6-chlorobenzo 01]-
quinoline (Vb). These compounds w e r e obtained by the method d e s c r i b e d above for IVa and Va. When IIb
was used, the yield of IVb with mp 164.5-165.5 ~ ( f r o m acetone) was 38%. Found: C 60.6; H 3.0; C1 28.6;
N 3.8%. ClgHt0C13NO. Calculated: C 61.0; H 2.7; C1 28.4; N 3.7%. The yield of Vb with mp 116-117 ~ (from
alcohol) was 15%. Found: C 66.8; H 3.4; C1 20.9; N 4.2%. Ct9HllC12NO. Calculated: C 67.1; H 3.3; C1 20.8;
N 4.1%.
3- (4-Chlorophenoxy)-4,6-dichlor obenzo [h]quinoline (IVc) and 3- (4-Chlorophenoxy)-6-chlorobenzo [h]-
quinoline (Vc). These compounds w e r e obtained by the p r o c e d u r e used to obtain IVa and Va. When IIc was

828
used, the yield of IVc with mp 155.5-156.5 ~ (from acetone) was 43%. Found: C1 28.3; N3.9%. C19H10C13NO.
Calculated~ C1 28.4; N 3.7%. The yield of Vc with mp 89-90 ~ (from alcohol) was 14%. Found: C1 20.8;
N 4.3%. C19HltC12NO. Calculated: C1 20.8; N 4.1%.
Reaction of IIc with thionyl chloride at r o o m t e m p e r a t u r e for 240 h gave IVe in 8% yield and Vc in 9%
yield.

3-Phenoxy-6-chlorobenzo[h]quinoline (Va). A mixture of 1 g (3 mmole) of IVa and 16 ml of 57% hy-

driodic acid was heated in a s e a l e d ampul at 200 ~ for 4 h. The oily l a y e r was separated, washed with wa--
t e r , and extracted with p e t r o l e u m ether. The p e t r o l e u m ether was r e m o v e d , and the residue was r e c r y s -
tallized f r o m alcohol to give 0.3 g (33%) of a product with mp 87-88 ~ No melting-point d e p r e s s i o n was ob-
s e r v e d for a mixture of this product with a sample of the product obtained by the method d e s c r i b e d above.
3 - P h e n o x y - 4 - h y d r o x y - 6 - c h l o r o b e n z o [ h ] q u i n o l i n e (Via). A mixture of 0.5 g (1.5 mmole) of IVa and 10
rnl of concentrated HC1 was heated in a sealed ampul at 200 ~ for 4 h. The solid material was r e m o v e d by
filtration, washed with w a t e r , and r e c r y s t a l l i z e d f r o m alcohol in the p r e s e n c e of sodium acetate to give 0.4
g (85%) of a product with mp 284-285 ~ Found: C1 11.0; N 4.5%. C19HI2C1NO2. Calculated: C1 11.0; N 4.4%.
3 - P h e n o x y - 4 - b e n z o x y - 6 - c h l o r o b e n z o [ h ] q u i n o l i n e . A mixture of 0.3 g (1 mmole) of Via, 0.14 g (1
mmole) of benzoyl chloride, and 10 ml of pyridine was refluxed for 4 h. The mixture was t r e a t e d with 25%
sulfuric acid and diluted with w a t e r , and the resulting c r y s t a l s were r e m o v e d by filtration and r e c r y s t a l -
lized f r o m alcohol to give 0.3 g (75%) of a product with mp 165-166 ~ PM:R s p e c t r u m (in DMSO), ppm: 6.92-
7.35 (protons of the phenyl ring of the phenoxy group), 7.45-7.70 and 7.96-8.17 (protons of the phenyl ring
of the benzoxy group), 7.70-7.90 (8-H and 9-H), 7.88 s* (5-H), 8.07-8.34 (7-H), 8.73 s (2-H), 9.0-9.29 (10-H).
IR s p e c t r u m (of a KBr pellet): 1736, 1237, and 1022 c m -1 (OCO). Found: C1 8 . 2 ; N 3.5%. C2GHI6C1NO3.
Calculated: C1 8.3; N 3.3%.

3- (2,4,6- Tr ibr o mophenoxy) - 6- chlor obe nzo [h] qninol ine (Vc), 3- (2,4,6- Tr ibr o mophenoxy)-4,6- dt c h l o r o -
benzo[h]quinoline (IVd), and 4,6-Dichlorobenzo[h]quinoline (IX). A mixture of 5.5 g (0.01 mole) of Id or IId
and 18 ml of thionyl chloride was refluxed for 2 h. It was then cooled, and the resulting c r y s t a l s of the hy-
drochloride of Vd were r e m o v e d by filtration and r e c r y s t a l l i z e d f r o m a c e t o n e - a l c o h o l in the p r e s e n c e of
sodium acetate to give 0.8 g (15%) of a product with mp 194-195 ~ (from acetone). PMI~ s p e c t r u m (in DMSO),
ppm: 7.60 d, J4,2 =2.9 Hz (4-H); 7.69-7.93 (8-H and 9-H); 7.99 s (5-H); 8.03 s (3'-H and 5'-H); 8.13-8.41
(7-H); 8.83 d, J2,4=2.9 Hz (2-H); 9.06-9.35 (10-H). Found: C 42.3; H 1.9; halogens 50.8; N 2.5%.
C19HgBr3C1NO. Calculated: C 42.1; H 1.7; halogens 50.7; N 2.6%.
After s e p a r a t i o n of Vd, the filtrate was decomposed with ice, and the resulting precipitate was r e -
moved by filtration, washed with water, t r e a t e d with sodium acetate, and extracted with alcohol. The al-
cohol was p a r t i a l l y r e m o v e d , and the residual solution was cooled. The resulting c r y s t a l s were r e m o v e d
by filtration and r e c r y s t a l l i z e d f r o m a l c o h o l - a c e t o n e to give 0.9 g (36%) of I:X with mp 146-147 ~ (from a c e -
tone). PMI~ s p e c t r u m (in CC14) , ppm: 7.51 d, J3,2 =5.0 Hz (3-H); 7.64-7.91 (8-H and 9-H); 8.16 s (5-H);
8.16-8.44 (7-H); 8.75 d, J2,3=4.8 Hz (2-H); 9.15-9.45 (10-H). Found: C 63.0; H 3.0; C1 28.3; N 5.7%.
C13HTC12N. Calculated: C 62.9; H 2.8; C1 28.6; N 5.6%.
6-Chlorobenzo[h]quinoline [Rf 0.61, e t h e r - h e x a n e (1:4)] was detected in the filtrate after separation
of IX by t h i n - l a y e r chromatograph~-(TLC) on aluminum oxide.
The alcohol-insoluble r e s i d u e was extracted with p e t r o l e u m ether. The solvent was r e m o v e d , and
the residue was r e c r y s t a l l i z e d f r o m acetone to give 0.1 g of IVd with mp 187.5-189.5 ~ PiV[R s p e c t r u m (in
DMSO), ppm: 7.70-7.91 (8-H and 9-H); 8.02 s (3'-H and 5'-H); 8.0-8.37 (7-H); 8.19 s and 8.27 s (2-H and
5-H); 8.93 and 9.20 (10-H). Found: N 2.6%. C19HsBr3Ct2NO. Calculated: N 2.4%.
Reaction of 2 g (4 mmole) of Id and 16 ml of thionyl chloride at r o o m t e m p e r a t u r e for 360 h gave 0.2
g (20%) of IX and 0.06 g (2.6%) of IVd.

4,6-Dichlorobenzo[h]quinoline (IX). A mixture of 0.12 g (0.5 mmole) of 4 - h y d r o x y - 6 - c h l o r o b e n z o [ h ] -

qulnoline and 2.5 ml of phosphorus oxychloride was refluxed for 2 h. The mixture was then decomposed
with water, made alkaline with sodium hydroxide, and e x t r a c t e d with ether. The ether was r e m o v e d to give
0.1 g (81%) of a product with mp 146-146.5 ~ (from acetone). No melting-point d e p r e s s i o n was o b s e r v e d for
a mixture of this product with the sample obtained by the method d e s c r i b e d above.

*Here and subsequently, s is singlet and d is doublet.

829
 4 - H y d r o x y - 6 - c h l o r o b e n z o [ h ] q u i n o l i n e (XI). A mixture of 2.3 g (0.01 mole) of 4 - o x o - 6 - c h l o r o - l , 2 , 3 , 4 -
tetrahydrobenzo[h]quinoline, 9.4 g (0.1 mole) of phenol, and 0.4 g of Raney nickel was heated at 195 ~ for 60
h. The m i x t u r e was then diluted with e t h e r , and the r e s u l t i n g p r e c i p i t a t e was r e m o v e d b y filtration and
d i s s o l v e d in aqueous s o d i u m hydroxide. The alkaline solution was acidified with h y d r o c h l o r i c acid, andthe
r e s u l t i n g c r y s t a l s w e r e r e m o v e d by filtration and r e c r y s t a l l i z e d f r o m alcohol in the p r e s e n c e of s o d i u m
a c e t a t e to give 0.3 g (13%) of a product with mp 327-328 ~ PM:R s p e c t r u m (in DMSO), ppm: 6.38 d, J3,2 =
6.7 Hz (3-H); 7.71-7.86 (8-H and 9-H); 7.97 d, J2 8 =6.7 Hz (2-H); 8.15 s (5-H); 8.0-8.34 (7-H); 8.56-8.86
(10-H). Found." N 6.1%. C13HsC1NO. Calculated: N 6.1%.
4-Benzoxy-6-chlorobenzo]h]quinoline. A solution of 0.12 g (0.5 mmole) of XI, 10 m.1 of pyridine, and
0.1 g (0.7 mmole) of benzoyl chloride' was refluxed for 4 h. The mixture was then t r e a t e d with 25% sulfuric
acid and diluted with w a t e r . The r e s u l t i n g c r y s t a l s w e r e r e m o v e d by filtration to give 0.13 g (78%) of a
product with mp 183.7-184.5 ~ (from alcohol). Found: C1 10.6; N 4.2. C20H12C1NO2 Calculated: C1 10.6;
N4.2 .
1 - A c e t y l - 2 - (2- c h l o r o p h e n o x y m e t h y l ) - 2 , 3 - d i h y d r o - 1H-benz [g]indole and 3- (2-Chlorophenoxy)- 1,2,3,4-
t e t r a h y d r o b e n z o [h]quinoline (Ib). A solution of 9.1 g (0.05 mole) of 7 a , 8 - d i h y d r o - 7 H - a z i r i n o [1,2-a]benz [g]-
indole (VII) and 6.4 g of o-chlorophenol in 20 ml of chlorobenzene was r e f l u x e d for 2 h. The m i x t u r e was
then t r e a t e d with aqueous sodium hydroxide solution and e x t r a c t e d with ether. The solvent was r e m o v e d ,
10 ml of acetic anhydride was added, and the mixture was held at r o o m t e m p e r a t u r e for 4 h. It was then
shaken with aqueous s o d i u m c a r b o n a t e solution in the p r e s e n c e of ether. The e t h e r was r e m o v e d , and the
r e s u l t i n g c r y s t a l s w e r e r e m o v e d by filtration and washed with ether to give 2.8 g (16%) of a product with
mp 163-164 ~ (from acetone). Found: C1 10.1; N 4.1%. C21H18C1NO2. Calculated: C1 10.1; N 4.0%.
After isolation of 1 - a c e t y l - 2 - ( 2 - c h l o r o p h e n o x y m e t h y l ) - 2 , 3 - d i h y d r o - 1H-benz [g]indole, the oily r e s i d u e
was c h r o m a t o g r a p h e d on a l u m i n u m oxide with elution with e t h e r - p e t r o l e u m e t h e r (1 : 1). The f r a c t i o n with
~19 0.64 was c o l l e c t e d to give 3.1 g (20%) of Ib with mp 106.5-108 ~ (from alcohol). Found: C1 11.4; N 4.6%.
H1GC1NO. Calculated: C1 11.4; N 4.5%.
1 - A c e t y l - 2 - ( 4 - c h l o r o p h e n o x y m e t h y l ) - 2 , 3 - d i h y d r o - l H - b e n z [ g ] i n d o l e and 3- ( 4 - C h t o r o p h e n o x y ) - l , 2 , 3 , 4 -
tetrahydrobenzo[h]quinoline (Ic). These compounds w e r e s i m i l a r l y s y n t h e s i z e d by acylation of the mixture
obtained In the r e a c t i o n of VII with p-chlorophenol. The yield of 1 - a c e t y l - 2 - ( 4 - c h l o r o p h e n o x y m e t h y l ) - 2 , 3 -
d i h y d r o - l H - b e n z [ g ] i n d o l e with rap 147.5-148.5 ~ (from alcohol) was 3.0 g (17%). Found: C1 10o3; N 4.0%.
C21H18C1NO2. Calculated: C1 10.1; N 4.0%. The yield of Ic with mp 94-95.5 ~ (from hexane) was 16%.
Found: C1 11.3; N 4.5%. C19H16C1NO. Calculated: C1 11.4; N 4.5%.
2 - ( 2 - C h l o r o p h e n o x y m e t h y l ) - 2 , 3 - d i h y d r o - l H - b e n z [g]indole (VIIIb). A solution of 1.8 g (0.005 mole) of
1 - a c e t y l - 2 - ( 2 - c h l o r o p h e n o x y m e t h y l ) - 2 , 3 - d i h y d r o - l H - b e n z [ g ] i n d o l e , 60 ml of ethanol, and 10 ml of concen-
t r a t e d HC1 was r e f l u x e d for 2 h. It was then shaken with aqueous sodium carbonate solution in the p r e s e n c e
of e t h e r , a f t e r which the e t h e r was r e m o v e d , and the oily r e s i d u e was t r e a t e d with alcohol to give 1.2 g
(78%) of a product with mp 53-54.5 ~ (from alcohol). Found: C1 11.4; N 4.6%. C19H16C1NO. Calculated:
C1 11.4; N 4.5%.
2- ( 4 - C h l o r o p h e n o x y m e t h y l ) - 2 , 3 - d i h y d r o - l H - b e n z [g]indole (VIIIc). This compound, with mp 7 8-79.5 ~
(from hexane), was s i m i l a r l y obtained in 84% yield f r o m 1 - a c e t y l - 2 - ( 4 - c h l o r o p h e n o x y m e t h y l ) - 2 , 3 - d i h y d r o -
1H-benz[g]indole. Found: C1 11.4; N 4.6%. C19H16C1NO. Calculated: C1 11.4; N 4.5%.
1 - A c e t y l - 3 - (2-chlorophenoxy)- 1,2 ,3 , 4 - t e t r a h y d r o b e n z o [h]quinoline. A 0.3-g (0.1 mmole) s a m p l e of
Ib was heated in 6 m_l of acetic anhydride at 80 ~ for 2 h, a f t e r which the mixture was shaken with aqueous
sodium c a r b o n a t e solution in the p r e s e n c e of ether. The ether was r e m o v e d , and the r e s i d u e was r e c r y s -
tallized f r o m alcohol to give 0.25 g (71%) of a product with mp 110-111 ~ Found.- C1 10.1; N 4.1%.
C21HlsC1NO2. Calculated: C1 10.1; N 4.0%.
1 - A c e t y l - 3 - (4-chlorophenoxy)- 1,2 ,3 , 4 - t e t r a h y d r o b e n z o [h]quinoline. This compound was s [ m i l a r l y ob-
tained f r o m Ic. The yield of product with mp 128.5-129.5 ~ (from alcohol) was 0.3 g (86%). Found: C1 10.1;
N 4.0%. C21H18C1NO2. Calculated: C1 10.1; N 4.0%.

LITERATURE CITED

i~ S. I. Kutkevichus and E. A. S a m a r s k i s , Khlm. G e t e r o t s i k l . Soedin., 685 (1974).

2. S. I. Kutkevichus and R. I. Valite, Khim. G e t e r o t s i k l . Soedin., 969 (1970).
3. S. I. Kutkevichus and K. S. S h e r e n a s , Khim. G e t e r o t s i k l . Soedin., 1526 (1970).

830
4. R. Poshyunas and S. Kutkev[chus, Material from Papers Presented at the 22nd Republican Scientific-
Technical Conference [in Russian], Karmas (1972), p. iii.
5, E. Besthorn and B. Geisselbrecht, Ber., 53, 1017 (1920).
6. H. R. Ing, J. Chem. Soe., 2195 (1931).
7. M. V. Rubtsov and A. P. Arendaruk, Zh. Obsheh. Khim., 16,215 (1946).
8. S. I. Kutkevtchus and V. A. Darashkaite, Khtm. Geterotsikl. Soedtn., 1224 (1972).
9. S. F. Mason, J. Chem. Soe., 4874 (1957).

831
QUANTUM-CHEMICAL INVESTIGATION
OF THE ~r-ELECTRONIC STRUCTURE
OF 3-HYDROXY-4-PHENYLA ZOQUINOLINE
AND 4-HYDROXY-3-PHE NYLA ZOISOQUINOLINE*

B. E. Zaitsev, G. V. S h e b a n , UDC 541.651'67 : 547.851.7'832.5'833.6.9

a n d K. M. D y u m a e v

The total bond e n e r g i e s , the atomization e n e r g i e s , the m o l e c u l a r d i a g r a m s in the ground

and f i r s t excited s t a t e s , the i n t e r a t o m i c distances in the ground state, and the e l e c t r o n i c
s p e c t r a of the azo and quinonehydrazone f o r m s of 3-hydroxy-4-phenylazoquinol[ne and 4-
h y d r o x y - 3 - p h e n y l a z o i s o q u i n o l i n e w e r e calculated by the MO LCAO method within the
Pariser-Parr-Pople a p p r o x i m a t i o n with the utilization of optimization of the i n t e r n u c l e a r
distances with r e s p e c t to the m i n i m u m of the atomization energy. It follows f r o m an a n a l -
ysEs of the AH values that the azo f o r m in the f i r s t c a s e is e n e r g e t i c a l l y m o r e advantageous
than the quinonehydrazone f o r m , while the opposite is t r u e in the seeond c a s e . The calcu-
l a t e d i n t e r a t o m i c distances and bond o r d e r s of the t a u t o m e r s c o r r e s p o n d to those in the azo
and quinonehydrazone s t r u c t u r e s . The a b s o r p t i o n bands in the e l e c t r o n i e s p e c t r a w e r e a s -
signed. The l o n g - w a v e band in the absorption s p e c t r a of the quinonehydrazone t a u t o m e r s is
due p r i m a r i l y to charge t r a n s f e r f r o m the b r i d g e - a m i n o - n i t r o g e n a t o m t o the quinoid s y s t e m .

3 - H y d r o x y - 4 - p h e n y l a z o q u i n o l i n e (I) exists p r i m a r i l y in the azo f o r m (Ia), while 4 - h y d r o x y - 3 - p h e n y l -

azolsoquinoline (II) e x i s t s p r i m a r i l y in the quinonehydrazone f o r m (IIb).
.."- O 1~

Ia ~ ~s I b

5 e H--O ~ ~ ~ /wt....q

18 I7
II a I! b

An evaluation of the stabilities of the t a u t o m e r s of I and II, obtaining of data on the e l e c t r o n i c s t r u c -

t u r e s and the s t r u c t u r e s of the t a u t o m e r s , and a s s i g n m e n t of the absorption bands in the e l e c t r o n i c s p e c t r a
s e e m of i n t e r e s t . In o r d e r to achieve this, we p e r f o r m e d a q u a n t u m - c h e m i c a l calculation of the ground and
excited s t a t e s of the t a a t o m e r s b y the P a r i s e r - P a r r - P o p l e (PPP) method with introduction of the " a p p r o x -
imation of the v a r i a b l e /3, [2]. The i n t e r a c t i o n of 25 singly excited configurations was taken into account
in the calculation of the s p e c t r a . The values of the o r b i t a I - i o n i z a t i o n p o t e n t i a l s (I), the o n e - c e n t e r i n t e r -
e l e c t r o n i c r e p u l s i o n integrals (y) (for the calculation of the excited states), and t h e / ~ - v a r i a t i o n p a r a m e t e r s

* C o m m u n i c a t i o n VI f r o m the s e r i e s "Structure and P r o p e r t i e s of Dyes.,' See [1] for communication V.

S c i e n t i f i c - R e s e a r c h Institute of Organic I n t e r m e d i a t e s and Dyes, Moscow. T r a n s l a t e d f r o m Khimiya

G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 7, pp. 952-957, July, 1974. Original a r t i c l e submitted May 17, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

832
 TABLE i. Energy Indexes of the Tautomerie Forms of I and 11
Form E rib. eV E oh, eV g b 9 eV an, eV ~Haz o - A H q h , eV

Ia 32,571 74,241 106,812 155,626 0,468

Ib 32,214 74,367 106,581 I55,158
IIa 32,510 74,236 106,745 155,559 -0,191
lib 32,785 74,389 I07,174 " 155,750

TABLE 2. Charges o n the Atoms (qr) of the T a u t o m e r i c F o r m s of

I and II in the Ground (Ia, Ib, IIa, and IIb) and F i r s t Excited (ia*,
Ib*, IIa*, and IIb*) States
qr
Atom -
Ia In* Ib, I b* IIa IIa* IIb llb*

1 0,019 0,048 0.028 0,056 0,021 0,040 0,011 0,043

2 0,022 ,009 --0,046 0,040 0,021 0205 --0,032 0,033
3 0,00 I 0,002 0,010 --0,001 - 0,002 0,003 0,010
4 0,013 0,008 --0,028 0,064 0,009 --00,004 -0,018 0,062
5 0,002 0,002 0,003 0,014 - 0,003 0,004 0,014
6 0,015 --0.009 --0,044 0,033 0,012 -0,018 - 0,033 0,020
7 0,083 -- 0,240 0,146 0,601 --0,092 -0,241 0,238 0,587
8 0,070 -0,262 --0.165 - 0,396 - 0,063 - 0,278 -0,149 -- 0,393
9 0,020 0,132 0.127 0,103 0,038 0,162 0,081 0,!34
I0 0,053 0,121 0,265 0,118 0,065 0,147 0,255 0,155
11 0.091 0.029 0,158 0,078 - 0,002 -0,043 0,001 --0,044
12 0,207 --0,221 --0.167 - 0.249 0 0,032 0,045 0.034
13 0,050 0,056 0,034 0,025 0,008 0,006 0,018 0,002
14 0,002 0,037 0,014 0,006 0,004 -- 0,003 0,019 - - 0,005
15 0,003 0,044 0,017 0,019 0,011 0,046 0,016 0,022
16 0,001 --0,016 0,009 --0,011 - 0,002 - 0,047 -0,003 --0,041
17 0,002 0,066 0,025 0,035 0,109 0,209 0.166 0,114
18 0,002 --0,041 --0,025 -0,039 --0,206 --0,252 -0,218 --0,255.
I9 0,068 0,236 --0,349 - 0,508 0,071 0,242 -0,403 --0,492

were taken f r o m [3]. The I and Y values (for the calculation of the ground state) and the p a r a m e t e r s for the
determination of the a - b o n d energies were taken f r o m [4]. Optimization of the internuclear distances with
r e s p e c t to the minimum of the atomization e n e r g y (AH) was used in the calculations. The optimization was
c a r r i e d out with r e s p e c t to a p r o g r a m that we c o m p o s e d that r e a l i z e s the Dewar a l g o r i t h m [4]. In the cal-
culations it was a s s u m e d that all of the molecules a r e planar s y s t e m s with angles between the bonds of
close to 120 ~ The positive direction of the angle of rotation of the vector of the moment of the transition
was s e l e c t e d as being clockwise f r o m the x axis.

~r-Electronic Structures
The position of the t a u t o m e r i c equilibrium between f o r m s I a ~ I b and I I a ~ I I b is determined by the en-
ergetic advantageousness of the c o r r e s p o n d i n g f o r m s . The bond energies of all f o r m s should be c o m p a r e d
in o r d e r to evaluate it [5]. Within the approximation of independence of the a and r e l e c t r o n s , the bond
e n e r g y (Eb) is r e p r e s e n t e d in the f o r m of the s u m of the 7r-bond (ETrb) and a - b o n d (Eab) e n e r g i e s , i.e.,
Eb =ETrb +Ecrb. A more c o r r e c t value for e v a h a t i o n o f t h e energetic stability of the t a u t o m e r s is the a t o m i -
zation e n e r g y AH [4]. The absolute values of all of the calculated e n e r g y values are p r e s e n t e d in Table 1.
It follows f r o m Table 1 that the E b and AH values for the azo t a u t o m e r of I a r e l a r g e r than for the
quinonehydrazone t a u t o m e r , while the relationship between Eb and AH is just the opposite of this for II.
Consequently, the azo f o r m of I is more favorable than the quinonehydrazone f o r m , while the quinonehydra-
zone t a u t o m e r is more favorable for II. These conclusions are confirmed by the experimental data [1]. It
should be noted that one cannot draw conclusions r e g a r d i n g the stability of the t a u t o m e r s only f r o m the
7r-bond or only f r o m the ~-bond e n e r g i e s , inasmuch as the bond lengths of the t a u t o m e r s differ markedly
f r o m one another, and an analysis only of these energies leads to conclusions that contradict the e x p e r i -
mental r e s u l t s and the relationship between the E b and AH values. The energetic advantageousness of f o r m
IIb as c o m p a r e d with IIa is probably due to the special position of the nitrogen atom in the ring.

Molecular Diagrams
It is apparent from the data on the bond lengths (Rrs) and orders (Prs) and also from the charges on
the atoms (qrs) of the molecules (Tables 2-4) that a unified 7r-electron s y s t e m of bonds is formed in the azo

833
 TABLE 3. Bond Orders and Lengths (Prs and Rrs) of the Tautomeric
Forms of I in the Ground (la, Ib) and First Excited (la*, Ib*) States
Prs (Rr,)
Bond
Ia Ia* Ib ' Ib*

1--2 0,612 (1,406) 0,546 0,631 (1,402) 0,513

1--6 0,609 (1,406) 0,546 0,631 (1,402) 0,515
1--7 0,386 (1,379) 0,496 0,316 (1,392) 0,563
2--3 0,677 (1,394) 0,699 0,674 (1,395) 0,710
3--4 0,661 (1,397) 0,637 0,662 (1,397) 0,626
4--5 0,656 (1,398) 0,633 0,662 (1,397) 0,624
5--6 0,683 (1,393) 0,703 0,674 (1,395) 0,711
7--8 0,834 (1,269) 0,562 0,207 (1,380) 0,336
8--9 0,409 (1,375) 0,559 0,850 (1,295) 0,638
9--!0 0,663 (1,397) 0,430 0,282 (1,463) 0,396
9--18 0,489 (1,427) 0,460 0,340 (1,453) 0,434
16--11 0,549 (1,416) 0,540 0,299 (1,460) 0,412
!0--19 0,264 (1,351) 0,476 0,847 (1,255) 0,683
11--12 0,740 (1,316) 0,707 0,871 (1,293) 0,786
i2--13 0,520 (1,355) 0,480 0,378 (1,381) 0,423
13--14 0,523 (I,421) 0,554 0,6!3 (1,405) 0,601
13--18 0,561 (1,414) 0,555 0,591 (1,409) 0,551
14--I5 0,757 (1,380) 0,707 0,684 (t,393) 0,690
15--16 0,569 (l,413) 0,595 0,645 (1,400) 0,625
16--17 0,751 (1,381) 90,706 0,679 (1,394) 0,697
17--18 0,539 (1,418) 0,549 0,625 (1,403) 0,580

TABLE 4. Bond Orders and Lengths (Prs and Rrs) of the Tautomeric
Forms of II in the Ground (IIa, lib) and First Excited (IIa*, lib*) States
P,, (Rr,)
Bond . . . . . . . . . . . . . . . . . . . . .

IIa IIa ~ nb lib*

1--2 0,613 (1,405) 0,542 0.631 (1,402) 0,517

1--6 0,6i0 (1,406) 0,541 0.631 (1.402) 0,518
1--7 0,389 (1,380) 0,503 0,308 (1,393) 0,551
2--3 0,677 (1,394) 0,702 0,675 (1,395) 0,713
3--4 0,661 (1,397) 0,624 0,662 (1,397~ 0,620
4--5 0,656 (1,398) 0,630 0.6G2 (1,397) 0,629
5--6 0.682 (1,393) 0,705 0,674 (1,395) 0,714
7--8 0,835 (1,269) 0,563 0,365 (1,352) 0,373
8--9 0,405 (1,376) 0,54i 0,797 (1,308) 0,614
9--10 0s (1,395) 0,428 0,321 (1,455) 0,377
9--18 0,503 (1,358) 0,493 0,385 (1,379) 0,476
10--11 0,506 (1.424) 0,498 0.330 (i,455) 0,392
10--19 0.271 (1,350) 0,493 0,8!5 (1,261) 0,713
11--12 0,535 (1,419) 0,542 0,624 (!,403) 0,604
11--16 0,567 (1,413) 0,533 0,508 (i,4o8) 0,552
12--13 0,750 (1,381) 0,728 0,680 (!,394) 0,690
13--1-t 0,575 (1,4!2) 0,575 0,644 (1,400) 0,623
14--15 0.748 (1,382) 0,716 0,687 (1,392) 0,698
15--16 0,542 (1,418) 0,562 0,6!2 (1,406) 0,588
i6--17 0,495 0,426) 0,462 0.376 (!,447~ 0,442
17--18 0,768 (I,31I) 0,731 0.842 (1,298) 0,741

f o r m s of I a n d II due to c o n j u g a t i o n of the azo g r o u p with the a r o m a t i c r i n g s . It follows f r o m a c o m p a r i s o n

of the P r s v a l u e s that the c o n j u g a t i o n of the q u i n o l i n e r i n g with the azo g r o u p is g r e a t e r b y a f a c t o r of 1.5
t h a n the c o n j u g a t i o n with the h y d r o x y l g r o u p . It s h o u l d be n o t e d that the P r s and R r s v a l u e s in the r i n g s
axe d i f f e r e n t . T h u s , w h i l e all of the P r s and R r s v a l u e s in the p h e n y l r i n g s a r e a p p r o x i m a t e l y e q u a l , the
P r s and R r s v a l u e s in the q u i n o l i n e r i n g take on a s l i g h t q u i n o i d c h a r a c t e r . In the f i r s t e x c i t e d s t a t e ('B),
the P C - N a n d P N =N v a l u e s a r e e q u a l i z e d , the n e g a t i v e c h a r g e s on the n i t r o g e n a t o m s of the azo g r o u p i n -
c r e a s e m a r k e d l y , and the oxygen a t o m s a c q u i r e an a d d i t i o n a l p o s i t i v e c h a r g e . This a t t e s t s to the p a r t i c i -
p a t i o n in the 'A--~'B t r a n s i t i o n of c h a r g e t r a n s f e r f r o m the oxygen a t o m in the 7r-conjugated s y s t e m p r i -
m a r i l y to the azo g r o u p , d u r i n g w h i c h the quinoid c h a r a c t e r of the p h e n y l r i n g s a l s o i n c r e a s e s , while the
7r b o n d s in the q u i n o l i n e r i n g b e c o m e m o r e d e l o c a l i z e d . B e c a u s e of r e d i s t r i b u t i o n of the c h a r g e s on the
a t o m s d u r i n g the ' A ~ ' B t r a n s i t i o n , the ~r dipole m o m e n t s (PTr) i n c r e a s e m a r k e d l y , and t h e i r d i r e c t i o n
changes.
The P C =N and P C =O v a l u e s in the g r o u n d s t a t e of the q u i n o n e h y d r a z o n e f o r m of Ib and IIb, l i k e the
RC =N a n d R C =O v a l u e s , a t t e s t to c o n s i d e r a b l e m u l t i p l i c i t y of t h e s e b o n d s . The o r d e r s of the C - C and
C - N b o n d s a d j a c e n t to C =O a n d C = N have d e p r e s s e d v a l u e s (0.282-0.385). The P r s and R r s v a l u e s of all
of the b o n d s in the b e n z e n e r i n g s of Ib and Kb a r e a p p r o x i m a t e l y e q u a l , and t h i s a t t e s t s to a c o n s i d e r a b l e
d e g r e e of d e l o c a l i z a t i o n of the Ir b o n d s . The c h a r g e s on the a t o m s of the b r i d g e - a m i n e - n i t r o g e n a t o m a r e

834
 TABLE 5. v Dipole Moments (Pr) and T h e i r Directions (q~o) for
the T a u t o m e r i c F o r m s of I and II in the Ground (Ia, Ib, IIa, and rib)
and F i r s t Excited (Ia*, I b * , I I a * , and lib*) States

Form Ia la* Ib Ib* IIa IIa* IIb IIb*

.Pn I 1,570 2.189 3,187 10,196 1,986 6,568 3,568 7,071

~ 1 41 161 219 177 125 185 196 5

TABLE 6. Calculated C h a r a c t e r i s t i c s of the E l e c t r o n T r a n s i t i o n s

of the T a u t o m e r i c F o r m s of I and II: Wavelengths (X), O s c i l l a t o r
F o r c e s (f), P o l a r i z a t i o n s (cP~ and E i g e n v e c t o r of the Conrigura-
tional I n t e r a c t i o n Matrix (CIM)
Com- State
pound ~, ~ f ~o CIM eigenvector

Ia '[ 'B 4156 0,85 185 0,98(t0--11)

tG+ 3288 0,33 55 0,91 (9--11) +0,29(10--13) +0,19(9--12)
~C- 2924 0,11 11 0,91 (8--11) -0,21 (9--11) --0,14(7--II)
2533 0,23 260 0,53(10--13) -0,50(10--12) +0,46(9--12).
"G- 2298 0,17 269 0,69(10--14) -0,51 (7--11) -0,35(8--14)
2188
t G -- 1,10 75 0,69(10--13) -0,64 ((9--12) -0,17(6--13)
Ib ~
!4988 0,52 0,98(10--11) --0,12(10--12)
3560 0,22 27 0,98 (9--11)
"C+ 2812 0,43 234 0,85(10--12) +0,36 (7--11) +0,18(9--12)
"G+ 2605 0,13 267 0,75(10--14) +0,52 (8--11) +0,33(8--15)
2243 0,37 241 0,77(10--13) --0,35 (7--12) +0,33(9--12)
!'(CH)- 2190 0,20 208 0,78(10--15) --0,44 (6--il) --0.30 (8--14)
~ 4147 1,05 I77 0,98(10--11) --0,11(10--12)
Ila '( )- 2796 0,61 212 0,74 (9--11) --0.4l(10--12) --0,31(7--12)
t IU+ 0,28 270 0,80(10--14) +0,48 (8--11) +0,28(9--14)
,'(UC) i 21612206 0,10 150 0,56 (9--12) -0,49 (7--12) +0,42(6--11)
llbi 'B 4623 0,89 180 0,98(t0--1I) +0,12(10--13)
I'(GC) 2711 0,15 219 0.82(10--12) --0,42 (7--11) +0,20 (8--11)
L ' 6 - I 2579 0,11 265 0,70 (9--11) -0,62(10--14) --0,30 (9--15)
!'(CG) ] 2494 0,61 193 0,77(10--13) +0,31(10--15) --0,30 (7--11)
!'(~H) 12244
2107
0,37
0,16
155
73
0,52 (8--12) --0,44 (7--12) +0,36(10--13)
1 J 0,75 (7--12) +0.34 (8--12) +0,32(10--15)

0.146 and 0.238, r e s p e c t i v e l y , f o r f o r m s Ib a n d rib. T h e p o s i t i v e c h a r g e on t h i s n i t r o g e n a t o m in t h e f i r s t

e x c i t e d s t a t e ('B) i n c r e a s e s b y a f a c t o r of 2.5 f o r Ib and b y a f a c t o r of 1.6 for IIb. This l e a d s to an i n c r e a s e
in P v f r o m 3.187 to 10.196 D f o r Ib and f r o m 3.568 to 7.071 D for i I b (Table 5). M o r e o v e r , the P v d i r e c -
t i o n s c h a n g e b y a l m o s t 180 ~ C o n s e q u e n t l y , d u r i n g t h e 'A --*TB t r a n s i t i o n t h e r e is p r o n o u n c e d c h a r g e t r a n s -
f e r f r o m the b r i d e - a m i n e - n i t r o g e n a t o m t o t h e v - c o n j u g a t e d s y s t e m of the m o l e c u l e . The quinoid c h a r a c -
t e r of t h e p h e n y l r i n g s i n c r e a s e s , w h i l e the q u i n o i d c h a r a c t e r of the q u i n o l i n e r i n g s d e c r e a s e s . The d e -
c r e a s e in P C =O and t h e i n c r e a s e in P C - N in the f i r s t e x c i t e d s t a t e a t t e s t s to an i n c r e a s e in t h e c o n j u g a t i o n
of the b r i d g e a m i n e n i t r o g e n a t o m w i t h t h e b e n z e n e r i n g .

Assignment of the 7r ~ v * Absorption Bands

The a b s o r p t i o n b a n d s in the e l e c t r o n i c s p e c t r a of the i n v e s t i g a t e d c o m p o u n d s w e r e a s s i g n e d w i t h a l -

! o w a n c e f o r t h e f o l l o w i n g d a t a : the a g r e e m e n t b e t w e e n the c a l c u l a t e d c h a r a c t e r i s t i c s and the e x p e r i m e n t a l
v a l u e s , t h e t y p e of o r b i t a l s b e t w e e n w h i c h t h e e l e c t r o n t r a n s i t i o n , d e t e r m i n e d f r o m the c o e f f i c i e n t s of e x -
p a n s i o n of t h e MO w i t h r e s p e c t to t h e AO, is r e a l i z e d , a l l o w a n c e f o r the c o n f i g u r a t t o n a l i n t e r a c t i o n , t h e
m a g n i t u d e a n d the d i r e c t i o n of the s h i f t of the v - e l e c t r o n d e n s i t y d u r i n g t r a n s i t i o n of t h e m o l e c u l e to the
e x c i t e d s t a t e , l o c a l i z a t i o n of the e l e c t r o n t r a n s i t i o n w i t h i n t h e l i m i t o f c e r t a i n f r a g m e n t s of the m o l e c u l e ,
a n d the d i r e c t i o n ( p o l a r i z a t i o n ) a n d i n t e n s i t y ( o s c i l l a t o r f o r c e ) of t h e t r a n s i t i o n .
A c c o r d i n g t o t h e l i t e r a t u r e d a t a [6], t h e l o n g - w a v e a b s o r p t i o n b a n d s i n t h e e l e c t r o n i c s p e c t r a of a z o c o m -
p o u n d s c a n b e c l a s s i f i e d a s Snv a n d Sv v* t r a n s i t i o n s . T h e Sn~r* b a n d s a r e of low int e n s i t y and a r e f r e q u e n t l y
o v e r l a p p e d by t h e m o r e i n t e n s e b a n d s of t h e Sv v* t r a n s i t i o n s . C o n s i d e r i n g the s t r u c t u r a l p e c u l i a r i t i e s of the
m o l e c u l e , t h e Sv v* t r a n s i t i o n s c a n b e d i v i d e d into s e v e r a l s e r i e s a c c o r d i n g t o the c l a s s i f i c a t i o n in [7, 8]. a b a n d
a s s o c i a t e d w i t h t h e l o n g - w a v e t r a n s i t i o n s o v e r t h e e n t i r e ~ r - c o n j u g a t e d s y s t e m - ' A --*VB (S~4r * o r S2pzV *))
b a n d s a s s o c i a t e d w i t h t h e r e m a i n i n g t r a n s i t i o n s o v e r t h e e n t i r e 7r s y s t e m - VA--*'C (Svr*), b a n d s a s s o -
c i a t e d w i t h t r a n s i t i o n s l o c a l i z e d in the a r o m a t i c r i n g s - ' A ' --*H ($4,~*) , and b a n d s a s s o c i a t e d w i t h t r a n s i -

835
tions between the MO of the entire 7r-conjugated s y s t e m of the molecule and the MO of the a r o m a t i c
r i n g s - ' A ~ ' G (S~r~. and S ~ r , } .
The calculated ~ max values of the intensities and polarizations of the absorption bands are in s a t i s -
f a c t o r y a g r e e m e n t with the experimental values [1]. This attests to a reliable selection of the computational
p a r a m e t e r s . The c h a r a c t e r i s t i c s of the most intense absorption bands r e l a t e d to the transitions with an o s -
cillator force of no less than 0.10 a r e p r e s e n t e d in Table 6.
The long-wave band in the s p e c t r u m of the azo f o r m of I at 432 nm is r e l a t e d to the 'A ~ ' B transition
with a small amount of participation of c h a r g e t r a n s f e r (~ 9%} of the unshared pair of electrons of the oxy-
gen a t o m to the r s y s t e m . According to the calculations, this band is due (96%) to transition f r o m the
upper occupied ~r MO (~UOMO) to the lower vacant 7r * MO (v *LVMO), and the t r a n s i t i o n is polarized along
the x axis. The calculated wavelength of this band (~ max 416 rim) is somewhat lower than the experimental
value (432 n m). This can be explained by the effect of the intramolecular hydrogen bond (IHB), which was
not taken into account in the calculations. The band at 326 nm is r e l a t e d to the 'A ~ ' G transition consisting
(to the extent of 83%) of t r a n s i t i o n between the ~r MO of the qulnoline s y s t e m and the ~ MO of the entire s y s -
t e m of the molecule. The o s c i l l a t o r f o r c e s of both transitions are in s a t i s f a c t o r y a g r e e m e n t with the ex-
peri mental values (f t h e o r / f exp = 3.7-3.9).
A c c o r d i n g to the calculations, the quinonehydrazone f o r m of I is c h a r a c t e r i z e d by a long-wave band
at 499 nm, which is r e l a t e d to the 'A -~'B t r a n s i t i o n polarized along the x axis. It follows f r o m an analysis
of the coefficients of expansion of the MO with r e s p e c t to the AO that this band is due to an S2pz7r . t r a n s i -
tion f r o m ~rUOMO to 7r* LVMO- The 2pz-AO of the b r i d g e - a m i n e - n i t r o g e n atom m~kes the g r e a t e s t con-
tribution (29%} to 7rUOMO. The second ihtense band at 356 nm is r e l a t e d to the 'A ~ ' C transition. The r e -
maining bands that c h a r a c t e r i z e both t a u t o m e r s of I are p r e s e n t e d in Table 6.
It is known [1] that II exists p r i m a r i l y in the f o r m of the quinonehydrazone tautomer. C o r r e l a t i o n of
the calculated and experimental s p e c t r a of the azo f o r m of II is t h e r e f o r e difficult. According to the c a l -
culations, the long-wave band that c h a r a c t e r i z e s the azo f o r m of II should appear at 415 nm. It is r e l a t e d
to the 'A -~'B t r a n s i t i o n f r o m ~UOMO to 7r *LVMO (S~r~r *} p o l a r i z e d along the x axis. Taking the IHB into
account, it can be a s s u m e d that this band should undergo a bathochromic shift of 15-20 nm; this is con-
f i r m e d by expansion of the electronic absorption s p e c t r a of II into Ganssian components [1].
The s p e c t r u m of the quinonehydrazone f o r m of ]I is of g r e a t e s t interest. The calculated s p e c t r u m of
this f o r m is c h a r a c t e r i z e d by the long-wave band of the ' A - ~ ' B transition polarized along the x axis. The
band at 462 n m is due p r i m a r i l y to transition f r o m ~rUOMO to ~*LVMO. I n a s m u c h as 29% of ~UOMO con-
sists of the 2pz AO of the b r i d g e - a m i n e - n i t r o g e n atomand apronounced shift of the electron density f r o m
this nitrogen a t o m to the quinoline ring o c c u r s during this transition, it can be classified as an S2pz7r .
t r a n s i t i o n with charge t r a n s f e r f r o m the b r i d g e - a m i n e - n i t r o g e n atom p r i m a r i l y to the ~r s y s t e m of the quin-
oline ring. The remaining intense bands are caused by a shift of the 'A ~'G and 'A ~'C transitions with
alternating predominance of one or another excited state (Table 6).

LITERATURE CITED

I. B. E. Zaitsev and T. A. Mikhailova, Khim. Geterotsikl. Soedin., 812 (1974}.

2. V. P. Zvolinskii (Zvolinsky), G. I. Kagan, G. M. Kagan, M. E. P e r e l ' s o n (Perelson}, and Ju. N. Shein-
ker, S u m m a r i e s of the Theory of Electronic Shells of Atoms and Molecules, Vilnius (1969), p. 44.
3~ K. Nishimoto and L. S. F o r s t e r , Theor. Chim. Acta, 4_, 155 (1966).
4. M. Dewar, Molecular Orbital T h e o r y of Organic C h e m i s t r y , McGraw-Hill (1969).
5. V. A. Kosobutskii, G. I. Kagan, V. K. Belyakov, and O. G. Tarakanov, Zh. Strukt. Khim., 12, 822
(1971}.
6. R. N. Nurmukhametov, Absorption and L u m i n e s c e n c e of A r o m a t i c Compounds [in Russian], Khimiya,
Moscow (1971}.
7. J. R. Platte, J. Chem. P h y s . , 1.~8, 1168 (1950}.
8. J. R. Platte, J. Opt. Soc., A m e r . , 43, 252 (1953}.

836
INVESTIGATION OF THE HALOGENATION
OF 5-BENYL-3-HYDROXYPYRIDINE

L . D. S m i r n o v , V. S. Z h u r a v l e v , UDC 547.823 : 542.941.1

V. P . L e z i n a , B . E. Z a i t s e v ,
a n d K. IV[. D y u m a e v

The halogenation of 5 - b e n z y l - 3 - h y d r o x y p y r i d i n e proceeds with the formation of 2,6-dihalo-

substituted compounds. The p r e s e n c e of a benzyl group in the 5 position activates the 6 po-
sition of the p - p y r i d o l ring with r e s p e c t to eleetroph[lic attack.

The halogenation of 3-hydroxypyridine and its derivatives has been studied quite extensively [11.
However, the halogenation of 3-hydroxypyridines with substituents in the 5 position has notbeen investigated
up until now. We have investigated the halogenation of 5 - b e n z y l - 3 - h y d r o x y p y r i d i n e (I) in o r d e r to study the
effect of a benzyl group on the r e a c t i v i t y of the fl-pyridol ring.
The halo derivatives obtained (I) a r e intermediates in the synthesis of polyhydroxy-substituted p y r i -
dines and their e t h e r s , which have proved to be e x t r e m e l y effective inhibitors of radical p r o c e s s e s .
The iodination of 5 - b e n z y l - 3 - h y d r o x y p y r i d i n e (I) with excess 12 in sodium carbonate solution at r o o m
t e m p e r a t u r e gave exclusively dtiodo derivative II (2-benzyl-3-hydroxypyridine is iodinated only at 100~ [2]).

H
I I[[

-- " .oL..wA.
II iV V

The s t r u c t u r e of II was established by means of its IN and PIVIN spectra. The IN s p e c t r u m of II in CCI~ is
c h a r a c t e r i z e d by the p r e s e n c e of an intense absorption band at 3462 c m -1, which, as shown in [3], is due to
the stretching vibrations of the OH group tied up in an [ntramolecular hydrogen bond of the OH...I type.
Consequently, one of the iodine atoms [s in the ortho position relative to the OH group. The d e f i n i t t v e o r i e n -
tation of the I atoms was established on the basis of the PMtt s p e c t r u m of II. The absence of the signals at
weak magnetic field that were p r e v i o u s l y assigned to the C2H and C6H protons in I attest to the p r e s e n c e of
2,6-substitution. The chemical shift of the signal at 3.12 ppm is close to the chemical shift of the C4H p r o -
ton of the starting compound. Its singlet s t r u c t u r e also provides evidence in favor of disubstitution. The
a r o m a t i c ring protons give a signal at 3.45 ppm, while the methylene group protons give a signal at 0.02
ppm. The i n t e n s i t y r a t i o s of all of the signals in the s p e c t r u m c o n f i r m the above assignment. Thus the
iodination of I p r o c e e d s at the 2 and 6 positions of the pyridine ring. Inasmuch as iodination of 3 - h y d r o x y -
pyridine under s i m i l a r conditions gives only a monoiodo derivative [4], the r e s u l t s obtained in this study in-
dicate that the benzyl group [n pyridine I activates the 6 position of the fl-pyridol ring with r e s p e c t to e l e c -
trophilic s ubstitution.

Institute of Chemical P h y s i c s , A c a d e m y of Sciences of the USStl, Moscow. T r a n s l a t e d f r o m Khimiya

Geterotsildicheskikh Soedinenii, No. 7, pp. 958-960, July, 1974. Original a r t i c l e submitted June 11, 1973.

9 Plenum Publishing Corporation, 227 West 17th Street, New York, N. 1I. 10011. No part o f this publication may be reproduced.
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

837
 The b r o m i n a t i o n of 5 - b e n z y l - 3 - h y d r o x y p y r i d i n e with an equ[molar amount of bromine in pyridine
gives dibromide HI, the s t r u c t u r e of which was also confirmed by IR and PMR s p e c t r a l data.
The chlorination of I with h y d r o c h l o r i c acid in the p r e s e n c e of 30% H202 did not give d e s i r a b l e r e s u l t s .
We w e r e able to a c c o m p l i s h the synthesis of 2 , 6 - d i m e t h o x y - 5 - b e n z y l - 3 - h y d r o x y p y r i d i n e (IV) by heating the
diiodo derivative (iI) of I with CH3ONa , while dibromo compound III did not undergo an exchange r e a c t i o n un-
der these conditions.
The s t r u c t u r e of IV was confirmed by the IR and PlVIR spectral data. Thus the IR s p e c t r u m of IV con-
tains bands at 1582 and 1602 c m -1, which are r e l a t e d to the vibrations of the a r o m a t i c r i n g s , and a band at
1303 c m - I f r o m the s t r e t c h i n g vibrations of the C - O bonds of ether groups. In addition, signals f r o m the
C2H and C~H protons w e r e absent in the PMR s p e c t r u m of IV, while two singlets at - 0 . 0 6 and 0.16 ppm f r o m
the protons of two OCH 3 groups w e r e present. The singlet at 3.14 ppm was assigned to the C4H proton,while
the signal at 3.42 ppm was assigned to the five protons of the phenylring. The protons of the CH 2 group
f o r m e d a singlet at 0.02 ppm. The a v e r a g e d signal of the OH group and the solvent lay in the 1.24 ppm r e -
gion. The intensity r a t i o of the signals in the s p e c t r u m confirmed the above assignment.
2 , 3 , 6 - T r i h y d r o x y - 5 - b e n z y l p y r i d i n e (V) was obtained in high yield when IV was heated with 40% H]Br.
The IR s p e c t r a l data for V in the crystalline state attested to its p r i m a r y existence in the pyridone f o r m
(vC =O 1701 cm-i). The elevated VNC =O frequency as c o m p a r e d with the ~NC =O frequency in the s p e c -
t r u m of 2-pyridone can be explained by the p r e s e n c e of t h r e e OH groups in the fi-pyridol ring. The intense
bands at 2650 and 2900-3150 c m -1 attested to the p r e s e n c e of OH and NH groups in V.

EXPERIMENTAL
The IR s p e c t r a of CC14 or CHC13 solutions of the compounds (3 9 10 -4 M) were r e c o r d e d with a UR-20
s p e c t r o m e t e r . The PMR s p e c t r a of 5 mole % solutions of the compounds in 1 N NaOD were r e c o r d e d with
an HA-100 s p e c t r o m e t e r with dtoxane as the internal standard.
2 , 6 - D i i o d o - 3 - h y d r o x y - 5 - b e n z y l p y r i d i n e (II). A solution of 0.15 mole of 12 and 0.15 mole of KI in 50
ml of water was added dropwise in the c o u r s e of 30 min at 20 ~ to a solution of 0.1 mole of I in 50 ml of 10%
Na2CO3, and the mixture was allowed to stand overnight. The precipitated product was r e m o v e d by f i l t r a -
tion and dried to give 2 g of II. Acidification of the filtrate with CO 2 gas yielded another 2.2 g of II. The
overall yield of product with mp 202-204 ~ (alcohol) was 93%. Found: C 32.8; H 2.1%. Ct2HgNOI2. Calcu-
lated: C 33.0; H 2.0%.
2 , 6 - D i b r o m o - 3 - h y d r o x y - 5 - b e n z y l p y r i d i n e (III). Pyridine p e r b r o m i d e (from 1.1 ml of Br 2 in 9 ml of
pyridine) was added dropwise at 20 ~ to a solution of 0.01 mole of I in 5 ml of pyridine, after which the mix-
ture was s t i r r e d for 1 h, and the precipitate was separated. The filtrate was poured into water, and the
aqueous mixture was acidified with HC1 and extracted with three 100-ml portions of ether. The organic
l a y e r was s e p a r a t e d and dried, and the solvent was r e m o v e d to give III with mp 59-60 ~ (after sublimation)
in 60% yield. Found: C 39.8; H 3.1%. C12HgNOBr2"H20. Calculated: C 39.9; H 3.0%.
2 , 6 - D i m e t h o x y - 3 - h y d r o x y - 5 - b e n z y l p y r i d i n e (IV). A solution of 0.01 mole of II in 25 ml of CH3ONa
(from 0.04 g - a t o m of Na and 25 ml of CH3OH ) was heated in an autoclave at 160 ~ for 10 h, after which the
solvent was r e m o v e d by distillation, and the r e s i d u e was dissolved in water. The aqueous solution was
acidified by bubbling CO 2 gas through it, and the resulting precipitate was s e p a r a t e d and dried to give IV
with mp 115-117 ~ (alcohol) in 70.5% yield. Found: C 68.6; H 6.1%. C14H15NO3. Calculated: C 68.6; H 6.0%.
2 , 3 , 6 - T r i h y d r o x y - 5 - b e n z y l p y r i d i n e (V). A 0.01-mole sample of IV was heated in 10 ml of concen-
t r a t e d HBr for 2 h on an oil bath at 160 ~ It was then cooled, and the precipitated product was r e m o v e d by
filtation to give V with mp 228-230 ~ (alcohol) in 71% yield. Found: C 66.4; H 5.1%. C12HllNO3. Calculated:
C 66.3; H 5.0%.

LITERATURE CITED

1. R . A . A b r a m o v i t c h and J. G. Saha, Advan. Heterocycl. Chem., 6, 229 (1966).

2. L . D . Smirnov, V. S. Zhuravlev, M. A. Gugunova, V. P. Lezina, and K. M. Dyumaev, Izv. Akad. Nauk
SSSR, Set. Khim., 1878 (1972).
3. B . E . Zaitsev, N. A. Andronova, K. M. Dyumaev, and L. D. Smirnov, Khim. Geterotsikl. Soedin., 1535
(1971).
4. O. Shickh, AoBinz, and A. Schulz,Bero, 6_99, 2593 (1936).
5. H . J . d e n H e r t o g , F. R. Scherpman, J. de Bruyn, and J. E. T h y s s 6 , R e c . T r a v . Chim., 69, 1281 (1950).

838
RECYCLIZATION REACTIONS OF HETEROCYCLES
XV.* REACTION OF ISOQUINOLINIUM SALTS WITH HYDRAZINES

V. S. G a r k u s h a - B o z h k o , O. P . S h v a i k a , UDC 547.833'792'883
L . M. K a p k a n , a n d S. N. B a r a n o v

The direction of r e c y c l i z a t i o n during hydrazination of isoquinolinium salts is p r a c t i c a l l y

independent of the substituent attached to nitrogen and the r e a c t i o n conditions and leads to
compounds with an N-aminoisoquinoline s t r u c t u r e .

Recyclization only to the c o r r e s p o n d i n g N-amino derivatives by the action of hydrazines has been de-
s c r i b e d for pyridinium and isoquinolinium salts [2, 3]. A c c o r d i n g to [3], the r e c y e l i z a t i o n of isoquinolinium
salt Ia proceeds through the intermediate formation of addition product H and hydrazone III, which cyclizes
under the influence of acids to N-aminoisoquinolinium salt VIII. We have investigated the hydrazination of
isoquinolinium salts I a - f in o r d e r to a s c e r t a i n the possibility of the formation of benzodiazepine s y s t e m IV.
In a study of the action of hydrazine, hydrazine hydrate, and lithium hydrazide on salts I in aqueous,
alcohol, and dioxane media, or in hydrazine itself, and also in the p r e s e n c e of alkali or an organic base un-
der various t e m p e r a t u r e conditions, we isolated (as a stable product) only a c o l o r l e s s solid with variable
physical p r o p e r t i e s but a constant e l e m e n t a r y composition, (CgHsN2)n (V), which was found to be a mixture
of o l i g o m e r s with n_>_2. In p a r t i c u l a r , individual o t i g o m e r s with n =2, 4, and 9 were isolated. The oligomer
r a t i o in the mixtures depends on the hydrazination conditions. The oligomer with n =2 is identical to the
dimer of N-iminoisoquinoline - t e t r a z a n VII [3, 4] - both with r e s p e c t to melting point and other p r o p e r t i e s
and does not depress the melting point of a sample obtained by the method in [3]. On acidification it r e a d i l y
f o r m s salt VIII (R =H), the neutralization of which does not yield m o n o m e r i c base VI (R =H) - t h e latter
d i m e r i z e d immediately to t e t r a z a n VII. It should be noted that o l i g o m e r s V with n > 2 are f o r m e d along with
dimer VII on rapid neutralization with concentrated alkali solution.
The VNH band is weak in the IR s p e c t r u m of VII. The PMR s p e c t r u m contains two groups of signals
at 5.32 and 6.49 ppm, which are split into a doublet (J =7.7 Hz) and a r e r e l a t e d to the - C H = C H - p r o t o n s , a
multiplet at 7.14 ppm, which is r e l a t e d to the signals of the benzene ring protons, and a singlet at 5.89 ppm,
which c o r r e s p o n d s to four protons. When the PMR s p e c t r a a r e r e c o r d e d at different t e m p e r a t u r e s , this
signal is initially split into two signals as the t e m p e r a t u r e r i s e s , and at 57-78 ~ one of t h e m is shifted to
s t r o n g e r field. These protons apparently participate in the formation of a hydrogen bond with the solvent
[dimethyl sulfoxide (DMSO)], and this makes it possible to assign this signal to the protons of the NH group.
Thus the PMR s p e c t r a l data unambiguously indicate t e t r a z a n s t r u c t u r e VII.
The s t r u c t u r e s of the higher oligomers (V) w e r e not a s c e r t a i n e d , although the absence of free t e r -
minal hydrazine groups (negative r e a c t i o n with benzaldehyde and Fehling solution) makes it possible to a s -
sume a m a c r o c y c l i c s t r u c t u r e for them.
The formation of only compounds with N-aminoisoqulnoline s t r u c t u r e (VI-VIID during the h y d r a z i n a -
tion of the isoquinolinium salts (in c o n t r a s t to the p y r y l i u m and thiapyrylium salts [5, 6]) may be a s s o c i a t e d
either with a r o m a t i z a t i o n of the 2,3-benzodiazepine s y s t e m (IV) or with the possibility of stabilization of

*See [1] for communication XIV.

Donetsk P h y s i c a l Organic C h e m i s t r y Branch, Institute of Physical C h e m i s t r y , A c a d e m y of Sciences

of the Ukrainian SSR. T r a n s l a t e d f r o m Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 961-965, July,
1974. Original article submitted July 10, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

839
intermediate hydrazone III in the syn configuration glib), as a r e s u l t of which ring closing to diazepine IV
is s t e r i c a l l y hindered, while the formation of the N-aminoisoquinoline s y s t e m VI should not depend markedly
on the configuration of intermediate hydrazone HI and, in addition, is t h e r m o d y n a m i c a l l y more favorable.
N-Iminoisoquinoline derivatives VI OR' = C O R " ) , which, because of delocalization of the negative
charge, are e x t r e m e l y stable also in the base f o r m , a r e f o r m e d in the r e a c t i o n of isoquinolinium salts with
a c y l h y d r a z i n e s , in which the am[de nitrogen atom usually manifests lower nucleophilic activity [6]. The
synthesis of N-acyliminoisoquinolines VI OR' =COR") f r o m isoquinoline N-sulfotrioxide {If) proved to be a
p a r t i c u l a r l y convenient method in a p r e p a r a t i v e r e s p e c t as c o m p a r e d with other methods [2]. I s o m e r i c c y -
clic s t r u c t u r e IX (X=O), which does not have separated c h a r g e s , can be proposed for N-acyliminoisoquino-
lines VI OR' = C O R " ) . However, the chemical p r o p e r t i e s , p a r t i c u l a r l y the high solubility in acids to give
salts VIII and the IR s p e c t r a l d a t a - the p r e s e n c e of c h a r a c t e r i s t i c frequencies of the ( - N - C - O ) (~ grouping
at 1550-1600 and 1350 c m -1 - constitute evidence in favor of betaine s t r u c t u r e VI, even when R =NH 2 or
CCHsNH (also see the data in [3]). However, in the case of r e c y c l i z a t i o n of isoquinolinium salts under the
influence of c a r b o h y d r a z i d e (under more s e v e r e conditions, of course) X was isolated along with a certain
amount of an unidentified product. The s t r u c t u r e of X and its difference f r o m open i s o m e r VI (1={,: ,
CONHNH2) are c o n f i r m e d by the s p e c t r a l and chemical data. The c h a r a c t e r i s t i c bands of the ( - N - C - O ) O
group a r e not o b s e r v e d in the IR s p e c t r u m of this substance, but the s p e c t r u m does contain an intense b r o a d
band at 1680 c m - i (C =O). In c o n t r a s t to betaines VI, it is not soluble in dilute mineral acids and does not
have a free hydrazine group. Benzylidene derivative XII is formed with benzaldehyde, and this constitutes
evidence for the p r e s e n c e of a free amino group. Monodeamination to give XI o c c u r s under the influence
of nitrous acid.

%NHNHR' 7

N--R

! a-f II [11 ap b IV
~ ___N"2"N-<~

V
X -!/ VI t: a
HO //H'

ng i ..

" t>=
IX VIII Vll

I a R=2,4-(NO.)2C6H. ~, X=EI; b R=CH 3, X : l ; c R=CH 3, X=p-CHsC.H SO-:

dR=C2Hs, X=I; e R=CH2CoHs, X=CI; fRX=-SO 3

In conclusion, we s i n c e r e l y thank V. M. Bilobrov for r e c o r d i n g the I1R spectra.

EXPERIMENTAL

The IR s p e c t r a of p o t a s s i u m bromide pellets of the compounds were r e c o r d e d with a UR-10 s p e c -

t r o m e t e r . The PMR s p e c t r a of DMSO solutions were r e c o r d e d with a YaM1R-5535 s p e c t r o m e t e r at 40 MI-Iz
r e l a t i v e to cyelohexane as the internal standard; the chemical shifts were converted to the t e t r a m e t h y l s i -
lane scale. The molecular weights w e r e determined by the Z i g n e r - C l a r k isothermal distillation method [8]
in c h l o r o f o r m .
The N-alkylisoquinolinium salts were obtained by heating equimolar amounts of freshly distilled alkyl
halides or methyl tosylate with isoquinoline in d r y dioxane. The melting points of the salts obtained were in
good a g r e e m e n t with the handbook values.
Isoquinoline N-sulfotrioxide was obtained by a somewhat modified method [7] by addition of f r e s h l y
distilled sulfur trioxide to an eqnimolar amount of isoquinoline in dry a l c o h o l - f r e e c h l o r o f o r m at 0-5 ~
Hydrazinolysis of N-Alkylisoquinolinium Salts I. In a typical experiment, a 1.5-fold amount of h y d r a -
zinc hydrate was added to an aqueous solution of the appropriate I salt, and the mixture was allowed to

840
 TABLE 1. N-Acyliminoisoquinolines VI (R' =COR")

Empirical Found, % I Calculated ~ IR spec-

rap. ~ formula
R~
C 7i 7 THai C !H N Hal =m.
cm'l o
.~

I ,
C6H5 [186--187"!CI6HI~N.O 77,2 4,8 11,3 --]77,4'.49i 11,3 - 13%,?o/97
p-CIC6H4 183--185 'CIGHuC1NeO 67,8 4,0 10,! 12,3 68,03,9 9,9 12,55 1350, 1565184
[ 1605!
p-BrC~H~ 186--190 C,aHnBrN20 58,5 3,5 841242 5873,4 8,6 94,4 I - - ~ ! 80
(dec.)
n~-NO2C6H4 i227--229 ClsHuNsOa -- 14,2! --, --[--[14,3 -- J1345 1560179
_

(dec.) l 160o '!

p- (CHa)2NC6H4216--219 C,sH,rNaO ! -- 14,2' -- - - / - - 14,4 - i137G 6o',
(dec.)
~'C~oHr >270 !80,84, 1 9,4,, --i8054,7~
I'![ 95 85 , - -

(dec.)

*According to [3], this compound has mp 188 ~

stand overnight. Slight warming was s o m e t i m e s n e c e s s a r y . The precipitate was separated, washed with
water, and vacuum dried over phosphorus pentoxtde without heating. The yields ranged f r o m 80 to 90%.
The p r e p a r a t i o n obtained by this method f r o m N-methylisoquinolinium iodide was an almost c o l o r l e s s pow-
der that began to decompose at ~ 130 ~ Found: C 74.8; H 5.3; N 19.7%. CgH8N2. Calculated: C 75.0; H 5.6;
N 19.4%. Substances of the same composition were obtained as follows: by r e a c t i o n of isoqutnolintum salts
I with lithium hydraztde in dioxane at r o o m t e m p e r a t u r e or by refluxing a suspension of the r e a c t a n t s , by
r e a c t i o n with absolute hydraztne in absolute alcohol at - 1 5 ~ and at r o o m t e m p e r a t u r e , and by reflaxtng the
r e a c t a n t s , and by reaction with p r i o r alkalization and subsequent addition of hydrazine,
The samples obtained (and the fractions subsequently isolated f r o m them) were found to have m o l e c -
ular weights of 130 to 180 by the Rast method in camphor; however, these r e s u l t s cannot be considered to
be c o r r e c t because of appreciable decomposition of the s a m p l e s during homogenization of the camphor melt.
An effective molecular weight of 500 was obtained by i s o t h e r m a l distillation in c h l o r o f o r m ; this value c o r -
responds to an a v e r a g e degree of p o l y m e r i z a t i o n of 3.5. In o r d e r to a c c o m p l i s h separation of the mixture
of oligomers into n a r r o w f r a c t i o n s , the mixture was subjected to fractional precipitation Prom dtoxane solu-
tion (the fractions precipitated in the o r d e r of d e c r e a s i n g molecular weight) or was fractionated on a l u m i -
num oxide (the fractions were elated in the o r d e r of increasing molecular weight). The n a r r o w fractions of
the o l i g o m e r s were c r y s t a l l i z e d until the products had acceptably constant melting points. The c h a r a c t e r -
istics of two of the samples obtained a r e p r e s e n t e d below.
Nonamer V (n=9). This compound was obtained as a c o l o r l e s s substance with mp 200-203 ~ (dec.,
f r o m d[oxane). Found: C 74.8; H 5.5; N 19.7%; M 1305. (CgH8N2)9. Calculated-" C 75.0; H 5.6; N 19.4%;
M 1296.
Dtmer V (n =2). This compound was obtained as c o l o r l e s s c r y s t a l s with mp 157-160 ~ (from benzene).
Found: C 75.1; H 5.7; N 19.4%; M 286. (CgHsN2)2. Calculated: C 75.0; H 5.6; N 19.4%; M 288.
B f s - ( 1 , 2 - d t h y d r o i s o q u t n o t i n o [ 2 , 1 - b : 2 , 1 - e ] ) - l , 2 , 4 , 5 - t e t r a z a n (VII). A 1.5-fold amount of 3-5% sodium
hydroxide solution was added in the cold to an aqueous solution of N-amtnoisoquinoliniam iodide, and the
mixture was allowed to stand for a s h o r t time. The resulting precipitate was s e p a r a t e d , washed r e p e a t e d l y
with water, and vacuum dried without heating to give a product in 70% yield. Crystallization f r o m benzene
in the p r e s e n c e of aluminum oxide gave c o l o r l e s s c r y s t a l s with mp 158-160 ~ that did not depress the melting
point of a sample of d i m e r V (n =2). A melting point of 147-150 ~ for VII ts p r e s e n t e d in [4]; this melting
point may be a s s o c i a t e d with the fact that the observed melting point of VII depends markedly on the heating
r a t e . It ts also possible that Hulsgen and c o - w o r k e r s [4] were dealing with a sample containing higher oli-
g o m e r s . We observed the formation of o l t g o m e r i c impurities in the d i m e r when concentrated solutions of
aminoisoquinoltntum salt VIII and sodium hydroxide were mixed rapidly.
N-Acyliminoisoquinoltnes (VI). A 2.1-g (10 mmole) sample of thoroughly pulverized [soquinoline N-
sulfotrioxide was added with vigorous s t i r r i n g to a cooled (to - 5 - 0 ~ solution of 2.4 g of sodium hydroxide
in 10 ml of water, 1-2 rain, after which 10 mmole of the approximate acylhydraztne was added. Stirring
was continued, and the s u b s t r a t e was allowed to w a r m up to r o o m t e m p e r a t u r e and was held at r o o m t e m -
p e r a t u r e until the initially f o r m e d color of the suspension almost disappeared. A s o l u t i o n o f l 0 m t o f a c e t i c
acid in 20 ml of w a t e r was then added to the mixture, and the mixture was boiled for 1-2 min. It was then

841
cooled and diluted with a t h r e e - to fourfold amount of w a t e r , and the p r e c i p i t a t e was s e p a r a t e d , washed with
w a t e r , v a c u u m dried and c r y s t a l l i z e d f r o m an a p p r o p r i a t e solvent. C o l o r l e s s c r y s t a l s that w e r e only
slightly soluble in m o s t organic solvents w e r e obtained. An intense vCO band at ~ 1700 c m -1 a p p e a r e d in
the IR s p e c t r a during salt f o r m a t i o n , while the ( - N - C - O ) e a b s o r p t i o n band d i s a p p e a r e d . The physical
constants and yields of the s y n t h e s i z e d compounds a r e p r e s e n t e d in Table 1.
1 - A m i n o - 2 - o x o - 2 , 3 , 3 a , l a - t e t r a h y d r o t r i a z o l o - l , 2 , 4 - [3,2-a]isoquinoline (X). A mixture of 3.15 g (10
mmole) of N-methylisoquinolinium t o s y l a t e and 0.9 g (10 mmole) of c a r b o h y d r a z i d e in 15 ml of d i m e t h y l -
f o r m a m i d e was held at 140 ~ for 3 - 4 h. The mixture was then cooled and diluted with w a t e r , and the p r e c i p -
itate was s e p a r a t e d and washed with 3% h y d r o c h l o r i c acid and s e v e r a l t i m e s with water. Vacuum drying
gave ~ 0.7 g (35%) of c o l o r l e s s c r y s t a l s with mp 315-320 ~ (dec., f r o m glacial acetic acid). Found: C 59.0;
H 5.1; N 27.4%. C10H10N40. Calculated: C 59.4; H 5.0; N 27.7%. LR s p e c t r u m : 1635, 1680, 3150, 3260, and
3350 c m -1.
1 - B e n z y l i d e n e a m i n o - 2 - o x o - 2 , 3 , 3 a , l a - t e t r a h y d r o t r i a z o l o - l , 2 , 4 - [ 3 , 2 - a ] i s o q u i n o l i n e (XII). A m i x t u r e
of 0.2 g (1 mmole) of X and 0.1 g (1 mmole) of benzaldehyde in 10 ml of glacial acetic acid was refluxed for
10 min in the p r e s e n c e of 0.05 g of sodium acetate. The mixture was then cooled and diluted with w a t e r ,
and the p r e c i p i t a t e w a s s e p a r a t e d , washed with w a t e r , alcohol, and e t h e r , and dried to give 0.25 g (86%) of
c o l o r l e s s c r y s t a l s with mp 255-257 ~ (dec., f r o m dilute acetic acid). Found: C 70.0; H 4.9; N 19.4%.
C17H14N40. Calculated: C 70.3; H 4.8; N 19.3%. IR s p e c t r u m : 1630, 1680 c m -1.
2 - O x o - 2 , 3 , 3 a , l a - t e t r a h y d r o t r i a z o l o - l , 2 , 4 - [ 3 , 2 - a ] i s o q u i n o l i n e (XI). A 0.1-g s a m p l e of X was dissolved
in 10 ml of acetic acid, 0.05 g of finely ground s o d i u m nitrate was added, and the mixture was s t i r r e d and
allowed to stand for 1 h. It was then diluted with w a t e r , and the r e s u l t i n g p r e c i p i t a t e was s e p a r a t e d , washed
with w a t e r , and t r e a t e d with dilute sodium hydroxide solution. The m i x t u r e was filtered, and the filtrate
was n e u t r a l i z e d with dilute h y d r o c h l o r i c acid. The white p r e c i p i t a t e was s e p a r a t e d , washed with w a t e r , and
v a c u u m dried to give 0.05 g (55%) of a product with mp 285-290 ~ (dec., in a sealed c a p i l l a r y ; f r o m dimethyl-
f o r m a m i d e - w a t e r ) that sublimed above 250 ~ Found: C 63.9; H 4.7; N 22.2%. C10HgN30. Calculated:
C 64.2; H 4.8; N 22.5%.

LITERATURE CITED

1. O. P. Shvaika and V. I. Fomenko, Zh. Organ. Khim., 10, 377 (1974).

2. Y. T a m u r a and N. T s u j i m o t o , Chem. Ind., 926 (1970).
3. B. Agai and K. L e m p e r t , T e t r a h e d r o n , 2._~8,2069 (1972).
4. R. Huisgen, R. G r a s h e y , and R. K r i s c h k e , T e t r a h e d r o n Lett., 387 (1962).
5. A. T. Balaban, T e t r a h e d r o n , 2_~4, 739, 743 (1968).
6. O. P. Shvaika and V. N. A r t e m o v , Usp. Khim., 41, 1801 (1972).
7. P. B a u m g a r t e n and J. Olshausen, B e r . , 6_~4,925 (1931).
8. N. C h e r o n i s , M i c r o - and S e m i m i c r o m e t h o d s of Organic C h e m i s t r y [Russian translation], Inostr. Lit.,
Moscow (1960), p. 179.

842
INVESTIGATION
OF 2,3-POL YMETHYLENEQUINOLINES
XX.* REACTION OF N-CYCLOHEXYLIDENEANTHRANILIC ACID
BENZ YLAMIDES WITH PHOSPHOR US OXYCHLORIDE

M. E. Konshin UDC 547.835.2.3

The r e a c t i o n of N-cyclohexylideneanthranilic acid benzylamides with phosphorus oxychloride

is accompanied by cycltzation at the ~ - m e t h y l e n e group of the cyclohexylidene ring to give
9-benzylamino-1,2,3,4-tetrahydroacridines.

9-Alkylamino- [2] and 9-arylamino-l,2,3,4-tetrahydroacridines [3] are formed by intramolecular cy-

clization of N-cyclohexylideneanthranilic acid alkyl(aryl)am[des by means of phosphorus oxychloride. This
reaction has been extended to benzylamides I in order to evaluate the reactivity of the benzene ring and the
- methylene gro up in eyel ohexyl idene imines.

N! HCH.C,-H.
z , J
N --C H.,C6[5~, NI--CHoC6Hs"]
,f H -
R.-..~6o /---~ Pool3 R ~ c~l~ -ct- y- , y cM~ t

It II1

CI NHCH2CeH 5

IV V 2 N= _.~
VI

a R=tl; b R=EI; c R~Br

Under the influence of phosphorus oxychloride, benzylamides I are apparently converted to c h l o r o -

imides II [4], which dissociate to ions III [5]. Ions III contain an electrophilic r e a c t i o n center - t h e n i t r i l -
ium - and two nucleophilic reation centers - the benzyl group and the cyclohexylidene ring. Although c y c l i -
zation may, as a consequence of this, lead to two products - 9 - b e n z y l a m i n o - l , 2 , 3 , 4 - t e t r a h y d r o a c r i d i n e s IV
and substituted isoindoles V - the formation of only t e t r a h y d r o a c r i d i n e s IV was observed. The higher r e -
activity of the e - m e t h y l e n e group as c o m p a r e d with the benzene ring can be explained by h y p e r c o n j u g a -
tion- ,~"~=c - CH~--H.

The str ucture of IVa was confirmed by alternative synthests f r o m 9 - c b l o r o - 1 , 2 , 3 , 4 - t e t r a h y d r o a c r i -

dine (VI) and by the IR s p e c t r u m , which contained an NH band at 3435-3445 c m -1.

* See [1] for communication XIX.

P e r m P h a r m a c e u t i c a l Institute. T r a n s l a t e d f r o m Khimiya Geterotsiklieheskikh Soedineni[, No. 7,

pp. 966-967, July, 1974. Original a r t i c l e submitted July 10, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy o f this article is available from the publisher for $15.00.

843
 EXPERIMENTAL
N - C y c l o h e x y l i d e n e a n t h r a n i l i c Acid B e n z y l a m i d e s (I). A solution of 0.01 mole of the b e n z y l a m i d e of
the a p p r o p r i a t e anthranilic acid and 0.01 mole of eyclohexanone in 10 ml of benzene was refluxed for 0.5-4
h, a f t e r which it was cooled, and the r e s u l t i n g c r y s t a l l i n e p r e c i p i t a t e was r e m o v e d by filtration and c r y s t a l -
lized. In the c a s e of Ia, the heating t i m e was 0.5 h, and the yield of product with mp 185-187 ~ (from b e n -
zene) was 80%. Found: N 9.3%. C20H22N20. Calculated: N 9.2%. In the c a s e of Ib, the heating t i m e was
4 h, and the yield of product with mp 215-217 ~ (from benzene) was 70%. Found: N 8.5%. C20H21C1N20. C a l -
culated: N 8.2%. In the c a s e of Ic, the heating t i m e was 4 h, and the yield of product with mp 214 ~ (from
benzene) was 75%. Found: N7.4%. C20H21BrN20. Calculated: N 7.3%.
9 - B e n z y l a m i n o - l , 2 , 3 , 4 - t e t r a h y d r o a c r i d i n e (IVa). A 0.01-mole s a m p l e of b e n z y l a m i n e was added to
a solution of 0.01 mole of VI [6] in 10 g of fused phenol, and the mixture was heated at 160-170 ~ for 20 h. It
was then t r e a t e d with 10% NaOH solution, and the r e s i d u e was c r y s t a l l i z e d to give IVa with mp 114 ~ (from
hexane) in 50% yield. Found: C 83.1; H 6.6; N 9.5%. C20H20N2. Calculated: C 83.3; H 7.0; N 9.7%. The
h y d r o c h l o r i d e had mp 252 ~ (from alcohol).
9 - B e n z y l a m i n o - l , 2 , 3 , 4 - t e t r a h y d r o a c r i d i n e s (IV). A solution of 0.05 mole of I in 3 ml of phosphorus
oxychloride was r e f l u x e d for 30 min, a f t e r which it was poured into w a t e r and n e u t r a l i z e d with 10% alkali
solution (after decomposition of the phosphorus oxychloride). The p r e c i p i t a t e d IV was r e m o v e d by f i l t r a -
tion and c r y s t a l l i z e d . Compound IVa with mp 114 ~ (from hexane) was obtained in 52% yield. No melting-
point d e p r e s s i o n was o b s e r v e d for a mixture of this product with a s a m p l e of IVa obtained in the p r e c e d i n g
e x p e r i m e n t . Compound IVb with mp 124 ~ (from alcohol) was obtained in 50% yield. Found: C 74.1; H 5.6;
N 8.2%. C2~-I19C1N2. Calculated.- C 74.5; H 5.9; N 8.3%. Compound IVc with mp 112 ~ (from alcohol) was
obtained in 60% yield. Found: C 65.1; H 5.0; N 7.7%. C2~tI19BrN2 . Calculated: C 65.4; H 5.2; N 7.9%.

LITERATURE CITED
1. M. E. Konshin, D. I. Uvarov, t~. S. A b r a m o c h k i n , A. S. Zaks, and T. A. Kapitonenko, K h i m . - F a r m a t s .
Zh. (197,i, in p r e s s ) .
2. M. E. Konshin and P. A. Petyunin, K h i m . - F a r m a t s . Zh., No. 11, 10 (1971).
3. P. A. Petyunin, M. E. Konshin, and Yu. V. Kozhevnikov, Zh. Vsesoyuzn. Khim. Obshchestva, 12, 238
(1967).
4. M. M. Sidiki and R. C. Shah, Chem. Abstr., 3761 (1938).
5. G. Fodor, I. Gal, and B. A. Phillips, Angew. Chem., 84, 947 (1972).
6. L. Sargent and L. Small, J. Org. Chem., 11, 359 (1946).

844
INVESTIGATION OF NAPHTHYRIDINES
VI.* METHOD FOR THE SYNTHESIS OF 9-AMINO-4-AZAACRIDINES

A. I. Mikhalev and M. E. Konshin UDC 547.836.3

A method for the synthesis of 9 - a m i n o - 4 - a z a a c r i d i n e s by cyclization of 2 - a r y l a m i n o n i c o t i n -

onitriles by heating with a l u m i n u m chloride is proposed. The 2 - a r y l a m i n o n i c o t i n o n i t r i l e s
w e r e obtained by condensation of 2 - c h l o r o n i e o t i n o n i t r i l e with a r y l a m i n e s .

2 - A r y l a m i n o n i c o t i n o n i t r i l e s (I-V, Table 1) w e r e obtained in the p r e s e n t r e s e a r c h by r e a c t i o n of 2-

ehloron[eotinonitrile with a r y l a m i n e s in o r d e r to study the p o s s i b i l i t y of the syn?;hesis f r o m them of 9 - a m i n o -
4 - a z a a c r i d i n e s , which a r e of i n t e r e s t as potential physiologically active substances. DesPite the data in [2],
the r e a c t i o n of 2 - e h l o r o n i c o t i n o n i t r i l e p r o c e e d s s u c c e s s f u l l y with a r y l a m i n e b a s e s but not with their salts.

[ N--,~cl. "l

NffA~j'
I-Y VI ~ VII-XI
0

[t
X|l

We w e r e able to a c c o m p l i s h the cyclization of I - V to 9 - a m i n o - 4 - a z a a e r i d i n e s (VH-XI, Table 2) by

heating t h e m with anhydrous a l u m i n u m chloride. A t t e m p t s to cyclize nitrile I by means of polyphosphoric
acid (-PPA) gave 4 - a z a - 9 - a c r i d o n e (XII).
The s t r u c t u r e of VII-XI was c o n f i r m e d by analytical data and hydrolytic cleavage of d e r i v a t i v e VII to
give 4 - a z a - 9 - a c r i d o n e . Because of the low solubility of the products in most solvents, the IR s p e c t r u m was
obtained only for a solution of VII in c h l o r o f o r m ; the s p e c t r u m of this solution contains NH 2 bands at 3450
and 3380 c m -1.
The eyclization of n i t r i l e s I - V is a p p a r e n t l y an i n t r a m o l e c u l a r electrophilic substitution r e a c t i o n that
p r o c e e d s through a step involving the f o r m a t i o n of ionic complex VI, in which the p o s i t i v e l y charged carbon
a t o m attacks the adjacent benzene ring.

EXPERIMENTAL
2 - A r y l a m i n o n i c o t i n o n i t r i l e s {I-V). A mixture of 0.01 mole of 2-ehloronicotinonitrile [3] and 0.01mole
of a r y l a m i n e was heated at 150-180 ~ for 20-30 rain, a f t e r which it was t r e a t e d with hot w a t e r , and the r e s t -
due was c r y s t a l l i z e d f r o m methanol.

*See [1] for communication V.

P e r m P h a r m a c e u t i c a l Institute. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 7, pp.

968-969, July, 1974. Original a r t i c l e submitted July 10, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy of this article is available from the publisher for $15.00.

845
 T A B L E i. 2-Arylaminonicotinonitriles (I-V)

Found, % Calculated %
Com- ~2
rap, ~
pound ~2P2uril:al /C(Hal;i -I-I-- N C(Hal) H

I H C12HgN3 74~ 43
II p-CH3 1141L~215 CI~HuNa 5~ 20-; 75 41
Ill o-CH3 102--103 C13HllNa 74,6 ] 5,5 20,1 74,6 [ 5,3 20,1 56
IV p-Br 141--142 CI2HsBrNa (29,5) -- 15,1 (29,2) I -- 15,3 58
V p-Cl 135--137 CI:HsC1N3 (15,5) 18,0 (15,3)1 18,3 55

T A B L E 2. 9-A m i n o - 4 - az a a c r i d i n e s (VII-X'I)

Found* Calculated
Com- rap, *C Empirical
pound R formula q)
C,% H, %[ N,% M C, % H. % N, %1 M

vii H 277--280 C12HgNa 738 218 205,5 739 F46

I , 215 1%1 42
VIII 7-CH3 295--297 ClaHuNa 74,6 I 19,8 211 74,61 53f 20,I 209 57
IX 5-CH3 278--280 CIaHllN3 74,7 20,0 218,9 74,6: 20,! 209 ] 45
X 7-Br 300--301 CI2HaBrNa -- 15,2 280 -- ] 15,3 274 50
XI 7-Cl 308--309 C12HsCIN3 18,3 233,7 -- i -- 18,3 229,6 65

*In t h e c a s e of VII a n d X-I, 2 a n d 2.1% a c t i v e h y d r o g e n a r e

found, r e s p e c t i v e l y .

9-Amino-4-azaacridines (VII-XI). A 1 . 5 - g s a m p l e of a n h y d r o u s a l u m i n u m c h l o r i d e w a s a d d e d to 0.01

m o l e of 2 - a r y l a m t n o n i c o t i n o n i t r i l e , and the m i x t u r e w a s h e a t e d at 180-200 ~ for 3 0 - 4 0 min. It w a s t h e n d e -
c o m p o s e d in the c o l d w i t h 10% HC1 s o l u t i o n , and e x c e s s 30% NaOH s o l u t i o n w a s a d d e d . The r e s u l t i n g p r e -
cipitate was removed by filtration and crystallized from ethanol.
4 - A z a - 9 - a c r i d o n e (XII). A m i x t u r e of 0.01 m o t e of 2 - a n i l i n o n i c o t i n o n i t r i l e a n d 10 ml of p o l y p h o s -
p h o r i c a c i d w a s h e a t e d at 150 ~ f o r 5 h, a f t e r w h i c h it w a s d i l u t e d w i t h w a t e r a n d n e u t r a l i z e d w i t h 10% a m m o -
n i u m h y d r o x i d e . The r e s u l t i n g p r e c i p i t a t e w a s c r y s t a l l i z e d f r o m m e t h a n o l to give 0.45 g (45%) of 4 - a z a - 9 -
a c r i d o n e w i t h m p 2 7 8 - 2 7 9 ~ [4]. A m i x t u r e of t h i s p r o d u c t w i t h VII m e l t e d a t 250 ~
H y d r o l y s i s of VII. A s o l u t i o n of 0.7 g of VII in 10 ml of 15% HC1 w a s r e f l u x e d on a s a n d b a t h f o r 5 h,
a f t e r w h i c h it w a s c o o l e d a n d n e u t r a l i z e d w i t h 10% a m m o n i u m h y d r o x i d e . The r e s u l t i n g p r e c i p i t a t e w a s r e -
m o v e d b y f i l t r a t i o n a n d c r y s t a l l i z e d f r o m m e t h a n o l to g i v e 0.24 g (34%) of a p r o d u c t w i t h mp 2 7 8 - 2 7 9 ~ No
m e l t i n g - p o i n t d e p r e s s i o n w a s o b s e r v e d f o r a m i x t u r e of t h i s p r o d u c t w i t h a s a m p l e of XII o b t a i n e d in the
preceding experiment.

LITERATURE CITED

I. V. A. K h a l d e e v a and M. E. K o n s h i n , Izv. Vuzov, K_him. (1974, in p r e s s ) .

2. P . N a n t k a - N a m i r s k i , A c t a P o l o n . P h a r m . , 24, 111 (1967).
3. O r g a n i c S y n t h e s e s [ R u s s i a n t r a n s l a t i o n ] , Vol. 9, I n o s t r . L i t . , M o s c o w (1959), p. 45.
4. S. C a r b o n [ , G a z z . C h i m . I t a l . , 85, 1201 (1955).

846
APPLICATION OF MASS SPECTROMETRY

IN STRUCTURAL AND STEREOCHEMICAL

INVES TIGATIONS
IV.* PECULIARITIES OF THE MASS SPECTRA
OF fl-OXOQUINUCLIDINES AND THEIR ANALOGS

A. I. Ermakov, Yu. N. Sheinker, UDC 547.834.4 : 543.51 : 541.61.63

and V. K. Potapov

The mechanis m of the p r o c e s s M +. ~ ( M - C O ) +" during fragmentation, under the influence

of electron impact, of some btcyclic amines with a nodal nitrogen atom and containing an
oxo group in various positions of the bridged s y s t e m is discussed. Data on the ionization
potentials and low-voltage mass s p e c t r a and f r o m high-resolution mass s p e c t r o m e t r y are
used.

It has been shown [2, 3] that the relative intensities of the M +. molecular ion peak and the peak of the
(M-CO) +. fragment in the mass s p e c t r a of various substituted fl-oxoquinuclidines at 10-70 eV are indepen-
dent of a change in the ionizing-electron energy. It follows f r o m Fig. 1 that the M +. and (M-CO) +. peaks and
their M + . / ( M - C O ) +. r a t i o have p r a c t i c a l l y equal values in the s p e c t r a of fl-oxoquinuclidine (I) at 70 and 12
eV. Regularities of this s o r t are absent in the m a s s - s p e c t r o m e t r i c disintegration of both monocyclic [4, 5]
and bicyclic [6] compounds containing a CO group.
In o r d e r to explain this unusual r e g u l a r i t y we determined the ionization potential of the fl-oxoquinu-
clidine molecule and the e n e r g y c h a r a c t e r i s t i c s of the formation of the fragment ions. These m e a s u r e m e n t s
may give an unambiguous answer to the nature of the e l e m e n t a r y act of ionization of the investigated c o m -
pounds, inas much as r e m o v a l of an electron fro m the unshared electron pairs of both the nitrogen atom and
the oxygen atom is possible during the formation of M +.. In addition, the r e s u l t s obtained make it possible
to estimate the activation energies of the p r o c e s s e s under consideration. The ionization and appearance po-
tentials were determined with a photoionization mass s p e c t r o m e t e r .
The ionization potentials (IP) and appearance potentials
(AP), the excess e n e r g y ( A P - I P ) n e c e s s a r y for the formation of
*" O
the ions, and the relative intensities (I) of the peaks formed at ion-
42 izing-photon energies of 12.08 eV a r e presented in Table 1.
55 69 125 (~4"')
The ionization potential of the ~-oxoquinuclidine molecule
,ul..... I, ,L (IP =7.95 eV) is typical for saturated amines. It is known that the
12eV 97(M -CO) ~"
I 125(M*'} ionization potentials of diethylamine and triethylamine, which a r e
8.0 and 7.58 eV, r e s p e c t i v e l y , c o r r e s p o n d to detachment of an
40 60 80 100 120 role electron f r o m the unshared electron pair of the nitrogen atom [7].
However, the ionization potentials of various oxo-eontaining c o m -
Fig. 1. _Mass s p e c t r u m of f l - o x o -
pounds usually are on the o r d e r of 9.1 eV and higher [8, 9]. F r o m
quinuclidine at 70 (a) and 12 eV (b).

*See [1] for communication tII.

S. Ordzhonikidze All-Union S c i e n t i f i c - R e s e a r c h P h a r m a c e u t i c a l - C h e m i s t r y Institute, Moscow.

Translated f r o m Khimiya Geterotsiklichesktkh Soedtnenii, No. 7, pp. 970-976, July, 1974. Original article
submitted April 2, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 17th Street. New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

847
 TABLE 1. Mass Spectrum of I and Its Energy C h a r a c t e r i s t i c s

IOQ ITIaSS, lionization (IP) andappear~ Activation energy

m/e Rel. intensity, I, % lance (AP) potentials, eV i (AP-IP), eV
i
125 40 E 7,95+0,03
97 100 i 8,40+0,05 0,45
82 17 ' 10,8 +0,05 2,85
69 26 ! 10,87+0,05 2,92
56 7
55 31
42 5 11,5< AP <12
41 2

42 a 30 eV Q_.~O
g6- -CH3CO'139(M+')
55 69 s2 I ' ~ - co
r~ ,,li, ,l,. ,L , I, 111 * 124 t
12 eV 139 (IvV")
E
69 S2 96 I
111

~=
c ' 30 I v ~97 ~o ~ 16g(M +')
42

o E J,. .,L L, . . . 9. 110 1.26

d 12eV 97,
," .,~ 159 (M*')

40 60 80 100 120 140 1,50 role

Fig. 2. Mass s p e c t r a of 4 - o x o - l - a z a b i c y c l o -
[3.2.2]nonane at 30 (a) and 12 eV (b) and of
fi-oxoquinuclidine ethyleneketal at 30 (c) and
12 e V (d).

a c o m p a r i s o n of these data one can probably conclude that the ionization of the fl-oxoquinuclidine molecule
is r e a l i z e d via the unshared pair of the nitrogen atom.
It follows f r o m the last column of Table i that the activation e n e r g y (c) for the elimination of carbon
monoxide f r o m M +- is 0.45 eV, d i s r e g a r d i n g the kinetic shift. Moreover, the values for all of the other p r o -
c e s s e s are higher by a factor of six or more than the analogous p a r a m e t e r for the r e a c t i o n M+" -*(M-CO) +-.
The kinetic shift usually does not exceed 0.2 eV [10]. Consequently, the predominance of the peak of the
(M-CO) +. f r a g m e n t in the s p e c t r a of the investigated compounds at 70 and 12 eV might have been explained
by the e x t r e m e l y low activation e n e r g y (~ =0.25 eV) for the splitting out of a neutral CO molecule. How-
e v e r , this assumption does not explain the constancy of the M+-/(M-CO) +. r a t i o as the ionizing voltage is
v a r i e d f r o m 12 to 70 eV.
On the basis of the l i t e r a t u r e data, this r e g u l a r i t y can be explained by two f a c t o r s : by a r e a c t i o n with
a low activation e n e r g y and a low frequency factor [11] and by fragmentation f r o m the isolated electronic
state [12-14].
As shown in [2, 3, 15, 19], the fragmentation of various functional substituted quinuclidines should be
c o n s i d e r e d f r o m t h e open f o r m of the molecular ion that is formed during cleavage of one of the bridge
bonds. On the basis of the low-voltage mass s p e c t r a and m e a s u r e m e n t s of the ionization potential with the
e n e r g y c h a r a c t e r i s t i c s of the appearance of the fragment ions it should be a s s u m e d that opening of M +" of
fi-oxoquinuclidine o c c u r s in only one way, namely, at the bridge bond containing the oxo group to give ion
A 1 (scheme 1). The open f o r m of molecular ion A 1 is a typical amine fragment. Subsequent splitting out of
a CO molecule f r o m A 1 is accompanied by the skeletal r e a r r a n g e m e n t B ~ C and the f o r m a t i o n o f r e a r r a n g e d
ion B [2, 3]. F r o m the m e a s u r e m e n t of the e n e r g y c h a r a c t e r i s t i c s of the disintegration of M +" of fl-oxo-
quinuclidine and an analysis of the l i t e r a t u r e data it can apparently t h e r e f o r e be concluded that the inves-
tigated fi-oxoquinuclidines are a class of compounds, in the disintegration of which the formation of an en-
e r g e t i c a l l y favorable amine fragment (fragmentation f r o m the isolated state) is s u c c e s s f u l l y coupled with
the subsequent r e a r r a n g e m e n t p r o c e s s M +- ~ ( M - C O ) +., which has a low frequency factor and an e x t r e m e l y
small activation energy. Unfortunately, it is impossible to evaluate the contributions of these effects s e p -

848
 142 a 157 30 eV95 _H2NCHO 1_40(M*')
I }1 8~ ,g7 *o~...
~" C2N4 112 - CO

.~ J - 95

~ J ._ C 57 30eV ~ND 141--'-{M*')

42 95 "

40 50 60 70 80 90 100 110 120 130 140 rnle

Fig. 3. Mass s p e c t r a of 3 - o x o - l , 4 - d i a z o b i -
cyclo[3.2.2]nonane at 30 (a) and 12 eV (b).

arately. This situation was p r e v i o u s l y noted in [16, 17], in which the possibility of fragmentation f r o m the
isolated electronic state for such compounds as altphat[c ketones, Sch[ff b a s e s , and ketals was discussed.
Scheme 1
.C=O
s

, ' 2
.+ II {', :l
L
CH~ CH~ CH~
~,lT'rn/e. 125 ~ " m/e 97
I A~ ~o B C

CH2
M2" m/e 139 .~ E;Il l ,
II Ar2 ,'~I~""nt//e 169 "
11! As

r .... i
O-- 0.~.~O+

. , +0~/0
I
9CH. CH~CH.

,'~;+" A~ D t? ,'e 9 ~'

The mechanisms for the disintegration of ions B and C that were p r e s e n t e d in [2] and were based on
a study of metastable ions are confirmed by a study of the h i g h - r e s o l u t i o n mass s p e c t r u m of I. The p r e -
cise m a s s e s of most of the f r a g m e n t s f o r m e d during the disintegration of quinuclidine I and the e m p i r i c a l
formulas of the ions (in parentheses) found f r o m them, which c o r r e s p o n d p r e c i s e l y to the s t r u c t u r e s found
in [2], are p r e s e n t e d below: 97.0900 (C~HllN); 96.0831 (C6H10N); 82.0668 (CsHsN); 70.0873 (C4HsN); 69.0605
(C4HTN); 68.0535 (C4H6N); 57.0588 (C3HTN); 56.0495 (C3H6N); 55.0444 (C3HsN).
One's attention is drawn to the fact that all of the fragments in the s p e c t r u m of I that are of medium
and high intensity contain nitrogen, and this once again indicates localization of the charge p r i m a r i l y on the
nitrogen atom. The fragmentation of other compounds s i m i l a r to it, which are considered below, s e r v e d as
a confirmation of the proposed m e c h a n i s m s of the disintegration of fl-oxoquinuclidines. The mass s p e c -
t r a of 4 - o x o - l - a z a b i c y c l o [3.2.]nonone (II) and fl-oxoqu[nuclidine ethyleneketal (HI) a r e p r e s e n t e d in Fig. 2.
It follows f r o m an examination of Fig. 2 (spectra a and b) that the peak of the (M-CO)+. fragment in the
s p e c t r u m of II ts of e x t r e m e l y low intensity at 30 and 12 eV. A p e c u l i a r i t y of the disintegration of I-III is
the p r e s e n c e in their s p e c t r a at mass n u m b e r s with m / e 97 and below of identical peaks of f r a g m e n t , m e t a -
stable, and doubly c h a r g e d ions. *

*The mass n u m b e r s of the metastable ions detected during the disintegration of I a r e p r e s e n t e d in [2].

849
 a 70 eV C6Hs-nCH3 291
xO,01
"~ 5~ 70 97105 129 221 1304 .
'~ Ill I, ,II .... I,,,
, dill ,hh .qrt! ,Irf ~l
24e262 '[I
,ll 291
1 I
h319(M ")
~. t b 12.eV ixO,0!'
=1
. . . . . . . . . . t. . .UI.,,
70 110 150 190 230 270 310 m/e

Fig. 4. Mass s p e c t r u m of 4 , 4 - d i ( p - t o l y l ) - 3 - o x o - 1 -
azabicyclo[3.2.2]nonane at 70 (a) and 12 eV (b).

In this cas e, it can be assumed that fragment ions with m / e 97 and below should have identical s t r u c t u r e s
in the fragmentation of I-III. We note that while the s i m i l a r i t y in the s p e c t r a of I and H is not so obvious,
the s p e c t r a of I and III a r e absolutely identical in the indicated range. The identical c h a r a c t e r of the dis-
integration of I - I I I and the e x t r e m e l y low intensity of the peak of the (M-CO) +. fragment in the s p e c t r u m of
II are due to the f o r m a t i o n of the open f o r m of the molecular ion for II and III in the f o r m of s t r u c t u r e s A 2
and A3, which a r e f o r m e d during a cleavage of the bond containing the functional group (scheme 1). In this
case, elimination of CO f r o m A 2 is impossible, and the known [2] disintegrative p r o c e s s e s lead to identical
f r a g m e n t s B and C for I-III. It is interesting to note two c i r c u m s t a n c e s that follow f r o m an examination of
Fig. 2 (spectrum d). F i r s t , the ion peak with m / e 97 at 12 eV in the s p e c t r u m of quinuelidine HI, in con-
t r a s t to I, is not of m a x i m u m intensity. Inasmuch as the A1--*B--43 and A s ~ B - - C p r o c e s s e s are identical,
this phenomenon apparently may attest to a considerable effect on the skeletal r e a r r a n g e m e n t of the stabil-
ity of the neutral p a r t i c l e s that are split out. Second, the mass of s p e c t r u m of III is an additional c o n f i r -
Ination of charge localization in M +" for I - I I I only on the nitrogen atom. In fact, in c o n t r a s t to the f r a g m e n -
tation of a number of ethyleneketal derivatives [18], the peak of c h a r a c t e r i s t i c f r a g m e n t D with m / e 99, for
the formation of which all of the n e c e s s a r y conditions are p r e s e n t in the disintegration of ketal HI
(M+. --*A'3 --*m/e 99), is of r e l a t i v e l y low intensity in the s p e c t r u m of III.
In view of the fact that the initial cleavage of the bridge bond in M +. stabilizes the i o n - r a d i c a l c e n t e r
on the nitrogen atom, the driving force of the disintegration of the compounds under consideration is the
p r e s e n c e of an unpaired electron on one of the carbon atoms in the open f o r m of M +..

Scheme 2

N.2c.o
C-%o -
*+
CH2 CH2
N:" m/e Iio A~ ~/. E m/e 95
IV
C m/e ~7

This assumption is illustrated graphically by an examination of the fragmentation of other compounds con-
taining an oxo group in various positions of the bridge.
The mass s p e c t r u m of 3-oxo-l,4-diazobicyclo[3.2.2]nonane (IV) and its deutero analog (IVa) a r e p r e -
sented in Fig. 3. The p e c u l i a r i t y of the disintegration of this compound is also explained by the s t r u c t u r e
of open molecular ion Ar (scheme 2). The elimination of a CONH r a d i c a l f r o m A 4 with subsequent cleavage
of a second bridge bond leads to known fragment C with m / e 97. Yet another possibility before the o c c u r -
r e n c e of the e n e r g e t i c a l l y f a v o r a b l e r e a r r a n g e m e n t p r o c e s s - formation f r o m A 4 of an ion with conjugated
bonds (E) with m / e 95 during elimination of a f o r m a m i d e molecule - is r e a l i z e d in the fragmentation of IV.
The r e a r r a n g e m e n t c h a r a c t e r of the formation of fragments with m / e 97 and 95 is confirmed by the low;
voltage mass s p e c t r u m , in which peaks of these ions are distinctly observed. The A 4 ~ E and A 4 ~ C m e c h -
a n i s m s a r e c o n f i r m e d by the s p e c t r u m of the deutero analog (IVa), in which the peaks of ions with m / e 97
and 95 have the same c h a r a c t e r i s t i c s as those o b s e r v e d for IV. It follows f r o m an examination of Fig. 3
that the (M-CO) +. ion peak in the s p e c t r u m of 3-oxo-l,4-dtazobicyclo[3.2.2]nonane at 70 and 12 eV has an
approximately constant r e l a t i v e intensity. In this connection, it s e e m s of interest to us to also study the
mass s p e c t r a of other compounds s i m i l a r to IV but substituted, for example, in the 4 position. The mass
s p e c t r a of 4 , 4 - d i ( p - t o l y l ) - 3 - o x o - l - a z a b i c y c l o [ 3 . 2 . 2 ] n o n a n e (V) and 4 , 4 - d i m e t h y l - 3 - o x o - l - a z a b i c y c l o [ 3 . 2 . 2 ] -
nonane (VI) a r e p r e s e n t e d in Figs. 4 and 5. In c o n t r a s t to II mid IV, (M-CO) +. fragments G (with m / e 291)

850
 .~
i b
l
12 C V
i; 1139

I
1 2 1
167(M *')

124
rv 40 50 60 70 ~ 0 g O 100 110 120 130 I/-+0150160 r~/e

Fig. 5. Mass spectrum of 4,4-dimethyl-3-oxo-

1-azabicyclo [3.2.2]nonane at 70 eV.

and H (with m/e 139) are primarily formed during the disintegration of V and VI at both 70 and 12 eV. The
fundamental mechanisms of the disintegration of V and VI are presented in scheme 3. From an examination

Scheme 3
C~Hs--CH3 II_ A II 1 ', : I

~
]4 . c~:o ~ ( l ' _ ,

2) I; 'i
M~" m/e 29t CH, CH 2 CH 2

v A~ F G m/e 29t

of this scheme it should be assumed that the ease of elimination of a CO molecule from open molecular ions
A 5 and A 6 is apparently due to the effective stabilization in the (M-CO) +" ion of the radical center at C 4. In
the first case, this is achieved through the effect of conjugation of the unpaired electron with the ~ electrons
of the tolyl substituent, while in the second case it is achieved through inductive stabilization of the radical
center by two electron-donor groups. Inasmuch as the process M +. ~(IK-CO) +. for V is not accompanied
by simultaneous skeletal rearrangement, the practically constant M+./(M-CO) +. ratio in the spectrum of
V at 70 and 12 eV can apparently be explained only by fragmentation from the isolated electronic state of
the A 5 ion. It is obvious that the process F ~G facilitates this to a great extent.

CH 3 C11~
\ /CH 3 \ /CH 3
/C~.co ~c

CH 2 CH 2
,~I:" ra/e 167 As H m/e 139
VI

Thus it follows from an examination of the mass spectra of I-VI that the (M-CO) +. ion is observed
during the disintegration of all of the investigated bicyclic compounds with a nodal nitrogen atom and con-
taining oxo groups inthe /3 position. However, predominant elimination of a CO molecule is observed only
if: a) the formation of the open form of M +" occurs at the bridge bond that immediately contains the oxo
group; b) stabilization of the radical center in the (M-CO) +. ion is realized as a result of the energetically
favorable skeletal rearrangement or due to other stabilizing factors. In this case, the process
M +" -*(M-CO) +. can be characterized by a low frequency factor and a low activation energy or by fragmen-
tation from the isolated electronic state.

EXPERIMENTAL

The low-resolution mass spectra were investigated with an MKh 1303 spectrometer and an LKV-9000
chromatographic mass spectrometer with introduction of the substances directly into the ion source; the
ionizing voltage was 10-70 eV, and the cathode emission current was 0.75 pA (MKh 1303) or 60 pA (LKV-
9000). The inlet temperature of the substances was 20-50~ and the ionization chamber temperature was
125 ~ (MKh 1303) or 250 ~ (LKV-9000). The ionization and appearance potentials were determined with an
MKh 1311 photoion[zat[on mass spectrometer. The high-resolution mass spectrum was recorded with an
IMS-01 SG-2 mass spectrometer with an automatic system for information processing.

851
 The compounds were synthesized and purified by the method described for I [2], II [19], III [20], IV
[21], V [22], and VI [22].
In conclusion, the authors thank E. E. Mikhlina, A. D. Yanina, V. Ya. Vorob'eva, and L. I. Mastafanova
for kindly providing us with the compounds used in this r e s e a r c h .

LITERATURE CITED
1. A . I . Ermakov, Yu. N. Sheinker, E. E. Mikhlina, A. D. Yanina, L. N. Yakhontov, and R. G. Kostyanov-
skii, Khim. Geterotsikl. Soedin., 825 (1972).
2. A . I . Ermakov, Yu. N. Sheinker (Shenker), E. E. Mikhlina, L. I. Mastafanova, V. Ya. Vorob'eva(Vorob-
jova), A. D. Yanina, L. N. Yakhontov, and R. G. Kostyanovskii (Kostyanovsky), Org. Mass Spectr., 5,
1029 (1971).
3. A . I . Ermako% Yu. N. Sheinker, E. E. Mikhlina, L. I. Mastafanova, V. Ya. Vorob'eva, A. D. Yanina,
L. N. Yakhontov, and R. G. Kostyanovskii, Khim. Geterotsikl. Soedin., 1404 (1972).
4. E. Land, H. Budzikiewicz, J. M. Wilson, and C. Djerassi, J. Amer. Chem. Soc., 8_55,941 (1963).
5. E. Lurid, H. Budzikiewicz, C. Djerassi, and J. M. Wilson, J. Amer. Chem. Soc., 8_5.5,1528 (1965).
6. J. Karliner, H. Budzikiewicz, and C. Djerassi, J. Amer. Chem. Soc., 87, 580 (1965).
7. R . G . Kostyanovskii, V. K. Potapov, L. I. Iskako~-, and V. G. Plekhanov, Dold. Akad. Nauk SSSR, 204,
913 (1972).
8. I. Kanomata, Bull. Chem. Soc. Japan, 34, 1864 (1961).
9. D.N. Shigorin, A. D. Filyugina, and V. K. Potapov, Teor. i I~ksperim. Khim., 4, 554 (1966).
10. R. Cooks, J. Howe, and D. H. Williams, Org. Mass Spectr., 2, 197 (1969).
11. D.H. Williams and R. G. Cooks, Chem. Commun., 663 (1968).
12. R. Brant and C. Djerassi, Helv. Chim. Acta, 5.1, 1750 (1968).
13. H.M. Rosenstok and M. Kraus, Mass Spectrometry of Organic Ions, Academic P r e s s (1963), Chap. 4.
14. J . H . Beynon, Mass Spectrometry and Its Applications to Organic Chemistry, American Elsevier
(1960).
15. A . I . Ermakov, Yu. N. Sheinker, E. E. Mikhlina, A. D. Yanina, L. N. Yakhontov, V. Ya. Vorob'eva,
and R. G. Kostyanovskii, Khim. Geterotsikl. Soedin., 1411 (1972).
16. R . G . Cooks, A. N. Yeo, and D. H. Williams, Org. Mass Spectr., 2, 985 (1969).
17. P. Brown, Org. Mass Spectr., 3, 1345 (1970).
18. G. Mutzenbecher, Z. Pelah, D. Williams, H. Budzikiewicz, and C. Djerassi, Steroids, 2, 475 (1963).
19. V. Ya. Vorob'eva, E. E. Mikhlina, K. F. Turchin, L. M. Alekseeva, Yu. N. Sheinker, and L. N. Ya-
khontov, Khim. Geterotsikl. Soedin., 1037 (1970).
20. L . I . Mastafanova, K. F. Turchin, L. M. Alekseeva, Yu. N. Sheinker, and L. N. Yakhontov, Khim.
Geterotsikt. Soedin., 1665 (1971).
21. M.V. Rubtsov, E. E. Mikhlina, V. Ya. Vorob'eva, andA. D. Yanina, Zh. Obshch. Khim., 3_44,2222
(1964).
22. E . E . Mikhlina, A. D. Yanina, K. F. Turehin, T. Ya. Filippenko, A. I. Ermakov, Yu. N. Sheinker, and
L. N. Yakhontov, Zh. Organ. Khim., 1_.00,396 (1974).

852
SYNTHESIS AND PROPERTIES OF 1-METHYL(ARYL)-
7 - E T H O X YC A R B O N Y L I N D O L I Z I N E S

E. E. M i k h l i n a , A . D. Y a n i n a , UDC 547.759.4.07
T. S. L o s e v a , K. F . T u r c h t n ,
a n d L . N. Y a k h o n t o v

The p r e v i o u s l y unknown 2-substituted indolizine-7-earboxylic acids and their derivatives

were synthesized, and some of their p r o p e r t i e s were studied.

A communication r e g a r d i n g the synthesis of 2 - m e t h y l - 8 - e t h o x y c a r b o n y l i n d o l i z i n e appeared in 1972

[1], but the p r o p e r t i e s and t r a n s f o r m a t i o n s . o f this compound have not been studied.
F r o m the point of view of the mutual effect of the p y r r o l e and pyridine rings in the condensed s y s t e m s
on the r e a c t i v i t t e s of the compounds obtained it s e e m e d of interest to us to synthesize the p r e v i o u s l y un-
known e s t e r s of 2-substituted i n d o l i z i n e - 7 - c a r b o x y t i c acids and investigate some of their nueleophilic and
electrophilic subst [tution r e a c t ions.
Indolizines III were obtained via the following s c h e m e :

COOC2H~ COOC2H5 COOC2HS

] B7 I
CH2COR CH =C--R COR'
I
o- III Vl-Vl!

R"oo~-~_ R ~"~"~~ R
IV V
I, If, Ill, V a R=CH3; bR=C6Hs; IV a R=CsH~, R"=Na; bR=C6Hs, R"=H; VI a R=R'=
=CH3; b R=CH3, R'=C6FIs; c R=CH3, R'=C6H4CI-p;VII a R=C6Hs, R'=CH3; b R=R'=
=C6H5; c R=C6H~, R'=C~H4CI-p

Ethyl 2-methylisonicotinate was converted to q u a t e r n a r y pyridinium salts I by r e a c t i o n with b r o m o a c e t o n e

and phenacyl bromide. Cyclization of salts t by the standard Chichibabtn method by heating with aqueous
sodium bicarbonate solution gave a negative r e s u l t for salt Ia (the r e a c t i o n proceeded with pronounced
resinification), while sodium 2 - p h e n y l i n d o l i z i n e - 7 - c a r b o x y l a t e was obtained in 60.7% yield f r o m salt Ib un-
der these conditions. As a consequence of the e x t r e m e l y low solubility of the sodium salt in water and o r -
ganic solvents, further t r a n s f o r m a t i o n s of it proved to be difficult, and this r e s t r i c t e d the practical p o s s i -
bilities of this synthetic method. Other methods for the conversion of q u a t e r n a r y salts Ia and Ib to [ndol-
[zincs were studied. The most efficient method for the synthesis of ethyl 2 - p h e n y l i n d o l i z i n e - 7 - c a r b o x y l a t e
glib) was conversion of salt Ib to anhydro base IIb by the action of a m m o n i u m hydroxide or aqueous sodium
carbonate solution and subsequent cyclization of lib by heating in an organic solvent. However, we were un-
able to synthesize indolizine IIIa by means of this method. As in the f i r s t c a s e , the formation of a b r i g h t -
colored allhydro base, which, in the case of IIa, was not isolated because of its high solubility in water, was

S. Ordzhonikidze All-Union S c i e n t i f i c - R e s e a r c h P h a r m a c e u t i c a l - C h e m i s t r y Institute, Moscow.

T r a n s l a t e d f r o m Khimiya Geterotsiklicheskikh Soedinenit, No. 7, pp. 977-981, July, 1974. Original article
submitted August 8, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this pub#cation may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

853
 TABLE 1. C h e m i c a l Shifts of the P r o t o n s of 2 - M e t h y l ( p h e n y l ) - 3 -
acyl-7-ethoxycarbonylindolizines

Corn- H, Hs H6 H, CH2 CH~ R, I~

pound

Via 6,50 9,86 7,28 8,08 4,39 1,40 2,59 2,56

VIb 6,53 9,53 7,31 8,15 4,40 1,40 1,95 7,00--7,70
VIe 6,53 9,55 7,28 8,16 4,39 1,42 1,98 7,35--7,70
Vlla 6,66 9,88 7,33 8,20 4,40 1,41 ~ 7,40 2,08
Vllb 6,8l 9,53 7,30 8,28 4,42 1,43 ~ 7,00 6,80--7,50
Vllc 6,81 9,54 ~7,35 8,28 4,42 1,42 ~ 7,05 6,90--7,50

o b s e r v e d d u r i n g the a c t i o n of a m m o n i u m h y d r o x i d e or an equivalent amount of s o d i u m h y d r o x i d e on s a l t Ia.

A s m a l l amount of 2 - m e t h y l i n d o l t z i n e - 7 - c a r b o x a m t d e was f o r m e d on s u b s e q u e n t heating of the a m m o n i a s o -
lution. Ethyl 2 - m e t h y l i n d o l t z i n e - 7 - c a r b o x y l a t e (Ilia) was obtained by heating q u a t e r n a r y s a l t Ia in a b s o l u t e
ethanol in the p r e s e n c e of s o d i u m b i c a r b o n a t e .
The h y d r a z t n a t i o n of e s t e r s IIIa and IIIb was studied. R e a c t i o n with h y d r a z i n e h y d r a t e p r o c e e d e d only
on p r o l o n g e d r e f l u x i n g of IIIa and IIIb with a s l i g h t e x c e s s of h y d r a z i n e h y d r a t e . The c o n s i d e r a b l y m o r e
s e v e r e conditions n e c e s s a r y for the p r e p a r a t i o n of h y d r a z i d e s of 2 - s u b s t i t u t e d i n d o l i z i n e - 7 - c a r b o x y l t c a c i d s
f r o m t h e i r e s t e r s as c o m p a r e d with the conditions for the c o n v e r s i o n of the e s t e r s of i s o n i c o t i n t c a c i d to its
h y d r a z i d e a t t e s t to the s u b s t a n t i a l effect of the r - e l e c t r o n s y s t e m of indoliztne [2] on the c a r b e t h o x y group,
which l e a d s to an i n c r e a s e in the e l e c t r o n d e n s i t y on the c a r b o n y l c a r b o n .
The a c y l a t i o n of i n d o l i z i n e s I I I - an e l e c t r o p h t l i c s u b s t i t u t i o n r e a c t i o n - p r o c e e d s quite c o m p l e t e l y un-
d e r m i l d conditions to give 3 - a c y l i n d o l i z i n e s . The p o s i t i o n of the acyl r e s i d u e s was u n a m b i g u o u s l y e s t a b -
l i s h e d f r o m PM1R s p e c t r a l data.
The c h e m i c a l s h i f t s of the p r o t o n s o f V I a - c a n d V i l a - c a r e p r e s e n t e d in Table 1. The s i g n a l s w e r e a s -
s i g n e d to the p r o t o n s of the indolizine r i n g on the b a s i s of a c o m p a r i s o n of the o b s e r v e d s p i n - s p i n coupling
c o n s t a n t s (JH,H- ~ 0.8 Hz, JH1H6, JH1H 8 -< 0.4 Hz, JHsH6 ~ 7.5 Hz, JH5H8 ~ 1 Hz, and JH6H8 ~ 1.9 Hz) with the
c o r r e s p o n d i n g h t e r a t u r e data [3].

A n a l y s i s of the d a t a in Table 1 shows that the s i g n a l of the H 5 p r o t o n in all of the i n v e s t i g a t e d c o m -

pounds is o b s e r v e d at v e r y w e a k f i e l d (9.5 ,~ 9.9 ppm) as c o m p a r e d with u n s u b s t i t u t e d indolizine (7.76 p p m
[3]). A n u m b e r of i n v e s t i g a t o r s have noted that e s t e r , a l d e h y d e , t h i o a l d e h y d e , and a c y l s u b s t i t u e n t s in the
3 p o s i t i o n s t r o n g l y d e s h t e l d the p r o t o n s a t t a c h e d to C 5 of the indolizine r i n g [1, 4, 5]. The i n d i c a t e d w e a k -
f i e l d shift of the H 5 s i g n a l in the s p e c t r a of VIa-e and VIIa-c t h e r e f o r e u n a m b i g u o u s l y a t t e s t s to the p r e s -
ence of an a c y l s u b s t i t u e n t in the 3 p o s i t i o n in t h e s e compounds.

EXPERIMENTAL
The PMR spectra of deuterochloroform solutions of the compounds were recorded with a JNM-4H-
i00 spectrometer with hexamethyldisiloxane as the internal standard (5 0.04 ppm).
l-Acetonyl-2-methyl-4-ethoxycarbonylpyridinium Bromide (fa). A solution of i0 g (60 mmole) of
ethyl 2-methylisonieotinate and 8.3 g (60 mmole) of bromoaeetone in 25 ml of acetone was refluxed for 12 h.
It was then cooled, and the resulting precipitate was removed by filtration and washed with acetone to give
16.8 g (91.5%) of a product with mp 105-107 ~ (from acetone). Found: C 47.2; H 5.4; Br 26.0%. CI2HIGBrNO 3.
Calculated: C 47.6; H 5.4; Br 26.3%.
A similar procedure was used to prepare l-aeetonyl-2-methyl-4-methoxycarbonylpyridinium bro-
mide, with mp 107-109 ~ (from acetone-ethanol), in 52.5% yield from methyl 2-methylisonicotinate and bro-
moaeetone. Found: C 45.5, H 5.0; Br 27.7%. CIIHI4BrNO 3. Calculated: C 45.8; H 4.9; Br 27.8%.
l-Phenaeyl-2-methyl-4-ethoxyearbonylpyridinium Bromide (Ib). This compound, with mp 138-139 ~
(from acetone), was obtained in 78% yield by the method used to prepare la. Found: Br 22.0%. CITHIsBrNO 3.
Calculated: Br 21.9%.
l-Phenacyl-2-methyl-4-ethoxyearbonylpyridinium Anhydro Base (fib). A 15-ml sample of a 25% am-
monium hydroxide solution was added to a solution of I0 g (27.4 mmole) of ib in 75 ml of water. A copious
orange precipitate of the anhydro base formed. The mixture was cooled for 1 h at 0 deg, and the precipitate
was removed by suction filtration, washed with water, and dried to give 7.4 g (95%) of Iib. Found: C 71.9;
H 6.0%. CITHITNO 3. Calculated: C 72.1; H 6.0%.

854
 2 - M e t h y l i n d o l t z i n e - 7 - c a r b o x a m i d e . A solution of 5 g (33 mmole) of methyl 2-methylisonicotinate and
4.5 g (33 mmole) of b r o m o a c e t o n e in 30 ml of acetone was refluxed for 12 h, after which the mixture was
v a c u u m evaporated, and the r e s i d u e was dissolved in 50 ml of water. The aqueous solution was extracted
with ether and t r e a t e d with 15 ml of 25% a m m o n i u m hydroxide. Cooling of the solution precipitated the
b r i g h t - r e d anhydro base (0.2 g), which was r e m o v e d by filtration and washed with a s m a l l amount of cold
water. The substance decomposed on standing in air and also in a v a c u u m d e s i c c a t o r . The aqueous a m m o -
nia solution Was heated for 3 h on a water bath, and the precipitated c r y s t a l s were r e m o v e d by filtration and
r e c r y s t a l l i z e d f r o m ethanol to give a product with mp 209-210 ~ Found: C 69.2; H 5.8; N 16.0%. Ci0H10N20.
Calculated: C 69.3; H 5.8; N 16.1%.
Ethyl 2 - m e t h y l i n d o l i z [ n e - 7 - c a r b o x y l a t e (IIIa). A mixture of 9.2 g (30 mmole) of In, 5.1 g (60 mmole)
of sod[urn bicarbonate, and 120 ml of absolute ethanol was refluxed with vigorous s t i r r i n g for 3 ho The
ethanolwas then r e m o v e d by vacuum distillation, and the residue was dissolved in 60 ml of water. The
aqueous solution was extracted with ether to give 3 g (49%) of a product with mp 55-57 ~ (from hexane).
Found: C 70.6; H 6.3; N 7.0%. C12Ht3NO2. Calculated: C 70.6; H 6.4; N 6.9%. Methyl 2 - m e t h y l i n d o l i z -
i n e - 7 - c a r b o x y l a t e , with mp 74-76 ~ (from hexane), was s i m i l a r l y obtained in 28% yield f r o m 1 - a c e t o n y l -
2 - m e t h y l - 4 - m e t h o x y c a r b o n y l p y r i d i n i u m b r o m i d e . Found: C 69.6; H 5.9; N 7.4%. CllHltNO 2. Calcu-
lated: C 69.9; H 5.9; N 7_.4%.
Ethyl 2 - P h e n y l i n d o l i z i n e - 7 - c a r b o x y l a t e (IIIb). A) A 7.4-g (26 mmole) sample of IIa was dissolved by
heating in 70 ml of 2-propanol, and the solution was refluxed for 10 rain. It was then cooled at 4 ~ for 24 h,
and the precipitated c o l o r l e s s c r y s t a l s were r e m o v e d by suction filtration and washed with 2-propanol to
give 5.8 g (83.5%) of a product with mp 142-143 ~ (from acetone). Found: C 77.0; H 5.9%. C17HlsNO2. Cal-
culated: C 77.0; H 5.7%.
B) A 7.4-g (70 mmole) sample of sodium bicarbonate was added to a solution of 12 g (33 mmole) of
IIa in 70 ml of water. A b r i g h t - o r a n g e precipitate of the anhydro base formed. The r e a c t i o n mass was
heated on a boiling-water bath for 4 h, during which the color of the precipitate changed f r o m orange to
greenish. The mixture was cooled, and the precipitate was r e m o v e d by filtration and washed with water to
give 5.2 g (60.7%) of sodium 2 - p h e n y l i n d o l [ z i n e - 7 - c a r b o x y l a t e (IVa), which was p r a c t i c a l l y insoluble in cold
and hot water. The product did not melt on heating to 350 ~.
2 - P h e n y l i n d o l i z i n e - 7 - e a r b o x y l i c Acid (IVb). A) A suspension of 0.5 g (20 mmole) of sodium salt IVa
in 30 ml of concentrated h y d r o c h l o r i c acid was refluxed for 4 h, during which the color of the precipitate
changed f r o m l i g h t - g r e e n to light-yellow, but it did not dissolve. The mixture was cooled, and the p r e c i p -
itate was r e m o v e d by filtration and washed with water to give 0.4 g (89%) of a product with mp 274-276 ~
(dec., f r o m ethanol). Found: C 75.9; H 4.8; N 5.8%. CIsHIiNO2. Calculated: C 75.9; H 4.7; N 5.9%.
B) A suspension of 0.5 g (19 mmole) of IIIb in 50 ml of concentrated h y d r o c h l o r i c acid was refluxed
for 3 h, after which it was cooled, and the r e s u l t i n g precipitate was r e m o v e d by filtration and washed with
water to give 0.4 g (87%) of a product with mp 274-276 ~ (dec.). The acids obtained by the two methods were
identical a c c o r d i n g to their IR s p e c t r a . A homogeneous solution was f o r m e d by heating a suspension of acid
IVb in a 20-fold amount of 10% ethaaolic hydrogen chloride solution for 10 h. Cooling of this solution p r e -
cipitated e s t e r IIIb with mp 137-139 ~ (from acetone). The e s t e r s obtained by esterification of acid IVb and
cyclization of anhydro base lib were identical.
2 - M e t h y l i n d o l i z i n e - 7 - c a r b o x y l i c Acid Hydrazide (Va). A suspension of 0.5 g (2.46 mmole) of e s t e r
IIIa in 6 ml of hydrazine hydrate was refluxed for 20 h. The resulting precipitate was r e m o v e d by suction
filtration and washed r e p e a t e d l y with water to give 0.4 g (84%) of a product with mp 158-159 ~ (from water).
Found~ C 63.2; H 5.8; N 22.2%. Ci0HilN30. Calculated: C 63.5; H 5.8; N 22.2%.
2 - P h e n y l i n d o l i z i n e - 7 - c a r b o x y l i c Acid Hydrazide (Vb). This compound, with mp 224-225 ~ (dec.), was
obtained in 93% yield by the method used to p r e p a r e Va. The product was obtained as l i g h t - g r e e n c r y s t a l s
that were insoluble in w a t e r , acids, and o r d i n a r y organic solvents. Found: C 71.7; H 5.2; N 16.3%.
CisH13N30. Calculated: C 71.7; H 5.2; N 16.7%.
2 - P h e n y l i n d o l i z i n e - 7 - c a r b o x y l i c acid N - a c e t y l h y d r a z i d e , with mp 273-274 ~ (dec.), was f o r m e d when
the hydrazide was heated in glacial acetic acid until all of the solid had dissolved. Found: C 69.2; H 5.2;
N 14.2%. C17Hi5N302. Calculated: C 69.6; H 5.1; N 14.3%.
Ethyl 2 - M e t h y l - 3 - a c e t y l i n d o l i z i n e - 7 - c a r b o x y l a t e . A mixture of 0.5 g (2.46 mmole) of IIIa and 5 ml of
a c e t i c anhydride was refluxed for 14 h, after which the solution was vacuum evaporated, and the r e s i d u e

855
was r e c r y s t a l l i z e d f r o m e t h e r - p e t r o l e u m ether to give 0.4 g (67%) of a product with mp 104-106 ~ Found:
C 68.5; H 6.1%. Ct4Hi~NO3. Calculated: C 68.5; H 6.2%.
Ethyl 2 - P h e n y l - 3 - a c e t y l i n d o l i z i n e - 7 - e a r b o x y l a t e (VIIa). A mixture of 2 g (7.5 mmole) of IIIb and 40
ml of acetic anhydride was r e f l a x e d for 30 h. The acetic anhydride was then r e m o v e d by v a c u u m d i s t i l l a -
tion, and the r e s i d u e was mixed with 25% p o t a s s i u m carbonate solution. The carbonate solution was e x -
t r a c t e d with e t h e r to give 2 g (85%) of a product with mp 104-106 ~ (from hexane). Found: C 74.4; H 5.5%.
CigH17NO3. Calculated: C 74.3; H 5.6%.
Ethyl 2 - M e t h y l - 3 - b e n z o y l i n d o l i z i n e - 7 - c a r b o x y l a t e (VIb). A solution of 1.2 g (6 mmole) of IIIa and 0.83
g (6 mmole) of benzoyl chloride in 8 ml of benzene was held at r o o m t e m p e r a t u r e for 48 h, and the p r e c i p -
itated c r y s t a l s w e r e r e m o v e d b y suction f i l t r a t i o n and w a s h e d with benzene to give 1.4 g (77%) of a product
with mp 147-148 ~ (from e t h e r - a c e t o n e ) . Found: C 73.8; H 5.5%. C19H17NO3. Calculated.~ C 74.3; H 5.5%.
Ethyl 2 - P h e n y l - 3 - b e n o z y l i n d o l i z i n e - 7 - c a r b o x y l a t e (VIIb) o A mixture of 2 g (7.5 mmole) of Illb and 10
ml of benzoyl chloride was heated at 70-80 ~ for 1 h. The r e a c t i o n mixture was then poured into 150 ml of
p e t r o l e u m e t h e r , and the s t a r t i n g m a t e r i a l was r e m o v e d by filtration. The p e t r o l e u m ether and e x c e s s b e n -
zoyl chloride w e r e r e m o v e d by v a c u u m distillation, and the r e s i d u e was r e c r y s t a l l i z e d f r o m ethanol to give
1.4 g (50%) of a p r o d u c t with mp 93-94 ~ Found: C 77.8; H 5.3%. C24HigNO3. C a l c ~ a t e d : C 78.0; H 5.2%.
Ethyl 2 - M e t h y l - 3 - ( p - c h l o r o b e n z o y l ) i n d o l i z i n e - 7 - c a r b o x y l a t e (VIc). This compound, with mp 137-139 ~
( f r o m e t h e r ) , was obtained in 73% yield by the method used to p r e p a r e VIb. Found- C 67.0; H4.8; C1 10.4%.
CIgH16C1NO3. Calculated: C 66.7; H 4.7; C1 10.4%.
2 - M e t h y l - 3 - ( p - c h l o r o b e n z o y l ) i n d o l i z i n e - 7 - c a r b o x y l i c Acid. A solution of 0.31 g (7.8 mmole) of s o -
dium hydroxide in 10 ml of ethanol was added to a solution of 2.6 g (7.8 mmole) of VIb in 150 ml of ethanol,
and the m i x t u r e was r e f l u x e d for 10 h. It was then cooled, and the r e s u l t i n g p r e c i p i t a t e d sodium s a l t was
r e m o v e d b y suction filtration, w a s h e d with alcohol, and dissolved in 100 ml of w a t e r . The aqueous solution
was acidified with acetic acid, and the p r e c i p i t a t e was r e m o v e d b y suction filtration and washed with w a t e r
to give 2.2 g (88%) of a product with mp 177-179 ~ Found: C 64.8; H 4.0; C1 11.1%. C17HI2C1NO3. Calcu-
lated: C 65.1; H 3.9; C1 11.3%.
Ethyl 2 - P h e n y l - 3 - ( p - c h l o r o b e n z o y l ) i n d o l i z i n e - 7 - e a r b o x y l a t e (VIIc). A mixture of 2 g (7.5 mmole) of
IIIb and 8 ml of p - e h l o r o b e n z o y l chloride was heated at 80-90 ~ for 5 h, a f t e r which it was cooled and mixed
with 150 ml of p e t r o l e u m ether. The r e s u l t i n g p r e c i p i t a t e was r e m o v e d by suction filtration and washed
with p e t r o l e u m ether to give 2.45 g (77.53%) of a product with mp 108-110 ~ (from ethanol). Found: C 71.3;
H 4.6; C1 8.6%. C24HisC1NO3. Calculated." C 71.4; H 4.5; C1 8.8%.

LITERATURE CITED

i. J. Dalnis, A u s t r a l . J. Chem., 25, 1003 (1972).

2. W. Engewald, M. Miihelstadt, and C. W e i s s , T e t r a h e d r o n , 27, 851 (1971).
3. P. I. Black, M. L. Heffernan, L. M. Yackman, Q. N. P o r t e r , and G. R. Underwood, Austral. J. Chem.,
1_~7, 1128 (1964).
4. R. M. Aeheson and D. A. Robinson, J. Chem. Soc., C, 1633 (1968).
5. S. McKenzie and D. H. Reid, J. Chem. Soe., C, 145 (1970).

856
SYNTHESIS OF PYRAZOLINE DERIVATIVES
FROM HA L O V I N Y L A C E T Y L E N E S AND HALOALLENES*

M. G . V o s k a n y a n , G. G. Khudoyan, UDC 547.772.2.07

a n d S h . O. B a d a n y a n

The r e a c t i o n of halovinylacetylenes and haloallenes with h y d r a z i n e and phenylhydrazine in the

p r e s e n c e of a mixture of copper powder and cuprous chloride gives substituted p y r a z o l i n e s .

It has been shown that the r e p l a c e m e n t of a halogen by h y d r a z i n e and phenylhydrazine in p r o p a r g y l

halides gives g a m m a products f r o m which 5 , 5 - d i a l k y l - 3 - v i n y l p y r a z o l i n e s can be isolated in low yields [2,3].
Continuing t h e s e investigations, we have o b s e r v e d that the yields of p y r a z o l i n e s i n c r e a s e c o n s i d e r a b l y when
the r e a c t i o n is c a r r i e d out in the p r e s e n c e of a mixture of copper powder and cuprous chloride. The r o l e
of the catalyst, which leads to high yields of p y r a z o l i n e s in the case of ionic substitution, is p r o b a b l y e x -
plained by the fact that its p r e s e n c e facilitates the r e a c t i o n of the complex h y d r a z i n e with the h a l o v i n y l a c e t -
ylenes and also facilitates subsequent cyclization of the i n t e r m e d i a t e l y f o r m e d v i n y l p r o p a r g y l h y d r a z i n e to
a p y r a z o l i n e . The p o s s i b i l i t y of r e a c t i o n via a r a d i c a l m e c h a n i s m also cannot be excluded. Thus a s u b -
stituted vinylacetylenie r a d i c a l , which is r e a d i l y oxidized to a e a r b o n i u m ion in the p r e s e n c e of divalent
copper [4], is f o r m e d in the initial act of the r e a c t i o n as a r e s u l t of e l e c t r o n t r a n s f e r f r o m the h y d r a z i n e -
c o p p e r c o m p l e x to the halovinylaeetylene. The e a r b o n i u m ion r e a c t s with hydrazine to give a vinylethynyl
h y d r a z i n e , which c y c l i z e s to a pyrazoline.

~r~c(x)c~cc(r')=cH2 cu/cu (I)~ r,r:dc~cc(r,)=cn2.cux2, hydrazine

'C(R~)=CH: ~ t
r~ - - r,r~cc~cc(r,}=cH~ ~ [r~r~cc~ce(r,l=cH2-cuX~. hydrazme]
I NHNHR~
RI=tI.CH3: R~=CH3; R3=CH3.C2HS:R4=H,C6H5

It is also known that if stable r a d i c a l s a r e f o r m e d in the initial act of the r e a c t i o n , t h e r e is a p o s s i -

bility of t h e i r e s c a p e f r o m the complex. A p p a r e n t l y owing to t h e i r stability, the r e s u l t i n g vinylacetylenie
r a d i c a l s on p a r t i a l l y escaping f r o m the complex subsequently r e c o m b i n e to give highly unsaturated h y d r o -
c a r b o n s , which w e r e not investigated in detail.
The exclusive f o r m a t i o n of 5 , 5 - d i a l k y l - 3 - v i n y l p y r a z o l i n e s indicates that, in c o n t r a s t to the r e a c t i o n
of halovinylacetylenes with s e c o n d a r y a m i n e s [5], the r e a c t i o n with hydrazine in the p r e s e n c e of cuprous
chloride p r o c e e d s by means of attack of the nueleophile on the carbon a t o m bonded to the halogen with s u b -
sequent cyclization of the r e s u l t i n g substituted h y d r a z i n e s to vinylpyrazolines.

* C o m m u n i c a t i o n XTI f r o m the s e r i e s "Reactions of Unsaturated Compounds.', See [1] for c o m m u n i c a -

tion XI.

Institute of Organic C h e m i s t r y , A c a d e m y of Sciences of the A r m e n i a n SSR, E r e v a n . T r a n s l a t e d

f r o m Khimiya G e t e r o t s i l d i c h e s k i k h Soedinenii, No. 7, pp. 982-983, July, 1974. Original a r t i c l e s u b m i t t e d
March 28, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

857
 TABLE 1
CH3~ R'

R" bp, ~ (ram) riD20

f6rm ula fou calc. ~

I
H II CH3 ] 60--62 (32)5 1,4600 C6HIoNz 67
H H C2H5[ 63--64 (14)6 1,4625 C6HI~Ne 55
'C6H5 H CH6 I 98--100 (4)3 1,5540 CI1HI4N~ 58
H CH=CH.~ CH6 ] 47--48 (3) 7 t,5050 CTHmN2 50
H CH=CH2 C2H5| 57--59 (2) 7 1,5045 CsHI4N2 46
C6H5 CH=CH2 CHs ] 80--81" CI3HI6Nu 75
'C6H~ CH=CH2 C2H51 114--116 (2) 1,5-860 C~4H~sN2 12,9 13,1 44
H C (CH3)--CH= CH3 I 56--58 (2) 1,4920 C6HI4N2 19,8 20,3 25

* T h i s i s t h e m e l t i n g p o i n t of the c o m p o t m d .

U n d e r s i m i l a r c o n d i t i o n s , a m i x t u r e of c o p p e r p o w d e r and c u p r o u s c h l o r i d e c a t a l y z e s the r e p l a c e -
m e n t of h a l o g e n in h a l o a l l e n e s b y h y d r a z i n e a n d its d e r i v a t i v e s to g i v e a l k y l - ~ 2 - p y r a z o l i n e s in high y i e l d s .

NH~NHR~
A,R~C=C=C..r ~ m\[----~
R~/~N~N
I
R3 RJ=CH3; R2=CH3,C2Hs; R3=H, C6H3

T h e s t r u c t u r e s of t h e s y n t h e s i z e d p y r a z o l i n e s w o r e p r o v e d b y d a t a f r o m t h e i r IR s p e c t r a and a l s o b y
c o m p a r i s o n w i t h a u t h e n t i c s a m p l e s [6, 7].

EXPERIMENTAL
Alkyl-Substituted Pyrazolines. A solution of 0.1 mole of dialkylvinylethynylchloromethane (or a-bro-
moallene) in 10 ml of ether was added dropwise with stirring in the course of 30 rain to a mixture of 0.2
mole of hydrazine (or phenylhydrazine), 0.i g of cuprous chloride, and 0.i g of copper powder in 30 ml of
ether (the addition of ether is not obligatory). The temperature of the reaction mixture rose to 40 ~. It was
then stirred at room temperature for 8 h and acidified with hydrochloric acid. The aqueous solution was
neutralized with potassium carbonate and extracted with ether, and the extract was dried with magnesium
sulfate. The ether was removed by distillation, and the residue was vacuum distilled in a stream of nitro-
gen. The physical constants of the pyrazolines obtained are presented in Table I.

LITERATURE CITED

1. Sh. O. Badanyan and K. L. Sargisyan, Arm. Khim. Zh., 26, 733 (1973).
2. Sh. O. Badanyan, M. G. Voskanyan, and G. G. Khudoyan, Arm. Khim. Zh., 2_22, 1041 (1969).
3. Sh. O. Badanyan, M. G. Voskanyan, and G. G. Khudoyan, Arm. Khim. Zh., 2__5,657 (1972).
4. C. L. Lenkins and J. K. Kochi, J. Amer. Chem. Soc., 944, 856 (1972).
5. S. A. Vartanyan and Sh.O.Badanyan, Angew. Chem., 7_55,1034 (1963).
6. B. V. Ioffe and D. D. Tsitovich, Zh. Obshch. Khtm., 3__3,3449 (1963).
7. E. G. Darbinyan, A. Kh. Makhmudyan, and S. G. Matsoyan, Arm. Khlm., Zh., 22, 508 (1969).

858
PYRIMIDO [I,2-b]INDAZOLES
FROM 3-AMINOINDAZOLES AND fi-DIKETONES

Yu. M. Volovenko and V. A. C h u i g u k UDC 547.859'779

3-Aminoindazole and its hydrochloride r e a c t with fl-diketones to give pyrimido[1,2-b]in-

dazoles and their hydrochlorides.

3-Aminopyrazoles r e a c t with/3-diketones with closing of the pyrimidine ring to give pyrazolo [1,5-a]-
pyrimidines [1]. For 3-aminoindazole (I) the reaction with fi-diketones also proceeds quite readily to give
pyrimido [1,2-b]indazoles (IIa-e).

~--~/nil2 o=c/r ,o
+ c-r'--~l~ . ~ r , ~~. . . ~!n . ~ / / "
~4 \r" R"
I II a - e

The P_MIR spectra confirm structure II. The signal of the 3-H pyrimidine proton (6.54 ppm) and the
signals of two methyl groups at 2.52 and 2.70 ppm (the latter is related to 4-CH3, inasmuch as it is lower
and broader as a consequence of splitting by the pyrimidine proton) are observed in the spectrum of the
product of condensation of I with acetylacetone (in carbon tetrachloride). The 3-H proton couples with 4-CH3
to a greater extent than with 2-CH3, as a consequence of the fact that the 3-4 bond is primarily a double
bond, while the 2-3 bond is primarily a single bond [2]. The doublet at 8.10 ppm with J =9 Hz, related to
10-H, which is deshielded by the electron pair of the nitrogen atom in the 1 position as a consequence of
rigid fixing of this atom by the pyrimidine ring, serves as yet another confirmation of the formation of a
pyrimidine ring. The corresponding proton (4-H) in the PMR spectrum of the starting 3-aminoindazole ab-
sorbs together with the remaining phenylene protons at stronger field.
Three maxima- Xmax, nm (log e): 225-230 (4.11-4.14), 275-280 (4.05-4.12), and 330-335 (3.20-
3.25) - are observed in the UV spectra of If. The addition of a drop of concentrated hydrochloric acid to
the euvettes containing alcohol solutions of these compounds does not change the form of the spectra at
all; this attests to the low basicity of II.
3-Aminoindazole hydrochloride (Ill) reacts with/3-diketones even more readily than the base. The
reaction products are salts IV, which are converted to bases II by the action of ammonia. The 3-H signal
in the PIVIIR spectra of salts IV (in trifluoroacetic acid) is shifted sharply paramagnetically (7.30 ppm) as
compared with the 3-H signal in the spectrum of II, while the signals of the methyl groups are shifted only
slightly (2.62 and 2.75 ppm for IVa).
The PMR spectra serve as a basis for the selection of the structure of the products of condensation
of I and III withunsymmetricalfl-diketones. Benzoylacetone reacts with Ill to give one isomer - IVe (one
signal of a methyl group at 2.64 ppm is observed in the PMIR spectrum of the crude product of condensa- ,
rich). The structure of the condensation product was established on the basis of the character of the phenyl
signal, which, together with the signals of the phenylene protons, has the form of a complex band at 7.25-
7.75 ppm; the 3-H signal also falls in this region, and its chemical shift is no more than 7.5 ppm. Conse-
quently, the phenyl group is in the 4 position, where its signal is split into two groups of bands, the distance

T. G. Shevchenko Kiev State University. Translated from Khimiya Geterotsiklicheskikh Soedinenii,

No. 7, pp. 984-986, July, 1974. Original article submitted July 13, 1972; revision submitted February 25,
1974.

9 76 Plenum Publishing Corporation, 22 7 West 17th Su'eet, New York, A~ Y. 10011. No part o f this pubfication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

859
 T A B L E 1. P y r i m i d o [ 1 , 2 - b ] t n d a z o l e s (II) and T h e i r S a l t s (IV)

Com- R' R" ~P' Empirical formula

pound o

I i
i
IIa CHa H I CHa 140 C12HnNa 21,3 21,3 94
lib CGHs H ~C6Hs 142 C2~H~sNa t3,1 13,1 74
IIc CHa CI , CH3 170 CI~HIoCINa CI 15,4 15,3
lid CHa H ,CsHs 145 C:THIaNa ~N 16,0 16,2 __*
lie CHa H ] C3Hst 102 CI4Ht3Na I
N 19,1 18,8
IVa CHa H CHa 230 CI~HuNa.HCI04 Cl I1,7 11.9 98
IVb CHa CHa CH~ 2O8 CIaHI3Na.HCIO4 CI 11,1 11,4 100
IVc CHa H I CsH5 255 ClvHIaNa'HCIO4 CI 9,6 9,8 1O0
IVd CHa [ CaH~'t 195 C14HIaNa'HC104 CI ll,0 I1,0 96

*Obtained from corresponding salt IV.

Cyclopropyl.

between the centers of which is no morethan 0.4ppm, which is characteristic for this sort of molecular
fragment [3]. The phenyl group in the 4 position, being at a considerable angle relative to the plane of the
system, weakly deshields the 3-H proton. The phenyl group in the 2 position is split more strongly and has
a stronger effect on 3-H, as attested to by the spectrum of the product of the condensation of I with diben-
zoylmethane (Ill3in trifluoroacetic acid): despite the superimposition of the signals of the phenylene group
and the two phenyl groups, a group of peaks centered at ~-7.9 ppm, which corresponds in intensity to two
protons, is distinctly isolated in the spectrum, and 6 3-H =7.71 ppm.
On condensation with HI, l-cyclopropylbutane-l,3-dlone also gives one isomer (IVd), the structure of
which was established on the basis of the fact that the ratio of the heights of the 3-H signals (7.00 ppm) and
methyl signals (2.59 ppm) increased markedly as compared with the ratio for IVa. This change in ratios
is explained by the fact that the 3-H proton in the product of condensation with cyclopropylbutanedione is not
split by the methyl group, which is consequently in the 2 position. In addition, the considerable diamagnetic
shift of 3-H in the spectrum of this compound as compared with IVa attests to the fact that the cyclopropyl
group is in the 4 position, inasmuch as a cyclopropyl group in the a position relative to the bridge nitrogen
atom in the pyrimidine ring in other similar condensed pyrimidinum salts, for example, in 1,3,4-thiadia-
zolo[3,2-a]pyrimidinium salts [3], markedly shifts the fi proton diamagnetically, while a cyclopropyl group
in the c~ position shifts the fi proton slightly.
3-Cbloroacetylacetone reacts with Ill like other fl-diketones rather than as an a-ehloro ketone to give
corresponding salt IV, which was converted to base IId.

EXPERIMENTAL
The PM:R spectra were recorded with a ZKR-60 spectrometer with hexamethyldisiloxane as the in-
ternal standard. The UV spectra of 5 9 10 -5 M ethanol solutions were recorded with an SF-4 spectropho-
tometer.
3-Amtnoindazole hydrocbloride was obtained by treatment of 3-aminoindazole [4] with 57% perehlorie
acid.
Condensation of 3-Aminoindazole (1) and Its Hydrochloride (HI) with fi-Diketones. A mixture of I or
I I I w i t h a 1 0 - 1 5 % e x c e s s of t h e f l - d l k e t o n e w a s h e a t e d on a w a t e r b a t h for 5 - 1 0 m i n (for a l i p h a t i c k e t o n e s ) o r
f o r 3 0 - 4 0 m t n (for b e n z o y l a e e t o n e a n d d i b e n z o y l m e t h a n e ) . The r e a c t i o n m i x t u r e w a s t h e n c o o l e d a n d w a s h e d
r e p e a t e d l y w i t h e t h e r , a n d t h e p r o d u c t w a s c r y s t a l l i z e d f r o m e t h a n o l (IV) o r a q u e o u s (1 : 1) e t h a n o l (II).
C o m p o u n d 1I w a s a l s o o b t a i n e d f r o m IV b y a d d i t i o n of a m m o n i u m h y d r o x i d e to an a q u e o u s a l c o h o l s u s p e n -
s i o n of IV. C o m p o u n d II w a s o b t a i n e d a s c o l o r l e s s y e l l o w i s h o r y e l l o w (lib) c r y s t a l s , w h i l e IV w a s o b t a i n e d
as yellow crystals.

LITERATURE CITED
1, S. C h e c c h t , P . P a p i n [ , a n d M. R i d l , G a z z . C h i m . I t a l . , 8__55,1160 (1955); C h e m . A b s t r . , 50, 10,098 (1956).
2. A. P o l l a k , B. S t a n o v n i k , a n d M. T i l l e r , J. O r g . C h e m . , 3_66, 2457 (1971).
3. M. K. P o r d e l i a n d V. A. C h u i g u k , K h i m . G e t e r o t s i k l . S o e d i n . , 199 (1973).
4. C. K w a r t e r a n d P . L u c a s , J. A m e r . C h e m . S o c . , 65, 1804 (1943).

860
PMR SPECTFA OF ALKYL-SUBSTITUTED
AI-P YRA ZOLINES

N. M. A n o d i n a and B. V. I o f f e UDC 547.772.2 : 543.422.25

Data f r o m the P1V[R s p e c t r a of A l - p y r a z o l i n e s and their acyclic analogs - azo compounds -

were compared. It is shown that the difference in the chemical shifts of s i m i l a r fragments
in these compounds is due to the peculiarities of the t h r e e - d i m e n s i o n a l s t r u c t u r e s , which
lead to different contributions to shielding f r o m the unshared electron pairs of nitrogen and
the magnetically anisotropic N =N bond.

The l i t e r a t u r e c u r r e n t l y contains PIVIR s p e c t r a l data OD.lyfor a few alkyl-substituted A l - p y r a z o l i n e s

( 3 - m e t h y l - , 3 , 5 - d i m e t h y t - , and 3 , 3 , 5 - t r i m e t h y l - A I - p y r a z o l i n e s ) [1-4], the s p e c t r a of which were in-
t e r p r e t e d in relationship to the conformation of the pyrazoline ring. It has been shown that the nonequiv-
alence of the 4-H protons of 3 - m e t h y l - A l - p y r a z o l i n e is due to the p r e f e r a b l e n e s s of the Ib f o r m , while in
the case of the equilibrium Ia~-~IIa the equal populations and rapid t r a n s f o r m a t i o n s f r o m Ia to IIa lead to
equivalence of these protons. Functionally, a r y l - s u b s t i t u t e d A ' - p y r a z o l i n e s also exist as mixtures of anal-
ogous c o n f o r m e r s [5-7], and the fold angle of the envelope flap is ~25 ~
H

N N

'rl H
H
! a, b I1" a, b

I, II a R=H; b R=CH~

It s e e m s of interest to examine the peculiarities of the P1VIR s p e c t r a of alkyl-substituted A l - p y r a z o -

lines in c o m p a r i s o n with the s p e c t r a of their acyclic analogs - azoalkanes. Insofar as the latter a r e con-
cerned, the signals of the CH3N=N and RCH2N =N groups in the t r a n s f o r m s of the aliphatic azo compounds
a r e observed at quite weak field (5 3.5-3.8 ppm); this was explained by a change in the state of h y b r i d i z a -
tion of the carbon atoms bonded to the nitrogen and the contribution of m e s o m e r i e dipolar s t r u c t u r e s
C H 3 + = N - N - - R and R C H 2 + = N - N - - R [8]. T h e c i s f o r m s a r e c h a r a c t e r i z e d by c o n s i d e r a b l y g r e a t e r
shielding of these protons (A6 ~ 0.1-0.4 ppm), but an attempt to a r r i v e at a theoretical explanation
of the difference in the chemical shifts of the signals of the s t e r e o i s o m e r i c f o r m s of a n u m b e r of
phenylazoalkanes [9] did not give definite results, possibly because of the relative complexity of the
subjects of the investigation, which contain phenyl groups. P r e c i s e l y the simplest A l - p y r a z o l i n e s are
of considerable interest in connection with this problem, inasmuch as they have an azo group that is r i -
gidly fixed in the cis configuration, and they a r e free of the effects of a r o m a t i c rings and rotation of the
substituents about the N - C bond.

We have investigated five alkyl-substituted A l - p y r a z o l i n e s . A s u m m a r y of the chemical shifts and the

s p i n - s p i n coupling constants of the protons of these p y r a z o l i n e s is p r e s e n t e d in Table 1 along with the l i t -
e r a t u r e data for A l - p y r a z o l i n e and three of its homologs. A c o m p a r i s o n of the chemical shifts of the ring
protons of A l - p y r a z o l i n e s with the shift of the analogous f r a g m e n t s of the aliphatic azo compounds r e v e a l s
interesting and substantial differences. As seen f r o m Table 1, the chemical shifts of the signals of the 3-H
and 5-H pyrazoline protons lie in the 4.0-4.5 ppm region, which differs markedly f r o m the r e g i o n of c h e m -

A. A. Zhdanov Leningrad State University. T r a n s l a t e d f r o m Khimiya Geterotsiklieheskikh Soedinenii,

No. 7, pp. 987-989, July, 1974. Original a r t i c l e submitted October 22, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored hz a retrieval system, or transmitted, in any form or by a~y means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

861
 T A B L E 1. P a r a m e t e r s of the P M R S p e c t r a of A 1 - P y r a z o l i n e s

Chemical shift, 5, ppm; J, Hz

Compound 3-H 4-H 5-H GH3a

AI-Pyrazoline [2] 4,27 1,46 4,27

8-Methyl-AX-pyrazoltne [3] 4,29; 0,99, 1,73; 4,43, 1,38;
I /~4=8,5, 4,10; J'H,CH =6,9
134,=7,5, 14~=9,6, J45= 8,0,
18s=2,3, 14,~= 5,0, J4,5,=9,3,
]~s,=2,0 144,=12,3 i 1~5' [ = 16,8
ci$ 4,20; 1,28; 4,20 1,44;
3,5-Dimethyl-Al-pyrazoline! ]84=8,5 14v= 12,5 J~,c~ =7,0
[1] trans i 4,57; 1,27 4,57 1,29;
i ]84~ 8,5 /~c~ =7,0
3,3,5-Ttime thyl-ZXl-Pyraz- I 0,62, 1,78; 4,40 1,43 (5),
oline [3] I 2,4O (31,
I 1,13 (3)
I 1144,[ = 12,5
a,8-Dimethyl-Zxl-pyrazolin~ 1,30; 4,29; 1,20
l~5= 8,0 JO~H=141
3,9-Diethyl-Al-pyrazoline 1,30; 4,29;
145 = 8,0 Jc,JH=I40
3-Methyl-3-ethyl-A1- 1,20, 4,32; 1,19c
pyrazoline 9 1,41; ]45 = ] 4 ' 5 = 8,
[J44' [ = 12,3 ]C~JH ~ 141
4-Methyl-Al-pyrazoline 4,07 2,04 4,O7; 0,75
Jc,~r =t40
4-Ethyl-A~-pyrazoline 3,91 2,78 3,91,
JC,3H=141

a T h e p o s i t i o n of the methyl g r o u p in the r i n g is indicated in p a r e n -

theses.
bEthyl g r o u p s : 5 CH 2 1.69 ppm, ~ CH 3 0.76, J = 7 . 5 Hz.
CEthyl g r o u p : ~ CH 2 1.66 ppm, 5 CH 3 0.79, J = 7 . 5 Hz.

ical shifts of the analogous g r o u p s in azo c o m p o u n d s (3.7 ppm). This d i f f e r e n c e cannot be explained by a
change in the s t a t e of h y b r i d i z a t i o n of the c a r b o n a t o m , i n a s m u c h as the JNC13H values in both c a s e s a r e
c l o s e (140-141 Hz for A l - p y r a z o l t n e s and 138-139 Hz for azo c o m p o u n d s [8]) and c o r r e s p o n d to 28% s c h a r -
a c t e r of the h y b r i d i z e d o r b i t a l [10]. The r e a s o n for t h e s e deviations a p p a r e n t l y c o n s i s t s in the different
shielding of the a d j a c e n t p a i r of unbonded e l e c t r o n s . In the c a s e of A i - p y r a z o l i n e s , the p o s i t i o n of the 3 - H
and 5-H p r o t o n s is r i g i d l y fixed r e l a t i v e to the u n s h a r e d p a i r of the a d j a c e n t n i t r o g e n (which l i e s in the
plane of the r i n g and is a l w a y s equidistant f r o m the p r o t o n s of the methylene group), while r o t a t i o n of the
alkyl g r o u p s and m o r e e f f e c t i v e shielding of t h e m b y the u n s h a r e d p a i r s o c c u r in a z o a l k a n e s . The r e l a t i o n -
ship b e t w e e n the d i f f e r e n c e in the c h e m i c a l sh(fts of the p r o t o n s a d j a c e n t to the azo g r o u p in A l - p y r a z o l i n e s
and in azo c o m p o u n d s and the effect of the u n s h a r e d p a i r of the n i t r o g e n a t o m is also c o n f i r m e d by the fact
t h a t the c h a n g e in the c h e m i c a l shifts of the p r o t o n s of the methylene g r o u p s a t t a c h e d to the C =C bond a r e
insignificant (~ 0.05-0.2 ppm) on p a s s i n g f r o m olefins to c y c l o p e n t e n e [11].
The r e s o n a n c e s i g n a l s of the 4-H p r o t o n s lie at m u c h s t r o n g e r field (6 1.3 ppm) than the s i g n a l s of
the 3(5)-H p r o t o n s , so that t h e y a r e s h i e l d e d m o r e s t r o n g l y by the c o r r e s p o n d i n g g r o u p s in a z o a l k a n e s (6
1.6 ppm). This shielding of the 4 - H p r o t o n is explained by the fact that, as a c o n s e q u e n c e of bending of the
r i n g of A L p y r a z o l i n e s , t h e y fall in the r e g i o n of i n c r e a s e d shielding b y the N =N bond. At the s a m e t i m e ,
the analogous g r o u p i n g s of a z o a l k a n e s a r e s i t u a t e d n e a r the plane of the N =N double bond b e c a u s e of the
a b s e n c e of s t e r i c h i n d r a n c e , and this c o r r e s p o n d s to the deshielding r e g i o n .

EXPERIMENTAL
P r e p a r a t i o n s o b t a i n e d by i s o m e r i z a t i o n of A 2 - p y r a z o l i n e s [12] w e r e used in this r e s e a r c h . The PMR
s p e c t r a of the p u r e liquids w e r e r e c o r d e d with a V a r i a n HA-100D with h e x a m e t h y l d i s i l o x a n e as the internal
s t a n d a r d at r o o m t e m p e r a t u r e . The s p e c t r a of the azo c o m p o u n d s , which w e r e p r e p a r e d f r o m h y d r a z o n e s
[13], w e r e obtained with a J N M - 4 H - 1 0 0 s p e c t r o m e t e r .
c b a
Data f r o m the PMR S p e c t r a of the Azo C o m p o u n d s . d A z o p r o p a n e (CH3CH2CH2N=)2-6 , ppm-" CH 3 0.92,
d c b a
CH 2 (a) 3.70, CH 2 (b) 1.70; Jab = J b c = 6 . 8 Hz. A z o b u t a n e (CHjCH2CH2CH2N = ) 2 - 6 , p p m : CH 3 0.90, CH 2 (a}
3.67, CH 2 (b) 1.65, CH 2 (c) 1.37; J a b = J b c = J c d = 6 . 8 Hz.

862
 LITERATURE CITED

1. R. J. Crawford and A. Mishra, J. Amer. Chem. Soc., 8__77,3768 (1965).

2. R. J. Crawford, A. Mishra, and R. J. Dummel, J. Amer. Chem. Soc., 8_~7,3023 (1965).
3. R. J. Crawford, A. Mishra, and R. J. Dummel, J. Amer. Chem. Soc., 88, 3959 (1966).
4. C. J. O v e r b e r g e r , N. Weinshenker, and J. P. Anselm, J. Amer. Chem. Soc.,'87, 4119 (1965).
5. D. E. M c G r e e r , N. W. K. Chiu, M. G. Vinje, and K. C. K. Wong, Can. J. Chem., 4_.33,1407 (1965).
6. M. R. C a r r i e and R. Danion-Bougot, Comptes Rend., C, 270, 1135 (1970).
7. T. V. Van Auken and K. D. Rinehart, J. Amer. Chem. Soc., 84, 3736 (1962).
8. V. S. Stopskii and B. V. Ioffe, Zh. Organ. Khim., 5, 802 (1969).
9. S. N. Ege and R. R. Sharp, J. Chem. Soc., B, 2014 (1971).
10. C. W. Rathjens, J. Chem. P h y s . , 36, 2401 (1962).
11. J. E m s l e y , J. Feeney, and L. Sutcliffe, High-Resolution Nuclear Magnetic Resonance Spectroscopy
P e r g a m o n , Oxford (1965, 1966).
12. B. V. Ioffe and N. B. Burmanova, Khim. Geterotsikl. Soedin., 956 (1971).
13. B. V. Ioffe, Z. I. Sergeeva, and V. S. Stopski[, Dokl. Akad. Nauk SSSR, 1677_, 831 (1966).

863
HETERYLIMIDAZOLES
III.* POLAROGRAPHIC OXIDATION OF 2 - H E T E R Y L -
4,5-DIAR YLIMIDAZOLE ANIONS

Yu. A. Rozin, V. E. Blokhin, UDC 543.253 : 547.78*5.1

Z . V. P u s h k a r e v a , a n d V. I . Elin

The anions of 2-quinolinyl- and 2 - ( 9 - a c r i d i n y l ) - 4 , 5 - d i a r y l i m i d a z o l e s w e r e subjected to po-

l a r o g r a p h i c oxidation. The l i n e a r r e l a t i o n s h i p between the h a l f - w a v e potentials and the
substituent constants was investigated.

I n f o r m a t i o n r e g a r d i n g the effect of n i t r o g e n - c o n t a i n i n g h e t e r o c y c l e r e s i d u e s on p o l a r o g r a p h i c oxida-

tion is absent in the data on the p o l a r o g r a p h i c oxidation of t r i a r y l i m i d a z o l e s [2], t h e i r anions [3, 4], and
h e t e r o a n a l o g s of t r i a r y l i m i d a z o l e s containing furan and thiophene r e s i d u e s [5].
We have p r e v i o u s l y s y n t h e s i z e d a n u m b e r of heteroanalogs of t r i a r y l i m i d a z o l e s (Ic-VIIIa-d, Table 1)
containing i s o m e r i c quinolinyl and 9 - a c r i d i n y l groups as substituent R 3 [1, 6]. Oxidation of their anions with
p o t a s s i u m f e r r i e y a n i d e gives the c o r r e s p o n d i n g r a d i c a l s , which r e c o m b i n e in the d a r k at r o o m t e m p e r a t u r e
to diimidazolyls, which display p h o t o c h r o m t s m and ther m o c h r o m i s m owing to r e v e r s i b l e dissociation into
r a d i c a l s [1].

P'~%n'yN',~__R~
p- R 2 C 6 H 4 / ~ I -
I c-VII! a-d

I n a s m u c h as the p o l a r o g r a p h i c oxidation of t r i a r y l i m i d a z o l e anions also gives r a d i c a l s [3], it was e x -

pedient to use this method to e s t a b l i s h the quantitative r e l a t i o n s h i p between the chemical s t r u c t u r e of i m i d -
azole anions I c - V I I I a - d and their ability to f o r m r a d i c a l s . The v o l t - a m p e r e c u r v e s of the anions under-
going oxidation have a single wave with a half-wave potential (El/2) ranging f r o m 0.335 to 0.61 V (Table 1).
The anions of VIIb-VIId, for which this wave is e x p r e s s e d weakly and l i e s on the boundary of the background
o p e r a t i n g c h a r a c t e r i s t i c s , constitute an exception to this.
As expected, e l e c t r o n - d o n o r substituents facilitate oxidation of the anions, while e l e c t r o n - a c c e p t o r
substituents hinder oxidation. A l i n e a r relationship, which is e x p r e s s e d by the following equations for the
s e r i e s , exists between the oxidation potentials and the overall constants of the p a r a substituents of the phen-
yl rings in the 4 and 5 positions: III AE1/2=0.141E~ (r =0.945, s =0.003), V AE1/2=0.135Ecr (r =0.991, s =
0.008}, VI AEt/2 =0.122~ff (r=0.992, s =0.012), andVIIIAEy'2= 0.105~ ~ (r =0.996, s =0.007).
On examination of the effect of substituents in the 2 position it is apparent that the oxidation potential
d e c r e a s e s in the following direction: phenyl > ~ - n a p h t h y l > t3-naphthyl > 9-anthracenyl.
On passing f r o m a - and fl-naphthyl- and 9 - a n t h r a c e n y l - s u b s t i t u t e d anions to their a z a analogs (Ic-
VIIIc), the oxidation potential i n c r e a s e s b e c a u s e of the e l e e t r o n - a c c e p t o r effect of the nitrogen atom. It
follows f r o m a c o m p a r i s o n of the data of s e r i e s VIII and III that 9 - a c r i d i n y l is a s t r o n g e r a c c e p t o r than
4-quinolinyl.

*See [1] for communication If.

S. M. Kirov Ural Polytechnic Institute, Sverdlovsk. T r a n s l a t e d f r o m Kh[miya G e t e r o t s i k l i c h e s k i k h

Soedinenii, No. 7, pp. 990-992, July, 1974. Original a r t i c l e submitted July 24, 1973.

9 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photoeopying, microft'lming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the pubOsher for $15.00.

864
 TABLE 1. Half-Wave Potentials of the Oxidation (El/2, V) of 2-
H e t e r v l - 4 , 5 - d i a r y l i m i d a z o l e Anions (Ic-VIIIa-d)*

RI=H,
CO1TI - R'=R2=CH30 R I = R : = CIt~. W=R==H R,=R~=Br
pound R~
C"

I 2- Quinolinyl m 0,610
11 3-Quinolinyl 0,340 0,406 0,475
III 4-Quinoli@l 0,435 0,470 0,490 0.570 0,625
1V 5-Quinolinyl 0,413 0,460
V 6- Quinolin)l 0,335 0,380 0,427 0,470 0,525
VI 7- Quinolinyl 0,350 0,400 0,450 0,490 0,520
VII 8.Quinolin)I 0,600 >0,6 >0,7 >0,7
VIII 9-Acridinyl 0,472 0,505 0.540 0,580

* For 2,4,5-triphenylimidazole anions (IX), El/2 = 0.465 V, while

E =0.450 and 0.435 V, r e s p e c t i v e l y , for 2- (a -naphthyl)- and 2-
(fi-naphthyl)-4,5-diphenylimidazoles (X and XI); El/2 = 0.430 V for
2,9-anthracenyl diphenyl i midazol e (XII).

A linear relationship between El/2 and the cr constants of

i s o m e r i c quinolinyls, which is e x p r e s s e d by the equation El/2 =

0,~0 ~' ~ 9' ~ ~~ 0.410+0.133cr (r =0.951, s =0.007), except for the point c o r r e -
sponding to anion Ic, is observed in the s e r i e s of anions of 2 - h e t :
e r y l - 4 , 5 - d i p h e n y l i m i d a z o l e s containing i s o m e r i c quinolinyl r e s i -
dues (Fig. 1). The i n c r e a s e d El/2 value (0.61 V) for anion Ic is
0p45 ,
probably due to the peculiar ortho effect of the nitrogen atom of
2-quinolinyl. 8-Quinolinyl-substituted imidazoles have unexpec-
0,40 tedly high oxidation potentials, if one proceeds f r o m the value of
0~0 012 0~4 0',6 018 the ~r constant [7] of this substituent (-0.06). The high oxidation
Fig. 1. C o r r e l a t i o n between the potential here apparently is determined in many r e s p e c t s by the
oxidation potentials of anions I I c - effect of the field of the nitrogen atom of the quinolinyl substitu-
VIc, IX, and XI and the ~ - s u b s t i t u - ent. The high negative potentials are apparently the r e a s o n that
ent constants: 1) IX; 2) XI; 3) Vc; prevents the p r e p a r a t i v e oxidation of anions Ic and VIIa-d by the
4) VIc; 5) IVc; 6) IIc; 7) IHc. action of p o t a s s i u m f e r r i c y a n i d e [6].
It should be noted that the point of IX c o r r e s p o n d i n g to the
triphenylimidazole anion also lies above the c o r r e l a t i o n line. This
is probably due to the i n c r e a s e d stabilization of the r e s u l t i n g r a d i c a l s , which contain a t w o - r i n g substituent;
this is not taken into account by the available a - s u b s t i t u e n t constants [7].

EXPERIMENTAL
The polarographic oxidation was carried out with a rotating carbon electrode relative to a saturated
calomel half-cell in a thermostated (25 0.2 ~ cell in dioxane solution containing a borate buffer (pH 9.18).
The dioxane-buffer volume ratio was 3:2, and the depolarizer concentration was 10 -3 M. The rate of rota-
tion of the electrode was 632 rpm, and the area of the carbon electrode was 3.4 mm 2. The polarograms
were recorded by means of a IP-60 polarograph, The half-wave potentials were found graphically by semi-
logarithmic treatment of the normalized polarographic carve. The accuracy in the determinations was
0.005 V.
The ~ constants of i s o m e r i c quinolinyls were taken f r o m [7], while those for the r e m a i n i n g c o m -
pounds were the Jaffe values [8].

LITERATURE CITED

1. Yu. A. Rozin, V. E. Blokhin, Z. V. P u s h k a r e v a , V. I. Elin, and M. E. Sukhova, Khim. Geterotsikl.

Soedin., 1105 (1973).
2. V. N. Shishkin, B. S. Tanaseichuk, L. G. Tikhonova, and A. A. Bardina, Khim. Geterotsikl. Soedin.,
387 (1973).
3. W. Sttmmermann and H. Baumgtirtel, Ber. Bunsen-Ges. Phys. Chem., 74, 19 (1970).
4. W. St~mmermann and H. Baumg/irtel, Coll. Czech. Chem. Commun., 36, 575 (1971),

865
5. S. V. Yartseva, P. I. Levin, L. P. Lebedeva, V. N. Shishkin, and B. S. Taaaseichuk, Vysokomol.
Soedin., 13, 2260 (1971).
6. Yu. A. Rozin, V. E. Blokhin, Z. V. P u s h k a r e v a , and M. E. Sukhova, Khim. Geterotsikl. Soedin., 681
(1972).
7. R. C. Elderfield and M. Siegel, J. A m e r . Chem. See., 7_33,5622 (1951).
8. Yu. A. Zhdanov and V. I. Minkin, Correlation Analysis in Organic C h e m i s t r y [in Russian], Izd. R o s -
tovsk. Gos. Univ. (1967).

866
NUCLEOPHILIC SUBSTITUTION OF HYDROGEN
(3-H) IN QUINOXALONE BY ARYLAMINES

O. N. Chupakhin, E. O. Sidorov, UDC 547.863.16 + 543.422.25.4

and I. Ya. Postovskii

When quinoxalone is heated with a r o m a t i c amines in acetic acid in the p r e s e n c e of a m m o -

nium nitrate, a hydrogen undergoes nucleophilic substitution to give the corresponding
3- (4'-aminophenyl) quinoxalones.

A r e a c t i o n for the introduction of a r y l a m i n e r e s i d u e s into the 2-quinazolone molecule was described

in [1]. In the p r e s e n t study we have checked the possibility of the use of this t r a n s f o r m a t i o n for an i s o m e r i c
h e t e r o c y c l i c compound - quinoxalone (I).
The carbon atoms in the 2 and 3 positions in quinoxaline have pronomlced electroph[lic p r o p e r t i e s [2].
However, up until now, the study of nucleophflic substitution reactions in the quinoxaline s e r i e s has been
limited mainly to investigation of the substitution r e a c t i o n s of halogens in the 2 and 3 positions [3]. It is
also known that quinoxalines r e a d i l y r e a c t with such nucleophiles as o r g a n o m a g n e s i u m compounds to give
products of addition to the C =N bond; the r e a c t i o n with diazomethane leads to C-methylation [5]. The p a r -
ticipation of quinoxalines and qulnoxalone in r e a c t i o n s with weak nucleophiles such as a r y l a m i n e s is un-
known.
Quinoxalone proved to be inert with r e s p e c t to dimethylaniline even when it was refluxed for many
hours in an excess of the latter. The use of sulfur or selenium in a c c o r d a n c e with the method in [6] r e -
quires high t e m p e r a t u r e s , in which case the yields of products a r e low (< 5%) because of pronounced r e s i n -
ificationofthe r e a c t i o n mixture.
We have found that the r e a c t i o n of I with a r y l a m i n e s p r o c e e d s in s a t i s f a c t o r y yield when it is c a r r i e d
out with acetic acid as the solvent in the p r e s e n c e of eqnlmolar amounts of a m m o n i u m nitrate. When a m -
monium nitrate is absent, the yield is reduced markedly. The condensation may also be c a r r i e d out in fused
a m m o n i u m nitrate, but the yields of products amount to only 5-10%.
On the basis of the l i t e r a t u r e data [4, 8] it might be a s s u m e d that the r e a c t i o n proceeds with the in-
itial formation of addition products II, which are then oxidized to III-XII (Table 1).

/r, ]
R~\N/R2 . .~N\r~| ~ N~r,
.[011 n r ~'r'

II IlI-XII

The a m m o n i u m nitrate in this r e a c t i o n possibly functions as a mild oxidizing agent or has a catalytic
effect. The c h a r a c t e r of the oxidizing agent is of substantial significance: the use of such oxidizing agents
as KMnO4, Na2Cr2OT, Cr203, H202, and Pb(CH3COO)4 leads to intensive r e s i n i f i c a t i o n o f the r e a c t i o n mixture
because of oxidation of the a r o m a t i c amine; on the other hand, aminoarylation does not occur when oxidizing
agents of low activity such as oxygen [7] are used. Chloraail cannot be used as the oxidizing agent because
of complexing with the a r y l a m i n e s .

S. M. Kirov Ural Polytechnic Institute, Sverdlovsk. T r a n s l a t e d f r o m Khimiya GeterotsiklichesMkh

Soedinenii, No. 7, pp. 993-996, July, 1974. Original a r t i c l e submitted September 10, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval O,stem, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

867
 4444444 44 4
- ; ~- .... ") ; d,ppm

i,!I
$

3',5'-2H I 2',6'-2H 3 ' z ~ , . NH 2

'o,
4444444 44 4
~ - ~ ~

; ;" -) ; d,ppm
" 5'~H ] 6'-H
3'-; ~, ~ ,k cH,
c l (~ II tl f.L :.NH2

h ,~i ' ' H

j U <b ;Jt it_

~ "t ~ 6, ppm
Fig. I. PIVIR spectra of I, IX, and
X in dimethyl sulfoxide.
.~
Our method is a g e n e r a l one, and the c o r r e s p o n d i n g
3 - (4'-aminophenyl)qutnoxalones can be r e a d i l y obtained fro m
quinoxalone by r e a c t i o n with p r i m a r y , s e c o n d a r y , and t e r t i a r y
O
a r o m a t i c a m i n e s (Table 1}.
Absorption bands at 1650-1670 c m - l , which are c h a r -
a c t e r t s t i c for the s t r e t c h i n g vibrations of the C =O group, a r e
: ,, t.,~tra%D'r wa'~
o b s e r v e d in the LR s p e c t r a of III-XII. Absorption bands at
3300-3500 c m -1 are absent for the compound with a t e r t i a r y
['~ i - - i
A amino group, while a band at 3400 c m -1 is o b s e r v e d for the
i U i ~ ~ ' ~ " " "
!
s e c o n d a r y amino group. The p r i m a r y amino group of IX, XI,
I
and XII appears as three bands at ~ 3360, 3440, and 3480
ooooooo o~ 8
d c m -~. The appearance of a band at 3360 c m -1 is evidently due
~D to strong inter m o l e c u l a r hydrogen bonds [9]. The bands at
N
O GGGUGGG dd d 1620 c m -1 can be a s s i g n e d to the deformation vibrations of a
,.Q
free amino group.
O A study of the PM:R s p e c t r a of s o m e of the compounds
@q
I
0
obtained in this r e s e a r c h c o n f i r m e d that substitution p r o c e e d s
I in the 3 position of the h e t e r o r i n g and also made it p o s s i b l e
d to e s t a b l t s h t h a t a r y l a m i n e s r e a c t at the para position. The
r
3-H methyl[dyne proton which appears as a singlet at 8.2 ppm
N (Fig. 1, s p e c t r u m a), is not p r e s e n t in the s p e c t r a of the s u b -
9 stitution products 9 The two doublets at 8.2 ppm and 6.6 ppm
< with J =8 Hz (Fig. 1, s p e c t r u m b) are c h a r a c t e r i s t i c for p - d i -
I
substituted a r o m a t i c compounds. A t h r e e - s p i n s y s t e m of the
I 0 AMX type, which can be r e a d i l y analyzed according to the
eQ
r u l e s for s p e c t r a of o r d e r 1, is o b s e r v e d for compounds with
,4 o - s u b s t i t u t e d a r y l a m t n e s (Fig. 1, s p e c t r u m c).
~q
=>>~==~ ~ -
The e l e c t r o n i c s p e c t r a of the investigated 3 - ( 4 ' - a m i n o -
phenyl)quinoxalones contain t h r e e absorption bands at 2 2 8 -
2 3 1 , 2 6 0 - 3 2 0 , and 390-425 n m , which can be a s s i g n e d to ~r-r *
t r a n s i t i o n s . The introduction of an a r o m a t i c amine r e s i d u e
into the qutnoxalone m o l e c u l e ( ~ m a x 230, 282, and 348 rim)

868
leads to a pronounced shift of the long-wave maximum and an increase in the molar extinction coefficient
by a factor of about four. The medium-wave maximum sustains an appreciable hypsochromic shift, during
which the absorption intensity also increases. The position of the short-wave band lies in approximately
the 230 nm range. The expected bathochromic shift of the long-wave maximum is observed as the degree
of alkylation of the nitrogen atom of the amino group increases.
Bases III-XII are yellow and form mono- and diprotonation products; they are red in acetic acid and
yellow in concentrated H2SO 4. An additional absorption (Xma x 520-540 nm, log ~ 2.9-3.4) appears in the
spectrum of an acetic acid solution in the visible region as a shoulder on the long-wave maximum, which
disappears in concentrated H2SO 4. The mesomeric structure of ion XIV, which has a p-quinoid system of
bonds, explains the bathochromic effect observed in weakly acidic solutions. The unshared pair of electrons
of the amino group is blocked (XV) in strong acid, and the formation of a mesomeric p-quineid structure be-
comes impossible.

+H/RI
/~/N\R2 ~N/RI

~ , f ~.N/~ 0 ......
H
XV Xlll XIV

EXPERIMENTAL
The electronic absorption spectra of 4" 10 -4 mole/liter solutions of the compounds in alcohol were re-
corded with a Specord spectrophotometer. The IR spectra of mineral-eilsuspensions (NaCI prism) and per-
fluorocarbon oil suspensions (LiF prism) of the compounds were recorded with an IKS-14 spectrometer.
The PMR spectra of 5~ solutions in dimethyl sulfoxide were recorded with a Varian-60T spectrometer.
3-(4'-N,N-Dimethylaminophenyl)quinoxalone (III}. A mixture of 1 g (6.8 mmole) of quinoxalone, 0.86
ml (6.8 mmole) of dimethylaniline, and 0.54 g (6.8 mmole) of ammonium nitrate was refluxed in 12 ml of
acetic acid for 2 h, and the resulting hot solution was poured into I00 ml of 1 N HCI. The resulting in-
tensely red solution was allowed to stand for ~ 5 h in order to precipitate unchanged I. The solution was
then copious filtered, and the filtrate was neutralized to pH 6-7. The copious yellow precipitate was re-
moved by filtration, washed on the filter with warm water, and dried at I00 ~
3-(4'-N,N-Dibenzylaminophenyl)quinoxalone (IV). A mixture of 1 g (6.8 mmole) of quinoxalone, 2.05 g
(7.5 mmole) of dibenzylaniline, and 0.54 g (6.8 mmole) of ammonium nitrate was refluxed in 12 ml of acetic
acid for ~ 5 h until a copious precipitate formed. The suspension was cooled, and the crystalline precip-
itate was removed by filtration, washed with ether, and dried at i00 ~
Compounds V-XII. A 0.82-mi (13.6 mmole) sample of glacial acetic acid was added to a mixture of
6.8 mmole of quinoxalone, 7.5 mmole of arylamine, and 6.8 mmole of ammonium nitrate, and the mixture
was heated on an oil bath to 130-135 ~ and stirred for 2 h. The reaction mass was dissolved by heating in
50 ml of alcohol, and the alcohol solution was separated with a 30 1000 preparative column filled with
activity II Al203 (elution with chloroform). The unchanged arylamine and the resinification products were
eluted with chloroform (the first red-violet zone), and the substitution products were eluted with acetone-
chloroform (i 9 i) or alcohol. The solvent was removed by distillation, and the dry residue was crystallized
from a suitable solvent (Table i).

LITERATURE CITED
i. I. Ya. Postovski[, O. N. Chupakhin, T. L. Pilicheva, and Yu. Yu. Popelis, Dokl. Akad. Nauk SSSR, 21__22,
1125 (1973).
2. G. W. H. Cheeseman, Recent Advances in Quinoxaline Chemistry, Advances in Heterocyclic Chem-
istry, Vol. 2, Academic Press (1963), p. 212.
3. R. C. Elderfield (editor), Heterocyelic Compounds, Wiley (1950-1957).
4. H. Gilman, G. Eisch, and T. Soddy, J. Amer. Chem. Soc., 79, 1945 (1957).
5. G. W. H. Cheeseman, J. Chem. Soc., 1804 (1955).
6. O. N. Chupakhin, V. A. Trofimov, and Z. V. Pushkareva, Dokl. Akad. Nauk SSSR, 188, 376 (1969).
7. V. E. Posazhennikova, O. N. Chupakhin, and I. Ya. Postovskii, Khim. Geterotsikl. Soedin., 1384 (1970).

869
8o A. F. P o z h a r s k i i and A. M. Simonov, Chichibabin Amination of H e t e r o c y c l e s [in Russian], Izd. R o s -
tovsk. Univ. (1971), p. 14.
9. L. Bellamy, I n f r a r e d Spectra of Complex Molecules, Methuen (1958).

870
a-OXIDES IN REACTIONS WITH N- H ACIDS
OF THE HETEROCYCLIC SERIES
I. ALKYLATION OF 3-NITRO-5-BROMO-I,2,4-TRIAZOLE
WITH EPOXIDES

T. P. Kofman, G. A. Zykova, UDC 547.792T787T867.2 : 542.953

V. I. Manuilova, T. N. Timofeeva,
and M. S. Pevzner

The r e a c t i o n of epoxides with 3 - n i t r o - 5 - b r o m o - l , 2 , 4 - t r i a z o l e gave a s e r i e s of 1 - ( f i - h y -

droxyalkyl)- 3 - n i t r o - 5-bro too- 1,2,4-tr [azoles, which, under the influence of b a s e s , undergo
i n t r a m o l e c u l a r cyclization with HBr elimination to give an ew h e t e r o c y c l i c s y s t e m -
2 - n i t r o - 5 , 6 - d i h y d r o o x a z o l o [2,3-e]- 1,2,4-triazole.

The alkylation of N - H acids of the n i t r o a z o l e s e r i e s by epoxides has not been s y s t e m a t i c a l l y studied.

The published c o m m u n i c a t i o n s with r e g a r d to this p r o b l e m touch upon only the s y n t h e s i s of N - f l - h y d r o x y -
alkyl d e r i v a t i v e s of 5 - n i t r o i m i d a z o l e [1] and 5 - n t t r o p y r r o l e [2]. The r e a c t i o n s of 3 ( 5 ) - n i t r o - l , 2 , 4 - t r i a z o l e s
with epoxides have not been investigated.
The r e a c t i o n of 3 - n i t r o - 5 - b r o m e - 1,2,4-tr iazole (I) with epoxides gives fl-hydroxyalkyl der ivatives
(II-VII), during which the oxide ring in the u n s y m m e t r i c a l l y substituted epoxides opens in c o n f o r m i t y with
the K r a s u s k i i rule. Compounds II-VII w e r e obtained as undistillable oils and w e r e identified by synthesis
of d e r i v a t i v e s VIII-XI (Table 1). The f o r m a t i o n of s e c o n d a r y alcohols was c o n f i r m e d by oxidation of 1-(fi-
h y d r o x y p r o p y l ) - 3 - n i t r e - 5 - b r o m o - l , 2 , 4 - t r i a z o l e (III) to the c o r r e s p o n d i n g ketone (VIII).

N "NO2 N ~ NO2 N /NO 2

u I I 11
CH2--CH(OH) R CH~CR

1 II-VII 9111

Xll-XVll CH--C H (ONO 2) R

IX-Xl
II. XII R=H; lII, VIII, IX, XIII R~CH3; IV. X. XIV R=CH2CI; V, XV R=CH.~OH; VI. XVI
R=CH..ON02; VII, XVII R~CH.-OCH~

The alkylation of t r i a z o l e I with epoxides in aqueous alcohol media p r o c e e d s both in the p r e s e n c e and
in the absence of b a s e s and is a c c o m p a n i e d by a r e g u l a r i n c r e a s e in the pH of the medium, which is a s s o -
ciated with consumption of the acidic component. The buildup of alkylation products II-VII, the bulk of
which (up to 60%) is f o r m e d at the instant the pH of the m e d i u m r e a c h e s a value that excludes the p r e s e n c e
of the f r e e NH acid in solution (pH > 5, pK a 3.05}, is s i m u l t a n e o u s l y noted.*

* D e t e r m i n e d by p o t e n t i o m e t r y .

Lensovet L e n i n g r a d Technological Institute. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedin-

enii, No. 7, pp. 997-1002, July, 1974. Original a r t i c l e s u b m i t t e d July 19, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

871
 TABLE 1. 1- (fl-Nitr o h y d r o x y a l k y l ) - 3 - n i t r o - 5 - b r o m e - 1,2,4-tr iazoles
Found I Calculated
o R Empirical formula
]
'.,! B~,
c.o/o:O/o, O/o j!.,o/o M c, 0ioi.,
O/o B,,I
,
O/o, ~,
O/o ' M ~
:

ixX ]CH~
CH2CI
114
100
! CsH6BrNsO5
C~HsBrC1N~Os
20,5 2,3/ 27,5123
b 6413071 03 i 2,0~L27,0 23,6!296! 3
18,o 1,41 -- 121,21326118,1i ~,,5 -- [21,2 330163
XI CH~OCHa 69 C6HsBrN~ 21,8 1,9], 24,9L21,6i322[ 22,11 24'5i 21,5i326],52

&pH 3
2,8

2,0
2,4 2 1

1,6

%2

Or8

0,4

20 40 60 80 100 120 140

Fig. 1. Change in the pH of the m e d i u m

during the alkylation of t r i a z o l e I with
e p i c h l o r o h y d r t n as the b a s e (NaOH) concen-
t r a t i o n ( m o l e / l i t e r ) is v a r i e d : 1) 0; 2)
0.0526; 3) 0.115. The r e a g e n t c o n c e n t r a -
tions ( m o l e / l i t e r ) w e r e as follows: I 0.0526,
epichlorohydrin 1.115 (the m e d i u m was 80%
ethanol).

The e x p e r i m e n t a l data on the alkylation of I under various conditions indicate a substantial depen-
dence of the r a t e of the p r o c e s s on the b a s e concentration (Fig. 1), the r e a c t i v i t y of the epoxide (Fig. 2),
and the p r o p e r t i e s of the m e d i u m (Table 2).
The s u c c e s s f u l alkylation of 3 - n i t r o - 5 - b r o m o - l , 2 , 4 - t r i a z o l e in aprotic and p r o t o n - d o n o r solvents
in the a b s e n c e of an e x t e r n a l c a t a l y s t a t t e s t s to possible r e a l i z a t i o n of the p r o c e s s during acid c a t a l y s i s
(H+ or H+A -) via the s c h e m e adopted in the m o d e r n c h e m i s t r y of epoxides [3, 4]. In this c a s e , the a c c e l -
e r a t i o n ofthe p r o c e s s in ether as c o m p a r e d with ethanol is evidently explained by the a b s e n c e of solvation
of the oxygen of the oxide ring at which p r i m a r y attack of the s t a r t i n g acid o c c u r s . On the other hand, the
a c c e l e r a t i o n of the alkylation in ethanol when b a s e is introduced (Fig. 1) indicated the p a r t i c i p a t i o n of the
anion of I in the r e a c t i o n . In this c a s e , an i n c r e a s e in its concentration should affect the p r o c e s s e s c a t a -
lyzed by both acids (2) and b a s e s (1).

~,~=c,, + ~N: [ ~-...c,2-c,d L:...c,~-c., [

"o" --, + ,or '+"" -- L <.0j--,c,2c.,o,,,+~,: <~1
L ,a 0 ]

-- Fl : ....... 04""~ 1+ ,--- [.0,...,...o:&,

L ~

Kinetically speaking, t h e s e v a r i a n t s a r e indisthaguishable, while the p r o b a b i l i t y of one or the other

p r o c e s s is d e t e r m i n e d by the acidity of the s u b s t r a t e [5]. However, the fact that propylene oxide p r o v e d to
be m o r e r e a c t i v e than epoxides with e l e c t r o n - a c c e p t o r substituents in the r e a c t i o n with t r i a z o l e I a p p a r -
ently is evidence in favor of the s c h e m e p r e s e n t e d above, which is m o r e r e a l i s t i c for r e a g e n t i - a s u b -
st-rate of sufficiently high acidity.
Judging f r o m the identical c h a r a c t e r of the n i t r a t e s obtained in the nitration of the crude alkylatton
p r o d u c t s , the r e a c t i o n of t r i a z o l e I with epichlorohydrin under various conditions leads to the p r e d o m i n a n t

872
 TABLE 2. Alkylation of 3 - N i t r o - 5 - b r o m o - l , 2 , 4 - t r i a z o l e with Epoxides
[ RClt--cI~2(D 0,526 m o l e / l i t e r , epoxide 1.15 m o l e / l i t e r ]
\/
o
Hof medium[ ]
Com- Temper- Solvent NaMOH, - - - - !Time !Tield,
i s
pound ature, ~ ~t~rt e~d Ih %
I

II H 80%0Ethanol 0,0526 2,54 5,84 110 62

H Ether 0 1,25 4,01 120 60
Ill CHa 80% Ethanol 0,0526 2,95 6,08 90 62
CHa Ether 0 2,00 5,57 96 72
IV CH2CI 80% Ethanol 0,115 2,88 5,73 69 68
CH2CI 80% Ethanol 0,0526 2,78 5,91 160 67
CHaC1 80% Ethanol 1,93 2,91 864 28
CH=CI 80% Ethanol 0 1,91 4,10 55 46
CH2C1 Ether 1,24 3,35 90 42
V CH20H 80% Ethanol 0,0526 2,44 5,62 215 52
VI CH2ON02 80% Ethanol 0,0526 2,53 5,64 145 62
VII CH2OCHa 80% Ethanol 0,0526 2,41 5,41 208 65

I ApH
4,0b
2
3,5 5 4 $'
! X
3~0 3

2,5

2jO

%5

I pO

C~5

2o ~o 6o 8o ~oo ~2o ~o ~6o ~so 2oo

Fig. 2. Change in the pH during the alkylatton of t r i -

azole I with epoxides: 1) propylene oxide; 2) ethylene
oxide; 3) epichlorohydrin; 4) glyctdol; 5) nitroglycidol;
6} methoxyglycidol [the r e a g e n t concentrations {mole/
liter) were as follows: I 0.526, NaOH 0.0526, and
epoxide 1.16].

formation of vic[nal halohydrin IV, the s t r u c t u r e of which might have been proven by dehydrocMorination to
the c o r r e s p o n d i n g epoxide. However, the substance that we obtained upon alkaline t r e a t m e n t of IV did not
c o r r e s p o n d to the t a r g e t epoxide with r e s p e c t to its chemical p r o p e r t i e s and s p e c t r a l and analytical data.
Similar compounds that do not contain a hydroxyl group and bromine were obtained by r e a c t i o n of other
1- (fi-hydr oxyalkyl)-3 - n t t r o- 5-br o m o - i ,2,4-tr iazoles with bases.
On the basis of the data obtained in this study and considering the known tendency of bromine in 3 - n i -
t r o - 5 - b r o m o - l , 2 , 4 - t r i a z o l e derivatives to undergo nucleophilic substitution [6], we concluded that alcohols
II-VH undergo [ntramolecular cyclization with HBr elimination to give a new h e t e r o c y c l i c s y s t e m - 2 - n [ t r o -
5 , 6 - d i h y d r o o x a z o l o - [ 2 , 3 - e ] - l , 2 , 4 - t r i a z o l e {Table 3). An example of analogous cyclization to give a t w o - r i n g
s t r ucture is known for 1- ( f l - h y d r o x y e t h y l ) - 2 - a c y l - 5 - n i t r o p y r r o l e der[vatives [2 ].
The formation of different t w o - r i n g derivatives - 2 - n i t r o - 6 - h y d r o x y m e t h y l - 5 , 6 - d i h y d r o o x a z o l o [2,3-e]-
1 , 2 , 4 - t r t a z o l e s (XV) when the s e c o n d a r y hydroxyl group participates in the r e a c t i o n and 2 - n i t r o - 6 - h y d r e x y -
5,6,7-tr thydro- 1,3-oxaz ino [2,3-e ] - 1 , 2 , 4 - t r iazole (:<VIII) for r e a c t i o n with the pri m a r y hydroxyl group - is
fundamentally possible in the cyelization of dtol V.
_ (O"~Ny NO2
V uo ''~-,/N-N

XVII!

873
 T A B L E 3. 2-Nitro-5-R-5,6-dihydroxazolo [2,3-e]-l,2,4-triazoles

Crystallization Found, % Calculated. %

Empirical
solvent formula .c. . . . H I N IV
CrH N

XI! 141 Ethanol C4H4N4Oa 31,2 2,2 35,2 30,8 2,6 35.9 85
XIII cHHa 85 ]CCI4--Hexane (1 : 2)
XIV CH2CI* I 153 CCI4--CHCla, (1:1)
CsH6N4Oa 34,71 3,6
CsHsC1N4Os 29,3' 2,6
32,8 35,3t 3,5 32,9186
26,9/ 29,31 2,41 27,4i 89
XV CH2OH } 1291CH2C12 CsH4N404 131,913,1 30,0/32,3 3,2 30,1 7S
XVI CH2ONO~ 124 Ethanol CsHsNsO6 26,2 1,7 304!260 2,2 30,3 81
XVII CH2OCH3 113 CCI4 C6HsN404 35,8 3,7 27,6 36,0 4,0 ]28,0/85
it

* F o u n d : C1 17.39%. Calculated: C1 17.36%.

T A B L E 4. P a r a m e t e r s of t h e P M R S p e c t r a of 1 - ( f l - H y d r o x y a l k y l ) -
3 - n l t r o - 5 - b r o m o - 1 , 2 , 4 - t r [ a z o l e s and T h e i r N i t r a t e s
Corn- ]
pound*'~ R 8C:H.~ 6CH 6CH~O 6OCHa 0CHa 6 CH2CI

It H 4,35 (t)l" 4,50(t)

J=6 Hz /=6 Hz
Ill CH3 4,45 (d) 3,85(m)? 1,2o(d)
J=6 Hz Y=7Hz
V CH2OH 5,20 (d) 4,5o (m) 4,05(d)
J=5 Hz ]=6 Hz
VII CH2OCHal 5,20 (d) 4,50 (m) 3,65(d) 3,40 (s)'~i
! ]=6Nz ]=5 Hz
IX CH3 i 4,75 (d) 5,72 (m) 1,52(d)
7=5 Hz ]=7 Hz
X CH2CI ! 4,98 (d) 6,02 (m) 4,22(d)
' ] = 6 Hz ]=5 Hz
XI CH2OCH3 4,92(d) 5,90 (m) 3,90 (d) 3,40 (s)
t 1=6 Hz J=5 Hz

* The s p e c t r a of II, V, a n d VH w e r e o b t a i n e d f r o m n i t r o b e n z e n e
s o l u t i o n s , w h i l e t h e s p e c t r a of t h e r e m a i n i n g c o m p o u n d s w e r e o b -
tained from acetone solutions.
, S y m b o l s : s i s s i n g l e t , d is d o u b l e t , t is t r i p l e t , a n d m is
multiplet.

The f o r m a t i o n of s t r u c t u r e XV w a s p r o v e d b y c o n v e r s i o n to the c o r r e s p o n d i n g n i t r a t e , which was

i d e n t i c a l to p r o d u c t XVI o b t a i n e d b y e y c l i z a t i o n of VI.
It s h o u l d be n o t e d t h a t i n t r a m o l e c u l a x c y c l i z a t i o n of N - s u b s t i t u t e d f l - h y d r o x y a l k y l - 3 - n i t r o - 5 - b r o m o -
1 , 2 , 4 - t r i a z o l e s w i t h H B r e l i m i n a t i o n to g i v e X I I - X V I I is p o s s i b l e o n l y if a l k y l a t i o n of t r i a z o l e I w i t h e p o x -
i d e s p r o c e e d s at t h e N(9 h e t e r o a t o m . S u b s t i t u t i o n at t h e o t h e r r i n g n i t r o g e n a t o m s iN(2 ) and N(4)] d u r i n g
c y c l i z a t i o n w o u l d l e a d to e l i m i n a t i o n of t h e m o r e l a b i l e (as c o m p a r e d w i t h h a l o g e n ) n i t r o g r o u p [7].
The s t r u c t u r e s of t h e c o m p o u n d s o b t a i n e d w e r e c o n f i r m e d b y m e a n s of t h e i r P M R s p e c t r a . The s p e c -
t r a l p a r a m e t e r s o f a l c o h o l s II, III, V, and VII a n d n i t r a t e s I X - X I a r e p r e s e n t e d in T a b l e 4.
A r i g i d s y s t e m of r i n g s is f o r m e d d u r i n g d o s h n g of t h e d i h y d r o o x a z o l e r i n g (XII-XVII), a n d t h i s l e a d s
to a c o m p l e x P M R s p e c t r u m of t h e ABX o r A A ' B B ' t y p e due to the n o n e q u [ v a l e n c e of the p r o t o n s of the
m e t h y l e n e g r o u p . In the a l c o h o l s and n i t r a t e s in w h i c h f r e e r o t a t i o n of the m e t h y l e n e g r o u p is p o s s i b l e , its
protons are equivalent and give simple ftrst-order PMR spectra.
A d e t a i l e d s t e r e o c h e m i c a l a n a l y s i s of the P M R s p e c t r a of t h e d i h y d r o o x a z o l o t r i a z o l e s w i l l b e p r e -
s e n t e d in o u r n e x t c o m m u n i c a t i o n .

EXPERIMENTAL
T h e P M R s p e c t r a w e r e r e c o r d e d w i t h a P e r k i n - E l m e r s p e c t r o m e t e r w i t h a n o p e r a t i n g f r e q u e n c y of
60 MHz. The i n t e r n a l s t a n d a r d w a s h e x a m e t h y l d i s i l o x a n e (HMDS). The IR s p e c t r a w e r e r e c o r d e d w i t h a
UR-20 spectrometer.
1-(fl-Hydroxyalkyl)-3-nitro-5-bromo-l,2,4-trtazoles (II-VID. A mix[tare of 5 g (26.3 m m o l e ) of t r i -
a z o l e I [8], 0.106 g (26 m m o l e ) of s o d i u m h y d r o x i d e , and 52.6 m m o l e of the e p o x i d e w a s p l a c e d in a 5 0 - m l

874
v o l u m e t r i c flask and diluted to the mark with 80% ethanol. The r e a c t i o n mixture was maintained in a sealed
volume with periodic monitoring of the pH of the medium. When the pH was g r e a t e r than 5.5, the mixture
was diluted to twice its volume with water, the ethanol was evaporated, and the r e s i d u e was extracted with
ethyl acetate. The extract was dried over anhydrous magnesium sulfate, the solvent was r e m o v e d , and the
r e s i d u e was subjected to f a r t h e r t r e a t m e n t without purification.
1 - ( f l - N i t r o h y d r o x y a l k y l ) - 3 - n i t r o - 5 - b r o m o - l , 2 , 4 - t r i a z o l e s (IX-XI). A total of 5 g of III, IV, or VII was
added with cooling and s t i r r i n g to 20 ml of an acidic mixture p r e p a r e d f r o m equal volumes of concentrated
H2SO4 and HNO 3 (sp. gr. 1.51), after which the mixture was held at 5-10 ~ for 4 h. It was then poured over
ice, and the resulting precipitate was r e m o v e d by filtration, washed with water, and purified by c r y s t a l l i z a -
tion (Table 1).
1 - ( f l - O x o p r o p y l ) - 3 - n i t r o - 5 - b r o m o - l , 2 , 4 - t r i a z o l e (VIII). A solution of 1 g of alcohol III in 3 ml of con-
centrated H2SO4 was added to a mixture of 10 ml of w a t e r , 4 ml of concentrated sulfuric acid, and 1 g (6.5
mmole) of p o t a s s i u m dichromate heated to 60 ~ and the mixture was held at 60 ~ for 30 rain. It was then
cooled, and the precipitate was r e m o v e d by filtration and washed with water to give a product with mp 123-
124" (from chloroform) in 60% yield. Found: C 24.4; H 2.1; Br 32.6; N 23.0%. CsHsBrN403. Calculated:
C 24.1; H 2.0; Br 32.1; N 22.5%. IR s p e c t r u m : 1560, 1315 (nitro group), 1100, 1745 c m - I (C =O).
2 - N i t r o - 5 - R - 5 , 6 - d i h y d r o o x a z o l o [ 2 , 3 - e ] - l , 2 , 4 - t r i a z o l e s (XII-XVII). A 10% solution of sodium hydrox-
ide [1.2 mole per mole of starting 1 - ( f i - h y d r o x y a l k y l ) - 3 - n i t r o - 5 - b r o m o - l , 2 , 4 - t r i a z o l e ] was added in p o r -
tions with cooling to 5 g of alcohols II-VII in 50 ml of dioxane. After 2 h, the r e a c t i o n mixture was diluted
to twice its volume with water and extracted with ethyl acetate. The solvent was r e m o v e d , and the product-
was purified by c r y s t a l l i z a t i o n (Table 3).
2 - N i t r o - 5 - n i t r o x y - 5 , 6 - d i h y d r o o x a z o l o [ 2 , 3 - e ] - l , 2 , 4 - t r i a z o l e (XVI). This compound was also obtained
by nitration of XV under conditions s i m i l a r to those used in the synthesis of IX-XI.

LITERATURE CITED
1. M. Holler, U. S. Patent No. 3,493,582 (1960); Referativny[ Zh. Khim., 6N38OP (1971).
2. V. Vecehietti, E. Dradi, and F. Lauria, J. Chem. Soc., C, 2554 (1971).
3. R. E. Parker and N. S. Isaaks, Chem. Rev., 59, 737 (1959).
4. N. N. Lebedev and K. A. Gus'kov, Kinetika i Kataliz, 4, 581 (1963).
5. V. F. Shvets and N. N. Lebedev, Trudy MKhTI im. Mendeleeva, 4, 72 (1963).
6. L. I. Bagal, M. S. Pevzner, V. Ya. Samarenko, and A. P. Egorov, Khim. Geterotsikl. Soedin., 1701
(1970).
7. M. S. Pevzner, V. Ya. Samarenko, and L. I. Bagal, Khim. Geterotsikl. Soedin., 848 (1972).
8. J. T. Witkowski and P. K. Robins, J. Org. Chem., 35, 2635 (1970).

875
LETTERS TO THE EDITOR

REACTION OF AROMATIC ALDEHYDES

WITH 1-METHYLINDOLE-2-CARBOX YLIC

ACID AND ITS ESTERS

N. A. Kogan and M. I. Vlasova UDC 5 4 7 . 7 5 6 ' 7 7 8 . 4

I n a l a r g e n u m b e r of s t u d i e s the r e a c t i o n of a l d e h y d e s with 2 - s u b s t i t u t e d i n d o l e s , i n c l u d i n g 2 - c a r -
b e t h o x y i n d o l e s [1], it w a s e s t a b l i s h e d that the r e a c t i o n p r o d u c t s a r e d i i n d o l y l p h e n y l m e t h a n e s . In the p r e s -
e n t s t u d y we have i s o l a t e d c o m p o u n d s t h a t a r e p r o d u c t s of a d i f f e r e n t t r e n d of t h i s r e a c t i o n .

We found t h a t 1 - m e t h y l i n d o l e - 2 - c a r b o x y l i c a c i d a n d its methyl e s t e r r e a c t e x o t h e r m i c a l l y with a r o -

m a t i c a l d e h y d e s in e t h e r s a t u r a t e d w i t h h y d r o g e n c h l o r i d e to give 1 - m e t h y l - 2 - c a r b o x y ( c a r b o m e t h o x y ) - 3 -
( a - c h l o r o b e n z y l ) i n d o l e s (IV-XI, s e e T a b l e 1). 1 - M e t h y l - 2 - c a r b o x y ( c a r b o m e t h o x y ) - 3 - ( a - b r o m o b e n z y l ) i n -
doles (I-III) a r e f o r m e d i n g l a c i a l a c e t i c a c i d s a t u r a t e d with h y d r o g e n b r o m i d e . 1 - M e t h y l - 2 - c a r b o x y ( c a r b o -

It,..
-~C'~x
/~R"
~vY'-sT-OR
(;H3 0

T A B L E i. 1-Methyl-2-carboxy(carbomethoxy)-3-( e - X - b e n z y l ) -
indoles

Compound R x R' rap, ~ Empirical formula

I CH3 Br H 164--167 ] CIsHI6BrNO2

II CHa Br p-N02 145--148 I CisHisBrN~O4
III CHa Br o-CI 150--152 I C1aHIsBrC1NO2
IV CHa C1 o-N02 130--132 [ C18HasCIN~O4
V CHs Cl p-N02 130--132 ; CIsHIsC1NzO4
VI CHa Cl o-C1 132--134 CIsHIsCI2NO2
VII CHa C1 2.4-C1 102--104 CIsHL4CIaNO2
VIII H CI H 150 C~rH~4CINO2
IX H CI o-CI 148 C~rH~aCI2NO=
X H CI o-N02 140 CIrHIaC1N204
XI H Cl p-N02 156 CIvHIaCIN=O4
XII CHa OC=H5 H 73 C2oH=~NOa
XIII CHa OC2Hs o-C1 128--130 C2oH2oCINO3
XIV CHa OCHa o-Cl 95--97 C19H18C1NQ
XV CHa OC2Hs o-N02 138--140 C2oH~oN~O5
XVI CHa OC2H5 p-N02 90--93 C~oH2oN~Os
XVII H OC~H~ o-C1 125 CIgHIeCINOa
XVIII H OCHa o-C1 135 CIsHI6C1NOa
X1X CHa O--Ae H 120--122 C=0HIgNO4
XX CHa O--Ac p-N02 138--140 C=0HIsN206
XXI CHa O--Ae o-N02 134--136 C2oH18N20s
XXII CHa O--Ac o-C1 158--160 C2oHIsCINO4
XXIII H OH o-Cl 125 CITHI4CINOa
XXIV H I OH p-NO~ 185 CirH14N~Os
XXV H OH o-N02 157 C~vH~4N205
XXVI H ! OH H 124 C~rH~sNOa

Leningrad Pharmaceutical Chemistry Institute. Translated from Khtmiya Geterotsiklichesk{kh

S o e d i n e n i i , No. 7, pp. 1003-1004, J u l y , 1974. O r i g i n a l a r t i c l e s u b m i t t e d N o v e m b e r 11, 1973; r e v i s i o n s u b -
m i t r e d F e b r u a r y 11, 1974.

9 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

876
m e t h o x y ) - 3 - ( a - a l k o x y b e n z y l ) i n d o l e s (XII-XVIID a r e f o r m e d when the r e a c t i o n is c a r r i e d out in alcohol s a t -
ttrated with HC1. Compounds XIII and XIV a r e also obtained by c r y s t a l l i z a t i o n of VI f r o m ethanol (XIII) and
methanol (XIV). S t r u c t a r e XIII was c o n f i r m e d by PMR s p e c t r a l data - a r o m a t i c protons (SH, 7.3 ppm),
OC2Hs(q,* 3H, 3.53 ppm, t 2H, 1.19 ppm), O - C H ~ (s 3H, 3.79 ppm), N - C H ~ (s 3H, 3.97 ppm), benzyl group
(1H, 6.52 ppm). l - M e t h y l - 2 - c a r b o m e t h o x y - 3 - ( a - a c e t o x y b e n z y l ) [ n d o l e s (XIX-XXII) a r e f o r m e d by refluxing
alkoxy d e r i v a t i v e s XII-XV in acetic anhydride for 0.5 h. Aeetoxy d e r i v a t i v e XXII was also obtained by h e a t -
ing chloride VI in acetic anhydride. 1 - M e t h y l - 2 - c a r b o x y - 3 - ( a - h y d r o x y b e n z y l ) i n d o l e s (XXIII-XXVI) w e r e
obtained by dissolving halides VIII-X in dilute alkali and acidification of the r e s a l t i n g solutions with acetic
acid. C h r o m a t o g r a p h y of all of the s y n t h e s i z e d compounds on Siltffol with a c y c l o h e x a n e - e t h y l acetate s y s -
tern (3 : 1) showed that the alkoxyacetoxy d e r i v a t i v e s and the halides give one spot, while hydroxy d e r i v a t i v e s
XXIII-XXVI contain d i ( 1 - m e t h y l - 2 - c a r b o x y - 3 - i n d o l y l ) p h e n y l m e t h a n e s as [mpttr[ties. The e l e m e n t a r y a n a l -
y s e s of all of the compounds w e r e s a t i s f a c t o r y . The yields w e r e 50-80%.

LITERATURE CITED
1. C. Granacher, A. Mahal, and M. Gerb, Helv. Chim. Acta, 7, 579 (1924).

*Symbols: s is singlet, t is t r i p l e t , and q is quartet.

877
SPIROPYRANS OF THE 3,4-DIHYDtlOISOQUINOLINE
SERIES

E. V. Bashut-skaya, ]~. R . Zakhs, UDC 547.814v833

a n d L . S. t ~ f r o s

The intensely c o l o r e d 1 - ( 2 - o x i d o s t y r y l ) - 2 - m e t h y l i s o q u i n o l t n i u m ions a r e capable of undergoing con-

v e r s i o n to c o l o r l e s s s p i r o p y r a n s [1]. We have found that 1 , 2 - d i m e t h y l - 3 , 4 - d i h y d r o t s o q u t n o l i n i u m iodide un-
dergoes condensation in the cold with o - h y d r o x y aldehydes, during which c o l o r l e s s spLropsrrans (Ia, b) m a y
be i m m e d i a t e l y obtained in the p r e s e n c e of e x c e s s piperidine. The p y r a n ring of Ia, b ts opened only when
an alcohol solution of the compound is heated. The product of the r e a c t i o n with 3 , 5 - d t b r o m o s a l t c y l a l d e h y d e ,
in c o n t r a s t to the c o r r e s p o n d i n g d e r i v a t i v e of the [soqutnoline s e r i e s , can be isolated not only in the
m e r o c y a n i n e f o r m (II) but also in the s p i r o p y r a n f o r m (Ic), which is c o n v e r t e d to the m e r o e y a n i n e f o r m on
dissolving in alcohol, as c o n f i r m e d by the a b s o r p t i o n s p e c t r a . The e a s e of f o r m a t i o n and the g r e a t e r s t a -
bility of s p t r o p y r a n s I a - c as c o m p a r e d with the d e r i v a t i v e s of the Lsoqulnoltne s e r i e s is explained by the
i n c r e a s e d c h a r g e concentration on the nitrogen a t o m b e c a u s e of the d e c r e a s e in its conjugation with the b e n -
zene ring.

1 a-C |l

l~t R=6'-OCH3; ~9 1~=8'-OCH3; C R=6",8"-Br2

EXPERIMENTAL
2 - M e t h y l - 6 ' - m e t h o x y s p i r o ( 1 , 2 , 3 , 4 - t e t r a h y d r o i s o q u l n o l i n e - l , 2 ' - [ 2 H ] c h r o m e n e ) (Ia). A 0.33-ml (2.5
mmole) s a m p l e of 5 - m e t h o x y s a l t c y l a l d e h y d e and 0.45 ml (5 mmole) of piperidine w e r e added to a s u s p e n -
sion of 0.72 g (2.5 mmole) of 1 , 2 - d i m e t h y l - 3 , 4 - d i h y d r o i s o q u i n o l i n l u m iodide in 2 ml of isopropyl alcohol,
whereupon the r e s u l t i n g solution w a r m e d up and took on a d a r k - l i l a c color. After 5-7 min, 0.7 g (84%) of
c o l o r l e s s needles of Ia with mp 125-126 ~ [from hexane (1:20)] precipitated. Found: C 77.5; H 6.8; N 4.4%.
CIgHIgNO2. Calculated: C 77.8; H 6.5; N 4.8%.
2 - M e t h y l - 8 ' - m e t h o x y s p t r o ( 1 , 2 , 3 , 4 - t e t r a h y d r o t s o q u l n o l i n e - l , 2 ' - [2H]chromene) (l-b). This compound
was s i m i l a r l y obtained in 80% yield (condensation in ethanol) as c o l o r l e s s c r y s t a l s with mp 114-115 ~ [from
hexane (1 : 15)]. Found: C 77.8; H 7.0; N 4.6%. CIgHlgNO2 . Calculated: C 77.8; H 6.5; N 4.8%.
2 - M e t h y l - 6 ' , 8 ' - d t b r o m o s p t r o ( 1 , 2 , 3 , 4 - t e t r a h y d r o i s o q u l n o l i n e - l , 2 ' [2H]chromene) (Ic) and 2 - M e t h y l - I -
( 2 - o x i d o - 3 , 5 - d i b r o m o s t y r y l ) - 3 , 4 - d i h y d r o i s o q u i n o l i n i u m (II). The condensation with 3 , 5 - d i b r o m o s a l i c y l a l -
dehyde was c a r r i e d out as in the p r e c e d i n g e x p e r i m e n t . W a t e r (20 m l ) w a s added to the r e s u l t i n g s u s p e n -
sion, and the d a r k - b r o w n c r y s t a l s of II w e r e r e m o v e d by filtration and c r y s t a l l i z a t i o n f r o m 25% aqueous
[sopropyl alcohol to give c r i m s o n c r y s t a l s of II with mp 167-168 ~ in 60% yield. UV s p e c t r u m in alcohol,
X m a x , n m (log ~): 237 (4.43), 335 (3.71), 525 (3.64). Found: Br 38.2%. CIsHIsBr2NO. Calculated: Br
38.0%. A 0.6-g s a m p l e of m e r o c y a n i n e II was dissolved in 6 ml of benzene, and the solution was filtered.

L e n s o v e t L e n i n g r a d Technological Institute. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i e h e s k i k h Soedin-

enii, No. 7, pp. 1004-1005, July, 1974. Original a r t i c l e s u b m i t t e d J a n u a r y 6, 1974.

9 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

878
The filtrate was vacuum e v a p o r a t e d to d r y n e s s and the r e s i d u e was c r y s t a l l i z e d f r o m p e t r o l e u m ether
(1 .~10) to give 0.4 g of c o l o r l e s s c r y s t a l s of Ic with mp 97-98 ~ UV s p e c t r u m in hexane, ~t max, n m (log e):
237 (4.50), 330 (3.41). The a b s o r p t i o n s p e c t r u m in alcohol was identical to the s p e c t r u m of m e r o c y a n i n e II.
Found: Br 37.9%. C18HisBr2NO. Calculated: Br 38.0%.

LITERATURE CITED
1. E. V. B a s h u t - s k a y a , ]~. R. Zakhs, and L. S. l~fros, Khim. Geterotsild. Soedin., 1580 (1973).

879
SYNTHESIS OF HETEROCYCLIC COMPOUNDS
FROM CYCLOHEXANE-I,3-DIONES (REVIEW)

A. Ya. Strakov, I~. Yu. Gudrinietse, UDC 547.594.3 +547.7 +547.8

and D. R. Zitsane

The l i t e r a t u r e data on the synthesis of p a r t i a l l y h y d r o g e n a t e d h e t e r o c y e t t c compounds con-

taining a 3-oxocyclohexene s t r u c t u r a l f r a g m e n t condensed with f i v e - , s i x - , or s e v e n - m e m -
b e r e d o x y g e n - , n i t r o g e n - , and s u l f u r - containing h e t e r o r i n g s fro m c y d o h e x a n e - 1,3-drones
and t h e i r d e r i v a t i v e s a r e e x a m i n e d in this r e v i e w .

The well-known t r e n d of intensive development of the c h e m i s t r y of h e t e r o c y c l i c compounds is also

finding l i v e l y e x p r e s s i o n in the publication of an e v e r i n c r e a s i n g n u m b e r of studies devoted to the synthesis
of h e t e r o c y c l e s f r o m c y c l o h e x a n e - l , 3 - d i o n e s (I) and t h e i r s i m p l e s t d e r i v a t i v e s . Only the general s c h e m e s
for the s y n t h e s i s of h e t e r o c y c l i c compounds containing, as a r u l e , a c o m m o n s t r u c t u r a l f r a g m e n t - 3 - o x o -
eyclohexene - a r e e x a m i n e d in the p r e s e n t r e v i e w , in which the l i t e r a t u r e up to J a n u a r y 1, 1973, is in-
cluded. All of the m a t e r i a l in this r e v i e w has been s y s t e m a t i z e d with r e s p e c t to the c l a s s e s of h e t e r o -
cycles.

Benzofurans and Dibenzofurans

The m o s t universal and convenient method for the synthesis of benzofurans (III, IV) f r o m cyclohex-
a n e - l , 3 - d i o n e s (I) is r e a c t i o n of the l a t t e r with a - h a l o ketones [1-10]. In the e a s e of a - b r o m o e t h y l ketones,
the f i r s t step is alkylation in the 2 - p o s i t i o n to give III, while aldol condensation is the f i r s t step in the c a s e
of a - h a l o c y c l o h e x a n o n e s [4], a - k e t o - f l - b r o m o b u t y r i c acid, and a - c h l o r o a c e t o a c e t t c e s t e r [3]. However,
2 - b r o m o c y c l o b u t a n o n e r e a c t s with dtmedone (Ib) to give cyclopropyl 5 , 5 - d t m e t h y l - l , 3 - d i o x o - 2 - c y c l o h e x y l
ketone [11]. 2 - P r o p a r g y l c y c l o h e x a n e - 1,3-dione, obtained fro m c y c l o h e x a n e - 1,3-drone (Ia) and p r o p a r g y l
b r o m i d e by the action of zinc c a r b o n a t e , was c o n v e r t e d [12] to 2 - m e t h y l - 4 - o x o - 4 , 5 , 6 , 7 - t e t r a h y d r o b e n z o -
furan (IV, R 2 =IRa =H).
O R2
~" ~ ~ ~ O H 0 R3
1 OH
fi
v-2 r

o o R~ O R2

g,1 Rt, RI #3
~5 ~tA
Here and subsequently, R=R;=H;bR=R*=CHa; cR=H, Rt-Csit~;dR=H,R~=CHa

Riga Polytechnic Institute. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s M k h Soedinentt, No. 8, pp.

1011-1030, August, 1974. Original a r t i c l e s u b m i t t e d May 22, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, .~ Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, mierofihning,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available froth the publisher for $15.00.

881
The products (V) of the crotonic condensation of diketones I with cyclohexanone give decahydrodibenzofurans
(VI) when they a r e heated with phosphoric acid [13].
P e r e k a l i n and c o - w o r k e r s [14-17] have shown that c y c l o h e x a n e - l , 3 - d i o n e s (I) r e a c t with 1 - b r o m o - 1 -
nitroalkenes in the p r e s e n c e of basic agents to give 2 - n i t r o - 4 - o x o - 2 , 3 , 4 , 5 , 6 , 7 - h e x a h y d r o b e n z o f u r a n s (VII),
w h e r e a s , as a r e s u l t of denitration, they r e a c t with e x c e s s base to give 4,5,6,7-tetrahydrobenzofurans IV
(R3 =H). Reaction of dimedone (Ib) with w - n i t r o s t y r e n e gives 2 - i s o n i t r o s o - 3 - p h e n y l - 4 - o x o - 4 , 5 , 6 , 7 - t e t r a -
hydrobenzofuran (VIII) [18], which r e f u t e s the s t r u c t u r e s proposed e a r l i e r in [19-21].
Benzofuran derivatives (IX, X) w e r e obtained as a r e s u l t of reactLons of 2 - a c e t y l c y c l o h e x a n e - l , 3 -
diones (XI) [22, 23] and their enol ethers (XIIa) [24] with diazomethane:

R2CH=C~
NO2 ~ R2
er z, R --- I~ (, R'~=H)
I RI NO2
C6HsCH=CHNO2 VII
O O O
Rj ~ C6H5 r~COCH3 CH2N2 F~CH3

v,,--] R] r~

O O
F~COCH3 CH2N
2 ~ C H 3

The possibilities of the p r e p a r a t i o n of spfrans XIV - g r L s e o f u l v i n analogs - f r o m bis (1,3-dioxo-2-

cyclohexyl)methanes XIII have been studied in detail. Spfrans XIV w e r e obtained f r o m the disodium salt of
tetraketone XIII and iodine [25] and also by bromination of ketone XIII in c h l o r o f o r m [26] or in acetic acid
[27]. The l a t t e r method is the most universal and convenient method. Spirans XIV a r e also f o r m e d by oxi-
dation of ketones XIII with iron (Ill) h e x a c y a n o f e r r a t e [28, 29] or by anodic oxidation of dimedone [30].
It has been shown [31] that the oxidation of dimedone ('[b) with hydrogen peroxide in alkaline media
gives the diol t h r e e - r i n g f o r m of 2-hydroxybisdimedone (XV).
Oxidation of 1,2-bis (1,3-dioxo-5,5-dimethyl-2-cyclohexyl)ethane (XVI) with oxygen gives XVII, while
oxidation with iron (III} h e x a c y a n o f e r r a t e gives spiran XVIII [32].
Glycolaldehyde [33] and monochloroacetaldehyde [34] r e a c t with dimedone (Ib) to give 3-(1,3-dioxo-
5,5-di methyl -2 -cyclohexyl) - 4 - o x o - 6,6-di methyl-2,3,4,5,6,7-hexahydrobenzofuran (XIX) o

O R2 O O Rz O

N R " N 1

0
x,~__~ xj_~v

OHx-V ~ " ~
xv._! IO
o.~

xt~__~ xw,'--~ xvi._.A

882
 L e s s c o m m o n methods for the syntheses of benzofttran d e r i v a t i v e s f r o m diketones I a r e also known.
Thus, 2 - p h e n y l - 4 - o x o - 6 , 6 - d i m e t h y l - 4 , 5 , 6 , 7 - t e t r a h y d r o b e n z o f u r a n was obtained b y t r e a t m e n t of 2 - b r o m o -
dimedone with copper phenylacetylEde in d i m e t h y l f o r m a m i d e (DMF) [35]. Alkaline h y d r o l y s i s of the p r o d -
uct of condensation of c y c l o h e x a n e - l , 3 - d i o n e (In) with t e t r a c y a n o e t h y l e n e gives 2 - c a r b a m i d o - 3 - c y a n o - 4 -
o x o - 4 , 5 , 6 , 7 - t e t r a h y d r o b e n z o f t t r a n [36]. T h r e e - r i n g s y s t e m XXI was obtained b y the action of acetic a n -
hydride on substituted succinic acid XX [37].

CH2COOH

~
o I
CHiCOOH
--
C
(H
3C0
1
20 ~0 IL
o

OH
CH3
x-~

Indoles and Carbazoles

The m o s t general and tmEversal method for the s y n t h e s i s of 4 - o x o - 4 , 5 , 6 , 7 - t e t r a h y d r o i n d o l e s (XXII)

f r o m I is C - a l k y l a t i o n of the l a t t e r with ~ - b r o m o ketones and subsequent t r e a t m e n t of 1,4-diketones II or
t h e i r cyclization p r o d u c t s - b e n z o f u r a n s IV - w i t h a m m o n i a or p r i m a r y a m i n e s [1, 10, 12, 38]. Dibenzo-
fttrans III a r e s i m i l a r l y c o n v e r t e d to c a r b a z o l e d e r i v a t i v e s [38]. 3-Unsubstituted 2 - m e t h y l - 4 - o x o - 4 , 5 , 6 , 7 -
t e t r a h y d r o i n d o l e s a r e conveniently obtained b y the action of a m i n e s on 2 - p r o p a r g y l c y c l o h e x a n e - l , 3 - d i o n e
in the p r e s e n c e of copper (I) chloride [12].
C y c l o h e x a n e - l , 3 - d i o n e s a r e e x t e n s i v e l y used as the ketone component for the K n o r r s y n t h e s i s of p y r -
r o l e s . (~-Isonitroso ketones a r e most often used for the g e n e r a t i o n of the a - a m i n o ketone component in the
r e d u c t i o n p r o c e s s [20, 39-41], but it has r e c e n t l y been shown [42] that b e t t e r r e s u l t s a r e achieved when
a - d i k e t 0 n e monopher~ylhydrazones a r e used. The p o s s i b i l i t y of the d i r e c t use of N - m o n o s u b s t i t u t e d
a - a m i n o ketones was d e m o n s t r a t e d by the p r e p a r a t i o n of indole XXII CR2 =R s =Rt=CGHs) f r o m diketoaes I
and (~-phenylaminobenzyl phenyl ketone [43]. Indoles XXII can also be obtained with equal s u c c e s s f r o m
3 - a m i n o - 2 - c y c l o h e x e n - l - o n e s (XXtII) and (~-hydroxy ketones [44, 45].

HO p2
R4NH2
_ -- R -'---- R +
~" Or IV -- ~ R1 R3 R NH 2 H O " ~ " ' ~ R3-
R~
XXIII

T+
O y
Y7
R2 T +
[HI
O~--yR2
R4

H O N / / k . ~ R 3 -- C 6 H s N H N / / L ~ R 3

O O O R4(H)
COOH r~OCOCH3 ~OH
11-N"1(%c%~ R-)..JL,JL, R
RI," v ~'R4 =- )

xx---~ xxv---], xx~V

1,2,3,4-Tetrahydro-4-oxo-6-hydroxycarbazoles (XXIV) were obtained as a result of the addition of

enamines :x~III to p-quinones [46].
i n , m i n e s XXV, obtained f r o m diketones I and ~ - a m i n o a c i d s , including N - m o n o s u b s t i t u t e d acids, a r e
r e a d i l y cyclized [47] under the influence of a c e t i c anhydride to 3 - a c e t o x y - 4 - o x o - 4 , 5 , 6 , 7 - t e t r a h y d r o i n d o l e s (XXVI).
2,3-Unsubstituted 4 - o x o - 4 , 5 , 6 , 7 - t e t r a h y d r o i n d o l e s w e r e obtained [48] in r e a c t i o n s of diketones I with
a c e t a l s of N - m o n o s u b s t i t u t e d a m i n o a c e t a l d e h y d e s .
C y c l o h e x a n e - l , 3 - d i o n e monophenylhydrazones undergo the F i s c h e r r e a c t i o n to give 4 - o x o - l ,2 ,3 ,4-
t e t r a h y d r o c a r b a z o l e s (XXVII) [50-52]. B e n z o I b ] p y r r o c o l i n e d e r i v a t i v e s (XXIX) a r e obtained f r o m 2 - a l k y l -
cyclohexanedione monophenylhydrazone XXVIII in this c a s e [51]. Enehydrazines XXX, obtained f r o m c y c l o -
h e x a n e - l , 3 - d i o n e s and N , N ' - d i m e t h y l h y d r a z i n e , r e a o t with eyelohexanones, including 3 - k e t o s t e r o i d s , in the
p r e s e n c e of acids to give o c t a h y d r o c a r b a z o l e s XXXI [53].

883
 9- Methyl-4-oxo- 1 , 2 , 3 , 4 - t e t r a h y d r o c a r b a z o l e s a r e the main products of the photoche mica1 t r a n s f o r -
mation of 3 - ( N - m e t h y l a n i l i n o ) - 2 - c y c l o h e x e n - l - o n e s , while the N-phenyl derivatives give 5 - h y d r o x y - 3 , 4 -
hydrobenzazocines [49].
O O

R'~
)(XVll XXVIII XXI.X

R
.r-h,~ NNHCH3
CT~ R l
I CH 3
CH 3
xx'~, xxx~

4-Oxo-2,3,4,5,6,7-hexahydroindoles (XXXII) a r e obtained [19, 54, 55] by reduction of 2- (fl-nitroethyl)-

c y c l o h e x a n e - l , 2 - d i o n e s (XXXIII). T r a n s h e t e r o c y c l i z a t i o n to give hexahydroindoles XXXII o c c u r s during the
hydrogenation of nitrobenzofurans VII in methanol on Raney nickel [16, 17, 56]. However, when nitro d e r i v -
atives VII axe refluxed in the p r e s e n c e of a Raney nickel catalyst in ethanol, XXXII a r e dehydrogenated to
t e t r a h y d r o i n d o l e s XXII (R3=R 4 =H) [17].
R2
o I o
f~CH--CH2NO2 I" R~ R2
vD,_[

H
XXXlll XXXII

4 - O x o - 7 - a m i n o - l , 2 , 3 - 4 - t e t r a h y d r o c a r b a z o l e was obtained by hydrogenation of 2- (2,4-dinitrophenyl)-

cyclohexane- 1,3-dione [52].

Benzisoxazoles and Benzoxazoles

2 - A c e t y l e y c l o h e x a n e - l , 3 - d i o n e s (XI) have been used for the p r e p a r a t i o n of 4 - o x o - 4 , 5 , 6 , 7 - t e t r a h y d r o -
benzisoxazoles. One might expect the formation of two i s o m e r s - tndoxazene derivatives (XXXIV) and
anthranil derivatives (XXXV) - in the r e a c t i o n of hydroxylamine with triketones XI and with any u n s y m m e t -
r i c a l e t s - f i x e d enol f o r m of a/3_diketone. It has been shown [57-59] that the r e a c t i o n proceeds s t r u c t u r a l l y
s e l e c t i v e l y to give exclusively i s o m e r XXXIV. The electrophtlte center in the e t h e r s of enol f o r m s XII is
in the 3-position, and only 4 - o x o - 4 , 5 , 6 , 7 - t e t r a h y d r o a n t h r a n i l derivatives (XXXV) a r e f o r m e d by the action
of hydroxylamine, while 3 - c h l o r o - 2 - a c e t y l - 2 - c y c l o h e x e n - l - o n e s (XXXVI) give 4 - o x o - 4 , 5 , 6 , 7 - t e t r a h y d r o -
O O O
~ C H 3 1,1H20H ~./C OCH, NH2OH ~,r__....rfiCH3
-y. - - k
. R1/ v "OH RI/ v -O
xx----~
x " ~ N 3 xq

\ rco .,
R "

:1" ~ ' ~ k ~ OCH3 RI~CL

xi__2 xxxv----A

0 0 0 0

-I-~"~,~ O RI~",-.,,.,..~OH R!/ v ~OCzH5 R1/V_~N'-

"~xXVll X XL
O O Ph O

F~ 3 Ph___ R"
XLL-'-'] XL---I XLill

884
indoxazene (XXXIV) [59-61]. Tetrahydroanthranil XXXV is also obtained by reaction of chloro ketone
XXXVI with sodium azide [62].
The reaction of 2-anilinomethylenecyclohexane-l,3-diones (XXXVII) with hydroxylamine gives [63, 64]
2-cyanocyclohexane-1,3-diones (XXXVIII), the ethers of the enols (XXXIX) 0s which react with hydroxyl-
amine to give 3-aminoanthranils (XL). The preparation of 4-oxo-4,5,6,7-tetrahydroindoxazene in the r e a c -
tion of 2-(m-anisidinomethylene)cyclohexane-l,3-dione with hydroxylamine was noted in [65].
The formation of benzoxazole derivatives (XLI) was observed [66] only when 2-acetamidocyclohexane-
1,3-diones (XLII) were refluxed in acetic anhydride.
Enamines obtained f r om cyelohexane-l,3-dlones and 2,4,5-triphenyl-6-aminoresoreinol axe cyclized
during oxidation [67] to 6,3'-dioxo-4,5,6-triphenyl-6H-spiro(benzoxazole-2,1,-cyclohexanes) (XLIII).

Indazoles
A large number of 4-oxo-4,5,6,7-tetrahydroindazoles have been obtained in the reaction of 2-aeyley-
clohexane-l,3-diones and their enol ethers and enamines with hydrazines [57, 58, 60, 62, 65, 68-76]. The
reaction was first realized in [68] and was subsequently studied in greatest detail in the eases of the readily
accessible 2-acetylcyclohexanediones (XI) and their fixed derivatives (XII, XXXVII, etc.} It has been proved
[58, 59, 74] that of the two possible structurally isomeric indazoles, XLV and XLVI, in reactions with mono-
arylhydrazines, triketones XI give precisely l-aryl-3-methyl-4-oxo-4,5,6,7-tetrahydroindazoles (XLV, R 2 =
CH3) , and intermediate arylhydrazones XLIV have been isolated and characterized [74]. 2-Aryl-4-oxo-
4,5,6,7-tetrahydroindazoles XLVI were obtained from ethers XII and arylhydrazines [59, 60, 76], while aryl-
indazoles XLV were obtained from XXXVI [62]. A mixture of isomeric tetrahydroindazoles is formed in
the reactions of XI with alkylhydrazines [75, 77].
3-Unsubstituted tetrahydroindazoles (XLV, R2=H) are primarily obtained [65, 70, 72, 78] by trans
amination of 2-arylaminomethylenecyelohexanediones (XXXVII} - the products of the reaction of I with the
ethyl esters of N-arylformimidic acid or with N,N'-diarylformamidines [70, 79-81] - with arylhydrazines
and subsequent eyelization of the intermediate 2-hydrazinomethyleneeyelohexanediones (XLIV, R 2 =H).
2-Cyano-3-ethoxy-5,5-dimethyl-2-eyclohexen-l-one (XXXIXb) reacts with hydrazine and phenylhydra-
zinc to give the corresponding 3-amino-4-oxo-6,6-dimethyl-4,5,6,7-tetrahydroindazoles (XLVII) [64].
I-A mino-3- methyl-4-oxo-4,5,6,7-tetrahydro [ndazoles (XL VIII) are for reed instead of the expected
N-unsubstituted indazoles in the reaction of indoxazenes XXXIV with hydrazine. Nitrosation of XLVIII gives
l,l-bis(3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydroindazole) [82, 83].
General methods for the preparation of 3-aryl-4-oxo-4,5,6,7-tetrahydroindazoles, the synthesis of
which from 2-aroylcyelohexane-l,g-dione is markedly hampered in veiw of the limited accessibility of the
latter, have been proposed [84, 85]. N-Unsubstituted 3-aryl-4-oxo-4,5,6,7-tetrahydroindazoles (L) have
been obtained [84] from aromatic aldehydes and 3-phenylsulfonylhydrazino-2-cyclohexen-l-ones (XLIX).
Phenylazocyelohexenones LII, obtained by oxidation of 3-phenylhydrazino-2-cyclohexen-l-ones (LI), react
with benzaldehyde and furfural to give the corresponding 2,3-diaryl-4-oxo-4,5,6,7-tetrahydroindazoles
(LIII).
2,3-Diphenyl derivative LIII (Ar =C~Hs) has also been obtained [86] directly from dimedone ([b) and
1,3,4-oxadiazolium perchlorate (LIV) by refluxing in acetonitrile in the presence of triethylamine for 3 h.
A general method for the synthesis of 1,3-disubstituted (including 3-aryl-) 4-oxo-4,5,6,7-tetrahydro-
indazoles (LVI) by the action of N-monosubstituted aldehyde hydrazones on cyclohexane-l,3-diones in re-
fluxing benzene has been proposed [77]. Air oxygen is sufficient for the oxidation of the intermediate py-
razolines (LV -~LVl).
Reaction of 3-chloro-2-cyclohexen-l-one with N-aminopyridine hydrochloride gave enamine LVII,
which is converted to ylid LVIII in aqueous potassium carbonate solution; LVII is converted to 10-oxo-
7,8,9,10-tetrahydropyrido [l,2-b]indazole (LIX) on heating in toluene [87].
R2
o I o
H2NNHAr R ~C--NHNHAr ~ RI~NIN R~N
RI'~O R

XXXVII XXXVI

885
 o O o
__ H2NNHAP R ~ F~CH3 (~.~7CH3 R2NHNH2 ~~ F '~NH2
XXXIV ,,t"I2NNH2 . :,~..,~ NI.~ I----~ b
XXX
R1~ N ' N ' , A r ~'-~N.N\R 2
I xCV~i
XLVI XLVIII NH2

0 0
R ArCHO . R
R1 NHNHSO2C6H
5 -- C6HBSO2H RI
H
XLIX

R [O] R APCH~ N--N

R'/V\NHNHC6H5 R'/V"N=NCsH5 Rl/ v ~N'NI'~C6H5 C6H~"~ -O CH 3
LI LII LIII LIV

O R2 O R2 O 0 0
R2ICH=NNH R3i

~1 i~3 NH--
C[
EVIl LVIII LI-~
Benzimidazoles
2-Aminodimedone (LX), which reacts with cyanamide [88] to give 2-amino-4-oxo-4,5,6,7-tetrahydro-
benzimidazole (LXI) and with phenyl isothiocyanate [89] and phenyl isocyanate [90] to give 2-thio-4-oxo- and
2,4-dioxo-l-phenyl-6,6-dimethyl-2,3,4,5,6,7-hexahydrobenzimidazoles (LXII), respectively, has been used
for the synthesis of 4-oxo-4,5,6,7-tetrahydrobenzimidazoles. 1-Phenyl-4-oxo-6,6-dimethyl-4,5,6,7-tetra-
hydrobenzimidazole [89] was obtained by catalytic hydrogenation of thio derivative LXII (X =S) in the pres-
ence of Raney nickel.
0 0 0

~~'NH~ . H2NCN ~OH2 ~ . ~ NH

NH 2 H X
C6H5
LXI LX LXII
Nitrosation of derivatives of a-amino acids and their esters (LXIII)gives oximes LXIV, which, when
R ~ = g , are cyclized by refluxing in ethanol to benzimidazoles LXV, but, when R 2 =alkyl and aralkyl, are de-
carboxylated to give alkylbenzimidazoles LXVI [91]. Reductive acylation of 5,5-dimethylcyclohexane-l,2,3-
trione monophenylhydrazone (LXVII) and subsequent treatment of the reaction product with ammonium ace-
tate gives benzimidazole LXVI (I={2 =CHs) [92].

O O OH -2 O
COOR3 . , ... R3 = Alku
~ V ~ N H C l HR2 ~ N ""~ \R2 COOR3
__H
LXi'il LXV
O O

" ~ ~O 2) CH3COONH 4 R2
H
LXVII LXVI
Benzothiazoles
2-Amino-, 2-alkyl-, and 2-aryl-6-oxo-4,5,6,7-tetrahydrobenzothiazoles (LXIX) are obtained by reac-
tion of 2-halocyclohexane-l,3-diones (LXVIII) with thioureas [93-96] and thioamides [93-98]. Amines LXIX

886
(R 2 =NH2) can be s y n t h e s i z e d d i r e c t l y f r o m diketones I and t h i o u r e a in the p r e s e n c e of f r e e halogen [93].
Amine LXIX (R 2 =NH2) was also obtained f r o m 3 - a m i n o - 2 - c y c l o h e x e n - l - o n e (XXIII) and H2NSCN through
2-th[ocyanato d e r i v a t i v e LXX [99].

O O O O

t..XVIII LXiX L X.__XX XXlll

Benzotriazoles
A convenient method for the s y n t h e s i s of 1 - a r y l - 4 - o x o - 4 , 5 , 6 , 7 - t e t r a h y d r o b e n z o t r i a z o l e s (LXXII) con-
s [ s t s in t r e a t m e n t of 3 - a r y l a m [ n o - 2 - c y c l o h e x e n - l - o n e s (LXXI) with tosyl azide in the p r e s e n c e of p - t o l u -
e n e - s u l f o n i c acid [100].
o o

R ' -,,,, R N
R NHAP R! I
AP
LXXI LXXil

Xanthenes and Benzopyrans

With r e s p e c t to the n u m b e r of compounds that exist, the m o s t prolific c l a s s of h e t e r o c y c l e s obtained
f r o m c y c l o h e x a n e - l , 3 - d i o n e s a r e 1 , 8 - d i o x o - l , 2 , 3 , 4 , 5 , 6 , 7 , 8 - o c t a h y d r o x a n t h e n e s (LXXIII). Reaction of dike-
tones I with aldehydes in neutral media gives, as a r u l e , b [ s ( 1 , 3 - d i o x o - 2 - c y c l o h e x y l ) m e t h a n e s (XIII), which
a r e dehydrated to octahydroxanthenes LXXHI by means of acids. Some condensation products p r e v i o u s l y
d e t e r m i n e d to be XIII a r e actually hydroxydecahydroxanthenes LXXIV [101, 102].
0 Rz O O R2 0

_ R R R

Xlll LXXlll

H4OH " p O R2 O

R R
R1 R1
OH
LXXV LXXVI ~.XXlV

Dimedone [103-109] has been used most e x t e n s i v e l y in t h e s e r e a c t i o n s . The r e f e r e n c e s p r e s e n t e d at

at the end of this p a p e r include only the principal studies. It has been p r o p o s e d that the xanthenes obtained
f r o m Ia [110], 5 - p h e n y l - and 5 - ( p - h y d r o x y p h e n y l ) c y c l o h e x a n e - l , 3 - d i o n e s [111, 112], and 4 , 6 - d i b r o m o d i m e -
done [113] be used for analytical p u r p o s e s . Acetals m a y be used in place of aldehydes [114, 115]. 3,3,6,6-
T e t r a m e t h y l - 9 - ( 3 - h y d r o x y - 5,5 - d [ m e t h y l - 1 -oxo - 2 - cyclohexenyl) - 1,2,3,4,5,6,7,8-octahydroxanthene- 1,8 -
dione was obtained b y r e a c t i o n of dimedone with f o r m i c acid d e r i v a t i v e s [116, 117]. In the condensation of
dimedone with salicylaldehyde, the i n t e r m e d i a t e bis product f o r m s 5 , 6 , 7 , 8 - t e t r a h y d r o - 8 - x a n t h e n o n e LXXV
as a r e s u l t of f u r t h e r dehydration [118, 119]. The c o - c o n d e n s a t i o n of salicylaldehyde, Ib, and 4 - h y d r o x y -
acetophenone gives diketone LXXVI [118]. 1-Oxo- 1,2,3,4-tetrahydrobxanthene was obtained f r o m Ia and
salicyl alcohol in h e x a m e t a p o l [120].
The s y n t h e s i s of hydrogenated b e n z o p y r a n and, p a r t i c u l a r l y , c o u m a r i n d e r i v a t i v e s has been d e s c r i b e d
in m a n y p a p e r s . 5 - O x o - 3 , 4 , 5 , 6 , 7 , 8 - h e x a h y d r o c o u m a r i n LXXVIII is f o r m e d by refluxing 2- 03 - c a r b e t h o x y -
ethyl}dimedone (LXXVII) with acetic anhydride [37]. 3 - C h l o r o - 5 - o x o - 5 , 6 , 7 , 8 - t e t r a h y d r o c o u m a r i n (LXXIX)
was obtained by heating dimedone with t r i c h l o r o a c r o l e t n in methanol for 3 h [121].
O O O

LXXVII LXXVIII LXXIX

887
 Cyclohexane-l,3-diones react with the amide and N-alkylamides of acetoacetic acid in reflaxing tol-
uene in the presence of pyridine [122] and also with its ethyl ester in diethylanUine [122] or trifluoroacetic
acid [123] to give 5-oxo-5,6,7,8-tetrahydroooumarins LXXX (R2 =CH3). Chromones LXXXII were obtained
[123] from the products of w-acylation of 2-acetyldimedone (LXXXI), while isomeric coumarins LXXX (R2=
COOC2H5) were obtained from dimedone and oxalacetic ester.
O R2

+ R2COCH2COA ~ O
_ "- R
T R2 = all3 f COOC2H5; RI
A = NHALI'. ,~ OC2H 5
LXXX

0 0 0
. ~ cOCH2COR2 R2" =COOC2H 5 ,H

. v "OH RZ
LXXXI LXXXII

oXo o~o

0 OH 0 R2

R~I - _T R ,-.PCO 2 .~ CH3COCH3~

R O RI 0
LXXXV LXXXVI
~ ] " 4-- C30 2

The reactions of cyelohexane-l,3-diones with isopropylidene malonate (LXXXIII) [124] and its deriv-
atives (LXXXIV) [125] have also been used for the synthesis of coumarin derivatives LXXXV and LXXXVI.
4-Hydroxy-5-oxo-5,6,7,8-tetrahydrocoumarins (LXXXV) have also been obtained [126] from I and carbon
suboxide.
Hexahydrobenzopyran derivatives have been obtained from cyclohexane-l,3-diones by several meth-
ods. 3,4,5,6,7,8-Hexahydro-2H-benzopyran LXXXVII was obtained from methyl vinylacrylate and the potas-
sium salt of dimedone [127].
1,5-Diketones LXXXVIII [128] and LXXXIX [129] were converted to benzopyran (XC) and xanthene
(XCI) derivatives, respectively, by hydrogenation by means of Raney nickel [128] and by reduction with so-
dium borohydride [129].
2-Amino-3,4,4-tricyano-5-oxo-5,6,7,8-tetrahydro-T-chromene was obtained by the action of tetra-
cyanoethylene on I [36]. Chromanone XCII was obtained by refluxing 2-(T-ketobutyl)cyclohexane-l,3-dione
in acetic anhydride [130].
9-Oxaphenanthrene derivatives (XCIII) are formed from' I and o-bromobenzoic acids in the presence
of copper salts [131, 132].
0

CH2COOCH 3
I-XXXVII v ~OH O ~ ~ R 3

O LXXXVIII t LXXXlX

O R2

o?, F~I I x ! 7 c__

x 2,

R
LXXXVIII , XC R2 : H ~ R3 : CH 3
R
XClI-'~I L_XXXIX , XC_~I R2 -- R 3 = (CH2) 4

888
Condensed Heterocycltc Compounds Containing
a Pyridine Ring
One should first of all note a number of variations of the Hantzsch method involving the use of dike-
tones I and their simplest derivatives, which lead to condensed heterocycles containing 1,4-dihydropyridine
fragments - mainly decahydroaeridine-l,8-diones XCIV and 1,4,5,6,7,8-hexahydro-5-quinolones. Decahy-
droacridines XCIV were obtained by the action of ammonium acetate or amines on bis (l,3-dioxo-2-eyclo-
hexyl)methanes (XIII) [133-135] or on octahydroxanthenes LXXIII [119, 136, 137], or directly from eyclo-
hexane- 1,3-diones, aromatic aldehydes, and ammonium acetate [138], from eyelohexane- 1,3-diones and
urotropin [139], and from 3-amino-2-eyclohexen-l-one and aldehydes [140].
In condensations involving the participation of diketones I, an aldehyde, and an enamine, 4-aminoura-
cils [143, 144] have been used as enamines in addition to fi-aminoerotantes [138, 141, 142].
Polycondensed systems XCV, which include 1,4-dihydropyr[dine, were also obtained by the action of
cyclohexanedione [mines (XXIII) on 2-arylidenecyeloalkane-l,3-diones [145, 146] and also on mixtures of
the corresponding aldehydes and diketones [144, 147] or 5-aryHdenebarbituric acids [144].

0 R2 0 0 0
(

xc~Y xcv.

All of the N-unsubstituted 1,4-dthydropyridines mentioned above are r e a d i l y oxidized to the c o r r e -

sponding pyridines [148].
Enamines XXIII r e a c t with the c i s - f i x e d e n d f o r m s of fl-dicarbonyl compounds to give [149] the c o r -
responding 5-oxo-5,6,7,8-tetrahydroquinolines XCVI (R2 and Rt=Alk, Ar; R3=H), 1 - o x o - l , 2 , 3 , 4 , 5 , 6 , 7 , 8 - o e -
tahydroacrid[ne XCVI [R2 =H, R 3 =R4 =(CH2i4], and 5-oxo-l,2,3,4,5,6,7,8-octahydrophenanthridine XCVI
[R2 R 3 = (CH2)4]. Enamine XXIII r e a c t s with acetoacetic e s t e r to give quinolone XCVII (R2 =CH 3 [149]. The
r e a c t i o n of enamine XXIII with propargylaldehyde [150] and methyl propiolate [151-153] has also been used
for the d i r e c t synthesis of 5-oxo-5,6,7,8-tetrahydroquinolines of the XCVI and XCVII types.

0 R3 b R2

RZ'~"R4Ho
O R~ D3
R1 NH2 R1 R4
iXtll
-t- HC~-~-CCHO
0 R2 O O

H ~ 1 CH3
CH3
Vl
xC
____! ~,~:v,,,
3 - M e t h y l a m i n o - 5 , 5 - d i m e t h y l - 2 - c y c l o h e x e n - l - o n e r e a c t s with dtketene to give [154] 4,5-dioxo-
1,4,5,6,7,8-hexahydroquinoline XC VIII. 2,5-Dioxo- 1,2,3,4,5,6,7,8-octahydroquinoline CII (R2 = CH2C ~H5) was
obtained [155] f r o m 3 - { N - b e n z y l a m i n o ) - 2 - c y c l o h e x e n - l - o n e s and a c r y l o y l chloride. Octahydroquinoline CII
(R2 = H) ts for med [156] by hydrolys[s of 2- (fi -cyanoethyl) cyclohexane- 1,3- dione (CI), while hydro genation
of the l a t t e r on a nickel catalyst gives [157] 5-oxo-l,2,3,4,5,6,7,8-octahydroquinolines C. The l a t t e r w e r e
also obtained [158] by heating 3 - ( 7 - h y d r o x y p r o p y l a m i n o ) - 2 - c y c l o h e x e n - l - o n e (XCIX) with pyridine hydrto-
dide.
0 OH O O O

R ~ R ' ~ R

R1 R1 OH R1
H H
xcYk ~' . ~T c=-i

889
 The synthesis of cyano derivatives of quinoline from dtketones I and tetracyanoethylene [36] and also
from 2-acetylcyclohexane-l,3-dtones and malononitrtle in the presence of a base [159] should be noted.
The synthesis of a number of acridine derivatives, quite apart from different variants of the Hantzsch
reaction, is known. 1-Oxo-l,2,3,4-tetrahydroaeridines CIII were obtained from cyclohexane-l,3-diones and
aromatic o-aminocarbonyl compounds [160-162]. The reaction of methylenebisdihydroresorcinol with phe-
nylsulfonylhydrazine gives dihydrazone CIV [84], while refluxing methylenebisdihydroresorcinol di(phenyl-
hydrazone) in acetic acid gives monophenylhydrazone CV [85].

0 R2 A NNHR

~ ~,~
CI...~V A = NNHSO2C6H 5 ~ R = 502C6H 5 ; C_.~V A = O , R=C6H 5

Enamines CVI, obtained from 2-acylcyclohexane-l,3-diones and primary aromatic amines, give the
corresponding 7-oxo-7,8,9,10-tetrahydrophenanthr idines (C VII) when they are heated with polyphosphor ic
[58, 65, 163] or sulfuric acid [164]. Phenanthridone CVIII was obtained [46] from 2-carbomethoxyquinone
and enamine XXIIIb. 8ehiff bases from fl- and a-naphthylamines readily add cyclohexane-l,3-diones to
give 7-oxo-5,6,7,8,9,10-hexahydrobenzo [a ]- (CIX) and -benzo [c]phenanthridines (CX), respectively [165-
168]. Benzophenanthridines CIX can also be obtained from fl-naphthlamine and bis (1,3-dioxo-2-cyclohexyl)-
methanes [169] or by cocondensation of the aldehyde, fi-naphthylamine, and I. Hexahydrobenzophenanthri-
dines CIX and CX are readily oxidized to the corresponding 7,8,9,10-tetrahydro derivatives, CXI and CXII
[167, 168].

O O2

R ~

~ H

CVI c v.,]2 cv m

R2 R2

R R
R1/ ~ "T Rw ~ ~T
Ar Ar
c[_._xx ~ c xx cx._~L~ cxi___Z
Cl__XX~ C X l R2= I~2- bcnzo ; C x ~ CxII RZ= 3 ~ 4 - b e n z o

The condensation of 2-acetylcyclohexane-l,3-diones (XI) with 3,4-dihydroisoquinoltne makes it pos-

sible to arrive at azasteroid analogs - dibenzo [a,f] quinolizines (CXIII) [170, 171]. The corresponding di-
benzopyrrocoltnes (CXV) [172] were obtained as a result of B a e y e r - V i l l i g e r oxidation of the latter, subse-
quent alcoholysis of lactone CXIV, and condensation.
O O O O

H202
R1 RI

H___j
CX CXIV

-1- R2OH
- - H20

O
R2 0 0 C

o~ C

890
 1-Methyl-6-oxoquinolizidine (CXVI) is f o r m e d [173] by hydrogenation of 2 - m e t h y l - 2 - ( f i - c y a n o e t h y l ) -
c y c l o h e x a n e - l , 3 - d i o n e o v e r a Raney nickel c a t a l y s t in the p r e s e n c e of alkali.

Quinazolines
2 - P h e n y l - 5 - o x o - 5 , 6 , 7 , 8 - t e t r a h y d r o q u i n a z o l i n e s (CXVIII) a r e obtained by r e a c t i o n of 2 - f o r m y l - and
2 - a c e t y l c y c l o h e x a n e - l , 3 - d i o n e s (CXVII) with benzamidine [174-176]. The use of ant[ides CXIX in place of
t h e i r 2-acyl d e r i v a t i v e s i n c r e a s e s the yields of quinazolines CXVIII [176, 177]. Aeetamidine and f o r m a m i -
dine display only an [minating effect with r e s p e c t to CXVII, but f o r m the c o r r e s p o n d i n g qninazoline in r e -
actions with enol e t h e r s XII. An u n s y m m e t r i c a l amid[he - 3 - a m i n o - s y m - t r i a z o l e - r e a c t s with e t h e r s XII
and t r i k e t o n e s CXVII to give qninazoline d e r i v a t i v e s CXX and CXXI, r e s p e c t i v e l y [178].

O O R2 O

"~NH 2 ( y ~N -( NH 2

CXVll CXVIII 1...~1

X

O 0 0

N C~NHC6H5 N--N
'R R
R N R1/~/~" O ~1 N'~j

CXXI CX~X CXX

The imination of 2 - b e n z a m i d o m e t h y l e n e - 5 , 5 - d i m e t h y l c y c l o h e x a n e - 1,3-dione (CXXII, R 2 = C 6H5) also

gives CXVIII (1R2=H, 1R3 =C6H5) , while 2 - a c e t a m i d o m e t h y l e n e d e r i v a t i v e CXXII (R 2 =CH3) gives CXXIII [117].
4-Anilino- (CXXIV, R 2 = C 6H5) and 4 - a m i n o - 2 - p h e n y l - 7 , 7 - d i m e t h y l - 5 - o x o - 5 , 6 , 7 , 8 - t e t r a h y d r o q u i n a z l i n e
(CXXIV, R 2 =H) have also been synthesized; the f o r m e r was p r e p a r e d f r o m 5 , 5 - d i m e t h y l e y c l o h e x a n e - l , 3 -
d i o n e - 2 - t h i o e a r b o x y l i c acid antiide (CXXV) and b e n z a m i d i n e [179], while the l a t t e r was obtained f r o m 2-
c y a n o - 3 - e t h o x y - 5 , 5 - d i m e t h y l - 2 - c y c l o h e x e n - l - o n e (XXXIXb) and b e n z a m i d i n e [64].

0 H O O
. ~ NHCOR2 ~

3 ~ O R3 : CH 3
CXXI/ CXXIII

O O NHR 2 O

OH 6 5 zH5
CXXV CXXIV X ~

Condensed Systems Containing Pyraztne

and Pyridazine
The self-condensation of 2-aminocyclohexane-l,3-diones (CXXVI) to 1,5-dioxodecahydrophenazines
(CXXVII) was carried out in [66, 180] in the presence of acids. Deeahydrophenazines are readily oxidized
by hydrogen peroxide to octahydrophenazines CXXVIII.
0 0 0

OH R N
H O O
CXXVI CXXVII CXXVlll

R ~N--N .~

CXXIX r

891
 3 , 4 , 5 , 8 , 9 , 1 0 - H e x a h y d r o - 1 , 2 , 6 , 7 - t e t r a a z a p y r e n e s CXXX w e r e obtained [181] by oxygen oxi dation of
diazines CXXIX, s y n t h e s i z e d both d i r e c t l y f r o m I and hydrazine and also f r o m c y c l o h e x a n e - l , 3 - d i o n e mono-
and dihydrazones.

Other Stx-Membered Heterocycles with Two

and Three Heteroatoms
Sulfides, which a r e c o n v e r t e d to 4 - o x o - l , 2 , 3 , 4 - t e t r a h y d r o p h e n o t h i a z t n e s (CXXXI) by reduction with
zinc in acetic acid, w e r e obtained [182] f r o m dtketones I and o - n i t r o a r e n e s u l f e n y l chlorides. A dibenzo-
[b,e]oxatine d e r i v a t i v e (CXXXII) is f o r m e d in 80% yield [183] b y refluxing bisdimedonyl sulfide in acetic
anhydride.
0 0 O, 0

R N
9 < V ~ . N . ,H. . C6Hs

cxxXi cxxx-, cxxxHi

The only e x a m p l e of the s y n t h e s i s of a t r i a z i n e d e r i v a t i v e is [85] cyelizat[on of 2 - a c e t a m i d o c y c l o h e x -

a n e - 1,3- dione phenylhydrazone to 5-oxo - 1,2,5,6,7,8-hexahydrobenzo- 1,2,4-tr iaz ine CXXXIII in acetic ac id.

Condensed Systems Including Azepine

and 1,4-Diazeptne
Schiff b a s e s f r o m 2 - a c y l c y c l o h e x a n e - l , 3 - d i o n e s and o - p h e n y l e n e d i a m i n e (CXXXIV)are cyclized [184,
185] to 1 , 2 , 3 , 4 - t e t r a h y d r o - l l H - d t b e n z o ( b , e ) - l , 4 - d i a z e p i n - 4 - o n e s a l t s (CXXXV) b y the actEon of acids. The
c o r r e s p o n d i n g b a s e s have also been isolated and the pathways for their c o n v e r s i o n to b e n z i m l d a z o l e d e r i v -
atives CXXXVI [186] have b e e n d e m o n s t r a t e d . 5-Substituted 2 , 2 - d i m e t h y l - 1,2,3,4,5,6-hexahydro- l l H - d t -
b e n z o ( b , e ) - l , 4 - d t a z e p i n - 4 - o n e s w e r e obtained [187] in r e a c t i o n s of 3 - ( o - a m i n o a n i l i n o ) - 5 , 5 - d i m e t h y l - 2 - c y -
c l o h e x e n - l - o n e with aliphatic and a r o m a t i c aldehydes.

oR, H R. R1 H R R1

H2N X--
CXXXIV CXXXV CXXXVI

Ketones of the CXXXVII type have been used to obtain condensed s y s t e m s including azepine. Two
methods have b e e n used for this: the Beckmann r e a r r a n g e m e n t of their o x i m e s and the Schmidt r e a c t i o n .
Both p o s s i b l e i s o m e r s (CXXXVIIIc and CXXXIXc) w e r e isolated [188] only f r o m the products of the B e c k -
mann r e a r r a n g e m e n t in polyphosphoric acid of 1 - m e t h y l - 4 - o x o - 4 , 5 , 6 , 7 - t e t r a h y d r o i n d o l e oxime. 4-Oxo-
1 , 2 , 3 , 4 - t e t r a h y d r o c a r b a z o l e oxime was c o n v e r t e d [51] to CXXXVIIIa, 2 - m e t h y l - 7 - o x o - 4 , 5 , 6 , 7 - t e t r a h y d r o -
benzothlazole o x i m e was c o n v e r t e d to C X X X I X [189], and 2 - p h e n y l - 4 , 7 , 7 - t r i m e t h y l - 5 - o x o - 5 , 6 , 7 , 8 - t e t r a -
hydroquinazoline o x l m e was c o n v e r t e d to CXXXIXd [190].
The Schmidt r e a c t i o n (the action of h y d r a z o i c acid in polyphosphoric acid} is suitable only for
CXXXVIId and gives the s a m e CXXXIXd [190].

0 0 0 0

p1 R~ / ~ / ~"R3 R~/ ~ R s H
CXXXVIII CXXXVII CXXXIX CXI

CH 3

= a b c d
~3 CH3 , C6H5
H CH 3

892
 2,4-Dioxo-l,2,3,4,5,6-hexahydroazepine CXLwas obtainedby photoehemicaldecomposition of 3-azido-
5,5-dimethyl-2-cyclohexenone in tetrahydrofuran [191, 192],
Of other general pathways for the subsequent construction of polycondensed heterocycl[c systems by
means of ketones CXXXVII, one should note reactions involving their a-formylat[on with subsequent syn-
thesis of the heteroeycle f r o m an a - f o r m y l ketone structural fragment [193-195].
Two-ring systems of the CXXXVII type (4-oxo-4,5,6,7-tetrahydromdazoles [71, 72], 7-oxo-4,5,6,7-
tetrahydrobenzothiazoles [98], 5-oxo-5,6,7,8-tetrahydroquh~ol[nes [~52], and 4-oxo-4,5,6,7-tetrahydrobenzo-
fttrans [196]) have also been used in place of 6-methoxytetralone for the synthesis, via the Torgov scheme,
of heterocyclic analogs of estrone with a modified A ring.

LITERATURE CITED
1. H. Stetter and E. Siehnhold, Ber., 8_~8,271 (1955).
2. J . N . Chatterjea and R. R. Ray, Bet., 922, 998 (lb59).
3. H. Stetter and R. Lauterbach, Ber., 93, 603 (1960).
4. H. Stetter and R. Lauterbach, Ann., 652, 40 (1962).
5. E . B . McCall, A. J. Neale, and T. J. Rawl[ngs, J. Chem. Soc., 4900 (1962).
6. E . B . McCall, A. J. Neale, and T. J. Rawlings, J. Chem. Soc., 5291 (1962).
7. J . N . Chatterjea and V. N. Mehrotra, J. Indian Chem. Soc., 39, 599 (1962).
8. V.A. Barkhash, V. S. Velezheva, and I. V. Machinskaya, Zh. Organ. Khim., 2, 1083 (1966).
9. K. Takagi and T. Ueda, Chem. Pharm. Bull. (Tokyo), 19, 1218 (1971).
10. R. Nagarajan and R. Shah, Tetrahedron Lett., 1467 (1972).
11. V. S. Velezheva, I. V. Machinskaya, and V. A. Barkhash, Zh. Vsesoyuzn. Kh[m. Obshchestva, 14, 467
(1969).
12. U . E . Schulte, J. Reisch, and H. Lang, Bet., 96, 1470 (1963).
13. S .I . Zav'yalov, G. V. Kondrat'eva, and D. F. Kundryavtseva, Zh. Obshch. Kh[m., 3_!, 3695 (1961).
14. A.S. Sopova, V. V. Perekalin, and V. M. Lebedneva, Zh. Obshch. Khim., 3_~3,2143 (1963).
15. A . S . Sopova, V. V. Perekalin, and V. M. Lebedneva, Zh. Obshch. Kh[m., 3_44,2638 (1964).
16. O . I . Yurchenko, A. S. Sopova, V. V. Perekal[n, V. M. Berestovitskaya, A. S. Polyanskaya, and N. I.
Aboskalova, Dokl. Akad. Nauk SSSR, 171, 1123 (1966).
17. V.M. Berestovitskaya, A. S. Sopova, and V. V. Perekal[n, Khim. Geterots[kl. Soedin., 396 (1967).
18. S . J . Dominianni, M.O. Chaney, and N. D. Jones, Tetrahedron Lett., 4735 (1970).
19. H. Stetter and K. Koehne, Ber., 9_~1,1344 (1958).
20. H.O. Larson, T. C. Oo4, A. K. Siu, K. H. Hollenbeak, and F. L. Cue, Tetrahedron, 2_5, 4005 (1969).
21. A . T . Nielsen and T. G. Archibald, Tetrahedron, 2_.55,2393 (1969).
22. G. Nowy, W. Riedl, and H. Simon, Ber., 9_~9,2075 (1966).
23. A.A. Akhrem, A. M. Mo[seenkov, and F. A. Lakhvich, Dokl. Akad. Nauk SSSR, 193, 1053 (1970).
24. A.A. Akhrem, A. M. Moiseenkov, F. A. Lakhvich, and A. I. Poselenov, Izv. Akad. Nauk SSSR, Ser.
Khim., 143 (1972).
25. F . H . Greenberg, J. Org. Chem., 3_00,1251 (1965).
26. G . B . Kondrat'eva, G. A. Kogan, and S. I. Zav'yalov, Izv. Akad. Nauk SSSR, Otd. Khim. Nauk, 1441
(1962).
27. I. ]~. Lielbried[s and l~. Yu. Gudr[nietse, Izv. Akad. Nauk Latv. SSR, Ser. Khim., 192 (1968).
28. O. Mattsson and C. Wachtmeister, Acta Chem. Seand., 22, 49 (1968).
29. O. Mattsson, B. Sj~Jquist, and S. Wachmeister, Aeta Chem. Scand., 244, 3326 (1970).
30. R. Brette and D. Seddon, J. Chem. Soe., 2174 (1970).
31. S.I. Zav'yalov, A.F.Vasil'ev, andL. P. Vinogradova, Izv. Akad. Nauk SSSR, Otd. Khim. Nauk, 850
(1961).
32. O. Mattsson, Tetrahedron Lett., 2489 (1969).
33. D.C. Smith, J. Chem. Soc., 1244 (1956).
34. E. Kopp and J. Smith, Ann., 693, 117 (1966).
35. K. Gump, S. Moje, and C. Castro, J. Amer. Chem. Soc., 8._99,6770 (1967).
36. H. Junek and H. Aigner, Z. Natarforsch., 25b, 1423 (1970)~
37. H.J. Schaeffer and R. V[nce, J. Org. Chem., 27, 4502 (1962).
38. H. Stetter and R. Lauterbaeh, Ann., 655, 20 (1962).
39. C.D. Nenitzescu (Nenitzesky), Bull. Soc. Chim. Romania, i_00,134 (1928}.
40. S. Hauptmann, H. Blume, G. Hartmann, D. Haendel, and P. Franke, Z. Chem., 6, 107 (1966).

893
41. A . N . Kost, L. G. Ovseneva, and T. V. Shuvaeva, Khim. Geterots[kl. Soedin., 717 (1966).
42. V . I . Shvedov, L. B. Altukhova, and A. N. Grinev, Khim. Geterotsikl. Soedin., 342 (1972).
43. H . J . Roth and H. E. Hagen, Arch. P h a r m . , 304, 70 (1971).
44. H . J . Roth and P. Lepke, Arch. P h a r m . , 305, 159 (1972).
45. H . J . Roth and H. E. Hagen, Arch. P h a r m . , 304, 159 (1971).
46. R. Littel, G. Morton, and G. Allen, J. Amer. Chem. Soc., 92, 3740 (1970).
47. R. F r i a r y , R. F r a n c e , and J. ~s Chem. Commun., 283 (1970).
48. J . M . Bobbit and C. P. Dutta, Chem. Commun., 1429 (1968).
49. H. Yamada, T. Konakhara, S. Ishihara, H. Kahamori, T. Itoh, K. Kimura, and H. lida, Tetrahedron
Lett., 2513 (1972).
50. G.R. Clemo and D. G. I. Felton, J. Chem. Soc., 700 (1951).
51. H.J. Teuber, D. Cornelius, and E. Worbs, Tetrahedron Lett., 331 (1964).
52. H.J. Teuber, D. Cornelius, and U. Woleke, Ann., 696, 116 (1966).
53. W. Sucrow and E. Wiese, Ber., 103, 1767 (1970).
54. V.V. Perekalin and K. S. Parfenova, Zh. Obsheh. Khim., 30,388 (1960).
55. E.M. Danilova and V. V. Perekalin, Zh. Organ. Khim., I, 1708 (1965).
56. E.M. Danilova, V. V. Perekalin, and T. Ya. Paperno, Zh. Organ. Khim., 3, 1860 (1967).
57. A.W. Crossley and N. Renouf, J. Chem. Soc., 1524 (1912).
58. H. Smith, J. Chem. Soc., 803 (1953).
59. A.A. Akhrem, A. M. Moiseenkov, and M. B. Andaburskaya, Izv. Akad. Naak SSSR, Ser. Khim., 2846
(1969).
60. A.A. Akhrem, A. M. Moiseenkov, M. B. Andaburskaya, and A. V. Mkhitaryan, Izv. Akad. Nauk SSSR,
Ser. Khim., 1196 (1969).
61. A.A. Akhrem, A. M. Moiseenkov, F. A. Lakhvich, and S. P. Smul'skii, Izv. Akad. Nauk SSSR, Ser.
Khim., 1089 (1971).
62. A.A. Akhrem, A. M. Moiseenkov, and F. A. Lakhvich, Izv. Akad. Nauk SSSR, Set. Khim., 2786 (1971).
63. A.A. Akhrem, A. M. Moiseenkov, A. Ya. Strakov, and M. B. Andaburskaya, Izv. Akad. Nauk SSSR,
Ser. Khim., 836 (1973).
64. A. Ya. Strakov, M. B. Andaburskaya, A. M. Moiseenkov, and A. A. Akhrem, Izv. Akad. Naak Latv.
SSR, Ser. Khim., 330 (1973).
65. G. Lehmann, Angew. Chem., 7_~7,383 (1965).
66. A.K. Area and D. V. Bite, Khim. Geterotsikl. Soedin., 1283 (1971).
67. W. Ried and A. Str~itz, Ann., 764, ii (1972).
68. W. Diekcmann and R. Stein, Ber., 3_~7,3370 (1904).
69. 1~. Yu. Gudrinietse and I. A. Strakova, Izv. Akad. Nattk Lair. SSR, Ser. Khim., 128 (1963).
70. I.A. Strakova and I~. Yu. Gudrinietse, Izv. Akad. Nauk Latv. SSR, Ser. Khim., 680 (1966).
71. G. Lehmann, H. Wehlan, and G. Hilgetag, Bet., I00, 2967 (1967).
72. G. Lehmann, H. Weblan, and G. Hilgetag, Tetrahedron Left., 123 (1967).
73. I.A. Strakova, Ya. Ya. Linaberg, and 1~. Yu. Gudrinietse, Izv. Akad. Nauk Latv. SSR, Ser. Khim., 188
(1968).
74. I.A. Strakova, A. Ya. Strakov, M. T. Strautzele, and ]~. Ya. Gudrinietse, Izv. Akad. Nauk Latv. SSR,
Ser. Khim., 597 (1968).
75. I.A. Strakova, I~. Yu. Gudrinietse, Ya. Ya. Linaberg, A. Ya. Strakov, and D. R. Kreitsberga, Khim.
Geterotsikl. Soedin., 520 (1970).
76. A.A. Akhrem, A. M. Moiseenkov, F. A. Lakhvich, M. B. Andaburskaya, A. V. Mkhitaryan, G. N. Sed-
letskaya, and V. A. Petukhov, Izv. Akad. Nauk SSSR, Ser. Khim., 594 (1971).
77. W. Suerow, M. Slopianka, and A. Neophyton, Ber., 105., 2143 (1972).
78. I.A. Strakova, A. Ya. Strakov, and 1~. Yu. Gudrinietse, Izv.Akad. Naul{ Latv. SSR, Ser. Khim., 593 (1973).
79. N. Rogers and H. Smith, J. Chem. Soe., 341 (1955).
80. S. Forsen and M. Nilson, Arkiv Kemi, 19, 569 (1962),
81. D.V. Brutane, A. Ya. Strakov, and I. A. Strakova, Izv. Akad. Nauk Lair. SSR, Ser. Khim., 485 (1970).
82. A.A. Aldlrem, A. M. Moiseenkov, M. B. Andabarskaya, and A. Ya. Strakov, Izv. Akad. Nauk Lair.
SSR, Set. Khim., 740 (1970).
83. A.A. Akhrem (Achrem), A. M. Moiseenkov, M. B. Andaburskaya (Andaburskaja), and A. Ya. (J.)
Strakov, J. prakt. Chem., 314, 31 (1972).
84. H.J. Teuber andR. Braun, Ber., i0___00,1353 (1967).
85. H.J. Teuber, E. Worbs, and D. Cornelius, Ber., I01, 3918 (1968).
86. G.V. Boyd and S. R. Dando, J. Chem. Soe., C, 225 (1971).

894
 87. Y. Tamura, N. Tsujimoto, Y. Sumida, and N. Ikeda, Tetrahedron, 28, 21 (1972).
88. E. V. Vanag, V. Ya. Grinshtein, and A. E. Sausin', Izv. Akad. Nauk Latv. SSR, Ser. Khim., 215 (1964).
89. A. K. Aren and D. V. Bite, Zh. Vsesoyuzn. Kh}m. Obshchestva, 1__22,708 (1967).
90. F. A. Grunsberg, Author's Abstract of Dissertation, Riga (1970).
91. A. Cross and A. Deer, Chem. Ind., 1_88,731 (1966).
92. V.I. Shvedov, L. B. Altukhova, and A. N. Grinev, Khim. Geterotsikl. Soedin., 131 (1972).
93. I.K. Gaile, I~. Yu. Gudrinietse, and G. Ya. Vanag, Dokl. Akad. Nauk SSSR, i_446, 817 (1962).
94. I.K. Gaile, I~. Yu. Gudrinietse, and G. Ya. Vanag, Izv. Akad. Nauk Latv. SSR, Set. Khim., 523 (1962).
95. H. Albers and W. Mohler, Ber., 9__66,357 (1963).
96. G. Lehmann, B. L[icke, H. Schick, and G. Hilgetag, Z. Chem., I I, 422 (1967).
97. M. M/ihlstadt and E. Bordes, J. prakt. Chem., 2_O0,285, (1963).
98. G. Lehmann, H. Sehick, B. Lficke, and G. Hilgetag, Ber., i01, 787 (1968).
99. E. Schmitz and H. Stiegler, J. prakt. Chem., 313, 1125 (1971).
I00. M. Regitz and H. Schwall, Ann., 72__~8,99 (1969).
101. I.E. Lielbriedis and Is Yu. Gudrinietse, Izv. Akad. Nauk Lair. SSR, Ser. Khim., 684 (1966).
102. Ya. Ya. Lemba and I. }~. Lielbriedis, Izv. Akad. Nauk Latv. SSR, Ser. Khim., 598 (1973).
103. D. Vorlander, Z. anal. Chem., 7_77,241 (1929).
104. G. Klein and H. Linser, Mikrochemie Pregl-Festschrift (Vienna), 204 (1929); Chem. Zentrallblat,
I, 2085 (1930).
105. E. Hornig and M. Hornig, J. Org. Chem., 1:1, 95 (1946).
106. D. Spencer and T. Henshall, J. Amer. Chem. Soe., 7_~7, 1943 (1955).
107. C. Dural and Nguen Dat Kuong, Anal. Chim. Acta (Amsterdam), i0, 47 (1955); Chem. Zentrallblat,
9870 (1958).
108. J. Thomas, E. Sanborn, M. Mukai, and B. Tebbens, Ind. Eng. Chem., 5:1, 774 (1959).
109. E. Padilla, An. Fac. Farmac. Bioquim., 7, 598 (1956); Chem. Zentrallblat, 3924 (1962).
ii0. F. King and D. Felton, J. Chem. Soe., 1371 (1948).
Iii. Desai and M. Wali, J. Indian Chem. Soc., i__33,735 (1936).
112. P.E. Papadakis, J. Org. Chem., 1__9.9 , 51 (1954).
113. T. Vo}tila, Suomen Kemistilehti, 100, (14), 25 (1937).
114. Zh. A. Krasnaya, S. S. Yufit, and V. F. Kucherov, Izv. Akad. Nauk SSR, Otd. Kh[m. Nauk, 1104
(1967).
115. W. Back and E. Mutsehler, Arch. Pharm., 300, 955 (1967).
116. B. Akehurst and J. Bartels-Keith, J. Chem. Soc., 4798 (1957).
117. A. Ya. Strakov, D. V. Brutane, S. P. Valter, and IV[. T. Shultsa, Izv. Akad. Nauk Latv. SSR, Ser.
Khim., 141 (1971).
118. L. Jurd, J. Org. Chem., 3:11639 (1966).
119. J. Baldas and Q. Porter, Tetrahedron Left., 1351 (1968).
120. P~ Yates, D. Bichan, andJ. McCloskey, Chem. Commun., 839 (1972).
121. A. Roedig and S. Schodel, Ber., 9_ii,330 (1958).
122. G.V. Kondrat'eva, V. I. Gunar, L. F. Ovechkina, S. I. Zav'yalov, and A. I. Krotov, Izv. Akad. Nauk
SSR, Ser. Khim., 633 (1967).
123. J.H. Sellstedt, J. Org. Chem., 37, 1337 (1972).
124. E. Ziegler, H. Junek, and U. Herzog, Monatsh., 102, 1616 (1971).
125. P. Margaretha, Tetrahedron Lett., 1449 (1970).
126. A. Omori, N. Sonoda, Y. Uchida, and S. Tsusumi, Bull. Chem. Soc. Japan, 4_22,3233 (1969).
127. S. Danishefsky, G. Koppel, and R. Lewine, Tetrahedron, 2_44,2257 (1968).
128. G. Sauer, U. Eder, and G. Hoyer, Ber., i0__55,2358 (1972).
129. V.I. Gunar, L. F. Ovechkina, S. I. Zav'yalov, G. N. Persh}n, and S. N. Milovanova, Izv.Akad. Nauk
SSSR, Otd. Khim. Nauk, 1827 (1964).
130. S .I . Zav'yalov, G. V. Kondrat'eva, and L. F. Kudryavtseva, Izv. Akad. Nauk SSSR, Otd. Khim. Nauk,
529 (1961).
131. H. Fales, E. Warnhoff, and H. Wildman, J. Amer. Chem. Soc., 7_77, 5885 (1955).
132. H. Stetter and E. Sienhold, Ber., 8__88,1223 (1955).
133. G. Ya. Vanag and l~. I. Stankevieh, Zh. Obsheh. Khim., 3_00,3287 (1960).
134. ]~. I. Stankevich and G. Ya. Vanag, Izv. Akad. Nauk Latv. SSI~, Ser. Khim., 223 (1961).
135. I. ~.. Lielbriedis and ]~. Yu. Gudrinietse, Izv. Akad. Nauk Latv. SSR, Ser. Kh[m., 318 (1967).
136. H. Antak[, J. Chem. Soc., 2263 (1965).
137. D. Vorl~inder and F. Kalkow, Ber., 30, 1801 (1897).

895
138. H. Antaki, J. Chem. Soc., 4877 (1963).
139. M . V . Ionescu and V. N. Georgescu, Bull. Soc. Chim. France, 4_~1,692 (1926).
140. D.V. Shveits, l~. I. Stankevich, and O. Ya. Neiland, Izv. Akad. Nauk Latv. SSR, Ser. Khim., 213
(1968).
141. t~. I. Stankev[ch, ]~. E. Grinshtein, and G. Ya. Vanag, Khim. Geterotsikl. Soedin., 583 (1966).
142. ]~. t~. Grinshtein, ]~. I. Stankevich, and G. Ya. Dubttr, Khim. Geterotsikl. Soedin., 1118 (1967).
143. l~. l~. Grinshtein, ]~. I. Stankevich, and G. Ya. Dubur, Khim. Geterotsikl. Soedin., No. 1,395 (1967).
144. Yu. ]~. Pelcher, ]~. ]~. Grinshtein, ]~. I. Stankevieh, and G. Ya. Vanag, Khim. Geterotsikl. Soedin.,
No. 1, 406 (1967).
145. t~. I. Stankevich and G. Ya. Vanag, Zh. Obshch. Khim., 32, 1146 (1962).
146. A. Ya. Ozola, ]~. I. Stankevieh, and G. Ya. Dubur, Khim. Geterotsikl. Soedin., 632 (1971).
147. ]~. I. Stankevich and G. Ya. Vanag, Dokl. Akad. Nauk SSSR, 14_~0,607 (1961).
148. U. Eisner and K. Kuthan, Chem. Rev., 72, 1 (1972).
149. C. Ruanopiyanand, H. J. Rimek, and F. Zymalkowski, Ber., 10_._33,2043 (1970).
150. F. Bohlmann and R. Mayer-Mader, Tetrahedron Lett., 171 (1965).
151. M. Sluyter, U. Pandit, W. Speckamp, and H. Huisman, Tetrahedron Lett., 87 (1966).
152. N. Finch and C. W. Gemender, J. Org. Chem., 3_55,3114 (1970).
153. M . A . T . Dubas-Sluyter, W. N. Speckamp, and H. Huisman, Rec. Tray. Chim., 91, 157 (1972).
154. S . I . Zav'yalov, I. A. NIikhaitopulo, V. I. Gunar, and L. F. Ovechkina, Izv. Akad. Nauk SSSR, s e t .
Khim., 859 (1967).
155. P . W . Hickmott and G. Sheppard, J. Chem. Soe., C, 2112 (1971).
156. H. Dugas, M. E. Hazenberg, Z. Valenta, and K. Wiesner, Tetrahedron Lett., 4931 (1967).
157. C . A . Grob and H. R. Kiefer, Helv. Chim. Acta, 4_88,799 (1965).
158. H. Dugas, R. A. Ellison, Z. Valenta, K. Wiesner, and C. M. Wong, Tetrahedron Lett., 1279 (1965).
159. ]~. Yu. Gudrinietse and A. D. Yukhnevieh, Izv. Akad. Nauk Latv. SSR, Ser. Khim., 622 (1972).
160. B . H . Iyer and G. C. Chakravarti, J. Indian Inst. Sci., A14p 157 (1932); Chem. Zentrallblat, 1, 2953
(1932).
161. G. Kempter and G. Mobiuss, J. prakt. Chem., 306,298 (1966).
162. G. Kempter and P. Klug, Z. Chem., 1_~t, 61 (1971).
163. W. Kirkor and J. Baranowicz, Acta Chim., 8, 69 (1962).
164. G . M . Chopra and B. H. Iyer, Current Sci. (India), 22,210 (1953); Chem. Abstr., 4__99,887 (1955).
165. I. t~. Lielbriedis, V. V. Chirkova, and t~. Yu. Gudrinietse, Izv. Akad. Nauk Latv. SSR, Set. Khim.,
251 (1968).
166. I. ]~. Lielbriedis, V. V. Chirkova, and }~. Yu. Gudrinietse, Izv. Akad. Nauk Latv. SSR, Set. Khim.,
197 (1969).
167. I. }~. Lielbriedis and N. I. Veretennikova, Izv. Akad. Nauk Latv. SSR, Ser. Khim., 453 (1971).
168. I. ]~. Lielbriedis, S. R. Trusov, and l~. Yu. Gudrinietse, Izv. Akad. Nauk Latv. SSR, Ser. Khim., 39
(1971).
169. I. ]~. Lielbriedis and t~. Yu. Gudrinietse, Izv. Akad. Nauk Latv. SSR, Ser. Khim., 193 (1969).
170. A . A . Akhrem, A. M. NIoiseenkov, and A. I. Poselenov, Dokl. Akad. Nauk SSSR, 20__33,95 (1972).
171. A . A . Akhrem, A. M. Moiseenkov, V. A. Krivoruchko, F. A. Lakhvich, and A. I. Poselenov, Izv.
Akad. Nauk SSSR, Ser. Khim., 2078 (1972).
172. A . A . Akhrem, A. M. Moiseenkov, and A. I. Poselenov, Izv. Akad. Nauk SSSR, Ser. Khim., 2579
(1972).
173. V.I. Gunar and S. I. Zav'yalov, Dokl. Akad. Nauk SSSR, 13__~9, 367 (1961).
174. G. Lehmann, B. L~ieke, H. Wehlan, and G. Hilgetag, West German Patent No. 62,062 (1967); Ref. Zh.
Khim., 20N428 (1969).
175. D.V. Brutane and A. Ya. Strakov, Izv. Akad. Nauk Latv. SSR, Ser. Khim., 248 (1969).
176. D.V. Brutane and A. Ya. Strakov, Izv. Akad. Nauk Latv. SSR, Ser. Khim., 202 (1970).
177. D.V. Brutane, A. Ya. Strakov, and I. A. Strakova, Izv. Akad. Nauk Latv. SSR, Ser. Khim., 485
(1970).
178. D.V. Brutane, A. Ya. Strakov, A. M. Moiseenkov, and A. A. Akhremo Izv. Akad. Nauk Latv. SSR,
Ser. Khim., 610 (1970).
179. A. Ya. Strakov, D. V. Brutane, and V. V. Leieh, Izv. Akad. Nauk Latv. SSR, Ser. Khim., 248 (1970).
180. A.K. Aren, and D. V. Bite, Izv. Akad. Nauk Latv. SSR, Set. Khim., 246 (1971).
181. J.K. S%ille, J. M. Unglaube, and M. E. Freeburger, J. Amer. Chem. Soe., 90, 7076 (1968).
182. V.I. Shvedov, L. B. Altukhova, V. M. Lyubchanskaya, and A. N. Grinev, Khim. Geterotsikl. Soedin.,
1509 (1972).

896
183. R. Gompper, H. Euchner, and H. Kast, Ann., 675, 151 (1964).
184. A. Ya. Strakov, Ya. Ya. Linaberg, M. T. Stratltzele, and D. A. Lautsenietse, Izv. Akad. Nauk Latv.
SSR, Ser. Khim., 722 (1968).
185. M.T. Shultsa and A. Ya. Strakov, Izv. Akad. Nauk Latv. SSR, Ser. Khim., 329 (1971).
186. A. Ya. Strakov and M. T. Shultsa, Izv. Akad. Nat~k Lair. SSR, Ser. Khim., 355 (1972).
187. S. Miyand and N. Abe, Chem. Pharm. Bull. (Tokyo), 20, 1588 (1972).
188. A. Stoll and F. Troxler, Helv. Chim. Acta, 5_~1,1864 (1968).
189. 57. Buu-Hoi, A. Crossy, P. Jacquignon, and A. Martani, J. Chem. Soc,, C, 1109 (1971).
190. D.V. Brutane and A. Ya. Strakov, Izv. Akad. Nauk Lair. SSR, Ser. Khim., 225 (1973).
191. S. Sato, Bull. Chem. Soc. Japan, 41, 2524 (1968).
192. Y. Tamura, Y. Yoshim~ra, T. Nishimura, S. Kato, and Y. Kita, Tetrahedron Left., 35 (1973).
193. W. Kemers, R. Roth, G. Gibs, and M. Weiss, J. Org. Chem. 3_66~1232 (1971).
194. W. Remers and M. Seiss, J. Org. Chem., 36, 1241 (1971).
195. I.A. Strakova, A. Ya. Strakov, and I~. Yu. Gudrir~ietse, Izv. Akad. Nauk Latv. SSR, Ser. Khim., 627
(1972).
196. G. Lehmann and B. Liieke, Ann., 727, 88 (1969).

897
 SYNTHESIS OF PYRYLIUM SALTS BY CONDENSATION
OF fl-CHLOROCINNAMALDEHYDES WITH CARBONYL
COMPOUNDS

G . N. Dorofeenko and A. I. P y s h c h e v UDC 547.814.816.07 : 542.953

A method is p r o p o s e d for the s y n t h e s i s of u n s y m m e t r i c a l unsubstituted p y r y l i u m s a l t s by

condensation of f l - c h l o r o c i n n a m a l d e h y d e s with methyl and methylene ketones and f l - d i c a r -
bonyl compounds ha the p r e s e n c e of HC104 or Lewis acids. The p r o b a b l e s c h e m e of the r e -
act[on is examined.

P y r y l i u m s a l t s of v a r i o u s s t r u c t u r e w e r e obtained by condensation of fi-cMorovinyl ketones with p h e -

nols [1] a c t i v a t e d by ketones [2] or enamines [3]. We have used the m o r e active f i - c h l o r o e i n n a m a l d e h y d e s '
(In-c), which a r e r e a d i l y obtained f r o m the c o r r e s p o n d i n g acetophenones and the V i l s m e i e r r e a g e n t [4].
In the condensation of such aldehydes with ketches one might have expected the f o r m a t i o n of p y r y l i u m
s a l t s via one of the following s c h e m e s :

H,,~/W d " ~ ' w cto- ,~"~"~'

It .t ~ IP .I -'--'. I1~.1 c~o:

ArCCI=CH--CHO + (' II
H0 / ' ~ R" ~ Ar Ar

u/~o o//%R,, -H2O ~.oJ.~.R,, el~

III

I 8. Ar=C6Hs; b Ar~4-O2NC6H4; C Ar~3,4-(CH30)~C6H 3

Scheme A might have been r e a l i z e d by e l e c t r o p h i l i c a t t a c k of the methylene group of the ketone by

the c a r b o n a t o m of the aldehyde group and subsequent f o r m a t i o n of y - u n s u b s t i t u t e d p y r y l i u m s a l t s (II),
while s c h e m e B, in analogy with condensations of fi-ehlorovinyl ketones, should lead to ~ - u n s u b s t i t u t e d
p y r y l i u m s a l t s IH.
It was found that only the known 2 , 6 - d i p h e n y l p y r y l i u m p e r c h l o r a t e is obtained in the r e a c t i o n of
f i - c h l o r o c i n n a m a l d e h y d e Ia with acetophenone; this c o r r e s p o n d s to s c h e m e A.
The o c c u r r e n c e of the r e a c t i o n via s c h e m e A is c o n f i r m e d by the fact that compounds 16, 19, and 23
(see Table 1) a r e identical to known s a m p l e s obtained by other methods.
f l - C h l o r o e i n n a m a l d e h y d e s p r o v e d to be convenient r e a g e n t s for the synthesis of u n s y m m e t r i c a l
p y r y l t u m s a l t s with an a c t i v a t e d y - p o s i t i o n , including also compounds containing functional substituents;
p r e v i o u s a t t e m p t s to a c c o m p l i s h this synthesis w e r e unsuccessful.
The use of aldehydes Ia and Ib m a k e s it p o s s i b l e to obtain p y r y l i u m s a l t s f r o m dimedone and indane-
d[one (compounds 20, 21, and 22); this cannot be a c c o m p l i s h e d when other fl-diearbonyl compounds and
t h e i r analogs a r e used. The p r e s e n c e in the a r y l r e s i d u e of e l e c t r o n - d o n o r substituents (Ic) p a s s i v a t e s the

Rostov State U n i v e r s i t y . S c i e n t i f i c - R e s e a r c h Institute of P h y s i c a l and Organic C h e m i s t r y , R o s t o v -

on-Don. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 8, pp. 1031-1035, August, 1974.
Original a r t i c l e s u b m i t t e d July 31, 1973.

9 76 Plenum Publishing Corporation. 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

898
 g .:

.~ <.~ <D <D (O <..] {,D {D Z ~ %9 r,D (_) <D L ] %9 ( D ;-{~ %.,~ (3 <D qD <D

9= = ========== ======= ~ ~ ~
~ J ~2JJJ6OOJdd OJ@dJ06 o o ~s ~s

oo o ~ ,~
D9 r r ~ (.o ~ a-.~ ~ ~..] ~r r ~-.~ ~ r ~ ~ ~ c~ ~ I

U 'E lo x~
9 ~0 ~.--~ U
~P

m~
CP o :Z =~, "~ E ff ff
0
<oo

GG G
~q

899
 TABLE 2

[M0c,.~ 1
Hexachlorostibiates ?entachtorostannates
No. R' R"
mp, ~ Yield,%
mp, ~ ~ Yield,%

24 H C6Hs 242 ] 18 (13)* 267 19t

25 COCsHs C6Hs 147 60 (64) 133 72
26 H CH3 160 10 (20) t70 33
27 CH3 C~H~ 130 12 (lO) 196 29
28 COOC2H5 CHa 140 15 (51) 173 66

* T h e s e are the yields for r e a c t i o n in CH3COOH (in CH2C12).

t This is the yield for r e a c t i o n in CH2C12.

aldehyde group, and this leads to a d e c r e a s e in the yield of the p y r y l i u m salt and an increase in the r e -
action time.
As the e l e c t r o n density in the aryt ring of a l i p h a t i c - a r o m a t i c ketones i n c r e a s e s , their ability to un-
dergo condensation with fl-chlorocinnamaldehyde d e c r e a s e s . Only p o l y m e r i c products a r e isolated when
phenols are used as the ketone component during acid c a t a l y s i s , but the c o r r e s p o n d i n g naphthopyrylium salt
is f o r m e d in the condensation of Ia with fi-naphthol (1 : 1), apparently as a consequence of predominant r e -
action at the more active a - p o s i t i o n .

Admixtures of i s o m e r i c p y r y l i u m salt III were not detected in a single c a s e , and aldehydes I n - c , in

c o n t r a s t to fl-chlorovinyl ketones, consequently undergo condensation with ketones in the p r e s e n c e of HC10 4
exclusively at the carbon atom of the carbonyl group. Complexing catalysts (SnC14 and SbC15) in protic and
aprotic solvents can be used in place of p e r c h l o r i c acid, but even this does not make it possible to direct
the p r o c e s s via s c h e m e B.
The p y r y l i u m pentacblorostannates and hexachlorostibiates obtained in this manner (Table 2) were
converted to p e r c h l o r a t e s and proved to be identical to samples obtained when p e r c h l o r i c acid was used.
The SnC14 catalyst is somewhat more active than SbC15. P e r c h l o r i c acid is more favorable for con-
densation of fi-chlorocinnamaldehyde with a l i p h a t i c - a r o m a t i c ketones and some dicarbonyl compounds.
However, the use of SnC14 provides b r o a d e r synthetic possibilities, inasmuch as the r e a c t i o n p r o c e e d s under
v e r y mild conditions.

EXPERIMENTAL
The IR s p e c t r a of mineral oil suspensions of the compounds were r e c o r d e d with a UR-10 s p e c t r o m -
eter.
Synthesis of P y r y l i u m Salts by Condensation of fi-Chlorocinnamaldehydes (I) with Ketones. A. In
the p r e s e n c e of p e r c h l o r i c acid. Acetic anhydride (3 ml) was added to a mixture of 0.012 mole of the ke-
tone, 10 ml of glacial acetic acid, 0.01 mole of I, and 1 ml of 70% HC104, and the r e s u l t i n g solution was r e -
fluxed for 5-10 min (in the case of Ia) or 10-20 min (Ib, c) until vigorous HC1 evolution ceased. The c r y s -
tals that f o r m e d when the solutions were cooled were r e m o v e d by filtration and washed s u c c e s s i v e l y with
ethyl acetate and ether. An additional amount of p y r y l i u m salt precipitated f r o m the filtrate. The IR s p e c -
t r a of the synthesized compounds contain intense bands at 1600-1620, 1580-1600, and 1090-1100 c m - l , which
are r e l a t e d to the vibrations of the p y r y l i u m cation, the a r o m a t i c substituents, and the C10 4- anion, r e s p e c -
tively. Intense absorption bands at 1660-1705 c m -1 also appeared for compounds containing carbonyl groups
in the fi-position of the p y r y l i u m ring.
The introduction of a nitro group into the 4-position of the aryl substituent causes a s h o r t - w a v e shift
at 10-20 c m - I of the s t r e t c h i n g vibrations of the p y r y l i u m cation.
B. In the p r e s e n c e of complexing catalysts. A 0.003-mole sample of SnC14 or SbC15 was added slowly
to a mixture of 0.002 mole of aldehyde Ia, 0.002 mole of the ketone, 10 ml of glacial acetic acid, and 10 ml
of ether, during which the mixture began to boil. The solution was allowed to stand for 10-12 h, and the
precipitated c r y s t a l s were r e m o v e d by filtration and washed with dry ether. The r e a c t i o n was c a r r i e d out
s i m i l a r l y by r e p l a c i n g the acetic acid by 5 ml of methylene chloride.

900
 In o r d e r to synthesize the p y r y l i u m p e r c h l o r a t e s , the pentaehlorostannates or hexachlorost[b[ates
w e r e d i s p e r s e d in acetone or acetic acid with e x c e s s 70% HC104. The mixture was refluxed for 10 min and
diluted with ether, and the precipitated c r y s t a l s w e r e r e m o v e d by filtration. The p e r c h l o r a t e s f o r m e d in
this manner did not d e p r e s s the melting point of the samples d e s c r i b e d above.

LITERATURE CITED
i. A. N. Nesmeyanov, N. K. Kochetkov, and M. I. Ryb[nskaya, Dokl. Akad. Nauk SSSR, 93, 71 (1953).
2. G. Fischer and W. Sehroth, Z. Chem., 3, 266 (1963).
3. G. W. Fischer and W. Schroth, Ber., 102, 590 (1969).
4. K. Bodendorf and R. Moyer, Ber., 98, 3554 (1965).
5. V. V. Mezher[tskH and G. N. Dorofeenko, Kh[m. Geterotsikl. Soedtn., 232 (1970).
6. G. N. Dorofeenko, E. P. Olekhnovtch, and L. I. Laukh[na, Kh[m. Geterotsikl. Soed[n., 435 (1971).
7. G. N. Dorofeenko and L. N. l~tmetchenko, Khim. Geterotstkl. Soedin., 250 (1970).
8. V. V. iV[ezheritskii, A. L. Vasserman, and G. N. Dorofeenko, Kh[m. Geterotsikl. Soedin., 1163 (1972).

901
REACTION OF 2,4,6-SUBSTITUTED PYRYLIUM
SALTS WITH COMPOUNDS CONTAINING A C = N BOND

G . N. D o r o f e e n k o , t~. A. Z v e z d i n a , UDC 547.813.828

M. P . Z h d a n o v a , V. V. D e r b e n e v ,
a n d E . S. M a t s k o v s k a y a

2,4,6-Substituted p y r y l i u m s a l t s add a z o m e t h i n e s to give p y r i d i n i u m s a l t s and a r o m a t i c alde-

hydes. The l a t t e r can be condensed with the methyl groups of the p y r i d i n i u m salts. B e n z a l -
doxime, b e n z a l a z i n e , benzalphenylhydrazine, u r e a , thiourea, and phenyl isothiocyanate r e -
act with 2 , 4 , 6 - t r i p h e n y l p y r y l i u m p e r c h l o r a t e s i m i l a r l y to give, r e s p e c t i v e l y , 2 , 4 , 6 - t r i p h e n y l -
pyridine N-oxide, 2 , 4 , 6 - t r i p h e n y l p y r i d i n e , or N - s u b s t i t u t e d 2 , 4 , 6 - t r i p h e n y l p y r i d i n i u m p e r -
chlorates.

It was r e c e n t l y shown that thionylamines r e a c t in an "ylid-like" s t r u c t u r e with p y r y l i u m salts via a

dipolar 1,2-cycloaddition s c h e m e [1]. As we have a l r e a d y r e p o r t e d [2], a z o m e t h i n e s of a r o m a t i c a m i n e s
(I), for which an " y l i d - l i k e " s t r u c t u r e is also p o s s i b l e , r e a c t s i m i l a r l y with 2,4,6-substituted p y r y l i u m
salts. In this c a s e , 1 - a r y l p y r i d i n i u m s a l t s (III) and a r o m a t i c aldehydes a r e f o r m e d f r o m 2 , 4 , 6 - t r i p h e n y l -
p y r y l i u m p e r c h l o r a t e (II):

+ - + ~ + RC6H4CilO

c~o; | i\cuqu,r | r' cn clo~ r' clo,

R'
"" " I ,o:J IV I I I a -e~, V | a - g

I, III: a) R =H, R' =phenyl; b) R =H, R' = p - t o l y l ; c) R =H, R' = o - t o l y l ; d) R =H, R' = p - a n i s y l ; e) R =H, R' =
p-nitrophenyl. V, Vh a) R =p-NO2, R' = 2 - p y r i d y l ; b) R =p-NO2, R' = 4 - p y r i d y l ; c) R =p-NO2, R' = 2 - b e n z i -
midazolyl; d) R =m-NO2, R' = 1 - m e t h y l - 2 - b e n z i m i d a z o l y l ; e) R =p-NO2, R' = l - e t h y l - 2 - b e n z i m i d a z o l y l ; f)
R =p-NO2, R ' = 1 - n o n y l - 2 - b e n z i m i d a z o l y l ; g) R =NO2, R' = 1 , 5 , 6 - t r i m e t h y t - 2 - b e n z i m i d a z o l y l .
The r e a c t i o n a p p a r e n t l y p r o c e e d s b y nucleophilic attach of the azomethine at the a - p o s i t i o n of the
p y r y l i u m r i n g with subsequent r i n g opening, 1,2-cycloaddition, and, finally, t h e r m a l cleavage of f o u r - m e m -
b e r e d complex IV. The a b s e n c e of w a t e r in the r e a c t i o n mixture excludes the p o s s i b i l i t y of h y d r o l y s i s of
the a z o m e t h i n e s and, consequently, the p r e s e n c e of an a r o m a t i c amine. The r e a c t i o n p r o c e e d s quantita-
tively when the components a r e r e f l u x e d in absolute d i m e t h y l f o r m a m i d e (DMF) for 1 h. In the c a s e of p e r -
c h l o r a t e II and benzalaniline, it was shown that the r e a c t i o n in glacial acetic acid is 70% complete a f t e r 3 h,
is 55% c o m p l e t e in absoiute n i t r o m e t h a n e a f t e r the s a m e t i m e , and does not o c c u r at all in absolute ethanol.
I n a s m u c h as the r e a c t i o n goes to completion much m o r e r a p i 4 l y in absolute DMF, all of the r e a c t i o n s w e r e
studied p r i m a r i l y in this solvent.
We have also extended the r e a c t i o n to a z o m e t h i n e s of h e t e r o a r o m a t t c a m i n e s (V).
2 - M e t h y l - 4 , 6 - d i p h e n y l p y r y l i u m p e r c h l o r a t e (VII) r e a c t s via this s a m e s c h e m e , but the aldehyde
f o r m e d in the r e a c t i o n condenses at the methyl group to give s t y r y l d e r i v a t i v e s VIII:

Rostov State University. S c i e n t i f i c - R e s e a r c h Institute of P h y s i c a l and Organic C h e m i s t r y , R o s t o v -

on-Don. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 8, pp. 1036-1040, August, 1974.
Original a r t i c l e s u b m i t t e d July 19, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored Oz a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopyhzg, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

902
 C6H5 ~ 6H5
C~Hs H;) + RC6H4CH--N--R'

CIO~"
VII VIII a-d

VlIh a) R =H, R' =phenyl; b) R =H, R' =p-tolyl; c) R =p-NO2, R ' = l - e t h y l - 2 - b e n z i m i d a z o l y l ; d) R =p-NO2,
R ' = 1,5,6-tr i methyl- 2 -benz i mi dazolyl.
The fact that the r e a c t i o n does not o c c u r in ethanol excludes the possibility of c a r r y i n g it out with
p e r c h l o r a t e VII without simultaneous condensation at the methyl group.
The s t r u c t u r e of VIIIa was confirmed by alternative synthesis [3]. Intense absorption bands of the
pyridinium r i n g (1620-1640 and 1555-1580 c m - l ) , bands of the C104- anion (110 cm-1), and, for VIc, a b s o r p -
tion bands of a benzimidazole NIt group at 3200 c m - i a r e p r e s e n t in the IR s p e c t r a of the p y r i d i n i u m p e r -
chlorates obtained in this study.
2 , 4 , 6 - T r i m e t h y l p y r y l i u m p e r c h l o r a t e r e a c t s with azomethines to give a mixture of substances that
are difficult to separate.
We also subjected other compounds for which the "quasi-ylid" s t r u c t u r e is possible to the r e a c t i o n
under consideration. Benzaldehyde and 2,4,6-triphenylpyridine a r e isolated f r o m the r e a c t i o n of p e r c b l o -
r a t e IT with benzaldoxime in DMF. It can be a s s u m e d that the initially f o r m e d 2,4,6-triphenylpyridine N - o x -
ide, which is unstable [4], is deoxygenated. In fact when the r e a c t i o n is c a r r i e d out in glacial acetic acid
(it is ~ 40% complete after 5 h), the N-oxide can be isolated. Up until now, only alkyl-substitnted p y r y l i u m
salts could be converted to pyridine N-oxides [5-7]. However, in an attempt to obtain the N-oxide f r o m
p e r c h l o r a t e 1T arid hydroxylamine we isolated 3,5-diphenylisoxazole [8]. Thus, 2,4,6-triphenylpyridtne N-
oxide can be obtained by means of this r e a c t i o n also f r o m p e r c h l o r a t e II, which contains phenyl substituents.
I n t e r m e d i a t e IX in the r e a c t i o n of p e r c h l o r a t e 1T with benzalazine is apparently unstable. It d e c o m -
poses to give 2,4,6-triphenylpyridine and benzonitrile:

~6Hs CsH~ 9

II 4+ (C.6H[,GH=N)2~ + C6HsC~N
C6H("L~+ I ~ c 6Hs -HCIO4 C6H5/ \C6H 5

N=CHC6H 5
cto~
IX

This c o n v e r s i o n r e p r e s e n t s an example of an aminonitxile r e a r r a n g e m e n t [9] in which the excess ben-

zalazine acts as the base. The r e a c t i o n p r a c t i c a l l y does not o c c u r in glacial acetic acid.
The r e a c t i o n of p e r e h l o r a t e II with benzalphenylhy4vazine in DMF gives an e a s i l y r e s i n i f i e d substance
that reddens on standing, does not contain chlorine, and could not be purified. The r e a c t i o n in glacial acetic
acid goes to N 60% completion after 5 h to give N - a n i l i n o - 2 , 4 , 6 - t r i p h e n y l p y r i d i n i u m p e r c h l o r a t e .
The r e a c t i o n s under consideration apparently p r o c e e d via the s a m e m e c h a n i s m as in the case of a z o -
methines, but ill DMF go to completion in the p r e s e n c e of a twofold excess of the "ylid-like~ compounds;the
excess amount is probably n e c e s s a r y to tie up the p e r e h l o r i c acid.
In the r e a c t i o n of p e r c h l o r a t e II with urea and thiourea, the r e s o n a n c e s t r u c t u r e s of which can also
be c o n s i d e r e d to be of the ylid type, 2,4,6-triphenylpyridine is f o r m e d :

'~H 5 C6H3

i?" +o++,
CIO~

X - O Or S

Addition at the C =S bond does not occur in the case of thiourea. The r e a c t i o n with phenyl isothiocya-
ante also p r o c e e d s p r e f e r a b l y at the C =N group, and t h i o p y r y l i u m salts t h e r e f o r e cannot be obtained via
this path.

903
 T A B L E 1. A z o m e t h i n e s of H e t e r o c y c l i c A m i n e s (V)
Found, % I_Calculated, %
rap, *C
_

Corn - Empirical formula

pound (from r
ethanol) H I C H iN
Va 143~6 C~H~N,O~ 58,6 4,7 17,3 58,8 4,5 17,1 82
Vb 108 CI~HgN30~'H~O 58.7 4,8 16,9 58,8 4,5 17,1 75
Vc 253* C~aH~oN~O: 63,7 4,2 20,9 63,2 3,8 21,0 75
Vd 178 C:3H:zN~O~ 64,2 4,7 20,4 64,3 4,3 20,0 70
Ve 178~1 C~H~4N40~ 65,4 5,0 19,2 65,3 4,8 19,0 68
Vf 118 C23H28N402 70,4- 7,6 14,6 70,4 7,2 14,3 78
Vg 227 C~7H~6N40~ 66,3 5,1 18,7 66,2 5,2 18,2 70

* From xylene.

T A B L E 2. P y r i d i n i u m P e r c h l o r a t e s (III, VI, a n d VIII)

Found, % Catcul_a_t_ed, %
Corn - Empirical formula l
pound rap, *C* C H CI N C H C1 N .O

IIIa 265--26612 C29H22C1NO4 72,3 72,0 80

Illb 24412 CaoH24CINO4 72,6 72,3 90
Illc 25312 C3~H~4CINO4 72,5 72,3 80
Illd 241~2 C~oHa4C1NO5 69,9 70,1 90
IIIe 242 C29H2~C1N2OG 65,3 65,8 82
Via 230--231 C2sH21CIN204 59,7 69,4 89
Vlb 300--301 C2sH21C1N204 59,4 69,4 83
Vie 255 C3oH~C1N304 59,0 68,8 65
VId 144--146 C31H24C1N304"H~O 67,2 66,9 70
Vie: 140--142 C~H~6CIN304"H20 67,8 67,4 94
Vlf 103--105 C39H4oCIN304 72,4 72,0 47
VIg 3OO C3~H~sCINaO4 70,2 70,0 75
Villa 145--1503 C31Ha4CINO4 72,8 73,0 88
VIIIb! 145--150 C32H~6C1NO4 73,0 73,4 83
VIIlc 168--170 C34H~7C1N406"H20 54,0 63,7 49
VIlld 213--214 C3~H29CIN406 65,6 66,0 47

* The following s o l v e n t s w e r e u s e d to r e c r y s t a l l i z e the p r o d u c t s :

g l a c i a l a c e t i c a c i d (IIIa-c, V i a - b , VIg, and VIIId), e t h a n o l (IIId, e),
b u t a n o l (VIc), c h l o r o f o r m - e t h e r (VId, e, VIIIa-c), and m e t h a n o l (VID.

EXPERIMENTAL

The IR s p e c t r a of m i n e r a l oil s u s p e n s i o n s of the c o m p o u n d s w e r e r e c o r d e d with a U R - 2 0 s p e c t r o m -

eter.

The azomethines were obtained by refluxing alcohol solutions of equimolecular amounts of the alde-
hyde and amine for i-I0 h [I0] (Table I).
Reaction of Percblorate II with Azomethines. A 2.5-mmole sample of percblorate II was refluxedwith
3 mmole of azomethine in i0 ml of absolute DMF for 1 h. The addition of ether precipitated the solid re-
action product. However, if the product separated out as an oil, it was crystallized by the addition of water
(Table 2). The mother liquor formed a yellow-orange precipitate of benzaldehyde 2,4-dinitrophenylhydra-
zone with mp 235-236 ~
The reaction of Vli with azomethine proceeds similarly, except that a hydrazone was not formed in
the m o t h e r l i q u o r . T h e s t y r y l d e r i v a t i v e s (Table 2) w e r e p u r i f i e d b y two to t h r e e r e p r e c i p i t a t i o n s f r o m c o l d
solvents.

R e a c t i o n of P e r c h l o r a t e II with B e n z a l d o x i m e . A) A 0 . 5 1 - g (125 m m o l e ) s a m p l e of p e r c h l o r a t e II w a s
r e f l u x e d w i t h 0.3 g (2.5 m m o l e ) of b e n z a l d o x i m e in 3 ml of a b s o l u t e D M F for 2 h. The a d d i t i o n of a b s o l u t e
e t h e r p r e c i p i t a t e d the p e r c h l o r a t e of the s t a r t i n g b e n z a l d o x i m e , a f t e r w h i c h the m o t h e r l i q u o r was e v a p o -
r a t e d b y h e a t i n g i n vacuo (water a s p i r a t o r ) . The a d d i t i o n of a few d r o p s of alcohol c r y s t a l l i z e d out 0.32 g
(84%) of 2 , 4 , 6 - t r i p h e n y l p y r i d i n e w i t h mp 137 ~ ( f r o m alcohol) [13].

B) The r e a c t i o n w a s c a r r i e d out in 3 ml of g l a c i a l a c e t i c a c i d with the s a m e a m o u n t of r e a c t i o n s u b -

s t a n c e s for 5 h. C o o l i n g p r e c i p i t a t e d 0.31 g of s t a r t i n g p e r c h l o r a t e II. T h e e x c e s s s o l v e n t w a s r e m o v e d b y
v a c u u m d i s t i l l a t i o n (water a s p i r a t o r ) , a n d a few d r o p s of alcohol w e r e added to the cold r e s i d u e to give 0.07
g (18%) of 2 , 4 , 6 - t r i p h e n y l p y r i d i n e N - o x i d e with mp 184 ~ ( f r o m alcohol) [4]. IR s p e c t r u m : 1250 c m -1 (N-
oxide).

904
 The reaction of perchlorate II with benzalaz[ne was carried out as in method A, and the yield of 2,4,6-
triphenylpyr[dine was 82%.
N - A n i l i n o - 2 , 4 , 6 - t r i p h e n y l p y r i d i n i u m P e r c h l o r a t e . A 0.51-g (1.25 mmole) s a m p l e of p e r c h l o r a t e II
was refluxed with 0.49 g (2.5 mmole) of benzalphenylhydrazine in 5 ml of gtacial acetic acid for 5 h. Cool-
ing gave a b l a c k r e s i n o u s p r e c i p i t a t e , f r o m which 0.21 g of nnchanged p e r c h l o r a t e II was isolated a f t e r
t r e a t m e n t with ether and c h l o r o f o r m . The addition of ether to the c h l o r o f o r m solution p r e c i p i t a t e d 0.31 g
(50%) of g r e e n N - a n i l i n o - 2 , 4 , 6 - t r i p h e n y l p y r i d i n i u m p e r c h l o r a t e with mp 175 ~ (from c h l o r o f o r m - e t h e r ) .
Found: C 70.2; H 4.7; C1 7.0; N 5.7%. C29H23C1N2O4. Calculated: C 69.9; H 4.7; C1 7.1; N 5.6%.
Reaction of P e r c h l o r a t e II with Urea. A 2.04-g (5 mmole) s a m p l e of p e r c h l o r a t e II was refluxed with
0.3 g (5 mmole) of u r e a in 20 ml of absolute DMF for I h, a f t e r which the mixture was cooled, diluted with
w a t e r , and e x t r a c t e d with ether to give 1.44 g (93~) of 2,4,6-triphenylpyridine.
P e r c h l o r a t e II r e a c t e d s i m i l a r l y with thiourea, and the yield of 2,4,6-triphenylpyridine was 90~.
The r e a c t i o n of p e r c h l o r a t e II with phenyl isothiocyanate was c a r r i e d out under the s a m e conditions
but for 10 h. The mixture was then cooled and diluted with ether to give 1.72 g (73%) of 1 , 2 , 4 , 6 - t e t r a p h e n y l -
p y r i d i n i u m p e r e h l o r a t e with mp 265-266 ~ [2].

LITERATURE CITED
i. N.S. Zefirov, G. N. Dorofeenko, and T. M. Pozdnyakova, Zh. Organ. Khim., 9, 387 (1973).
2. G.N. Dorofeenko, I~. A. Zvezdina, and V. V. Derbenev, Zh. Organ. Kh[m., 9, 1079 (1973).
3. R. Wizinger and K. Wagner, Helv. Chim. Acta, 34, 2290 (1951).
4. J. Meisenheimer, Ber., 59, 1848 (1926).
5. E. Schmitz, Ber., 91, 1488 (1958).
6. A.T. Balaban and C. D. Nenitzescu, Ann., 74, 625 (1959).
7. G.N. Dorofeenko, E. I. Sadekova, and V. M. Goncharova, Khim. Geterots[kl. Soedin., 1308 (1970).
8. A.T. Balaban, Tetrahedron, 2_44,5059 (1968).
9. C. J. Overberger, J.-P. Anselme, and J. G. Lombard[no, Organic Compounds with Nitrogen-Nitrogen
Bonds, Ronald Press (1966).
i0. Yu. A. Zhdanov, I. A. Sadekov. A. D. Oarnovsk[i, and V. I. IViinkin, Inv. Vuzov, Ser. Khim., 8, 954
(1965).
ii. A.M. S[monov and A. F. Pzoharskii, 14him. Geterotsikl. Soedin., 203 (1965).
12. W. Dilthey and H. D[erichs, J. prakt. Chem., 144, 1 (1936).
13. G.N. Dorofeenko and S. V. Krivun, Zh. Obsheh. Kh[m., 34, 105 (1964).

905
SYNTHESIS OF 3-(p-METHOXYPHENYL)-
1,3-DIMETHYLSPIRO(INDOLINE-2,2'- [2H-1]-
BENZOPYRANS) AND INVESTIGATION
OF THE ELECTRONIC ABSORPTION SPECTRA
OF THEIR MEROCYANINE FORMS

M. A . Gal'bershtam and N. P. Samoilova UDC 541.145 : 547.752'814.1.07 : 543.422.6

P h o t o c h r o m i c indoline s p i r o p y r a n s containing a p - m e t h o x y p h e n y l substituent in the 3 - p o s i -

tion w e r e s y n t h e s i z e d , and the e l e c t r o n i c a b s o r p t i o n s p e c t r a of t h e i r m e r o c y a n i n e f o r m s
were measured.

In o r d e r to study the effect of substituents on the p h o t o c h r o m i c p r o p e r t i e s of 1 , 3 - d i m e t h y l - 3 - a r y l -

substituted indoline s p t r o p y r a n s [1] we s y n t h e s i z e d s o m e 3 - ( p - m e t h o x y p h e n y l ) - l , 3 - d i m e t h y l s p i r o ( i n d o l i n e -
2 , 2 ' - [2H-1]benzopyrans) (IIa-c) f r o m 1 , 3 - d i m e t h y l - 3 - ( p - m e t h o x y p h e n y l ) - 2 - m e t h y l e n e t n d o l i n e I, which was
obtained b y the F i s c h e r r e a c t i o n f r o m 3 - ( p - m e t h o x y p h e n y l ) - 2 - b u t a n o l [2] and a - m e t h y l p h e n y l h y d r a z t n e .
Compound I w a s subjected, without isolation, to r e a c t i o n with the a p p r o p r i a t e n i t r o s a l i c y l a l d e h y d e s .

OCH s
I. C~ItsN(CHa)N H~.
2. Z n C I ,
CH2 U
CHCOCH 3
[
..;-%_?,
cH~ R
I II a - c

II a R=II; b R=Br; C R=OCH 3

Molecular p e a k s with m / e 414 and 444, r e s p e c t i v e l y , a r e o b s e r v e d in the m a s s s p e c t r a of s p i r o p y r a n s

IIa, c. Two m o l e c u l a r p e a k s at m / e 494 and 492, which c o r r e s p o n d to molecules containing 81Br and ?9Br
isotopes, a r e c h a r a c t e r i s t i c for s p i r o p y r a n IIb, which contains a b r o m i n e atom. P e a k s of f r a g m e n t s f o r m e d
b y splitting out of one, two, and t h r e e methyl groups f r o m the m o l e c u l a r ion a r e also o b s e r v e d in the s p e c -
t r a . The m o s t intense p e a k in the m a s s s p e c t r a of the investigated s p i r o p y r a n s is the p e a k with m / e 251,
which c o r r e s p o n d s to the [ndoltne f r a g m e n t
OcH3

,,
CH 3

role 25J

Spiropyrans IIa-c have photochromic properties at room temperature: colorless solutions in toluene
and dioxane take on a blue-azure color on irradiation with UV light that gradually disappears after irra-
diation is discontinued. Alcohol solutions of spiropyrans IIa-c are red-violet, and the intensity of their col-
oration increases during UV irradiation and decreases on irradiation with the total light of an incandescent
lamp.
S c i e n t i f i c - R e s e a r c h Institute of Organic I n t e r m e d i a t e s and Dyes, Moscow. T r a n s l a t e d f r o m Khimiya
G e t e r o t s i k l i c h e s k i k h Soedineni[, No. 8, Pp. 1041-1043, August, 1974. Original a r t i c l e s u b m i t t e d August 21,
1973.

9 76 Plemtm Publishing Corporation, 22 7 West 1 7th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retHel,al s3,stem, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or othenvise, without writteH permissiolt o f the publisher. A cop), o f this article is available from the publisher for S15. 00.

906
 TABLE 1. A b s o r p t i o n S p e c t r a of the M e r o c y a n t n e F o r m s of S p t r o -
pyrans IIa-c

CO1TI -
I band II band
Solvent
pound ~.,,ax,mmI 8max ~ rn a x ,mFFi 8max

lla Alcohol 537 32000 0,43 363 15000 0,38

IIa Dioxane 585 36000 0,45 367 17000 0,33
IIa Toluene 587 71000 0,83 374 31000 0,47
lib Alcohol 551 30000 0,41 370 21000 0,52
IIb Dioxane 584 36000 0,49 375 19000 0,34
IIb Toluene 591 46000 0,55 379 25000 0,40
IIc Alcohol 552 21000 0,35
IIc Dioxane 595 55000 0,83 397 38000 0,61
IIc Toluene 597 67000 0,67 399 27000 0,46

* This band could not be m e a s u r e d b e c a u s e of the low s e n s i t i v i t y

of the solution to the effect of i r r a d i a t i o n in the UV and v i s i b l e
region.

F r o m the s p e c t r a l data (Table 1) it can be c o n c l u d e d that the e l e c t r o n i c a b s o r p t i o n s p e c t r a of the c o l -

o r e d f o r m s of the s p i r o p y r a n s a r e s u b j e c t to the r e g u l a r i t i e s c h a r a c t e r i s t i c for m e r o c y a n i n e dyes. They
contain two n o n o v e r l a p p e d s y m m e t r i c a l bands at 320-700 nm. On p a s s i n g f r o m alcohol to dioxane and
toluene t h e i r m a x i m u m a r e s h i f t e d b a t h o c h r o m i c a l l y by 30-50 n m for the band at 540 n m and by 4-10 n m
for the m a x i m u m at 360-370 nm. Thus, n e g a t i v e s o l v a t o c h r o m i s m is c h a r a c t e r i s t i c for the c o l o r e d f o r m s
of the s p i r o p y r a u s o b t a i n e d in this study [4]. As in the c a s e of 3 - p h e n y l - s u b s t i t u t e d compounds [1], r e p l a c e -
ment of the h y d r o g e n a t o m in the 8 ' - p o s i t i o n by a b r o m i n e a t o m or a methoxy group for s p i r o p y r a n s I I a - c
l e a d s to an a p p r e c i a b l e b a t h o c h r o m i c shift of both b a n d s . A c o m p a r i s o n of the data obtained in this study
with the X max v a l u e s for 1 , 3 , 3 - t r i m e t h y l - 6 ' - n t t r o s p t r o ( i n d o l i n e - 2 , 2 ' - [2H-1]benzopyran) and a l s o with the
v a l u e s for 3 - p h e n y l - s u b s t i t u t e d compounds [1] m a k e s it p o s s i b l e to conclude that r e p l a c e m e n t of a methyl
group by an a r y l group does not l e a d to a s u b s t a n t i a l change in the s p e c t r a of the p h o t o c o l o r e d f o r m s . The
p o s i t i o n of the a b o s r p t t o n bands does not change in dtoxane, a b a t h o c h r o m i c shift is o b s e r v e d in alcohot,
while a h y p s o c h r o m i c shift is o b s e r v e d in toluene; the shift in the bands on p a s s i n g f r o m alcohol to toluene
for 3 - a r y l - s u b s t i t u t e d compounds is s o m e w h a t l e s s than in the c a s e of 3 - m e t h y l - s u b s t i t u t e d s p i r o p y r a n s .

Thus, m o d i f i c a t i o n of the p r o p e r t i e s of the s p t r o p y r a n s by i n t r o d u c t i o n of the n e c e s s a r y s u b s t i t u e n t s

into the 3 - p o s i t i o n is p o s s i b l e without a s u b s t a n t i a l change in the s p e c t r a l c h a r a c t e r i s t i c s of the p h o t o c o l -
ored forms.

EXPERIMENTAL
The measurement of the absorption spectra of solutions of the spiropyrans, calculation of the extinc-
tion coefficient of the colorless and colored forms at various wavelengths, and approximation of the data
obtained by means of Gaussian curves with an M-220 computer were carried out as described in [3]. The
m a s s s p e c t r a w e r e m e a s u r e d with a MATCH-6 s p e c t r o m e t e r at an ionization p o t e n t i a l of 70 eV.

1 , 3 - D t m e t h y l - 3 - ( p - m e t h o x y p h e n y l ) - 2 - m e t h y l e n e i n d o l i n e (I). A m i x t u r e of 17.8 g (0.1 mole) of

3 - ( p - m e t h o x y p h e n y l ) - 2 - b u t a n o n e [2] and 12.2 g (0.1 mole) of a - m e t h y l p h e n y l h y d r a z t n e was h e a t e d on a b o i l -
i n g - w a t e r bath for 24 h, a f t e r which it was cooled, 123 ml of a b s o l u t e ethanol and 135.3 g of fused zinc c h l o -
r i d e w e r e added, and the m i x t u r e was h e a t e d for a n o t h e r 1.5 h. It was then cooled and d e c o m p o s e d with 150
ml of 30~ s o d i u m h y d r o x i d e solution and e x t r a c t e d with e t h e r . The e x t r a c t was d r i e d o v e r p o t a s s i u m h y -
d r o x i d e , the e t h e r was e v a p o r a t e d , and the r e s i d u e was v a c u u m d i s t i l l e d to give 8 g (30%) of 1 , 3 - d i m e t h y l -
3 - ( p - m e t h o x y p h e n y l ) - 2 - m e t h y l e n e i n d o l i n e as a yellow oil with bp 150-160 ~ (12 mm); the p r o d u c t was r a p i d l y
o x i d i z e d on s t o r a g e .
S p i r o p y r a n s I I a - c . An 8 - m m o l e s a m p l e of the a p p r o x p r i a t e n i t r o s a l t c y l a l d e h y d e in 10 ml of ethanol
w a s r e f l u x e d with 7.8 m m o l e of 1 , 3 - d i m e t h y l - 3 - ( p - m e t h o x y p h e n y l ) - 2 - m e t h y l e n e i n d o l t n efor 2 h. The s o l i d
m a t e r i a l was r e m o v e d by f i l t r a t i o n aud c r y s t a l l i z e d f r o m alcohol. S p i r o p y r a n IIa: with mp 186-187 ~ was
o b t a i n e d in 46~ y i e l d . Mass s p e c t r u m , m / e : 414, 399, 384, 369, and 251. Found: C 72.3; H 5.3; N 6.7%.
C25H22N20 4. C a l c u l a t e d : C 72.4; H 5.3; N 6.7%. Compound Hb with mp 146-147 ~ was obtained in 45% yield.
Mass s p e c t r u m , m / e : 494, 492, 379, 377, 3 6 4 , 3 6 2 , 349, 347, and 251. Found: C 61.0; H 4.4; N 5.8%.
C25H2IBrN20 4. C a l c u l a t e d ~- C 60.8; H 4.3; N 5.7%. Compound IIe with mp 192-193 ~ was o b t a i n e d in 33%
y i e l d . Mass s p e c t r u m , m / e : 444, 429, 414, 399, and 251. Found: C 70.4; H 5.5; N 6.0%. C26H2r 5.
Calculated~ C 70.3; H 5.4; N 6.3%.

907
 LITERATURE CITED
1. M. A. Gal'bershtam and N. P. Samofiova, Kh[m. Geterotsikl. Soedia., 1209 (1973).
2. E. Okerberger and H. Gacner, J. Amer. Chem. Soc., 8__00,4556 (1958).
3. M. A. Gal'bershtam, L. M. M[kheeva, and N. P. Samoilova, Kh[m. Geterots[kl. Soedia., 1534 (1972).
4. A. I. Kipriaaov, Usp. Kh[m., 29, 1336 (1960).
5. E. V. Braude and M. A. Gal'bershtam, Khim. Geterotsikl. Soedin., 943 (1974).

908
REACTION OF SOME AMINES WITH UNSATURATED
N-AC YLBENZOXAZOLONES

N. A. Alter, R. Razakov, UDC 547.787.3 +542.951.1

N. D. Abdullaev, and Ch. Sh. Kadyrov

It is shown that the addition of aniline proceeds at the c a r b o n - c a r b o n double bond of N-

a c r y l o y l - , N - c h l o r o a c r y l o y l - , and N - m e t h y l a c r y l o y l b e n z o x a z o l o n e s . The bastc[ty of the
amine has a substantial effect on the c o u r s e of the r e a c t i o n with various amines. T r a n s -
amidatton of the acryloyl r e s i d u e o c c u r s with s t r o n g l y basic amines.

We have previously shown [i] that benzoxazolone (I) adds readily to N-acryloylbenzoxazolone (IIa).
The present paper is devoted to a study of the addition of various nucleophiltc reagents to unsaturated N-
acylbenzoxazolones. The facts available in the literature indicate that nucleophilie addition of the base to
the carbonyl group of oxazolone I with ring opening occurs in the reaction of amines [2] and hydrazines [3]
with var io us benzoxazolones.
On the basts of [1, 2], it may be a s s u m e d that addition to the c a r b o n - c a r b o n double bond (formation
of IVa), to the carbonyl group of the a c r y l o y l r e s i d u e , or to the C =O group of the oxazole ring with s u b s e -
quent cleavage of either the c a r b o n - o x y g e n or c a r b o n - n i t r o g e n bond is possible in the r e a c t i o n of aniline
(III) with IIa.

~ N--CO--C~Cn~ + C6HsNH 2 r~--N--cO--CH_CH2_NHC6H$

II III IV a - c

IVa R=H; bR=cHa; cR=CI

It was shown on the basts of the s p e c t r a l data that the first of the addition paths indicated above f o r -
mation of IVa) is r e a l i z e d .
The signals f r o m the a r o m a t i c ring protons in the PMR s p e c t r u m of IIa appear as multiplets at 6.86
ppm (G-H, 6-H, 7-H) and 7.64 ppm (4-H). The shift of the 4-H signal to weak field is due to the s t e r i c de-
shielding effect of the C =O group of the aeryloyl residue. The equivalence of all of the a r o m a t i c protons
of I (stnglet at 6.83 ppm) may be a confirmation of this. The signals f r o m the protons of the a c r y l o y l r e s t -
due of IIa a r e found at 7.21 ppm ( - C H = , JCH+CH2=17.3 and 10.5 Hz) and 6.34 and 5.79 ppm (=CH2). As
one should have expected, on passing f r o m IIa to IVa, one o b s e r v e s that the P ~ s p e c t r u m of the latter
contains, tn place of the vanished signals from the vinyl protons, a two-proton triplet at 3.35 ppm and an
unresolved multiplet with a chemical shift of 3.66 ppm, which are affiliated, respectively, with the protons
of the COCH2CH 2 and CH2-CH2-N fragments. S[nglets from the C6H 5 and NH protons are found at 7.16 and
8.67 ppm, respectively. The parameters of the signals of the aromatic protons of the benzoxazolone ring
for IVa are the same as those for Ha.
The absence of an OH- group was confirmed by qualitative reaction with FeCI 3.
Compound IVa was also synthesized by alkylatton of amine III with N-(fl-chloroprop[onyl)benzoxazo-
lone tn the presence of K2CO3; the products obtained by the two methods were identical.

Institute of the C h e m i s t r y of Plant Substances, Academy of Sciences of the Uzbek SSR, Tashkent.
T r a n s l a t e d f r o m Khimiya Geterotsikliehesktkh Soedinenit, No. 8, pp. 1044-1048, August, 1974. Original
a r t i c l e submitted August 30, 1973.

9 Plenum Publishing Corporation, 227 West 17th Street, New York, iV.. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfihning,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

909
 The p r e s u m e d product of the r e a c t i o n with opening of the h e t e r o r i n g s - 2-(acryloylamino)phenyl N-
p h e n y l c a r b a m a t e (VI) - w a s synthesized by acylation of o-aminophenol with a c r y l o y l chloride and subsequent
t r e a t m e n t of the r e s u l t i n g N - a c r y o y l - o - a m i n o p h e n o l (V) with phenyl isocyanate.
The PMII s p e c t r u m of c a r b a m a t e VI contains two b r o a d singlets at 7.78 and 8.49 ppm, which a r e r e -
lated to the protons of the NH groups. The signals of equivalent a r o m a t i c protons are found at 6.93 ppm.
The multiplets f r o m the protons of the - C H = a n d =CH 2 groups r e s o n a t e at 5.61 and 6.11 ppm, r e s p e c t i v e l y .
It should be noted that the use of 2 moles of aniline per mole of Ha does not promote the r e a c t i o n with
opening of the h e t e r o r i n g , i.e., addition product IVa was isolated in quantitative yield in this case also.
Thus, nucleophilic addition of aniline to the double bond of the acryloyl r e s i d u e of IIa occurs in the c a s e s
p r e s e n t e d above. The double bond in IIa is evidently p o l a r i z e d , and this facilitates the addition of a proton.
In addition, it is possible that the acyl group d i r e c t l y bonded to the nitrogen atom s t e r i c a l l y hinders attack
on the C =O r e a c t i o n center in the oxazolone ring by the base.
In o r d e r to c o m p a r e the r e a c t i v i t i e s , we c a r r i e d out reactions of benzoxazolone I with a c r y l a m i d e and
acrylanilide. We were unable to a c c o m p l i s h these r e a c t i o n s under the conditions developed for the addition
of I to various N - a c r y l o y l b e n z o x a z o l o n e s . More s e v e r e conditions and the use of a catalyst were r e q u i r e d
for the synthes is of N- (fl-carboxyethyl)benzoxazolone amide (VII) and N- (fl-carboxyethyl)benzoxazolone
anilide (VIII). The s t r u c t u r e of amide VIH was c o n f i r m e d by alternative s y n t h e s i s , for which N-benzox-
a z o l o n y l - f l - p r o p i o n y l chloride was used.
Various b a s e s did not add to N - ~ - m e t h a c r y l o y l b e n z o x a z o l o n e (IIb) under the above r e a c t i o n condi-
tions, and s t a r t i n g I and Ha were r e c o v e r e d . A CH 3 group introduced into the 3-position, in addition to its
+ I effect, also markedly shields the double bond, i.e., additional s t e r i c interactions of the CH 3 group with
the r e a c t i n g molecule of I a r e a p p a r e n t l y p o s s i b l e in the t r a n s i t i o n state.
When we c a r r i e d out the r e a c t i o n of lib with aniline, we were able to obtain N - ( a - m e t h y l - f i - p h e n y l -
aminopropionyl)benzoxazolone (IVb, R =CH3).
Singlets f r o m the protons of CH 3 and 2 groups are found at 1.73 and 5.37 ppm, r e s p e c t i v e l y , in the
PMI~ s p e c t r u m of IIb. Multiplets with a signal intensity ratio of 3 : 1, which are found at 6.90 and 7.62 ppm,
are affiliated with the 5-H, 6-H, 7-H, and 4-H protons. However, in the case of IVb the signal of the
methyl group at 1.13 ppm is a doublet, and, in addition, signals r e l a t e d to the following groups appeared in
place of the absent singlet f r o m the CH 2 group (in the s p e c t r u m of IIb): - C - C H 2 - N - ( 3 . 5 9 p p m ) , - C O - C H -
(4.06 ppm), NH (8.60 ppm), and C6H 5 (7.12 ppm). Signals f r o m 4-H and the r e m a i n i n g a r o m a t i c protons are
found at 7.62 and 6.90 ppm, r e s p e c t i v e l y .
The mass s p e c t r u m of IVb (R =CH3) completely confirms the a s s u m e d s t r u c t u r e and is analogous to
the mass s p e c t r u m of IVa.
It was a s s u m e d that, in contrast to the addition r e a c t i o n p r e s e n t e d above, the addition of aniline to
N - ( ~ - e h l o r o a c r y l o y l ) b e n z o x a z o l o n e (IIc) should p r o c e e d more readily, i.e., the e l e c t r o n - a c c e p t o r chlorine
substituent additionally intensifies the polarization of the c a r b o n - c a r b o n bond. In addition to this, the in-
troduced group could p r o m o t e the addition of base also to the C =O group of the f i v e - m e m b e r e d ring of IIc,
inasmuch as the n i t r o g e n - c a r b o n bond in the oxazolone ring is weakened in this case. A product of addition
to the double b o n d - N-(~-chloro-f~-phenylaminopropionyl)benzoxazolone ( I V c ) - w a s obtained in quantitative
yield as a r e s u l t of r e a c t i o n of unsaturated IIc with aniline. This is in good a g r e e m e n t with the r e s u l t s [1]
that we obtained for the addition of I to IIc.
The protons of the COCH(C1)CH2N f r a g m e n t in the PMR s p e c t r u m of IVc f o r m an A2X s y s t e m with
the following chemical shifts: doublet at 3.92 ppm (CH2) and triplet at 5.70 ppm (CO-CH). Multiplets f r o m
the (5-7)-H and 4-H protons are found at 6.93 and 7.63 ppm. The singlet at 7.22 ppm is affiliated with the
equivalent protons of the phenyl group.
The mass s p e c t r u m of IVc contains peaks of chlorine-containing ions with m / e 316 (M +, 15%), 154
(6%) and of c h l o r i n e - f r e e ions with m / e 146 (12%), 135 (15%), 118 (7%), 106 (100%), 79 (9%), and 77 (10%).
A c h a r a c t e r i s t i c feature of the mass s p e c t r a of IVa-c is the maximum intensity of the peak of the a m m o -
nium ion with m / e 106 and the p r e s e n c e in t h e m of the peak of a benzoxazolone (I) ion radical.
However, the formation of ions with m / e 106 and 135 is excluded in the case of the alternative s t r u c -
t u r e s with opening of the oxazolone ring. The s t r u c t u r e s and pathways for the formation of the most c h a r -
a c t e r i s t i c fragments in the mass s p e c t r a of I V a - c are p r e s e n t e d in the s c h e m e below:

910
 .+

a-C ~ C6Hs--NH~CH2
~O/C~ O a C IVa-c

rn/e135 J ~ ~ m/e ,06

f~.l__,~_co_~.=~.~] co.~+ c~.~.~l

~'~J~'-o ~ c = ~ ~/e 77 ~/~ 93
role 189

~__CH=CH2 --C|
&q/e 55 m/e 154 role 118

The nature of substituent R introduces its own specifics into the mass spectrum. For example, an
analog of the ion with m/e 189 that is observed for IVa is absent in the spectra of IVb, c, and this is pos-
sibly associated with steric factors. An ion peak with m/e 154, the analog of which is absent in the spectra
of products IVa, b, appears in the spectrum of IVc.
Reaction of IIa with diethylamine under various conditions gives benzoxazolone I in high yields. The
transamidation reaction below apparently occurs in this case
O
I}
H a + (C2Hs)2NH ~ I + Cfl~=CHCN(C2H5) 2

It seemed that the basicity of the amine plays the deciding role. For this reason, we carried out the
reaction of IIa with the bulky but weakly basic diphenylamine. In fact, we found that diphenylamine does not
add to Ha, and starting IIa is recovered from the reaction mixture.

EXPERIMENTAL

The mass spectra were recorded with an MKh-1303 spectrometer at 100 ~ and an ionizing electron
energy of 40 eV; the m/e values of the chlorine-containing fragments were taken with respect to C135. The
PMR spectra of trifluoroacetie acid solutions of the compounds were recorded with a JEOL 4H-1O0 spec-
trometer with hexamethyldisiloxane (HMDS) as the internal standard. The chemical shifts are presented
on the 6 scale. The LR spectra were recorded with a UR-20 spectrometer. Thin-layer chromatography
(TLC) was carried out on a fixed layer of silica gel (Silufol) in benzene-alcohol (21:2).
N-(~-Phenylaminopropionyl)benzoxazolone (IVa). A) An alcohol solution of 0.95 g of freshly distilled
aniline was added slowly with stirring and cooling to 0 deg to a solution of 1.9 g (0.01 mole) of IIa in abso-
lute alcohol. Stirring was continued at 0 deg for 30 rain and subsequently at room temperature for 30 men.
The precipitated crystals were removed by filtration, and an additional amount of IVa was isolated from
the filtrate to give a total of 2.56 g (91.4%) of a product with mp 138 ~ (from alcohol). Mass spectrum: M +
with m/e 283 (30%); peaks of fragments with m/e 189 (7%), 147 (8%), 135 (i0%), 106 (i00%), 93 (15%), 77
(8%), and 55 (60%). Found: N 9.4%. CiGHI4N20 ~. Calculated: N 9.9%. Compound IVa reacted with hydro-
ehlorie acid (I : i) to give a hydrochloride with mp 197-200 ~
B) An acetone solution of 1.12 g (0.005 mole) of N-(/~-chloropropionyl)benzoxazolone was added slowly
to an aqueous acetone solution of 0.47 g (0.005 mole) of freshly distilled aniline and 0.42 g of Na2CO ~. Stir-
ring was continued at room temperature for 30 min, after which the mixture was stirred on a boiling-water
bath for 1 h. The solvent was evaporated, and the resulting precipitate was washed with i00 ml of water,
dried, and reerystallized from alcohol to give 0.98 g (70%) of a product with mp 137-138 ~ (alcohol) and Rf
0.9. No melting-point depression was observed for a mixture of this product with the product obtained by
method A.
M-(a-Methyl-~-phenylaminopropionyl)benoxazolone (IVb). Reaction of I g (0.005 mole) of IIb via
method A gave 0.6 (40%) of a product with mp 124-126 ~ (from ethyl acetate). Mass spectrum: M-~ 296 (70%),
161 (6%), 135 (I0%), 106 (i00%), 93 (10%), 77 (I0%), and 69 (15%).
N-(a-Chloro-~-phenylaminopropionyl)benzoxazolone (IVe). Similarly, 1.15 g (0.005 mole) of IIe gave
a quantitative yield of IVc with mp 140 ~ (from alcohol).
Reaction of IIa with Diethylamine. Under the conditions of method A, 1.9 g (0.01 mole) of Ha and 0.75
g (0.01 mole) of diethylamine gave 0.72 g (53%) of benzoxazolone I with mp 130-133 ~ (mp 135-137 ~ [I]) and
Rf 0.32.

911
 Benzoxazolone I was also obtained in high yield when the r e a c t i o n was c a r r i e d out in n-butanol-ethanol
or when the components w e r e r e f l u x e d in isopropyl alcohol.
Starting Ira (Rf 0.76) was r e c o v e r e d f r o m the r e a c t i o n of IIa with diphenylamine under the conditions
of method A or at 45-50~ the f o r m a t i o n of I was not o b s e r v e d .
N - A c r y l o y l - o - a m i n o p h e n o l (V). A solution of 2 g (0.02 mole) of Na2CO 3 in 10 ml of w a t e r and 20 ml of
acetone was added to an acetone solution of 4.36 g (0.04 mole) of o-aminophenol, a f t e r which 3.7 g (0.04
mole) of a c r y l o y l chloride was added with vigorous s t i r r i n g and cooling. S t i r r i n g was continued at r o o m
t e m p e r a t u r e , a f t e r which the m i x t u r e was heated on a b o i l i n g - w a t e r bath for 30 min and allowed to stand
overnight. It was then acidified slightly with HC1 (1 : 1), and the p r e c i p i t a t e d product was r e m o v e d by f i l t r a -
tion and r e c r y s t a l l i z e d f r o m w a t e r with decolorization by activated c h a r c o a l . The yield of V with mp 118-
119 ~ (from benzene) was 2.4 g (32.3%). The product was quite soluble in acetone and alcohols, but only
slightly soluble in n - h e x a n e and p e t r o l e u m ether. Found: N 8.5%. C9H~NO. Calculated~ N 8.6%.
2-(Acryloylamino)phenyl N - P h e n y l c a r b a m a t e (VI). A m i x t u r e of 0.8 g (0.005 mole) of V, 0.5 g (0.004
mole) of phenyl i s o c y a n a t e , and a v e r y s m a l l amount of hydroquinone was r e f l u x e d in 8 ml of m - x y l e n e for
12 h, a f t e r which the mixture was allowed to stand overnight. The r e s u l t i n g p r e c i p i t a t e was r e m o v e d by
f i l t r a t i o n and r e c r y s t a l l i z e d f r o m ethyl a c e t a t e to give 0.34 g (24.2%) of a product with mp 152-154 ~ Found:
N 10.1%. CI6HI4N203. Calculated: N 9.9%.
LR spectrum of V: 3410 (OH-), 3130-3170 (NH), 1660 (am[de C =O), and 980 cm -I (terminal double
bond}. A split absorption band was observed in the spectrum of VI in the region of the NH stretching vibra-
tions at 3300-3400 em -I.
N-(fl-Carboxyethyl)benzoxazolone Amide (VII). A mixture of 6.75 g (0.05 mole} of I and 7.1 g (0.i
mole) of acrylamide in 50 ml of dry dioxane and 0.6 g of finely ground KOH was heated at 80 ~ for 2 h, after
which it was cooled to room temperature, and the solvent was partially removed. The residue was treated
with 2% aqueous KOH (300 ml), and the insoluble material was removed by filtration and dried to give 2.4
g (23.3%) of a product with mp 170-171 ~ (from alcohol).
N-(fl-Carboxyethyl)benzoxazolone Anilide (VIII). A method similar to the preceding method was used
to obtain 0.6 (42.5%) of a product with mp 157-159 ~ Found~ N 9.9%. Ci6HitN203. Calculated: N 9.9%.

LITERATURE CITED
I. N. A. Aliev and N. N. Mel'nikov, in: Chemical Agents for the P r o t e c t i o n of Plants [in Russian], Vol.
4, Moscow (1973), p. 61.
2. V. Kalcheva and D. Simov, Khim. G e t e r o t s i k l . Soedin., 1333 (1971).
3. S. D. Danilov, A u t h o r ' s A b s t r a c t of M a s t e r ' s D i s s e r t a t i o n , Moscow (1973).

912
SYNTHESIS AND LUMINESCENCE PROPERTIES
OF ANHYDRIDES AND N-PHENYLIMIDES
OF SUBSTITUTED 4-(5-PHENYL-2-OXAZOLYL)-
NAPHTHALIC ACIDS

B . M. K r a s o v i t s k i i , S. E. Kovalev, UDC 547.787.2'828'83.07:535.37:543.422.6

a n d V. M. S h e r s h u k o v

Anhydrides and N-phenylimides of 4 - ( 5 - p h e n y l - 2 - o x a z o l y l ) n a p h t h a l i c acids with various s u b -

stituents in the p a r a position of the phenyl r i n g w e r e synthesized. E l e c t r o n - d o n o r s u b s t i t u -
ents, p a r t i c u l a r l y the dimethylamino group, induce an a p p r e c i a b l e l o n g - w a v e shift of the a b -
s o r p t i o n m a x i m a and the l u m i n e s c e n c e due to t h e i r interaction with the earbonyl group of the
p e r i - a n h y d r i d e grouping. A l a r g e Stokesian shift and a high p h o t o h m i n e s c e n c e quantum
yield a r e c h a r a c t e r i s t i c for the d i m e t h y l a m i n o - s u b s t i t u t e d anhydrides.

The union of mutually conjugated 2 , 5 - d l a r y l o x a z o l e and naphthalic anhydride groupings has led [1-3]
to the p r e p a r a t i o n of Ia (R =H), which a b s o r b s and e m i t s light o v e r a c o n s i d e r a b l y l o n g e r - w a v e region than
each of the indicated f r a g m e n t s of its molecule.
It is known [4, 5] that the a r y l groups in 2 , 5 - d i a r y l o x a z o l e s and 2 , 5 - d i a r y l - l , 3 , 4 - o x a d l a z o l e s interact
with one another b e c a u s e of the pronounced e l e c t r o n - a c c e p t o r p r o p e r t i e s of the h e t e r o r i n g s . The l a r g e dif-
f e r e n c e in the s p e c t r a l c h a r a c t e r i s t i c s of 2 - ( ~ - n a p h t h y l ) - 5 - p h e n y l o x a z o l e and phenyloxazolylnaphthalic an-
hydride indicates that the e l e c t r o n - a c c e p t o r p r o p e r t i e s of the h e t e r o r i n g in the molecules of the l a t t e r un-
der the influence of the m a r k e d l y a c c e p t o r anhydride grouping play a c o n s i d e r a b l y s m a l l e r r o l e in the d i s -
tribution of the e l e c t r o n density than in molecules of unsubstituted 2 , 5 - d l a r y l o x a z o l e s . N e v e r t h e l e s s , the
e l e e t r o n - a c c e p t o r c h a r a c t e r of the h e t e r o r t a g does r e t a i n a c e r t a i n value, inasmuch as an analogous c o m -
pound that contains a s t r o n g e r e l e c t r o n a c c e p t o r - the oxidiazole ring - a b s o r b s light and l u m i n e s c e s o v e r
a s h o r t e r - w a v e region of the s p e c t r u m [2].
We have s y n t h e s i z e d I b - f with v a r i o u s substituents in the p a r a position of the phenyl r i n g in o r d e r to
follow the effect of the e l e c t r o n i c nature of the substituents on the optical c h a r a c t e r i s t i c s of the compounds
obtained (Table 1). The s y n t h e s i s was a c c o m p l i s h e d by condensation of 4 - c h l o r o c a r b o n y l n a p h t h a l i c anhy-
dride [6] with substituted w - a m i n o a c e t o p h e n o n e s and subsequent dehydration of the i n t e r m e d i a t e s .

p_RC(H4COCH2NH2+ Ct_OC_~._CO~o~ -HCI p.RC6H4COCH2NH_OC_~/

~ x)_CO~POCl_
0 -H~O

~ ,.=0..,
~ CO/ -H20

[ a-f II a - f

All-Union S c i e n t i f i c - R e s e a r c h Institute of Single C r y s t a l s , Scintillation M a t e r i a l s , and U l t r a p u r e

Chemical Substances, K h a r ' k o v . T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 8, pp. 1049-
1052, August, 1974. Original a r t i c l e s u b m i t t e d October 15, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15. 00.

913
 The halogen atoms, like the nitro group, cause a b a r e l y
noticeable h y p s o c h r o m i c shift of the K band. A different pat-
t e r n is o b s e r v e d when e l e c t r o n - d o n o r substituents are i n t r o -
duced. Even under the influence of a methoxy group, the max-
~Z i m u m of the long-wave band in the absorption s p e c t r u m of
toluene solution is shifted b a t h o c h r o m i c a l l y by more than 20
nm. This effect is s h a r p l y intensified when a p - d i m e t h y l a m i n e
group is introduced (AX = 74 am). The long-wave band in the
o,I r o-~ ~..~:1~b.. r o.3 c.,l ~ s p e c t r u m of If is a c h a r g e - t r a n s f e r band caused by electronic
interaction of the dimethylamino and carbonyl groups, which
are situated at opposite ends of the conjugation chain. Charge
t r a n s f e r is confirmed by a c o m p a r i s o n of the molecular dia-
GO ~O O0 b - b - t'~ MOO
g r a m s of Ia and If. The overall charge on the naphthalic anhy-
dride r e s i d u e in Ia in the ground state is - 0 . 1 1 2 e, while in the
f i r s t excited state it is - 0 . 1 9 7 e; the c o r r e s p o n d i n g overall
charges in If a r e , r e s p e c t i v e l y , - 0 . 0 2 5 and - 0 . 5 7 4 e [7]. Con-
sequently, when s t r o n g e l e c t r o n - d o n o r substituents are p r e s e n t
the mutual effect of oppositely c h a r g e d ends of the t e r m i n a l
groups proves to be more significant than the e l e c t r o n - a c c e p t o r
effect of the oxazole ring. A s i m i l a r principle was noted for
o= the c o r r e s p o n d i n g 1,3,4-oxadiazole derivatives [8].
One's attention is drawn to the l a r g e long-wave shift of
.<
LO the l u m i n e s c e n c e maxima under the influence of e l e c t r o n - d o n o r
s ubstituents, which r e a c h e s ~ 150 n m for d i m e t h y l a m i n o - s u b -
~O stituted derivatives. A l a r g e Stokesian shift, which attests to
O the considerable s t r u c t u r a l changes that it undergoes on p a s s -
ing to the excited state, is c h a r a c t e r i s t i c for If. In p a r t i c u l a r ,
2 " c o m p r e s s i o n , " which is p r o m o t e d by an appreciable i n c r e a s e
1 in the o r d e r of the bond connecting the h e t e r o r i n g with the
naphthalic anhydride r e s i d u e , is possible. The excited mole-
cule emits light, after which it exists in a more planar c o n f o r -
mation. The absolute photoluminescence quantum yield (V) of
b~ ~ t l ~1 I If intoluene t s m u c h higher than in the case of the other sub-
M
0
stituted phenyloxazolylnaphthalic anhydrides.
Condensation of anhydrides Ib-f with aniline gave N - p h e -
nylimides IIb-f. Compound IIa was p r e v i o u s l y described in [2,
O
[/1
3].
i = The absorption and lumkaescence s p e c t r a of toluene solu-
tions of the phenylimides differ only sl~ght.ly f r o m the s p e c t r a
e~ of the c o r r e s p o n d i n g anhydrides, although the luminescence
{D
ddo ~ dd maxima of II are shifted to the s h o r t - w a v e region; this is dis-
zzo~o ff~dd
1 ~=zzz umzzz played more distinctly in the case of the d i m e t h y l a m i n o - s u b -
stituted compounds.

d The quantum yield and the Stokesian shift of the dimethyl-

[/1
09 a m i n o - s u b s t i t u t e d phenylimide IIf in toluene are c o n s i d e r a b l y
O less than in the case of the c o r r e s p o n d i n g anhydride (Ib). This
~9
is apparently due to weakening of the e l e c t r o n - a c c e p t o r p r o p -
O~ O~ erties of the imide group as c o m p a r e d with the anhydride group
and, consequently, to weakening of its interaction with the di-
methylamino group.

N The l u m i n e s c e n c e maxima of toluene solutions of I - I I lie

6o over a b r o a d r a n g e and e n c o m p a s s the region f r o m the g r e e n
to the red. These compounds a b s o r b and emit light over a
l o n g e r - w a v e r e g i o n than the c o r r e s p o n d i n g 1,3,4-oxadiazole
derivatives [81.

914
 Because of the quenching effect of the nitro group, Id and lid do not luminesce.

EXPERIMENTAL
The absorption s p e c t r a of toluene solutions of the compounds w e r e m e a s u r e d with an SF-4A s p e c -
t r o p h o t o m e t e r . The l u m i n e s c e n c e s p e c t r a were r e c o r d e d with an apparatus consisting of a ZMR-3 m i r r o r
m o n o c h r o m a t o r , an FI~U-18 radiation detector, and an M-95 m i c r o a m m e t e r . P h o t o h m i n e s c e n c e was ex-
cited with an SVDSh-500 l a m p , f r o m the s p e c t r u m of which light with wavelength 365 n m was isolated by
means of a DMR-4 quartz m o n o e h r o m a t o r . The absolute l u m i n e s c e n c e quantum yields w e r e determined by
the method of equal absorption [9]. Toluene (ultrapure) was used as the solvent for the s p e c t r a l m e a s u r e -
ments.
4 - ( - A r y l - 2 - o x a z o l y l ) n a p h t h a l i c Anhydride (Ib-f). A 10% solution of sodium carbonate was added with
vigorous s t i r r i n g to a mixture of solutions of equimolecular amounts of 0.01 mole of 4 - c h l o r o c a r b o n y l naph-
thalic anhydride [6] in a 15-fold amount of benzene and w-aminomethyl aryl ketone hydrochloride in a 20-
fold quantity of water until the mixture was alkaline (pH ,~ 9). Stirring was then continued at r o o m t e m p e r -
ature for 30 rain, after which the mixture was weakly acidified with HC1. The r e s u l t i n g precipitate was r e -
moved by filtration, dried, and reflaxed for 3 h with 15-fold amount of phosphorus oxycbloride. The solution
was p o u r e d o v e r ice, and the r e s u l t i n g precipitate was r e m o v e d by filtration, washed with water (80-90~
dried, and r e c r y s t a l l i z e d f r o m acetic anhydride (except for If, which was r e c r y s t a l l i z e d f r o m xylene)
(Table 1).

4 - ( 5 - A r y l - 2 - o x a z o l y l ) n a p h t h a l i c Acid N - P h e n y l i m i d e s (IIb-f). A 1.5-fold excess of f r e s h l y distilled

aniline was added to a solution of 1 mmole of anhydride 1-b-f in a 10-fold amount of glacial acetic acid, and
the mixture was refluxed for 4 h. The precipitate that f o r m e d when the mixture was cooled was r e m o v e d
by filtration, washed s u c c e s s i v e l y with 5% HC1, w a t e r , 5% sodium carbonate solution, and water until the
wash w a t e r s were neutral. The product was then dried and r e c r y s t a l l i z e d f r o m xylene (Table 1).

LITERATURE CITED

i. S. E. Kovalev, B. M. Krasovitskii, and I~. A. Shevehenko, USSR Author's Certificate No. 327,226;
Byul. Izobr., No. 5, 76 (1972).
2. B. M. Krasovitskii and S. E. Kovalev, in: Scintillators and Organic Luminophores [in Russian], VNII
Monokristallov, Kharkov (1972), p. 63.
3. S. E. Kovalev, B. M. Krasovitskii, and V. M. Shershukov, Khim. Geterotsikl. Soedia., 1331 (1973).
4. A. E. Lutskii, A. V. Shepel', O. P. Shvaika, N. P. Demchenko, and G. P. Klimisha, Khim. Geterotsikl.
Soedin., 364 (1968).
5. A. E. Lutskii, A. V. Shepel', O. P. Shvaika, and G. P. Klimisha, Khim. Geterotsikl. Soedin., 461
(1969).
6. B. M. Krasovitskii, A. M. Kuznetsov, D. G. Pereyaslova, I~. A. Shevchenko, V. V. Korshak, G. F.
Slezko, V. V. Mikulenko, A. N. Izyneev, M. M. Seleznev, USSR Author's Certificate No. 292,953;
Byul. Izobr., No. 5, 94 (1971).
7. S. E. Kovalev, Author's Abstract of Master's Dissertation, Kharkov (1973).
8. S. E. Kovalev, B. M. Krasovitskii, and N. A. Popova, Khim. Geterotsiki. Soedin., 461 (1974).
9. A. S. Cherkasov, Zh. Fiz. Khim., 29, 2209 (1955).

915
SYNTHESIS OF r-4-ETHOXYCARBONYLAMINO-
t-3-HYDROXY-c-2- (8 - M E T H O X Y C A R BONYLBUTYL)-
THIOPHAN

S. D. M i k h n o , T . M. F i l i p p o v a , UDC 547.732.07
T . N. P o l y a n s k a y a , I. G. Razumova,
a n d V. M. B e r e z o v s k i i

Condensation of 4 - e t h o x y c a r b o n y l a m i n o - 3 - o x o t h i o p h a n with methyl y - f o r m y l b u t y r a t e gives

4 - e t h o x y c a r b o n y l a m i n o - 3 - o x o - 2 - (8 -methoxycarbonlybutyl)thiophan, its o x i m e , and r - 4 - e t h -
o x y c a r b o n y l a m i n o - t - 3 - h y d r o x y - c - 2 - (8 - methoxyc axbonylb utyl)thiophan.

In a continuation of our r e s e a r c h [1, 2] on the condensation of 4 - a m i n o s u b s t i t u t e d 3-oxothiophaas with

aldehydes and ketones, we have investigated the r e a c t i o n of 4 - e t h o x y c a r b o n y l a m i n o - 3 - o x o t h i o p h a n [2] with
methyl T - f o r m y l b u t y r a t e .
Condensation of 4 - e t h o x y c a r b o n y l a m i n o - 3 - o x o t h i o p h a n (I) with methyl y - f o r m y l b u t y r a t e in the p r e s -
ence of piperidine and pyridine a c e t a t e was unsuccessful, and s t a r t i n g I was r e c o v e r e d . We w e r e able to
effect the condensation in the p r e s e n c e of piperidine. This r e a c t i o n was m o n i t o r e d by PlVIR s p e c t r o s c o p y .

INCOOC211_ ~IlNCOOCoH~ HNCOOC2H s ]

OtlC(CH2)3COOCtt3 ~ CtI(CII2)3COOCtl3-- S./~CII(CH2)agOOCtl3 -

I II III

HNCOOC2H 5
/INOH

HNCOOC211s - f ~'S'/~'(CH2)4COOCH~
\ __~;O Y

S \(CH2)4CO~CH3 HNCOOC2~Is

VI

If 4 - e t h o x y c a r b o n y l a m i n o - 3 - o x o - 2 - ( 5 - m e t h o x y c a r b o n y l b u t y l i d e n e ) t h i o p h a n (II) is f o r m e d in the r e -
action, the signal of a vinyl proton should a p p e a r in the PMR s p e c t r u m . In fact, a t r i p l e t at 5 6.57 ppm,
which is c h a r a c t e r i s t i c for a proton attached to a double bond, is detected in the PMR s p e c t r u m of the m i x -
t u r e r e c o r d e d 1 h a f t e r the s t a r t of the r e a c t i o n . However, we w e r e unable to isolate II in pure f o r m , i n a s -
much as it is an oily s u b s t a n c e that r e a d i l y d e c o m p o s e s during h i g h - v a c u u m distillation.
Compound II was subjected to reduction with NaBH 4 (without isolation f r o m the r e a c t i o n mixture). A c -
cording to the PMR s p e c t r u m of the r e a c t i o n product the signal of the proton attached to the exocyclic
double bond is shifted to s t r o n g e r field (5 5.62 ppm), which attests to the f o r m a t i o n of III [in the s p e c t r u m
of 4 - b e n z a m i d o - 3 - h y d r o x y - 2 - ( 5 - m e t h o x y c a r b o n y l b u t y l i d e n e ) t h i o p h a n the proton attached to the double bond
a p p e a r s at 5 5.92 p p m [3] ].

All-Union S c i e n t i f i c - R e s e a r c h Vitamin Institute, Moscow. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h -

eskikh Soedinenii, No. 8, pp. 1053-1055, August, 1974. Original a r t i c l e s u b m i t t e d August 30, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 17th Street, New Yorkl N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval O,stem, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

916
 T A B L E 1. P a r a m e t e r s of the PMR Spectra of Solutions of V and VI
in Deuteropyr idine
8,ppm ~,Hz
5H" 3/] 4H CH3 (CH2)4 5H'. 5 5Ht~', 4H,
5H" NH
]
V ] 0.4 4,57 3.35 2,81 - - [ 5,15 4361 132 1,40--2,55--10.5[ 6.6 9,9 8,]
VI t 0,5 3,10--3,50 3,23 2,84 3,90--4,60 4,10I 1,19 1,40--2,45[--t0,7i 7.1 ! 8,5 --

When the r e a c t i o n product containing HI is allowed to r e a c t with methanol s a t u r a t e d with hydrogen

chloride it undergoes p r o t o t r o p i c i s o m e r i z a t i o n [4] - the signal of the p r o t o n attached to the double bond
vanishes in the PMR s p e c t r u m - and p r i m a r i l y (~ 75-80%) one s t e r e o i s o m e r of 4 - e t h o x y c a r b o n y l a m i n o - 3 -
o x o - 2 - ( 6 - m e t h o x y c a r b o n y l b u t y l ) t h i o p h a n (IV) is f o r m e d . Compound IV is an oily s u b s t a n c e that r e a d i l y
f o r m s c r y s t a l l i n e oxime V in 42% yield.
4 - E t h o x y c a r b o n y l a m i n o - 3 - h y d r o x y - 2 - ( 5 - m e t h o x y c a r b o n y l b u t y l ) t h i o p h a n (VI) was isolated in 78% yield
on subsequent reduction of IV with NaBH 4 in methanol at 0~
The s t r u c t u r e s of V and VI and the configuration of VI w e r e e s t a b l i s h e d by PMR s p e c t r o s c o p y . The
s p e c t r u m of VI, like the s p e c t r u m of V, contains a group of signals, the c h e m i c a l shifts of which a r e c h a r -
a c t e r i s t i c for protons attached to tile a - c a r b o n a t o m s of the thiophan r i n g , two complex signals at 1.40-2.55
p p m , which a r e affiliated with the protons of the methyleue groups of the substituent attached to C 2 [3], and
signals that c h a r a c t e r i z e the portions of substituents attached to C 3 (in VI) and C 4 (see Table 1) [3]. The
signals of the protons attached to C 2 and C 4 of V (52H 4.57, 64H 5,15 ppm) a r e shifted to w e a k field as c o m -
p a r e d with the c o r r e s p o n d i n g signals of VI (5 2H 3.10-3.50, 5 4H 3.90-4.60 ppm), which is a p p a r e n t l y e x -
plained by the deshielding effect of the hydroxylamino group. The signal of the proton attached to C 3 in the
PMR s p e c t r u m of VI is found in one group of signals with the proton attached to C 4 and the protons of the
methylene group of the ethoxycarbonyl substituent attached to the amino group (6 3.90-4.60 ppm).
In an e a r l i e r study of the PMR s p e c t r a of i s o m e r s of 4 - b e n z a m i d o - 3 - h y d r o x y - 2 - m e t h o x y c a r b o n y l -
thiophan [5] and 4 - b e n z a m i d o - 3 - h y d r o x y - 2 - ( 5 - m e t h o x y c a r b o n y l b u t y l ) t h i o p h a n [3] it was shown that {he
r - 4 - t - 3 - t - 2 e o n f i g u r a t i o n o f the substituents is c h a r a c t e r i z e d b y a r e l a t i v e l y s m a l l value of the s u m of the
vicinal s p i n - s p i n coupling constants with r e s p e c t to the C 4 - C 5 bond (E J4-5 = 8.9-12.4 Hz), while a s u b s t a n -
tially l a r g e r value of this s u m (E J4_5=16.4-18.5 Hz) is c h a r a c t e r i s t i c for the other t h r e e i s o m e r s
( r - 4 - t - 3 - c - 2 , r - 4 - c - 3 - t - 2 , and r - 4 - c - 3 - c - 2 ) . Compound VI is c h a r a c t e r i z e d by a l a r g e value of the s u m
of JtH,sH' and JtH,sH" (15.6 Hz, Table 1) and, consequently, cannot be the r - 4 - t - 3 - t - 2 i s o m e r . The c h e m -
ical shifts of the geminal protons attached to C5 p r a c t i c a l l y coincide (AS 5H',5H" 0-0.08 ppm) in the s p e c t r a
of r - 4 - c - 3 - t - 2 - i n v e s t i g a t e d compounds, just as in the s p e c t r a of a n u m b e r of i s o m e r s of 3 , 4 - s u b s t i t u t e d
t h i o p h a n s , t h a t differ with r e s p e c t to the substituent attached to the n i t r o g e n in the 4 - p o s i t i o n [5]. F o r VI,
A5 ~H,,sH,, is 0.39 p p m (Table 1), which makes it p o s s i b l e to r e g a r d the r - 4 - c - 3 - t - 2 configuration for it as
i m p r o b a b l e . The vtcinal constant between the protons attached to C~ and C 4 is s m a l l (J3H,4H 3.2 Hz) [3]
in the s p e c t r u m of the c o m p l e t e c i s - 2 , 3 , 4 - s u b s t i t u t e d thiophan. I n a s m u c h as the l e a s t distance between the
two individually o b s e r v e d e x t r e m e compounds of the signal of the proton attached to C 4 for VI is 7.1 Hz,
J3H,tI-I cannot be l e s s than 7.1 Hz, i.e., the s p e c t r u m of the investigated compound is not in a g r e e m e n t with
a cis configuration of all of the substituents. The large~ value of the s u m of JtH,sH', J4H,sH" (15.6 Hz), and
J3H,tH (>7.1 Hz), as well as the o b s e r v e d difference in the c h e m i c a l shifts of the geminal protons attached
to C 5 (AS 5H',sH" 0.39 ppm) for VI, a r e in complete a g r e e m e n t with the r - 4 - t - 3 - c - 2 configuration of the
substituents (E J4, 5 16.4, J3H,tH 8.1-9.0 Hz, A5 5H',~H" 0.37 p p m [3]). Thus, VI is r - 4 - e t h o x y c a r b o n y l -
amino - t - 3 - h y d r o x y - c -2 - (6 - methoxycarbonylbut yl) thiophan.

EXPERIMENTAL
The PMR s p e c t r a w e r e r e c o r d e d with a Hitachi P - 2 0 A s p e c t r o m e t e r . T e t r a m e t h y l s i l a n e was used
as the internal standard. The a c c u r a c y in the d e t e r m i n a t i o n of the c h e m i c a l shifts was 0.01 p p m , while the
a c c u r a c y in the d e t e r m i n a t i o n of the s p i n - s p i n coupling constants was 0.1 Hz. The a s s i g n m e n t of the s i g -
nals to definite protons of the investigated compounds was c o n f i r m e d by the r a t i o of the integral intensities
of the signals and d o u b l e - r e s o n a n c e e x p e r i m e n t s .
4 - E t h o x y c a r b o n y l a m i n o - 3 - o x o - 2 - ( 5 - m e t h o x y c a x b o n y l b u t y l ) t h i o p h a n (IV). A 2 . 5 - m l (22 mmole) s a m -
ple of methyl y - f o r m y l b u t y r a t e and 0.4 ml of piperidine w e r e added to a cooled (to 0 deg) solution of 4 g

917
(21 mmole) of 4 - e t h o x y c a r b o n y l a m i n o - 3 - o x o t h i o p h a n (I) in 26 ml of methanol, and the mixture was s t i r r e d
at 0 deg for 2 h. A 0.52-g (14 mmole) s a m p l e of s o d i u m b o r o h y d r i d e was then added in the c o u r s e of 30
min, and the mixture was s t i r r e d at 0 deg for 1 h. A 10-ml s a m p l e of methanol s a t u r a t e d with hydrogen
chloride (up to 30%) was added, and the mixture was s t i r r e d for 30 min. W a t e r (20 re_l) was added, and the
mixture was e x t r a c t e d with c h l o r o f o r m . The c h l o r o f o r m e x t r a c t s w e r e washed with s a t u r a t e d s o d i u m c a r -
bonate solution and d r i e d with s o d i u m sulfate. The c h l o r o f o r m was r e m o v e d in vacuo, and the s y r u p y r e s -
idue was dried at 50-60 ~ (0.5 mm) for 3 h to give 1.5 g (31.2%) of product. Fotmd: C 51.8; H 6.6; N 4.8%.
Ci3H21NOsS. Calculated: C 51.5; H 7.0; N 4.6%.
4 - E t h o x y c a r b o n y l a m i n o - 3 - o x i m i n o - 2 - ( 5 - m e t h o x y c a r b o n y l b t t t y l ) t h i o p h a n (V). A 0.25-g (4 mmole)
s a m p l e of hydroxylamine hydrochlor[de was added to a solution of 1 g (3 mmole) of IV in 5 ml of pyridine,
and the mixture was s t i r r e d at 18-20 ~ for 12 h. C h l o r o f o r m (25 re_l) and c r u s h e d ice w e r e added, a f t e r which
2.5 N h y d r o c h l o r i c acid was added ia portions with shaking until the aqueous l a y e r had pH 1. The c h l o r o -
f o r m l a y e r was washed with s o d i u m b i c a r b o n a t e solution and w a t e r and dried with s o d i u m sulfate. The
c h l o r o f o r m was r e m o v e d ia vacuo, 2 ml of alcohol was added to the r e s i d u e , and the mixture was allowed
to stand at 0 deg for 18-20 h. The r e s u l t i n g p r e c i p i t a t e was s e p a r a t e d to give 0.44 g (42~) of a product with
mp 130-130.5 d e g ( f r o m a l c o h o l ) . Found: C 49.4; H 6.8; N 9.1%. ClaH22N2OsS. Calculated: C 49.0; H 7.0; N
8.8%.
r - 4 - E t h o x y c a r b o n y l a m i n o - t - 3 - h y d r o x y - c - 2 - ( 6 - m e t h o x y c a r b o n y l b u t y l ) t h i o p h a n (VI). A 0.13-g (3
mmole) s a m p l e of sodium b o r o h y d r i d e was added at 0 deg in the c o u r s e of 30 min to a solution of 1 g (3
mmole) of IV in 8 ml of methanol, and the mixture was s t i r r e d at 0 deg for 2 h. W a t e r (10 ml) was added,
and the mixture was acidified to pH 1-2 with h y d r o c h l o r i c acid and e x t r a c t e d with c h l o r o f o r m . The solvent
was r e m o v e d , ether and alcohol in a r a t i o of 20 : 1 w e r e added to the r e s i d u e , and the mixture was held at
0 deg for 24 h. The r e s u l t i n g p r e c i p i t a t e was s e p a r a t e d to give 0.75 g (78%) of a product w i t h m p 83-84deg
(from e t h e r - m e t h a n o l ) . Found: C 51.1; H 7.7; N 4.6%. CI3H23NOsS. Calculated: C 51.1; H 7.6; N 4.6%.

LITERATURE CITED

I. S. D. Mikhno, V. M. B e r e z o v s k i i , and N. A. P r e o b r a z h e n s k i i , Zh. Vsesoyuzn. Khim. O b s h c h e s t v a ,

357 (1963).
2. S. D. Mikhno, T. N. P o l y a n s k a y a , and V. M. B e r e z o v s k i i , Khim. G e t e r o t s i k l . Soedia., 615 (1967).
3. S. D. Mikhno, T. M. Filippova, N. S. Kulachkina, T. N. P o l y a n s k a y a , I. M. Kustanovich, and V. M.
B e r e z o v s k i i , Khim. G e t e r o t s i k l . Soedin., 397 (1972).
4. S. D. Mikhno, T. N. P o l y a n s k a y a , and V. M. B e r e z o v s k i i , Khim. G e t e r o t s i k l . Soedin., 175 (1973).
5. S. D. Mikhno, T. M. FUippova, N. S. Kulachkina, T. N. P o l y a n s k a y a , V. V. Mishchenko, I. K. S h m y r e v ,
I. M. Kustanovich, and V. M. B e r e z o v s k i i , Khim. G e t e r o t s i k l . Soedin., 760 (1972).

918
SYNTHESES OF DI- AND TETRAHYDROPYRROLES
X.* SYNTHESIS OF 3 , 3 - D I M E T H Y L - 2 - M E T H Y L E N E - 5 - P Y R R O L I D O N E
AND ITS DERIVATIVES. INVESTIGATION OF THE E L E C T R O P H I L I C
ADDITION OF ALCOHOLS AND WATER TO THEM

B . M. S h e i m a n , L. Ya. Denisova, UDC 547.743.1'745.07

S. F . D y m o v a , and V. M. B e r e z o v s k i [

DehydratLon of 2 , 3 , 3 - t r i m e t h y l - 2 - h y d r o x y - 5 - p y r r o l i d o n e and its 1 - m e t h y l and 1-phenyl de-

r i vat[ ve s gave 3,3 -di m e t h y l - 2- methyl erie- 5 - p y r r o l i done and its 1- methyl and 1-phenyl a n a -
logs. T h e i r alcoholysis and hydration w e r e studied.

2 - M e t h y l e n e - 5 - p y r r o l i d o n e s and 2 - h y d r o x y ( a l k o x y ) - 5 - p y r r o l i d o n e s a r e of i n t e r e s t as key compounds

in the s y n t h e s i s of model and n a t u r a l c o f f i n s [2-4]. In this connection, the development of methods for the
s y n t h e s i s of t h e s e compounds and the investigation of t h e i r propertLes takes on g r e a t significance. 3,3-DL-
m e t h y l - 2 - m e t h y l e n e - 5 - p y r r o l [ d o n e (Ia) and its 1-methyl (Ib) and 1-phenyl (Ic) analogs w e r e obtained by de-
hydration of the c o r r e s p o n d i n g 2 - h y d r o x y - 5 - p y r r o l [ d o n e s (IIIa-c), which we p r e v i o u s l y d e s c r i b e d in [1, 4].
Methylenepyrrolidones Ia, c w e r e isolated by v a c u u m sublimation of h y d r o x y p y r r o l [ d o n e s Ilia, c at 130-
160~ while m e t h y l e n e p y r r o l i d o n e Ib was isolated by v a c u u m distillation of IIIb (or by keeping it in vacuo
at 20~
Methylenepyrrolidones I a - e r e a c t exceptionally r e a d i l y with m o i s t a i r to give s t a r t i n g h y d r o x y p y r o l t -
dones HIa-c. Compounds Ia and Ic, whLch we w e r e able to obtain without a d m i x t u r e s of s t a r t i n g Ilia and IIIe
only in solutions (with r a p i d dissolving of f r e s h l y s u b l i m e d s a m p l e s in anhydrous organic solvents), p r o v e d
to be p a r t i c u l a r l y unstable. The PMR s p e c t r a of t h e s e compounds show the p r e s e n c e of signals only of I
(Table 2; see [4] for a d e s c r i p t i o n of t h e i r s p e c t r a ) . Compound Ib Ls somewhat m o r e stable than Ia and Ic
and was isolated in the individual state (according to the PM:R s p e c t r o s c o p i c data and e l e m e n t a r y analysis).
It should be e m p h a s i z e d that the signals of t a u t o m e r i c 2 , 3 , 3 - t r [ m e t h y l - 5 - o x o - l - p y r r o l i n e in solutions of
3 , 3 - d i m e t h y l - 2 - m e t h y l e n e - 5 - p y r r o l i d o n e (Ia) w e r e not detected in any of the solvents used (even when s o -
lutions of Ia in CDC13 and nitrobenzene w e r e allowed to stand for 1-1.5 months). Thus, the [ m i n e - e n a m i n e
t a u t o m e r [ e e q u i l i b r i u m in 3 , 3 - d i m e t h y l - 2 - m e t h y l e n e - 5 - p y r r o l [ d o n e " (Ia) is shifted m a r k e d l y to favor the
l
enamine f o r m (evidently, as a consequence of the f o r m a t i o n of the conjugated C ~ C - - , N - - C = O system),
I I t I
in c o n t r a s t to 1 - p y r r o l i n e s , in which it is shifted to favor the im[ne f o r m [5].
It is known that the p r o d u c t s of dehydration of 2 - h y d r o x y - 5 - p y r r o l i d o n e d e r i v a t i v e s that have a double
bond in the r i n g r e a d i l y add w a t e r [6-8] but do not add methanol (even tn the p r e s e n c e of acid c a t a l y s t s
[9-10].

* F o r Communication IX see [1].

All-Union S c i e n t i f i c - R e s e a r c h Vitamin Institute, Moscow. T r a n s l a t e d f r o m Khimiya G e t e r o s i k l i -

eheskikh Soedinenii, No. 8, pp. 1056-1060, August, 1974. Original a r t i c l e s u b m i t t e d September 24, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming.
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

919
 T A B L E 1. P a r a m e t e r s of the P M R S p e c t r a of 2 , 3 , 3 - T r i m e t h y l - 2 -
a l k o x y - 5 - p y r r o l i d o n e D e r i v a t i v e s (Ha-g)
Chemical. shifts, 6, ppm
T
Com- R' Solvent 3-(CH3)2C, 12"CHsC' <N
pound 4-CHAHB, q
s 1 s

Illa a CHs CDC13 1,02 1,07 1,27 1,72; 2,00; 2,33; 2,65 16,8
Ilia ~ CH3 C~HsNO~ 1,12 1,22 1,45 1,87; 2,14; 2,47; 2,75 16,5
Ilia CDa CDaOD 1,02 1,07 1,28 1,72; 2,02; 2,40; 2,66 16,8
lllb C2D5 C6HsNOa 0,98 1,09 1,30 1,80; 2,07; 2,43; 2,70 16,2
IIIc H i-CaD7 C6HsNO2 0,95 1,04 1,29 1,95; 2,23; 2,59; 2,86 15,6
llld b CHa CH5 C~HsNO2 1,00 1,19 1,40 1,96; 2,22; 2,45; 2,71 15,6
Illd b CHa CDs CDsOD 1,01 1,19 1,33 1,83; 2,10; 2,30; 2,67 16,5
llle b CH3 C~Ds C~DsOD 0,98 1,08 1,30 1,77; 2,05; 2,25; 2,54 16,8
llI.fb CHa i-CaD7 i-CaDrOD 1,00 1,10 1,31 1,84; 2,12; 2,36; 2,64 16,8
lllgC CaH5 CHs CeHsN02 1,05 1,14 1,14 2,02; 2,30; 2,55; 2,82 16,5

a 5 0 C H 3 , s, 3.16 p p m (CDC13); 3.33 p p m (nitrobenzene); NH 7.8 p p m

(CDC13). b N - C H 3 , s, 2.30 p p m (nitrobenzene); 2.78 p p m (CD3OD); 2.73
p p m (C2D5OD); 2.75 p p m (iso-C~D7OD); OCH3, s, 3.10 p p m (nitroben-
zene), eOCH3, s, 3.27 p p m (nitrobenzene).

We have shown that 2 - m e t h y l e n e - 5 - p y r r o l i d o n e s I a - c , which contain an e x o c y c l i c double bond, r e a d i l y

u n d e r g o not only h y d r a t i o n (to give h y d r o x y p y r r o l i d o n e s I I a - e ) but a l s o a l c o h o l y s i s [to give the c o r r e -
sponding a l k o x y d e r i v a t i v e s (IIa-g)].
The a l c o h o l y s i s of I a - g p r o c e e d s at r o o m t e m p e r a t u r e in an e x c e s s of the c o r r e s p o n d i n g alcohol w i t h -
out the use of a c i d c a t a l y s t s .

(:H CH CH~ Clt~ CH3 CH~

//--
C[13\~. ~on "- HOH
R0 ""xNi O CIi2~ -.N/ ~.() i|O...~ N/,O
I i 1
1~' R' R"
a--g II I a-e
III a - C

I, IIIa W=H; b R'=CHa; c R'=C6Hs; II a R'=H, R=CH3; b R'=H, R=C2Ds; c R'=H,

R=i-CsDz; d R'=CH3, R=CH3; e R'=CHs, R=C2Ds; f R'=CH3, R=i-CaDT; g R'=C6Hs,
R=CH~
The s t r u c t u r e of the 2 - a l k o x y p y r r o l i d o n e s (II) o b t a i n e d was p r o v e d in detail in the c a s e of 2 , 3 , 3 - t r i -
m e t h y l - 2 - m e t h o x y - 5 - p y r r o l i d o n e (IIa). The P M R s p e c t r a of this c o m p o u n d (Table 1) c o n f i r m s its c y c l i c
s t r u c t u r e and (except for the s i g n a l of the C H 3 - O group) c o i n c i d e s with the s p e c t r a of the p r e v i o u s l y i n v e s -
t i g a t e d s u b s t i t u t e d 2 - h y d r o x y - 5 - p y r r o l i d o n e s . The c h a r a c t e r i s t i c (for the c y c l i c f o r m ) s i g n a l s of n o n e q u i v -
alent g e m i n a l m e t h y l g r o u p s and nonequivalent p r o t o n s of the methylene g r o u p in the 4 - p o s i t i o n (AB s y s -
t e m ) , as well as a s i n g l e t of the 2 - C H 3 g r o u p in the s t r o n g - f i e l d r e g i o n (1.20-1.45 ppm), a r e o b s e r v e d in
the P M R s p e c t r a of this compound. As c o m p a r e d with the PM:R s p e c t r a of h y d r o x y p y r r o t i d o n e IIIa [1, 4],
the PMR s p e c t r a of its m e t h o x y d e r i v a t i v e (IIa) contains a d i a m a g n e t i c shift of the signal of the p r o t o n a t -
t a c h e d to the n i t r o g e n ( f r o m 8.04 p p m to 8.53 p p m in s a t u r a t e d CD3OD solution) and a s m a l l p a r a m a g n e t t c
shift of the s i g n a l s of all of the r e m a i n i n g p r o t o n s (0.03-0.09 p p m in 0.4 M solutions of a l c o h o l s , c h l o r o -
f o r m , b e n z e n e , and n i t r o b e n z e n e ) . A s i n g l e t of a m e t h o x y g r o u p at 3.16 and 3.33 p p m , r e s p e c t i v e l y , is p r e s -
ent in the s p e c t r a of m e t h o x y p y r r o l i d o n e IIa in CDC13 and n i t r o b e n z e n e solutuins. The m o s t intense p e a k s
i n t h e m a s s s p e c t r u m o f I I a a r e t w o p e a k s of ions with m a s s e s 125 and 110, w h i c h a r e f o r m e d as a c o n s e q u e n c e
of s u c c e s s i v e splitting out of a methanol m o l e c u l e and a methyl g r o u p upon e l e c t r o n impact. A l o w - i n t e n -
s i t y (3.5%) m o l e c u l a r ion p e a k with m a s s 157 is o b s e r v e d in the m a s s s p e c t r u m of IIa r e c o r d e d at an ion-
[zing voltage of 12 eV. T h e IR s p e c t r u m of a thin l a y e r of m e t h o x y d e r i v a t i v e IIa contains the a b s o r p t i o n o f
an a s s o c i a t e d NH g r o u p at 3330 c m -1 (in c h l o r o f o r m s o l u t i o n it is shifted to 3430 c m -1) and the s t r o n g a b -
s o r p t i o n of a l a c t a m c a r b o n y l g r o u p at 1700-1730 c m -1 with a s h o u l d e r at 1670-1680 c m -I.
It s h o u l d be noted that t h e r m o l y s i s of m e t h o x y d e r i v a t i v e IIa (in n i t r o b e n z e n e o r in v a c u o at 120-140 ~
l e a d s to s t a r t i n g m e t h y l e n e p y r r o l i d o n e Ia.
The s t r u c t u r e s of the o t h e r a l k o x y d e r i v a t i v e s ffIb-g) w e r e e s t a b l i s h e d on the b a s i s of the identical
c h a r a c t e r of t h e i r P M R s p e c t r a and the s p e c t r u m of IIa.
The f o r m a t i o n of d e r i v a t i v e s I I a - g w a s followed q u a n t i t a t t v e l y b y m e a n s of P M R s p e c t r o s c o p y . It vcas
found that the r a t e of e l e c t r o p h f l i c addition of a l c o h o l s depends m a r k e d l y on the s u b s t i t u e n t s a t t a c h e d to the

920
 TABLE 2. P a r a m e t e r s of the PlV[R Spectra of 3 , 3 - D i m e t h y l - 2 -
m e t h y l e n e - 5 - p y r r o l i d o n e and Its Derivatives (Ia-c)
Chemical shifts 6, p p m
Com- ~ Solvent 3-(Clio):, 4 ('II:, HAa, Hna,
pound ]:I.4H B,
S g e Hz

la H CC14 1,25 2,50 3,97 4>25 1,87

la H C6H6 0,96 2. l l 3,97 4,40 1,50
!a H CDCIa 1,27 2.35 4,01 4,25 1,87
la H CGHsNQ 1,20 2,3O 4,05 432 1,80
la H CsD~N i 1,09 2,27 4,00 4,32 1,80
Ia H CDaCOOD , 1,27 2,42 4,21 4,33 1,80
Ia H b D:~O 1,24 2,29 4,24 438 1,80
Ib CHa CDCIa !,27 2,32 4,18s
Ic CGHs C6HsNO2 [ !,30 250 3,95 ! 4,08 1,95
lc Cg-ts CDCIa i 1,35 2,48 4.02 4,12 1,80
lc CsHs C~H~N ; 1,15 2,4! 4,00 -I,07 1,15
lc Coils DMSO 1,30 2,43 3,90 4,21 1,80
Ic D_~O+CD~OD ~ 1,40 2.60 4,00 4,31 1,95
i C3!a

aCenter of a doublet, b6N_CH 3 2.95 ppm.

nitrogen atom of the methylenepyrroltdone molecule (Ia-c) and d e c r e a s e s in the o r d e r CH 3 > H > C6H5 (Ib >
Ia > Ic) in c o n f o r m i t y with the d e c r e a s e in this o r d e r of the nucleophtlicity of the nitrogen a t o m and the a s -
sociated magnitude of the negative c h a r g e on the carbon of the methylene group. Thus, at 20 ~ and in the
p r e s e n c e of e x c e s s alcohol (at a I a - c concentration of 0.4 m o l e / l i t e r ) the addition of methanol to 1 , 3 , 3 - t r i -
m e t h y l - 2 - m e t h y l e n e - 5 - p y r r o l i d o n e (Ib) proceeds v e r y r a p i d l y (in 7 min). Methanol adds much more slowly
to 3 , 3 - d t m e t h y l - 2 - m e t h y l e n e - 5 - p y r r o l t d o n e (Ia) - t h e p r o c e s s is complete in 22 days - w h e r e a s methanol
does not add to 3 , 3 - d i m e t h y l - l - p h e n y l - 2 - m e t h y l e n e - 5 - p y r r o l i d o n e (Ic) under these conditions (in the c o u r s e
of 30 days). Methanol (in an approximately threefold excess) adds much more r a p i d l y to m e t h y l e n e p y r r o l i -
done I a t n nttrobenzene solution (see [11] for the a c c e l e r a t i o n of such r e a c t i o n s by a r o m a t i c solvents), and
the r e a c t i o n is 85% complete after 1.5 h and goes to completion after ~ 24 h. In nttrobenzene solution, meth-
anol adds to 3 , 3 - d i m e t h y l - l - p h e n y l - 2 - m e t h y l e n e - 5 - p y r r o l t d o n e (Ic). In the equilibrium mixture (equilib-
r i u m is established after 7 mtn), the percentage of 2 , 3 , 3 - t r t m e t h y l - l - p h e n y l - 2 - m e t h o x y - 5 - p y r r o l i d o n e (IIg)
is 53-55%. Ethanol and isopropyl alcohols add more slowly than methanol to 3 , 3 - d l m e t h y l - 2 - m e t h y l e n e -
5 - p y r r o l i d o n e (Ia) in nitrobenzene solution - the equilibrium mixtures contain 80 and 60% of alkoxy d e r i v -
atives lib and IIc, r e s p e c t i v e l y . The more highly r e a c t i v e 1 , 3 , 3 - t r i m e t h y l - 2 - m e t h y l e n e - 5 - p y r r o l i d o n e (Ib)
adds ethanol and isopropyl alcohols quantitatively in 5-10 min to give He and Hf, r e s p e c t i v e l y .
Water adds to methylenepyrrolidones I a - c more r e a d i l y than alcohols. The 2 - h y d r o x y - 5 - p y r r o l t d o n e
derivatives (IIIa-e) that we p r e v i o u s l y described in [1, 4] are f o r m e d as a r e s u l t of hydration. The same
effect of the substituting groups attached to the nitrogen of methylenepyrrolidones I a - c on the r a t e of addi-
tion of water as in the c a s e of the addition of alcohosl is observed. Thus, in 0.4 M solutions of methylene
p y r r o l i d i n e s Ia, b in D20 , hydration of 1 , 3 , 3 - t r i m e t h y l - 2 - m e t h y l e n e - 5 - p y r r o l i d i n e ([b) is 100% complete
after 20 min, while in the case of 3 , 3 - d i m e t h y l - 2 - m e t h y l e n e - 5 - p y r r o l i d o n e (Ia) the r e a c t i o n is 80% c o m -
plete after 20 mtn (it is 100% complete after 30 rain). In view of the fact that 3 , 3 - d i m e t h y l - l - p h e n y l - 2 -
m e t h y l e n e - 5 - p y r r o l i d o n e (Ic) is insoluble in w a t e r , its hydration was c a r r i e d out in CDsOD-D20 (1 : 1).
Equilibrium was established in 6 h after dissolving in this mixture: 92% hydroxypyrrolidone IIIe and 8%
m e t h y l e n e p y r r o l tdone Ic.
Our data on the addition of alcohols and w a t e r to I a - c are in a g r e e m e n t with the principles of e l e c -
trophilic addition of alcohols and w a t e r s to olefins, which o c c u r s under acid catalysis conditions, obeys the
Markownikoff r u l e , and is a c c e l e r a t e d by e l e c t r o n - d o n o r substituents attached to the double bond [12-14].

EXPERIMENTAL
The PMR s p e c t r a were r e c o r d e d with a H i t a c h i - P e r k i n - E l m e r R-20A s p e c t r o m e t e r . The solution
concentration was 0.4 m o l e / l i t e r , and the internal standards were hexamethyldistloxane (HMDS) and sodium
2 , 2 - d i m e t h y l - 2 - s i l a p e n t a n e - 5 - s u l f o n a t e (for aqueous solutions). The mass s p e c t r a were r e c o r d e d with a
JMS-01G2 s p e c t r o m e t e r with "direct" introduction of the sample into the ion s o u r c e at an ionizing voltage
of 75 eV and a sample t e m p e r a t u r e of 50 ~ Peaks with intensities g r e a t e r than 10% of the m a x i m u m a r e
presented. The n u m b e r s in front of the p a r e n t h e s e s indicate the mass number, while the n u m b e r s in p a r e n -
theses indicate the r e l a t i v e intensity of the ion peak with r e s p e c t to the m a x i m u m peak.

921
 3 , 3 - D i m e t h y l - 2 - m e t h y l e n e - 5 - p y r r o l i d o n e (In). A) A 2 - g (0.014 mole) s a m p l e of 2 , 3 , 3 - t r i m e t h y l - 2 -
h y d r o x y - 5 - p y r r o l i d o n e (IIIa) was v a c u u m sublimed at 160-165 ~ and 1-2 m m for 6 min to give 1.75 g (87.5%)
of white c r y s t a l s , which dissolved r a p i d l y in an anhydrous organic solvent (benzene, c h l o r o f o r m , etc.) in a
d r y nitrogen a t m o s p h e r e . According to the PMR s p e c t r a the compound is p u r e m e t h y l e n e p y r r o l i d o n e Ia,
which does not contain a d m i x t u r e s of other compounds (Table 2).
The compound is "very r e a d i l y h y d r a t e d by moist a i r , and a mixture of m e t h y l e n e p y r r o l i d o n e Ia and
h y d r o x y p y r r o l i d o n e IIIa (1 : 1 according to the PM:R s p e c t r u m of a solution in c h l o r o f o r m ) is f o r m e d during
e l e m e n t a r y a n a l y s i s . Found: C 62.6; H 9.3; N 10.3%. CTHllNO-CTH13NO2. Calculated: C 62.7; H 9.1;
N 10.4%.
B) S i m i l a r t r e a t m e n t of 0.47 g (3 mmole) of 2 , 3 , 3 - t r i m e t h y l - 2 - m e t h o x y - 5 - p y r r o l i d o n e (IIa) gave 0.36
g (96%) of white c r y s t a l s of IIIa, which was identical to the compound d e s c r i b e d above, a c c o r d i n g to the
PMIR s p e c t r a .
3 , 3 - D i m e t h y l - l - p h e n y l - 2 - m e t h y l e n e - 5 - p y r r o l i d o n e (ic). The p r o c e d u r e used to obtain Ia was used to
p r e p a r e 0.19 g (95%) of this compound by sublimation of 0.22 g (10 mmole) of 2 , 3 , 3 - t r i m e t h y l - l - p h e n y l - 2 -
h y d r o x y - 5 - p y r r o l i d o n e ('iIIc). Found: C 75.3; H 7.4; N 6.7%. C13H15NO- 0.5CI3H17NO 2. Calculated: C 75.5;
H 7.6; N 6.8%.
1 , 3 , 3 - T r i m e t h y l - 2 - m e t h y l e n e - 5 - p y r r o l i d o n e (Ib). A 2 0 - m l s a m p l e of liquid methylamine was added
to a solution of 1.62 g (0.01 mole) of 4 - c b l o r o - 3 , 3 , 4 - t r i m e t h y l - 4 - b u t a n o l i d e in 10 ml of c h l o r o f o r m , and the
m i x t u r e was maintained in a b o m b at 20 ~ for 4 days. The solvent was allowed to e v a p o r a t e f r e e l y , and the
methylamide hydrochloride was s e p a r a t e d to give 1.54 g (98%) of oily 1 , 2 , 3 , 3 - t e t r a m e t h y l - 2 - h y d r o x y - 5 -
p y r r o l i d o n e (IIIb),which, according to the PlVIR s p e c t r a , was identical to the s a m p l e obtained by another
method [1]. The isolated h y d r o x y p y r r o l i d o n e (IIlb) was then maintained in a v a c u u m (8-10 mm) at 20 ~ for
3 h to give a quantitative yield of m e t h y l e n e p y r r o l i d o n e lb. Found: 9.8%. CsH13NO. Calculated: N 10.0%.
The yield of m e t h y l e n e p y r r o l i d o n e Ib with bp 75-79 ~ (0.03 mm) was 83% when 1 , 2 , 3 , 3 - t e t r a m e t h y l -
2 - h y d r o x y - 5 - p y r r o l i d o n e (IIlb) was v a c u u m distilled.
2 , 3 , 3 - T r i m e t h y l - 2 - m e t h o x y - 5 - p y r r o l i d o n e (IIa). A 0.50-g (4 mmole) s a m p l e of 3 , 3 - d i m e t h y l - 2 - m e t h -
y l e n e - 5 - p y r r o l i d o n e (In) was dissolved in 50 ml of absolute methanol, and the mixture was maintained at
20 ~ for 30 days. The methanol was then r e m o v e d b y v a c u u m distillation at 30-40 ~ and a r e s i d u a l p r e s s u r e
of 15 m m , and the r e s i d u e was d r i e d thoroughly in vacuo (2 mm) at 20 ~ to give 0.63 g (100%) of an oily p r o d -
uct. Found: C 61.4; H9.0; N 8.9%; M (Mass s p e c t r o m e t r i c a l l y ) : 157. CsI-]IsNO2. Calculated: C 61.1; H9.6; N
8.9%; M 157.2. M a s s s p e c t r u m : 27 (25.3), 28 (11.9), 29 (15.5), 39 (54.7), 40 (18.8), 41 (97.3), 42 (44.0), 53 (12.1),
55 (20.4), 56 (32.4), 57 (11.5), 67 (20.4), 82 (49.3), 83 (12.1), 110 (100), 125 (29.1).

LITERATURE CITED
1. B . M . Sheiman, L. Ya. Denisova, S. F. Dymova, and V. M. B e r e z o v s k i i , Khim. Geterotsild. Soedin.,
21 (1973).
2. A. E s c h e n m o s e r , Quart. R e v . , 244,366 (1970).
3. R . B . Woodward, P u r e and Applied C h e m i s t r y , 17, 519 (1968).
4. B . M . Sheiman, L. Ya. Denisova, S. F. Dymova, A. A. S h e r e s h e v s k i i , I. M. Kustanovich, and V. M.
B e r e z o v s k i i , Khim. G e t e r o t s i l d . Soedin., 1190 (1971).
5. B . M . Sheiman, S. F. Dymova, V. B. Spiro, I. M. Kustanovich, and V. M. B e r e z o v s k i i , Khim. G e t e r -
otsikl. Soedin., 475 (1971).
6. R. Lukew and F. S o r m , Co11. Czech. Chem. C o m m u n . , 12, 637 (1947).
7. R. L u k e ' , F. K a s t n e r , J. Gut, and T. H e r b e n , Coll. Czech. Chem. Commun., 1-2, 647 (1947).
8. K . E . Schulte and J. R e i s c h , Arch. P h a r m . , 292, 125 (1959).
9. I . H . Robson and F. M a r e u s , Chem. Ind., 1022 (1970).
10. F. F a r i n a , M. V. Martin, and M. C. P a r e d e s , Synthesis, 167 (1973).
11. B . A . T r o f i m o v , O. N. Vylegzhanin, and M. G. Voronkov, Dold. Akad. Nauk SSSR, 207, 1137 (1972).
12. A . G . Evans and I. Halpern, T r a n s . F a r a d a y Soc., 4_88, 1034 (1952).
13. S. Winstein and J. L u c a s , J. A m e r . Chem. Soc., 59, 1461 (1937).
14. F . G . Ciapetta and M. Kilpatrick, J. A m e r . Chem. Soc., 70, 639 (1948).

922
SYNTHESES OF DI- AND TETRAHYDROPYRROLES
XI.* ALCOHOLYSIS AND CYANATION OF 2 , 3 , 3 - T R I M E T H Y L -
2-HYDROXY-5-PYRROLIDONE AND ITS DERIVATIVES

B . M. S h e r m a n , L. Ya. Dentsova, UDC 547.743.1.07 : 542.938

S. F . D y m o v a , and V. M. B e r e z o v s k i i

The alcoholysts and cyanatton of 2 - h y d r o x y - 5 - p y r r o l t d o n e d e r i v a t i v e s are nucleophilic s u b -

stttutton r e a c t i o n s that take place at the hydroxyl and alkoxy groups.

2 - A l k o x y - and 2 - c y a n o - 5 - p y r r o l i d o n e s a r e i m p o r t a n t i n t e r m e d i a t e s in the synthesis of c o r r i n s [2, 3].

In the p r e s e n t r e s e a r c h we have intestigated the alcoholysis and cyanation of 2 , 3 , 3 - t r t m e t h y l - 2 - h y -
d r o x y - 5 - p y r r o l i d o n e (In) and its substituted d e r i v a t i v e s (Ib-d). In c o n t r a s t to the data in the l i t e r a t u r e r e -
garding the inert c h a r a c t e r of the hydroxyl group of substituted 2 - h y d r o x y - 5 - p y r r o l t d o n e s in a n u m b e r of
c h e m i c a l r e a c t i o n s (with dtazomethane, dtmethyl sulfate, t s o c y a n a t e , acetic anhydride, acetyl chloride, and
thtonyl chloride) [4-11], we have shown that the hydroxyl group in the 2 - p o s i t i o n in 2 , 3 , 3 - t r t m e t h y l - 2 - h y -
d r o x y - 5 - p y r r o l t d o n e (Ia) and its substituted d e r i v a t i v e s (Ib-d) is r e a d i l y r e p l a c e d by alkoxy and cyano
groups.
The alcoholysts of I a - d p r o c e e d s with unusual e a s e in alcohol solutions in the a b s e n c e of acid c a t a -
l y s t s . Thus methanolysts of h y d r o x y p y r r o l t d o n e Ia~ at 20~ is complete in 3 h. According to all of the
data obtained (I_R, PIVIR, and m a s s s p e c t r a , e l e m e n t a r y a n a l y s i s , and v a c u u m t h e r m o l y s i s ) , IIa p r o v e d to be
identical to the p r e v i o u s l y d e s c r i b e d [1] 2 , 3 , 3 - t r i m e t h y l - 2 - m e t h o x y - 5 - p y r r o l t d o n e . Like methoxy d e r t v a -

Cll, CH~ r'

CHa~ 11a-e
HO.--'~.N/':O
IR' ~ 2 0 IKCN'KHCOa'GHaOH
c~J"cH3r'
! a-d CH3.%~ O
NC/ ~N"
I
R'
III a,b,d
I, lIIa R'=R"=H; b R'=CHa, R"=H; c R'=CsHs, R"=H; d R'=H, R"=CONH2; It a--e
R"=H; a R'=H, R=CHa; b R'=H, R=C=Ds; c R'=H, R=i-CaDr;d R'=CH3, R=CDa;
eR'=C6Hs, R=CHa; II f R"=CONH2, R'=H, R=CDa

tive IIa, the other alkoxy d e r i v a t i v e s (IIb-f) have c h a r a c t e r i s t i c PMR s p e c t r a that a r e s i m i l a r to those
p r e s e n t e d in [1]~

* For Communication X see [1].

[ W e have p r e v i o u s l y a s s u m e d [12, 13] the p o s s i b i l i t y of the development of the 2 - t m t n o t e t r a h y d r o f u r a n
f o r m , which is a t a u t o m e r of h y d r o x y p y r r o l t d o n e Ia, for Ia in alcohol solution.

All-Union S c i e n t i f i c - R e s e a r c h Vitamin Institute, Moscow. T r a n s l a t e d f r o m Khtmtya G e t e r o t s i k l i c h -

eskikh Soedinenit, No. 8, pp. 1061-1065, August, 1974. Original a r t i c l e s u b m i t t e d S e p t e m b e r 24, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publicatio, may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electro,ic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15. 00.

923
 The aleoholysis of h y d r o x y p y r r o l i d o n e s Ia and Id is r e a d i l y followed quantitatively by c o m p a r i s o n of
the intensities of the signals of the protons of the methylene groups in the 4-position (AB s y s t e m ) or of the
2-CH 3 groups in the hydroxy(alkoxy) compounds. Monitoring of the alcoholysis of 1 - m e t h y l - and 1-phenyl-
2 , 3 , 3 - t r i m e t h y l - 2 - h y d r o x y - 5 - p y r r o l i d o n e (Ib and Ic, r e s p e c t i v e l y ) in alcohol solutions p r o v e d to be i m p o s -
sible b e c a u s e of the s u p e r i m p o s i t i o n of the c h e m i c a l shifts of the signals of the hydroxy and methoxy d e r i v -
atives. In o r d e r to quantitatively follow the methanolysis of these compounds we used solutions of h y d r o x y -
p y r r o l i d o n e s Ib, c in n i t r o b e n z e n e in the p r e s e n c e of a threefold e x c e s s of methanol. Under t h e s e condi-
tions, it b e c o m e s p o s s i b l e to quantitatively follow the c o u r s e of the p r o c e s s using a c o m p a r i s o n of the in-
t e n s i t i e s not only of the signals l i s t e d above but also of the signal of the methoxy group at 3.10 and 3.27
p p m of IId and IIe, r e s p e c t i v e l y . The alcoholysis of h y d r o x y p y r r o l i d o n e Ia in ethanol and 2-propanol p r o -
ceeds with s o m e w h a t m o r e difficulty than methanolysis. Thus, at 34 ~ the p e r c e n t a g e of ethoxy d e r i v a t i v e
IIb is 78% (after 6 days), while the p e r c e n t a g e of IIc is 16% (after 7 days). It should be noted that in t h e f a c e
of such a prolonged t i m e r e q u i r e d to e s t a b l i s h equilibrium, spontaneous dehydration of h y d r o x y p y r r o l i d o n e
Ia begins to a p p e a r (see [14]); the p r e s e n c e of 3 , 3 - d i m e t h y l - 2 - m e t h y l e n e - 5 - p y r r o l i d o n e (13% in ethanol and
18% in isopropyl alcohol, r e s p e c t i v e l y ) is detected in e q u i l i b r i u m m i x t u r e s of I a - I I b , c.
A s i m i l a r p a t t e r n is o b s e r v e d in the methanolysis of the methyl (l-b) and phenyl (Ic) analogs of hy-
d r o x y p y r r o l i d o n e Ia. Thus, in nitrobenzene solution in the p r e s e n c e of a threefold e x c e s s of methanol, the
p e r c e n t a g e s in the e q u i l i b r i u m mixture of the c o r r e s p o n d i n g methoxy d e r i v a t i v e (II) and m e t h y l e n e p y r r o l -
idone a r e ~ 4 2 and 35% (after 31 days) for the methyl analog fib) and ~ 2 4 and 32% (after 42 days) for the
phenyl d e r i v a t i v e (Ic).
2 , 3 , 3 - T r i m e t h y l - 2 - h y d r o x y - 4 - c a r b a m i d o - 5 - p y r r o l i d o n e (Id) [14], which is r e s i s t a n t to dehydration in
solutions, does not undergo this r e a c t i o n in methanol solution; methoxy d e r i v a t i v e IIf (44%) and s t a r t i n g hy-
d r o x y p y r r o l i d o n e Id (56%) a r e detected in it 8 months a f t e r dissolving.
P r a c t i c a l l y no d e u t e r i u m exchange of the hydrogen attached to nitrogen or in the methyl group in the
2 - p o s i t i o n o c c u r s in the alcoholysis of h y d r o x y p y r r o l i d o n e s I a - d in deuterated alcohol solutions. This p r o -
r i d e s a b a s i s for a s s u m i n g that the r e a c t i o n p r o c e e d s as d i r e c t nucleophilic substitution with the p a r t i c i -
pation of the hydroxyl group of I r a t h e r than b y addition of alcohol to the initially f o r m e d (as a consequence
of dehydration) 2 - m e t h y l e n e - 5 - p y r r o l i d o n e ( 5 - o x o - l - p y r r o l t n e ) d e r i v a t i v e s or to the open t a u t o m e r i c f o r m s
of I a - e (with subsequent r e c y c l i z a t i o n ) , i n a s m u c h as d e u t e r i u m exchange in the NH or 2-CH 3 groups should
have been o b s e r v e d in these c a s e s . In addition, as we have shown in [1], genuine substituted 2 - m e t h y l e n e -
5 - p y r r o l i d o n e s add alcohol (under s i m i l a r conditions) and f o r m atkoxy d e r i v a t i v e s v e r y slowly.
As it turned out, the alcoholysis of 2 - h y d r o x y p y r r o l i d o n e s I a - d is a r e v e r s i b l e p r o c e s s . Methoxy-
p y r r o l i d o n e IIa is v e r y r e a d i l y c o n v e r t e d to h y d r o x y p y r r o l i d o n e Ia by the action of water. An i n c r e a s e in
the t e m p e r a t u r e a c c e l e r a t e s the alcoholysis and shifts the e q u i l i b r i u m to the right. When the hydroxypyr-
rolidone concentration is i n c r e a s e d , alcoholysis is inhibited, and the e q u i l i b r i u m is shifted to the left. The
addition of acidic (phenols and acetic acid) and alkaline (NaOD, CD.~ONa) agents does not have a significant
effect on the r a t e of the p r o c e s s and the s t a t e of the equilibrium.
We have p r e v i o u s l y [15] shown that the hydroxyl group in h y d r o x y p y r r o l i d o n e Ia is capable of being
r e p l a c e d by a cyano group. In the p r e s e n t r e s e a r c h we have e s t a b l i s h e d that 1 , 2 , 3 , 3 - t e t r a m e t h y l - 2 - h y -
d r o x y - 5 - p y r r o l i d o n e (Ib) and 2 , 3 , 3 - t r l m e t h y l - 2 - h y d r o x y - 4 - e a r b a m i d o - 5 - p y r r o l i d o n e (Ib) undergo cyanation
in the p r e s e n c e of p o t a s s i u m b i c a r b o n a t e and p o t a s s i u m cyanide in D20 solution, while 2 , 3 , 3 - t r i m e t h y l - 2 -
m e t h o x y - 5 - p y r r o l i d o n e (IIa) undergoes cyanation in methanol solution. In this c a s e , methoxypyrrolidone
Ha f o r m s 2 , 3 , 3 - t r i m e t h y l - 2 - e y a n o - 5 - p y r r o l i d o n e (IIIa), which has a c h a r a c t e r i s t i c PMR s p e c t r u m that is
identical to the s p e c t r u m of the s a m p l e p r e v i o u s l y obtained in [15].
In c o n t r a s t to n i t r o g e n - u n s u b s t i t u t e d h y d r o x y p y r r o l i d o n e Ia, cyanation does not p r o c e e d at all in the
c a s e of Ib and Id. C a r b a m i d o h y d r o x y p y r r o l i d o n e Id f o r m s unstable cyano d e r i v a t i v e IIId (which d e c o m p o s e s
on subsequent cyanatton). In this c a s e the p r o c e s s is i n t e r r u p t e d (it is c a r r i e d out for a few minutes), and
the yield of cyano d e r i v a t i v e IIId in this case is 51%.
R e p l a c e m e n t of the hydroxyl group in Id b y a eyano group in the 2-position leads to a shift to strong
field of the signal of the 4-H p r o t o n (by 0.21 ppm) and a s m a l l shift to w e a k field of the signal of the 2-CH 3
group (by 0.06 ppm; see [14]) in the PMR s p e c t r u m of cyano d e r i v a t i v e IIId in pyridine solution.
Cyanation of Ib gives an e q u i l i b r i u m mixture containing, according to PlV[R s p e c t r o s c o p i c data, 67%
1,2 ,3 , 3 - t e t r a m e t h y l - 2 - c y a n o - 5 - p y r r o l i d o n c (IIIb) and 33% of s t a r t i n g h y d r o x y p y r r o l i d o n e Ib, which could not
be s e p a r a t e d . The conclusion r e g a r d i n g the f o r m a t i o n of cyano d e r i v a t i v e IIl-b in this c a s e was made on the

924
b a s i s of the coincidence of its PIVIR s p e c t r a with the PMR s p e c t r a of 1-unsubstituted analog IIIa in D20 ,
CC14, and CDCt 3 solutions. In the PMR s p e c t r u m of IIIb in CDC13, for e x a m p l e , one o b s e r v e s the c h a r a c -
t e r i s t i c (also for IIIa) signals of g e m i n a l methyl groups at 1.09 and 1.36 p p m and of the 2-CH 3 group at 1.51
p p m , which a r e shifted to the w e a k e r field as c o m p a r e d with the c o r r e s p o n d i n g signals of s t a r t i n g h y d r o x y -
p y r r o l i d o n e Ib (see [14]). The protons in the 4-position of I]Ib a p p e a r as a singlet at 2.32 ppm, while the
signal of the methyl group attached to the nitrogen a p p e a r s at 2.88 ppm. In c o n t r a s t to IIIa, cyano d e r i v a -
tive IIIb is r e a d i l y h y d r o l y z e d by w a t e r to h y d r o x y p y r r o l i d o n e Ib; this is a p p a r e n t l y r e l a t e d to the +I effect
of the methyl group in the 1-position. 2 , 3 , 3 - T r i m e t h y l - l - p h e n y l - 2 - h y d r o x y - 5 - p y r r o l i d o n e (Ic) does not un-
dergo cyanation. The effect of substituents attached to the nitrogen a t o m of h y d r o x y p y r r o l i d o n e s I a - c on
cyanation m a k e s it p o s s i b l e to suppose that this r e a c t i o n does not p r o c e e d through r i n g opening with sub-
sequent r e c y c l i z a t i o n , inasmuch as N - p h e n y l h y d r o x y p y r r o l i d o n e Ic, which f o r m s an open t a u t o m e r i c f o r m
m o s t r e a d i l y of all of the compounds [14], shouldbe most r e a c t i v e in this case.
In the cyanation of substituted 2 - h y d r o x y - 5 - p y r r o l i d o n e Ia, b in D20 solution, cyano d e r i v a t i v e s IIIa, b
a r e f o r m e d m o r e r a p i d l y (on the b a s i s of an analysis of the PMI~ s p e c t r a ) than the protons of the 2-CH 3
group undergo d e u t e r i u m exchange. It follows f r o m this that the cyanation of In, b does not p r o c e e d via ad-
dition of a cyanide ion to the initially f o r m e d (during dehydration) 2 - m e t h y l e n e - 5 - p y r r o l i d o n e or its N - a c y l -
ketimine f o r m (see [3, 16]). Thus, the cyanation (like the alcoholysis) of substituted 2 - h y d r o x y - 5 - p y r r o l -
idones I a - d p r o b a b l y should be c o n s i d e r e d to be a r e a c t i o n involving nucleophilic substitution of the h y -
droxyl group in the 2-position.
In this c a s e , the i n c r e a s e d e l e c t r o n density on the 2-C a t o m , which a r i s e s as a consequence of the
inductive effective (or the +C effect) of the nitrogen a t o m , will p r o b a b l y facilitate the f o r m a t i o n of the
t r a n s i t i o n s t a t e during nucleophilic r e a c t i o n s .

EXPERIMENTAL
The IR spectra of the compounds were recorded with a UR-10 spectrometer. The PMIR spectra were
recorded with a Hitachi-Perkin-Elmer R-20A spectrometer. The solution concentrations were 0.4 mole/
liter. Hexamethyldisiloxane and sodium 2,2-dimethyl-4-silapentane-l-sulfonate (for D20 solutions) were
used as the internal standard. The mass spectra were recorded with JMS-01SG2 spectrometer with "di-
rect" introduction of the sample into the ion source at an ionizing voltage of 75 eV and a sample tempera-
ture of 50 ~.*
2,2,3-Tr imethyl -2-methoxy-5-pyrrolidone (IIa). A 0.70-g (5 mmole) sample of 2,3,3-tri methyl-2-hy-
droxy-5-pyTrolidone was dissolved in 100 ml of absolute methanol, and the mixture was maintained at 20 ~
for 24 h, after which the methanol was removed by vacuum distillation at 20-30 ~ and the residue was dried
thoroughly in vacuo (2 mm) at 20 ~ to give a quantitative yield of oily methoxypyrrolidone fla.
Mass spectrum: 27 (22.8), 28 (14.9), 29 (20.6), 39 (48.7), 40 (16.5), 41 (85.1), 42 (48.1), 43 (Ii.i), 53
(13.0), 55 (21.3), 56 (49.6), 57 (16.4), 67 (25.7), 82 (46.4), 83 (14.9), ii0 (I00), 125 (30.9), 126 (i0). PIV~
spectrum, 5, ppm (in nitrobenzene): 3-(CH3) 2 1.10 (s, 3H) and 1.17 (s, 3H); 2-CH 3 1.40 (s, 3H); 4-CHAH B
1.87/2.14/2.47/2.75/ (q, AB system, 2H, JAB =16.5 Hz); 2-OCH 3 3.16 (s, 3H). The PMR spectrum of a
nitrobenzene solution of the sample showed that it contained 0.37 mole of methanol. Found: C 59.5; H 9.4;
N 8.2%; M (Mass spectrometrically) 157. CsHIsNO 2 +0.37 CH3OH. Calculated: C 59.4; H 9.8; N 8.2%; M
157.2.
Reaction of 2,3,3-Trimethyl-2-methoxy-5-pyrrolidone (IIa) with Potassium Cyanide. A 0.33-g (3.3
mmole) s a m p l e of p o t a s s i u m b i c a r b o n a t e and 0.22 g (3.3 mmole) of p o t a s s i u m cyanide w e r e added to a s o -
lution of 0.47 g (3 mmole) of methoxypyrrolidone IIa in 3 ml of absolute methanol, and the mixture was r e -
fluxed and s t i r r e d for 40 h, after which the alcohol was r e m o v e d by distillation, and the r e s i d u e was ex-
t r a c t e d with c h l o r o f o r m . The e x t r a c t was e v a p o r a t e d , and the product was v a c u u m dried at 20 ~ (2 ram) to
give 0.23 g (51%) of c r y s t a l l i n e 2 , 3 , 3 - t r i m e t h y l - 2 - c y a n o - 5 - p y r r o l i d o n e (Ilia) with mp 192-192.5 ~ (mp 192 ~
[15]). PMR s p e c t r u m , 5, p p m (in CHC13): 3-(CH3) 2 1.18 (s, 3H) and 1.43 (s, 3H); 2-CH 3 1.59 (s, 3H);
4-CHAH B 2.05/2.33/2.43/2.71 (q, 2H, J A B = 1 6 . 8 Hz).
Reaction of 1 , 2 , 3 , 3 - T e t r a m e t h y l - 2 - h y d r o x y - 5 - p y r r o l i d o n e (I-b) with P o t a s s i u m Cyanide. As in the
preparation of IIa, a solution of i.I g (7 mmole) of hydroxypyrrolidone Ib, 0.5 g (7.7 mmole) of KCN, and
0.77 g (7.7 mmole) of KHCOs in 20 ml of water was heated at 85-95 ~ for 1.5 h to give 1.04 g of a colorless

*The authors thank V. A. Zamureenko and Zh. K. Torosyan for recording the mass spectra.

925
oily product containing, according to the PMR spectrum, 75% 2-cyanopyrrolidone IIIb (67% yield) and 25%
of 2-hydroxypyrrolidone Ib (23.6% yield). PMR spectrum of I]/b, 6, ppm (in CHC13): 3-(CH3)2 1.09 (s, 3H)
and 1.36 (s, 3H); 2-CH 3 1.51 (s, 3H); 4-CH 2 2.32 (s, 2H); CHs-N 2.88 (s, 3H).
2-Cyano-2,3,3-trimethyl-4-carbamido-5-pyrrolidone (IIId). A 1.1-g (11 mmole) sample of potassium
bicarbonate and 0.72 g (11 mmole) of potassium cyanide were added to a refluxing solution of 1.36 g (10
mmole) of 2,3,3-tr[methyl-2-hydroxy-4-carbamido-5-pyrrolidone in 7 ml of water. After 7 min, the r e -
action mixture was poured over ice, and the precipitated crystals were removed by filtration, washed with
water, and vacuum dried to give 1 g (51.3%) of 2-cyano-2,3,3-trimethyl-4-earbamido-5-pyrrolidone ~ith
mp 213-213.5 ~ PMR spectrum, 6, ppm (in C~HsN): 3-(CH3) 2 1.02 (s, 3H) and 1.09 (s, 3H); 2-CH 3 1.51 (s,
3H); 4-CH 3.27 (s, 1H). Found: C 55.2; H 6.7; N 21.7%. C9H13N302. Calculated: C 55.3; H 6.7; N 21.5%.

LITERATURE CITED
1. B.M. Sheiman, L. Ya. Denisova, S. F. Dymova, and V. M. Berezovskii, Khim. Geterotsikl. Soedin.,
1056 (1974).
2. R.B. Woodward, Pure and Applied Chemistry, 1_~7,519 (1968).
3. Y. Yamada, H. Nilikovie, P. Wehrli, B. Golding, P. Lolig, K. Kuss, K. Muller, and A. Eschenmoser,
Angew. Chem. Int. Ed., 8, 343 (1969).
4. E. Walton, J. Chem. Soe., 438 (1940).
5. R. Filler and L. M. Hebron, J. Amer. Chem. Soe., 8._11,391 (1959).
6. Y.S. Rao and R. Filler, Chem. Ind., 1862 (1964).
7. M. Robertson and H. Stephen, J. Chem. Soe., 863 (1931).
8. I.K. Kalnin' and I~. Yu. Gudrinietse, Izv. Akad. Nauk LatvSSR, Ser. Khim., 110 (1972).
9. J.H. Helberger, S. Ulubay, and H. Civelekoglu,Ann., 561,219 (1949).
10. F. Farina, M. V. Martin, and M. C. Paredes, Synthesis, 167 (1973).
11. R.E. Lutz and F. B. II[ll, J. Org. Chem., _6, 175 (1941).
12. B.M. Sheiman, L. Ya. Denisova, S. F. Dymova, T. M. Filippova, I. M. Kustanovieh, and V. M. Berez-
ovskii, in: Material from theThirdAll-Union Conference on the Investigation of the Structures of
Organic Compounds by Physical Methods [in Russian], Kazan' (1971), p. 323.
13. R. I~. Valter, Usp. Khim., 42, 1072 (1973).
14. B.M. Sheiman, L. Ya. Denisova, and V. M. Berezovskii, Khim. Geterotsikl. Soedin., 21 (1973).
15. B.M. Sheiman, L. Ya. Denisova, S. F. Dymova,A. A. Shereshevski[, I. M. Kustanovieh, and V. M.
Berezovski[, Khim. Geterotsikl. Soedin., 1190 (1971).
16. R.V. Stevens, C. C. Christensen, W. L. Edmonson, M. Kaplan, E. B. Reid, and M. R. Wentland, J.
Amer. Chem. Soe., 93, 6629 (1971).

926
INDOLE DERIVATIVES
VII.* REACTION OF INDOLE WITH AZIRIDINES

E. P. Styngach, F. Sh. Rivilts, UDC 547.752'717'821.411.2'759.3

N. M. F r o l o v a , Kh. Sh. Khariton,
and A. A. Semenov

The r e a c t i o n of substituted a z i r t d t n e s with indole was studied. It is shown that the p r e s e n c e

of e l e c t r o n - d o n o r substituents attached to the carbon a t o m or of bulky substttuents attached
to the nitrogen a t o m in a z i r i d t a e s f a v o r s cleavage of the aztridine r i n g b y indole to give de-
r i v a t i v e s of t r y p t a m i n e and tryptophan.

It is known that aztridine r e a c t s with indole or [ndolylmagnesium b r o m i d e to give t r y p t a m i n e [2, 3].

In addition, we have p r e v i o u s l y e s t a b l i s h e d that 3 - p h e n y l a z i r i d i n e - 2 - c a r b o x y l t c acid e s t e r is cleaved by in-
dole to give /3-phenyltryptophan e s t e r [4]. In the p r e s e n t c o m m u n i c a t i o n we d e s c r i b e e x p e r i m e n t s u n d e r -
t a k e n in o r d e r to d e t e r m i n e the r a n g e of application of this r e a c t i o n for the synthesis of t r y p t a m t n e s and
t r y p t o p h a n s substituted in the side chain. In doing so we e s t a b l i s h e d that neither mono- and 2 , 3 - d i a l k y l -
a z i r i d t n e s t h e m s e l v e s nor t h e i r t e t r a f l u o r o b o r a t e s r e a c t with indole or i n d o l y l m a g n e s i u m halides. We w e r e
also unable to introduce tmsubstituted or 1- and 3 - a l k y l - s u b s t i t u t e d e s t e r s of a z i r i d i n e c a r b o x y l i c acid into
this r e a c t i o n . In all of t h e s e c a s e s , p o l y m e r i z a t i o n of the e t h y l e n e t m t n e s p r e d o m i n a t e d . However, 2 - p h e -
n y l a z t r i d i n e (I) r e a c t e d with indole under the influence of b o r o n t r i f l u o r i d e e t h e r a t e and p a r t i c u l a r l y r e a d i l y
when it was heated with t e t r a c e t y l diborate. According to the r e s u l t s of t h i n - l a y e r c h r o m a t o g r a p h y (TLC),
the a m i n e portion of the r e a c t i o n products consisted of one substance, for which it was shown that it was
identical to /3-phenyltryptamine. The facilitation of the r e a c t i o n of this c a s e is p r o b a b l y a s s o c i a t e d with
an e l e c t r o n i c factor - stabilization of the positively c h a r g e d C(2 ) carbon a t o m of the aztrtdine ring by con-
j u g a t i o n w i t h t h e r e l e c t r o n s of the benzene ring. H e t e r o c y c l t c substituents manifest a s i m i l a r effect. When
a z t r i d t n e Ib t was heated with indole and t e t r a c e t y l d i b o r a t e in n i t r o m e t h a n e , g l a s s y tryptophan e s t e r lib,
which we w e r e unable to p r e p a r e in analytically pure f o r m , was f o r m e d . It was saponified with alkali, and
/3-carboline IIIb was obtained a f t e r t r e a t m e n t with acetaldehyde and d i c h r o m a t e by the method in [4].
R' R'
I 1

H I H H q
R CH3
I a-c II a - d III b

[--Iti., R = R " - H , R'=C~Hs; b R=H, R ' = l - b e n z i m i d a z o l - 2 - y l , R~=CO2--/-CaH7;

c R=C tCHa)a, R'=H, R"=CO..--i-CaH7; I:d R=C(CHa)a, R'=CQ--i-CaHT, R"=H:

Steric f a c t o r s also affect the r e a c t i o n under consideration. A bulky substituent, by hindering poly-
m e r i z a t i o n , f a v o r s r e a c t i o n with indole. However, s t r u c t u r a l s p e c i f i c i t y in this c a s e is p r o b a b l y lost.

* For Communication VI see [1].

For the s y n t h e s i s of Ib, 1 - b e n z y l - 2 - f o r m y l t m i d a z o l e was condensed with i s o p r o p o x y e a r b o n y l b r o m o e t h y l -
e n e t r i p h e n y l p h o s p h o r a n e [5] to give ( 1 - b e n z y l - 2 - t m i d a z o l y l ) - a - b r o m o a c r y l i c acid e s t e r , which was cyclized
to Ib by t r e a t m e n t with a m m o n i a in dimethyl sulfoxtde. The s i m i l a r l y obtained indole b r o m o a c r y l a t e did
not undergo the cycltzation r e a c t i o n .
Institute of C h e m i s t r y , A c a d e m y of Sciences of the Moldavian SSR, Kishinev. T r a n s l a t e d f r o m K h i m -
iya G e t e r o t s i k l i c h e s k i k h Soedtnenii, No. 8, pp. 1066-1069, August, 1974. Original a r t i c l e s u b m i t t e d July
31, 1973.

9 76 Plemtm Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced.
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, micrQfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

927
Thus, t r e a t m e n t of 1 - t e r t - b u t y l a z i r i d i n e c a r b o x y l i c acid e s t e r Ie and indole with boron trifluoride etherate
gave two i s o m e r s , which we were able to s e p a r a t e by c h r o m a t o g r a p h y on silica gel. Intense peaks with
m / e 172, 130, and 74, which c o r r e s p o n d to ions a, b, and c, were r e c o r d e d in the mass s p e c t r u m of the
h i g h e r - m e l t i n g product. One cannot exclude the possibility that the peak with m / e 130 is a composite peak
+
containing a contribution f r o m the (CH3)3C - N H = C H - C O O H fragment ion, which is f o r m e d f r o m ion a after
loss of a propylene molecule with hydrogen migration. The p r e s e n c e of ion a attests to the fact that the iso-
propoxycarbonyl r e s i d u e is in the (x-position with r e s p e c t to the amine nitrogen, and the high-melting p r o d -
uet, consequently, has s t r u c t u r e IIc.

I~H3_C(CH3)~.
(~ t
+
(CH3):,C--NH:CH--CO2--C3H 7 ~'~-~ ~cH2

H
+
m/~ ,r2 b ,,/~ ~3o c m/e 74 d m/e 217

~ H
CHCOOH f ~ . V _ . _ ~ C H= CH2

H
e m/e 171 f m/e ,4:~ g m/e ,~6

The mass s p e c t r u m of the l o w - m e l t i n g product contains intense peaks with m / e 217, 174, 143, and 86,
which c o r r e s p o n d to ions d, e, f, and g. The e s t e r function is, consequently, in the fl-position with r e s p e c t
to the amine nitrogen, and i s o m e r i c s t r u c t u r e lid should be assigned to the low-melting product.
The other peaks in the mass s p e c t r a c o n f i r m the proposed f o r m u l a s . The stability of the molecular
ions with r e s p e c t to electron impact (WM) and the selectivity (SJ2) proved to be g r e a t e r for the h i g h - m e l t -
ing product.

EXPERIMENTAL

The melting points were determined with a Koffler block and were not c o r r e c t e d . The IR s p e c t r a of
KBr pellets of the compounds w e r e r e c o r d e d with a UR-10 s p e c t r o m e t e r . The UV s p e c t r a of alcohol s o l u -
tions of the compounds were obtained with a Speeord UV VIS s p e c t r o p h o t o m e t e r . The mass s p e c t r a were
r e c o r d e d with an MKh-1303 s p e c t r o m e t e r at an i o n i z i n g - c h a m b e r t e m p e r a t u r e of 150 ~ and an ionizing vol-
tage of 70 eV.
Isopropyl 2 - B r o m 0 - 3 - ( 1 - b e n z y l - 2 - i m i d a z o l y l ) a c r y l a t e . A 7.5-g (0.04 mole) sample of 2 - f o r m y l i m i d -
azole [6] was added cautiously to a solution of 20 g (0.04 mole) of i s o p r o p o x y c a r b o n y l b r o m o m e t h y l e n e t r i -
phenylphosphorane in 75 ml of pure methylene chloride, and the mixture was allowed to stand at r o o m t e m -
p e r a t u r e for 20 h. It was then extracted with 5% HC1, and the precipitated hydroehloride was r e m o v e d by
filtration and s t i r r e d with a s a t u r a t e d sodium bicarbonate solution. The solution was then extracted with
ether. The e x t r a c t was dried, and the ether was evaporated to give white c r y s t a l s , which were c r y s t a l l i z e d
f r o m benzene to give a product with mp 128-130 ~ in 68% yield. IR s p e c t r u m , c m - l : 530 ( C - B r ) , 1620
(C =C), and 1670 (C =O). Found.. C 55.4; H 5.4; Br 22.9; N 8.0%. C16Ht2BrN202. Calculated: C 55.0; H 4.9;
Br 23.1; N 8.0%.
Isopropyl 3 - ( 1 - B e n z y l - 3 - i n d o l y l ) - 2 - b r o m o a c r y l a t e . A solution of 4.61 g (0.0105 mole) of isopropoxy-
c a r b o n y l b r o m o m e t h y l e n e t r i p h e n y l p h o s p h o r a n e and 2.35 g (0.01 mole) of 1 - b e n z y l - 3 - f o r m y l i n d o l e in 24 ml
of benzene was refluxed for 8 h, after which the solvent was r e m o v e d by distillation, and the r e s i d u e was
extracted thoroughly with boiling p e t r o l e u m ether. The p e t r o l e u m ether was r e m o v e d , and the r e s i d u e was
e h r o m a t o g r a p h e d on 120 g of activity III aluminum oxide with b e n z e n e - p e t r o l e u m ether (1 : 9) to give 1.5 g
(40%) of c o l o r l e s s c r y s t a l s . C r y s t a l l i z a t i o n f r o m cyclohexane gave an analytically pure sample with mp
87.5-89 ~. IR s p e c t r u m , e m - L 700 ( C - B r ) , 1620 (C =C), and 1715 (C =O). Found: C 63.5; H 5.1; Br 20.1;
N 3.3%. C21H20BrNO2. Calculated: C 63.3; H 5.0; Br 20.1; N 3.5%.
2-(3-Indolyl)-2-phenylethylamine (IIa). A mixture of 344 nag (2.9 mmole) of indole and 950 mg (3.5
mmole) of t e t r a a c e t y l d i b o r a t e illl.Sml of nitromethane was maintained at 20 ~ for 15 min, after which 294
mg of phenylhydrazine [7] in 1.5 ml of nitromethane was added. The mixture was s t i r r e d f r o m 3 h, after
which dilute h y d r o c h l o r i c acid was added, and the mixture was extracted with ether. The aqueous l a y e r w a s
made alkaline with p o t a s s i u m carbonate and extracted with methylene chloride. The e x t r a c t was dried with

928
sodium sulfate and e v a p o r a t e d , and the r e s i d u e was c r y s t a l l i z e d f r o m benzene to give 300 mg (65%) of IIa
with mp 127-130 ~ No melting-point d e p r e s s i o n was o b s e r v e d for a mixture of this product with a s a m p l e
of known s t r u c t u r e [4].
T e t r a a c e t y l diborate was obtained by heating a s u s p e n s i o n of 20 g of b o r i c acid with 130 ml of acetic
anhydride until a vigorous r e a c t i o n developed. The hot solution was then f i l t e r e d , and the product was
c r y s t a l l i z e d by cooling the filtrate.
1 - M e t h y l - 4 - ( 1 - b e n z y l - 2 - i m i d a z o l y l ) - f i - c a r b o l i n e (IIIb). A 10.0-g (0.035 mole) s a m p l e of aziridine Ib
was added with w a t e r cooling to a s t i r r e d solution of 19.2 g (0.07 mole) of t e t r a a c e t y l diborate and 6.2 g
(0.053 mole) of indole in 50 ml of n i t r o m e t h a n e , and the mixture was maintained at 25 ~ for 20 h. It was then
poured into dilute h y d r o c h l o r i c acid, and the acidic mixture was e x t r a c t e d with ether. The aqueous l a y e r
was made alkaline with p o t a s s i u m carbonate and e x t r a c t e d with ethyl acetate. The e x t r a c t was cooled in a
r e f r i g e r a t o r , the p r e c i p i t a t e d c r y s t a l s w e r e s e p a r a t e d , and the f i l t r a t e was dried with sodium sulfate and
e v a p o r a t e d to d r y n e s s to give 8.5 g of crude t r y p t o p h a n e s t e r lib. A 7-g s a m p l e of this product was dis-
solved in 17.5 ml of 2 N aqueous alcoholic s o d i u m hydroxide, and the solution was maintained at r o o m t e m -
p e r a t u r e for 26-30 h. It was then n e u t r a l i z e d with 35 ml of 1 N sulfuric acid, and the r e s u l t i n g oil was s e p -
a r a t e d and d i s s o l v e d in 70 ml of 50% f o r m i c acid. The f o r m i c acid solution was mixed with 7 ml of a c e t a l -
dehyde, and the mixture was allowed to stand at 17 ~ for 48 h. The acid and w a t e r w e r e r e m o v e d by v a c u u m
distillation to give 5.2 g of crude r e s i d u e ; 4.2 g of this r e s i d u e was dissolved in 440 ml of w a t e r , and the
solution was heated to the boiling point and mixed with 122 ml of 12% p o t a s s i u m d i c h r o m a t e and 26 ml of
acetic acid. The m i x t u r e was r e f l u x e d for 5 rain, after which it was cooled and t r e a t e d with sodium sulfite
and n e u t r a l i z e d with p o t a s s i u m carbonate. The r e s u l t i n g s u s p e n s i o n was e x t r a c t e d with c h l o r o f o r m , and
the s u b s t a n c e that p a s s e d into the c h l o r o f o r m phase was purified by c h r o m a t o g r a p h y on activity III a l u m i -
n u m oxide. B e n z e n e - p e t r o l e u m ether eluted a f i r s t f r a c t i o n , which was discarded. Benzene elated 0.76 g
of solid c o l o r l e s s f l - c a r b o l i n e lIIb. UV s p e c t r u m , A.max, n m (log ~): 212 (4.44), 241 (4.45), 254 (4.46), 285
(3.98), 294 (4.13), 349 (3.79), and 357 (3.90). The dihydrocbloride of IIIb had mp 360 ~ (from methanol, in a
s e a l e d capillary). Found.* C 64.1; H 5.2; C1 16.9; N 13.7%. C22H18N4.2HC1. Calculated: C 64.0; H 4.9;
C1 17.1; N 13.7%.
I s o p r o p y l 2 - t e r t - B u t y l a m i n o - 3 - ( 3 - i n d o l y l ) p r o p i o n a t e (IIc) and I s o p r o p y l 3 - t e r t - B u t y l a m t n o - 2 - ( 3 - i n -
dolyl)propionate (IId). A solution of 0.50 g (2.7 mmole) of a z i r i d i n e c a r b o x y l i c acid e s t e r Ic [8] and 0.48 g
(4.1 mmole) of indole in 4 ml of t e t r a h y d r o f u r a n (THF) was added to a cooled solution of 0.35 g (2.5 mmole)
of b o r o n t r i f l u o r i d e e t h e r a t e in anhydrous THF. The solvent was then r e m o v e d r a p i d l y in vaeuo, and the
r e s i d u e was heated at 100 ~ for 3 h. The g l a s s y r e a c t i o n mixture was shaken with 5% h y d r o c h l o r i c acid and
e t h e r , and the aqueous l a y e r was s e p a r a t e d and made alkaline with s o d i u m b i c a r b o n a t e . The alkaline m i x -
t u r e was e x t r a c t e d with ether to give 0.5 g of an oil, which c r y s t a l l i z e d on t r i t u r a t i o n with cyclohexane.
According to TLC, t h e s e c r y s t a l s constituted a mixture of two s u b s t a n c e s . They w e r e s p e a r a t e d by c h r o -
m a t o g r a p h y with a column filled with s i l i c a gel and elation with b e n z e n e - p e t r o l e u m ether (4 : 1) s a t u r a t e d
with a m m o n i u m hydroxide. The f i r s t fractions contained 0.14 g of tryptophan d e r i v a t i v e lic with mp 120 ~
(from carbon t e t r a c h l o r i d e ) . IR s p e c t r u m , c m - l : 1740 (CO), 3300 (NH), and 3420 (indole NH). Mass s p e c -
t r u m , m/e (%): 302 (6), 287 (0.4), 245 (0.5), 230 (16), 215 (12), 188 (0.8), 172 (74), 159 (15), 130 (77), 116
(59), 74 (100), 57 (48), 43 (12), 41 (25). Found.* C 66.9; H 7.9; N 8.6%. CIsH2~N202.H20. Calculated: C67.5;
H 8.1; N 8.7%.
Workup of the subsequent f r a c t i o n s gave 0.1 g of lid with mp 101-103 ~ (from c a r b o n t e t r a c h l o r i d e ) .
IR s p e c t r u m : 1740 (CO), 3310 (NH), and 3400 (indole NH). Mass s p e c t r u m , m / e (%): 302 (12), 287 (3), 245
(1), 230 (2), 217 (24), 175 (20), 174 (33), 159 (8), 157 (11), 143 (32), 130 (44), 86 (I00), 57 (66), 44 (40), 43
(45), 41 (71).

LITERATURE CITED
1. K. I. Kuchkova and A. A. Semenov, Khim. G e t e r o t s i l d . Soedin., 1069 (1970).
2. R. Bucourt and M. Vignau, Bull. Soc. Chim. F r a n c e , 1190 (1961).
3. E. Pfail and U. H a r d e g g e r , Angew. Chem., 79, 188 (1967).
4. E. P. Styngach, K. I. Kuchkova~ T. M. E f r e m o v a , and A. A. Semenov, Khim. G e t e r o t s i l d . Soedin., 1523
(1973).
5. G. M / r k l , B e r . , 94, 2996 (1961).
6. P. E. I w e r s e n and H. Lurid, Acta Chim. Scand., 20, 2649 (1966).
7. T. A. Foglia and D. Swern, J. Org. Chem., 32, 75 (1967).
8. L. Bouteville, Y. G e l a s - M i a l h e , and R. V e s s i e r e , Bull. Soc. Chim. F r a n c e , 3264 (1971).

929
CHEMISTRY OF INDOLE
X L I . * ORIENTING E F F E C T OF SUBSTITUENTS DURING
THE NITRATION OF PROTONATED INDOLES

L. G . Y u d i n , A . N. K o s t , UDC 547.752.753 : 542.958.1 : 543.51'422.25.6

E. Ya. Zinehenko, and A. G. Zhigulin

The nitration of indoles containing donor substituents in the 5- and 7-positions in s t r o n g l y

acidic media involves the protonated f o r m and gives p r i m a r i l y compounds with a nitro group
in the 6-position. The s t r u c t u r e s of the products w e r e p r o v e d by PMR, UV, and m a s s s p e c -
t r o m e t r y.

The orientation of the e n t r y of substituents during e l e c t r o p h i l i c attack of the benzene r i n g of indole

s t r u c t u r e s has been studied p r i m a r i l y in the c a s e of the a c c e s s i b l e 2 - m e t h y l - 3 - c a r b e t h o x y ( a c y l ) i n d o l e s [2],
which a r e r e l a t i v e l y stable with r e s p e c t to d i m e r i z a t i o n , oxidation, and addition to the C 2 - C s double bond.
If s u c h compounds a r e p r o t o n a t e d in s t r o n g l y acidic media, n a m e l y , at the oxygen a t o m of the carbonyl
group, no s u b s t a n t i a l change in the distribution of the e l e c t r o n density in the a r o m a t i c r i n g o c c u r s [3]. Con-
sequently, it might be a s s u m e d that the o b s e r v e d p r i n c i p l e s c o r r e s p o n d to orientation of the substituents
during a t t a c k of the unprotonated molecule. In addition, the p r e s e n c e itself of an e l e c t r o n - a c c e p t o r group
in the p y r r o l e r i n g cannot r e f l e c t the distribution of the e l e c t r o n density and c o m p l i c a t e s an evaluation of
the orienting effect of substituents in the benzene r i n g of the indole s t r u c t u r e s .
It is known that nitration of 2,3-dimethylindole [4] takes place in the 5-position, while nitration of 2-
m e t h y l - 3 - c a r b e t h o x y i n d o l e takes place in the 6- and 4-positions [2]. Initial protonation of the p y r r o l e r i n g
(attack of a proton at Cs) has been e s t a b l i s h e d for 2,3-dimethylindole, arid the substantial difference in the
orientation t h e r e f o r e depends not only on substitution of the e l e c t r o n - d o n o r CH s group by the e l e c t r o n - a c -
ceptor COOR group (with a c o r r e s p o n d i n g change in the distribution of the e l e c t r o n density in the benzene
ring), but, above all, on the difference in the s t r u c t u r e of the indole ring itself undergoing attack (the p r o -
tonated and unprotonated s t r u c t u r e s ) .
The fact that a m i n o m e t h y l a t i o n (which p r o c e e d s as e l e c t r o p h i l i c attack but not in acidic media) is, to
a f i r s t a p p r o x i m a t i o n , subject to the s a m e p r i n c i p l e s of o r i e n t a t i o n as nitration or b r o m i n a t i o n , s e r v e s as
a c o n f i r m a t i o n of the above ration'ale. F o r e x a m p l e , the dialkylaminomethyl group attacking 2 - m e t h y l - 3 -
c a r b e t h o x y - 5 - h y d r o x y i n d o l e p r e f e r a b l y e n t e r s the 4 - p o s i t i o n [5]. If the indole molecule does not contain
a 3 - c a r b e t h o x y group, a m i n o m e t h y l a t i o n of 5-hydroxyindoles also takes place in the 4-position [6]. Under
the s a m e conditions, 7-hydroxykadoles a r e a m i n o m e t h y l a t e d in the 6-position [6].
It thus b e c o m e s n e c e s s a r y to study the orienting effect of substituents of the benzene r i n g under con-
ditions of known protonation of the p y r r o l e ring. As model s t r u c t u r e s , we s e l e c t e d 2 - m e t h y l i n d o l e s that
have e l e c t r o n - d o n o r substituents (CH3, OH, and CHsO) in the 5- or 7-positions. If compounds of this type
undergo nitration in the unprotonated f o r m , a t t a c k on Cs, i.e., substitution in the p y r r o l e r i n g , is p r e f e r a b l e .
If the p y r r o l e - r i n g protonated f o r m undergoes the r e a c t i o n , the substituent should e n t e r the benzene ring.

* F o r Communication XL s e e [1].

M. V. L o m o n o s o v Moscow State University. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedin-

enii, No. 8, pp. 1070-1078, August, 1974. Original a r t i c l e s u b m i t t e d N o v e m b e r 5, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A cop), o f this article is available from the publisher for $15.00.

930
 0~ ' p I o [ ~

~6

0.)

b-
9
~ ~ zr z4 04

, ,...~
. . . . . . . . ~o~ ~o"
,m
' ( H N ) i~ON ~oo ~U 9 ~o4 r
~-~
L~O9
co--
IZ~eO ~cozm L~CO
z~
m _

. :I:

-- 0

o ~o ~. ~ ~ ~ ~ ~ "~

.~ .-, ~ ~ ~ ~ ~ ~ ~ .~.

~ ~ ~ ~-~ ~ ~ ~= ..~

....... q ---o .... ~

Z Z Z Z Z
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ,,.a
0 0 ~

~ - ~ ~ I ~

9 c~ - - m~-~
m
oo : : = -~ ~ ~ ~

93].
 It was found that a complex mixture of deeply colored substances, f r o m which nitration products could
not be isolated, is f o r m e d by the action of a nitrating mixture or nitric acid solutions of various c o n c e n t r a -
tions on 5-hydroxyindoles (Ia-c). However, if the hydroxyindoles and their O-substituted derivatives a r e
carefully dissolved in concentrated sulfuric acid with cooling ( t o - 10 ~ and the nitration is then c a r r i e d out
at - 2 0 to - 2 5 ~ p r i m a r i l y 6-nitroindoles a r e formed. T h i n - l a y e r c h r o m a t o g r a p h y (TLC) of the r e a c t i o n
It

~N/'CH a "-.~/~NT~C H 3 N0 ~ " ~ N , , / ~ C H3

I i I
R R R
! a-C II a-C

!-I| a R=H, W=CH3, R2=OCH3; b R=CH 3, RL=H, R2=OCH3; C R=H, RI=R2=CH 3

mixture in the nitration of 1,2-dimethyl-5-methoxyindole (Ib) made it possible to detect a v e r y s m a l l a m o u n t

of the 4 - n i t r o i s o m e r , which, with r e s p e c t to its c h r o m a t o g r a p h i c behavior in various s y s t e m s , is identical
to 1 , 2 - d i m e t h y l - 4 - n i t r o - 5 - methoxyindole (III), obtained by hydrolys is and decarboxylation of 1,2-dimethyl-
3 - c a r b e t h o x y - 4 - n i t r o - 5 - m e t h o x y i n d o l e (IIIa) [7]. We w e r e able to isolate 4-nitro i s o m e r IVa p r e p a r a t i v e l y
in v e r y low yield only f r o m the products of nitration of 1,2-dimethyl-5-hydroxyindole (Id) (IV : IVa =9 : 1).
~(o2

CH3 NO2 j H3 C ,r-~'~

Ci; 3 CH3 ~;H,~

CH3 CH~
IVC IVb

3-Nitroindoles were not detected in any of the e x p e r i m e n t s , and this excludes the possible nitration
of the unprotonated f o r m . The PM:R s p e c t r a of the s t a r t i n g indoles, even in t r i f l u o r o a c e t i c acid, indicate
protonation of the C 3 a t o m (for IIb a singlet of two protons attached to C 8 and a shift of the signal of the
2-CH~ protons to weak field a r e o b s e r v e d because of partial localization of the positive charge on C2). When
a nitro group is introduced, the b a s i c i t y d e c r e a s e s , and the addition of sulfuric acid is r e q u i r e d for c o m -
plete protonation. In t r i f l u o r o a c e t i c acid, these compounds give s p e c t r a with a broadened signal of 4-H p r o -
tons and protons of the methyl groups in the 2- and 3-positions (IIa and IIc), apparently as a consequence
of exchange with t r i f l u o r o a c e t i c acid; in dimethyl sulfoxide (DMSO) or acetone, these signals are visible as
s h a r p peaks. The s a m e observations were also made for some other indoles. They c o r r e l a t e with direct
m e a s u r e m e n t s of the basicities of these substances. In fact, the s p e c t r o p h o t o m e t r i c determination of the
pK a values of a number of the starting indoles and their nitro derivatives gave the following values, ex-
p r e s s e d on the Hinman scale [8] in sulfuric acid concentration (by weight), in which the indicator ratio log
J = 0 (i.e., the r a t i o of the ionized f o r m of indole to the nonionized f o r m is 1):

pK~ H2SO4, %

Ia -- 1,0_0,10 15,3
Ib + 0,8-- 0,30* --
Ic -- 1,0_0,15 15,4
IIa --4,15-0,15 45,4
Iib --2,25_+0,15 28,3
IIc -4,20_0,15 46,4
* F r o m the additive contribution of
the substituents to the b a s i c i t y of the
co mpo unds.
Thus, the introduction of a nitro group into the benzene ring substantially d e c r e a s e s the b a s i c i t y of
the indole s t r u c t u r e s (up to 3 units on the Hinman scale), which is one of the few n u m e r i c a l c h a r a c t e r i s t i c s
in the l i t e r a t u r e r e l a t i v e to the t r a n s m i s s i o n of the effect of a subsfituent f r o m the benzene ring to the p y r -
role r i n g in indole s t r u c t u r e s .

932
 The UV s p e c t r a make it p o s s i b l e to d i s t i n g u i s h the 4 - and 6 - n i t r o - i n d d e s , i n a s m u c h as the f o r m e r
differ with r e s p e c t to the shift of the l o n g - w a v e m a x i m u m b y 1 0 - 2 0 n m in the v i s i b l e p o r t i o n of the s p e c -
t r u m (Fig. 1). The s t r u c t u r e of IV is c o n f i r m e d b y the PM:R s p e c t r u m , w h i c h [s i d e n t i c a l to the s p e c t r u m
of a s a m p l e o b t a i n e d b y h y d r o l y s i s and d e c a r b o x y l a t i o n of IVc [7].

In the n i t r a t i o n of 7 - m e t h o x y i n d o l e s V and Va u n d e r s i m i l a r c o n d i t i o n s , the c h i e f p r o d u c t is the 6 - n i -

t r o i s o m e r , a l t h o u g h the p r e s e n c e of a s m a l l a m o u n t of a s e c o n d i s o m e r ( a p p a r e n t l y the 4 - n i t r o compound)
a n d of o x i d a t i o n p r o d u c t s was d e t e c t e d b y c h r o m a t o g r a p h y .

The PM1R s p e c t r a of n i t r o i n d o l e s VI and Via c o n t a i n two d o u b l e t s of p r o t o n s w i t h a s p i n - s p i n s p l i t t i n g

c o n s t a n t of 9 Ha in the a r o m a t i c r e g i o n . The PIV[R s p e c t r u m does not give a n u n a m b i g u o u s a n s w e r to the
c h a r a c t e r of the s u b s t i t u t i o n , i n a s m u c h as the s p e c t r u m of the 4 - i s o m e r would give a s i m i l a r p a t t e r n .
M e t h y l a t i o n of n i t r o i n d o l e VI w i t h d i m e t h y l s u l f a t e in DMSO w i t h s o d i u m h y d r i d e g i v e s n i t r o c o m p o u n d Via,
a n d the m e t h y l g r o u p a t t a c h e d to the n i t r o g e n a t o m of the indole r i n g , c o n s e q u e n t l y , does not a f f e c t the o r i -
entation.

TABLE 2. Results of Calculation by the Pariser-Parr-Pople

Method for 5- a n d 7 - H y d r o x y i n d o l e s

Atom Total Charge

density

~o I +0,370 0,256 N=C2 0,490

2 +0,080 0,033 C2=Ca 0,787
HO~cHa 3 --0,110 0,317 Ca=Ca 0,500
4 --0,078 0,544 C9=C4 0,547
I a +0,008 0,286 C4=Cs 0689
CH --0,060 0,003 Cs~Om 0,345
7 --0,036 0,273 Cs=C6 0,550
8 -0,091 0,066 CG=C7 0,743
9 --0,041 0,018 Cv=C8 0,548
10 0,119 0,212 C8=Co 0,576
1o 1 + 0,349* 0,235 N=C2 0,500
2 + 0,022 0,075 Ca=Ca 0,787
678 3 --0,171 0,404 Ca=C9 0,491
4 -0,083 0,562 C9=C4 0,552
H. 5 +0,008 0,234 C4=Cs 0,693
6 -0,068 O,OII Ca=Oto 0,344
7 -0,352 0,274 Ca=C6 0,556
8 --0,104 0,024 CG~C? 0,736
9 -0,035 0,005 C7=C~ 0,558
10 +O, II8 0,173 C8=C9 0,577
1 +0,368 0,201 N=C2 0,489
2 --0,083 0,09l Ca=Ca 0,787
3 -0,I03 0,286 Ca=C9 0,502
4 --0,036 0,47I C9=C~ 0,534
5 -0215 0,Ill C4~C6 0,743
6 -0,087 0,289 C5=C6 0,589
7 -0,007 0,338 C6:C 7 0,869
8 --0,1ll 0,013 C7~Oto 0,338
--0,048 0,003 CT=Ca 0,516
+0,t17 0,200 C6=C~ 0,587
~:~ CHa 1 +0,342* 0,193 N=C2 0,475
2 --0,043 0,202 C2=C3 0,789
3 -0,066 0,406 Ca=C9 0,503
Hi,to H 4 -0,042 0,416 C9=C4 0,533
5 -0,019 0,083 C4=Cs 0,743
6 -0,093 0,286 Cs=C6 0,589
7 --0,008 0,268 Cr 0,696
8 -0,123 0,003 CT~Om 0,231
9 --0,064 0,013 C7=Cs 0,520"
10 +0.116 0,144 Cs=C~ 0,582

10 N 1 +0,588 0,0007 N~C~ 0,826

2 +0,245 0,222 C9=C4 0,719
4 +0,028 0,3t0 C4=:Cs 0,579
5 +0,116 0,299 C~=C6 0,576
tt 6 -0,024 0,289 C5=0~o 0,436
7 +0,037 0,017 C6=Cr 0323
8 --0,I36 0,457 CT=Ca 0,574
9 +0,025 0,016 C8=C~ 0,577
10 +0,176 0,193

* The i n d u c t i v e effect of the m e t h y l g r o u p s was t a k e n into a c c o u n t .

933
 TABLE 2 (continued)

H 1 +0,534* 0,006 N=C2 0,819

2 + 0,368 0,164 C9=C4 0,708
t 2 4 - 0,031
- 0,312 C4=Cs 0,588
+0,I00 0,314 C~=O,o 0,422
CH 3
- 0,026
- 0,294 C5=C6 0,587
+0,025 0,023 C~=C7 0,711
--0,14'3 0,450 C7=C8 0,595
+0,007 0,022 C8=C9 0,696
lO +0,167 0,404
H +0,583 0,0004 N=C: 0,826
+0,252 0,101 C9=C4 0.716
4 +0,016 0,504 C4=C5 0,614
+ 0,097 0,032 C5=C6 0,691
- 0,023 0,274 C6=C7 0,6t5
HO +0,068 0,364 C7=0~o 0,346
-0,157 0,202 CT=Cs 0,558
9 +0,013 0,902 C8=C9 0,571
10 +0,152 0,326

H +0,525* 0,004 N=C2 0,817

+ 0,373 0,080 C9=C4 0,705
4 +0,011 0,504 C4=C5 0,624
o~HN~ cH3 5 +0,082 0.040 Cs=C6 0,689
6 0,023
- - 0,259 C6~C: 0,615
HO 7 +0,054 0,378 C:=O,0 0,382
8 --0,165 0,226 CT=Cs 0,576
9 -0,001 0,171 Cs=C9 0,591
10 +0,143 0,338

The m a s s s p e c t r u m of VI, in addition to an intense m o l e c u l a r ion,

Ig8 contains two intense ions with m / e 203 and 173,

4)0
"~ .......j
i ,:,v
~ H CH3 ~ [~]'---~ CH3

CHa NO2/~'~NM./~C H3
CH30 CH30
V VI

1: : I
t; :1 CH3 ~ ~ CH3
t: "I
3~0 CH3 NO2 CH3
L: :1
CH30 CH3 CH30 CH3
;L)ilrfl Va Via
t r I i ,
200 300 ~00 500
which a r e f o r m e d , r e s p e c t i v e l y , by loss by the m o l e c u l a r ion of 17 and,
Fig. 1. UV s p e c t r a of n i t r o - subsequently, 30 ainu, which is c o n f i r m e d by peaks of m e t a s t a b l e ions
indoles (alcohol): 1) 1,2-di- with m / e 187.3 and 147.2. This type of disintegration is c h a r a c t e r i s t i c
m e t h y l - 5-hydroxyindole (Id);
2) 1,2-di m e t h y l - 5 - h y d r o x y -
6-nitroindole (IV); 3) 1,2,di- -OH"

methyl-4-nitro-5-hydroxyin- 0T-
I I
CHa O= N~",,..~ ~ N ~ xCH3
I
dole (IVa). OH OCH3 CH30
M+ 220 m/e 203

+/'...~-.N-/-c. 3 o=~#-..S~N/.--%. 3

~H/cH2 VI ra/e 173 m/e 173

f o r a r o m a t i c n i t r o c o m p o u n d s with a n o r t h o g r o u p that i n c l u d e s a h y d r o g e n a t o m [9]. C o n s e q u e n t l y , the

s t r u c t u r e of the 6 - i s o m e r c a n be a s s i g n e d to VI.

We h a v e p r e v i o u s l y o b s e r v e d the p r e s e n c e of a n M-17(OH) ion in a n a n a l y s i s of the m a s s s p e c t r a of

1 , 2 , 5 - a n d 1 , 2 , 7 - t r i m e t h y l - 3 - c a r b e t h o x y - 6 - n t t r o i n d o l e s [1], a n d we a s c r i b e d it to s p l i t t i n g out of OH f r o m
the n e i g h b o r i n g n i t r o a n d m e t h o x y g r o u p s . P e a k s f o r m e d b y the l o s s b y the m o l e c u l a r ion of 17 and, s u b -
s e q u e n t l y , 30 u n i t s w e r e a l s o o b s e r v e d in the m a s s s p e c t r u m of o - n i t r o a n i s o l e , w h i l e the m o s t c h a r a c t e r -

934
istic p r o c e s s for p - n i t r o a n i s o l e was l o s s of 16 a m u or even the f r a g m e n t a t i o n c h a r a c t e r i s t i c for a r o m a t i c
nitro compounds ( s u c c e s s i v e l o s s of NO and CO).
The a p p e a r a n c e of a m a x i m u m c h a r a c t e r i s t i c for 6-nitroindoles is o b s e r v e d in the UV s p e c t r a of in-
doles VI and Via in the 4 0 0 - n m region.
Nitroindoles IIc, IV, and VI w e r e r e d u c e d to the c o r r e s p o n d i n g a m i n e s (IVb, VII, and VIIa) (Table 1).
Calculation of the e l e c t r o n density b y the LCAO MO method within the P a r i s e r - P a r r - P o p l e approx-
imation* for 1 , 2 - d i m e t h y l - 5 - h y d r o x y i n d o l e Id and its p r o t o n a t e d f o r m (Table 2) does not make it p o s s i b l e
to f o r m a p r e f e r e n c e for nitration in the 6- or 4 - p o s i t i o n s both with r e s p e c t to the o v e r a l l e l e c t r o n density
and with r e s p e c t to the c h a r g e density in the upper occupied orbital (the boundary orbital).
Substantial deviations in o r i e n t a t i o n w e r e r e v e a l e d for 7 - s u b s t i t u t e d indoles. It is known that the
chief product of n i t r a t i o n in sulfuric acid of 2 , 3 - d i m e t h y l - l , 7 - t r i m e t h y l e n e i n d o l e (in which the t r i m e t h y l e n e
bridge can be c o n s i d e r e d to be a 1,7-dialkyl grouping) is the 5 - i s o m e r (up to 90%) with a s m a l l a d m i x t u r e
of the 6 - n i t r o d e r i v a t i v e [10]. In our c a s e , the 7 - m e t h o x y group o r i e n t e d nitration p r i m a r i l y in the 6 - p o s i -
tion under the s i m i l a r conditions. The total charge on C 6 for 7-hydroxyindoles is higher than the total
c h a r g e on C a for the p r o t o n a t e d f o r m , and this is in a g r e e m e n t with the e x p e r i m e n t a l r e s u l t s .

EXPERIMENTAL
The IR spectra of mineral oil suspensions of the compounds were recorded with an IKS-22 spectrom-
eter. The UV spectra of alcohol solutions were recorded with a Cary-15 speetrophotometer. The PMR
spectra of tr[fluoroacetic acid solutions were recorded with a Varian S-60T spectrometer with hexamethyl-
disiloxane (HMDS) as the external standard. The mass spectrum of Vl was recorded with an MKh-!303
spectrometer with a system for the introduction of the sample directly into the ion source (50 eV, 110-120~
The reactions were monitored by means of thin-layer chromatography (TLC) on activity II (Broekmann
classification) a l u m i n u m oxide in the following s y s t e m s : b e n z e n e - e t h y l a c e t a t e - h e p t a n e ( 4 : 1 : 3 ) for I I a - c
and VII, b e n z e n e - e t h y l a c e t a t e (3 : 1) for l-b, IV, and IVa, and b e n z e n e - p e t r o l e u m ether (10 : 3) for 7 - m e t h -
oxyindoles VI and Via.
G e n e r a l Method for the P r e p a r a t i o n of 6 - N i t r o - and 5- a~d 7-Substituted Indoles. A 5 - m m o l e s a m p l e
of the indole was d i s s o l v e d in 20 ml of 96% sulfuric acid (-10~ a f t e r which the solution was cooled to - 2 5 ~
and a solution of 0.32 g (5 mmole) of nitric acid (sp. gr. 1.5) in 10 ml of 96% sulfuric acid was added. The
m i x t u r e was s t i r r e d at this t e m p e r a t u r e for 1-2 h (with c h r o m a t o g r a p h i c monitoring), a f t e r which it was
poured o v e r ice. The r e s u l t i n g p r e c i p i t a t e was r e m o v e d by filtration, w a s h e d with w a t e r , dried, and r e -
c r y s t a l l i z e d (Table 1).
6- and 4 - N i t r o - l , 2 - d i m e t h y l - 5 - h y d r o x y i n d o l e s (IV and IVa). The m i x t u r e of i s o m e r s f o r m e d after
nitration of 1 , 2 - d i m e t h y l - 5 - h y d r o x y i n d o l e (Id) by the method d e s c r i b e d above was p a s s e d through a column
containing activity II a l u m i n u m oxide with elation with b e n z e n e - e t h y l a c e t a t e (3 : 1). The f i r s t (dark) f r a c -
tion yielded 6-nitroindole IV, a f t e r which 4-nitroindole IVa was isolated (Table 1).
1 , 2 - D i m e t h y l - 5 - h y d r o x y - 6 - a m i n o i n d o l e (iVb). A 0.824-g (4 mmole) s a m p l e of 1 , 2 - d i m e t h y l - 5 - h y -
d r o x y - 6 - n i t r o i n d o l e (IV) was suspended in 80 m_l of ethanol, and a s m a l l amount of Raney nickel and h y d r a -
zine h y d r a t e (8 ml) (dropwise) w e r e added until all of the nitro compound had dissolved (~ 40 rain). The
mixture was then heated on a b o i l i n g - w a t e r bath until the solution had d e c o l o r i z e d (30 min). The hot s o l u -
tion was f i l t e r e d and v a c u u m e v a p o r a t e d to d r y n e s s , and the r e s i d u e was r e c r y s t a l l i z e d f r o m dioxane to
give 0.36 g (51%) of aminoindole IV with mp N200 ~ (dec.). Found: C 68.4; H 7.1%. CIoH12N20. Calculated:
C 68.2; H 6.9%. UV s p e c t r u m (2 N solution in H2304) , ~'max, n m (log e): 223 (4.03) and 294 (4.00).
2 , 3 , 5 - T r i m e t h y l - 6 - a m i n o i n d o l e (VII). As in the p r e p a r a t i o n of IVb, 0.816 g (4 mmole) of 1 , 2 , 5 - t r i -
m e t h y l - 6 - n i t r o i n d o l e IIc gave, a f t e r r e c r y s t a l l i z a t i o n f r o m aqueous alcohol, 0.613 g (72%) of aminoindole
VII with mp 163-164 ~ and R f 0.2. Found: C 75.9; H 8.1%. CI1Hi4N 2. Calculated: C 75.7; H 8.2%. IR s p e c -
t r u m : 3100-3350 c m - i (NH). UV s p e c t r u m (alcohol), Xmax, n m (log e): 233 (4.53), 274 (3.78), and 308
(3.s5).
2 , 3 - D i m e t h y l - 6 - a c e t a m i d o - 7 - m e t h o x y i n d o l e (VIII). The reduction of 0.88 g (4 mmole) of 1 , 2 - d i m e t h y l -
6 - n i t r o - 7 - m e t h o x y i n d o l e VI was c a r r i e d out as in the c a s e of IVb. At the end of the reduction, 10
ml of acetic anhydride was added to the m i x t u r e , and it was r e f l u x e d for ,~ 15 min. The hot solution was
f i l t e r e d , the solvent was v a c u u m e v a p o r a t e d , and the r e s i d u e was poured into cold water. The r e s u l t i n g
*The calculations w e r e p e r f o r m e d by V~ I, Minkin (Rostov State University).

935
precipitate was r e m o v e d by filtration, washed with w a t e r , air dried, and r e c r y s t a l l i z e d f r o m aqueous eth-
anol to give 0.896 g (85%) of acetamidoindole VIII with mp 194-195 ~ and R f 0.3 [ c h l o r o f o r m - m e t h a n o l
(25:1)]. Found: C 67.7; H 7.1%. C13H16N202. Calculated: C 67.3; H 6.970. IR s p e c t r u m : 3200 (NH) and
1685 (CO) c m -1. UV s p e c t r u m (alcohol), ~ m a x , n m (log e): 229 (4.79), 280 (3.99), and 377 (1.85).
1 , 2 - D i m e t h y l - 4 - n i t r o - 5 - m e t h o x y i n d o l e (lII). A 1.46-g (5 mmole) sample of 1 , 2 - d i m e t h y l - 3 - c a r b e t h -
o x y - 4 - n i t r o - 5 - m e t h o x y i n d o l e (IVc) was suspended in 40 ml of glacial acetic acid containing 2 ml of 96%
sulfuric acid, and the mixture was refluxed for 10 min, cooled, and n e u t r a l i z e d with 2 NaOH. The resulting
precipitate was r e m o v e d by filtration, washed with w a t e r , dried, and r e c r y s t a l l i z e d s u c c e s s i v e l y f r o m ben-
z e n e - p e t r o l e u m ether (2 : 1) and methanol to give 0.46 g (42%) of III with mp 139-140 ~ and R f 0.66. Found:
C 60.3; H 5.6; N 13.3%. C11H12N203. Calculated: C 60.0; H 5.5; N 12.8%. IR spectrum: 1500 and
1330 c m - i (NO2). UV s p e c t r u m (alcohol), ~'max, n m (log e): 216 (4.57) and 383 (3.80).
1 , 2 , 3 - T r i m e t h y l - 7 - m e t h o x y i n d o l e (Va). A 1.75-g (10 m m o l e ) s a m p l e of 2 , 3 - d i m e t h y l - 7 - m e t h o x y i n -
dole (V) was dissolved in 17 ml of d r y DMSO, and 0.5 g (20 mmole) of d r y dimethyl sulfate was added in
small portions with s t i r r i n g . The r e a c t i o n mixture heated by spontaneously to 50-60 ~. It was s t i r r e d for
2-3 h (with c h r o m a t o g r a p h i c monitoring) and poured into water. The precipitate was r e m o v e d by filtration,
washed with w a t e r , air dried, and r e c r y s t a l l i z e d f r o m aqueous methanol (with activated charcoal) to give
1.7 g of Va. An analytical sample was purified by elution with benzene in a column filled with aluminum ox-
ide. The yield of V a w i t h mp 74-75 ~ a n d R f 0.Swas 1.55 g (82%). Found: C 76.7; H 8.0,N7.8%. CI2H15NO.
Calculated: C 76.3; H 8.0; N 7.4%. UV s p e c t r u m (alcohol), ~'max, n m (log e): 280 (4.69), 276 (3.84), 285
(3.83), and 296 (3.79).
1 , 2 , 3 - T r i m e t h y l - 6 - n i t r o - 7 - m e t h o x y i n d e l e (Via). The p r o c e d u r e used to obtain Va was used to obtain
this compound by methylation of 2.2 g (10 mmole) of 2 , 3 - d i m e t h y l - 6 - n i t r o - 7 - m e t h o x y i n d o l e (VI). The yield
of nitreindole Via was 2.2 g (90%); with r e s p e c t to its melting point and IR s p e c t r a , the product was iden-
tical to the nitroindole obtained by nitration of Va.

LITERATURE CITED
1. A . N . Kost, L. G. Yudin, E. Ya. Zinchenko, A. B. Belikov, and O. A. Solov'ev, Khim. Geterotsikl.
Soedin., 375 (1974).
2. L . G . Yudin, A. I. Pavlyuchenko, V. A. Budylin, V. I. Minkin, and A. N. Kost, Khim. Geterotsikl.
Soedin., 1506 (1971).
3. V . A . Budylin, A. N. Kost, E. D. Matveeva, and V. I. Minkin, Khim. Geterotsikl. Soedin., 68 (1972).
4. W. Noland, H. Smith, and D. Johnson, J. Org. Chem., 2_~8,2534 (1962).
5. S . A . Monti and W. O. Johnson, T e t r a h e d r o n , 2_66,3685 (1970).
6. F. T r o x l e r , G. Berman, and F. Seeman, Helv. Chlm. Aeta, 5_1, 1203 (1968).
7. E. Ya. Zinchenko, L. G. Yudin, a n d A . N. Kost, Khim. Geterotsikl. Soedin., 1646 (1973).
8. R . L . Hinman and I. Lang, J. Amer. Chem. Soc., 8_.66,3796 (1964).
9. S. Meyerson, I. P u s k a s , and E. K. Fields, J. A m e r . Chem. Soc., 88, 4974 (1966).
10. A . N . Kost, L. G. Yudin, and V. A. Budylin, Khim. Geterotsikl. Soedin., 39 (1966).

936
NUCLEOPHILIC ADDITION OF INDOLE
AND ITS DERIVATIVES TO fi-AROYLACRYLIC ACIDS

S. G. A g b a l y a n , G. V. G r i g o r y a n , UDC 547.757
a n d A. A. D z h a n t n y a n

Condensation of f l - b e n z o y l - and fl-toluylaerylic acids with indole and its derivative gave
P - b e n z o y l - and f l - t o l u y l - a - ( 3 - i n d o l y l ) p r o p i o n t c acids and their derivatives.

Indole and its derivatives r e a c t with unsaturated compounds in which the double bond is activated by
conjugation with one or s e v e r a l e l e c t r o n - a c c e p t o r groups. The r e a c t i o n with some monosubstttuted and
a ,fi-disubstituted ethylenes, for example, with n i t r o s t y r e n e and ehalcone, proceeds at the C (3) atom of the
indole ring in the p r e s e n c e of acid catalysts [1-5]. Attempts to obtain adducts of [ndole with cinnamic acid
and some other a , f i - d i s u b s t i t u t e d olefins under the same conditions were unsuccessful [6]. Consequently,
the s u c c e s s of the r e a c t i o n depends on the nature of the substituting groups that p r o m o t e e l e c t r o n depletion
of the ethylene bond.

The a i m of our investigation was to study the nncleophilic addition of indole and its derivatives to the
a ,fl-disubstituted double bond o f / ~ - a r o y l a e r y l i c acids.
The r e s e a r c h of a number of investigators has shown that in the case of olefins with u n s y m m e t r i c a l
s t r u c t u r e s the orientation of nucleophilic attack is determined by the relative stability of the intermediately
f o r m e d earbantons, and an unambiguous direction of attack of a nucleophilic agent to give a earbanion of the
aeetophenone type [7] has been established for a r o y l a c r y l i c acids.

In the r e a c t i o n of indole and its derivatives with f i - a r o y l a c r y l t c acids one might s i m i l a r l y expect the
intermediate formation of a zwttterton cr complex that is subsequently stabilized to the corresponding fi-
a r o y l - a - (3-tndolyl)propionic acid.

I
R'

When b e n z o y l a c r y l i c and p - t o l u y l a c r y l i c acids a r e refluxed in benzene, in the absence of c a t a l y s t s ,

with indole and its derivatives, f l - a r o y l - a - i n d o l y p r o p i o n i c acids are f o r m e d in s a t i s f a c t o r y yields (Table 1).
The LR s p e c t r a of the l a t t e r contain absorption bands c h a r a c t e r i s t i c for an acid carbonyl group at 1700
e m -t and for a carbonyl group conjugated with an a r o m a t i c r i n g at 1670-1680 c m -t.

The UV s p e c t r a of f i - b e n z o y l - a - s u b s t i t u t e d propionic acids (A max 280 nm, ~ rain 265 nm) differ sub-
stanttally f r o m the s p e c t r a of f i - t o h y l - a - s u b s t i t u t e d proptonic acids (~. max 255 am, ~ rain 235 nm).

Institute of Organic Chemistry, Academy of Sciences of the Armenian SSR, Yerevan. Translated
from Khimiya Geterotsiklichesldkh Soedinenii, No. 8, pp. 1079-1082, August, 1974. Original article sub-
mitted September 7, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this pubfication may be reproduced,
stored hz a retrieval system, or rransmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

937
 T A B L E 1. a - R ' - f l - A r o y l p r o p i o n i c A c i d s RCCH~C~(R')COOClt3
II
O
@-
Empirical Found, % Calc., %
formula
C H iN C [H [ N
i i ,' ] i
CsHs 3 -Indolyl 66 150 CIsHIsNO3 74,1 i 4,8 4,6173,7 J5,2 4,8 41
C~H~ 1-Methyl-3-indoly] 137 C19HITNO3 74,0 5 515,0 74,2 !s,6 4,6 55
C6H~ 1-'(~-Cyanoethyl)- 6 170 C21HI8N~O3 73,1 ] 5,5 7,9 !72,8 15,2 8,1 42
3 -indolyl
C~Hs 2-Methyl-3-indoly] 0,2 145-- I CIgHIrNO3 73,9 !5,7 i4,7174,2 5,6 !4,5 55
--147
C~Hs 1,2-Dimethyl- 5- 0,2 180 C21H2tNO4 71,6 [57 142 , 71,8 ! 6,0 4,0 80
methoxy-34ndolyll
p-CHaC~H4 3-Indolyl ! 12 260 C~gHtTNO3 74,1 i 5,9 J4,9 ' 74,2 ! 5,6 ; 4,6 98
p-CHsC6H~ 1-Meth~)l-3-indolyl112 185 C2oH~gNO~ 74,9 5,6 ~4,4 174,8 i 5,9 ~4,6 99
p-CHzCaH4 1-(~-Cyanoethyr}-! 12 178 C22H2oN203 72,9 15,3 : 7,7,73,3 5,6 7,8 99
8 -indolyl I
p-CH3CsH4 2,-Methyl-3-indolyl! 0,2 190 C2oHlgNO3 74,8 !63 i4,5 ]74,7 5,9 4,3 81
p-CHzC~H~ 1,2-Dimethyl-5- '0,2 123 C2~H23NO4 72,6,6,5
I ' I
3,5'72,3 6,3,3,8 87
methoxy-34ndolylI I
t
'
' i
i
I

In o r d e r to d e t e r m i n e t h e s i t e of a d d i t i o n of t n d o l e we c a r r i e d out t h e d e c a r b o x y l a t i o n o f / 3 - b e n z o y l -
a - ( 3 - i n d o l y l ) p r o p i o n i c a c i d to t h e k e t o n e , t h e s t r u c t u r e of w h i c h c o u l d b e r e p r e s e n t e d b y the f o l l o w i n g f o r -
m u l a s , depending on the s t r u c t u r e of the s t a r t i n g a c i d :

(/ \)--c--eft--Ell 3

ti
I II

The f o r m a t i o n of II is n e g a t e d b y the PMR s p e c t r a (the a b s e n c e of a CH 3 group). Thus, tndole adds to the

a - c a r b o n a t o m of f i - b e n z o y l a c r y l i c a c i d in a c c o r d a n c e with the s c h e m e p r e s e n t e d above.
The m e t h y l e s t e r s w e r e obtained f r o m the s y n t h e s i z e d a c i d s . I n a s m u c h as the p r o b a b i l i t y of the f o r -
mutton of a d i m e r and t r t m e r of indole under the influence of f i - a r o y l a c r y l i c a c i d s is not excluded, we r e a l -
ized the s y n t h e s i s of methyl f i - b e n z o y l - a - ( 3 - [ n d o l y l ) p r o p i o n a t e f r o m methyl f i - b e n z o y l a c r y l a t e and [ndole:

It

The f o r m a t i o n of the m e t h y l e s t e r s was c o n f i r m e d by m a s s - s p e c t r a l d e t e r m i n a t i o n of the m o l e c u l a r

weights. The IR s p e c t r a of the e s t e r s contain a b s o r p t i o n bands c h a r a c t e r i s t i c f o r a conjugated c a r b o n y l
g r o u p at 1720-1730 c m -1 and for a c a r b o n y l g r o u p c o n j u g a t e d with an a r o m a t i c r i n g at 1670-1680 c m -1 [8].
C o n d e n s a t i o n of a - k e t o a c i d s with h y d r a z i n e h y d r a t e gave 6 - p h e n y l - and 6 - ( p - t o l y l ) - 4 - s u b s t i t u t e d
2 , 3 , 4 , 5 - t e t r a h y d r o - 3 - p y r t d a z i n o n e s , the IR s p e c t r a of which contain a b s o r p t i o n bands c h a r a c t e r i s t i c for a
c a r b o n y l g r o u p in a p y r i d a z i n e s y s t e m (1600-1680 c m - i ) .
N--NH
RC~ilt4--U=O

R,.t~ fR"'
I
R"
A c c o r d i n g to the r e s u l t s of p r e l i m i n a r y t e s t s , the s o d i u m s a l t s of the s y n t h e s i z e d acids have g i b b e r -
e l l i n - l t k e a c t i v i t y in doses of 0.1 m g / m l . T h e y do not have a u x i n - l i k e activity.

EXPERIMENTAL
The s y n t h e s i z e d a c i d s w e r e c h r o m a t o g r a p h e d on S[lufol in a c e t o n e - c h l o r o f o r m ( 1 : 2 ) . The I:R s p e c -
t r a of m i n e r a l oil s u s p e n s i o n s w e r e r e c o r d e d with a U R - 1 0 s p e c t r o m e t e r . The UV s p e c t r a w e r e obtained
with an S F - 4 s p e c t r o p h o t o m e t e r . The PM:R s p e c t r a w e r e r e c o r d e d with a V a r i a n s p e c t r o m e t e r (60 MHz).

938
 T A B L E 2. Methyl a-R'-fi-Aroylpropionates

i / i I Calc., % l*-
R' %P'/ Em Pirical ~ Found, %
formula - - T - - I
/
o
r

C6H5 .3-Indolyl
:l-Methyl-3-indolyl
115
103
CIoHt;NOa 74,615.0 4,8 742 5,6 4,6
C..oH,~NOa 72,3,58 4,! 72,8 6,0 -t4
77
83
C6H~
C~H~ ':l-(l~-Cyanoethyl)-a-indolyl 109 C~2H~0N~Oa73,7 5,8 7,4 73,3 5,6 7,8 75
C6H~ 2-Methyl-3-indolyl 50 C~oH~gNOa 74,8,5,9 4,4 74,8 5,9 4,4 43
C~H~ 1,2-Dimethyl..5-methoxy- 128 C22H~aNO4 72,4,6,3 3,8 72,3 6,3 3,8 44
' 3-indolyl
p-CH~C~H~ 3-Indolyl 139 C~0H19NOa 74,5 5,9 4,3 73,8 6,0 4,4 86
p-CHaC6H~ ]l-Methyl-3-indolyl 117 C~H~NOa 75,1 5,9 4,2 75,2 6,3 4,2 89
-(B-Cyanoethyl)-34ndolyl III C~aHs=N=Oa73,9 5,67,2 73,8 5,9 7,5 90
p-CHaC6H4
p-CHaC6H4 II3-Methyl-3-indolyl 81 C21H~:NOa 75,5 6,7'4,5 75,2 6,3 4,2 50
p-CHsC6H~ ,1,2-Dimethyl-5-methoxy- 154 CeaHesNO4 72,5 6,63,9 72,8 6,6:3,7 48
i 3-indolyl

T A B L E 3. 6-.R-4-R'-2,3,4,5-Tetrahydro-3-pyr[dazinones
N--NH

Found,

C6Hs 13-Indolyl
tg,
I

1202
Empirical
formula
ii
C~sHIsN30 74,9' 5,2
ciH
I
14,4' 74,9 '5.2! 14,5'82
C6H5 {1-Methyl-3-indolyl 1216 CIgHITNaO 74,115,9 14,2175,2' 5:6 ': 13,9 98
C~H~ i 1-(~-Cyanoethyl)-34ndolyl 1208 C21HIsN40 74,515,2 16,6i 74,7 , 5,3 116,5 88
C6H5 ,2-Methyl-3-indolyl ! 174 C[gHIrN30 75,1! 5,4 13,7, 75,2 ! 5,6 i 13,8 81
C6H5 i 1,2-Dimethyl4-methoxy- {196 C~lH21N302 ,73,0 5,9 11,7 72,6 ,6,1 ~12,1 61
i 3-indolvl i
p-CH3C6H4 ',3-Indoly'l . , 1250 ClgHIrN~O 75,3;'6,1 1 3 , 9 ; 7 5 , 2 i 5 , 6 13,9i97
p-CHaC6H4 [1-Methyl-3-inamyl 245 C2oH~gNaO i75,4 6,0 13,2i 75,7 ' 6,0 13,2~35
p-CHaC6H4 1-(5-Cyanoethyl)-34ndolyl 237 C22H2oN40 73,815,7 15,7 74,1 ,5,7 15,7,90
p-CHaC6H4 / 2-Methyl-3-indolyl 1256 C20HLgN~O 175,7'6.4 13,4 75,7 6,l 13,2157
p-CHaC6H4 il,2-Dimethyl-5-methoxy-: 216 CnH23,N302 173,5!6,5 11,8'73,1 6,4 11,6; 6
(3-indolyl ! / t

fl-Aroyl-a-(.3-indoly!)propionic Acid_ A mixture of 1.17 g (0.01 mole) of [ndole and 0.01 mole of
aroylacrylic acid in i0 ml of dry benzene was heated on a water bath for 0.5-12 h. The resulting precip-
itate was r e m o v e d by filtration and dissolved in 5% sodium hydroxide solution. The sodium hydroxide solu-
tion was then filtered to r e m o v e impurities, and the filtrate was treated with dilute HC1 to precipitate the
product, which was washed with hot benzene.
The products of condensation with substituted [ndoles were similarly obtained and purified by reerys-
tallization from benzene (Table I).
Decarboxylation of/3-Benzoyl-a-(3-indolyl)propionic Acid. A 2.93-g (0.01 mole) sample of/3-ben-
zoyl-a-(3-[ndolyl)propionic acid was added to 20 ml of glycerol heated to 140 ~ The mixture was then
heated at 150-160 ~ for 10-15 min to complete the decarboxylation. A transparent solution formed during
the heating period. Water (70 ml) was added to it, and the following day the resulting phenyl /3-(3-[ndolyl)-
ethyl ketone was removed by filtration to give 2.3 g (79%) of a product with mp 121-122 ~ (benzene) and R/
0.42. LR spectrum: 1674 cm -i (C =O). The doublet of a methyl group was not detected in the PMR spec-
trum (pyridine). Found: C 81.5; H 6.1; N 5.3%. CI7HIsNO. Calculated: C 81.9; H 6.11; N 5.6~. The ox[me
was obtained as cream-colored crystals with mp 172 ~ Found: N 10.4%. CnHI6N20. Calculated: N I0.6%.
Methyl fl-Aroyl-.(3-indolyl)propionates. A) A 10-ml sample of a 0.5% solution of hydrogen chloride
in methanol was added to 0.05 mole of the appropriate /3-aroyl-a-(3-indolyl)propionic acid, and the mixture
was a/lowed to stand at room temperature for a few days. It was then heated on a water bath for 1 h, after
which it was cooled and poured into water. The resulting precipitate was removed by filtration, dried, and
recrystallized from ethanol, or the methanol was evaporated, and the residue was recrystallized from dilute
ethanol (Table 2).
B) A 0.58-g (0.005 mole) sample of indole and 10 ml of benzene were added to 0.005 mole of the
methyl ester of the appropriate fl-aroylacrylic acid, and the mixture was refluxed for 6 h. The resulting
precipitate was removed by filtration, washed with dry ether, and recrystallized from dilute ethanol.

939
 . 6 - A r y l - 4 - R ' - 2 , 3 , 4 , 5 - t e t r a h y d r o - 3 - p y r [ d a z i n o n e s . A mixture of 0.005 mole of the a p p r o p r i a t e
f l - a r o y l - a - ( 3 - i n d o l y l ) p r o p i o n [ c acid and 4 ml of 80~ hydrazine hydrate was heated on a w a t e r bath for 2-4
h. The r e s u l t i n g p r e c i p i t a t e was washed with hot alcohol or r e c r y s t a l l [ z e d f r o m alcohol (Table 3).

LITERATURE CITED

i. G. W. Sa[~sen, V. A. E a g e l h a r d t , and W. J. Widdleton, J. A m e r . Chem. Soc., 8_.00,2815 (1958).

2. N. E. Noland, W. C. Kuryla, and R. F. Lange, J. A m e r . Chem. Soc., 8_~1, 6010 (1959).
3. Z. R a p p o p o r t , J. Chem. Soc., 4498 (1963).
4. R. F o s t e r , P. F o s t e r , and P. Hanson, T e t r a h e d r o n , 2_~1, 255 (1965).
5. Y. Shirota, S. Esaki, S. Kusabajashi, and H. Mikawa, Bull. Chem. Soc. Japan, 455, 836 (1972).
6, J. R. Merchant, K. M. Chhatriwalla, S. S. Salgar, and J. R. P a r t e l l , J. Ind. Chem. Soc., 4..88, 613 (1971).
7, A. N. N e s m e y a n o v , M. I. R y b i n s k a y a , and L. V. Rybin, Usp. Khim., 3_66, 1089 (1967}.
8. J. A. Ballantine, C. B. B a r r e t t , R. J. S. B e e r , B. G. Boggiano, S. Eardly, B. E. Jennings, and A. Rob-
e r t s o n , J. Chem. Soc., 2227 (1957).

940
INDOLES
XLIV.* SYNTHESIS OF 1-SUBSTITUTED TRYPTOPHANS

I. I. G r a n d b e r g and G. P . Tokmakov UDC 547.755.07

1-Substituted tryptophans were obtained by heating ~ - f o r m y l - T - b u t y r o l a c t o n e with N l - s u b -

stttuted a r y l h y d r a z i n e s in aqueous acidic media.

The known methods for the synthesis of tryptophols are based either on the use of an a l r e a d y existing
indole ring or on the r e a c t i o n of a r y l h y d r a z i n e s with T - a c y l p r o p y l alcohols, which are obtained f r o m
a - a c y l - T - b u t y r o l a c t o n e s . However, T - h y d r o x y b u t r y a l d e h y d e cannot be obtained by hydrolysis and d e c a r -
boxylation of ( ~ - f o r m y l - 7 - b u t y r o l a c t o n e (I), inasmuch as acid cleavage to butyrolactone and f o r m i c acid
o c c u r s . Thus, tryptophols that do not have substituents in the 2-position cannot be synthesized by this
method.
We have p r e v i o u s l y r e p o r t e d the synthesis of 1,2-disubstttuted tryptophols directly f r o m a - a c e t y l -
T - b u t r y o l a c t o n e [2], b y - p a s s i n g the step involving the production of acetylpropyl alcohol. We t h e r e f o r e a s -
s u m e d that h y d r o l y s i s and decarboxylation of a r y l h y d r a z o n e s of a - f o r m y l - ~ / - b u t y r o l a c t o n e would occur un-
der s i m i l a r conditions because of the d e c r e a s e in the p o l a r i t y of the C 3 - C 4 bond in s t r u c t u r e A when the
oxygen a t o m (X =O) is r e p l a c e d by a nitrogen a t o m (X =NR).

"0"%0
i " I~
A

By c a r r y i n g out the r e a c t i o n of lactone I with Nl-substituted phenylhydrazines we were able to obtain

2-unsubstituted tryptophols (IIa-d) in good yields. The a s s u m e d r e a c t i o n s c h e m e is presented in [2].
.CLIO . -~,. .... .CH:CH2OH
9
7"-~-']" + C:I.I.N(R)NH 2 t1~' . !i I!
" - 0 / / -0 "\~/""--N f"
I
R
I Ii

II a R=CcIIs; b R=CH:C.;tl3; C R =Cliff d R=CH(CH2) 2

EXPERIMENTAL
The UV s p e c t r a of [sopropyl alcohol solutions of the compounds were r e c o r d e d with an Hitachi
E P S - 3 T s p e c t r o p h o t o m e t e r . The IR s p e c t r a of CC14 solutions were r e c o r d e d with a UR-20 s p e c t o m e t e r .
The PM1R s p e c t r a of CC14 solutions were r e c o r d e d with a Varian T-60 s p e c t r o m e t e r (60 MHz) with hexa-
methyldisiloxane (HMDS) as the internal standard. The melting points were determined with a Mettler
F - P 5 apparatus. Analysis by g a s - l i q u i d c h r o m a t o g r a p h y (GLC) was c a r r i e d out with a Yanaco-G 800 T
c h r o m a t o g r a p h at a c a r r i e r gas (H2) flow r a t e of 40 m l / m i n . Column I consisted of 5c7cSE-30 silicone on
C h e z o s o r b (Czechoslovakian SSR), 0.25-0.36 mm, washed with acid arid silantzed with HMDS; the packing
had a polarity of 12% with r e s p e c t to /3 ,/3 ,-dihydroxydiproptonitrile [3]. Column II consisted of 5% poly-

* For Communication XLIII see [I].

K. A. T i m i r y a z e v Moscow A g r i c u l t u r a l Academy. T r a n s l a t e d f r o m Khimiya Geterotstkltcheskikh
Soedinenii, No. 8, pp. 1083-1084, August, 1974. Original a r t i c l e submitted August 6, 1973.

9 76 Plenum Publishing Corporation, 22 7 [Vest 17th Street, New York, iV. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval s3,stem, or transmitted, in any form or by an), means, electronic, mechanical, photocopying, microfihning,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available .(root the publisher for $15. 00.

94"1
ethylene glycol (molecular weight 6000) on Porolit (Czechoslovakian SSR), 0.25-0.35 mm, containing 5%
KOH with a relative polarity of 39%. Corrected retention times (trI and tr II) were obtained, and the Kovaes
retention indices (II and IIi) were calculated for the l-alkyltryptophols (200 and 220 ~ and for the l-aryl-
tryptophols (220 and 240~ Chromatography was carried out in a thin layer of activity II AI203 in benzene-
isopropyl alcohol (20 : 1). The chromatograms were developed with iodine vapors.
Commercial-grade salts of l-benzyl-l-phenyl-, l-methyl-l-phenyl-, and l,l-diphenylh~rdrazines
were used. l-lsopropyl-l-phenylhydraz[ne hydrochloride was obtained by the method in [4]. a-Formyl-
T-butyrolactone (I) was obtained by the method in [5].
General Method for the Preparation of Tryptophols (IIa-d). A solution of 0.04 mole of lactone I and
0.04 mole of Ni-substituted phenylhydrazine in a mixture of 50 ml of isopropyl alcohol, 30 ml of water, and
5 ml of concentrated hydrochloric acid was refluxed for 5 h, after which the solvents were evaporated with
a rotary evaporator, and 40 ml of benzene and 60 ml of water were added to the residue. The benzene was
evaporated, and the residue was vacuum distilled. The resulting crude product (2 g) can be subjected to
additional purification with a chromatographic column (50 by 2.5 cm) filled with activity II Al203 by elution
initially with benzene and then with benzene- isopropyl alcohol (40 : I). The yield of pure sample from the
column was 1.4-1.5 g.
l-Phenyltryptophol (IIa). This compound, with bp 170-173 ~ (i mm and Rf 0.58 was obtained in 62%
yield* from l,l-diphenylhydrazine hydrochlorlde. GLC: 220 ~ (tri=7.92 , II=2268: tr II =37.5, Iii=3543),
240 ~ (tri=3.64, II =2261; trII=lg.50, Iii =3557). Found: C 81.1; H 6.4%. CI6HIsNO. Calculated: C 81.0;
H 6.4%. According to [6], this compound has bp 185 ~ (I mm).
1-Benzyltryptophol (lib). This compound, with mp 53 ~ (ether-pentane) and Rf 0.59, was obtained in
58% yield from l-benzyl-l-phenylhydrazine hydrochloride. GLC: 220 ~ (trI =9.30, Ii=2320; trII=50.0, Iii =
3623), 240 ~ (trI=4.40, Ii=2333; trll =24.80, Iii =3651). According to [6], this compound has mp 51 ~ (from
pentane).
l-Methyltryptophol (IIc). This compound, with bp 130-133 ~ (0.5 ram) and Rf 0.55, was obta[ned in 46%
yield from l-methyl-l-phenylhydrazine hydrosulfate. GLC- 200 ~ (trI=2.70, II =1733; trli=22.91, III=2718),
220 ~ (trI=l.67, Ii=1758;trii=4.36, Iii=2755). PMR spectrum,t 5,ppm: 2.41s (OH), 2.78t (J=7 Hz,3-
~-CH2) , 3.47 s (I-CH3) , 3.63 t (J =7 Hz, 3-fl-CH2) , 6.59 s (2-H), and-6.80-7.50 m (aromatic protons). Found:
C 75.0; H 7.5%. CIIHi3NO. Calculated: C 75.4; H 7.5%. According to [6], this compound has bp 158-160 ~
(1 mm).
l-Isopropyltryptophol (lid). This compound, with mp 78.3 ~ (from hexane) and Rf 0.60, was obtained
in 54% yield from l-isopropyl-l-phenylhydrazine hydrochloride. GLC: 200 ~ (trl =3.51, Ii=1813; tr II=
32.60, Iii =2829), 220 ~ (trI = 2. 075, II = 1829; tr I'l= 5.43, Ill =2834). UV spectrum, ~. max: 226, 280 (lnfl) nm
(log ~: 4.52, 3.67, 3.72, and 3.68). LR spectrum. ~ 3630 (OH),1612 em -~ (ring stretching vibrations). PIVIIR
spectrum, 6,ppm: 1.38 d [J=7 Hz (CH3)2C],2.15 s (OH), 2.83t(J=7Hz,3-a-CH2),3.68t (J=7 Hz, 3-fl-
CH2) , 4.48 m (J=7 Hz, I-CH), 6.70-7.50 m (2-H and aromatic protons). Found: C 77.0; H 8.5%. CI3HITNO.
Calculated: C 76.8; H 8.4%.

LITERATURE CITED
i. R. A. Khmel'nitskii, N. A. Klyuev, A. F. Dolgikh, N. I. Bobrova, and I. I. Grandberg, Izv. Timiryazev.
Sel'skokhoz. Akad., i, 176 (1974).
2. I. I. Grandberg and G. P. Tokmakov, Khim. Geterotsikl. Soedin., 204 (1974).
3. B. A. Rndenko, l~. L. Ii'kova, V. F. Kucherov, and N. A. Kerimova, Zh. Analit. Khim., 2__55,1405 (1970).
4. I. I. Grandberg and S. N. Dashkevieh, Khim. Geterotsikl. Soedin., 342 (1971).
5. T. Kaneko, K. Wakabayashi, and H. Katsura, Bull. Chem. Soc. Japan, 3_55, 1149 (1962).
6. I. I. Grandberg and T. P. Moskvina, Khim. Geterotsikl. Soedin., 1366 (1972).

*Here and subsequently, the yields are indicated for the product obtained after distillation. The spectral
characteristics are given for substances purified by chromatography.
t The following abbreviations are used here and subsequently: s is singlet, d is doublet, t is triplet, and m
is multiplet.

942
INDOLES
XLVI.* SALTS OF ARYLHYDRAZINES AND BISULFITE
DERIVATIVES OF T-HALO CARBONYL COMPOUNDS
IN THE SYNTHESIS OF TRYPTAMINES

I. I. Grandberg and N. I. Bobrova UDC 547.752.07

The f o r m a t i o n of t r y p t a m i n e s instead of the usual F i s c h e r cyclization is o b s e r v e d when s a l t s

of a r y l h y d r a z i n e s a r e heated with T - h a l o carbonyl compounds. Bisulfite d e r i v a t i v e s of T - h a l o
earbonyl compounds with both a r y l h y d r a z i n e s t h e m s e l v e s and with t h e i r s a l t s can also be
used in the s y n t h e s i s of the t r y p t a m i n e s .

In an investigation of the p o s s i b i l i t y of the use of the method in [2, 3] for the synthesis of t r y p t a m t n e s
b a s e d on the condensation of a r y l h y d r a z i n c s with 7 - h a l o carbonyl compounds we o b s e r v e d that the s a l t s
of a r y l h y d r a z i n e s (I), which a r e m o r e stable than the c o r r e s p o n d i n g b a s e s (Table 1, path A), can also be
used as the s t a r t i n g compounds.
At f i r s t glance, the r e s u l t s may s e e m unexpected. It is known that the s a l t s of a r y l h y d r a z i n e s undergo
F i s c h e r cycltzation to indoles on heating with carbonyl compounds. In p a r t i c u l a r , the a r y l h y d r a z o n e s ff
T - h a l o carbonyl compounds f o r m 3 - ( f i - c h l o r o e t h y l ) i n d o l e s (XVII) under acidic conditions [7-10]. This also
might have been expected in our e a s e , i n a s m u c h as a r y l h y d r a z o n e s XIII a r e f o r m e d v e r y r a p i d l y when s a l t s
I a r e mixed with carbonyl compounds II [3].
The r a t e of the F i s c h e r r e a c t i o n (path A) is d e t e r m i n e d p r i m a r i l y by protonation of the a r y l h y d r a z o n e
[11, 12] o r , m o r e p r e c i s e l y , b y the r a t e of f o r m a t i o n of the e n e h y d r a z i n e [13].
The a r y l h y d r a z o n e s of c a r b o n y l compounds a r e w e a k b a s e s with pK a values of the conjugate acids of
~ 1 . 5 [141.
Path B i-~"~ ~It2CH~CH2Cl Path A
L~'L N-- N// \ R "
H
XlIt

fl\ / A H\C/
f/ ~ ~ I ~("- h +1,/
r {\ IJ. +~c.. ~ l. II /c\ ' "
~"~../"N--N z --R" ~'~.//~N--N \R H+ ~"~./:'~N--N / \R"
N/ ' HCI H H H H H H
XVlll XlV XV XVI
L 1
Usualsteps in the syn- Usualsteps inthe
thesis of tryptamines Fischer reaction

'%~2<Nr
It H
III XVll

* F o r Communication XLV see [1].

K. A. T i m i r y a z e v Moscow A g r i c u l t u r a l A c a d e m y . T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h
Soedinenti, No. 8, pp. 1085-1088, August, 1974. Original a r t i c l e s u b m i t t e d October 16, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 1 7th Street, New York, N, Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15. 00.

943
 T A B L E 1. C h a r a c t e r i s t i c s of t h e C o m p o u n d s O b t a i n e d
A (from salts I B (from
I " HX) bisulfite.
Com- R" R" rap, *C bp, ~ _ __ denva-
pound R (ram) Yield Itives of
x ~o 'lid yield,
" I% k
III H H 113--115~ 185--187 ! CI 78 i 78
(0,5) r
IV CH3 H 135(2)1362 HSO4 78 !83
!nz)2~ 1,6021 ,
V CH2C6H6 H H 93--942 157--161 -- -- 78
(0,1)
VI H 5-CH3 H 95--962 150--155 HSO4 45 --
(0,1)
VII H ! 5-OCH2C6H6 H 84--864 62
VIII H H CH3 1085 214--216 CI 74 74 (91")
i (1,5)
IX CI-16 H CH6 54--556 170--172 HSO4 75 i8o (6o-i-)
(0,2) !

X H 5-CHa CH6 100--101s 210--212 HS04 71 !_

I
r (8) I
i
XI H 7-CHs CH3 160--161s I 209--211 C1 64 i--
1
(7) E
i
XII CH2C6H6 H CHs 54--556 170--172 i CI 74 I--
(0,5) ,
[ J

* O b t a i n e d b y h e a t i n g in a s e a l e d a m p u l in 90% m e t h a n o l at 170-180 ~
f o r 2 h.
F r o m a r y l h y d r a z i n e s a l t I and b i s u l f i t e d e r i v a t i v e of l i b b y r e f l u x -
ing in 60% m e t h a n o l .

Such l o w b a s i c i t i e s a r e r e s p o n s i b l e for the f a c t t h a t t h e s a l t ~ - b a s e (XIII-XIV) e q u i l i b r i u m u n d e r o u r

c o n d i t i o n s of a q u e o u s a l c o h o l s o l u t i o n s ( t h e i r pH is ~ 1.75) is s h i f t e d to f a v o r the u n p r o t o n a t e d h y d r a z o n e
(XIII) (N70% o f t h i s f o r m is p r e s e n t ) .
In t h i s c o n n e c t i o n , t h e u s u a l F i s c h e r r e a c t i o n (path A) d o e s not o c c u r , but a c o m p e t i t i v e p r o c e s s -
q u a t e r n i z a t i o n a t the f l - n i t r o g e n a t o m in h y d r a . z o n e XIII to g i v e N - a n i l i n o p y r r o l i n e XVIII and final c o n v e r -
s i o n to t r y p t a m i n e t l I (path B) - d o e s t a k e p l a c e .
A n i n c r e a s e in t h e a c i d i t y [7-10] s h i f t s the e q u i l i b r i u m to f a v o r p r o t o n a t e d h y d r a z o n e XtV, d e c r e a s i n g
t h e p o s s i b i l i t y o f q u a t e r n i z a t i o n , a n d , in a d d i t i o n , i n c r e a s e s t h e r a t e o f c o n v e r s i o n of h y d r a z o n e XIII to e n e -
h y d r a z o n e XVI (which is r e m o v e d f r o m the r e a c t i o n ) , i n c r e a s i n g t h e r a t e of i n d o l i z a t i o n [15] (path A).
O n l y t h e f o r m a t i o n of e n e h y d r a z i n e XVI c a n l e a d to i n d o l e XVII, b u t a p p a r e n t l y d o e s not o c c u r d u r i n g
e a c h a c t of i t s d e v e l o p m e n t , i n a s m u c h a s t h e e n e h y d r a z i n e f o r m is e x t r e m e l y u n f a v o r a b l e [16] and is r a p -
i d l y c o n v e r t e d to h y d r a z o n e XIII t h r o u g h t h e s a m e s t e p s v i a the a b o v e - i n d i c a t e d s c h e m e ( X V I - X V - X I V - X I I I ) .
H o w e v e r , in t h e c a s e of q u a t e r n i z a t i o n , s t r u c t u r e XVIII, w h i c h is i d e a l for t h e s u b s e q u e n t s i g m a t r o p i c
[3,3] s h i f t [3], is f o r m e d . S h i f t i n g of t h e double b o n d to t h e n i t r o g e n a t o m in t h e m o l e c u l e of u n p r o t o n a t e d
b a s e c a n n o t o c c u r h e r e , and t h e r e a c t i o n p r o c e e d s r e a d i l y a l o n g t h e p a t h o f f o r m a t i o n of the t r y p t a m i n e
(path B).
The k i n e t i c d a t a s h o u l d a l s o be t a k e n into a c c o u n t . The r a t e - d e t e r m i n i n g s t e p in the s y n t h e s i s of
t r y p t a m i n e s is q u a t e r n i z a t i o n of t h e f i - n i t r o g e n a t o m of h y d r a z o n e XIII [12].
It f o l l o w s f r o m a c o m p a r i s o n o f t h e r a t e c o n s t a n t s of F i s c h e r r e a c t i o n s c a t a l y z e d b y a c i d s [17] a n d
p r o c e e d i n g u n d e r t h e i n f l u e n c e of a l l y l b r o m i d e [12] u n d e r c o m p a r a b l e c o n d i t i o n s t h a t t h e s e r a t e s a r e f i r s t -
o r d e r v a l u e s (K 1 0 . 5 . 1 0 -3 a n d 4.7 9 10 -3, r a i n - i , r e s p e c t i v e l y ) ,
The d i f f e r e n c e b e t w e e n o u r r e a c t i o n a n d t h e a b o v e r e a c t i o n s c o n s i s t s in t h e f a c t t h a t q u a t e r n i z a t i o n
of t h e f i - n i t r o g e n a t o m p r o c e e d s i n t r a m o l e c u l a r l y , i . e . , t h e p r o b a b i l i t y f a c t o r , w h i c h a l w a y s p r o m o t e s an
i n t r a m o l e c u l a r r e a c t i o n , s h o u l d a l s o b e t a k e n into a c c o u n t .
W e w e r e a l s o a b l e to find a n o t h e r v a r i a n t of the m e t h o d for t h e s y n t h e s i s of t r y p t a m i n e s III b a s e d on
t h e use of t h e s t a b l e b i s u l f i t e [18] d e r i v a t i v e s o f T - h a l o c a r b o n y l c o m p o u n d s (XX). T h i s is p a r t i c u l a r l y i m -

944
portant for the synthesis of 2-unsubstituted t r y p t a m i n e s , inasmuch as T - c b l o r o b u t y r a l d e h y d e itself (IIa) is
an e x t r e m e l y unstable compound.
Derivatives XX a r e r e a d i l y obtained via the usual s c h e m e [18]. Condensation of the l a t t e r with a r y l -
hydrazines XIX o c c u r s when the compounds are r e f l u x e d in 60% methanol in a neutral medium (no r e s i n i f i -
cation is observed). The yields of the t r y p t a m i n e s (Table 1, path B) are b a s i c a l l y even higher than when
f r e e 7 - h a l o carbonyl compounds are used [2]. In this c a s e , c a r r y i n g out the r e a c t i o n at higher t e m p e r a -
t u r e s (by heating in a sealed ampul at 170-180 ~ for 2 h) p r o m o t e s a f u r t h e r i n c r e a s e in the yields (Table 1,
path B, compound VIII).
Salts of a r y l h y d r a z i n e s I can also be used in this s a m e r e a c t i o n , but, despite variations in the condi-
tions (changes in the t e m p e r a t u r e and the r e a g e n t r a t i o s ) , the yields of the t r y p t a m i n e s are considerably
lower (Table 1, path B, compound IX).

EXPERIMENTAL
The IR spectra of KBr pellets of the compounds were recorded with a UR-20 spectrometer. The UV
spectra of ethanol solutions were recorded with an EPS-3T spectrophotometer. Thin-layer chromatography
(TLC)v~as carried out on SUufol UV-254 in [sopropyl alcohol-25% ammonia (90: 15) (RF); paper chroma-
tography was carried out on Volodarski[ "fast' paper in n-butanol-acetic acid-water (4 ~"1 ~ 5) 0Rf). The
chromatograms were developed with Erlich's reagent.
T-Chlorobutyraldehyde (IIa). This compound was obtained by Rosemund reduction [18] of T-ebloro-
butyryl chloride in tetralin at 130-140%
T-Chloropropyl Methyl Ketone (lib). This compound was obtained in 66% yield by the method in [19]
by refluxtng acetylpropyl alcohol with excess concentrated HCI.
Bisulfite Derivative of T-Chlorobutyraldehyde (XXa). This compound was obtained in 96% yield by
the method in [18] and was 90% pure.
Bisulfite Derivative of T-Chloropropyl Methyl Ketone (XXb). This compound was similarly prepared
in 92~ yield and was 95% pure.
p-Benzyloxyphenylhydrazine. A total of 143 g (0.625 mole) of p-nitrophenol benzyl ether was added
gradually in 10-15-g portions (until all of the solid had dissolved) to a refluxing m[xtttre of 400 ml of meth-
anol, 400 rnl of hydrazine hydrate, and 3 g of Raney nickel (type W-2 [20]), after which the mLxture was re-
fluxed for 1 h. The hot solution was decanted away from the catalyst, and the alcohol was removed by vac-
uum distillation. The crystalline residue was removed by filtration and washed with 600 ml of hot water
(in 200-ml portions). The moist,well-squeezed solid was dissolved in 500 ml of hot [sopropyl alcohol, and
concentrated HCI was added until the mixture was acid to Congo red (~ 50 ml). The precipitated crystalline
salt (~ i00 g) was removed by filtration and washed with ether. The filtrate was then vacuum evaporated
until a precipitate began to form. An additional 32 g of p-aminophenol benzyl ether hydrochlor[de was ob-
tained. The overall yield was 132 g (90%); mp 210-212 ~ (from aqueous isopropyl alcohol [22].
The diazonium salt from p-aminophenol benzyl ether was reduced with stannous chloride in hydro-
chloride. The yield of the hydrazine was 70%; mp 106-107 ~ [22].

General Method for the Preparation of Tryptamines (III). A) A solution of 0.05 mole of T-chloro-
butryaldehyde (IIa) or T-chloropropyl methyl ketone (IIb) in I0 ml of methanol was added to a refluxing so-
lution of an equimolar amount of arylhydrazine salt I in 60 ml of 90% methanol, and the mixture was re-
fluxed for I0 h. The alcohol was then removed by distillation, and the residue was dissolved in 50 ml of
water. The neutral impurities were extracted with ether (two 20-ml portions). The aqueous solution was
cooled and made alkaline, and the resttlting oil was extracted with benzene (three 20-ml portions). The ex-
tract was dried with fused KOH and vacuum distilled. The crystalline compounds were additionally purified
by crystallization.

B) A solution of 0.05 mole of arylhydrazine XIX or its salt (1) in the minimum amount of methanol
was added all at once to a refluxing solution of 0.05 mole (based on the principal product) of bisulfite deriv-
ative XX in I00 ml of 60% methanol, and the mixture was refluxed on a water bath for 14 h. The alcohol
was removed with a rotary evaporator, and the residue was dissolved in 50 ml of 1 N HCI. The reaction
mixture was then worked up as in the preceding method (A).

945
 The individuality of all of the t r y p t a m i n e s obtained (HI) was monitored by c h r o m a t o g r a p h y on S i h f o l .
The identification of the c r y s t a l l i n e compounds was e s t a b l i s h e d by means of mixed melting point determin--
ations.
5-Benzyloxytryptamine (VII). This compound, with mp 84-86 ~ [4], was obtained in a yield that was
62% of that expected from theory B (it began to crystallize after evaporation of the benzene extract, which
had first been filtered through a layer of aluminum oxide): Rf 0.60, IRf 0.86. Found: C 76.7; H 6.8%.
CITHIsN20. Calculated: C 76.7; H 6.8%. IR spectrum: 3350, 3290 (NH); 1620, 1590, and 1490 cm -I (ring).
UV spectrum, ~.max, nm (log e): 277 (3.67), 285 (3.62), and 291 (3.57). The picrate, with mp 222.5-224 ~
(dec.), was obtained in absolute ether with a molar amount of pieric acid and was recrystaliized from the
minimum amount of alcohol. Found: N 14.1%. C17HIsN20. C6H3N3OT. Calculated: N 14.2%.

LITERATURE CITED
i. I.I. Grandberg and N. M. Przheval'skii, Izv. Timiryazev. Sel'skokhoz. Akad., 2, 177 (1974).
2. I.I. Graadberg and N. I. Bobrova, Khim. Geterotsikl. Soedin., 213 (1973).
3. I.I. Graadberg, Khim. Geterotsikl. Soedin., 579 (1974).
4. L.M. Morozovskaya, G. N. Tsvetkova, N. N. Suvorov, I. S. Tubina, E. I. Mikhailovskaya, and A. A.
Chemerisskaya, Zh. Vsesoyuzn. Khim. Obshchestva, i i, 477 (1966)o
5. I.I. Grandberg and T. I. Zuyanova, Khim. Geterotsikl. Soedia., 875 (1968).
6. I.I. Grandberg, N. I. Afonina, and T. I. Zuyanova, Khim. Geterotsild. Soedin., 1038 (1968).
7. E. Sehaww and D. M. Woolley, J. Amer. Chem. Soc., 7_55, 1877 (1953).
8. B. MeKay, Can. J. Chem., 41, 2585 (1963).
9. M. Sletzinger, W. Gaines, and W. Ruyle, Chem. Ind., 1215 (1957).
I0. U.S. Patent No. 3,014,043 (1961); Chem. Abstr., 5_~6,15,486 (1962).
11. K.H. Pausaeker and C. J. Schubert, J. Chem. Soc., 814 (1950).
12. I.I. Grandberg and N. M. Przheval'skH, Izv. Timiryazev. Sel'skokhoz. Akad., 2, 192 (1972).
13. D. Desaty and D. Keglevic, Croat. Chem. Aeta, 36, 103 (1964).
14. V.I. Sorkin, Master's Dissertation, Moscow (1973).
15. I.I. Grandberg, Izv. Timiryazev. Sel'skokhoz. Akad., 5, 188 (1972).
16. I.I. Grandberg, T. I. Zuyanova, N. M. Przheval'skii, and V. I. Minkin, Khim. Geterotsikl. Soedin.,
750 (1970).
17. p.J.T. Scheltus, Kinetic Investigations of the Fischer Indole Synthesis, Leiden (1959), p. 21.
18. I.I. Grandberg and N. I. Bobrova, Izv. Timiryazev. Sel'skokhoz. Akad., 6, 170 (1970).
19. A.P. Meshcheryakov and V. G. Glukhevtsev, Izv. Akad. Nauk SSSR, Otd. Khim. Nauk, 780 (1958).
20. A. Pavlic and H. Adkins, J. Amer. Chem. Soc., 6_88,1471 (1946).
21. N.N. Suvorov, Doctoral Dissertation, Moscow (1962).
22. C. Mentzer, C. Beaudet, and M. Bory, Bull. Soc. Chim. France, 421 (1953).

946
LAC TAM ACETALS
XI.* REACTIONS OF N - M E T H Y L - 2 - P Y R R O L I D O N E DIETHYLACETAL
WITH SOME NUCLEOPHILIC AND ELECTROlC'HILIC REAGENTS

A. M. Z h i d k o v a , V. G . G r a n t k , UDC 547.745
N. S. K u r y a t o v , V. P . P a k h o m o v ,
O. S. A n i s t m o v a , and R. G. Glushkov

It is shown in the c a s e of the r e a c t i o n of N - m e t h y l b u t y r o - , N - m e t h y l v a l e r o - , and N - m e t h -

y l c a p r o l a c t a m diethylacetals with benzyl cyanide that the f t v e - m e m b e r e d acetal is the m o s t
r e a c t i v e in the r e a c t i o n with compounds having an active methylene link. 1 - M e t h y l - 3 - ( w -
p h e n y l - w - b e n z o x y m e t h y l e n e ) - 2 - p y r r o l t d o n e is p r i m a r i l y f o r m e d in the r e a c t i o n of N - m e t h y l -
2 - p y r r o l t d o n e diethylacetal with C6HsCOC1. The r e a c t i o n of N - m e t h y l c a p r o l a c t a m dtethyl-
acetal with a c r y l o n t t r i l e gives a mixture of N - m e t h y l c a p r o l a c t a m , 1 - m e t h y l - 2 - e t h o x y - 3 -
( f l - c y a n o e t h y l ) - 4 , 5 , 6 , 7 - t e t r a h y d r e a z e p i n e , and 2 - m e t h y l - l , 9 - d e h y d r o - 9 - c y a n o - 2 - a z a b i c y c l o -
[5.2.0]nonane.

The a i m of the p r e s e n t r e s e a r c h was to study the r e a c t i o n s of N - m e t h y l - 2 - p y r r o l i d o n e diethylacetal

(Ia) with s o m e nucleophilic and e l e c t r o p h i l i c r e a g e n t s and to c o m p a r e the data obtained with the r e s u l t s of
analogous r e a c t i o n s of N - m e t h y l v a l e r o - (Ib) and N - m e t h y l c a p r o l a c t a m s (Ic). In 1961, Meerwein and co-
w o r k e r s [2] p r o p o s e d , on the b a s i s of m e a s u r e m e n t s of the e l e c t r i c a l conductivtties of solutions of acetal
Ia, that it d i s s o c i a t e s with splitting out of an ethoxtde anion and the f o r m a t i o n of amb[dent cation Ha. The
ability of l a c t a m a c e t a l s I a - c to act as alkylating agents may be a direct consequence of this s o r t of d i s -
sociation. In fact, ethyl benzoate is f o r m e d in p r a c t i c a l l y quantitative yield [according to g a s - l i q u i d c h r o -
m a t o g r a p h y (GLC)] when a solution of acetal Ia and benzoic acid tn c h l o r o f o r m is refluxed, while ethyl-
malonic e s t e r and N - m e t h y l - 2 - p y r r o l i d o a e (IV) in a r a t i o of 1 : 1 w e r e detected in addition to the c o n d e n s a -
tion product - 1 - m e t h y l - 2 - ( 2 - d i c a r b e t h o x y m e t h y l e n e ) p y r r o l i d i n e ( I l I ) - by GLC in the r e a c t i o n of acetal Ia
with malontc e s t e r . It should be noted that this r a t i o of the amounts of l a c t a m IV and ethylation product
f o r m e d in the r e a c t i o n indicates indirectly that the r a t e of s i m u l t a n e o u s ethylation and condensation is a p -
p a r e n t l y higher in this c a s e than in the c a s e of a c e t a l s Ib, c, for which p r e d o m i n a n c e of the amount of the
N - m e t h y l l a c t a m o v e r the ethylation product (due to decomposition of the a c e t a l s during the reaction) has
always b e e n o b s e r v e d [3, 4]. As s e e n f r o m the fact of the f o r m a t i o n of III, a c e t a l Ia r e a d i l y undergoes con-

CH~ R' CH 3 Cit3 - O C ? t 5 CH 3

III~V~V! 1 a-C,n=l-3 II a-C VII a-C

II1 n = l , R=R'=COOC2115; V a-C n=1-13, R=C6Hs, P,'-CNt; Vl n=3, R=COOC2H5, R'=CN

densatton with compounds that have an active methylene link, and qualitative o b s e r v a t i o n s have even shown
that the r a t e of this r e a c t i o n depends s u b s t a n t i a l l y on the s i z e of the l a c t a m ring. C o m p e t i t i v e r e a c t i o n of
a mixtttve of a c e t a l s I a - c with benzyl cyanide and subsequent a n a l y s i s of the r e a c t i o n mixture b y GLC

* F o r Communication X see [11.

S. Ordzhonikidze All-Union S c i e n t i f i c - R e s e a r c h P h a r m a c e u t i c a l - C h e m i s t r y Institute, Moscow.

T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 8, pp. 1089-1093, August, 1974. Original
a r t i c l e s u b m i t t e d August 21, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. ]I. 10011. No part o f this pubOcation may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15. 00.

947
showed that the t a r g e t enamines (Va-c) a r e f o r m e d in a r a t i o of 1 5 : 2 : 1, i.e., f i v e - m e m b e r e d acetal Ia is
substantially more r e a c t i v e than its six- (Ib) and s e v e n - m e m b e r e d (Ic) analogs. It was found that, in addi-
tion to the ring size, the c h a r a c t e r of the substituent in the compound with the active methylene link also
has a substantial effect on the condensation. Thus, enamine VI (GLC) is exclusively f o r m e d in the r e a c t i o n
of acetal Ie with a mixture of C6HsCH2CN and CNCH2COOC2H5. The i n c r e a s e d r e a c t i v i t y of f i v e - m e m b e r e d
aeetal Ia indicates that conformational changes play an important role in the r a t e - d e t e r m i n i n g step in this
case, and the p r o c e s s includes a change in the sp 8 hybridization of the r e a c t i o n center to sp 2.

It should be noted that just as in the l a c t a m acetal s e r i e s , the g r e a t e s t r e a c t i v i t y of pyrrolidone de-

rivatives in r e a c t i o n s with compounds that have an active CH2 group is also c h a r a c t e r i s t i c for the c o r r e -
sponding l a c t i m ethers. Thus, while O - m e t h y l b u t y r o l a c t i m undergoes r e a c t i o n with C6HsCH2CN r e l a t i v e l y
r e a d i l y , O - m e t h y l c a p r o l a c t i m and O - m e t h y l v a l e r o l a c t i m cannot be made to undergo this r e a c t i o n [5, 6].
As shown in [7], in addition to ambident cations of the I I a - c type, a - a l k o x y e n e a m i n e s VIIa-c also p a r -
ticipate in the equilibrium with aeetals I n - c , and this c r e a t e s the p r e r e q u i s i t e s for c a r r y i n g out the r e a c -
tions with electrophiles in the 3-position of the l a c t a m ring. C a r r y i n g out the r e a c t i o n of acetal Ia with ben-
zoyl chloride showed that the r e a c t i o n , on the whole, p r o c e e d s via a p r e v i o u s l y d e s c r i b e d s c h e m e [7]. At
the end of the r e a c t i o n , the mixture contained (GLC) l a c t a m IV, ethyl benzoate, 1 - m e t h y l - 3 - ( w - p h e n y l - T -
b e n z o x y m e t h y l e n e ) - 2 - p y r r o l i d o n e (VIII), 1 - m e t h y t - 3 - b e n z o y l p y r r o l i d o n e (IX), and ethyl N - m e t h y l - N - b e n -
z o y l - T - a m i n o b u t y r a t e (X) in a r a t i o of 3 : 7 : 12 : 1 : 2. Compounds IX and X could not be isolated f r o m the
r e a c t i o n mixture,* and they w e r e identical (GLC) to the compounds obtained by alternative synthesis. C o m -
pound IX was obtained by h y d r o l y s i s of VIII, while e s t e r X was synthesized f r o m N - m e t h y l - T - a m i n o b u t y r i c
acid via a known method [9].

C6tt5
(C,H2)n-~C--OCOC6 H5 ,-COCGH-
%~/% . .+ c~,.cooco.~
. .
1 1 COC6115
CH3 CH3
Vlll IX X

A c o m p a r i s o n of the r e s u l t s of benzoylation of acetal Ia with the r e s u l t s obtained in the r e a c t i o n of

acetals lb, c with benzoyl chloride shows that an open e s t e r of the X type is f o r m e d in significant amounts
only in the case of s i x - m e m b e r e d acetal lb. I n a s m u c h as the formation of this compound is apparently a s -
sociated with attack of benzoyl chloride at the N - a t o m of the l a c t a m acetals [8], it can be a s s u m e d that con-
formational f a c t o r s a r e the decisive factors in this case. In the case of the s i x - m e m b e r e d ring, approach
of the C6H5CO group to the nitrogen atom is l e a s t hindered, while the b a r r i e r s that a r i s e during s i m i l a r r e -
action of acetals Ia, c with C6HsCOC1 exert c o n s i d e r a b l e hindrance to N-benzoylation.
A r e c e n t communication [10] indicated that the r e a c t i o n of acetals Ia, b with CH 2 =CHCN gives, r e -
spectively, 1 - m e t h y l - 3 - ( f l - c y a n o e t h y l ) - 2 - p y r r o l i d o n e and 1 - m e t h y l - 3 , 3 - b i s (fl-cyanoethyl)-2-piperidone.
Reaction of acetal Ie with a c r y l o n i t r ile gives a mixture of N - m e t h y l c a p r o l a c t a m (XI),~ 1- m e t h y l - 2 - e t h o x y -
3 - f l - c y a n o e t h y l - 2 , 3 , 4 , 5 - t e t r a h y d r o a z e p i n e (XII), and 2 - m e t h y l - 1 , 9 - d e h y d r o - 9 - c y a n o - 2 - a z a b i c y c l o [5.2.0]-
nonane (XIII) in a r a t i o (GLC) of 1 : 5 : 4 (Trel values of 1, 5.6, and 6.9, respectively}. The IR s p e c t r u m of

(CH ) /CH~CH~CN CH 2 ) 3 ~ . ~
~.2~~,.O
3 + ( + Xl
lc~ i
C H~ L".N/L-7----~CN
CH3 CHa
XII Xlll

t w o - r i n g compound XIII contains absorption bands c h a r a c t e r i s t i c for enaminonitriles at 2180 ( C - N group)

and 1640 c m -1. A m a x i m u m at 277 n m (log c 4.19), which is also c h a r a c t e r i s t i c for the - N - C = C - C N

* The mixture of IX and X was subjected to mass s p e c t r o m e t r i c a n a l y s i s , and it was shown that it contains
two compounds with mass n u m b e r s of 203 and 249, r e s p e c t i v e l y . In addition, it was o b s e r v e d that a small
admixture of a substance with molecular weight 231, to which the 1 - m e t h y l - 2 - e t h o x y - 3 - b e n z o y l - 2 - p y r r o l i n e
s t r u c t u r e can be a s s i g n e d in analogy with [8], is p r e s e n t in this mixture.
t S p e c i a l experiments by means of GLC showed that under the r e a c t i o n conditions, acetal Ic is p a r t i a l l y con-
verted to l a c t a m XI and diethyl ether, i.e., ambident cation IIc is an alkylating agent with r e s p e c t to the
ethoxide anion.

948
fragment, is o b s e r v e d in the UV s p e c t r u m . The s t r u c t u r e of XIII was established by mea.qs of mass s p e c -
t r o m e t r i c analysis. The molecular weight (162) and the c h a r a c t e r of the s p e c t r o m e t r i c fragmentation c o r -
r e s p o n d to the p r o p o s e d t w o - r i n g s t r u c t u r e - VII. The principal pathways of the fragmentation are p r e -
sented in the s c h e m e below:

c,~=m=c.~ - - xm -6-" c. 2 )_~__~ ' " ~ I

,.uoLt~ + ~N (+

Y CHa . \- fill3 "

"-t

ella ctl~= N C N
161 CHa CH3
1,17 I31

The r e m a i n i n g ions o b s e r v e d in the s p e c t r u m (119, 110, 108, 107, 93, 82, 68, and 55) a r e explained by sub-
sequent disintegration of the f r a g m e n t s depicted in the s c h e m e and also by other possible pathways for the
disintegration of the molecular ion. The formation of t w o - r i n g compound XIII could be the r e s u l t of sub-
sequent cyclization of enamine XII. However, an i n c r e a s e in the time that the r e a g e n t s a r e heated in ben-
zene does not lead to any appreciable change in the r a t i o of XII and XKI. It can t h e r e f o r e be a s s u m e d that
these compounds a r e f o r m e d via independent s c h e m e s , for example, as follows:

CH2~CHCN
IC
/
L CH 3 "J " ~ " ~ Xlll
XIV

In other w o r d s , stabilization of intermediate dipolar ion XIV may p r o c e e d via two paths: by p r o t o t r o p i c
t r a n s i t i o n (Hs - ~ H ) or by cyclization with subsequent splitting out of an alcohol molecule.
However, the possibility of the c o n v e r s i o n of XII to XIH was shown by heating XII at a higher t e m p e r -
ature (in diethylene glycol). In this c a s e , cyclization of enamtne XII to t w o - r i n g compound XIII is o b s e r v e d
(according to GLC).

EXPERIMENTAL
The IR spectra of mineral oil pastes of the compounds were recorded with a UR-10 spectrometer.
The UV spectra of alcohol solutions (~ 104 M) of the compounds were recorded with an EPS-3 spectrophoto-
tometer. Gas-liquid chromatographic analysis (GLC) was curried out with an IGC-810 chromatograph with
a flame-ionization detector and a 60 by 0.3 cm chromatographic column; the stat[onury phase was 1% SE-30
and 1% OV-17 on Chromosorb W. The currier gas (helium) flow rate was 60 nfl/min. The components of
the mixtures were separated with temperature programming: Tin 75 ~ (2 min) and Tfin 200 ~ The heating
rate was 6 deg/min. Quantitative calculations were made from the data obtained with a Chromalog-2 elec-
tronic integrator. The mass spectra were recorded with an MI~-1303 spectrometer equipped with a device
for direct introduction of the samples into the source at an ionizing volatage of 50 eV.
Reaction of Aeetal Ic with Malonic Ester. A mixture of 3.46 g (0.02 mole) of acetal la and 3.2 g (0.02
mole) of malonic ester was held at i00 ~ for 3 h. Analysis of the mixture by GLC showed that it contained
12.5% lactam IV (Tre I i), 12.4% ethylmalonie ester (Trel 1.8), and 68.6% Ill (~'rel 14.3). Distillation of the
reaction mixture gave III with bp 156-157 ~ (3 mm) and n~ 1.5181. UV spectrum: X max 289 Clog ~ 4.23).
IR spectrum: 1580 (C =C), 1695 (ester C =O) cm -i. Found: C 59.9; H 8.1%. CI2H20NO 4. Calculated: C 59.5;
H 8.3~c.
N-Methyl-2-(2-phenyl-2-cyanomethylene)pyrrolidone (Va). A mixture of 3.8 g (0.022 mole) of acetal
Ia and 2.6 g (0.022 mole) of benzyl cyanide was heated for 6 h (the bath temperature was i15-120~ after
which the alcohol was evaporated, and the residue was distilled to give Va with bp 206-207 ~ (4 mm) and n~
1.6206 in 69% yield. UV spectrum: Xmax 299 nm (log a 4.19). IR spectrum: 1585 (C=C), 2170 (C~N)
crn -I. Found: C 78.6; H 7.1; N 14.1%. CIsI-II~N 2. Calculated: C 78.8; H 7.2; N 14.1%.

949
 Competitive Reaction of Acetal Ic with Benzyl Cyanide and Cyanoacetic E s t e r . Acetal Ic (0.004 mole)
was added to a mixture of benzyl cyanide and cyanoacetic e s t e r (0.02 mole of each), and the mixture was
s t i r r e d at 20 ~ for 1 h. Analysis by GLC showed the quantitative formation of VI.
Competitive Reaction of a Mixture of Acetals I a - c with Benzyl Cyanide. Benzyl cyanide (0.002 mole)
was added to a mixture of acetals I a - c (0.02 mole of each), and the mixture was s t i r r e d at 90-96 ~ for 2 h,
after which it was analyzed by GLC. The ratio of Va to Vb to Vc was 15 : 2 : 1.
1 - M e t h y l - 3 - { w - p h e n y l - w - b e n z o x y m e t h y l e n e ) - 2 - p y r r o l i d o n e (VIII). T r i e t h y l a m i n e (6.5 g ) w a s added to
7.5 g (0.43 mole) of acetal Ic in 20 mI of dry c h l o r o f o r m , after which the mixture was cooled and maintained
at 25-30 ~ while a solution of 4.7 ml (0.43 mole) of benzoyl chloride in 10 ml of d r y c h l o r o f o r m was added
dropwise. The mixture was s t i r r e d at r o o m t e m p e r a t u r e for 1 h, after which water was added, and the
c h l o r o f o r m , and the combined extracts were dried with anhydrous Na2SO 4. The solution was filtered, the
c h l o r o f o r m was r e m o v e d by distillation, and the r e s i d u e was distilled to give a fraction with a boiling point
no higher than 100 ~ (12 mm). The r e s i d u e was dissolved in alcohol, and the solution was t r e a t e d in the cold
with activated charcoal. The solution was then filtered and evaporated. The residual oil was t r i t u r a t e d
with p e t r o l e u m ether, and the mixture was filtered to give 3.8 g (29%) of VIII with mp 110-112 ~ A sample
for analysis was c r y s t a l l i z e d f r o m 50% ethanol to give a product with mp 127-127.5 ~ IR s p e c t r u m : 1635
(C =C), 1670 (lactam C =O), and 1725 (ester C =O) c m -1. Found: C 74.4; H 5.6%. C19H17NO3. Calculated:
C 74.3; H 5.5%.
1 - M e t h y l - 3 - b e n z o y l - 2 - p y r r o l i d o n e (IX). A 2.0-g sample of l a c t a m VIII was added to a solution of
2.0 g of KOH in a mixture of 5 ml of water and 30 ml of methanol, and the solution was refluxed for 5 min,
after which it was acidified to pH 6 with 15% HC1, and the alcohol was r e m o v e d by distillation. Water was
added to the r e s i d u e , and the r e a c t i o n product was e x t r a c t e d with c h l o r o f o r m . The e x t r a c t was dried with
Na2SO 4 and filtered, and the c h l o r o f o r m was r e m o v e d f r o m the filtrate by distillation. The r e s i d u e was
fractionated at 164-165 ~ (5 mm). The yield of IX was 1.2 g (90%). IR s p e c t r u m : 1675 (lactam C =O), 1695
(ketone C =O) e m -1. UV s p e c t r u m : Xma x 282, 247 nm (log ~ 3.26, 4.11). Found: C 71.0; H 6.6; N 6.6%.
C12H13NO2. Calculated: C 71.0; H 6.4; N 6.7%.
Reaction of N - M e t h y l c a p r o l a c t a m Diethylacetal (III) with A c r y l o n i t r i l e (IV). A mixture of 10.8 g
(53.9 mmole) of acetal IIc and 2.86 g (53.9 mmole) of a c r y l o n i t r i l e in 40 ml of d r y benzene was r e f l u x e d f o r
20 h, after which the benzene was r e m o v e d by distillation, and the r e s i d u e was fractionated to give i g of
l a c t a m XI with bp 70-72 ~ (l mm) and n}~ 1.4825, and2.9 g of enamiue XII with bp 129-130 ~ (1 mm) and n}~
1.4912. UV s p e c t r u m : Xmax 236 n m (log ~ 3.69). l:R s p e c t r u m : 1660 (C=C), 2230 (C--N) c m -1. Found:
C 69.3; H 9.5; N 13.6%. C12H20N20. Calculated: C 69.2; H 9.6; N 13.5%. T w o - r i n g compound XIII (2.4 g)
with bp 142-144 ~ (1 mm) and n ~ 1.5432, was also obtained. Found: C 73.9; H 8.8; N 16.8%. C10H14N2.
Calculated: C 74.1; H 8.6; N 17.3%.

LITERATURE CITED
1. A. 1V[. Zhidkova, V. G. Granik, R. G. Glushkov, T. F. Vlasova, O. S. Anisimova, T. A. Gus'kova, and
G. N. P e r s h i n , K_him. Geterotsikl. Soedin., 670 (1974).
2. H. Meerwein~ W. Florian, N. Sch~Jn, and G. Stopp, Ann., 641., 1 (1961).
3. V.G. Granik, A. N. Akalaev, and R. G. Glushkov, Zh. Organ. Khim., 7, 2429 (1971).
4. V . G . Granik, A. G. Sukhoruchkin, N. S. Kuryatov, V. P. Pakhomov, and R. G. Glushkov, Khim. Get-
erotsikl. Soedin., 954 (]973).
5. T. Onaka, T e t r a h e d r o n Lett., 5711 (1968).
6. V.G. Granik and R. G. Glushkov, Zh. Organ. Khim., 7, 1146 (1971).
7. V.G. Granik, N. S. Kuryatov, V. P. Pakhomov, E. M. Granik, I. V. P e r s i a n o v a , and R. G. Glushkov,
Zh. Organ. Khim., 8, 1521 (]972).
8. V.G. Granik, A. G. Suk_horuchkin, N. S. Kuryatov, V. P. Pakhomov, O. S. Anisimova, and R. G. Glush-
kov, Khim. Geterotsikl. Soedin., 958 (1973).
9. F. Korte, K. Bffchel, H. M~.der, O. R S m e r , and H. Schulze, B e r . , 95, 2424 (1962).
10. T. Oishi, H. Nakakimura, H. Mori, and Y. Ban, Chem. P h a r m . Bull., 20, 1735 (1972).

950
NITRATION OF 2- AND 5-BENZYL-3-HYDROXYPYRIDINES
AND THEIR N-OXIDES

L. D. S m i r n o v , V . S. Z h u r a v l e v , UDC 547.823 : 543.422.25.4 : 542.958.1

V. P. Lezina, and K. M. Dyumaev

The nitration of 2- and 5 - b e n z y l - 3 - h y d r o x p y r i d i n e s and t h e i r N-oxides t a k e s place in the p a r a

position of the phenyl ring. The introduction of an N-oxide group into the /3-pyridol ring does
not affect the o r i e n t a t i o n of substitution.

The o r i e n t a t i o n p r i n c i p l e s in the nitration of i s o m e r i c p h e n y l - and b e n z y l p y r i d i n e s and t h e i r d e r i v a -

t i v e s [1-4] are e x t r e m e l y complex. Thus~ a m i x t u r e of o - (5%), m - (35%), and p - (42%) nitro i s o m e r s is
f o r m e d in the nitration of 2-phenylpyridine [2, 3], while 3-phenylpyridine [2] is n i t r a t e d e x c l u s i v e l y in the
p a r a position. However, a c c o r d i n g to the g e n e r a l p r i n c i p l e s of e l e c t r o p h i l i c substitution of m o n o n u c l e a r
a r o m a t i c s y s t e m s , the p r e d o m i n a n t f o r m a t i o n of m - n i t r o d e r i v a t i v e s should have been expected in both
c a s e s . The e x p e r i m e n t a l data a t t e s t e d that weakening of the e l e c t r o n e g a t i v e effect of the ring nitrogen is
a c c o m p a n i e d by p r e d o m i n a n t f o r m a t i o n of the p a r a i s o m e r , while strengthening of this effect leads to m e t a
orientation [2]. F o r e x a m p l e , p - n i t r o d e r i v a t i v e s a r e e x c l u s i v e l y f o r m e d on p a s s i n g f r o m 2-phenyl- to 2-
b e n z y l - [1, 2] o r 2-phenyl-3-hydroxypyridine [5].
In the light of the r e s u l t s set forth above, it s e e m e d of i n t e r e s t to investigate the nitration of 2- and
5 - b e n z y l - 3 - h y d r o x y p y r i d i n e s and t h e i r N - o x i d e s (Ia-d). Nitration of Ia and Ib u n d e r conditions s i m i l a r
to those d e s c r i b e d in [5] o c c u r r e d in the p a r a position of the phenyl ring.
In the c a s e of 2-(4'-nitrobenzyl)-3-hydroxypyridine (IIa), the c h a r a c t e r of the PMR s p e c t r u m of the
p r o t o n s of the phenyl ring - two groups of s y m m e t r i c a l m u l t i p l e t s c e n t e r e d at 6.8 and 7.5 ppm (A2B2 type) -
a t t e s t s to the p a r a position of the nitro group. The p r o t o n s of the C4, C5, and C~ a t o m s of the h y d r o x y p y r i -
dine ring give s i g n a l s at 7.03 and 6.5 ppm. The r a t i o of the i n t e g r a l intensities of the signals is in a g r e e -
ment with the p r o p o s e d s t r u c t u r e - Ha.
The c h a r a c t e r of the s p e c t r u m of 2- (4 V - n i t r o b e n z y l ) - 3 - h y d r o x y - l - p y r i d i n e 1-oxide (IIb) is s i m i l a r
(signals of the protons of the hydroxypyridine ring at 7.17 and 6.95 ppm with an intensity ratio of 1 : 2, and
two groups of s y m m e t r i c a l signals of phenyl ring protons at 6.97 and 7.78 ppm).

I |l
a R= 8 - h y d r o x y - 2 - p y r i d y l , b R= 3 - h y d r o x y - N - o x i d o - 2 - p y r i d y l , c R = 3-hydroxy-
5-py~idyl,d R= 3-hydroxy-N-oxido-5-pyridyl
Only the nitrates of Ia, b were obtained from the reaction of la, b with a mixture of concentrated nitric
acid and glacial a c e t i c acid.
The nitration of p y r i d i n e s Ic, d is of s p e c i a l i n t e r e s t , i n a s m u c h as h e r e it is p o s s i b l e to c o m p a r e the
r e a c t i v i t i e s of the phenyl ring in the /3-position (with a m i n i m a l e l e c t r o n - a c c e p t o r effect of the h e t e r o a t o m )
with the activity of the 2-position of the f i - p y r i d o l ring, occupied by a benzyl group in the case of Ia, b.
A n a l y s i s of the PMR s p e c t r a of the s y n t h e s i z e d nitro compounds (Tic, d) indicates that nitration in this c a s e
also is d i r e c t e d to the p a r a position of the phenyl ring. Thus, two groups of s y m m e t r i c a l m u l t i p l e t s cen-

Institute of C h e m i c a l P h y s i c s , A c a d e m y of Sciences of the USSR, Moscow. T r a n s l a t e d f r o m Khimiya

G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 8, pp. 1094-1095, August, 1974. Original a r t i c l e submitted N o v e m b e r
5, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. ]I, 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means', eleetronie, mechanical, photocopying, microfilming,
recording or otherwise, without written permissiou o f the publisher. A eopy o f this artiele is available from the publisher for $15.00.

951
 TABLE 1. Nitro Compounds II

Found, % Calc., %
CO1TI -
rap, ~ Empirical yield, %
pound formula C H C H

IIa 223--224 C,:HIoN203 62,8 4,4 62,6 4,4 85

IIb 250--252 (dec.) CI2HIoN204 58,7 4,1 58,6 4,1 85
IIe 235--236 CI2H1oN203 62,8 4,5 62,6 4,4 90
lid 163--164 C12H~oN204 58,6 4,1 58,6 4,1 80

t e r e d a t 6.5 and 7.2 ppm (as in the PMR s p e c t r u m of IIa) are p r e s e n t in the spectrum of 5 - ( 4 ' - n i t r o b e n z y l ) - 3 -
hydroxypyridine (IIc). The signals of the protons attached to the Cs, C2, and C 4 atoms of the hydroxypyridine
ring and of the CH 2 groups are found at 7.18, 6.91, 6.33, and 3.10 ppm.
Thus, the r e s u l t s obtained in this investigation attest to higher reactivity of the p a r a position of the
phenyl ring as c o m p a r e d with the 2-, 6-, and 4-positions of the ~ - p y r i d o l ring. The introduction of an
N-oxide group is not reflected in the orientation of substitution. The predominance of p a r a substitution
o v e r ortho substitution in the nitration of 2- and 4 - b e n z y l p y r i d i n e s has been explained [4] by pronounced
deactivation of the phenyl ring of the protonated p y r i d y l group due to the effect of the field of positive charge,
which weakens with distance and, by virtue of this, affects the p a r a position to a l e s s e r degree than the
ortho and meta positions. Our r e s u l t s can apparently also be explained by this rationale.

EXPERIMENTAL
The PMR s p e c t r a of solutions in 1 N NaOD (Ha-c) and dimethyl sulfoxide (DMSO) (IId) were r e c o r d e d
with a Varian H A - t 0 0 s p e c t r o m e t e r at 29 ~ (on the 5 scale relative to t e t r a m e t h y t s i l a n e ) . The purity of the
products was monitored by t h i n - l a y e r c h r o m a t o g r a p h y (TLC) on A1203 in m e t h a n o l - b e n z e n e (1 : 9).
Compounds IIa-d. A 0.01-mole sample of concentrated HNO 3 was added to 0.01 mole of I in 5 ml of
c o n c e n t r a t e d H2SO4 at 0 ~ and the mixture was allowed to stand for 24 h at room t e m p e r a t u r e . It was then
poured into 10 m l of ice water, and the aqueous mixture was filtered. The solid product was r e c r y s t a l l i z e d
from ethanol. Data on II are presented in Table 1.

LITERATURE CITED
1. F. Bryans and F. L. l>yman, J. Chem. Sot., 552 (1929).
2. A. R. Hands and A. R. Katritzky, J. Chem. Sec., 1754 (1958).
3. A. R. Katritzky and M. Kingsland, J, Chem, Soe., B, 862 (1968).
4. F. de Sarlo and J. H. Ridd, J. Chem. Soc., B, 712 (1971).
5. L. D. Smirnov, V. i. Kuz'min, V. P. Lezina, and K. M. Dyumaev, Izv. Akad. Nauk SSSR, Ser Khim.,
1897 (1970).

952
EFFECT OF ANNELATION ON THE REACTIVITIES
OF BENZOQUINOLINES IN HETARYLATION*

A. K. Sheinkman, M. M. Mestechkin, UDC 547.832 : 539.194 : 541.67 : 543.422.6

A. P. Kucherenko, N. A. Klyuev,
V. N. Poltavets, G. A. Mal'tseva,
L. A. Palagushkina, and Yu. B. Vysotskii

The r - e l e c t r o n c h a r g e s , bond o r d e r s , dipole m o m e n t s , and e l e c t r o n i c s p e c t r a of benzoquino-

lines w e r e calculated by the s e l f - c o n s i s t e n t - f i e l d (SCF} method with allowance for the c o u l o m -
bic repulsion of the e l e c t r o n s ; the r e s u l t s of the calculations w e r e in s a t i s f a c t o r y a g r e e m e n t
with the e x p e r i m e n t a l data. The effect of the position of annelation of the benzene ring on the
e l e c t r o n i c c h a r a c t e r i s t i c s of benzoquinolines and t h e i r b a s i c i t i e s and b e h a v i o r during h e t a r y l a -
tion in the p r e s e n c e of acyl halides was evaluated.

In a p r e c e d i n g c o m m u n i c a t i o n [1] we e x p r e s s e d the a s s u m p t i o n that the p r i n c i p a l p a r a m e t e r s that

d e t e r m i n e the activity of N - h e t e r o a r o m a t i c s y s t e m s in h e t a r y l a t i o n in the p r e s e n c e of acyl halides a r e the
b a s i c i t i e s of the h e t e r o r i n g s , the o r d e r of the C - N ring bond, andthe magnitude of the positive c h a r g e onthe
ce- (or y) c a r b o n a t o m . To v e r i f y this a s s u m p t i o n , we calculated the distribution of v - e l e c t r o n c h a r g e and
the bond o r d e r s in the m o l e c u l e s of all of the possible benzoquinolines (Fig. 1) by the s e l f - c o n s i s t e n t - f i e l d
(SCF) method with allowance for eoulombic r e p u l s i o n of the e l e c t r o n s . The dipole m o m e n t s and the e l e c -
t r o n i c and PMR s p e c t r a can be c o n s i d e r e d to be the m o s t d i r e c t r e f l e c t i o n of the e l e c t r o n distribution.
T h e s e c h a r a c t e r i s t i c s of the m o l e c u l e s w e r e t h e r e f o r e also calculated on the b a s i s of the e l e c t r o n d i s t r i b u -
tion found. The s a m e method for the calculation of the e l e c t r o n distribution and the s p e c t r a as was e m -
ployed in the c a s e of the h y d r o c a r b o n analogs of the compounds u n d e r c o n s i d e r a t i o n [2] was used. The p a -
r a m e t e r s of the nitrogen a t o m ( r e s o n a n c e i n t e g r a l /3CN = - 2.57 eV, e l e c t r o n e g a t i v i t y 6 w = - 1.6 8 eV, and c o u l -
ombic i n t e g r a l 7NN =+ 10.4 eV) w e r e s e l e c t e d f r o m the e l e c t r o n i c s p e c t r u m of pyridine, while the y (R) de-
pendence was of the s a m e type as that for c a r b o n [3]. T h e s e s a m e p a r a m e t e r s p r o v e d to be acceptable for
the calculation of the s p e c t r a of pyridine and 4 , 9 - d i a z a p y r e n e [1]. The goal that we set for o u r s e l v e s in-
cluded not only the i n t e r p r e t a t i o n of the s p e c t r a , but also quantitative r e p r o d u c t i o n of the lower bands. As
s e e n f r o m Table 1, not only a r e the t h r e e l o w e r a b s o r p t i o n bands, the a s s i g n m e n t of which c o r r e s p o n d s to
the data in o t h e r studies [4, in s a t i s f a c t o r y a g r e e m e n t with the e x p e r i m e n t a l r e s u l t s , but, in addition, the
l o w e r t r i p l e t level is also in good a g r e e m e n t with the p h o s p h o r e s c e n c e m a x i m u m [5].
The position of the l o w e r a b s o r p t i o n bands, p a r t i c u l a r l y the f i r s t , in b e n z o p y r i d i n e s (quinoline and
isoquinoline) is m o r e s a t i s f a c t o r y than in [6] and r e p r o d u c e s the e x p e r i m e n t a l data. The lower levels,
which differ little f r o m one another, display a b a t h o c h r o m i c shift with r e s p e c t to pyridine. It is n a t u r a l
to c o m p a r e the l o w e r and w e a k e r t r a n s i t i o n with the weak a band in naphthalene at 3.93 eV, and the second
and m o r e intense t r a n s i t i o n in both m o l e c u l e s can be r e l a t e d to the p band of naphthalene at 4.3 eV [3].
A f u r t h e r b a t h o c h r o m i c shift of the l o w e r band is o b s e r v e d in the s p e c t r a of benzoquinolines, and o n e ' s
attention should be d i r e c t e d to the c l o s e n e s s of the s y m m e t r i c a l and a s y m m e t r i c a l bands in the s p e c t r u m
of acridine; the l o w e r band in the s p e c t r u m of benzo[g]quinoline is c l o s e r to the s y m m e t r i c a l band, while
the next band is c l o s e r to the a s y m m e t r i c a l band. The l o w e r t r a n s i t i o n , which is m o r e intense, is close
to 3.3-3.4 eV in the s p e c t r a of all of the benzoquinolines (Table 1,) and c o r r e s p o n d s to the p band of a n t h r a -
* C o m m u n i c a t i o n XXIX f r o m the s e r i e s " R e a c t i o n s of C y c l a m m o n i u m Cations." F o r Communication X-XVIII
see [1l.
T r a n s l a t e d f r o m K h i m i y a G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 8, pp. 1096-1105, August, 1974. O r i g -
inal a r t i c l e s u b m i t t e d August 6, 1973.

9 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

953
 TABLE I. E l e c t r o n - T r a n s i t i o n Energies (eV)
Sym - Triplet
Compound metry $ingletT!exptil [5]
calc. calc. lexp~l. [5]

Pyridine A 6,2984 0,01 6,36 3,7854 I 3,68

7,4686 0,91 7,04 4,4882
B 4,6484 0,03 4.96 4,2646
8,0456 O,12 5,2398
Quinoline 3,8279 0,03 3,96 2,5794 2.69
4.2184 0,12 4,43 3,7650
4,59
Isoquinoline 3,8287 0,07 3,89 2,5500 2,53
4.1944 0,21 4,59 3,8108
4,68
Benzo[b]quinoline (acri- A 3,2967 0,195 3,18 1,6889 1.94
dine) 6,1037 0,112 5,82 3,9812
B 3,3527 0,026 3,50 2,9B02
4>1918 0,005 3,5404
Benzo[clquinolin~ (phen- 3,4075 0>016 3,53 2,6341 2>73
an~hridine) 4,0659 0,171 3,3364
Benzo[f ]quinoline 3,4025 0,018 2,5864 2,7 t
4,8567 0,191 , 3,4254 3,35
Benzo[g]quinoline 3,2360 0,076 t 1,6725
4,4283 0,025 3,1995
Benzo[h]quinoline 3,3966 0,022 2,5819 230
4,0965 0,166 3,3028 3,32

~A~ in Russian original-Publisher.

- O~OOL:~
~ ~ 016196 0~0056 Z~ ' - ' ~ / . 0 ~
i

- 0#0024\ - v I 0 ~0032 O O

%\o.ss~6/~ o, \%_ @I <~

- 0#0397~070040
,+.0" 0~ ~ ^
_0,0,,00,66, 0,0065
o,~844 Z ~ ~%~%,oo~9
9X ~' / v~ - o oo66 ~

o -o,oo,.~o, oo~. -o,o4o.~,~:,oo,~

- 0 0 0 ~ ~ 0~4857 /~Y ~\ ..... o Z ~" "O~ -0 0452
i -0 uluuuu ~_~ ~ .0

-0,00,5 .*,<0
'l t~\v,
,~o oo:+// "~,-
%y<z-J<~-o, oo~o -~,~-^~3~O'-C'----JOlO0
...... ,~9

- 010~66~10034
.% ~7 ~176
~.0 0~0043 0.5964 0,0076

- 0~0096 O ~ , 0 0 3 .3O
"; 0,5124
0~0003 0'5759 0,0019 0,0033 ~ - 0 ~ 0 2 0 3

-o,o~%<~- -%~,o~o~
- 0.00
~ 4 . ,
' X~%
o~% ~<o
o oo,,, . -
- ~ 0,.~o/~
0'0048~O~m'
-0/~963-~0
l "u0,0024 0,1775'@Z ~ ~0,0625

27~
-o, oo4170 ~>s 0~010~0 O,5748010062
\% /~
- o,o43~ ~o\'/ .~ 4~
~',70%~51_o" 0~0003 -o,oo,.~; J,%~ - o ,_2,0 oo,o
0,18770Z k/~0-0i0470 -0,0645 , ~ 0 t0028

- 0510~4 050077
- 0~0017 0,0044 ~0" "~
-O,0645 ~ eOo,ooas

- 0,0 0.0016
-o,o1.~7~ ,~2oo,oo~6

- o,o~ @../o,~oL.x.-,

o l e ~ <~"
z --~A-o,o~oo

- 0,0904 075
016131

F i g . 1. M o l e c u l a r d i a g r a m s o f p y r i d i n e and b e n z o - a n d
dibenzopyridine s.

954
 T A B L E 2. Dipole M o m e n t s of B e n z o q u i n o l i n e s

Compound W,Qo e~ c~ v~.. ~ PePcm

s cm
3P=, Ix, D U*.calc.D

Acridine 0,1966 2,2785 3,050 1,14403 -0,274 67.9 148,331 1,98 2,56
0,2438 2,2799 3,036 1,14388 -0,283
0,3006 2.2816 3,027 1,14372 -0,283 i
0,3497 2,2831 3,032 1,14359 -0,280
aav=3,036 i ~av=-0,280
Benzoic]quinoline 0,1633 2,2788 3,85711,14412]-0,275 70,3 176,60, 2,28 2,38
!
0,1995 2,28021 3,859'1,14402]-0,276
0,2473 2,282l 3,881 1,14389--0,275
0.3775 2,287l 3,867 1,143541--0,273
aav=3,866 :~av=--0,275]
Benzo[f ]quinoline 0(I978 2,2788] 3,185 A,143941-0,3181 66.9 152,22, 2,04 2.23
0,2493 2 28051 3,209:1,14352/-0,301 I
0,3038 2,2822 3,193 1,14365 -0,3031 i
0,3475 2,2836 3,1941,14352 -0,3021
Benzo[g]quinoline
aav=3,195 J ~av=--0,308 ' I
0,01133 2,27301 4,325 1,144481--0,794 62,0 146,70 2,03 2,24
0,02272 2,2735t 4,312 1,144391--0,792i
0,04575 2,2745 4,35511,144191--0,8311
0,06347 2,2753 4,396i1,144951--0,819~ I
' aav=4, 347 I ~av=-0,809 1
Benzo[h]quinotine 0,1972 2,27711 2,332 1,143961--0,309 66,9 121,961 1,64 2,14
0,2454 2,27811 2,282 1,143791--0,318
0,3030 2,2795 2,310 1,143611--0,317,
0,3801 2,2813 2,315 1,14337,-0,31T
aav=2,313 ~av=--0.315 ;

T A B L E 3. D i a m a g n e t i c S u s c e p t i b i l i t i e s of N i t r o g e n H e t e r o c y c l e s
(- 10 -6 c m 3 / m o l e )
n-Electron contributions AXzz Xzz Xm
Molecut.e expd.~
calc. ealc. calc. I[15_]
r idine 31,55 -0,30 31,25 I 57,46 86,75 48,41 48,4
inoline 93,29 -25,66 67,63 ] 111.34 160,09 85,80 86,0
Isoquinoline 93,17 -26,07 67,10 I 110,81 159,56 85,63 83,9
Acridine 191,92 -77,08 114,85 1 176,06 244,27 126,81 114,9
Phenanthridine 194,22 -96,61 100,61 J 161,82 230,03 122,07 --
Benzo[f]quinoline 197,21 --96,60 I00,61 161,82 230,03 122,07 --
Benzo[g]quinoline 191,81 --76,81 115,00 176,21 244,42 126,86 --

c e n e a t 3 . 3 4 e V . The l o w e r band in the s p e c t r a o f the p h e n a n t h r e n e a n a l o g s is s o m e w h a t m o r e of a s h o r t -

wave band (3.4 eV) and c o r r e s p o n d s to the weak ~ band of p h e n a n t h r e n e at 3.54 eV [3]. The l o n g e s t - w a v e
t r a n s i t i o n is the t r a n s i t i o n in the d i a z a p y r e n e m o l e c u l e ill, w h e r e , as in the c a s e of a c r i d i n e , two c l o s e
and quite intense bands a r e o b s e r v e d , but in this c a s e t h e y have the s a m e s y m m e t r y . It is n a t u r a l to c o m -
p a r e t h e m with the ~ and p bands of p y r e n e , which a r e a l s o c l o s e to one a n o t h e r (3.24 and 3.50 eV).
T h u s , l i n e a r a n n e l a t i o n leads to a s o m e w h a t g r e a t e r b a t h o e h r o m i c shift. This s o r t of effect is m o r e
c l e a r l y e x p r e s s e d in the c a s e of p h o s p h o r e s c e n c e t e r m s , w h e r e the l o w e r t r i p l e t ( p h o s p h o r e s c e n c e ) level
of p h e n a n t h r e n e a n a l o g s d i s p l a y s a s m a l l h y p s o c h r o m i c shift, while the a n t h r a c e n e a n a l o g s display a s u b -
s t a n t i a l b a t h o e h r o m i c shift with r e s p e c t to quinoline, such t h a t p h o s p h o r e s c e n c e in the visible r e g i o n can
be o b s e r v e d f o r the f o r m e r , and p h o s p h o r e s c e n c e in the IR r e g i o n c a n be o b s e r v e d f o r the l a t t e r .
T h i s is c o n f i r m e d b y the bands r e p o r t e d in [5, 7], which did not a p p e a r in the v i s i b l e r e g i o n of a b -
s o r p t i o n of a c r i d i n e , which, as shown by s u b s e q u e n t i n v e s t i g a t i o n s [5], d i s p l a y s p h o s p h o r e s c e n c e in the
s a m e r e g i o n as a n t h r a c e n e (~2 eV). H o w e v e r , in the c a s e of b e n z o [ f ] - and b e n z o [ g ] q u i n o l i n e s , the e x p e r i -
m e n t a l l y d e t e r m i n e d [5] p o s i t i o n s o f both the f i r s t and s e c o n d t r i p l e t l e v e l s a r e in e x c e l l e n t a g r e e m e n t with
the r e s u l t s o f o u r c a l c u l a t i o n s . T h u s , the above d e s c r i p t i o n of the s p e c t r a , which is in a g r e e m e n t with the
e x p e r i m e n t a l data, c o n f i r m s the r e s u l t s of c a l c u l a t i o n s of the m o l e c u l a r d i a g r a m s of b e n z o q u i n o l i n e s .
T a b l e 2, in which the c a l c u l a t e d 1r-electron dipole m o m e n t s , which, a f t e r i n t r o d u c t i o n of a c o r r e c t i o n
f o r the dipole m o m e n t o f the ~ bond ( a s s u m e d to be 1.55 D and d i r e c t e d along the u n s h a r e d p a i r of the n i t r o -
gen atom), p r o v e d to be in good a g r e e m e n t with the v a l u e s that we found e x p e r i m e n t a l l y and with the l i t e r a -
t u r e data, m a y s e r v e as a f u r t h e r c o n f i r m a t i o n of the a d e q u a c y of the e l e c t r o n d i s t r i b u t i o n found.
The d i a m a g n e t i c s u s c e p t i b i l i t i e s c a l c u l a t e d by the m e t h o d developed in [8], of the n i t r o g e n h e t e r o -
c y c l e s u n d e r i n v e s t i g a t i o n in the p r e s e n t p a p e r a r e p r e s e n t e d in T a b l e 3. The p r e s e n c e of h e t e r o a t o m s
l e a d s , within the f r a m e w o r k of the 7r-electron v a r i a n t of the SCF MO LCAO m e t h o d , to additional additive
p a r a m e t e r s that c h a r a c t e r i z e the d i a m a g n e t i c p r o p e r t i e s of the C - N ~ bonds, in addition to y i e l d i n g the

955
 TABLE 4. Proton Chemical Shifts of a Series of Nitrogen Hetero-
cycles relative to t e t r a m e t h y l s i l a n e in ppm)

Molecule Calc. Exptl. Molecule Galc.

Pyridine 4 2 1,56 1,71n Phenanthridine 1 1,89

9 i
3
4
2,95
2,91
3,23 I
2,85 /
2
3
4
2,58
2,54
1,84
6 0,78
Isoquinoline 1 0,93 0 86~ 7 2,20
5 4 3 1,33 1",55 ~ Ns 8 2,49
4 2,38 2,50 9 2,53
5 2,37 2,30 10 1,86
7 2 6 2,69 2,44
7 2,70 2,521 Benzo[fJquinoline 2 1,08
8 2,34 2,t5 3 2,52
4 1,81
1,86
Quinoline 2 1,25 1,1OtZI 2,56

~
8 4 3 6
5 4 3 2,65 2,66[ 7 2,52
4 2,27 2,o4/ 8 2,26
5 2,34 2,24] 2,26
7 ? 6 2,70 2,50 ,o 7 9
2,31 i0 1s
7 2,69
8 1,92 1,91 i Benzo[g]quinoline 2 1,04
I 3 2,44
Acridine 1 1,96 2,06~-j 9 ,o , 4 1,94
9 i 2 2,44 2,501 5 1,49
3 2,42 2,18 I r 6 1,96
4 1,55 1,65 a 7 2,44
3 9 1,49 1,35 8 2,43
I 9 1,99
1 10 1,09

T A B L E 5. 6 - S u b s t i t u t e d 5 - A c y l - 5 , 6 , 7 , 8 , 9 , 1 0 - h e x a h y d r o p h e n a n t h r i d -
i n e s (IVa-g) a n d 2 - S u b s t i t u t e d 1 - A c y l - l , 2 - d t h y d r o b e n z o If ]quinolines
( V a - g)
I mp, *C t M~
(crystal- -. . . . Empirical Found, % Calc.,% ~S
3g.! s~
llizati~ found calcJ] formula c i n iIN C rlH / N
I [ . , ,
IVa IC6H5 3-Indolyl 223--224 [404 404 rC28H24N20 ;183,3i 6,1 i 6,8! 83,l ' 5,9'] 6,91I 51
(ethanol)
3-Indolyl 252--254 342 342 liC_~3HnN~O 80,4],6,8 8,1 80,71 6,4[ 8,2 "46
:(ethanol) ;
1-Methyl-3- ' 241--242 418 418 ;iC.gH26N,20 I,83,4! 6,3: 6,51;83,2.6,2' 6,7 37
indolyl ifethanol) ; . I i
!Vd CGH~ 2-Methyl-3- i272--273 418 418 IC~gH.~6N~O 83,9 6,5' 6,71 83,2, 6,2 6,7 55
] indolyl (benzene)i
IVe C6Hs il-Metl~yl-2- 289--291 ,368 368 C~5i-1~4N~O
I i ] ~
sL316,6,7,8.81,9~% 7,6,
' 13
pyrrolyl !(ethanol)] i
IVf C6H5 i2-Methyl-5- , 285--286 !369 369 'C~H23NO~ 796 64!3918I 3:62:3712
! furyl i (prop,a-i ] I ~ I. i I I
i
] : no]) , , i I '
IV C6H5 t-Methyl-l,2,3,, 208--2104417 434 ~c3oH3oN~O i82.7, 7,1[ 6,7' 82,96,9' 6,517
4-tetrahydro- '(heptane)l " ' '
S-quinOllnyl I i [ : i } i
Va CHa 1,3-Indolyl , 171--172 '338 :338 Ceal-llaN~ 79,8 6,1 8,8' 81.6 5,4 8,3 64
( ' O '
; ; (ethanol)4 1 ' [ " ' '5,3' i
\rb: m-CHa,lg-Indolyl ' 241--242 414 l 414 iC29HezNzO J 83 3i 6,0 7,1 i 84,0, 6.7' 58
r C6H4 [ i (hexane) ' , i ' ' '
\ c CHs ,1-Methyl-3- , 140--141 352 [ 352 'C24H2aN~O179,8 5,0 '~8,0i 81,8' 5,7, 8,0" 62
indolyl . (heptane) ! i ' i ~ I i 5,3 i
\-d C~Hs 1-MetSyl-3- 159--160 414 !414!c29n22NzO!84,154167i8401 6,7i50
/ indolvl (heptane)i ' i : } ' ' i
\re IC0t-I5 ,2-Metfiyl-3-
indolyl (heptane)l
244--2451414. 414 ,i C29H22N20 I'83,T, 5'51 6'51 84'0!, 6'311' 6'7; 58
Vf IC,Hs I1-Methyl-2- 140--142 1364 I 364 C2sH2oN~O! 82,51 5 5~7,1 82,4: 5,5i 7,7 42
l
vg/c0H~ i2 pyrrolvl
pyrrolyl '(heptane)!
1230-231i350 350 [Cz4I-I,sN20 I 82515,2 I 811822'52-8,0 11
(oenta-i " ~ ' ': ' ' '~, ' { {
I i hol) [ i I i i i ! I i

* Mass spectrometrically.
~By t h e R a s t m e t h o d .

956
r - e l e c t r o n p a r a m e t e r s of the Hamiltonian that a r e d e s c r i b e d above. In this c a s e , all of the a bonds were
a s s u m e d to be m a g n e t i c a l l y equivalent, and the t e n s o r of the diamagnetic susceptibility with components
XXXN = X z z N = - 2 . 5 8 . 1 0 -6 c m 3 / m o l e and X y y N =0, where X is the axis along which the u n s h a r e d p a i r is
d i r e c t e d , and Z is the axis p e r p e n d i c u l a r to the plane of the m o l e c u l e , was f o r m a l l y a s c r i b e d to the u n -
s h a r e d p a i r of nitrogen. T h e s e p a r a m e t e r s w e r e s e l e c t e d in such a way as to r e p r o d u c e the e x p e r i m e n t a l
data f o r pyridine [9].
We note that X m = 4 8 . 4 ~ 0 . 1 (48.41), AXZZ = 5 7 . 4 5 ~ 0 . 8 (57.46), XZZ =86.8~-0.8 (86.75), X X X = 3 0 . 4
0.5 (30o45), and X y y = 2 8 . 3 (28.02). The r e s u l t s of our calculations a r e given in p a r e n t h e s e s ; all of
the quantities a r e given in units o f - 1 0 -6 c m 3 / m o l e .
A c o m p a r i s o n of the data in Table 3 with the calculations of t h e h y d r o c a r b o n analogs of the h e t e r o -
a r o m a t i c s y s t e m s u n d e r c o n s i d e r a t i o n [8] shows that the p r e s e n c e of a nitrogen atom leads to a slight in-
c r e a s e (with r e s p e c t to the modulus) of the v - e l e c t r o n contributions to the diamagnetic susceptibility and
d e m o n s t r a t e s the weak s e n s i t i v i t y of the d i a m a g n e t i c susceptibility to the position of the h e t e r o a t o m in the
moleculeo At the s a m e t i m e , the c h e m i c a l shifts of r e l a t e d compounds (for e x a m p l e , quinoline and isoquin-
o l i n e , a c r i d i n e and phenanthridine, and benzoDe ]quinoline and benzo [g]quinoline) that we e x a m i n e d differ a p -
p r e c i a b l y (Table 4).
In o u r c o m p a r i s o n of some of the calculated c h e m i c a l shifts with the e x p e r i m e n t a l data available Ln
the l i t e r a t u r e [10-13], the effect of the u n s h a r e d p a i r of the nitrogen atom was taken into account by m e a n s
of the additive p a r a m e t e r - 1 . 3 7 p p m f o r the protons noted in T a b l e 4 by m e a n s of a s t e r i s k s [sic] and - 0 . 4 8
ppm for the protons adjacent to the h e t e r o a t o m . As s e e n f r o m Table 4, the calculation s a t i s f a c t o r i l y r e -
p r o d u c e s the p e c u l i a r i t i e s of the PMR s p e c t r a , and this constitutes evidence in f a v o r of the e l e c t r o n - d e n s i t y
distributions found and the e x t e r n a l m a g n e t i c field induced ~ - e l e c t r o n c u r r e n t s , which f o r m the b a s i s of the
calculation of the m o l e c u l a r m a g n e t i c p r o p e r t i e s .
Judging f r o m the m o l e c u l a r d i a g r a m s (Fig. 1) and our p r e v i o u s e x p e r i m e n t a l data, c o r r e l a t i o n between
the activity of the h e t e r o c y c l e in h e t a r y l a t i o n and the calculated C - I ~ bond o r d e r s and the c h a r g e on the
s - c a r b o n atom is not o b s e r v e d in the benzopyridine s e r i e s . If such a c o r r e l a t i o n did exist, we would have
o b s e r v e d higher activity of quinoline r a t h e r than of isoquinoline, which c o n t r a d i c t s o u r data. In addition,
this s o r t of relationship, n e v e r t h e l e s s , does exist in the benzoquinoline s e r i e s , although c o r r e l a t i o n with the
b a s i c i t i e s of the h e t e r o c y c l e s is absent. In fact, if the r e a c t i v i t i e s of compounds of the benzoquinoline s e r i e s
in h e t a r y l a t i o n a r e c o m p a r e d (by e s t i m a t i n g the m i n i m u m t e m p e r a t u r e and the r e a c t i o n t i m e , as well as
the yield of h e t a r y l a t e d compound and the p o s s i b i l i t y of h e t a r y l a t i o n of weak nucleophiles), it t u r n s out that
phenanthridine is le s s active in h e t a r y l a t i o n than a c r i d i n e , isoquinoline, and quinoline [15 ]. Benzo if ]quinol-
ine p r o v e d to be e v e n l e s s active: the r e a c t i o n could be c a r r i e d out only with the m o s t nucleophilic ~ - s u r -
plus h e t e r o c y c l e s - p y r r o l e and indole (Table 5) - and dialkylanilines and s i m i l a r activated a r o m a t i c c o m -
pounds w e r e not h e t a r y l a t e d even u n d e r s e v e r e conditions.
We did not study the activity of benzo[g]quinoline in h e t a r y l a t i o n , but, judging f r o m the calculated
v a l u e s , this h e t e r o c y c l e should be m o r e active than benzo[f]quinoline and somewhat less active than phen-
anthridine. Benzo[h]quinoline does not undergo h e t a r y l a t i o n even u n d e r s e v e r e conditions, p r o b a b l y as a
consequence of shielding of the ring-nitrogen atom in it and the i m p o s s i b i l i t y of the f o r m a t i o n of N - a c y l
salts.
In o r d e r to differentiate between the effects of s t r u c t u r a l and e l e c t r o n i c f a c t o r s on the activity of
the h e t e r o c y c l e s , we i n v e s t i g a t e d the b e h a v i o r in this r e a c t i o n of 7,8,9,10-tetrahydrophenanthridine. It
was found that this h e t e r o e y c l e r e s e m b l e s its e l e c t r o n i c analog - quinoline - m o r e with r e s p e c t to its a c -
tivity than phenanthridine. V a r i o u s 7 , 8 , 9 , 1 0 - t e t r a h y d r o p h e n a n t h r i d i n e d e r i v a t i v e s of indoles, p y r r o l e s ,
~ - m e t h y l f u r a n , and 1 - m e t h y l - l , 2 , 3 , 4 - t e t r a h y d r o q u i n o l i n e w e r e r e l a t i v e l y e a s i l y obtained. However, the
yields in 'a n u m b e r of c a s e s w e r e low b e c a u s e of c o n s i d e r a b l e r e s i n i f i c a t i o n .
The s t r u c t u r e s of all of the synthesized compounds w e r e proved by c o m p a r i s o n of the IR and
UV s p e c t r a with the s p e c t r a of compounds of known s t r u c t u r e , which were synthesized via the s c h e m e
on the following page.
The m a s s s p e c t r a of the s y n t h e s i z e d compounds also c o n f i r m e d t h e i r s t r u c t u r e . We have p r e v i o u s l y
[16, 17] e s t a b l i s h e d the p r i n c i p l e s of the d i s s o c i a t i v e ionization (during a m a s s - s p e c t r a study) of p a r t i a l l y
h y d r o g e n a t e d N - a c y l d e r i v a t i v e s of quinoline and isoquinoline. It was l e g i t i m a t e to a s s u m e that the d i s -
i n t e g r a t i o n of I I I - V u n d e r e l e c t r o n impact would p r o c e e d v i a a s i m i l a r s c h e m e .

957
 I u \r~,,
C6n4CHa \~'4,
NH 2 OHC COOH I ~'j .

~'~ coon / o7 " . ~ n

~ ~ If. C6H4CH3

H r' II R' COR

III IV a-g v a-g

However, the m a s s s p e c t r a of I I I - V contain substantial d i f f e r e n c e s in the t r e n d of the disintegration:

t h e r e a r e no p e a k s of ions c o r r e s p o n d i n g to dehydrogenation of the m o l e c u l a r ion, and elimination of a
h e t a r y l r e s i d u e f r o m the phenanthridine o r 5,6-benzoquinoline p o r t i o n of the molecule in the f i r s t stage
of disintegration of the m o l e c u l a r ion is not o b s e r v e d . Consequently, N - b e n z o y l - o r N-aeetylphenanthridine
cations o r 5,6-benzoquinolinium cations a r e not f o r m e d . The m a x i m u m peaks a r e those of the ions f o r m e d
by elimination of acetyl or benzoyl r e s i d u e s f r o m the m o l e c u l a r ion (this was c o n f i r m e d by the c o r r e -
s p o n d i n g m e t a s t a b l e p r o c e s s e s ) , i.e., t h e s e compounds d i s i n t e g r a t e in a m a n n e r s i m i l a r to the d i s s o c i a t i v e
ionization of a r o m a t i c a m i n e s .

The high intensity of the ( M - R C O ) + i o n peak, where B =CH 3 and CGHs, is evidently due to a r e a r r a n g e -
m e n t p r o c e s s a s s o c i a t e d with m i g r a t i o n of a hydrogen atom f r o m the t e t r a h e d r a l c a r b o n atom to the n i t r o -
gen a t o m of the phenanthridine o r 5,6-benzoquinoline ring. The r e a r r a n g e m e n t p r o c e s s p r o m o t e s a r o m a t i -
zation of the ( M - R C O ) + i o n . The dehydrogenation that follows this p r o c e s s leads to the f o r m a t i o n of ions
with the s t r u c t u r e s of p o l y c y c l i c - h e t e r o c y c l i c compounds with a bridge-nitrogen atom [18-20], as a t t e s t e d
to by the a p p e a r a n c e of the c o r r e s p o n d i n g group of doubly c h a r g e d ions with m a s s e s (M-I~CO) 2+, [(M-RCO)
- H ] 2+, and [ ( M - R C O ) - 2 H ] 2+.
Elimination of a n e u t r a l HCN o r CH3CN p a r t i c l e f r o m the p y r r o l e ring of indole f r o m the [ ( M - R C O ) -
H] +" ion r a d i c a l shows that the s - p o s i t i o n of the indole ring is not blocked, and the l a t t e r m a k e s it possible
to f o r m a judgment r e g a r d i n g the site of fusion of the phenanthridine o r 5,6-benzoquinoline ring with the
indole ring in I I - V .
The position of the m e t h y l group in the indole f r a g m e n t of the m o l e c u l e is also readily e s t a b l i s h e d
by c o m p a r i s o n of the intensities of the ( [ ( M - I ~ C O ) - H ] - C H ~ + - i o n p e a k s . It is known [21] that the inten-
sity of the (M-CH3) + p e a k in the s p e c t r u m of N - m e t h y l i n d o l e is c o n s i d e r a b l y higher than in the s p e c t r a
of its homologs with a m e t h y l substituent in any o t h e r position of the ring.
Thus, the disintegration of HI-V can be r e p r e s e n t e d by the s c h e m e * on the following page (in the
c a s e of a compound of the III type, the p r e p a r a t i o n of which we have p r e v i o u s l y d e s c r i b e d ) .
In s y n t h e s i z e d b i s h e t e r o c y e l i c s y s t e m s of the I I I - V type, in which conjugation between the rings is
absent b e c a u s e of the p a r t i a l hydrogenation of one of t h e m , the C - C bond between the h e t e r o r i n g s is cleaved
during e l e c t r o n impact. This s o r t of p r o c e s s is not o b s e r v e d in those c a s e s where both h e t e r o r i n g s in the
s y s t e m a r e c o m p l e t e l y a r o m a t i c [18]. The detachment of one of the h e t e r o r i n g s in I I I - V is c o n f i r m e d by
the p r e s e n c e of a r a t h e r intense p e a k of an ion with the s t r u c t u r e of the c o r r e s p o n d i n g h e t e r o c y e l i e s u b -
stitutent (the N - m e t h y l i n d o l e f r a g m e n t of the m o l e c u l e , which r e a r r a n g e s to the m o r e stable quinolinium
cation - see the following disintegration s c h e m e - is r e c o r d e d in the m a s s s p e c t r u m ) .

' * T h e n u m b e r s u n d e r the f o r m u l a s denote the m a s s n u m b e r s , while the n u m b e r s in p a r e n t h e s e s a r e

the intensities in p e r c e n t of the total ion c u r r e n t .

958
 I OC H5 -C'sH5 CO-I" -C9 HsN'~"

H H ~ 179 10,5)

+ ~ ,o~.5) ~'~ ~ -c.~c. ~ i"~d~-'-C ".

:.'+. ,A'?
CIt 3
130 13.11 I

IL

I!

t30 113) 307 (1.71 293 11.11

It should be noted that additional disintegrative channels a s s o c i a t e d with a r o m a t i z a t i o n of the hyc r o -

genated ring are not o b s e r v e d in the s p e c t r a of IVa-g, which have a hydrogenated phenanthridine ring. A c -
cording to the m a s s spectra, the p r e s e n c e of a hydrogenated ring in benzoquinoline is easily detected, in-
a s m u c h as intense ion peaks with m / e 184 and 183 a p p e a r in the m a s s s p e c t r u m as a result of cleavage of
the C - C bond.

EXPERIMENTAL
The m a s s s p e c t r a were r e c o r d e d with an SN-6 s p e c t r o m e t e r with a s y s t e m for direct introduction
of s a m p l e s into the ion source at a cathode e m i s s i o n c u r r e n t of 1.5 mA, a t r a p c u r r e n t of 15-20 mA, and
an ionization c h a m b e r t e m p e r a t u r e of 180 ~.

The dipole m o m e n t s were calculated from the f o r m u l a p =0.221 ' [ P o o - PeP where P ~ is the p o l a r i z a -
tion at infinite dilution, and Pel is the m o l e c u l a r r e f r a c t i o n , which is equal to the electronic polarization
and is calculated from the r e f r a c t i v e indices and the densities. The r e f r a c t i v e indices of the solutions were
m e a s u r e d with an I R F - 2 3 r e f r a c t o m e t e r with the cuvette d e s c r i b e d in [22]. The densities were d e t e r m i n e d
p y c n o m e t r i c a l l y . The P~ value was calculated by the method in [23], and all of the m e a s u r e m e n t s were
made at 25 9 0.005 ~ The " c r y o s c o p i e a l l y . p u r e - g r a d e benzene was purified by the method in [24] and had
bp 79.8 ~ (740 ram), d42g 0.87369, n2949,793,and e29 2.2725.
C h r o m a t o g r a p h y in a loose thin l a y e r of aluminum oxide was r e a l i z e d in b e n z e n e - h e x a n e - c h l o r o f o r m
(6 : 1 : 30). 7,8,9,10-Tetrahydrophenanthridine was obtained by the method in [25] and had mp 61-62 ~ and
Rf 0.65.
Typical Hetarylatien Method. A 0.01-mole sample of acetyl chloride and 0.01 mole of the compound'
to be h e t a r y l a t e d were added to a solution of 0.02 mole of benzoquinoline in 25 ml of anhydrous benzene o r
d i m e t h y l f o r m a m i d e (DMFA), after which the r e a c t i o n mixture was held at room t e m p e r a t u r e or heated to
100 ~ for 2 to 10 h. At the end of the reaction (monitoring by TLC), the solvent was r e m o v e d by distilla-
tion, and the residue was neutralized with ammonium hydroxide, washed with hot water, dried, and c r y s t a l -
lized from a suitable solvent. The yields and c h a r a c t e r i s t i c s of the compounds obtained are p r e s e n t e d in
Table 5. The IR s p e c t r a of all IV and V contained c h a r a c t e r i s t i c bands at 1650-1700 c m 21 (VCO), while
bands at 3450 cm -i (Vl~H) were additionally o b s e r v e d in the s p e c t r a of IVa, b, d, e, and Va, b, e, g.
2 , 5 - D i ( 1 - b e n z o y l - l , 2 - d i h y d r o b e n z o [ f ] - 2 - q u i n o l i n y l ) p y r r o l e . This compound was obtained along with
Vg as d e s c r i b e d above by hetarylation of p y r r o l e with benzo if ]quinoline in the p r e s e n c e of benzoyl chloride.
The yield of product with mp 161-162 ~ (from pentanol) was 16%; R f 0.23. IR spectrum: 1680 (CO) and

959
3430 cm -1 (NH). Found: C 83.1; H 5.1; N 6.5%; M 642 (Rastmethod). Ct4H3~NsO2. Calculated: C 83.4; H4.9;
N 6.6%; M 633.
2-(3-Indolyl)benzo[f]quinoline. A) A solution of 0.7 g (91.7 mmole) of Vb and 0.58 g (1.7 mmole) of
triphenylmethyl perehlorate in 10 ml of acetonitrile was refluxed for 14 h, after which the mixture was
decomposed with ammonium hydroxide and extracted with chloroform. The extract yielded 0.4 g (85%) of
greenish crystalline 2- (3-indolyl)benzo if ]-quinoline with mp 304-305 ~ (from ethanol) and l~f 0.88. Found:
C 85.6; H 5.0; N 9.4%. C21H14N2. Calculated: C 85.7; H 4.8; N 9.5%. The picrate had mp 222-223 ~ (from
ethanol). Found: N 13.3%. C21Ht4N~.C~H~N30~. Calculated: N 13.4%.
B) A solution of 1.88 g (13 mmole) of 3-formylindole, 2 g (13 mmole) of fl-naphthylamine, and 1 ml
of H2SO4 in 20 ml of absolute ethanol was refluxed for 1 h, after which it was cooled to 60 ~ a solution of
1.2 g (13 mmole) of pyruvic acid in 10 ml of ethanol was added dropwise, and the mixture was refluxed for
another 3 h. It was then cooled, and the precipitated 2-(3-indolyl)benzo[f]quinoline-4-carboxylic acid was
separated to give 0.9 g (90%) of a product with mp 3 2 1 - 3 2 2 ~ (dec., from ethanol). Found: C 78.1; H 4.1;
N 8.2%. C22HItN202. Calculated: C 78.1; H 4.2; N 8.3%.
Decarboxylation of the acid at 200 ~gave 2-(3-indolyl)beuzo[f ]quinoline; no melting-point depress ionwas
observed for a mixture of this product with a sample obtained by method A.

LITEI~ATURE CITED
1. A . K . Sheinkman, M. M. Mestechkin, A. P. Kucherenko, V. V. Artemova, V. N. Poltavets, and Yu. B.
Vysotskii, Khim. Geterotsikl. Soedin., 537 (1974).
2. M . M . Mestechkin, L. Gutyrya, and V. N. Poltavets, Optika i Spektroskopiya, 2...88,454 (1970).
3. M.M. Mestechkin, Optika i Spektroskopiya, 32, 355 (1972).
4. R. Brown and M. Heffernan, Austral. J. Chem., 1__2,554 (1959).
5. S . P . MeGlynn, T. Adzumi, and M. Kinosita, Molecular Spectroscopy of the Triplet State, P r e n t i c e -
Hall (1969).
6. N. Mataga, Z. Phys. Chem., 1.~8, 285 (1958).
7. D. Graig and I. l~oss, J. Chem. Soc., 1589 (1954).
8. Yu. B. Vysotskii, Zh. Strukt. Khim., 1__2,289 (1971).
9. 1R. Mffller and F. Dorr, Elektrochemo, 52, 5636 (1970).
10. W. Brugel, Z. Elektrochem., 6__6,159 (1962).
11. F. Balkan and M. L. Heffernan, Austral. J. Chem., 2__44,2371 (1971).
12. I. Mozistima, K. Okada, and T. Yonezawa, J. Amer. Chem. Soc., 94, 1425 (1972).
13. I. Panca, I. Goia, and M. Ionescu, R e , . Rom. Chem., 1.7.7, 1423 (1972).
14. R. Mffller and F, Dorr, Elektrochem., 6__3,1150 (1959).
15. A . K . Sheinkman, A. P. Kucherenko, and S. N. Baranov, Khim. Geterotsikl. Soedin., 669 (1973).
16 A . K . Sheinkman, A. A. Dei+kalo, T. V. Stupnikova, N. A. Klyuev, and G. A. MalVtseva, Khim. Geterot-
sikl. Soedin., 1099 (1972).
17. A . K . Sheinkman, Ao N. Kost, A. N. Prilepskaya, and N. A. Klyuev, Khim. Geterotsikl. Soedin., 1105
(1972).
18. N . A . Klyuev, R. A. KhmePnitskii, G. A. Mal'tseva, A. K. Sheinkman, V. A. Ivanov, and B. M. Zolo-
tarev, Khim. Geterotsikl. Soedin., 979 (1973).
19. R . A . Khmel'nitskii, N. A. Klyuev, and P. B. Terent'ev, Zh. Obshch. Khim., 7, 395 (1971).
20. R . A . KhmelTnitskii, N. A. Klyuev, K. K. Zhigulev, and A. K. Sheinkman, Izv. Timiryazev. Sel'skokhoz.
Akad., 6, 200 (1970).
21. V . I . Vysotskii, Master's Dissertation, Moscow (1969).
22. B . V . Ioffe, 1Refractometrio Methods in Chemistry [in Russian], GNTIKhL, Leningrad (1960), p. 158.
23. I. Halverstadt and W. Kumler, J. Chem. Soc., 6__4,2988 (1942).
24. E . V . Titov and N. R. Kal'nitskii, Zh. Strukt. Khim., 13, 447 (1972).
25. B. Hollingsworth and V. Petrov, 3. Chem. See., 1573 (1948).

960
INVESTIGATION OF 2,3-POLYMETHYLENEQUINOLINES
XVIII.* KINETICS OF THE REACTION OF 4 - C H L O R O - 2 , 3 - P O L Y M E T H Y L E N E -
QU1-NOLINES WITH SODIUM METHOXIDE

M. E. Konshin, D. I . Uvarov, UDC 541.127 : 547.831

a n d I~. S. A b r a m o e h k i n

The r a t e of the r e a c t i o n of 4 - c h l o r o - 6 - 1 ~ - 2 , 3 - p o l y m e t h y l e n e q u i n o l i n e s with sodium methoxide

d e c r e a s e s as the n u m b e r of m e t h y l e n e groups i n c r e a s e s ; this is explained by the inductive aiad
s t e r i e e f f e c t s of the polymethylene chain. The r a t e constants of the r e a c t i o n a r e in c o n f o r m i t y
with the A r r h e n i u s equation and a r e found to e x i s t in a c o r r e l a t i o n relationship with the O'cat sub-
stituent constants for quinoline.

Although the kinetics of the nucleophilic substitution r e a c t i o n s of the chlorine atom in 2- and 4 - c h l o r o -
quinolines have been i n v e s t i g a t e d in detail [2, 5], t h e r e are only qualitative" o b s e r v a t i o n s with r e s p e c t to
the lability of the halogen in 4 - e h l o r o - 2 , 3 - p o l y m e t h y l e n q u i n o l i n e s [6-8]. In o r d e r to m a k e a quantitative
evaluation of the effect of the polymethylene chain on the r a t e of nucleophilie substitution of the halogen
in 4 - c h l o r o - 2 , 3 - p o l y m e t h y l e n e q u i n o l i n e s , we investigated the kinetics of the r e a c t i o n of these compounds
(I-XIV) with sodium methoxide, as a r e s u l t of which 4 - m e t h o x y - 2 , 3 - p o l y m e t h y l e n e q u i n o l i n e s (XV-X-X~II,
T a b l e 1) a r e f o r m e d .
C1 OCH3

H2)n H2) n

I-XIV XV-XXVII

I-V, XV-XIX n = 3 ; VI-X, XX-XXIII n = 4 ; XI-XIV, XXIV-XXVII n = 5

The r e s u l t s of the kinetic m e a s u r e m e n t s a r e p r e s e n t e d in Table 2. The r e a c t i o n is in c o n f o r m i t y

with the A r r h e n i u s equation, and this m a d e it p o s s i b l e to calculate its activation p a r a m e t e r s , which a r e
p r e s e n t e d in Table 2. It is seen f r o m the data in Table 2 that the m e t h o x y d e c h l o r i n a t i o n r a t e constants
(k) at 76.2~ d e c r e a s e as n i n c r e a s e s . The d e c r e a s e in the rate in the o r d e r I - V > V I - X > XI-XIV should
be explained by the e l e c t r o n - d o n o r p r o p e r t i e s of the m e t h y l e n e group, by which the compounds of the t h r e e
r e a c t i o n s e r i e s u n d e r c o n s i d e r a t i o n a r e distinguished, and also by s t e r i e hindrance on the p a r t of the
m e t h y l e n e groups bonded to the C(2) and C(3 ) a t o m s of the quinoline ring, which is m a n i f e s t e d m o s t m a r k e d l y
in VI-XIV. The c o n s i d e r a b l e d e c r e a s e in the activation e n t r o p y a t t e s t s to an i n c r e a s e in s t e r i e hindrance
on p a s s i n g f r o m compounds of the f i r s t r e a c t i o n s e r i e s in =3) to compounds of the second (n =4) and t h i r d
(n =5) r e a c t i o n s e r i e s . The o b s e r v e d phenomenon m u s t be explained by the following r e a s o n s .
In the compounds of the second and t h i r d r e a c t i o n s e r i e s the angles between the C ( 2 ) - C H 2 o r C ( 3 ) - C H 2
bond and the 6(2)--C(3 ) bonds a p p r o a c h 120 ~ In 4 - c h l o r o - 2 , 3 - t r i m e t h y l e n q u i n o l i n e s , owing to the g r e a t
rigidity of the s y s t e m , t h e s e s a m e v a l e n c e s a r e d i r e c t e d at a s m a l l e r angle (113~ As a consequence of
t h i s , the c a r b o n atom of the CH 2 groups in I - V is found at a sufficient distance f r o m the chlorine atom and
is not o v e r l a p p e d with it, while the c a r b o n atom of the CH 2 group in VI-XIV is c l o s e r to the chlorine a t o m
and p a r t i a l l y o v e r l a p s it. In addition, the hydrogen a t o m s of the CH 2 groups of I-V, which contain a f i v e -
* F o r C o m m u n i c a t i o n XVII see [1].

P e r m P h a r m a c e u t i c a l Institute. T r a n s l a t e d f r o m K h i m i y a G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 8,

pp. 1106-1109, August, 1974. Original a r t i c l e submitted M a r c h 15, 1973.

O19 76 Plenum Publishing Corporation, 22 7 West 17th Street, "New York, N. Y. 10011. No part o f this publication may be reproduced,
stored bz a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

961
 TABLE 1. 4-Methoxy-2,3-polymethylenequinolines (XV-XXVII)
N,%
C o r n

pound
-
mp, ~ Empirical
form ula found calc. ~0ield ,
XV H 71--72 CIsH~sNO 7,1 7,0 67
XVI 108--109 CI4HIsNO 6,5 6,6 70
XVI I 110--111 C13HI~CINO 6,1 6,0 79
XVIII CHaO I17--118 CI4HIsNO2 6,3 6,1 67
XIX pr 100 CIsHx2BrNO 5,2 5,0 78
XX 58 CI~HIsNO 6,4 6,6 40
XXI CH3 80 C~sH~TNO 6,1 6,2 35
XXlI CI 110 Ct4HI4CINO 5,4 5,7 52
XXIII 10i CI4H14BrNO 4,7 4,8 50
XX1V 74 CIsH17NO 6,3 6,2 27
XXV 65 C16H19NO 6,05 5,8 42
XXVI 95 CIsH16CI~NO 5,3 5,4 70
XXVI I Br 110--112 C15HI6BrNO 4,5 4,6 42

* Compounds XV, XX, and XXV were crystallized from petroleum

ether, while the remaining compounds were crystallized from
methanol.

T A B L E 2. K i n e t i c a n d T h e r m o d y n a m i c Parameters of the
Reaction of 4-Chloro-2,3-polymethylenequinolines with Sodium
Methoxide

Corn-[ k ' l O 4 , 1 i t e r ' m o l e ' l ' s e c - I I E, I I AF~ ,

pound n [ R i 66~ i 76,2~~ 8--5,7~ 97,2" I kcal/ lg4 /,S*,e.u. kcal/
mole mole
[
3 H ! -- 0,230 0,57 1,81 25,16 " 1I,I8 --9,97 27,95
II; 3 CHa ; -- 0,115 0,38 0,92 25,30 " 11,18 --10,95 28,43
III I 3 CHsO: -- 0,089 0,29 0,860 27,63 ' 12,26 --4,78 28,61
1V 3 C1 0,41 1,20 2,86 23,85 ii,00 --!0,41 26,80
V 3 Br 0,52 1,61 3,82 24,58 1!,57 --7.78 26,60
VI 4 H -- 0,095 0,17 0,47 19,56 7,20 -27,72 28,55
VII 4 CHa ] -- 0,052 0,11 0,24 18,53 6,32 -31,90 28,98
VIII 4 ICHaO 0,035 0,067 0,14 16,75 5,03 -37,76 29,25
IX 4 ~C1 0,19 0,43 0,74 t6,65 6,02 --33,12 27,52
X 4 ,Br : 0,22 0,67 1,057 19,24 7,78 -24,82 27,21
XI 5 H -- 0,045 0,111 0,28 22,52 8,82 --20,78 29,08
XII 5 'CH3 i -- 0,0245 0,06 0,16 23,28 ' 8 , 9 7 --19,81 29,50
XIII 5 C! ! -- , 0,285 0,645 1,71 22,45 9,50 --17,31 27,80
XIV 5 Br -- ~ 0,43 ' 1,042 2,70 22,70 9,87~ -15,78 27,52

TABLE 3. Parameters of the Correlation Dependence of log k

on a c a t

p
r
Compound Calc. log k ~ I r s
. . . . . . . . . . . . . . . . . . . ]. . . . . . . . . . . . [. . . . . . . . . . .

I--V 4,72 --4,60 0,994 II 0,054

VI--X 4,56 --4,99 0,993 l 0,058
XI--XIV 5,06 --5,36 0,991 1 0,107

m e m b e r e d r i n g s i t u a t e d in t h e s a m e p l a n e w i t h t h e q u i n o l i n e r i n g , a l s o a r e n o t o v e r l a p p e d w i t h c h l o r i n e ,
i n a s m u c h a s t h e l a t t e r i s l o c a t e d in t h e m i d d l e o f t h e d i h e d r a l a n g l e f o r m e d b y t h e v a l e n c e s o f t h e h y d r o -
g e n a t o m s ( c o n f o r m a t i o n a).

I Cl CII
H~C~H ' H~H

R R
a b
T h e e y c l o a l k e n e r i n g o f V I - X I V h a s a h a l f - c h a i r f o r m ( c o m p a r e w i t h t e t r a l i n [9]), a n d o w i n g t o t h i s t h e
dihedral angtesbetweenthe pseudoequatorial and pseudoaxial hydrogen atoms of the methylene groups ad-
jacent to the quinoline ring are divided by the plane of the quinoline ring into unequal fractions (conforma-
t i o n b). M o r e o v e r , t h e p s e u d o a x i a l h y d r o g e n i s c l o s e r t o t h e c h l o r i n e a t o m a n d p a r t i a l l y s h i e l d s i t .

962
 Sterie hindrance to solvation of VI-XIV is also o b s e r v e d due to the f o r m a t i o n of hydrogen bonds
between the m e t h a n o l and the h e t e r o r i n g nitrogen. The effect of methanol on the r e a c t i o n r a t e , which, as is
well known [3, 5], c o n s i d e r a b l y a c c e l e r a t e s side p r o c e s s e s , is t h e r e b y weakened.
The methox-ydechlorination r a t e constants of I - V at 76.2 ~ are l o w e r by a f a c t o r of 6-14 as c o m p a r e d
with the r a t e constants of the s a m e r e a c t i o n of 4 - c h l o r o q u i n o l i n e s at 75.2 ~ [2]; this is a s s o c i a t e d p r i m a r i l y
with the inductive effect of the polymethylene chain in I - V and, to a l e s s e r extent, with s t e r i c hindrance on
the p a r t of this s a m e chain.
The r a t e of m e t h o x y d e c h l o r i n a t i o n of the i n v e s t i g a t e d compounds depends on the group attached to
the C(6 ) a t o m and i n c r e a s e s as the e l e c t r o n e g a t i v i t y of the s u b s t i t u e n t s i n c r e a s e s : CH30 <CH z <H <C1 < B r .
A c o r r e l a t i o n dependence between the m e t h o x y d e c h l o r i n a t i o n r a t e constants of I-XIV at 76.2 ~ and the ~cat
substituent constant of quinoline [10] was found. The p a r a m e t e r s of the c o r r e l a t i o n dependence log k - ~ c a t
(Table 31 attest to g r e a t sensitivity of the r e a c t i o n c e n t e r to the effect of substituents attached to C(~). The
introduction of a polymethylene chain does not b r i n g about a s u b s t a n t i a l change in the r e a c t i o n constant.

EXPERIMENTAL
4-Chloro-2,3-polymethylenequinolines. These compounds were obtained by the methods in [6, II-14]
and were recrystallized three times from hexane. Anhydrous methanol was prepared by the method in [15].
Sodium methoxide was prepared by the usual method from analytically pure-grade sodium and anhydrous
m e t h a n o l . The sodium methoxide c o n c e n t r a t i o n was d e t e r m i n e d by t i t r a t i o n with 0.1 N h y d r o c h l o r i c acid
with m e t h y l r e d as the indicator.
The r e a c t i o n m i x t u r e f o r the kinetic m e a s u r e m e n t s was p r e p a r e d in a 2 5 - m l v o l u m e t r i c f l a s k by d i s -
solving a weighed s a m p l e of 4 - c h l o r o - 2 , 3 - p o l y m e t h y l e n e q u i n o l i n e in 15 m l of anhydrous methanol and by
subsequent addition of the calculated volume of sodium methoxide and the n e c e s s a r y amount of methanol.
The initial 4 - c h l o r o - 2 , 3 - p o l y m e t h y l e n e q u i n o l i n e and sodium methoxide concentrations were 0.012-0.052 M
and 0.060-0.160 M, r e s p e c t i v e l y . Samples (2 mD of the p r e p a r e d solutions w e r e u s e d f o r the d e t e r m i n a t i o n s
and w e r e placed in 2 0 - m l g l a s s a m p u l s . The a m p u l s w e r e sealed and s i m u l t a n e o u s l y i m m e r s e d in a
t h e r m o s t a t ; the t e m p e r a t u r e was m a i n t a i n e d constant with an a c c u r a c y of +0.05 ~ The t i m e of i m m e r s i o n
of the s a m p l e in the t h e r m o s t a t was t a k e n as the s t a r t of the r e a c t i o n . At the end of the reaction, the a m p u l
was cooled with ice, and the contents w e r e poured into 20 m l of 0.3 lq nitric acid solution. The chloride
ion c o n c e n t r a t i o n was d e t e r m i n e d by the Volhard method. The r a t e constants w e r e calculated f r o m the
s e c o n d - o r d e r equation
2.303 , b(a--x)
t(a-b) ~g-7~---TF '

where a and b are the m o l a r c o n c e n t r a t i o n s of sodium methoxide and the halo derivative, r e s p e c t i v e l y , and
x is the chloride ion c o n c e n t r a t i o n at t i m e t (in seconds). The slope of the dependence of log [ ( a - x ) / ( b - x ) ]
on t was c a l c u l a t e d by the method of l e a s t s q u a r e s . A c o r r e c t i o n for the t h e r m a l expansion of m e t h a n o l
[16] was introduced.
4 - M e t h o x y - 2 , 3 - p o l y m e t h y l e n e q u i n o l i n e s (XV-XXVII, T a b l e 1). A 0.005-mole s a m p l e of 4 - c h l o r o - 2 , 3 -
polymethylenequinoline was added to a solution of 0.5 g of sodium in 15 m l of methanol, and the m i x t u r e
was refluxed for 20-200 h. It was then cooled and p o u r e d into water, and the r e s u l t i n g p r e c i p i t a t e was
r e m o v e d by filtration and c r y s t a l l i z e d .

LITERATURE CITED
1~ D . I . Uvarov, A. S. Zaks, L. G. Z i l ' b e r m i n t s , T. A. Kapitonenko, and M. E. Konshin, Izv. Vuzov, Ser.
Khim. (1973, in p r e s s ) .
2. G. Illuminati and G. Marino, J. A m e r . Chem. Soc., 80, 1421 (1958).
3. G. IUuminati and G. Marino, Chem. and Ind., 1287 (1963).
4. G. B r e s s a n , G. Giardi, P. Linda, G. Sleiter, and G. Illuminati, J. Chem. Soc., B, 225 (1971).
5. G. Illuminati, G. Sleiter, and M. Speranza, J. O r g . Chem., 3_~6, 1723 (19711.
6~ O. Yu. Magidson and A. I. T r a v i n , Zh. Obshch. Khim., 7, 842 (19371.
7. L. Sargeat and L. Small, J . O r g . Chem., 1_!, 359 (1946).
8. A. Albert, R. G o l d a c r e , and E. Heymann, J . C h e m . Soc., 654 (1943).
9. E. Eliel, N. Allinger, S. Angyal, and G. M o r r i s o n , C o n f o r m a t i o n a l Analysis, Wiley (1965).
10. C h e m i s t ' s Handbook [in Russian], Vol. 3, Khimiya, L e n i n g r a d (19641, p. 964.

963
11. V. Petrow, J~ Chem. Soc., 634 ~1947).
12. M.S. Chadha, K. K. Chakravarti, and S. Siddighi, J. Sei. Ind. Res., 10B , 1 (1951).
13. L. Sargent and L. Small, J. Org. Chem., 12, 567, 571 (1947).
14. l~. S~ Abramochkin and M. E. Konshin, Khim.-Farmats. Zh., No. 7, 10 (1970).
15. Preparative Organic Chemistry [in Russian], GKhI, Moscow (1959), p. 157.
16. Chemist's Handbook [in Russian], Vol. 1, GKhI, Moscow (1962), p. 555.

964
PREPARATION OF 6-STYRYLPHENANTHRIDINES

E . V. G r i s h i n a , ]~. R. Z a k h s , UDC 547.836.3

a n d V. P . M a r t y n o v a

(6-Phenanthridinylmethyl)magnesium halides do not react with aromatic and aliphatic a r o -

matic ketones but do react with aromatic aldehydes to give the corresponding carbinols.
The latter are readily dehydrated to the corresponding 6-styrylphenanthridines. 6-Cyano-
methylphenanthridine reacts with aromatic aldehydes in the presence of sodium ethoxide
to give 6-(c~-cyanostyryl)phenanthridines and is converted to 5-acyl-6-cyanomethylene-5,6-
dihydrophenanthridine on heating with acetic anhydride or benzoyl chloride.

In connection with an investigation of phenanthridine derivatives containing conjugated groupings,

it seemed of interest to establish to what extent substitution of the double bond of 6-styrylphenanthridines
affects t h e i r physieochemical properties. In the present paper we report attempts to synthesize compounds
of this sort, inasmuch as only a few double-bond-unsubstituted styrylphenanthridines are described in the
literature. Most of the reported compounds were obtained by condensation of 6-methylphenanthridine with
benzaldehyde o r its derivatives in the presence of zinc chloride [1, 2]. We used this method to obtain
6-(p-methoxystyryl)phenanthridine in good yield. We also obtained it and 6-styryl-and 6-(p-nitrostyryl}-
phenanthridines by condensation of 6-methylphenanthridine with aldehydes in acetic anhydride. Howex er,
the indicated methods proved to be unsuitable for the preparation of styryls with substituted double bonds:
6-methylphenanthridine does not react with aliphatic aromatic ketones, while 6-alkylphenanthridines do not
react with aldehydes. In o r d e r to obtain an ~-methyl-substituted styryl, we attempted to cyclize o-methoxy-
~-methylcinnamtc acid 2-diphenylylamide by the method in [3]. However, treatment of the latter with
phosphorus oxychloride gave 3-methylcoumarin (I) instead of the corresponding styryl. There was also
partial dealkylation of the methoxy group and formation of 3-methylcoumarin in the preparation of o -m e th -
oxy-cv-methylcinnamoyl chloride. The cyclization of cinnamic acid diphenylylamides apparently holds
little promise for the preparation of styryls, inasmuch as 6-styrylphenanthridtne is formed in very low
yield also in polyphosphoric acid (PPA), and the chief product is 3,4-dihydro-4,8-diphenylquinolone (II) [4].
~ H5
.0% U% U% PPA
'= 3 J H
R' C6Hs CsH5
!
I[
In this connection, we attempted to synthesize 6-styrylphenanthridines by dehydration of the appropri-
ate alcohols. It seemed possible to obtain alcohols of this sort (IV, V) by reaction of (6-phenanthridinyl-
methyl)magnesium halides (Ha, b) with aryl carbonyl compounds. We were able to synthesize 1T[a from
6-ohloromethylphenanthridtne or by the convoy method with dibromoethane. It was found to be more
convenient to obtain IIllo by reaction of 6-methylphenanthridine with [sopropylmagnesium bromide, as
in the method described for quinaldine [5]. Compounds HI reacted with benzaldehyde and o-methoxy-
benzaldehyde to give the corresponding carbinols (IV, V), which were readily dehydrated to olefins
(VI, VII). However, IIIb, in contrast to the analogous compounds of a-picoline and quinaldine [5], did
not react with ketones in any of the investigated solvents [ether, tetrahydrofuran (THF), dioxane, anisole,
and hexamethylphosphoric triamide (hexametapol)]. Replacement of magnesium by lithium also did not
give positive results.

Lensovet Leningrad Technological Institute. Translated from Khimiya Geterotsiklicheskikh Soedin-

enti, No. 8, pp. 1110-1115, August, 1974. Original article submitted September 27, 1973.

9 76 Plenum Publishing Corporation, 22 7 ICest 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, #7 any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15. 00.

965
 OH
l

C2H4Br2 ~/
Iii a.b IV, V

IV, VI R=H; V , V I I R=o-OCH3,

a X=CI. b X=Br VI,VII

The l a c k of r e a c t i o n of IIIb with ketones is a p p a r e n t l y due to the g r e a t e r stabilization and, consequently,

l o w e r activity of the 6-phenanthridinyl anion as c o m p a r e d with the analogous anions f r o m ~ - p i o o l i n e and
quinaldine a s a consequence of the higher positive c h a r g e in the 6 - p o s i t i o n of phenanthridine [6, 7]. Con-
s i d e r i n g this, it might have been a s s u m e d that 6 - f o r m y l p h e n a n t h r i d i n e (VIII) has a high r e a c t i v i t y . How-
e v e r , it did not r e a c t with e i t h e r ~ - p h e n y l e t h y l m a g n e s i u m b r o m i d e o r even with the m u c h m o r e active
e t h y l m a g n e s i u m b r o m i d e . In addition, aldehyde VIII did not r e a c t in the p r e s e n c e of b a s e s with benzyl
cyanide - the usual r e a c t i o n for a r o m a t i c aldehydes. The r e a s o n f o r this low r e a c t i v i t y of 6 - f o r m y l p h e n -
anthridine is not c l e a r , although it m a y be due in p a r t to the s t e r i c effect of the hydrogen in the 7-position.
In o r d e r to reduce the effect of s t e r i c f a c t o r s and s i m u l t a n e o u s l y activate the methylene group, we s u b -
jected 6 - c y a n o m e t h y l p h e n a n t h r i d i n e (X) to condensation with a r o m a t i c aldehydes. This compound p r o v e d
to be quite active. The c o r r e s p o n d i n g ~ - c y a n o s t y r y l d e r i v a t i v e s (XI, XII) w e r e obtained in alcohol m e d i a
in the p r e s e n c e of sodium ethoxide with benzaldehyde and p - d i m e t h y l a m i n o b e n z a l d e h y d e . Condensation
also o c c u r s with p - n i t r o b e n z a l d e h y d e but is a p p a r e n t l y a c c o m p a n i e d by side p r o c e s s e s that hinder the i s o -
lation of the s t y r y l .
An a b s o r p t i o n band at ~ 340 rim, which is shifted b a t h o c h r o m i c a l l y under the influence of p - n i t r o and
p - m e t h o x y groups, is c h a r a c t e r i s t i c f o r d o u b l e - b o n d - u n s u b s t i t u t e d phenanthridine s t y r y l s . A b a t h o c h r o m i c
shift of 30-50 nm o c c u r s in acidic m e d i a . The p r e s e n c e of a nitrile group in the s - p o s i t i o n leads to o v e r -
lapping of the s h o r t - w a v e and long-wave a b s o r p t i o n bands of XI (Fig. 1). This o v e r l a p p i n g does not o c c u r
in the c a s e of p - d i m e t h y l a m i n o d e r i v a t i v e XII b e c a u s e of a pronounced b a t h o c h r o m i c shift of the long-wave
band (Fig. 2). Its c o l o r is shifted b a t h o c h r o m i c a l l y at pH 1 b e c a u s e of protonation of the nitrogen atom of
phenanthridine. In s t r o n g l y acidic m e d i a a proton also adds to the nitrogen a t o m of the dimethylamino
group, inducing an i n c r e a s e in the coloration (Fig. 2).
When X was heated in acetic anhydride it r e a c t e d with p - d i m e t h y l a m i n o b e n z a l d e h y d e to give s t y r y l
XII. However, the s a m e compound (XIII), which was yellow, was isolated in e x p e r i m e n t s with benzaldehyde
and p - n i t r o b e n z a l d e h y d e . However, XIII was also f o r m e d when X was refluxed in acetic anhydride in the
absence of aldehydes. This compound does not display e i t h e r acidic o r b a s i c p r o p e r i t e s . Its IR s p e c t r u m
contains bands of the s t r e t c h i n g v i b r a t i o n s of amide and CN groups. The e l e c t r o n i c s p e c t r u m of XIII dif-
f e r s f r o m the s p e c t r a of phenanthridine and 6 - s t y r y l p h e n a n t h r i d i n e d e r i v a t i v e s with r e s p e c t to the intense
a b s o r p t i o n band at ~400 nm (Fig. 1). A singlet of an acetyl group a p p e a r s in the PMR s p e c t r u m at ~2.6
ppm. 6-Methylphenanthridine was obtained in high yield as a r e s u l t of acid h y d r o l y s i s of XIII, and 6 - c y a n o -
methylphenanthridine was detected as an i n t e r m e d i a t e by T L C .

% ~
ArCHO
~
% Ac20

~CH~CN
. , OCH~
HaCN
COcH~

HCN

xl, xll x xlll

Xl At=C~Hs; Xll Ar=CoH4N(CH3)2-p

On the b a s i s of t h e s e r e s u l t s and the r e s u l t s of a d e t e r m i n a t i o n of the c o m p o s i t i o n and m o l e c u l a r
weight, we feel that XIII is 5 - a c e t y l - 6 - c y a n o m e t h y l - 5 , 6 - d i h y d r o p h e n a n t h r i d i n e . Compound XIII is a p p a r e n t l y
f o r m e d as a r e s u l t of detachment of a proton f r o m the c y a n o m e t h y l group of the initially f o r m e d 5 - a c e t y l -
6 - c y a n o m e t h y l p h e n a n t h r i d i n i u m salt.
Compound XIH is r e l a t i v e l y inert: it is not changed by the action of 2 M alkali at r o o m t e m p e r a t u r e ,
does not add hydrogen u n d e r n o r m a l conditions in the p r e s e n c e of Raney nickel, and does not r e a c t on h e a t -

966
 3 Lgg
~g c 't ! , t ~ ' s "

A
44'4,0~ l - -~~ ~-
\ '\ 4,4.
4,0".'
~'..\ ~,/ ",
"- v y ' ,,o_ ...-,,.:j\ .,,
L , , , l , , f' , , , . . . . . . ~, . j

500 ~.00 ~. ,nl'D_ 280 400 520 x ,,IllI1

Fig. 1 Fig. 2
Fig. 1. UV s p e c t r a of phenanthridine derivatives in alcohol: 1) 6-
(p-nitrostyryl)phenanthridine; 2) 6 - ( p - n i t r o s t y r y l ) p h e n a n t h r i d i n e at
pH 1; 3) 5 - a o e t y l - 6 - c y a n o m e t h y l e n e - 5 , 6 - d i h y d r o p h e n a n t h r i d i n e (XIII);
4) 6- (~-cyanostyryl)phenanthridine (XI).
Fig. 2. Absorption s p e c t r a of alcohol solutions of 6 - ( ~ - c y a n o - p -
dimethylaminostyryl)phenanthridine (XII): 1) neutral solution; 2) pH 1;
3) pH<0 (the log D+4.5 values are indicated in place of log a).

ing with benzaldehyde and its derivatives. However, when it is heated with p-dimethylaminobenzaldehyde
in acetic acid it is c o n v e r t e d to 6 - ( ~ - c y a n o - p - d i m e t h y l a m i n o s t y r y l ) p h e n a n t h r i d i n e . A compound s i m i l a r
to XIH was also obtained by reaction of X with benzoyl chloride [8].
It is interesting to note that compounds of the XIII type are also apparently f o r m e d from 6 - m e t h y l -
phenanthridine by heating with acetic anhydride o r benzoyl chloride, as can be judged from the c h a r a c t e r -
istic change in the absorption s p e c t r a . However, these compounds have not yet been isolated.

EXPERIMENTAL
o-Methoxy-o~-methylcinnamic acid was obtained in 50%yield by the method in [9].
o-Methoxy-c~-methylcinnamic Acid 2-Diphenylylamide. A m i x t u r e of 3 g (15 mmole) of o - m e t h o x y - ~ -
methylcinnamic acid and 6.7 g (93 mmole) of freshly distilled thionyl chloride was refluxed for 1 h, a f t e r
which the e x c e s s thionyl chloride was r e m o v e d by vacuum distillation, 15 ml of xylene and 2.64 g (15 mmole)
of 2-aminodiphenyl were added to the residue, and the m i x t u r e was refluxed until HC1 evolution ceased.
The xylene solution was washed with 5 M HC1, 15%Na2CO3, and water, and the xylene was r e m o v e d by dis-
tillation. The residue was refluxed for 2 rain in 25 ml of 5%NaOH, the mixture was cooled, and the p r e -
cipitate was r e m o v e d by filtration to give 1.5 g of the diphenylylamide with mp 90-91 ~ Crystallization from
50%alcohol (1: 10) and p e t r o l e u m e t h e r (1 : 70) gave a product with mp 94-95 ~ and Rf 0.52 (chloroform) and
0.15 (benzene).* IR s p e c t r u m in CC14:3450 and 1680 cm -l. PMR s p e c t r u m , 5, ppm(CHC13): 1.92 (C-CH3) ~
3.68 (OCHa). Found: C 80.7; H 6.6; N 3.8%. C23H21NO. Calculated: C 80.5; H 6.1; N 4.1%.
The diphenylylamide was heated at 130 ~ for 4-5 h with phosphorus oxychloride (1.2 ml p e r gram) to
give 3 - m e t h y l c o u m a r i n (60%) with rap 87-88 ~ [10] and Rf 0.7 (chloroform). IR spectrum: Vco (CC14) 1730
cm -1. PMR spectrum: 5CH 3 2.02 p p m (CHC13). UV s p e c t r u m , kma x (in alcohol), nm (log ~): 275 (4.07)
and 307 (3.85).
6 - ( 2 - P h e n y l - 2 - h y d r o x y e t h y l ) p h e n a n t h r i d i n e (IV). A solution of 3.86 g (0.02 mole) of 6-methylphen-
anthridine in 20 ml of benzene was added to 25 ml of a solution of isopropylmagnesium bromide obtained
from 0.48 g (0.02 g-atom) of magnesium and 2.68 g (0.02 mole) of isopropyl bromide in 20 ml of e t h e r .
Darkening of the m i x t u r e and gas evolution (propane) were o b s e r v e d . The solvents were r e m o v e d by dis-
tillation, and the residue was heated at 80-85" for 1.5 h, at the end of which the mixture began to solidify.
E t h e r (30 ml) was added to the solid m a s s , and the mixture was s t i r r e d with a glass rod. A solution of
2.12 g (0.02 mole) of benzaldehyde in 10 ml of e t h e r was added, and the m i x t u r e was s t i r r e d and refluxed
for 6 h. Saturated ammonium chloride solution (20 ml) was added, and the resulting precipitate was r e -
moved by filtration and washed with benzene and water. Two c r y s t a l l i z a t i o n s from alcohol (1 : 15) gave
1.7 g of IV with mp 162 ~ and Rf 0.15 (chloroform). IR spectrum: VOH 3270 cm -! (in KBr). UV spectrum,
Xmax in alcohol, nm (log e): 250 (4.7), 272 (4.09),** 290 (3.88)**, 330 (3.50), 346 (3.50). Found: C 84.0;
H 5.6; N 4.8%. C21HI?NO. Calculated: C 84.3; H 5.7; N 4.7%.
*The Rf values p r e s e n t e d w e r e obtained with a c t i v i t y 1I A120 3.
* *Here and subsequently, the inflection points and shoulders are designated by two a s t e r i s k s .

967
 6-Styrylphenanthridine (VI). C o n c e n t r a t e d sulfuric acid (2 ml) was added to a solution of 0.5 g (1.66
m m o l e ) of IV in 8 m l of glacial acetic acid, and the m i x t u r e was heated rapidly to the boiling point and r e -
fluxed for 2-3 m i n . It was then poured into 15 m l of cold w a t e r , and the aqueous m i x t u r e was cooled and
n e u t r a l i z e d with 10%NaOH and e x t r a c t e d with benzene to isolate VI. The e x t r a c t was dried with sodium
sulfate, and the product was isolated as the p i c r a t e with mp 228 ~ [3]. The b a s e was isolated f r o m the
p i c r a t e and dissolved in benzene, and the solution was f i l t e r e d through aluminum oxide. T h e benzene w a s
r e m o v e d by distillation, and the r e s i d u e was c r y s t a l l i z e d f r o m p e t r o l e u m e t h e r to give 0.4 g (86%) of VI
as slightly yellowish needles with mp 134-135 ~ (134 ~ [3]) and l~f 0.9 (chloroform). IR s p e c t r u m : v C =C
1635 cm -1 (KBr). UV s p e c t r u m , Xmax (in alcohol), nm (log ~)': 250 (4.51), 275 (4.38)* *, 330 (4.21), 350
(4.20)* *, UV s p e c t r u m in alcohol at pH 2, hmax, nm (D): 250 (1.16), 332 (0.264), 380 (0.244).
6- [2- (o-Methoxyphenyl)-2-hydroxyethyl]phenanthridine (V). This compound, with mp 195 ~ (from
C H C 1 3 - p e t r o l e u m ether), and Rf 0.2 (chloroform), was obtained in 25%yield by the method used to p r e p a r e
IV. IR s p e c t r u m , c m - I (KBr): "3350', 1240, and 1257 (broad, strong), UV s p e c t r u m , k m a x (in alcohol), nm
(log e): 250 (4.50), 273 (4.04)**, 295 (2.95)**, 330 (3.37), and 338 (3.33). Found: N 4.3%. C22H19~O2.
Calculated: N 4.3%.
6 - ( o - M e t h o x y s t y r y l ) p h e n a n t h r i d i n e (VII). This compound, with mp 114-115 ~ [from p e t r o l e u m e t h e r
(1 : 15)], was obtained in 67%yield by the method u s e d to p r e p a r e VI. I1~ s p e c t r u m , em -1 (in KBr): 1627
and 1253. UV s p e c t r u m , k m a x (in alcohol), nm (log e): 250 (4.63), 282 (4.41)**, and 330 (4.24). Found:
N 4.3%. C22HI?NO. Calculated: N 4.5%.
6-(p-Methoxystyryl)phenanthridine. A mixture of 0.98 g (5 mmole) of 6-methylphenanthridine, 0.68
g (5 mmole) of p-methoxybenzaldehyde, and 0.68 g (5 mmole) of anhydrous zinc chloride was heated at
150-160 ~ for 4 h, after which the styryl was extracted from the melt with chloroform. The chloroform was
removed from the extract by distillation, and the residue was dissolved in 50 ml of benzene. The solution
was filtered through aluminum oxide, and the filtrate was evaporated. The residue was crystallized from
a tenfold amount of alcohol-benzene (2 : 1) to give 0.7 g of light-yellow crystals with mp 140-141 ~ PMR
spectrum: 5 3.8 ppm (CHCI3). UV spectrum, kma x (in alcohol), nm (log e): 250 (4.65), 275 (4.35)**, and
360 (4.35). UV spectrum in alcohol at pH I, kmax' nm (D): 250 (1.12), 260 (i.0)** 330 (0.26), and 410
(0.23). Found: C 84.8; H 5.9; N 4.6%. C22HiTNO. Calculated: C 84.8; H 5.5; N 4.5%. An ~dentieal com-
pound was obtained in lower yield by refluxing equimolecular amounts of methylphenanthridine and anis-
aldehyde in a 20-fold quantity of acetic anhydride for 20 h.
6-(p-Nitrostyryl)phenanthridine. A 0.3-g (1.5 mmole) sample of 6-methylphenanthridine and 0.23 g
(1.5 mmole) of p-nitrobenzaldehyde were refluxed in 9 ml of acetic anhydride for 12 h, and the resulting
crystals were removed by filtration and washed with acetic anhydride and petroleum ether to give 0.4 g
(81.5%) of the s t y r y l . It was d i s s o l v e d in 40 m l of c h l o r o f o r m , and the solution was washed with 15 m l of
5% NaOH and w a t e r and dried with Na2SO 4. The solution was then t r e a t e d with activated c h a r c o a l and e v a p -
o r a t e d to one t h i r d of its original volume to give 0.18 g of b r i g h t - y e l l o w c r y s t a l s with mp 233-234% The
product was only v e r y slightly soluble in hot alcohol (1 : 1000) and had l~f 0.55. (benzene). UV s p e c t r u m ,
hma x (in alcohol), nm (log ~): 246 (4.55), 255 (4.47)** 295 (4.25), and 368 (4.39). UV s p e c t r u m in alcohol
at pH 1, hmax, nm (1:)): 248 (1.00), 330 (0.62), and 390 (0.49). Found: C 77.8; H 4.7; N 8.5%. C21HI4N20.
Calculated: C 77.3; H 4.3; N 8.6%.
6-Cyanomethylphenanthridine (X). T h i s compound, with mp 107-108 ~ f r o m alcohol (1 : 5) and p e t r o -
l e u m e t h e r (1: 25) and Rf 0.6 (CHC13), was obtained in 52%yield by the method in [11]. IR s p e c t r u m : vCN
2240 am -1 (in KBr). UV s p e c t r u m , hma x (in alcohol), nm (log e): 250 (5.1), 270 (4.74)**, 290 (4.57)**,
330 (3.97), and 350 (3.97).
6 - ( ~ - C y a n o s t y r y l ) p h e n a n t h r i d i n e (XI). A solution of sodium ethoxide f r o m 0.04 g of Na and 2 m l of
ethanol was added with s t i r r i n g to a solution of 0.4 g (2 m m o l e ) of X and 0.21 g (2 m m o l e ) of benzaldehyde
in 18 m l of ethanol, and the m i x t u r e was refluxed for 2 h. It was then cooled, and the r e s u l t i n g p r e c i p i t a t e
was r e m o v e d by filtration. C r y s t a l l i z a t i o n f r o m alcohol (1 : 10) gave 0.38 g (62%) of the s t y r y l with mp
201 ~ and R f 0.85 [ h e x a n e - e t h e r (1 : 1)]. IR s p e c t r u m (in KBr), a m - l : 2195, 1620, 1565, 1487, 1463, 1450,
1365, 1325, 1215, 1195, 1175, 965, 925, 860, 755, 735, 720, and 675. UV s p e c t r u m , h m a x (in alcohol), nm
(log ~): 248 (4.50), and 270-290 (4.3; a b r o a d shoulder that d e c r e a s e s slopingly to 320 nm and then s h a r p l y
to 380 nm). Found: C 86.5; H 4.4; N 9.2%. C22Ht4N2. Calculated: C 86.2; H 4.6; N 9.2%.
5 - A c e t y l - 6 - c y a n o m e t h y l e n e - 5 , 6 - d i h y d r o p h e n a n t h r i d i n e (XIII). A 0.2-g s a m p l e of X was refluxed in
6 m l of acetic anhydride for 4 h, a f t e r which the m i x t u r e was cooled and f i l t e r e d to give 0.15 g of XIII. The

968
product was crystallized from benzene (1 : 40) to give yellow needles with mp 214-215 ~ PMR spectrum
in CDC13, 6:2.55 ppm (COCH3, singlet). IR spectrum, era-: (KBr): 2180, 1630, 1600, 1585, 1530, 1500,
1480, 1405, 1360, 1225, 1170, 1140, 985, 935, 765, 750, and 710. UV spectrum, kmax (in alcohol), nm (log e):
241 (4.54), 255 (4.32)**, 272 (4.18), 293 (3.95), 320 (3.70), 335 (3.70), 370 (4.00)**, 387 (4.29), and408(4.32).
Found: C 78.7; H 4,9; N 11.1%; M 273 (witha Hewlett Packard 302 Bosmometer, in chloroform). CITHI2N20.
Calculated: C 78.5; H 4.6; N 10.8%; M 260. For hydrolysis, 0.1 g of XIII was heated with 6 ml of 30%
H2SO4 at 140~ for 8 h, after which the mixture was neutralized and extracted with benzene to give 0.06 g
(84%) of 6-methylphenanthridine with mp 81-82~ which was identical to a genuine sample.
6-(p-Dimethylamino-~-eyanostyryl)phenanthridine (XII). A) A 3-g (15 mmole) sample of X and 2.3 g
(15 mmole) of p-dimethylaminobenzaldehydewere refluxed in 80 ml of acetic anhydride for 8 h, after which
the mixture was cooled and filtered to give 1.3 g of XIII. The filtrate was vacuum evaporated to 20 ml,
cooled, and filtered to give 1.2 g of XII with mp 182~ Crystallization from benzene (1 : 15) gave 0.65 g of
styryl XII with mp 189~ and Rf 0.65 [hexane-ether (1 : 1)] and 0.5 [acetone-hexane (1 : 1)]. IR spectrum,
cm-i (in KBr): 2190, 1615, 1590, 1580, 1565, 1380, 1365, 1195, 1170, 965, 820, 760, and 725. UV spectrum,
kmax (in alcohol), nm (log ~): 247 (4.68), 298 (3.96), 307 (3.96) and 408 (4.50). UV spectrum in alcohol
at pH 1, kmax, nm (log e) 245 (4.59), 270 (4.24)**, 385 (4.07), 400-406 (3.94)* *, and 516 (4.24). UV spec-
trum in a strongly acidic alcohol solution, kmax, nm (D): 250 (1.40), 270 (0.48)**, 335 (0.367), 385 (0.178),
and 409 (0.125). Found: C 82.5; H 5.7; N 11.8%. C24HIgN3. Calculated: C 82.5; H 5.5; N 12.0%.
B) This compound, with mp 183-184~ (from benzene-petroleum ether), was obtained in 43%yield by
the method used to prepare XI.

LITERATURE CITED
1. R~ M. Acheson and A. O. Plunkett, J. Chem. Soe., 3764 (1962).
2. C.F.H. Allen, Six-Membered Heteroeyclie Nitrogen Compounds with Three Condensed Rings, New
York (1958), p. 300.
3. E.R. Ritchie, J. Proe. N. S. Wales, 78, 147 (1945); Chem. Abstr., 40, 877 (1946).
4. K.M. Johnston, J. Heterocyel. Chem., 6, 847 (1969).
5. A. Mareeov, Comptes Rend. Aead. Bulg. Sci., 9, 35 (1956).
6. H.C. Longuett-Higgins and C. A. Coulson, Trans. Faraday Soe., 4__33,87 (1947).
7. H.C. Longuett-Higgins and C. A. Coulson, J. Chem. Soc., 971 (1949).
8. E.V. Grishina, I~. R. Zakhs. and V. P. Martynova, Khim. Geterotsikl. Soedin., 138 (1974).
9. W. Ho Perkin, J. Chem. Sot., 3__55,415 (1877).
I0. Dictionary of Organic Compounds, Vol. 2, Oxford University Press (1965).
Ii. J. Finkelstein and S. M. Linden, J. Amer. Chem. Soe., 7_~3,302 (1951).

969
SYNTHESIS AND STRUCTURE OF QUATERNARY
SALTS OF ACRIDINYLHETARYLMETHANES AND
THEIR ANHYDRO BASES

O. N. Chapakhin, V. E. Kirichenko, UDC 547.835.07;543.422;541.623 : 542.953

and I. Ya. Postovskii

Q u a t e r n a r y s a l t s of 9 - a c r i d i n y l h e t a r y l m e t h a n e s w e r e obtained by condensation of acridine

with alkiodides of 2- and 4 - m e t h y l d e r i v a t i v e s of nitrogen h e t e r o c y c l e s in the p r e s e n c e of
a i r oxygen. A study of the s p e c t r a of the a c r i d i n y l h e t a r y l m e t h a n e s and t h e i r q u a t e r n a r y
s a l t s and anhydro b a s e s indicates t a u t o m e r i c t r a n s f e r of the hydrogen atom of the methylene
group to the nitrogen a t o m of the acridine f r a g m e n t in m o n o q u a t e r n i z e d a c r i d i n y l h e t a r y l -
methane s.

In a continuation of o u r r e s e a r c h on the condensation of a c r i d i n e s with nncleophiles in the p r e s e n c e

of an oxidizing agent [1], we have i n v e s t i g a t e d the r e a c t i o n of acridine and acridine hydrochloride with
alkiodides of nitrogen h e t e r o c y c l e s containing a m e t h y l group in the 2- and 4 - p o s i t i o n s . In d i m e t h y l f o r m -
a m i d e (DMFA) i n t h e p r e s e n c e of a i r oxygen the condensation t a k e s place at the m e t h y l group and gives
a c r i d i n y l h e t a r y l m e t h a n e de rivative s, f o r e x a m p l e ,

9 I

I I-
CH 3

When h e t e r o c y c l e s with m o s t active m e t h y l groups (2- and 4-methylquinolines) are used, side r e -
actions of oxidation of the d i h e t a r y l m e t h a n e d e r i v a t i v e to an acridone and s e l f - c o n d e n s a t i o n of the m e t h y l -
quinolines to cyanines a r e o b s e r v e d . Oxidation can be avoided when the acridine b a s e is used. Condensa-
tion at l e s s active m e t h y l groups (2- and 4 - p i c o l i n e s and 1 , 2 - d i m e t h y l b e n z i m i d a z o l e ) is r e a l i z e d s u c c e s s -
fully by using acridine h y d r o c h l o r i d e . Data on the s y n t h e s i z e d compounds a r e p r e s e n t e d in T a b l e 1.
The m o n o q u a t e r n i z e d a c r i d i n y l h e t a r y l m e t h a n e s (I-VI) a r e c o n v e r t e d by alkali to anhydro b a s e s I X -
XI and XV-XVII (Table 2), which a r e close analogs of u n s y m m e t r i c a l cyanine dyes.
The e l e c t r o n i c s p e c t r a of 9 - s u b s t i t u t e d (amino, aminophenyl, hydroxyphenyl, and a m i n o s t y r y l d e r i v -
atives) w e r e investigated in detail in connection with the p o s s i b l e t a u t o m e r i c a m i n o - i m i n o and o x o - h y d r o x y
f o r m s [2]. T h e r e a r e p o s s i b i l i t i e s in 9 - a c r i d i n y l h e t a r y l m e t h a n e s for t a u t o m e r i s m due to t r a n s f e r of a
hydrogen atom of the m e t h y l e n e group situated between two s t r o n g a c c e p t o r s to one of the nitrogen a t o m s .
This s o r t of t a u t o m e r i s m has been d e s c r i b e d in the diquinolylmethane s e r i e s [3].
We made a c o m p a r a t i v e study of the e l e c t r o n i c s p e c t r a of the a c r i d i n y l h e t a r y l m e t h a n e s obtained in
[1] and of t h e i r m o n o q u a t e r n a r y s a l t s (I-VIII) and anhydro b a s e s (IX-XVII). As one should have expected,
the m e t h y l e n e group b r e a k s the conjugation chain in a c r i d i n y l h e t a r y l m e t h a n e s , disrupting the mutual e l e c -

S. M. K i r o v U r a l Polytechnic Institute, Sverdlovsk. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i c h e s k i k h

Soedinenii, No. 8,pp. 1116-1120, August, 1974. Original a r t i c l e submitted D e c e m b e r 29, 1973.

9 Plenum Publishing Corporation, 227 West 17th Street, New York, IV. Y. 10011. No part o f this publication may be reproduced,
stored #z a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

970
 .4

mue3~ mC,l~

i
--!

-! i--~2;222~L
Igi--!__ _

i ~i N N N N N N g N I
- - I

m l

= N
E c m
9~ ~:~

III II~
"N
2. * IIiIIIIl ~ "~ ~ E
~ . . . . . . o .~
e ~

0 0
~ m i .Q
I
- ~ - ~
~ m ~ m ~ m m ~
o
0 ~ u ~ ' ~ ~S~.~ ~ ~
r/l
. . . . . . . . . . . . . . . . ~ 0

Cxl 0"~ C'N cp

0 m

~ 0 0 0 ~ I I
O' "~'~~~~~ ,N ~
I I I l l l l l ' ~

_=~>>~
QO
U ~

971
 *go4 ,q t r o n i c effects of the h e t e r o r i n g s . The e l e c t r o n i c s p e c t r a
5,0 .
of the a c r i d i n y l h e t a r y l m e t h a n e s t h e r e f o r e differ little

1 ..... ./
/ .-%. ,'-
,, ...." 2%;
from the s p e c t r u m of acridine and contain two absorption
bands with m a x i m a at 255 and 355-360 nm. At the same
time, the absorption of the introduced h e t e r o r i n g is
m a s k e d by the m o r e intense absorption of acridine, which
is found in the same region.
The e l e c t r o n s y s t e m of the entire molecule in the
anhydro bases is conjugated, and two new bands c h a r -
a c t e r i s t i c for this s y s t e m a r i s e at 280-320 and 500-600
300 400 500 k ~n n q nm. The m a x i m a experience a h y p o s c h r o m i c shift when
the a c c e p t o r c h a r a c t e r of the substituent of the nitrogen
Fig. 1. Electronic spectra of 4-pyridinyl-
of the h e t e r o r i n g i n c r e a s e s (IX-XIV) on passing from
9-acridinylmethane methiodide (I): 1) in
p y r i d y l - to quinolinylacridinylmethines (IX, and XVI, XV
water; 2) in dimethylformamide; 3) in
and XVII). T r a n s f e r of the e l e c t r o n density to the acridine
ethanol; 4) in chloroform,
f r a g m e n t of the molecule probably o c c u r s in the excited
state in IX-XVII, and the introduction of a c c e p t o r substi-
tuents that hinder this sort of t r a n s f e r also c a u s e s the
o b s e r v e d h y p s o c h r o m i c shift.
The s p e c t r a of the m o n o q u a t e r n a r y salts of a c r i d i n y l h e t a r y l m e t h a n e s contain two new (as c o m p a r e d
with the acridine compounds) absorption bands that are c h a r a c t e r i s t i c for the completely conjugated s y s -
t e m of the anhydro b a s e s (see Tables 1 and 2). The t r a n s i t i o n f r o m 2- to 4 - i s o m e r s of pyridine and benzo
annelation of the pyridine ring cause a b a t h o c h r o m i c shift of the m a x i m a of both bands. An i n c r e a s e in the
p o l a r i t y of the solvent leads to a h y p s o c h r o m i c shift of the m a x i m a , while in water and acetic acid these
bands are absent (Fig. 1).
The p r e s e n c e of these absorption bands in the e l e c t r o n i c s p e c t r u m is probably a s s o c i a t e d with t a u t o -
m e r i c t r a n s f e r of a hydrogen atom of the methylene group to the nitrogen atom of the acridine residue to
give a conjugated s y s t e m (resonance stabilization of the t a u t o m e r i c s t r u c t u r e p r o m o t e s this s o r t of tauto-
m e r i c transition). F o r example, for I,
CH 3 ~H3 ~H3

@,- 9 I
9 II
CN CH
I

H H

The possibility of this t r a n s i t i o n is absent in acetic acid, in which both h e t e r o a t o m s are in the a m -
monium f o r m , and the s p e c t r u m does not contain absorption bands in the regions c o r r e s p o n d i n g to the c o n -
jugated s t r u c t u r e . The t a u t o m e r i e equilibrium in water is shifted to the left, apparently due to the f o r m a -
tion of s t r o n g hydrogen bonds with the nitrogen atom of the acridine fragment. The IR s p e c t r a of I - I I I r e -
c o r d e d in c h l o r o f o r m also provide evidence in favor of t a u t o m e r i s m . A distinct absorption band in the
region of N - H bond vibrations (3450 cm -1) is o b s e r v e d in these s p e c t r a .

EXPERIMENTAL
The UV s p e c t r a of 10-4-5 910 -5 m o l e / l i t e r solutions were r e c o r d e d with SF-4 and SF-4A s p e c t r o -
p h o t o m e t e r s . The IR s p e c t r a of saturated solutions of the compounds in c h l o r f o r m were m e a s u r e d with a
UR-20 s p e c t r o m e t e r .
Condensation with Alkiodides of 2- and 4 - P i c o l i n e s and 1,2-Dimethylbenzimidazole. A i r was bubbled
through a solution of 20 m m o l e of acridine hydrochloride and 40 m m o l e of the alkiodide in 10-20 ml of DMFA
at 120 ~ for 6 h (at 135 ~ in the case of 1,2-dimethylbenzimidazole). The mixture was then cooled, and the
resulting precipitate was r e m o v e d by filtration and refluxed with 50 ml of water. The aqueous mixture
was filtered, and the acridone was collected on the filter, Sodium carbonate was added to the filtrate up
to pH 10-12, and the resulting precipitate was r e m o v e d by filtration and c r y s t a l l i z e d .
Condensation with Methiodides of 2- and 4-Methylquinolines and 2-Methylbenzothiazole. A i r was
bubbled through a solution of 20 m m o l e of acridine and 20 m m o l e of the methiodide in 10-20 ml of DMFA

972
at 120 ~ for 4 h (at 110 ~ in the case of lepidine). At the end of the p r o c e s s , the DMFAwas evaporated in a
s t r e a m of a i r at the r e a c t i o n t e m p e r a t u r e , and the residue was refluxed with 50 ml of acetone. The acetone
mixture was cooled, and the resulting precipitate was r e m o v e d by filtration and c r y s t a l l i z e d from ethanol.
Compounds VI and VII were c r y s t a l l i z e d fractionally to free them from the side products of the cyanine
condensation.
Anhydro B a s e s of the Q u a t e r n a r y Salts of A c r t d i n y l h e t a r y l m e t h a n e s (IX-XI, XV, and XVI). A cooled
aqueous solution o r suspension of I-VI was t r e a t e d with 10% NaOH solution until the pH was 10-12. The
anhydro bases were isolated quantitatively as a resinous m a s s , which gradually began to c r y s t a l l i z e . The
solid was r e m o v e d by filtration and c r y s t a l l i z e d from ethanol.

LITERATURE CITED
lj V. E. Posazhennikova, O. N. Chupakhin, and I. Ya. Postovskii, Khim. Geterotsikl. Soedin., 1384 (1970).
2. A. Albert, The Acridines, Arnold Press, London (1966).
3. G. Scheibe and E. Daltrozzo, in: Advances in Heterocyclie Chemistry, Vol. 7, New York-London
(1966), p. 153.
4. I. Ya. Postovskii, V. E. Posazhennikova, O. N. Chupakhin, and E. P. Darienko, Khim. Geterotsikl.
Soedin., 1090 (1971).

973
OXIDATION OF 4-STYRYL-2-PHENYL-5,6-BENZOQUINOLINE

WITH POTASSIUM PERMANGANATE

N. S. K o z l o v and G. S. S h m a n a i UDC 547.832.5'313:542.943

Oxidation of 4 - s t y r y l - 2 - p h e n y l - 5 , 6 - b e n z o q u i n o l i n e with potassium p e r m a n g a n a t e gave phenyl

2 - p h e n y l - 5 , 6 - b e n z o - 4 - q u i n o l y l diketone, 2 - p h e n y l - 4 - f o r m y l - 5 , 6 - b e n z o q u i n o l i n e , 2 - p h e n y l - 5 , 6 -
benzocinchoninic acid, and benzoic acid. It is shown that phenyl 2 - p h e n y l - 5 , 6 - b e n z o - 4 - q u i n o l y l
diketone is cleaved under the influence of OH- ions to the c o r r e s p o n d i n g aldehydes and c a r -
boxylic acids; this is explained by the decisive effect of the acidity of the m e d i a on the d i r e c -
tion of the reaction.

The oxidation of quinoline and 6,7-benzoquinoline derivatives to carboxylic acids by means of p o t a s -

sium p e r m a n g a n a t e is d i s c u s s e d in a n u m b e r of p a p e r s (for example, see [1, 2l). There is no information
in the l i t e r a t u r e r e g a r d i n g o t h e r products of the oxidation of such compounds.
We have found that the pH of the medium has a decisive effect upon the direction of the oxidation of
4 - s t y r y l - 2 - p h e n y l - 5 , 6 - b e n z o q u t n o l i n e (I) u n d e r the conditions of the Wagner reaction. In acetic anhydride,
which is a buffer (pH 7) in this reaction, the predominant oxidation product is phenyl 2 - p h e n y l - 5 , 6 - b e n z o -
4-quinolyl diketone (HI). The ratio of oxidation products changes in weakly alkaline media (pH 8), and
2 - p h e n y l - 4 - f o r m y l - 5 , 6 - b e n z o q u i n o l i n e (IV), 2-phenyl-5,6-benzocinchoninic acid (V), and benzoic acid (VI)
constitute a considerable fraction. The oxidation products in alkaline media (pH 9-12) are IV-VI and
2-phenyl-5,6-benzoquinoline (VII), which is probably f o r m e d by p a r t i a l decarboxylation of acid V (Table 1).
It is n a t u r a l to a s s u m e that hydrolytic cleavage of the u n s y m m e t r i c a l cy-diketone f o r m e d in the r e -
action o c c u r s as OH- ions accumulate.
The relatively low e l e c t r o n density in the 4-position of the h e t e r o r i n g should favor reaction via path
A, while the p r e s e n c e of s t e r i c hindrance on the part of the 5,6-benzoquinoline ring directs the reaction
via path B.
The e x p e r i m e n t a l data confirm the above assumption. At pH 13, a f t e r 1 h at 70~ c~-diketone III is
cleaved (42%) via pathA inthe s c h e m e following and viapath B (58%), w h i c h attests to the predominant effect
of s t e r i c factors on the cleavage.

TABLE 1. Dependence of the Yields of Reaction Products on the

Oxidation Conditions
Oxidation conditions Yield o~ reaction products
Expt. [ based on the amount of I
pH at I time, u~ed_in t B_ereaction, %
No. solvent end of ~, ~ . . . . . .
expt. h I I m ~v v vl vii

Aqueous dioxane (80%) I 88

30 ?s
m

100 25 n 10 --

9,5 100 25 10 14 22
Aqueous pyridine (85%) 20 28 36 11 --
19 55 10 --

Acetic anhydride-tolu- 7 5 54 -- 19 10 --

ene (1.5 : 1), [

Institute of P h y s i c a l Organic C h e m i s t r y , A c a d e m y of Sciences of the B e l o r u s s i a n SSR, Minsk. T r a n s -

lated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1121-1124, August, 1974. Original article
submitted May 30, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 1 7th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

974
 ~- OH Oil -] ) .)
C6HsCH= C H ~ / C 6 H 5 C61isCH--~H~6H s c~.~ 4-e.r:.--.w., c0.~
I i h
" ~/ I ~ +Y rgl

I H1

~ C6H s

+
H O O C ~ C 6 H

V
s

C6HsCOOH

Vl
k
CsHs~6Hs
IV

ISeO.
/C~H~
C H3"-,,~-~/C5 H5 ~
VIII

IX VII

According to [3, 4], the production of ~-diketones under the conditions of the Wagner reaction is ob-
s e r v e d only in exceptional c a s e s . This fact probably should be explained by the sensitivity of compounds of
this sort to changes in the acidity of the medium.
We have found that the solvent and reaction t e m p e r a t u r e affect the rate of oxidation. Thus, only a
v e r y small amount of oxidation o c c u r s in dioxane at 50-60 ~ - u p to 90%of the starting benzoquinoline i~; r e -
c o v e r e d after 3 h, and only t r a c e s of the oxidation products (Table 1) are formed. In refluxing dioxane,
70%oxidation is o b s e r v e d after 1 h. The use of pyridine o r acetic anhydride as the solvent makes it p o s -
sible to lower the t e m p e r a t u r e to 5 ~.
Thus, we have isolated all of the possible oxidation products, except ~ - g l y c o l II, in the oxidation of
benzoquinoline I with potassium p e r m a n g a n a t e and have determined the conditions for t h e i r directed s y n -
t h e s i s . We were unable to c a r r y out the oxidation under hydroxylation conditions because of the high h y d r o -
phobic c h a r a c t e r of the s t a r t i n g compound. This reaction may prove to be a convenient method for the syn-
t h e s i s of ~ - d i k e t o n e s from s t y r y l derivatives of nitrogen-containing h e t e r o c y c l e s .
/H\
o oH -o o
!I l
%~o-c-c.
9 I "~
i:-- .c.t-
,"~z ~ J C . H .
~C~...S-.y.%H~
i i

. I" It I ~ !. q I o~_~ v + %HsCHO

I|| o_ ~ /~/ ~ '%J<J ~

c. u s - c - c..,,.~-~..c. H. c~ c H;

_ 9 lV+Yl

The s t r u c t u r e s of the compounds that we obtained in this r e s e a r c h were proved by IR and UV s p e c t r o -

scopy and by c h e m i c a l t r a n s f o r m a t i o n s . Thus, the K band (315-330 nm) due to the exocyclic double bond
of the s t y r y l group vanishes in the e l e c t r o n i c s p e c t r a of the oxidation products, and the UV s p e c t r a take
on the form c h a r a c t e r i s t i c for 5,6-benzoquinolines [5].

EXPERIMENTAL
The individuality of the compounds obtained was verified by t h i n - l a y e r c h r o m a t o g r a p h y (TLC) on a
loose l a y e r of activity II aluminum oxide in a b e n z e n e - c y c l o h e x a n e (2: 1) s y s t e m with development by
iodine v a p o r s . The pH values were m e a s u r e d with a pH-262 l a b o r a t o r y pH m e t e r . The UV s p e c t r a of
ethanol solutions were r e c o r d e d with a Specord UV-vis s p e c t r o p h o t o m e t e r . The IR s p e c t r a of KBr pellets
were r e c o r d e d with a UR-20 s p e c t r o m e t e r .
Oxidation of 4-Styryl-2-phenyl-5,6-benzoquinoline (t). (General Method).
A 4o8-g (30 mmole) sample of finely ground potassium p e r m a n g a n a t e (in e x p e r i m e n t s 1, 2, and 6, 3 g of

975
KOH was also added) was added in portions to a solution of 3.6 g (10 m m o l e ) of benzoquinoline I [51 in an
a p p r o p r i a t e solvent. At the end of the e x p e r i m e n t , the m i x t u r e was worked up by one of the methods in-
dicated below, depending on the solvent. The solvent, the pH of the m e d i u m , the r e a c t i o n t i m e and t e m p e r a -
t u r e , and the yields of r e a c t i o n p r o d u c t s a r e p r e s e n t e d in Table 1.
A. Oxidation in Pyridine o r Dioxane. The d a r k - b r o w n p r e c i p i t a t e was r e m o v e d by filtration and
w a s h e d with solvent and hot w a t e r . The f i l t r a t e was c o n c e n t r a t e d to 50 ml, and the n e u t r a l r e a c t i o n p r o -
ducts w e r e e x t r a c t e d with benzene. The e x t r a c t was d r i e d with MgSO4, the solvent was r e m o v e d , and the
d r y r e s i d u e was e h r o m a t o g r a p h e d with a column filled with A1203 [by elution with b e n z e n e - c y c l o h e x a n e
(2: 1)], This p r o c e d u r e yielded unchanged benzoquinoline I imp 173 ~ Rf 0.86 (benzene)], phenyl 2 - p h e n y l -
5 , 6 - b e n z o - 4 - q u i n o l y l diketone (III) [bright-yellow needles with mp 200-201 ~ (from benzene) and Rf 0.59
(benzene); IR spectrum: 1670 and 1685 cm -i (CO). Found: C 83.5; H 4.6; N 3.6%. C2yHi?NO2. Calculated:
C 83.7; H 4.4; N 3.6%] and 2-phenyl-4-formyl-5,6-benzoquinoline (IV) imp 130-131 ~ (from aqueous dioxane),
Rf 0.77 (benzene). The 2,4-dinitrophenylhydrazone had mp 289-290~ (from dioxane). At pH 9.5-10, the
color of an aqueous dioxane solution changed from bright-yellow to red. Found: N 14.9%. C26HI?NsO4.
Calculated: N 15.1%. According to [6], aldehyde IV has mp 131 ~ (from aqueous dioxane), and its 2,4-di-
nitrophenylhydrazone has mp 249~ (from dioxane). Aldehyde IV was chromatographically and spectroscop-
ically identical to the compound obtained from benzoquinoline IX by the method in [6]]. The aqueous layer
was acidified to pH 2, and the precipitated 2-phenyl-5,6-benzocinchoninie acid (V), with mp 296-297~ (from
acetic acid) [7], was removed by filtration. Benzoic acid (VI), with mp 121-122~ (from water), was extracted
from the filtrate with ether.
B~ Oxidation in Acetic Anhydride. Ethyl acetate (50-70 ml) and 60 ml of 15%aqueous sodium bisul-
fite solution were added to the reaction mixture, and it was cooled and stirred until it became colorless.
The organic layer was washed repeatedly with water and alkali and concentrated to 30 ml. The concentrate
was dissolved in pyridine-ethyl acetate (1 : 1) and decomposed in the eoldwith 30 ml of water. The pre-
cipitated diketone (HI) was removed by filtration. The organic layer was washed with alkali, acid, and water
and dried. Evaporation of the solvent gave an additional amount of diketone III. Acids V and VI were iso-
lated from the aqueous layer as described in method A.
2 , 4 - D i n i t r o p h e n y l h y d r a z o n e of D i k e t o n e I l l . A total of10 ml of a solution of 2,4-di-
nitrophenylhydrazine in phosphoric acid and ethanol [8] was added to a solution of 0.39 g (1 mmole) of
diketone HI in alcohol-dioxane (2 : 1), and the mixture was heated on a boiling-water bath for 3 h. The
hydrazone was precipitated by the addition of ether to give 0.35 g (63%) of yellow needles. IR spectrum:
1335, 1500 (NO2); 1610-1620 (C =N); 1680 (C =O); 3280 (N-H) cm-i. A change in the color of an aqueous
dioxane solution of the hydrazone from bright-yellow to ruby red was observed at pH 8.7-9.0. Found:
C 70.0; H 3.8; N 12.3%. C33H21NsO5. Calculated: C 69.9; H 3.7; N 12.3%.
2-Phenyl-4-(2-phenyl-3-quinoxalyl)-5,6-benzoquinoline ( V I I I ) . A solutionof
0.5 g (1.3 m m o l e ) of diketone III and 0.15 g (1.5 m m o l e ) of o - p h e n y l e n e d i a m i n e in acetic acid was heated
at 125 ~ f o r 2 h, a f t e r which it was cooled and poured o v e r ice. The p r e c i p i t a t e d benzoquinoline (VIII) was
washed with w a t e r and dried to give 0.5 g (90%) of large cubical light-beige c r y s t a l s with mp 204-205 ~ (from
d i m e t h y l f o r m a m i d e - a l c o h o l ) ~ Found: C 86.1; H 4.7; N 9.1%. C33H21N3. Calculated: C 86.3; H 4.6; N 9,1%.
Hydrolytic Cleavage of ot-Diketone I I I . Aqueous alkali was added to a solution of l g
(2.5 m m o l e ) of diker,he HI in 150 m l of a l c o h o l - d i o x a n e up to pH 13, and the m i x t u r e was s t i r r e d and r e -
fluxed for lh. The solvent was then e v a p o r a t e d u n d e r n o r m a l conditions, during which the benzaldehyde
was oxidized to acid VI. The d r y residue was t r e a t e d with w a t e r and benzene, and the cleavage products
w e r e s e p a r a t e d by method A to give 0.31 g (40%) of aldehyde IV, 0.18 g (22%) of acid V, 0.22 g (70%) of
acid VI, and 0.043 g (6%) of benzoquinoline VH [(mp 188-189 ~ (from toluene) [5, 7]].

LITERATURE CITED
1. A. B. Lal and N. Singh, Chem. B e r . , 98, 2427 (1965).
2. H. B o j a r s k a - D a h l i g and W. Slawinsky, Roezn. Chem., 4_55, 1081 (1971).
3. C. D. Hurd, R. W. McNamee, and F. O. G r e e n , J. A m e r . Chem. S . c . , 61, 2979 (1939).
4. K. B. S h a r p l e s s , R. F. L a u e r , O~ Repic, A. Y. T e r a n i s h i , and D. 1~. Williams, J. A m e r . Chem. S . c . ,
933, 3303 (1971).
5o N. S. Kozlov, 5,6-Benozquinolines [in Russian], Nauka i Tekhnika, Minsk (1970), p. 91.
6. N. S~ Kozlov and V. V. Misenzhnikov, Ueh. Zap. P e r m s k . Ped. Instit., 3_~2, 50 (1965).
7. O. Dobner and K. Kunze, Ann., 24._.~9,109 (1888).
8. Houben-Weyl, Methoden d e r o r g a n i s e h e n Chemie, G e o r g T h i e m e Verlag, Stuttgart, (1960).

976
REACTION OF 2-ETHOXYCARBONYL-3-OXOQUINUCLIDINE
WITH NUCLEOPHILIC REAGENTS

E. E. Mikhlina, V. Ya, Vorob~eva, UDC 547.834.4

G. P. Londoreva, and L. N. Yakhontov

The quinuclidine ring in the r e a c t i o n of 2 - e t h o x y c a r b o n y l - 3 - o x o q u i n u c l i d i n e with nucleo-

philic r e a g e n t s u n d e r m i l d conditions is c l e a v e d at the C 2 - C 3 bond to give 1 - c a r b o x y m e t h y l -
isonipecotic acid and its d e r i v a t i v e s .

Some p e c u l i a r i t i e s of the r e a c t i o n of 2 - e t h o x y c a r b o n y l - 3 - o x o q u i n u c l i d i n e (I), which has a high b a s -

icity, with nucleophilic r e a g e n t s have b e e n studied. Thus, we have found that I readily u n d e r g o e s acid c l e a v -
age to give 1 - c a r b o x y m e t h y l i s o n i p e c o t i c acid (l-I) on b r i e f heating with w a t e r , o r diethyl e s t e r III on p r o -
longed heating with alcohol. Cleavage with alcohol is a c c e l e r a t e d by the addition of t r i e t h y l a m i n e . We have
p r e v i o u s l y shown that I e x i s t s p r i m a r i l y as the dipolar ion in h y d r o x y l - c o n t a i n i n g solvents (alcohol and
water) [1]. The d e c r e a s e in the e l e c t r o n density on the C(3) a t o m in p o l a r i z e d molecule Ia p r o m o t e s nucleo-

la

philic attack of the hydroxyl o r alkoxy group and subsequent cleavage of the quinuclidine ring at the C(2 ) -
C(3) bond. The absence of this effect in aliphatic ~ - k e t o e s t e r s (for e x a m p l e , in a c e t e a c e t i c e s t e r ) m a k e s
t h e m r e s i s t a n t to heating to 100~ with w a t e r and to 180" with alcohol [2].
2 - E t h o x y c a r b o n y l - 3 - a c e t o x y l - A 2 - d e h y d r o q u i n c l i d i n e (IV)~ which is s i m i l a r in s t r u c t u r e to Ia but l e s s
p o l a r i z e d , was obtained by r e a c t i o n of I with acetic anhydride at r o o m t e m p e r a t u r e . Refluxing I with acetic
anhydride gives 3-oxoquinuclidine (V), the g e n e r a t i o n of which can be explained by splitting out of an ethoxy-
c a r b o n y l group in IV to give a m i x e d anhydride of acetic and carbonic acids. Compound IV is c o n v e r t e d to
~ /OCOCH 3

"~N i x - C O 0 C2H5
CH2COOR 1
II, |ll L r-/~',,~ "~O

CONR
i V

CO "~Nf ~CONHC6H5 R'

CIt~CONR
Vl VII VIII a-C

!1 R = H ; II! R=C2Hs; Vlll a R,R'=CsHIoN; bR=CGH z, R ' = H ; C R=%H4OCHy R':~H

3-oxoquinuclidine (V) on heating with h y d r o c h l o r i c acid and to a m i x t u r e of V and keto e s t e r I on r e f l u x -

ing with ethanolic hydrogen chloride. The f i r s t step in the r e a c t i o n of IV with an alcohol solution of h y d r o -
gen chloride is a p p a r e n t l y c o n v e r s i o n of IV to I as a consequence of t r a n s e s t e r i f i c a t i o n , and the subsequent

S. Orclzhonikidze All-Union S c i e n t i f i c - R e s e a r c h P h a r m a c e u t i c a l Chemistry- Institute, Moscow. T r a n s -

lated f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 8, pp. 1125-1128, August, 1974. Original a r t i c l e
submitted August 8, 1973.

9 76 Plenum Publishing Corporation. 22 7 West 17th Srree5 New York, N. ]I. 10011. No part o f this publication may be reproduced,
stored hz a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

977
reaction of keto e s t e r I with dry hydrogen chloride leads to splitting out of ethyl c h l o r o c a r b o n a t e and k e -
tone V.
c o o
"-- -CH~C--O--C--OC~H~ IV _CH3COOCfll" I -C COOC~H- V
oil tl
o . . . . .
]
I H20

A s i m i l a r p r o c e s s is o b s e r v e d when keto e s t e r I is heated with aqueous sodium hydroxide.

NaOlt + Na2CO~
COONa

COONa

@ l
CH2COOC2tl 5

The prevailing reaction in this case is splitting out of a c a r b o x y l group u n d e r the influence of sodium
hydroxide to give sodium carbonate and ketone V; the quinuclidine ring is simultaneously cleaved at the
C ( 9 - C ( ~ ) bond to give a piperidine derivative.
Cleavage of keto e s t e r I at the c(2)-c(3) bond is also o b s e r v e d when I is heated with amines (piper-
idine, aniline, and p-anisidine). However, when the reaction is c a r r i e d out in a large excess of amine, it
p r o c e e d s in another direction to give either 3 - o x o q u i n u c l i d i n e - 2 - c a r b o x a m i d e acid VI (with piperidine) o r its
3-imino derivative (VII) (with aniline). However, in this case also, the introduction of catalytic amounts
of w a t e r p r o m o t e s opening of the quinuclidine ring to give diamides of 1 - c a r b o x y m e t h y l i s o n i p e c o t i c acid
(VIII).

EXPERIMENTAL
Reaction of 2-Ethoxycarbonyl-3-Oxoquinuclidine (I).
1. With Water. A 1-g (5 mmole) sample of keto e s t e r I was refluxed in 10 ml of water. The positive
reaction with f e r r i c chloride vanished a f t e r 2 h. At the end of the reaction, the aqueous solution was v a c u -
um evaporated, and the residue was r e c r y s t a l l i z e d from 2 ml of w a t e r to give 0.78 g (92%) of 1 - c a r b o x y -
methylisonipecotic acid (II) with mp 270-271 ~ (dec.). Found: C 51.2; H 6.8%. CsHi3NO 4. Calculated: C
51.2; H 6.9%.
2. With Ethanol. A solution of 2 g (10 mmole) of keto e s t e r I in 10 ml of absolute ethanol was r e -
fluxed for 24 h until it no longer gave a positive r e a c t i o n with f e r r i c chloride. The alcohol was then r e -
moved by vacuum distillation, and the residue was fractionated to give 2.05 g (83.5%) of ethyl 1 - e t h o x y c a r -
bonylmethylisonipecotate (HI). The IR s p e c t r a of the l a t t e r and of a sample obtained by the method in [3]
coincided. The product had mp 143-145 ~ (4 mm) and nD 2~ 1.4592. Found: C 59.5; H 8.7; N 6.0%. CI2H21NO4.
Calculated: C 59.2; H 8.7; N 5.8%.
The quinuclidine ring opened in 15 h when I was heated in ethanol solution in the p r e s e n c e of t r i e t h y l -
amine.
3. With Aqueous Sodium Hydroxide Solution. A solution of 3 g (15 mmole) of I in 32 ml of 1 M sodium
hydroxide was re fluxed for 6 h until it no longer gave a positive reaction with f e r r i c chloride. The aqueous
alkaline solution was vacuum evaporated, and the residue was dried and extracted with hot benzene. The
benzene was r e m o v e d by distillation to give 1.3 g (68.3%) of 3-oxoquinuelidine (V), which was identical to
a genuine sample. The solid m a t e r i a l r e m a i n i n g ' a f t e r r e m o v a l of 3-oxoquinuclidine was e s t e r i f i e d by h e a t -
ing with 30 ml of ethanoi and 3 ml of c o n c e n t r a t e d sulfuric acid to give 0.4 g (10%) of ethyl e s t e r III, which
was identical to a genuine sample a c c o r d i n g to its IR s p e c t r u m .
4. With Piperidine. A) A mixture of 3 g (15 mmole) of I and 25 ml of piperidine was refluxed for
10 h, a f t e r which the solution was vacuum evaporated, and the residue was fractionated to give 3 g (84%)
o f 3 - o x o q u i n u c l i d i n e - 2 - c a r b o x y l i c a c i d p i p e r i d i d e (VI) with bp 167-168 ~ (0.6 ram). Found: C 66.2; H 8.5;
N 11.6%. Ci3H20N202. Calculated: C 66.1; H 8.6; N 11.9%. IR spectrum: 1730 (ketone C =O) and 1630
(amide C =O) cm - t .
B) A solution of 2 g (10 mmole) of I and 3 ml of piperidine in 20 m l of benzene was refluxed for 10 h,
a f t e r which the mixture was vacuum evaporated, and the residue was fractionated to give 1.1 g (47.6%) of

978
amide VI with bp 167-168 ~ (0.6 m m ) . The r e s i d u e r e m a i n i n g a f t e r r e m o v a l of VI by distillation was t r i -
t u r a t e d with acetone, and the m i x t u r e was filtered to give 0.6 g (19%) of 1 - c a r b o x y m e t h y l i s o n i p e c o t i c acid
dipiperidide (VIIIa) with m p 261-262 ~ IR s p e c t r u m : 1630, 1700 c m -1 (amide C =O groups). Found: C 67.3;
H 9.6; N 13.8%. CisH3iI~30 2. Calculated: C 67.2; H 9.7; N 13.7%.
5. With Aniline. A) A solution of 3 g (15 m m o l e ) of I and 4.2 g (45 m m o l e ) of aniline in 30 m l of b e n -
zene was refluxed for 6 h, a f t e r which it was cooled, and the p r e c i p i t a t e was r e m o v e d by filtration and
washed s u c c e s s i v e l y with benzene and e t h e r to give 3 g (58.5%) of 1 - c a r b o x y m e t h y l i s o n i p e c o t i c acid dianil-
ide (VHIb) with mp 249-250 ~ (dec.). Found: C 71.5; H 6.6; N 12.0% C20H23N302. Calculated: C 71.2; H 6.8;
I~ 12.4%. According to the r e s u l t s of TLC [Silufol, a c e t o n e - b e n z e n e (1 : 1), development with b r o m t h y m o l
blue], the m o t h e r liquor r e m a i n i n g a f t e r s e p a r a t i o n of VIIIb contained t r a c e s of 3-phenyliminoquinuclidine-
2 - c a r b o x y l i c acid anilide.
B) A m i x t u r e of 2 g (10 m m o l e ) of I and 17 m l of aniline was heated at 100 ~ f o r 20 h, a f t e r which it
was cooled, and the r e s u l t i n g p r e c i p i t a t e was r e m o v e d by filtration and washed with e t h e r to give 1.7 g of
3 - p h e n y l i m i n o q u i n u c l i d i n e - 2 - c a r b o x y l i c acid anilide (VIIb). E v a p o r a t i o n of the m o t h e r liquor gave another
1 g of the s a m e product. The o v e r a l l yield of product with mp 189-191 ~ (ethanol) was 2.7 g (84%). Found:
C 75.3; H 6.5; N 13.2%. C20H21N20. Calculated: C 75.2; H 6.6; N 13.2%. The m o t h e r liquor contained 0.36
g of VIIIb.
C) A m i x t u r e of 1 g (5 m m o l e ) of I and 8 m l of aniline oontaining 0 . 1 % w a t e r was heated at 100 ~ for
6 h, a f t e r which it was cooled, and the r e s u l t i n g p r e c i p i t a t e was r e m o v e d by filtration and washed s u c c e s -
sively with benzene and e t h e r to give 1 g of a m i x t u r e containing equal amounts of VIIb and VIIIb ( a c c o r d -
ing to TLC); 0.3 g of the s a m e m i x t u r e was detected in the m o t h e r liquor.
6. With p - A n i s i d i n e . A solution of 3 g (15 m m o l e ) of I and 6.1 g (50 m m o l e ) of p - a n i s i d i n e in 30 m l
of benzene was refiuxed for 10 h, and the r e s u l t i n g p r e c i p i t a t e was r e m o v e d by filtration and washed s~c-
c e s s i v e l y with benzene and e t h e r to give 2.5 g (41.5%) of 1 - c a r b o x y m e t h y l i s o n i p e c o t i c acid di(p-anisidide)
(VIIId) with mp 231-233 ~ (dec.). Found: C 66.6; H 6.6; N 10.2%. C22H2?N304. Calculated: C 66.7; H 6.8;
lO.6%.

2- Ethoxycarbonyl-3-acet oxy-A 2-dehydroquinuclidine (IV).

A solution of 5 g (25 m m o l e ) of I in 100 m l of acetic anhydride was s t i r r e d at r o o m t e m p e r a t u r e for
7 h, a f t e r which the acetic anhydride was r e m o v e d by v a c u u m distillation, and the r e s i d u e was f r a c t i o n a t e d
to give 4.9 g (80%) of 2 - e t h o x y c a r b o n y l - 3 - a c e t o x y - A 2 - d i h y d r o q u i n u c l i d i n e (IV) with bp 110-112 ~ (0.8 ram).
Found: C 60.1; H 7.4; N 6.1%. CI2HITI~O4o Calculated~ C 60.2; H 7.2; N 5.8%.

Reaction of 2-Ethoxycarbonyl-3-oxoquinuclidine (I) w i t h

Boiling Acetic Anhydride
A solution of 2.5 g (12.5 m m o l e ) of I in 50 m l of acetic anhydride was refluxed for 5 h, a f t e r which the
acetic anhydride was r e m o v e d by v a c u u m distillation, and the r e s i d u e was t r e a t e d with 50%potassium c a r -
bonate solution and e x t r a c t e d with c h l o r o f o r m to give 1.6 g (92.5%) of 3-oxoquinuclidine (V). The p i c r a t e
had m p 210 ~ No m e l t i n g - p o i n t d e p r e s s i o n was o b s e r v e d for a m i x t u r e of this product with a genuine s a m p l e
[4].

Reaction of 2-Ethoxycarbonyl-3-acetoxy-A2-dehydroquinuclidine
(IV) with Aqueous and Ethanol Solutions of Hydrogen Chloride
A) A solution of 1 g (4.2 m m o l e ) of IV and 10 m l of 10%hydrochloric acid was refluxed f o r 20 h, a f t e r
which the m i x t u r e was v a c u u m e v a p o r a t e d , and the residue was t r i t u r a t e d with acetone to give 0.62 g (92%)
of 3-oxoquinelidine h y d r o c h l o r i d e with m p 311-313 ~ (dec., aqueous 2-propanol) [5].
B) A solution of 1 g (4.2 m m o l e ) of IV and 10 m l of 15%ethanolie hydrogen chloride was refluxed for
12 h, a f t e r which the m i x t u r e was v a c u u m e v a p o r a t e d , and the r e s i d u e was made alkaline with 50%potas-
sium c a r b o n a t e solution and e x t r a c t e d with benzene. The benzene was r e m o v e d , and the residue was v a c -
uum sublimed (0.6 m m ) to give 0.3 g of 3-oxoquinuclidine (V). The p i c r a t e had m p 210 ~ [4]. I% m e l t i n g -
point d e p r e s s i o n was o b s e r v e d f o r a m i x t u r e of this product with a genuine s a m p l e . The substance r e m a i n -
ing a f t e r sublimation of V was vacuum f r a c t i o n a t e d to give 0.4 of 2 - e t h o x y c a r b o n y l - 3 - o x o q u i n u c l i d i n e (I)
with bp 101-102 ~ (0.6 m m ) and m p 101-102 ~

979
 LITERATURE CITED
1. Yu. N. Sheinker, E. M. Peresleni, I. V. Persianova, E. E. Mikhlina, V. Ya. Vorob'eva, A. D. Yanina,
and L. N. Yakhontov, Khim. Geterotsikl. Soedin., 229 (1972).
2o A. Jsbert, Ann~ 234, 166 (1886).
3. G. Clemo and T. Metcalfe, J. Chem. Soc., 1989 (1937).
4. E. E. Mikhlina and M. V~ Rubtsov, Zh. Obshch. Khim., 2_99,118 (1959).
5. L. Sternbach and S. Kaiser, J. Amer. Chem. Soc., 74, 2215 (1952).

980
STEREOISOMERIC 1,2,3,4,5,5a,6,10b-OCTAHYDROINDEI~O
[1,2-c]AZEPINES

A. P. Boyakhchyan, L. L. Oganesyan, UDC 547.891 : 541.63

and G. T. Tatevosyan

S t e r e o i s o m e r i c 1,2,3,4,5,5a,6,10b-octahydroindeno[1,2-c]azepines were obtained by Beck-

mann r e a r r a n g e m e n t of o x i m e s . A conclusion r e g a r d i n g the s t r u c t u r e s of the final and
intermediate products was drawn by means of establishment of the nonidentical c h a r a c t e r
of the above-named azepines and one of the s t e r e o i s o m e r i c 1,2,3,4,5,5a,6,10b-octahydro-
indeno[1,2-d]azepines.

As we have already indicated in o u r preceding communications [1, 2] we have synthesized t h r e e - r i n g

azepine derivatives in o r d e r to study t h e i r p h a r m a c o l o g i c a l p r o p e r t i e s . The oetahydroindeno[1,2-c]aze-
pines (t) d e s c r i b e d in the p r e s e n t p a p e r were obtained by Beckmann r e a r r a n g e m e n t of the oximes of c i s -
and t r a n s - 3 - k e t o - 9 H - 1 , 2 , 3 , 4 , 4 a , 9 a - h e x a h y d r o f l u o r e n e s (II) [3]. The oximes (III) of both the c i s - and t r a n s
ketones were obtained in the form of the two possible syn-anti i s o m e r s ; this is apparently explained by the
ready i s o m e r i z a b i l i t y of the less stable i s o m e r .

II a b llla,b IVa,b la,b

i iVa--- [3,:C-cis, b-- .r3/C-trans, i' R=II. [" [~=C!%. i" I~=C2H~, 1\ :~ }~=!4
I\:" R=CHa. IV" R=CII3CO
R e a r r a n g e m e n t of oximes III by b r i e f heating with polyphosphorie acid (PPA) leads to s t e r e o i s o m e r i e
3 - o x o - l , 2 , 3 , 4 , 5 , 5 a , 6 , 1 0 b - o e t a h y d r o [ 1 , 2 - e ] a z e p t n e s ffW), which also p r o v e d to be individual substances.
L a c t a m s IV' were methylated by dimethyl sulfate and acetylated by acetic anhydride. 8 t e r e o i s o m e r i e 1,2,
3,4,5,5a,6,10b-octahydroindeno[1,2-c]azepines (I) and t h e i r N-alkyl derivatives were obtained by reduction
of lactams IV with lithium aluminum hydride.
The s t r u c t u r e s of bases I (and, consequently, the s t r u c t u r e s of intermediate lactams IV and oximes
III) was proved by c o m p a r i s o n of them with one of the i s o m e r i c 1,2,3,4,5,5a,6,10b-octahydroindeno[1,2-d]
azepines (V), which apparently has a t r a n s s t r u c t u r e . This compound was synthesized from cv,fi-unsatur-
ated t h r e e - r i n g ketone VI, which f o r m s two i s o m e r i c oximes; this is in all likelihood explained by the p r e s -
ence of a double bond in the a , f i - p o s i t i o n . The less stable (in a s t e r i c respect) i s o m e r (VII) is apparently
0 NOR RON 0

VI Vllla,b Vlla,b IX y

VII, VIII a R=~: b R=Ts

A. L. Mndzhoyan Institute of Fine Organic C h e m i s t r y , Academy of Sciences of the Armenian SSR,

Y e r e v a n . T r a n s l a t e d from Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 8, pp. 1129-1132, August, 1974.
Original article submitted August 8, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission of the publisher. A copy o f this article is available from the publisher for $15.00.

981
 T A B L E 1. N - S u b s t i t u t e d S t e r e o i s o m e r i c 3 - O x o - l , 2 , 3 , 4 , 5 , 5 a , 6 , 1 0 b -
O c t a h y d r o i n d e n o [ 1 , 2 - c ]azepine s

mp, Empirical .- F??nd,% -i- Ca}c--u-Iatef-'%-- ~Z

Compound *C ~** formula 9
' t [. . . . . . . . . . .

IV' a 146 0,73 ]CIaHI~NO 77,5 7,7 6,9[ i 92

b 170 i 0,61 77,8 7,4 6,7/77'6117'5 7,0 86
[V" a 117 0,8t Ct4H,TNO 78,a 7,7 6,4{ 78,1 I 7, 73
b 187 0,70 78, 7, 86
~V'" a 94 0,87 74,5 0,] }74, i7,0 5,8 92
b Ill 0,79 C~sH~TNO2 74,3 7,0 ' 5,4 I 91

* C h l o r o f o r m - alcohol (9 : 1).

T A B L E 2. N - S u b s t i t u t e d S t e r e o i s o m e r i c 1 , 2 , 3 , 4 , 5 , 5 a , 6 , 1 0 b -
O c t a h y d r o i n d e n o [1,2-c ]azepine s
[ Empir- [ Found, % Calculated, % Hydrochloride
Corn -
R t* ical ' .~p, Cl, % ~Z
pound formula C H ! N C
i
I H N
J found i calc.
8_9
0,320'47C~sH~TN 83,6 8,9 7,3
7,5 I 144 15,2 15,9
rr a
b 83,2 8,9 7,6 83,4 9,1 198 15,1 79
0,480'55C~4H~N 83,0 9,8 7,2 90
7,00 123 14,2 I4,9
I' a
b 832 9,4 6,6 83,6 II 9,4 183 I4,3 i
93
i" a 0,5t0'63!CIsH21N 83,6 9,6 6,8 83,7 i 9,8 138
6,5 I 204 13,8 ] 14,1 92
b 83,5 9,8 6,3 13,6 ~, 93

* Hexane-acetone-alcohol (30 : 3 : 1).

s o m e w h a t s t a b i l i z e d in this c a s e b e c a u s e of the f o r m a t i o n of a h y d r o g e n bond with the olefinic p r o t o n a t -

t a c h e d to C(4 ).
It is known that the olefinic p r o t o n of s y n - o x i m e s o f c~,/3-unsaturated k e t o n e s r e s o n a t e s at a w e a k e r
field than the s a m e p r o t o n of the anti i s o m e r s [4-6]. A c o m p a r i s o n of the PM12 s p e c t r a of the o x i m e s
that we obtained showed that h i g h - m e l t i n g i s o m e r VII, which is l e s s soluble in a l c o h o l and is f o r m e d in
l o w e r yield, is the s y n - o x i m e (the s i g n a l of the olefinic p r o t o n is at 7.33 ppm). The signal of the s a m e p r o -
ton in the s p e c t r u m of the anti i s o m e r (VIII), which is f o r m e d in h i g h e r yield, is at 6.5 ppmo
The e s t a b l i s h e d i m p o s s i b i l i t y of the m i g r a t i o n o f the o l e f i n i c c a r b o n a t o m d u r i n g B e c k m a n n r e a r -
r a n g e m e n t in the a n t i - c y c l o h e x e n o n e o x i m e s y s t e m [6-8] was a l s o a s c e r t a i n e d by us in an a t t e m p t to r e a l -
ize the r e a r r a n g e m e n t of a n t i - o x i m e VIII. The r e a r r a n g e m e n t of s y n - o x i m e VII was a c c o m p l i s h e d by r e -
fluxing its t o s y l a t e in m e t h a n o l . The IR s p e c t r u m of the c o m p o u n d o b t a i n e d (IX) contains bands of a c o n -
jugated double bond (1640), an a m i d e c a r b o n y l g r o u p (1670), and an a m i d e imino g r o u p (3350 c m - l ) , while
the UV s p e c t r u m c o n t a i n s a b s o r p t i o n c o r r e s p o n d i n g to the b e n z y l i d e n e a c e t o n e c h r o m o p h o r e (kma x 244 and
257; kmin, 234 nm). L a c t a m IX was r e d u c e d with lithium a l u m i n u m h y d r i d e . I n a s m u c h as the r e d u c t i o n
o f a , ? - u n s a t u r a t e d c a r b o n y l c o m p o u n d s with m e t a l h y d r i d e s u s u a l l y does not lead to s a t u r a t i o n of the C =C
bond, the r e d u c t i o n p r o d u c t , without i s o l a t i o n in p u r e f o r m , w a s t h e n r e d u c e d with sodium in boiling butyl
alcohol; this gave a z e p i n e V, the IR s p e c t r u m of which does not c o n t a i n the a b s o r p t i o n bands of a c o n j u g a t e d
double bond and of an a m i d e e a r b o n y l g r o u p . C h r o m a t o g r a p h y in a thin l a y e r showed that b a s e V is an in-
dividual s u b s t a n c e , a p p a r e n t l y with a t r a n s s t r u c t u r e , with R f 0.39, which does not coincide with any of the
Hf v a l u e s of the i s o m e r i c o e t a h y d r o i n d e n o [ 1 , 2 - c l a z e p i n e s (Rf cis 0.47, l~f i r a n s 0.32). The h y d r o c h l o r i d e
of V, which has the e l e m e n t a l c o m p o s i t i o n of h y d r o c h l o r i d e s I ' , m e l t s at 178 ~ (as c o m p a r e d with m p 144 ~
f o r I ' a and 198 ~ f o r I ' b ) . T h u s , the n o n i d e n t i c a l c h a r a c t e r o f b a s e V and any of b a s e s P m a y a p p a r e n t l y
s e r v e as a c o n f i r m a t i o n of o u r p r o p o s e d s t r u c t u r e f o r the l a t t e r .

EXPEBIMENTAL
The IR s p e c t r a of c h l o r o f o r m solutions w e r e r e c o r d e d with a U B - 2 0 s p e c t r o m e t e r . The UV s p e c t r a
of ethanol solutions w e r e r e c o r d e d with an S F - 4 s p e e t r o p h o t o m e t e r . The PMR s p e c t r a of d i m e t h y l s u l -
foxide (DMSO) solutions w e r e r e c o r d e d with a V a r i a n T - 6 0 s p e c t r o m e t e r with an o p e r a t i n g f r e q u e n c y of
60 MHz and t e t r a m e t h y l s i l a n e as the i n t e r n a l s t a n d a r d . T h i n - l a y e r c h r o m a t o g r a p h y (TLC) was c a r r i e d out
on a c t i v i t y II a l u m i n u m oxide.

982
 O x i m e s (III) of c i s - and t r a n s - 3 - K e t o - 9 H - 1 , 2 , 3 , 4 , 4 a , 9 a - h e x a h y d r o f l u o r e n e s . A m i x t u r e of 3.7 g
(0.02 mole) of ketone II (a o r b), 1.7 g (0.025 mole) of hydroxylamine hydrochloride, 2 g (0.025 mole) of
sodium a c e t a t e , 40 m l of alcohol, and 20 m l of w a t e r was refluxed f o r 5 h.
c i s - O x i m e (IIIa). The yield of this compound, with mp 68 ~ and Rf 0.68 [ c h l o r f o r m - a l c o h o l (9: 1),
development with iodine v a p o r s ] , was 3.9 g (98%). Found: C 77.6; H 7.5; N 6.9%. C~3HIsI~/O. Calculated:
C 77.6; H 7.5; b/ 7.0%.
t r a n s - O x i m e (HIb). The yield of this compound, with mp 122 ~ and Rf 0.56 (with the s a m e s y s t e m ) ,
was 3.4 g (85%). Found: C 77.5; H 7.5; N 7.0%. C13HIsI~O. Calculated: C 77.6; H 7.5; N 7.0%.
c i s - and trans-3-Oxo-l,2,3~4~5~5%6~10b-Octahydroindeno[l~2-c]azepines (IV'a, b). A 5-g (0.025
mole) s a m p l e of o x i m e H1 (a or b) was added to 150 g of heated (140 ~ polyphosphoric acid, and the m i x t u r e
was heated at this t e m p e r a t u r e f o r 10-15 rain, a f t e r which it was poured o v e r ice. The r e s u l t i n g c r y s t a l s
w e r e r e m o v e d by filtration and r e c r y s t a l l i z e d f r o m c h l o r o f o r m - p e t r o l e u m e t h e r (see Table 1).
c i s - and t r a n s , 2 - M e t h y l - 3 - o x o - l , 2 , 3 , 4 , 5 , 5 a , 6 , 1 0 b - O c t a h y d r o i n d e n o [ 1 , 2 - c ] a z e p i n e s (IV" a, b). A
m i x t u r e of 4 g (0~ mole) of l a c t a m IV', 3.8 g (0.03 mole) of dimethyl sulfate, and 40 m l of absolute b e n -
zene was refiuxed for 6 h, a f t e r which e x c e s s 50% p o t a s s i u m c a r b o n a t e solution was added, the benzene
l a y e r was s e p a r a t e d , and the benzene was r e m o v e d by distillation. The r e s i d u a l oil began to c r y s t a l l i z e
on t r i t u r a t i o n with absolute e t h e r , and the solid was r e c r y s t a l l i z e d f r o m m e t h a n o l (see Table 1).
c i s - and t r a n s - 2 - A c e t y l - 3 - o x o - l , 2 , 3 , 4 , 5 , 5 a , 6 , 1 0 b - O c t a h y d r o i n d e n o [ 1 , 2 - c ] a z e p i n e s ( I V " a , b). A
m i x t u r e of 5 g (0.025 mole) of l a c t a m IV' and 50 m l of acetic anhydride was refluxed for 4h, a f t e r which
the acetic anhydride was r e m o v e d in vacuo, and the r e s i d u e was t r e a t e d with e t h e r . The solid product was
r e c r y s t a l l i z e d f r o m hexane (see Table 1).
c i s - and t r a n s - 2 H - and 2 - A l k y l - l , 2 , 3 , 4 , 5 , 5 a , 6 , 1 0 b - O c t a h y d r o i n d e n o [ 1 , 2 - c ] a z e p i n e s (I). A solut~)n
of 0.01 m o l e of l a c t a m IV in 15 m l of dry dioxane and 30 m l of anisole was added gradually to a solution
of 0.02 m o l e of lithium aluminum hydride in 30 m l of absolute e t h e r (0.03 m o l e of the hydride p e r 0.01 mole
of compound was u s e d in the c a s e of the acetyl d e r i v a t i v e ) . The m i x t u r e was refluxed for 18 h, a f t e r which
it was d e c o m p o s e d with w a t e r . The u s u a l workup gave a viscous u n c r y s t a l l i z a b l e oil, which was purified
by r e p r e c i p i t a t i o n f r o m the hydroohloride. The yields, Rf values of the b a s e s , and the r e s u l t s of e l e m e n -
t a r y a n a l y s i s a r e p r e s e n t e d in Table 2.
3 - K e t o - 9 H - 1 , 2 , 3 , 9 a - T e t r a h y d r o f l u o r e n e O x i m e s (VIIa and VIIIa). A m i x t u r e of 3.9 g (0.021 mole) of
ketone VI, 1.6 g (0.023 mole) of h y d r o x y l a m i n e h y d r o c h l o r i d e , 1.1 g (0.026 mole) of sodium hydroxide, 26
m l of alcohol, and 13 m l of w a t e r was allowed to stand at r o o m t e m p e r a t u r e for 2 days, a f t e r which the p r e -
cipitate was r e m o v e d by filtration, dried, and r e c r y s t a l l i z e d f r o m alcohol. The c r y s t a l s that p r e c i p i t a t e d
f r o m the hot solution w e r e r e m o v e d by filtration and r e c r y s t a l l i z e d (the s y n - o x i m e ) . The a n t i - o x i m e was
obtained by e v a p o r a t i o n of the m o t h e r liquors and was also r e c r y s t a l l i z e d .
s y n - O x i m e (VIIa). The yield of this compound, with mp 136 ~ was 1.6 g (38%). PMR s p e c t r u m : 5
10.46 (1H, s,* OH), 7.38 (1H, s, olefinic proton), and 7.16 p p m (4H, m, a r o m a t i c protons). Found: C 78.5;
H 6.6; N 6.9%. CI3H13NO. Calculated: C 78.4; H 6.5; N 7.0%.
a n t i - O x i m e (VIIIa). The yield of this product, with mp 115 ~ was 2.4 g (57%). PMI~ s p e c t r u m : 5
10.66 (1H, s, OH), 7.26 (4H, m , a r o m a t i c protons), and 6.5 ppm (1H, s, olefinic proton), Found: C 78.6;
H 6.2; N 7.1%. C13H13NO. Calculated: C 78.4; H 6.5; N 7.0%.
Oxime p - T o l u e n e s u l f o n a t e s (VIIb and VIIIb). A solution of 2 g (0.01 mole) of p-toluenesulfonyl c h l o r -
ide in 5 m l of pyridine was added dropwise at 0 ~ to a solution of 2 g (0.01 mole) of the oxime in 12 m l of
pyridine, a f t e r which the m i x t u r e was allowed to stand at 0 ~ f o r 2 h. It was then poured into c r u s h e d ice
containing 2 m l of c o n c e n t r a t e d sulfuric acid, and the r e s u l t i n g p r e c i p i t a t e was r e m o v e d by filtration, washed
on the f i l t e r s e v e r a l t i m e s with water, and dried.
s y n - T o s y l a t e (VIIb). The yield of this compound, with mp 99-100 ~ was 3 g (86%). Found: N 4.2;
S 8.8%. C20H19~O3S. Calculated: N 4.0; S 9.0%.
a n t i - T o s y l a t e (VIIIb). The yield of this compound, with mp 121 ~ was 3.1 g (88%). Found: N 3.7;
S 8.4%. C20HigNO3S. Calculated: ~ 4.0; S 9.0%.
2-Oxo-2,3,4,5,5a,6-hexahydroindeno[l,2-d]azepix~e (IX). A m i x t u r e of 2.1 g (0.006 mole) of VIIb, 15
m l of methanol, and 10 m l of w a t e r was refluxed for 2 h, a f t e r which the slightly turbid solution was ill-
* H e r e and subsequently, s is singlet and m is multiplet.

983
t e r e d , the m e t h a n o l was p a r t i a l l y r e m o v e d f r o m the filtrate by distillation, and the residue was poured into
w a t e r containing 2 g of sodium hydroxide. The resulting oil was t r e a t e d with e t h e r , and the e t h e r solution
was washed with w a t e r and dried to give 1 g (84%) of c r e a m - c o l o r e d c r y s t a l s with mp 205 ~ ( c h l o r o f o r m -
p e t r o l e u m ether) and Rf 0.68 [ c h l o r o f o r m - e t h a n o l (9: 1)]. Found: C 78.6; H 6.4; N 6.9%. C13HI3NO. Cal-
culated: C 78.4; H 6.5; N 7.0%. IR spectrum: v 1610 (benzene ring), 1640 (conjugated C =C), 1670 (amide
CO), and 3350 cm -1 (amide NH). UV s p e c t r u m , kmax (log ~): 244 (3.92) and 257 (3.97); kmi n 234 nm (3.40).
Tosylate VIIIb did not dissolve on refluxing in methanol. Workup gave oxime VIIIa, which melted
at 115 ~ and did not d e p r e s s the melting point of the sample d e s c r i b e d above.
l~2,3,4,5,5a,6~10b-Octahydroindeno[1,2-d]azepine (V). A solution of 1.5 g (0.007 mole) of lactam IX
in 15 ml of dry dioxane and 15 ml of anisole was added gradually to a solution of 0.6 g (0.015 mole) of
lithium aluminum hydride in 20 ml of absolute e t h e r , and the mixture was refluxed for 18 h. It was then
worked up in the usual m a n n e r to give 1.2 g of crude product, which was dissolved in 70 ml of butyl alcohol.
A 5-g (0.2 g - a t o m ) s a m p l e of sodium was then added to the refluxing butyl alcohol solution, and the mixture
was refluxed for 2 h, a f t e r which the alcohol was r e m o v e d by steam distillation, and the residue was t r e a t e d
with e t h e r . The e t h e r solution was washed with w a t e r and dried. The solvent was r e m o v e d by distillation,
and the r e s i d u a l oil was purified by r e p r e c i p i t a t i o n from the hydrochloride to give 0.8 g (57%) of a viscous
u n c r y s t a l l i z a b l e oil with Rf 0.39 [ h e x a n e - a c e t o n e - a l c o h o l (30 : 3 : 1)]. The hydrochloride (from ether) had
mp 178 ~ Found: C 70.0; H 7.9; C1 15.4; N 5.8%. C13H18CIN. Calculated: C 69.8; H 8.0; C1 15.9; N 6.3%.

LITERATURE CITED

1. A. P. Boyakhchyan," L. L.Oganesyan, and G. T. Tatevosyan, Arm. Khim. Zh., 24, 1000 (1971).
2. A. P. Boyakhchyan and G. T. Tatevosyan, Arm. Khim. Zh., 2__66,44 (1973).
3. A. P. Boyakhchyan, L. L. Oganesyan, and G. T. Tatevesyan, Arm. Khim. Zh., 26, 944 (1973).
4. G. Slomp and W. J. Wechter, Chem. and Ind., 41 (1962).
5. C. W. Shoppee, M. J. Akhtar, and R. E. Lack, J. Chem. Soc., 3392 (1964).
6. T. Sato, H. Wawatsuka, and K. Amano, T e t r a h e d r o n , 27, 5381 (1971).
7. C. W. Shoppee, R. E. Lack, R. N. Mirington, and L. R. Smith, J. Chem. Soc., 5868 (1969).
8. F. Kohen, Chem. and Ind., 1378 (1966).

984
BROMINATION OF ALKALOIDS OF CAREX PARVAE

T. I. Shirshova, I. V. Terent'eva, UDC 547.759.3'821'743.1

G. V. Lazur'evskii, and V. M. Adanin

6 - B r o m o b r e v i c o l l i n e , 6 , 8 - d i b r o m o b r e v i c o l l i n e , 6 , 8 - d i b r o m o b r e v i c a r i n e , and t r i b r o m o -
b r e v i c a r i n e w e r e obtained by d i r e c t b r o m i n a t i o n of b r e v i c o l l i n e and b r e v i c a r i n e . 6 - B r o m o -
b r e v i c o l l i n e was isolated f r o m the m i x t u r e obtained by b r o m i n a t i o n of b r e v i c a r i n e dihydro-
chloride.

Little study has been devoted to the b r o m i n a t i o n of f i - c a r b o l i n e d e r i v a t i v e s , although the f i r s t studies

of this s o r t were a c c o m p l i s h e d by O. F i s c h e r in the 1930"s. In p a r t i c u l a r , the b r o m i n a t i o n of h a r m i n e was
studied, but the position of the b r o m i n e in the product was not e s t a b l i s h e d [1, 2].
The b r o m i n a t i o n of b r e v i c o l l i n e with b r o m i n e in acetic acid gives 6 - b r o m o b r e v i c o l l i n e (I, the base)
d i h y d r o b r o m i d e , the yield of which is r a i s e d c o n s i d e r a b l y when b r e v i c o l l i n e m o n o h y d r o c h l o r i d e is i n t r o -
duced into the r e a c t i o n instead of the b a s e .

H i
CH z
I

The b r o m i n a t i o n of b r e v i c o l l i n e hydrochloride u n d e r the conditions of b r o m i n a t i o n of h a r m i n e [2]

with an e q u i m o l e c u l a r amount of b r o m i n e in sulfuric acid gives v e r y low yields, and m o s t of the s t a r t i n g
alkaloid is r e g e n e r a t e d .
The 6 - b r o m o b r e v i c o l l i n e (I) f o r m e d by d i r e c t b r o m i n a t i o n is identical to the product obtained in [3].
Its IR s p e c t r u m contains the a b s o r p t i o n band at 605 cm -~ that is c h a r a c t e r i s t i c for the C - B r bond, but the
band at 740 cm -1 (substituted benzene rings containing four adjacent CH groups) that is p r e s e n t in the s p e c -
t r u m of the s t a r t i n g alkaloid is absent, and a band at 810 cm -1, which c o r r e s p o n d s to a 1 , 2 , 4 - t r i s u b s t i t u t e d b e n -
zene ring [4, 5], a p p e a r s . The UV s p e c t r u m of b r o m i d e I differs little f r o m the s p e c t r u m of b r e v i c o l l i n e
i t s e l f [6], but two new m a x i m a a p p e a r at 203 and 238 nm, and a s m a l l b a t h c h r o m i c shift is o b s e r v e d .
The m a s s s p e c t r u m of I is c h a r a c t e r i z e d by the p r e s e n c e of m o l e c u l a r ion peaks of equal intensity
with m / e 343 and 345; this r e f l e c t s the n a t u r a l b r o m i n e isotopic r a t i o and shows that the substance u n d e r
investigation is a m o n o b r o m i d e . P e a k s of doubly c h a r g e d m o l e c u l a r and f r a g m e n t p e a k s were also r e -

342/344 343/345 " - . 328/330

Institute of C h e m i s t r y , A c a d e m y of Sciences of the Moldavian SSR, Kishinev. Institute of the B i o -

c h e m i s t r y and Physiology of M i c r o o r g a n i s m s , A c a d e m y of Sciences of the USSR, P u s h c h i n o - o n - O k a . T r a n s -
lated f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 8, pp. 1133-1136, August, 1974~ Original a r t i c l e
submitted August 14, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

985
corded. Disintegration of the m o l e c u l a r ion leads to b r o m i n e - c o n t a i n i n g f r a g m e n t s that a r e f o r m e d due
to disintegration of the p y r r o l i d i n e ring, but, as in the disintegration of b r e v i c o l l i n e [6], the ion peak with
m / e 84 has the m a x i m u m intensity.
The m e t a s t a b l e ion p e a k s c o n f i r m the p r o p o s e d s c h e m e of the t r a n s i t i o n s .
6 , 8 - D i b r o m o b r e v i c o l l i n e is obtained by b r o m i n a t i o n of the d i h y d r o b r o m i d e of I. The IR s p e c t r u m of
the b r o m i n a t i o n product contains a b s o r p t i o n at 810 and 830 c m -t, which is c h a r a c t e r i s t i c for a 1 , 2 , 3 , 5 - s u b -
stituted benzene ring, and at 600 and 685 c m - I ( C - B r bond). The m a s s s p e c t r u m is c h a r a c t e r i z e d by t h r e e
m o l e c u l a r ion p e a k s with m / e 4 2 1 , 4 2 3 , and 425 in a configuration c o r r e s p o n d i n g to the isotopic b r o m i n e
c o m p o s i t i o n and by p e a k s of the c o r r e s p o n d i n g f r a g m e n t s f o r m e d v i a a s c h e m e analogous to the d i s i n t e g r a -
tion of I.
The b r o m i n a t i o n of b r e v i c a r i n e gave a m i x t u r e of two p r o d u c t s , which w e r e s e p a r a t e d by r e c r y s t a l -
lization f r o m methanol. The compound with a l o w e r c h r o m a t o g r a p h i c mobility on p a p e r c o r r e s p o n d s to the
6 , 8 - d i b r o m o b r e v i c a r i n e c o m p o s i t i o n (H). Its IR s p e c t r u m contains an a b s o r p t i o n band at 610 cm -t ( C - B r
band) and at 850 c m - t , which is c h a r a c t e r i s t i c for 1,2,3,5-substituted b e n z e n e s . A group of m o l e c u l a r ion
p e a k s with m / e 423, 425, and 427 is o b s e r v e d in the m a s s s p e c t r u m of dibromide II; this indicates the p r e -
sence of two b r o m i n e a t o m s . A m a x i m u m intensity p e a k with m / e 44 (CH 2 = N - C H 3) is also o b s e r v e d . J u s t
as in the c a s e of b r e v i c a r i n e [6, 7], the m o l e c u l a r ion of 6 , 8 - d i b r o m o b r e v i c a r i n e u n d e r g o e s f r a g m e n t a t i o n
through the alk-ylamino chain and gives a set of M-15, M-30, M-44, M-58, M-72, and M-84 f r a g m e n t s con-
taining two b r o m i n e a t o m s in the a r o m a t i c portion of the m o l e c u l e , as well as f r a g m e n t s with one b r o m i n e
atom, which a r e f o r m e d f r o m the M + - B r ion.
The compound with higher c h r o m a t o g r a p h i c mobility contains t h r e e b r o m i n e a t o m s - t r i b r o m o b r e v i -
c a r i n e (HI). Its IR s p e c t r u m contains two a b s o r p t i o n bands at 620 and 635 cm -1 ( C - B r band) and an in-
tense band at 860 cm -l, which is c h a r a c t e r i s t i c f o r 1,2,3,5-substituted benzene d e r i v a t i v e s . The UV s p e c -
t r u m of t r i b r o m o b r e v i c a r i n e differs f r o m the s p e c t r u m of 6 , 8 - d i b r o m o b r e v i c a r i n e ; this is due to the effect
of the s i d e - c h a i n b r o m i n e .
Br
I
~H.~(CH:)~ffCtl3 CH(CH~)3~.CH 3
I

~N

Br CH a Br CH 3

III

The m a s s s p e c t r u m of t r i b r o m i d e III contains four m o l e c u l a r ion peaks with m a s s n u m b e r s 500-505

and f r a g m e n t - ion peaks each containing t h r e e b r o m i n e a t o m s and a s s o c i a t e d with cleavage of the alkylamino
chain. The p r e s e n c e of a peak with m / e 429 ([M-72] +) p r o v e s that the t h i r d b r o m i n e atom is attached to
the a - c a r b o n atom of the aliphatic chain. Cleavage with the l o s s of a b r o m i n e atom in the f i r s t step o c c u r s
s i m u l t a n e o u s l y with the f r a g m e n t a t i o n path d e s c r i b e d above; the m o s t t y p i c a l f r a g m e n t r e c o r d e d at d i f f e r -
ent t e m p e r a t u r e s (even at 0 ~ is a group of p e a k s with m / e 421, 423, and 425.
Compounds I - I H w e r e isolated c h r o m a t o g r a p h i c a l l y in the b r o m i n a t i o n of b r e v i c a r i n e dihydrochloride
u n d e r s i m i l a r conditions. The f o r m a t i o n of 6 - b r o m o b r e v i c o l l i n e (I) f r o m b r e v i c a r i n e might have been r e -
p r e s e n t e d as p r o c e e d i n g through b r o m o a m i n e IV o r b r o m i d e V with subsequent closing of the aliphatic
chain to a p y r r o l i d i n e ring with subsequent b r o m i n a t i o n of the r e s u l t i n g b r e v i c o l l i n e .
Br
CH2(CH.).N< Br I
CIt(CII~)3NItCH 3
I " ~ CH a J -

U I
C1-13 It I
CH 3
I~'/ V

However, we w e r e unable to r e c o r d i n t e r m e d i a t e s IV o r V.
We o b s e r v e d s i m i l a r cyclization in the nitration of h y d r o x y b r e v i c a r i n e [8]. The direct t r a n s i t i o n
f r o m b r e v i c a r i n e to brevicoUine by m e a n s of m i c r o o r g a n i s m s was r e c e n t l y a c c o m p l i s h e d .

986
 EXPE RIMENTAL
The IR s p e c t r a of KBr pellets of the compounds were r e c o r d e d with a UR-10 s p e c t r o p h o t o m e t e r .
The UV s p e c t r a of ethanol solutions were r e c o r d e d with a Specord UV-vis s p e c t r o p h o t o m e t e r . The m a s s
s p e c t r a were obtained with an MS-1302 m a s s s p e c t r o m e t e r with direct introduction of the samples into
the ionization c h a m b e r at a h e a t e r t e m p e r a t u r e of 100-150", an e m i s s i o n c u r r e n t of 20 mA, an a c c e l e r a t -
ing voltage of 3 kV, and an ionizing voltage of 40 eV. The pK a values were determined by potentiometric
t i t r a t i o n of 0.01 M solutions of the substances with 0.1 N h y d r o c h l o r i c acid in 67% dimethylformamide (DMFA)
with a pH-340 p H - m e t e r - m i l l i v o l t m e t e r . C h r o m a t o g r a p h y was accomplished with activity III aluminum
oxide in columns and on plates with a loose l a y e r of activity HI A1203 (the solvent for the plates was c h l o r o -
form containing 5%methanol). Ascending c h r o m a t o g r a p h y on p a p e r (Leningrad slow filtering) was a c c o m -
plished with n - b u t a n o l - a c e t i c a c i d - w a t e r (10 : 1 : 5), organic phase.
.6-Bromobrevicolline (I). A 1-g (3.3 mmole) sample of brevicolline monohydrochloride was dissolved
in 25 ml of 50%acetic acid, and 0.4 ml (7.3 mmole) of b r o m i n e was added to its dropwise with vigorous
s t i r r i n g . The resulting b r i c k - r e d precipitate of the dihydrobromide of I was r e m o v e d by filtration and r e -
c r y s t a l l i z e d from methanol to give 1.4 g (83.4%) of a product with mp 270-272%
Base I was obtained by t r e a t m e n t of an aqueous alcohol solutions of the salt with 25%ammonium h y d r o -
xide. The yield of shiny c o l o r l e s s c r y s t a l s with mp 240-242 ~ (from methanol) was quantitative. A mixture
of this product with 6 - b r o m o b r e v i c o l l i n e obtained by the method in [3] melted without d e p r e s s i o n at 240-
243 ~.
The samples were identical with r e s p e c t to t h e i r c h r o m a t o g r a p h i c mobilities (Rf) on p a p e r (0.58) and
on plates (0.67) and with r e s p e c t to t h e i r IR s p e c t r a . UV s p e c t r u m , )'max: 203, 240, 248, 258, 285, 294,
350, and 364 nm (log e 4.15, 4.58, 4.58, 4.42, 3.75, 3.08, 3.60, and 3.66, respectively). PKal 6.64~=0.02,
PKa2 3 . 5 4 " 0.03 [9].
Similarly, 0.38 g (45.5%) of 6 , 8 - d i b r o m o b r e v i c o l l i n e h y d r o d r o m i d e , with mp 254-256 ~ was obtained
from 1 g (2 mmole) of the dihydrobromide of I in 25 ml of 50%acetic acid by bromination with 0.3 ml (5.5
mmole) of bromine. Found: N 8.4%. CI~HI~Br2Ns. HBr. Calculated: N 8.3%. Rf 0.62 (A1203). IR spec-
trum: 600, 685 (C-Br), 810, and 830 cm -i (l,2,3,5-substituted benzene). UV spectrum, )'max: 205, 238,
247, 258, 286, 294, 350, and 364 nm (log e 3.96, 4.40, 4.38, 4.26, 4.11, 4.31, 3.93, and 3.98, respectively).
pKal 6.05 ~-0.02, and PKa2 3.46 ~:0.03.
6,8-Dibromobrevicarine (II). A 0.38-mi (7 mmole) sample of bromine was added dropwise to a solu-
tion of I g (3.3 mmole) of brevicarine in 25 ml of 50%acetic acid, and the mixture was allowed to stand in
a refrigerator. The resulting precipitate of gold-yellow needles was removed by filtration and recrystal-
lized three times to give 1.46 g (66.7%) of white crystals of 6,8-dibromobreviearine dihydrobromide with
mp 269-270 ~ Found: N 7.2%. C1?HIgBr2N 3. 2HBr. Calculated: N 7.2%. UV spectrum, kmax: 203, 242,
248, 282, 293, 350, and 364 nm (log ~ 4.33, 4.57, 3.92, 4.01, 3.79, and 3.77, respectively).
The action of a concentrated alkali solution on a hot aqueous alcohol solution of the salt gave a greenish
resin; the solution was decanted from it, and it was washed thoroughly with distilled water and treated
with ether. White crystals of II with mp 153-155 ~ precipitated from the ether solution. Found: C 48.1;
H 4.8; Br 36.8; N 10.2%. CITHIgBr2N 3. Calculated: C 48.0; H 4.5; Br 37.6; N 9.9%. UV spectrum, kmax:
205, 242, 249, 283, 293, 350, and 366 nm (log e 4.45, 4.48, 3.88, 3.96, 3.78, and 3.85, respectively). PKal
9.58~:0.01, PKa2 4.93 ~0.02.
Tribromobrevicarine (III). The methanol mother liquor from the recrystallization of II was evapor-
ated, and the resulting precipitate was dissolved in water and treated with concentrated sodium hydroxide
solution. The resin that formed was extracted with hot benzene to give 0.18 g (10%) of colorless crystals
with mp 187-188 ~ Found: C 41.1; H 3.4; Br 47.6; N 8.8%. CITH~sBr3N 3. Calculated: C 40.5; H 3.6; Br
47.6; N 8.3%. UV spectrum, kmax: 253, 286, 295, 357, and 371 nm (log e 4.13, 3.52, 3.42, and 3.48, re-
spe ctive ly).
A 1 - g (2.7 mmole) sample of b r e v i e a r i n e dihydrochloride was b r o m i n a t e d with e x c e s s b r o m i n e as in
the case of I-III. The r e a c t i o n product was separated, r e c r y s t a l l i z e d f r o m methanol, dissolved in a small
amount of water, and t r e a t e d with c o n c e n t r a t e d alkali solution. The resulting r e s i n was washed with water,
dried on a watch glass, and dissolved in a s m a l l amount of alcohol. Aluminum oxide (1 g) was added, and
the methanol was evaporated. The r e s i d u a l mixture was t r a n s f e r r e d to a column filled with 10 g of the
s a m e adsorbent and eluted with benzene containing 1% m e t h a n o l t o give 0.4 g(39%) of 6 , 8 - b r o m o b r e v i c a r i n e

987
0.3 g (24%) of 6,8-dibromobrevicarine (II) and 0.3 g (200/0) of t ri brom obrevi cari ne (HI). The isolated b r o -
mides were identified from their melting points, chromatographic mobilities, and UV and IR spectra.

LITERATURE CITED
I. R. A. Abramovitch and I. D. Spenser, Advances in Heterocyelic Chemistry, Vol. 3 (1964), p. 79.
2. D. Barcovic and T. Bican, Ark. Kern., 20, 135 (1948); Chem. Abstr., 44, 5884 (1950).
3. T. I. Shirshova and I. V. Terent'eva, Khim. Geterotsikl. Soedin., 952 (1973).
4. L. Bellamy, Infrared Spectra of Complex Molecules, Methuen (1958}.
5. K. Nakanishi, Infrared Spectroscopy, Practical, Holden-Day, San Francisco (1962).
6. Colleetion: Brevieolline [in Russian], Kishinev (1969), pp. 5, 36.
7. I. V. Terent'eva, G. V. Lazur'evskii, and T. I. Shirshova, Khim. Prirod. Soedin., 397 (1969).
8. T. I. Shirshova, I. V. Terent'eva, P. A. Vember, and G. V. Lazur'evskii, Khim. Geterotsikl. Soedin.,
987 (1972).
9. T. I. Shirshova and I. V. Terent'eva, Izv. Akad. Nauk Moldav. SSR, Ser. Biol. i Khim. Nauk, 76 (1973).

988
SYNTHESIS OF 1- AND 7-SUBSTITUTED 2,3-DIHYDRO-
1H- PYRI~OLO [1,2-a]BEN ZIMIDA ZOLE S

Kh. A. Suerbaev and Ch. 8h. Kadyrov UDC 547.785.5'743.1:543.422.25

Cyclization of 5-substituted 2 - ( y - e h l o r o a l k y l ) b e n z i m i d a z o l e s in the p r e s e n c e of sodium eth-

oxide gave some b e n z e n e - and p y r r o l d i n e - r i n g - s u b s t i t u t e d 2 , 3 - d i h y d r o - l H - p y r r o l o [ 1 , 2 - a ] -
benzimidazoles.

2 , 3 - D i h y d r o - l H - p y r r o l o [ 1 , 2 - a ] b e n z i m i d a z o l e derivatives that contain s t r u c t u r a l elements that are

s i m i l a r to the natural alkaloid desoxypeganine [1] a r e of interest as potential physiologically active substances.
In o r d e r to make p h a r m a c o l o g i c a l t e s t s we synthesized a n u m b e r of b e n z e n e - and p y r r o l i d i n e - r i n g - s u b -
stituted 2 , 3 - d i h y d r o - l H - p y r r o l o [ 1 , 2 - a ] b e n z i m i d a z o l e derivatives via the following scheme:
" R"
H
R'-..~ ' ~ Nl'l 2 CIt2CH2Cl
H w'.dA"~-'n\ R"
,
+ [ | - I il ZC--CH2CHoCHOtt
~--.>/-.n. 2 o- c=o ~u-%..A~n :/ -
I a-f
R" \ %OO'~"
1 ~ It R"
R ' ~ N . / x " h ,. 2 m o l e C 2 H s O N a R"T~"~-~N \ {
9HCI I [[ zC--CH~CH2CH CI - HCI
2. HCI ~....L~N7
m a-f u a-f
a R'=H, R"=H; b R'=C1, R'=H; c R'=H, R"-CHa; d R'=C1, R"=CHa; e R'=H, R"=
=CrH~5; fR'=CI; R"=CTH~5

The starting 2 - ( y - h y d r o x y a l k y l ) b e n z i m i d a z o l e s (I) were obtained from the appropriate o - p h e n y l e n e -

diamines and ~/-lactones by refluxing e q u i m o l e e u l a r amounts of them [2] o r by condensation under the c o n -
ditions in [31 (Table 1).
On reaction with e x c e s s thionyl chloride, 2 - ( y - h y d r o x y a l k y l ) b e n z i m i d a z o l e s are converted to 2 - ( y -
ehloroalkyl)benzimidazole h y d r o c h l o r i d e s (II) (Table 2). The action of 2 m o l e s of sodium ethoxide on the
l a t t e r gave the c o r r e s p o n d i n g 2 , 3 - d i h y d r o - l H - p y r r o l l o [ 1 , 2 - a ] b e n z i m i d a z o l e derivatives (Ill), which were
isolated as the h y d r o c h l o r i d e s (Table 3). When we used the method in [3] to synthesize 1-substituted 2,3-
d i h y d r o - l H - p y r r o l o [ 1 , 2 - a ] b e n z i m i d a z o l e derivatives we were able to obtain only the 1 - m e t h y l derivative
(Hie) but in lower yield (15%).

The s t r u c t u r e s of the compounds obtained were confirmed by means of the m a s s and PMR s p e c t r a .

EXPERIMENTAL
The PMR spectra were recorded with a C-60-HL spectrometer wRh an operating frequency of 60
MHz and tetramethylsilane as the standard. The mass spectrum was recorded with an MKh-1303 mass
spectrometer.

2-(T-Hydroxyalkyl)benzimidazoles (I). A) A mixture of equimolecular amounts of o-phenylenediam-

ine and the appropriate T-butyrolactone was heated in a flask equipped with a Dean-Stark trap. The mix-
ture was heated to the boiling point in the course of 30 min and maintained at this temperature until water

Institute of the C h e m i s t r y of Plant Substances, A c a d e m y of Sciences of the Uzbek SSR, Tashkent.

T r a n s l a t e d from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1137-1139, August, 1974. Original
article submitted June 25, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, mierofihning,
recording or otherwise, without written permission of the publisher. A copy of this article is available from the publisher for $15.00.

989
 T A B L E 1. C o m p o u n d s I
t N, %
Com- rap, .~ Empirical formul Hydrochloride
pound Yield,
found calc. rap. ~

163,5--164a CmHI2N~O 157,5--158,5 80

Ib 167--170b CIoHHCINzO 188--189 60
Ic 122--123c CIlHI4N20 161,5--163 55
Id 138--139 CHHIsCI!N~O 176--178 30
Ie 117--11~1 CITH26N~'O 98--100 31
If 115--116 CIvH~sC1N~O 171.5---174 28

a A c c o r d i n g to [4], m p 161-163 ~ b A c c o r d i n g to [3], m p 1 6 0 - 1 6 4 ~

C A c c o r d i n g to [2], m p 115-116 ~ d A c c o r d i n g to [2], m p 111-112 ~

T A B L E 2. 2 - ( 7 - C h l o r o a l k y l ) b e n z i m i d a z o l e H y d r o c h l o r i d e s ffI)
N, %
Com- mp, ~ Empirical formula Yield, %
pound found calc.

IIa 194--196 CmH,,C1N2-HC'I 12,3 12.1 75

Itb 212--213 CIoHIoCI~N2-HCI i0,9 10,5 80
llc 217--218 C1,HIaCIN2-HCI 11,5 11,4 82
IId 232--233 CHH~CI2N2,HCI 10,2 10,0 74
IIe 170--172 C17H25CIN2,HC1 9,0 8,5 67
IIf 200--201 CITH24CI2N2.HC1 7,9 7,7 74

T A B L E 3. 2 , 3 - D i h y d r o - l H - p y r r o l o [ 1 , 2 - a ] b e n z i m i d a z o l e
H y d r o c h l o r i d e s (III)
N,%
Com - rap, ~ Empirical formula Yield, %
pound found calc.

IIIa 235--237 b CloHIoN2-HC1 70

IIlb 236--237 CmHoCIN~.HCI 12q2 72
IIIc 188--189 c CvHmN2.HC1 13,7 13,4 172 85
IIId 236--238 CIIHI1CIN2.HC1 11,6 ll,5 206 40
IIIe 93--95 ClvH24N2.HC1 9,7 9,6 256 38
IIIf 176--178 CIrH23C1N2-HC1 8,9 8,6 290 40

aBy mass spectrometry, bThe base had mp 115.5-116.5 ~

[3]. CThe b a s e had m p 6 8 . 5 - 7 0 ~

s e p a r a t i o n c e a s e d (2-3 h). I t w a s t h e n a l l o w e d t o s t a n d o v e r n i g h t . T h e c r y s t a l l i z i n g m i x t u r e w a s t h e n
treated with ether, and the product was purified by recrystallization (from methanol-water or dioxane-
heptane).
B) A m i x t u r e of 0.1 m o l e of 4 - c h l o r o - l , 2 - p h e n y l e n e d i a m i n e and 0.1 m o l e of t h e a p p r o p r i a t e 7 - b u t y r o -
l a e t o n e in 100 m l o f 4 N HC1 w a s r e f l u x e d f o r 5 h u n d e r n i t r o g e n , a f t e r w h i c h it w a s d e c o l o r i z e d t h r e e to
f o u r t i m e s w i t h a c t i v a t e d c h a r c o a l . N e u t r a l i z a t i o n of t h e f i l t r a t e with a m m o n i u m h y d r o x i d e gave an o i l ,
w h i c h c r y s t a l l i z e d on s t a n d i n g . T h e p r o d u c t w a s p u r i f i e d b y r e c r y s t a l l i z a t i o n ( f r o m m e t h a n o l - w a t e r o r
dioxane-petroleum ether).
2 - (y - C h l o r o a l k y l ) b e n z i m i d a z o l e H y d r o c M o r i d e s riD. T h e s t a r t i n g m a t e r i a l (II) w a s r e f l u x e d f o r 30
rain w i t h a s e v e n f o l d e x c e s s o f SOC12, a f t e r w h i c h t h e e x c e s s SOCI 2 w a s r e m o v e d by d i s t i l l a t i o n , and t h e
solid residue was treated with ether. The product was purified by reprecipitation from aIeohol solution
by the addition of ether.
2 , 3 - D i h y d r o - l H - p y r r o I o [ 1 , 2 - a ] b e n z i m i d a z o l e H y d r o c h l o r i d e s (HI). A) C o m p o u n d I I I a . A s o l u t i o n of
1.46 g (6.3 m m o l e ) o f I I a in 15 m t o f e t h a n o l w a s a d d e d w i t h s t i r r i n g in t h e c o u r s e o f 20 m i n t o 12.6 m m o l e
o f s o d i u m e t h o x i d e in 15 m l of e t h a n o l , a f t e r w h i c h t h e m i x t u r e w a s r e f l u x e d f o r 2 h. It w a s t h e n c o o l e d ,
a n d t h e p r e c i p i t a t e d NaC1 (0.715 g) w a s s e p a r a t e d . T h e f i l t r a t e w a s e v a p o r a t e d to d r y n e s s , and t h e s o l i d
r e s i d u e w a s r e c r y s t a l l i z e d f r o m e t h y l a c e t a t e t o give 0.7 g (70%7 of 2 , 3 - d i h y d r o - l H - p y r r o l o [ 1 , 2 - a ] b e n z i -
m i d a z o l e w i t h m p 1 1 5 . 5 - 1 1 6 . 5 ~ T r e a t m e n t o f t h e l a t t e r w i t h g a s e o u s h y d r o g e n c h l o r i d e in a l c o h o l gave
h y d r o c h l o r i d e I t I a a s h y g r o s c o p i c white c r y s t a l s w i t h m p 2 3 5 - 2 3 7 ~ ( a l c o h o l - - e t h e r ) .

990
 PMR s p e c t r u m (in pyridine) of the free base (6, ppm): two t r i p l e t s at 3.6 (J=6.7 Hz) (1-CH 2) and
2.75 (J =6.7 Hz) (3-CH2) , a t w o - p r o t o n m u l t i p l e t at 2.25 (2-CH2) , and multiplets at 7.0-7.7 (aryl protons).
B) 2 , 3 - D i h y d r o - l - h e p t y l - l H - p y r r o l o [ 1 , 2 - a ] b e n z i m i d a z o l e Hydrochloride (Hie). A solution of 1.93 g
(5.86 mmole) of He in 15 ml of ethanol was added with s t i r r i n g in the c o u r s e of 20 m[n to 11.7 mmole of
sodium ethoxide in 15 ml of ethanol, a f t e r which the mixture was s t i r r e d for 2 h. The precipitated NaC1
was separated, and the filtrate was e v a p o r a t e d to d r y n e s s . The oily residue was dissolved in 20 ml of hex-
ane, and the solution was s e p a r a t e d from the small amount of NaC1 by filtration. The filtrate was again
vacuum evaporated, the residue was dissolved in 10 m l of ethanol, and dry HC1 was p a s s e d through it until
it was saturated. The solvent was r e m o v e d , and the soil residue was purified by repreoipitation from ben-
zene solution by the addition of e t h e r to give 0.65 g (38%) of hydrochloride IIIe with mp 93-95 ~
The m a s s spectrum contains a m o l e c u l a r peak at 256 and M-15, M-29, M-43, M-71, and M-85 peaks
c o r r e s p o n d i n g to fragmentation of the h y d r o c a r b o n side chain. The most intense peak with m / e 157 c o r -
responds to the ~ j ~ - - - ~ / ' ~ fragment.

LITERATURECITED
lo Kh. N. Khashimov, M. V. Telezhenetskaya, and S. Yu. Yunusov, Khim. P r i r o d . Soedin., 5, 456 (1969).
2. A. A. Shazhenov, Ch. Sh. Kadyrov, and P. Kurbanov, Khim. Geterotsikl. Soedin., 641 (1972).
3. A. R. F r e e d m a n , D. S. Payne, and A. R. Day, J. H e t e r o c y c l . Chem., 3, 257 (1966).
4. W. Reppe et al., Ann, 596, 176, 209 (1955).

991
REACTION OF 2-AMINOPYRIMIDINES WITH ~-

HALOCARBOXYLIC ACIDS AND THEIR ESTERS

B. E. Mandrichenko, I. A. Mazur, UDC 547.853.7' 854.2/8'781

and P. M. Kochergin

N - P y r i m i d y l c a r b o x y l i c acids and t h e i r e s t e r s , which can be cyclized to t e t r a h y d r o m i d a z o -

[1,2-a]pyrirnidine-2,5-diones, a r e f o r m e d f r o m 2 - a m i n o p y r i m i d i n e and its C - s u b s t i t u t e d
d e r i v a t i v e s by r e a c t i o n with ~ - h a l o acids and t h e i r e s t e r s u n d e r m i l d conditions. Alkyla-
tion p r o c e e d s at the N1 and N 3 a t o m s of the p y r i m i d i n e ring during the action of u n s y m -
m e t r i c a l 2 - a m i n o p y r i m i d i n e s with c~-halo acids.

In o r d e r to s e a r c h f o r biologically active compounds in a n u m b e r of condensed imidazole s y s t e m s ,

we a c c o m p l i s h e d the p r e v i o u s l y uninvestigated r e a c t i o n of 2 - a m i n o p y r i m i d i n e s (I-IV) with o~-halo acids
and t h e i r e s t e r s . 1 , 2 - D i h y d r o - 2 - i m i n o - l - p y r i m i d y l a c e t i c acid e s t e r h y d r o b r o m i d e s (V, VI) a r e f o r m e d
in the r e a c t i o n of amine I with b r o m o a c e t i c acid e s t e r s . As in the case of the cyclization of N - ( 4 - p y r i m i d y l )
,~--'~N/CH 2C0 0 R

i V R=CH 3, VI R=C2H 5

a m i n o a c e t i c acid [1], colored products of unknown s t r u c t u r e a r e f o r m e d during a t t e m p t s to isolate the b a s e s

of e s t e r s V and VI o r to obtain 1 , 2 - d i h y d r o - 2 - i m i n o - l - p y r i m i d y l a c e t i c acid by alkaline h y d r o l y s i s of h y d r o -
b r o m i d e s V-VI.
The alkylation of u n s y m m e t r i c a l 2 - a m i n o p y r i r n i d i n e s with c~-halo acids p r o c e e d s at the N l and N 3
atoms of the p y r i m i d i n e ring. Thus, 2 - a m i n o - 4 - m e t h y l - 6 - o x o - l , 6 - and 1 , 4 - d i h y d r o - l - p y r i m i d y l a c e t i e
acids (VII and VIH) a r e isolated in a r a t i o of 4 : 1 when amine II is heated with haloacetic acids in w a t e r
in the p r e s e n c e of two equivalents of alkali. The s t r u c t u r e of acid VII was c o n f i r m e d by a l t e r n a t i v e s y n -
thesis f r o m guanidoacetic acid and a c e t o a c e t i c e s t e r [2]. The s t r u c t u r e of acid VIII also does not r a i s e
OH 0 0

~1 I

CIt3/~N/\N H~ . -H20 C
t n
R--CHCOOH
VIII VII IX-XII

II R ' ~ H ; III R'=NO~; IV R ' ~ B r ; VII, VIII R = W = H ; IX-XII R = H , Ai , R ' = H , Br~ NO2

any doubts, i n a s m u c h as it differs f r o m both acid VII and N - ( 4 - m e t h y l - 6 - h y d r o x y - 2 - p y r i m i d y l ) a m i n o a c e t i e

acid obtained by the method in [3].
When acid VII is heated in an aqueous o r alcohol solution of alkali, in glacial acetic acid in the p r e s -
ence of anhydrous sodium a c e t a t e , o r t r e a t e d with cold c o n c e n t r a t e d sulfuric acid, it is r e a d i l y cyclized

Zaporozhe Medical Institute. T r a n s l a t e d f r o m Khimiya G e t e r o t s i k l i e h e s k i k h Soedinenii, No. 8, pp.

1140-1142, August, 1974. Original a r t i c l e submitted N o v e m b e r 26, 1973.

9 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. ] 0011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic', mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

992
to give 7 - m e t h y l - 2 , 3 , 5 , 8 ( 1 ) - t e t r a h y d r o i m i d a z o [ 1 , 2 - a ] p y r t m i d i n e - 2 , 5 - d i o n e (IX). 2,3,5,8(1)~Tetrahydro-
i m i d a z o [ 1 , 2 - a ] p y r i m i d i n e - 2 , 5 - d i o n e s (IX-XII) are f o r m e d immediately when amines II-IV are refluxed
with a-halo acids in w a t e r o r alcohol in the p r e s e n c e of two equivalents of alkali.

EXPERIMENTAL
The IR spectra of mineral-oil suspensions of the compounds were recorded with a UR-20 spectro-
meter.
Methyl 1,2-Dihydro-2-imino-l-pyrimidylacetate Hydrobromide (V). A) A 1.75-g (II mmole) sample
of methyl bromoaeetate was added to a solution of 0.95 g (I0 mmole) of amine I in 5 ml of anhydrous meth-
anol, and the mixture was refluxed for 1 h (with activated charcoal for the last 5 nain). It was then fil-
tered, and 30 nal of ether was added to the filtrate. The precipitated hydrobronaide (V) was removed by
filtration and washed with ether to give 1.25 g (50%) of a product with mp > 280 ~ (dec., repreeipitation from
naethanol by the addition of ether). Found: C 33.5; H 4.3; Br 31.0; N 16.6%. C?H~N302. Calculated: C 33.8;
H 4.1; Br 31.2; N 16.9%.
B) A 3.5-g (22 mmole) sample of methyl bromoaeetate was added to a solution of 1.9 g (20 mmole) of
amine I in 6 nal of dimethylformamide (DMFA), andthe mixture was allowed to s rand at room temperature for
24 h. Ether (50 ml) was then added, and the precipitated hydrobromide (V) was removed by filtration,
washed with ether, and dried to give 3.9 g (80%) of product.
Ethyl 1,2-Dihydro-2-imino-l-pyrimidylaeetate Hydrobronaide (VI). Under the conditions of the pre-
ceding experiment, 30 mmole of amine I and 5.5 g (33 namole) of ethyl bromoacetate gave 4.5 g (57%) of
salt VI with rnp > 280 ~ (dee., by repreeipitation from ethanol by the addition of ether). IR spectrum, cm-t:
1665, 1750,(CO); 3080, 3220, and 3260 (NH or OH). Found: C 36.4; H 4.8; Br 30.6; N 15.6%. CsH~IN30 ~-HBr.
Calculated: C 36.6; H 4.6; Br 30.5; N 16.0%.
2 - A m i n o - 4 - n a e t h y l - 6 - o x o - l , 6 - d i h y d r o - l - p y r i m i d y l a c e t i e Acid (VII) and 2 - A m i n o - 4 - o x o - 6 - m e t h y l - l , 4 -
d i h y d r o - l - p y r i m i d y l a c e t i c Acid (VIII). A 2.5-g (20 mmole) sample of amine II and 22 mnaole of c h l o r o - ,
b r o m o - , o r iodacetie acid were added to a solution of 40 m m o l e of sodiurna hydroxide in 10 m l of water, and
the mixture was heated on a boiling-water bath for 2 h (until the medium was neutral). It was then cooled
and acidified to pH 4-5 with acetic acid, and the precipitate was r e m o v e d by filtration and washed with a
s m a l l amount of water. The yield of acid VII with nap 240-241 ~ (dec., from water) was 2.6 g (70%). IR
s p e c t r u m , era-i: 1710, 1760 (CO); 3090, 3300 (NH). According to [2], this compound has nap 240-241 ~ (dec.).
The solution r e m a i n i n g a f t e r s e p a r a t i o n of acid VII was e v a p o r a t e d to d r y n e s s , and the residue was washed
with cold w a t e r and c r y s t a l l i z e d from a s m a l l amount of water (with activated charcoal). The yield of
acid VIII with mp 228-230 ~ (from water) was 0.7 g (18%). IR s p e c t r u m , c m - l : 1670, 1765 (CO); 3090, 3300
(NH). Found: C 45.7; H 4.8; N 23.3%. C?HgN303. Calculated: C 45.7; H 4.8; N 22.9%.
7 - M e t h y l - 2 , 3 , 5 , 8 ( 1 ) - t e t r a h y d r o i m i d a z o [ 1 , 2 - a ] p y r i m i d i n e - 2 , 5 - d i o n e (IX). A) A 1.83-g (10 mmole)
sample of VII was refluxed for 1-2 h in 10 nal of glacial acetic acid in the p r e s e n c e of 2.0 g of anhydrous
sodium acid o r in 10 nal of a 4%alcohol o r water solution of sodium hydroxide, after which the solvent was
evaporated, and a 5% solution of HC1 was added to the residue to bring the pH to 2-3. The resulting p r e -
cipitate was r e m o v e d by filtration to give IX with nap 281-283 ~ [dec., from w a t e r (mp 310 ~ (dec.) [2]] in
75% yield.

B) A 1.83-g (10 mmole) sample of acid VII was added to 10 ml of 96%sulfuric acid, the mixture was
allowed to stand for 10-12 h, after which it was poured o v e r ice. A 20% solution of sodium hydroxide was
added to the aqueous mixture to bring the pH to 2-3, and the precipitate was r e m o v e d by filtration to give
1.2 g (73%) of IX.

C) A 2.5-g (20 mmole) sample of II and 2.78 g (22 mmole) of b r o m a e e t t c acid were added to a solu-
tion of 40 mnaole of sodium hydroxide in 40 ml of ethanol, and the mixture was refluxed for 9 h. The sol-
vent was then r e m o v e d by vacuum evaporation to d r y n e s s , and 15 nal of water and 5%HC1 were added to
the dry residue to pH 2. The resulting precipitate was r e m o v e d by filtration and washed with a s m a l l
amount of w a t e r to give 2.6 g (80%) of IX.

6 - N i t r o - 7 - m e t h y l - 2 , 3 , 5 , 8 ( 1 ) - t e t r a h y d r o i n a i d a z o [ 1 , 2 - a ] p y r i m i d t n e - 2 , 5 - d i o n e (X). A 2.38-g (20 mmole)

sample of b r o m o a c e t i c acid was added to a suspension of 3.4 g (20 mmole) of III in a solution of 1.6 g (40
namole) of sodium hydroxide in 40 m l of water, and the mixture was refluxed for 1 h. Workup of the r e -
action mixture as in the preceding e x p e r i m e n t gave 2.02 g (48%) of X as pale-yellow c r y s t a l s with mp 238-

993
240 ~ (dec., from water). IR spectrum, cm-l: 1715, 1790 (CO); 3350 (NH). Found: C 40.3; H 3.1; N 27.0%.
C?H6NtO4. Calculated: C 40.0; H 2.9; N 26.7%.
3,7-Dimethyl-2,3,5,8(1)-tetrahydroimidazo[1,2-a]pyrimidine-2,5-dione (XI). This compound, with
mp 281-283 ~ (dec., from water) [2], was obtained in 60% yield from amine II and a-bromopropionic
acid under the conditions of the preceding experiment.
6-Bromo-7-methyl- 2,3,5,8 (1)-tetrahydroimidazo [1,2-a ]pyrimidine:2~ 5-dione/XID. CompoundXII
[3.2 g (87%)], with mp 242-244 ~ (dee. from water), was obtained under the same conditions from 1.2 g
(30 mmole) of sodium hydroxide in 15 ml of water, 3.1 (15 mmole) of amine IV, and 1.98 g (17 mmole) of
bromoacetie acid. IR spectrum, am-l: 1690, 1780 (CO); 3090 (NH). Found: C 34.7; H 2.6; Br 32.6; N
17.4%. CTHGBrN302. Calculated: C 34.5; H 2.5; Br 32.7; N 17.2%.

LITERATURE CITED
1. T. Ueda and I. I. Fox, J. Org. Chem., 2.99, 1762 (1964).
2. M. A. Prokof'ev, E. G. Antonovieh, and Yu. P. Shvachkin, Dckl. Akad. Nauk SSSR, 783 (1952).
3. I. Kh. Fel'dman and Chih Chung-chi, Zh. Obshch. Khim., 3__00,3832 (1960).

994
2,3,5,8(1)-TETRAHYDROIMIDAZO [1,2-a] PYRIMIDINE- 2,5-
DIONF DERIVATIVES

B. E. Mandriehenko, I. A. Mazur, UDC 547.859'781

P. M. Kochergin, and P. N. Steblyuk

The c o r r e s p o n d i n g ylidene, azomethine, and azo derivatives of 2,3,5,8(1)-tetrahydroimidazo

[1,2-a]pyrimidine-2,5-dione were synthesized by reaction of 7 - m e t h y l - and 6 - b r o m o - 7 -
methyl-2,3,5,8 (1)-tetrahydroim idazo [1,2-a]pyrimidine- 2, 5-dione s with aldehyde s, ins atin,
a r o m a t i c nitroso compounds, and arenediazonium salts. Ylidene derivatives of 7 - m e t h y l -
2,3,5,8 (1)-tetrahydroimidazo [1,2-a]pyrimidine-2,5-dione were also obtained by re action of
2 - a m i n o - 4 - m e t h y l - 6 - o x o - l , 6 - d i h y d r o - l - p y r i m i d y l a c e t i c acid with carbonyl compounds.

In o r d e r to s e a r c h f o r biologically active compounds, we investigated the reactions of 2,3,5,8(1)-

t e t r a h y d r o i m i d a z o [ 1 , 2 - a ] p y r i m i d i n e - 2 , 5 - d i o n e s [1 ] with carbonyl compounds {aldehydes and isatin), nitroso
compounds, and diazonium salts at the active methylene grouping located between the two e l e c t r o n - a c c e p t o r
groups, just as was p r e v i o u s l y done for s i m i l a r s t r u c t u r e s (for example, see [2]).
It was found that 7 - m e t h y l - and 6 - b r o m o - 7 - m e t h y l - 2 , 3 , 5 , 8 ( 1 ) - t e t r a h y d r o i m i d a z o [ 1 , 2 - a ] p y r i m i d i ~ 9 -
2,5-diones (I, II) readily r e a c t with aliphatic, a l i p h a t i c - a r o m a t i c , a r o m a t i c , and h e t e r o c y c l i c aldehydes,
as well as isatin, on heating in ethanol in the p r e s e n c e of a catalyst (piperidine) o r in glacial acetic acid
in the p r e s e n c e of anhydrous sodium acetate to give ylidene derivatives (IV-XXI, Table 1).
Ylidene derivatives (VIII, XIII, XV, and XVI) were also obtained by reaction of 2 - a m i n o - 4 - m e t h y l - 6 -
o x o - l , 6 - d i h y d r o - l - p y r i m i d y l a c e t i c acid (III) [1] with aldehydes (by heating in glacial acetic acid in the p r e s -
ence of anhydrous sodium acetate).
An azomethine derivative (XXII) was obtained by r e a c t i o n of I with nitrosodimethylaniline in ethanol,
while diazo coupling products (XXIII-XXVI) were f o r m e d with arenediazonium salts (best of all with a r e n e -
diazonium t e t r a f l u o r o b o r a t e s ) in glacial acetic acid o r w a t e r in the p r e s e n c e of an e q u i m o l e c u l a r amount
of alkali.
The s t r u c t u r e s of IV-XXVI were c o n f i r m e d by t h e i r IR s p e c t r a , which contain distinct absorption
bands of CO and NH groups at 1640-1765 and 3080-3400 cm -1, r e s p e c t i v e l y .
O o O
R' J} o~,, II

0
I.II " ~ O IV-XXI III

o R
i C~"N
' 2B~ ~ o

Jf J}
R'- ~ / N =NCsiI4R R'~,~N_~__.~ N-- C6114--N(CH3)2-P

H H
XXIII-XXVI XXII

A large number of the synthesized substances are inactive with respect to Oram-negative and Gram-
positive m i c r o o r g a n i s m s , and only V, XVI, XVIII, and XXIV suppress the growth of Staphyloccoccus aureus
and E s c h e r i c h i a coli, Salmonella typhosa, and the d y s e n t e r y bacillus in 1 : 2000 and 1 : 4000 c u l t u r e s .
Zaporozhe Medical Institute. T r a n s l a t e d f r o m Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp.
1143-1145, August, 1974. Original article submitted N o v e m b e r 26, 1973.

@19 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15. 00.

995
 TABLE 1. Ylidene (IV-XXI), A z o m e t h i n e (XXII), and A z o D e r i v a t i v e s
(XXIII-XXVD of 2,3,5,8(1)-Tetrahydroimidazo[1,2-a]pyrimidine-2,5-
dione
! Found, % Calc., % Yield,
Com- R, ~P, gmpiricalformula c IHI N C H N %
pound

] I I [ 2
IV 1 Citral residue H C~TH21NaO2 li67'8] 67i 43f8 7,0:14 1!90
, I [
V IC~H4CH=CH H C sH 3N~O2,0,5H20 ]668 4,7 14 9 66,7 4,9 14,6f 90
VI p- (CHa)~CHCsH~ H CI7HITNsO2 !69 3 6,1 14 2 69,1 5,8 14,2 83
I ! I
CI4H NaOa.05H20 60,0 4,3i152604 4,415,1'
I i 56
H
;V:II!;:;:~s6HI

IX~ o-CH3OCsH4 ClsH,~N303.0,SH~O161,6!4,8 14,4 61,6 4,814,41 86

X p-CHaOC~H~ CIsHL~N~Oa 163,5 4,8 14 6 63,6 4,6 14,8, 64
XI p-BrCsH4 CI4HloBrN30~a , '510 34 t3"1'506'30:127 68
XII 2-HO--5-BrCsHa H D~ , , i , ' , , ,
Cl4HloBr,NaO2-HeO ' 5
46,0 3,4111,4459 33 1151 7
XIIIlp- (CHs) ~NCsH4 ClsHIsN402 64,5' 5 6' 19 1164,9' 5 4[ 18,9 83--87
XIVlp- (C2Hs)~NCsH4 C 8H2~N402 67,0 6,1 169'.66,7 6,2117,3 40
XV l o-OeNC~H4 H CI4HI,N404 156 41 3'0i 18'9 I56'41 3 3 18'8 43
XVI p-O~NCsH4 H CI4HIoN404 H20 53.4 ! 3 5 18 0153.2 3.8 17.7 80--93
q
XVII i 2-Furyl C12HgNaO3 ^ 59,2!II'i
4,1i17,5i59,3 ,i 3,7117,31 81

ii
XVIII I C i ~ a l residue C17H2oBrN~O2~ - - --:10 7 - - - - 11,1 73
ClsHl2BrN302 d 53,6 3,3 1114 53,6 3,4111,71 83
C 4H 0BrN3Oz 508:33 13 11506 301127 96
XXI Isatin residue IH CIsHIoN4Oa ]60,7~ 3,51 - - 161,2] 3:4 - 30
XXII!p- (CHa)eNC6H4N ClsHlsN~O~ 60,4 5,0 i - - 60,0[ 5,1 2-- 304098
XXIII H, C~HsN=N CsH NsO~ 58,2 41 26,358,( 4,1 6,1 - -
[
XXIVI H, p-CHaOC~H~N=N C 4HI~,N~O2 ~- 156,0' 4,5 23,7156,5 44234163
, 9 , - - 09
XXV~ H, p-BrCsH4,N=N C ~H~oBrN~O~~ 44 9' 3,0 20,444,8 2,9 20,1 46
XXVI H. p-H~NSO~CsH4,N=N I H CIaH~NsO4Sg 44,71 3,8 24,5.44,8 3,5 24,1 63--69

aFound: Br 23.5%. Calculated: Br 24.0%. bFound: Br 22.9%.

Calculated: Br 23.0%. CFound: Br 20.8%. Calculated: Br 2t.1%.
dFound: Br 22.0%. Calculated: Br 22.3%. eFound: Br 23.9%.
Calculated: Br 24.1%. fFound: Br 22.8%. Calculated: Br 23.0%.
gFound: S 9.4%. Calculated: S 9.2%.

EXPERIMENTAL
Ylidene D e r i v a t i v e s of 2 , 3 , 5 , 8 ( 1 ) - T e t r a h y d r o i m i d a z o [ 1 , 2 - a ] p y r i m i d i n e - 2 , 5 - d i o n e s (IV-XXI, Table 1).
A) A 0 . 0 1 - 0 . 0 1 1 - m o l e s a m p l e of the aldehyde and anhydrous sodium acetate (in amounts equal to the weight
of I o r II) w e r e added to a solution of 0.01 m o l e of I o r II in 10-15 m l of glacial acetic acid, and the m i x -
ture was refluxed for 1-3 h. It w a s then cooled, and 40-50 m l of w a t e r anda20% s o l u t i o n o f s o d i u m h y d r o x -
[de w e r e added to pH 5-6. The resulting precipitate was r e m o v e d by filtration and washed with water
to give IV-XIV and XVI-XX.
B) A 1.47-g (0.01 mole) sample of isatin and two to three drops of piper[dine were added to a s u s -
pension of 1.65 g (0.01 m o l e ) of I in 60 m l of absolute ethanol, and the mixture w a s refluxed for 40 h. It
was then cooled, and t h e p r e c i p i t a t e was r e m o v e d by filtration and washed s u c c e s s i v e l y with hot w a t e r and
ethanol. The yield of XXI w a s 0.88 g (30%).
C) A 0 . 0 1 - 0 . 0 1 1 - m o l e sample of the aldehyde was added to a mixture of 1.83 g (0.01 mole) of Ill and
1.83 g of anhydrous sodium acetate in 10-15 m l of glacial acetic acid, and the mixture was refluxed for
1-3 h and worked up as in e x p e r i m e n t A. The yields of VIII, XIII, XV, and XVI w e r e 59, 83, 43, and 80%,
re s p e c t i v e l y .
Compounds VI, X, XI, XV, and XX were p a l e - y e l l o w c r y s t a l l i n e s u b s t a n c e s , IV, V, VII-IX, XII, and
XVI-XIX w e r e y e l l o w c r y s t a l l i n e s u b s t a n c e s , XIII and XIV w e r e orange c r y s t a l l i n e substances, and XXI
was a red crystalline substance; they w e r e purified for a n a l y s i s by c r y s t a l l i z a t i o n from 80%acetic acid
(IV), DMFA (V, VI,VIII, IX, XI-XIII, and XVIII-XIX), DMFA - m e t h a n o l (1 : 1) (VII), glacial acetic acid (X, XIV),,
o r D M F A - - w a t e r (2 : 1) (XV, XVI, and XX).

996
 3- (p- Dimethylaminophenyl) az o m e t h i n o - 7 - m e t h y l - 2 , 3 , 5 , 8 ( 1 ) - t e t r a h y d r o i m idazo [1,2-a]pyrim idine-2, 5-
dione (XXII, Table 1). A 1.5-g (0.01 mole) s a m p l e of p - n i t r o s o d i m e t h y l a n i l i n e and two to t h r e e drops of
piperidine were added to a suspension of 1.65 g (0.01 mole) of I in 40 m l of absolute ethanol, and the m i x -
t u r e was refluxed f o r 15 h. The solvent was then e v a p o r a t e d , and the residue was washed with e t h e r . The
yield of XXII, which was obtained as brown c r y s t a l s with mp 189-191 ~ (dec., by r e p r e c i p i t a t i o n f r o m DMFA
by the addition of water), was 1.2 g (40%).
3 - A r y l a z o - 7 - m e t h y l - 2 , 3 , 5 , 8 ( 1 ) - t e t r a h y d r o i m i d a z o [ 1 , 2 - a ] p y r i m i d i n e - 2 , 5 - d i o n e s (XXIII-XXVI, Table 1).
A) A m i x t u r e of 1.65 g (0.01 mole) of I, 1.7 g of anhydrous sodium acetate, and 0.011 mole of arenediazonium
t e t r a f l u o r o b o r a t e in 15-20 m l of glacial acetic acid was heated on a b o i l i n g - w a t e r bath for 20-30 min, a f t e r
which it was diluted with 50-60 m l of water, and the r e s u l t i n g p r e c i p i t a t e was r e m o v e d by filtration and
washed s u c c e s s i v e l y with w a t e r and methanol to give XXIII-XXVI.
B) A 0.011-mole s a m p l e of the a r e n e d i a z o n i u m t e t r a f l u o r o b o r a t e was added to a solution of 1.65 g
(0.01 mole) of I and 0.4 g (0.01 mole) of sodium hydroxide in 20-30 m l of water, and the m i x t u r e was a l -
lowed to stand at r o o m t e m p e r a t u r e for 1.5-2 h. W a t e r (50-60 ml) was added to it, and the resulting p r e -
cipitate was r e m o v e d by filtration and washed with w a t e r and methanol. The yields of XXIII, XXIV, and
X X V w e r e 98, 99, and 69%, r e s p e c t i v e l y .
Compounds XXIII and XXVI w e r e yellow c r y s t a l l i n e s u b s t a n c e s , while XXIV and XXV w e r e orange
c r y s t a l l i n e s u b s t a n c e s ; they were purified for analysis by c r y s t a l l i z a t i o n f r o m 809~ acetic acid (XXIII),
glacial acetic acid (XXIV and XXV), o r D M F A - w a t e r (4:1) (XXVI).

LITERATURE CITED
14 B. E. Mandrichenko, I. A. Mazur, and P. M. Kochergin, Khtmo G e t e r o t s i k l . Soedin., 1140 (1974).
2. E. G. Knysh, A. N. K r a s o v s k i i , P. M. Koehergin, and P. M. Shabel'nik, Khim. G e t e r o t s i k l . Soedin.,
399 (1972).

997
SYNTHESIS OF 4,6-DIPHENACYLPYRIMIDINES

L. P. Prikazchikova, B. M. Khutova, UDC 547.85.4.2/8.07

and V. M. Cherkasov

Reaction of 4 , 6 - d i m e t h y l p y r i m i d i n e with the acyl chlorides of a r o m a t i c carboxylic acids gave

N - a c y l - 4 - p h e n a c y l - 6 - a c y l m e t h y l i d y n e p y r i m i d i n e s , which undergo alcoholysis to give the c o r -
responding diketones - 4,6-diphenacylpyrimidines.

We have p r e v i o u s l y shown [1] that the reaction of 4,6-dimethylpyrimidine (I) with the acyl chlorides
of a r o m a t i c carboxylic acids (II) gives N - a c y l - 4 - p h e n a e y l - 6 - m e t h y l e n e p y r i m i d i n e s (IV), which are h y d r o -
lyzed to 4 - p h e n a c y l - 6 - m e t h y l p y r i m i d i n e s . By changing the reagent ratio and the workup of the reaction
mixture we obtained, in addition to IV, which were p r e v i o u s l y d e s c r i b e d as the only reaction products,
N - a c y l - 4 - p h e n a c y l - 6 - a c y l m e t h y l i d y n e pyrimidines (HI), which are isolated when methanol is added to the
residue r e m a i n i n g a f t e r r e m o v a l of the e x c e s s t r i e t h y l a m i n e and acid chlorides from the reaction mixture.
CH3 CH2COAr ~H2CO--

(Cflt.)sN CHCOAr cH~

CH3 -
COAr COAr
I II1 a , b Iv a,b
Compounds III and IV are obtained in yields of 10 and 40%, r e s p e c t i v e l y . A trisubstituted base was isolated
as the hydrochloride (V) in the reaction of pyrimidine I with anisoyl chloride. One of the two possible s t r u c -
t u r e s c o r r e s p o n d i n g to t a u t o m e r i c f o r m s of dimethylpyrimidine [1] is p r e s e n t e d for III.
The N - a c y l group in t r i s u b s t i t u t e d bases III and h y d r o c h l o r i d e V is unstable, and the c o r r e s p o n d i n g
4,6-diphenacylpyrimidines (VI) are f o r m e d during the alcoholysis of these compounds. The formation of
diketones is proved by the production of dioximes (VII).
C,tl2COAr ~H2~Ar
Ill a , b ~ c4n~on NH20 H
V -" -~ " --CH,COAr - - N I ~ c H 2 c /fl
L'~"
NOel
VI a~C VII a-C

III, IV, VI, VII a Ar=C6Hs; b Ar=p-CIC6H4; VI, VII Ar=p-CH3OC6H 4

The IR s p e c t r u m of pyrimidine I contains absorption bands at 2930 (methyl group), 3020 (=CH 2 group),
and 3450 cm -1 (NH group). The p r e s e n c e of the c h a r a c t e r i s t i c absorption band for the NIt group c o n f i r m s
the t a u t o m e r i s m of 4 , 6 - d i m e t h y l p y r i m i d t n e .
Absorption bands at 1650 (carbonyl group) and 905 (=CH group) are o b s e r v e d in the IR s p e c t r u m of
base III, while an absorption band at 1640 em -1 (carbonyl group) is o b s e r v e d in the IR spectrum of 4,6-
diphenaeylpyrimidine.

EXPERIMENTAL

The IR s p e c t r a of K B r pellets of the compounds were r e c o r d e d with a UR-20 s p e c t r o m e t e r .

Institute of Organic C h e m i s t r y , Academy of Sciences of the Ukrainian SSR, Kiev. T r a n s l a t e d from

Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1146-1147, August, 1974. Original article submitted
October 31, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 1 7th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retriepal system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

998
 TABLE 1. C h a r a c t e r i s t i c s of the Synthesized Compounds
~ound, ~o_ CalCulated, ~o
CoITi -
rap, "C Empirical formula
pound T-H N ~o
ield,

IIIa 145--148 CuTH2oN2Oa 76,7 4,8 9~ 61,9

77,1 4,8 -- 9
IIIb 212--214 CurH~zCIaN=Oa 61,91 3,1 3,3 l0
V 163--165 C~oH~N206-HC1 66,11 4,9 65,9 5,1 39
Via 116--118 C2oHI6N~O2 75,81 5,1 75,8 5,1 8~ 47
VIb 170--173 C2oHI4Cl~N20~ 62,3] 3,9 - 62,4 3,7
- 91
VIc 155--156 C~2H2oN204 69,91 5,2 70,2 5,4 50
VIIa 164--166 C2oH~sN402 69,51 5,5 69,4 5,2 16,2 70
VIIb 203--205 C2oHI6Cl~N402 57,7 3,8 13,4J 57,4 3,9 13,5 77
VIIc 204--205 CmH22N404 65,2 5,5 -- li 65,0 5,5 94

N-A c y l - 4 - p h e n a c y l - 6 - a c y l m e t h y l i d y n e p y r i m i d i n es (Ilia, b) and N - (p-Anisoyl)-4- 0p-methoxyphenacyl)-

6 - ( p - a n i s o y l m e t h y l i d y n e ) p y r i m i d i n e Hydrocbloride (V). A solution of 0.06 mole of II in 10 ml of absolute ....
benzene was added with s t i r r i n g to a solution of 0.02 mole of I and 0.06 mole of triethylamine in 10 ml of
absolute benzene, and the mixture was refluxed for 2 h. It was then cooled, and the triethylamine h y d r o -
chloride (50%yield) was r e m o v e d by filtration. The filtrate was vacuum evaporated, and methanol was
added to the residue. A yellow precipitate of III, which was r e m o v e d by filtration and purified by r e p r e c i p i -
tation from benzene solution by the addition of methanol, s e p a r a t e d from the solution after 5-10 rain.
Hydrochloride V precipitated from the methanol solution 20-30 min a f t e r the addition of methanol
(hydrogen chloride is obtained as a result of alcoholysis of the r e s i d u a l anisoyl chloride) (Table 1).
N - A c y l - 4 - p h e n a c y l - 6 - m e t h y l e n e p y r i m i d i n e s (IVa, b). These compounds were obtained a f t e r s e p a r a -
tion of III from the methanol solution, in analogy with the method in [1]. Compounds IV were identical to
the compounds d e s c r i b e d in [1].

4,6-Diphenacylpyrimidines (Via-c). A solution of 0.001 mole of III o r V in 20 ml of butanol was r e -

fluxed for 3 h. The c o m p l e t e n e s s of aleoholysis was m o n i t o r e d by means of t h i n - l a y e r c h r o m a t o g r a p h y
(TLC) on activity II A120 3 with b e n z e n e - m e t h a n o l (10 : 1) and development in UV light. After cooling, the
p r e c i p i t a t e d Vi was r e m o v e d by filtration and c r y s t a l l i z e d from alcohol (Table 1).

4,6-Diphenacylpyrimidine Dioximes (VIIa-c). A bright-yellow suspension of 0.002 mole of VI and

0.004 mole of hydroxylamine hydrochloride in 15 ml of alcohol and 15 ml of pyridine was allowed to stand
for 2-3 days, during which the solid dissolved, and the solution became c o l o r l e s s .
The solution was vacuum evaporated, w a t e r was added to the residue, and the resulting precipitate
was r e m o v e d by filtration. C r y s t a l l i z a t i o n from alcohol gave shiny white c r y s t a l s of VII.

LITERATURE CITED
1. V. M. Cherkasov, L. P~ Prikazchikova, B. M. Khutova, I. F. V l a d i m i r t s e v , and I. V, Boldyrev, Khim~
Geterotsikl. Soedino, 1132 (1973),

999
PYRIMIDO [2,1-a]ISOQ UINOLINI UM S A L T S

I. P. Baehkovskii and V. A. Chuiguk UDC 547.859'833

1-Aminoisoquinolinium pe r c h l o r a t e r e a c t s with 3 - diketones and fl - chlorovinyl ketone s to give

pyrimido[2,1-a]isoquinolinium s a l t s that f o r m polymethine dyes.

J u s t as p r o t i c s a l t s of ~ - a m i n o a z a h e t e r o c y c l e s r e a c t with 3 - c h l o r o v i n y l ketones to give condensed

p y r i m i d i n i u m s a l t s with a q u a t e r n a r y r b r i d g e nitrogen atom [1, 2], 1-aminoisoquinolinium p e r c h l o r a t e (I)
r e a c t s with 3 - d i k e t o n e s and f i - c h l o r o v i n y l ketones to give the p r e v i o u s l y unknown p y r i m i d o [ 2 , 1 - a ] i s o q u i n -
olinium s a l t s flI, Table 1).
R'-
Nfl~
I " O~c/R ,, ~ ~/!~
N . HCIO4 + , ~ - - R . . . .
X--C
~[ ~ 7 ~ 6 tic2
\R'
I
X = 0 1 1 , CI

While isoquinoline I r e a c t s with f l - c h l o r o v i n y l ket0nes u n d e r m i l d conditions, the r e a c t i o n with B-

diketones p r o c e e d s only when the components a r e heated to 260~
The PMR s p e c t r a c o n f i r m the f o r m a t i o n of a condensed ring with a q u a t e r n a r y - b r i d g e nitrogen atom.
Thus, the signal of an a r o m a t i c proton at 7.5 ppm is o b s e r v e d in the PMR s p e c t r a when 1~" =H. The m e t h y l
groups in the 2- and 4 - p o s i t i o n s of I I a - c have c h e m i c a l shifts of 2.6 and 2.7 ppm, r e s p e c t i v e l y , while those
in the 3 - p o s i t i o n have c h e m i c a l shifts of 3 - 2 . 3 p p m . The 6-H proton gives a doublet at 8.2 ppm with J = 7.5
Hz, while the 7-H doublet is s u p e r i m p o s e d on the multiplet of phenylene protons at 7.7-7.9 ppm. The m u l t i -
plet at 9.0-9.1 ppm, which is r e l a t e d to l l - H , is also a c o n f i r m a t i o n of s t r u c t u r e II; the strong l l - H p a r a -
m a g n e t i c shift is explained by coupling with the e l e c t r o n p a i r of N(1 ), which is rigidly fixed by the p y r i m i d i n e
ring.
Benzoylacetone r e a c t s with aminoisoquino}ine I to give one i s o m e r , the s t r u c t u r e of which (IId) is c o n -
f i r m e d m a i n l y by the c h a r a c t e r of the phenyl signal, which a p p e a r s as a singlet at 7.31 ppm; this c o r r e s p o n d s
to a phony1 group in the s - p o s i t i o n r e l a t i v e to the bridge nitrogen a t o m [3-5]. Methyl and phenyl 3 - e h l o r o -
vinyl ketones r e a c t with I to give one i s o m e r (IIe and TTf), the s t r u c t u r e s of which a r e c o n f i r m e d by the PMR
s p e c t r a . The chief f a c t o r in the s p e c t r u m of IIe that c o n f i r m s its s t r u c t u r e is J2,3 =5 Hz [4, 5] (5 9.00, 2-H;
7.64, 3-H; 2.78 ppm, 4-CH3); in the case of IIf, not only this f a c t o r (J2,3 =5 Hz) but also the phenyl singlet
at 7.32 ppm s e r v e s as a c o n f i r m a t i o n of its s t r u c t u r e .
All s a l t s II, except for 1-If, give polymethine dyes u n d e r the usual conditions. Thus, red s t y r y l IIg
was obtained f r o m lid and p - d i m e t h y l a m i n o b e n z a l d e h y d e in acetic anhydride; IIa r e a c t s with p - d i m e t h y l -
aminobenzaldehyde at both methyl groups and gives a m i x t u r e of s t y r y l d e r i v a t i v e s {according to the PMR
s p e c t r u m , in which both unchanged m e t h y l groups a r e o b s e r v e d ) .

N. K. K r u p s k a y a K h e r s o n Pedagogical I n s t i t u t e . T : G. Shevchenko Kiev State U n i v e r s i t y . T r a n s -

lated f r o m Khimiya G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 8, pp. 1148-1149, August, 1974. O r i g i n a l a r -
ticle s u b m i t t e d M a r c h 13, 1973~ r e v i s i o n submitte d J a n u a r y 8, 1974.

9 Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011, No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

1000
 T A B L E i. P y r i m i d o [ 2 , 1 - a ] i s o q u i n o l i n i u m Salts
Cl, %
Com- R R' R" mp,*C Empirical formula Yield, %
pound] found calc.

Ila CHa CHa H 240 C,4HI3CIN204 11,6 II,5 54

IIb CHa CHa CH3 246 C~sH~sCIN204 11,1 10,9 41
IIc CHa CHa ~t2H5 241 C,6HITCIN204 10,7 10,7 24
lid C6H5 232 C19H15CIN204 9,5 9,6 4O
lie [ CHa HH 210 CI~HIICIN204 12,0 12,0 7O
IIf i C6Hs H 251 C,aH,3CINzO4 10,0 9,9 63
II g I C6Hs A* H >300 C28H24CINaO4 7,0 7,1 85

* A =CH =CH-CGHa-N (CH3)2-p.

EXPERIMENTAL
The PMR spectra of 15-20% solutions of the compounds in trifluoroacetic acid were recorded with
a Tesla BS487B spectrometer (80 MHz) with hexamethyldisiloxane as the standard. The spectrum of an
alcohol solution of the dye was recorded with an SF-10 spectrophotometer.
Condensation of l-Aminoisoquinoline with ~ -Diketones. A mixture of 0.005 mole of I, 0.008-0.01
mole of the fi-diketone, and 2 ml of acetic acid was heated in a sealed ampul at a bath temperature of 260 ~
for 2 h (3 h for benzoylacetone). The mixture was then cooled and washed with ether, and II were re-
crystallized from water (IIa, d), ethanol (lie), or acetic acid (IIb) with the addition of activated charcoal
(see Table i).
Condensation of l-Aminoisoquinoline with fl-Cblorovinyl Ketones, A 0.005-mole sample of I, 0~
mole of methyl or phenyl p -chlorovinyl ketone, and 5 ml of acetic acid were heated onawaterbathfor [-
I0 rain, after which it was allowed to stand at room temperature for 24 h. The resuRing precipitate was
separated and recrystallized from methanol.
4-(4-Dimethylaminostyryl)-2-phenylpyrimido[2,l-a]isoquinolinium Perchlorate (Hg). A mixture of
0.30 g (0.0008 m o l e ) of IId, 0.17 g (0.015 m o l e ) of p - d i m e t h y l a m i n o b e n z a l d e h y d e , a n d 2 m l of a c e t i c a n h y d r -
ide was h e a t e d at 120-125 ~ f o r 10 m i n . It was t h e n cooled, a n d the dye c r y s t a l s w e r e s e p a r a t e d and r e -
c r y s t a l l i z e d f r o m e t h a n o l . UV s p e c t r u m : k m a x 558 n m (log e 4.71).

LITERATURE CITED
I. A. N. Nesmeyanov and M. I. Rybinskaya, Dokl. Akad. Nauk SSSR, 118, 297 (1958).
V
2. V. A. Chuiguk, USSR Author's Certificate No. 350,793 (1972); Byull. Izobr., No. 27, 80 (1972).
3. A. Le Berre and C. Renault, Bull. Soc. Chem. France, 3139 (1969).
.V
4. A. Pollak, B. Stanovnik, and
v
M. T1sler, J. Org. Chem., 3_~6,2457 (1971).
5. S. I. Shul'ga and V. A. Chuiguk, Khim. Geterotsikl. Soedin., 637 (1972).

1001
THIOPYRANS (REVIEW)

V. G. Kharchenko, S. N. Chalaya, UDC 547.818 : 543.422

and T. M. Konovalova

I n f o r m a t i o n on methods f o r the p r e p a r a t i o n of and on the physical and c h e m i c a l p r o p e r t i e s

of monocyclic t h i o p y r a n s , a s well ~s t h e i r s p e c t r a l c h a r a c t e r i s t i c s , is c o r r e l a t e d .

One of the new fields of the c h e m i s t r y of h e t e r o c y c l i c compounds is the c h e m i s t r y of t h i o p y r a n s . The

f i r s t a t t e m p t s to s y n t h e s i z e the s i m p l e s t 4 H - t h i o p y r a n s w e r e undertaken in 1886 [1, 2], but t h e s e studies
did not undergo f u r t h e r development, a p p a r e n t l y b e c a u s e of the long-standing concept of the instability of
such s y s t e m s [3]. Only in 1961, when information r e g a r d i n g the s y n t h e s i s and s o m e p r o p e r t i e s of 2,4,6-
t r i p h e n y l - 4 H - t h i o p y r a n a p p e a r e d [4], did this c l a s s of compounds b e c o m e the subject of s y s t e m a t i c study.

PREPARATION OF THIOPYRANS
Thiopyrans from Glutara]dehyde and Its Substituted Derivatives
The s i m p l e s t 4 H - t h i o p y r a n was s y n t h e s i z e d in 1962 by the action of hydrogen sulfide and hydrogen
chloride on glutaraldehyde and subsequent heating of the m i x t u r e in vacuo in the p r e s e n c e of diethylaniline
[5]. This r e a c t i o n was extended to the s y n t h e s i s of substituted t h i o p y r a n s and t h e i r analogs [6-12].

RI RI

~
R1

R H2S~HC L (C 2H5) 2 NCIIH 5

H H

RpRI=H ,AL~

Thiopyrans from Thiapyrylium Salts

Depending on t h e i r s t r u c t u r e , t h i a p y r y l i u m s a l t s a r e r e d u c e d by LiA1H 4 to give m i x t u r e s of 4H- and
2 H - t h i o p y r a n s in v a r i o u s r a t i o s [4, 10, 13-15].
Thus, a m i x t u r e of 2H- and 4 H - t h i o p y r a n s in a r a t i o of 1 : 9 was obtained f r o m 2 , 4 , 6 - t r i p h e n y l t h i a -
p y r y l i u m iodide [16, 17]. 2 , 4 , 6 - T r i p h e n y l - 4 H - t h i o p y r a n containing the 2 H - i s o m e r was obtained by r e d u c -
tion of 2 , 4 , 6 - t r i p h e n y l t h i a p y r y l i u m p e r c h l o r a t e (I) [4].
R3 R3 R3
R 2 ~ R4 ,,- R 2 " ~ R4 R 2 ~ R4
9 L;At H 4 -I--
R~ ~ SY\ R5 RL-/'~"S/'~..R5 RI.-/~-S7~- R5

R = H , alkyl, aryl; x = Ct ,I ,CL04

As in the r e a c t i o n with LiA1H4, the addition of G r i g n a r d r e a g e n t s to t h i a p y r y i i u m s a l t s gives m i x -
t u r e s of 4H- and 2 H - t h i o p y r a n s . As in the c a s e of p y r y l i u m s a l t s [18-20], the d i r e c t i o n of a t t a c k of the
nucleophile depends on the nature of both r e a g e n t s . A m i x t u r e of the c o r r e s p o n d i n g 2H- and 4 H - t h i o p y r a n s
in a r a t i o of 3 : 1 is f o r m e d in the r e a c t i o n of m e t h y l - o r e t h y l m a g n e s i u m b r o m i d e with I (or the t e t r a -
fluoroborate) [13].

N. G. C h e r n y s h e v s k i i Saratov State University. T r a n s l a t e d f r o m K h i m i y a G e t e r o t s i k l i c h e s k i k h

Soedinenii, No. 9, pp. 1155-1170, S e p t e m b e r , 1974. Original a r t i c l e submitted S e p t e m b e r 17, 1973.

I 9 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, ~ ]I. 10011. No part of this publication may be reproduced,
I stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
l recording or other*vise, without written permission of the publisher9 A copy of this article is available from the publisher for $15. 00.

1003
 A m i x t u r e of i s o m e r s (56% 4H-thiopyran and 17% 2H-thiopyran) was also obtained f r o m benzylmag-
nesium chloride and p e r c h l o r a t e I [21, 22], while reaction with 2,4,6-triphenylthiapyrylium iodide gives
only the 4H-thiopyran [23]. The f o r m a t i o n of only the 4H-thiopyran has also been noted in other c a s e s
[13-151.
p3 R3 R6 R3

R~,RS: alkyl,aryl; a~, R4 =H, alkyl, aryl; R3tR5=H,~aryl; x =CL,I ,

CL04~, B~ ; M : C / , S r , l .
If the thJapyrylium salt does not contain a substituent in the 4-position, only 4H-thiopyrans a r e ob-
tained by the action of a Grignard reagent [14]. In the r e a c t i o n of thiapyrylium iodide with m e t h y l m a g n e s i -
urn iodide [10], 4 - m e t h y l - 2 H-thiopyran and 2 H- and 4H-thiopyrans [10] a r e detected along with the expected
4 - m e t h y l - 4 H - and 2 - m e t h y l - 2 H - t h i o p y r a n s . 4 - M e t h y l - 4 H - t h i o p y r a n apparently i s o m e r i z e s under the r e a c -
tion conditions to give 4 - m e t h y l - 2 H - t h i o p y r a n [6]. In addition, the thiapyrylium cation undergoes reduction
due to t r a n s f e r of a hydride ion.

Q_",'0' Cc.,
o -- o-
I j I J
8 : 1 : 2

Thiopyrans from 1-Substituted 1-Thiabenzenes and 1-Thiabenzene S-Oxides

In c o n t r a s t to Grignard r e a g e n t s , organolithium compounds on reaction with thiapyrylium salts attack
the sulfur atoms to give one alkyl- o r 1 - a r y l - l - t h i a b e n z e n e s [4, 13, 24-29]. 1 - A l k y l - l - t h i a b e n z e n e s a r e
e x t r e m e l y unstable and a r e r e a d i l y c o n v e r t e d to 2 H- o r 4H-thiopyrans [13]. 4 - B u t y l - 2 , 4 , 6 - t r i p h e n y l - 4 H -
and 2 - e y c l o p e n t a d i e n y l - 2 , 4 , 6 - t r i p h e n y l - 2 H - t h i o p y r a n s , r e s p e c t i v e l y , a r e f o r m e d in the r e a c t i o n of butyl-
and cyelopentadienyllithium with p e r c h l o r a t e I [13].

C6H5 C6H5 R C6H5 C6H5

p ~ L'R ~ . ~ 3Lr.~R
#k C6H5 Ar C6H5 ir C6H5 A C6H5
CLO4- R
R = ary%cyclopentadienyl, alkyl
1-Arylthiabenzenes a r e r e l a t i v e l y stable and can be s t o r e d in an inert medium for weeks and even
months, but in light at r o o m t e m p e r a t u r e they a r e i s o m e r i z e d to 4H-thiopyrans [4, 13, 16, 17, 24-29].
1 - P h e n y l - l - t h i a b e n z e n e , which does not change on prolonged storage in light and in the p r e s e n c e of oxygen,
is distinguished by high stability [16, 26]. The d e c r e a s e in the stability of substituted 1 - a r y l - l - t h i a b e n -
z e n e s as c o m p a r e d with unsubstituted compounds [24] is explained by s t e r i c f a c t o r s [16], which disrupt the
conjugation in the thiabenzene ring. The high stability of 1 - ( p - d i m e t h y l a m i n o p h e n y l ) - 2 , 4 , 6 - t r i p h e n y l - 1 -
thiabenzene (II) has been noted [28]. A peak c o r r e s p o n d i n g to splitting out of a p-dimethylaminophenyl-
m e r c a p t i d e ion is o b s e r v e d in its m a s s s p e c t r u m . Cleavage of the S - A t bond i s c h a r a c t e r i s t i c for other
1 - a r y l t h i a b e n z e n e s . The high stability of 1-thiabenzene 1I m a y be explained by the considerable contribu-
tion of the ylid s t r u c t u r e of bent c o n f o r m e r B [28].

C6H.~C~H ~ A C6HS B CGH~C6H5

"N(CH3)z N(CH3)2 + N(CH3)2

1004
 A continuous 7r orbital of a r o m a t i c rings conjugated through sulfur can be constructed for each con-
f o r m e r (A and B) while retaining the a r o m a t i c c h a r a c t e r of the thiabenzene ring. P a r t i c i p a t i o n in the c o n -
jugation of the 3p z orbital of sulfur in the case of c o n f o r m e r A and of one 3dx orbital of sulfur in c o n f o r m e r
B is c o n s i d e r e d probable. Thus, the stability of 1 - a r y l t h i a b e n z e n e s is a s s o c i a t e d with the p r e s e n c e of a
continuous conjugation chain including thiabenzene with retention of its a r o m a t i c c h a r a c t e r . This concept
makes it possible to explain the u n s u c c e s s f u l attempts to obtain 1 - a l k y l - l - t h i a b e n z e n e s [13] and 1-phenyl-
e t h y n y l - 2 , 4 , 6 - t r i p h e n y l - l - t h i a b e n z e n e s [28]. In the latter case, a mixture of 4-phenylethynyl-4H- and 2-
p h e n y l e t h y n y l - 2 H - 2 , 4 , 6 - t r i p h e n y l t h i o p y r a n s in a ratio of 7 : 4 was obtained by the action of phenylethynyl-
lithium on p e r c h l o r a t e I. The s t r u c t u r e of the 1 - a r y l t h i a b e n z e n e s is confirmed by their cleavage (by the
s u c c e s s i v e action of oxygen and hydrogen chloride in ether) to give an ylid and an a r y l m e r c a p t a n [13,
24, 28].
C6H 5 C=H 5 C6H 5 CsH 5
02 HCL i-'~-~( xO HC:.O 4

C6H5~J~"C 6H5 C6615 "SI - "C6H5 C61,.{~ "O" "C6H5 C6H C6H~
b Ar CLO~

A r = C 6 N s , p - CH3C6H 4 ~ rn- CH~C6H 4 , p - (CH3)zNC6It~

E x t r e m e l y stable 1-thiabenzene S-oxides (IID w e r e obtained by r e a c t i o n of substituted a , f l - a c e t y l e n i c

ketons with dimethyloxosulfonium methylide [30-32]. The hydrogen atoms of the S-CH3 group in III a r e ex-
changed by deuterium on refluxing in CH3OD-D20 containing NaOD, but are r e p l a c e d by methyl groups on
t r e a t m e n t with butyllithium and subsequent r e a c t i o n with methyl iodide to give thiabenzene S-oxides IV
and V [32].

Rc~C " C R1 11.t-BuNe 1

4- & . R ~ R 2.CH3I R~.~R . R ~ R '

CHz~/CH3 J-\ L ~" \ .- \

s o cH3 O C.%CH~ C C,CCH~) 2
o c% ~ '2 S
R , RI = alkyl, phenyl

In c o n t r a s t to 1 - a r y l t h i a b e n z e n e s , S-oxides Ill a r e not i s o m e r i z e d to thiopyrans in light and by heat-

ing but give a mixture of 2H- and 4H-thiopyrans in a ratio of 3 : 2 on reduction with t r i c h l o r o s i l a n e in r e -
fluxing benzene [31]. Their reduction with lithium aluminum hydride did not give definite results [32].
C6H5~ c6H5 HS;CL3 C6HsvC6H5 "+- C5H5~ C6H~"

Of ~'CH3
The formation of an extremely unstable l-methyl-3,5-diphenylthiabenzene was proved spectroscopical-
ly by careful hydrolysis of l-methyl-3,5-diphenylthiapyrylium tetrafluoroborate [31].

Thiopyrans from 1,5-Diketones

The formation of 2H- and 4H-thiopyrans in the reaction of 1,5-diketones with H2S and P4Sl0 [14, 15,
33-41] is more general in character, although some 1,5-diketones are readily condensed under these con-
ditions to give carbocyclic compounds [42-46].
The nature of the solvent has a great effect on the degree of conversion of 1,5-diketones with hydro-
gen sulfide under the influence of hydrogen chloride [14, 15]. Thus, mainly 4H-thiopyrans are obtained in
methanol, while mixtures of thiacyelohexanes and thiapyrylium chlorides are obtained in acetic acid [34,
35, 40].
R1 RI R! R~

Ar UO Ar Ar %" -Ar Ar " S- Ar A Ar

C[
R =H ~ CH 3 ; R1 = CH 3 ~ aryl; R2 = H TCH3 tC6H 5

On brief standing, the reaction mixture also contains thiopyrans. After 48 or more hours, depending on the
structure of the 1,5-diketone, the reaction products at 20 ~ are the corresponding thiapyrylium chloride and

1005
thiacyclohexane [34, 36, 40], The d e g r e e of c o n v e r s i o n of diketones with hydrogen sulfide under acid c a t a -
l y s i s conditions is also d e t e r m i n e d by the d e g r e e of t h e i r substituted c h a r a c t e r and the c h a r a c t e r of the
substituent [36, 41]. 1 , 5 - D i p h e n y l - l , 5 - p e n t a n e d i o n e and the 3 - m e t h y l d e r i v a t i v e r e a c t in methanol with
H2S and HC1 to give m i x t u r e s of t h i a p y r y l i u m s a l t s and thiacyclohexanes. 1 , 2 , 4 , 5 - T e t r a p h e n y l - l , 5 - p e n t a n e -
dione does not r e a c t with the s a m e r e a g e n t s in e i t h e r methanol o r acetic acid [14]. 1 , 5 - D i a r y l - l , 5 - p e n t a n e -
diones containing substituents in the 2 - and 4- o r 2 - , 3-, o r 4-positions r e a c t with hydrogen sulfide and hy-
drogen chloride in both methanol and acetic acid to give t h i o p y r a n s .
1,5-Diketones r e a c t with P4S10 to give 4 H - t h i o p y r a n s in pyridine [38]. In the absence of a solvent, the
r e a c t i o n p r o c e e d s in the s a m e way as the r e a c t i o n of 1,5-diketones with hydrogen sulfide and hydrogen
chloride in acetic acid [47]. T e t r a - and pentasubstituted 1,5-pentanediones do not r e a c t with P4S10 in p y r i -
dine [38]. The state of the e l e c t r o n density on the c a r b o n y l c a r b o n a t o m and the weakly basic c h a r a c t e r of
the catalyst, which does not sufficiently p r o m o t e either enolization of the ketones or cyclodehydration of
the initially f o r m e d unstable g e m - h y d r o x y t h i o l s , a r e a p p a r e n t l y m a n i f e s t e d in this c a s e [38].
New thianaphthene s y s t e m s (VIII) with a t e t r a v a l e n t sulfur atom a r e obtained by the action of p h o s -
phosphorus pentasulfide in pyridine on 1 , 2 - d i b r o m o - 5 , 6 - d i b e n z o y l a c e n a p h t h e n e (VI) and 1 , 4 , 5 , 8 - t e t r a b e n -
zoylnaphthalene (VII) [48-51].

P2 S5 P255 \
Nfl2 CP 20 7
C6 HsCO COC6H5 C6H5CO COC6Hi
, V~ V.--~ a,b Vi__~l
a R=Br ; b R=C6H 5

Starting t e t r a k e t o n e VII is f o r m e d in the oxidation of thiopyran VIIIb with sodium d i c h r o m a t e , while a

m i x t u r e of diketone IX and monothiodiketone X is obtained by the action of C r O 3 in pyridine. Monothiodike-
tone X r e a c t s with hydrogen chloride in e t h e r to r e f o r m thiopyran VIIIb:

V--~b +

C6H5CO COC6H5 C6H5CS COC6H5

Z
Specific Methods for the Preparation 0f 2H-Thiopyrans
The a b o v e - d e s c r i b e d methods lead to 4 H - t h i o p y r a n s o r to a m i x t u r e of the l a t t e r with 2 H - t h i o p y r a n s .
Individual r e a c t i o n s that give only 2 H - t h i o p y r a n s a r e known.
2 H - T h i o p y r a n XI is obtained by the action of hydrogen sulfide on a substituted pentadienal under
b a s i c c a t a l y s i s conditions [52, 53]:
fiH 3
HIS ~ pyridine

" ~C6H 5

2 H - T h i o p y r a n [11] and 2 - m e t h y l - 2 H - t h i o p y r a n [9, 11, 12] w e r e obtained f r o m 1 - t h i a - 3 , 5 - c y c l o -

hexanedione:

O O HO_ _HO~ ~ ~0H KSH

_ oo-
R : H ~CH 3
The f o r m a t i o n of 2 H - t h i o p y r a n XII in 15% yield by refluxing benzaldehyde with sodium sulfide in a l -
cohol solution was unexpected [54, 55]. The ethanol is a p p a r e n t l y oxidized to acetaldehyde, which con-
denses with benzaldehyde:

1006
 Na2S /CH CH2CHO
C~HsCHO + CH3CHO .. C6H~CH=CHCHO - S...CHCH2CHS--~

C6H5 .CHO C6H51~IHO OHC~CH2C6H 5

!~ C6H$CHO- S "
Ci C6H; HC6FI5 C6H5 -- C6H5
XJA

p - T o l u a l d e h y d e r e a c t s like benzaldehyde with sodium sulfide in a l c o h o l [54].

D i t h i o a c r y l a t e s r e a c t with m a l e i c anhydride in b e n z e n e to give adducts XIII, w h i c h a r e i m m e d i a t e l y
c o n v e r t e d to 2H-thiopyran XIV [56].

R1
NR z
R2NHc//C~'c-SCH3,IS ~ O0~F~1 ~--NHRT~
NHP~ " H O G C " ~ R~
+ ~~/ ~ - - - - - L~.S ; J . ' +
Oo:=
~ O SCH3 R2N~'o XlV---~ "SCH3

O
The intermediate f o r m a t i o n of adduct XIII is c o n f i r m e d by the s y n t h e s i s of its nitrogen analog (XV)
[56].
CH3

H S o. CH3
+ C6H5:N~~SCH3
xv
0 O
C6H5
The t h e r m a l c y c l i z a t i o n of propargyl vinyl sulfides in hexametapol o r dimethyl sulfoxide (I)MSO) in
the p r e s e n c e of a m i n e s , which g i v e s a mixture of 2H-thiopyrans and thiophenes, is of great interest [57-
59]. If there is an alkyl substituent in the 4 - p o s i t i o n of the thiopyran, a certain amount of 4 - a l k y l i d e n e d i h y -
drothiopyran is f o r m e d .
4 - E t h y l - 4 H - t h i o p y r a n is m o r e greatly inclined to give an "exo" i s o m e r than 4 - m e t h y l - 4 H - t h i o p y r a n .
When b e n z e n e , a l k a n e s , and aliphatic a l c o h o l s a r e used as the solvent in this reaction, vinyl propargyl s u l -
fides a r e r e s i n f f i e d on heating without a catalyst, while m i x t u r e s of the corresponding thiopyrans and t h i o -
phenes in low yields a r e f o r m e d in the p r e s e n c e of a m i n e s . The yield of thiophenes i n c r e a s e s in DMSO as
the b a s i c i t y of the a m i n e i n c r e a s e s , and the yield of thiopyrans i n c r e a s e s with the s a m e a m i n e s in hexa-
metapol. Only thiopyrans a r e f o r m e d in high yield in pure hexametapol [59].

R2 R3 H R3
N3_ C---~_C--C\
~ I I
H\/C=C=CI R2 --~C
H_C=C ~ R~/ \C~S --

t
R3 R3

R~'~ R~ R~%s - R~ R2

R4J"--.S~CH2R2 R4 R~

PROPERTIES OF THIOPYRANS AND THEIR DERIVATIVES

The s i m p l e s t 2H- and 4H-thiopyrans and their m o n o a l k y l - s u b s t i t u t e d derivatives change rapidly in
a i r and can be s t o r e d for a long ,Lime only in the solid state at t e m p e r a t u r e s below - 2 8 ~ in a nitrogen a t -
m o s p h e r e [5, 7, 59]. The m o r e substituents in the thiopyran ring, the m o r e stable the compounds are. 2,4,6-
T r i a r y l - and t e t r a - and pentaalkyl(aryl)thiopyrans a r e stable, but they darken in light in the p r e s e n c e of

1007
a i r oxygen and "deliquesce." 2 , 6 - D i a r y l - 4 - a l k y l - s u b s t i t u t e d compounds a r e less stable than 2 , 4 , 6 - t r i -
a r y l t h i o p y r a n s [14, 15, 39].
The dipole m o m e n t of 2 , 4 , 6 - t r i p h e n y l - 4 H - t h i o p y r a n is 1.35 D [60]. The dipole moment i n c r e a s e s by
0.2 and 0.4 D, r e s p e c t i v e l y , on s u c c e s s i v e r e p l a c e m e n t of the hydrogen atoms in the 3- and 5-positions by
a CH3 group. If dipole moments of 0, 0.4, and 0.4 D a r e adopted f o r the Csp2 ~ H, H ~-~ Csp3, and CH 3 ~-
Csp2 bonds, r e s p e c t i v e l y , it can be shown that the contribution to the total dipole moment of each CH~
group in the 3- and 5-positions of thiopyrans a - e will be 0.2 D [60].

5~5 C C6H5 .C6H5

,j6H 6H5 C6H5 b C6H5C6M5 Call5 C6H 5 CsH5

j/ 1,350 1,54 O 1,76 O 1,83 D
a b r d

Salt Formation of Thiopyrans

One of the basic p r o p e r t i e s of thiopyrans is t h e i r capacity under the influence of protic and nonprotic acids
to undergo c o n v e r s i o n to thiapyrylium salts with splitting out of a hydride ion. The thiopyran ring is fully
c o n v e r t e d to the thiapyrylium cation when a hydride-ion acceptor is p r e s e n t in the reaction mixture. Thus,
the hydride-ion a c c e p t o r in the r e a c t i o n of triphenylmethyl p e r c h l o r a t e is the triphenylmethyl cation [8-12 ].
R2 ~2
+" -
(C6H5) 3 CCIO4 R1
~ (C6H5)3 CCLO, ,-

CH 3
c l o 4-
~,~,Rz= H, alkyl
4H-thiopyrans are converted to thiapyrylium salts by the action of PCI 5, C12, and 12 [7, 8, 61]. In con-
trasfl to chlorine and iodine, bromine adds to the double bond of 4H-thiopyran [61].

Br Br Br2 9 9
CL2 e 12
er Sr X-
XVI

Under the influence of protic acids (HC1, I-ICIO4, and CF3COOH) , substituted thiopyrans d i s p r o p o r -
tionate with i n t e r m o l e c u l a r hydride-ion t r a n s f e r to give a m i x t u r e of the corresponding thiapyrylium salts
and thiacyclohexanes [36, 37, 40, 41, 62-64].
. R1 R1 R!

HX = 2 +
C6H~ 5- "CeH5 C6 H5 C6H~ =r C6H5
X-
R: H~ alkyl; Rt,1~: alkyl, aryl
Similarly, s y m - o c t a h y d r o d i b e n z o - 4 I I - t h i o p y r a n s disproportionate under the influence of f e r r i c chlo-
ride, p e r c h l o r i c acid, and hydrogen chloride [63-64]. The f o r m a t i o n of thiacyclohexanes along with thia-
pyrylium salts i n t h e r e a c t i o n of thiopyrans with p r o f i t acids' attests to the fact that the carbonium ions
that develop during protonation of the lr bonds of the thiopyrans and dihydrothiopyrans a r e hydride-ion
a c c e p t o r s in the disproportionation [40, 62].

' ~ HX HX . _p_

i H t-

J
HX

1008
 The carbonium ions ar e stabilized as a result of intermolecular hydride t r a n s f e r s .
4H-Thiopyrans ar e distinguished by high mobility of the hydride ion. Thus, a hydride ion is t r a n s -
f e r r e d in the reaction of pyrylium and selenopyrylium perchl orat es with 4H-thiopyran with the quantitative
formation of thiapyrylium perchlorate and pyran or selenopyran [65, 66]:
H

o Ct04"
-0 Ct04
X=O~Se

Sulfones and Sulfoxides of Thippyrans

Substituted and mono- and disubstituted H- and 4H-thiopyrans undergo profound transformations un-
der the influence of oxidizing agents (hydrogen peroxide, peracids, and manganese dioxide). The nature of
the oxidation products has not been studied [61].
T e t r a - and pentasubstituted 4H-thiopyrans are capable of undergoing oxidation to give sulfones [4,
13-15, 24, 37, 38].
R3 R2 R R3 R2
~5~i H202 ,~ 4 ~ Rt
C H5 C6H5"- ~UZ "C~15
R ! ~ R 3 , R 4 = H ~ alkyl, aryl; R2 = alkyl, aryl

The different behavior of substituted 2H- and 4H-thiopyrans with respect to oxidation is well known.
2,4,6-Triphenyl-4-methyl-4H-thiopyran is smoothly oxidized by hydrogen peroxide to the sulfone, while
the isomeric 2,4,6-triphenyl-2-methyl-2H-thiopyran forms a sulfoxide under the same conditions [13]. A n
attempt to oxidize the latter to the sulfone was unsuccessful [13]. 21-I-Thiopyrans are apparently more
stable than 4H-thiopyrans, and oxidation to the sulfone does not occur when two substituents are present in
the 2-position because of steric factors.
In connection with the fact that the oxidation of the simplest thiopyrans leads to disruption of the
heteroring, a number of indirect methods for the preparation of their sulfones and sulfoxides have been
developed [61, 67-76]. The sulfone of 2H-thiopyran was obtained as the result of oxidation and subsequent
dehalogenation with zinc dust of 2,3,5,6-tetrabromothiacyelohexane (XVD [61] and also from l-thia-3,5-
cyclohexanedione [68].
Br. Br

V.
X__!~
_

XVI__J
_ [ (C2H5)3hi
0~0. L;ALHc ~. OH 1. SOCL2 . ~2 CL
2. [o]

Only the corresponding sulfoxide is readily formed in the oxidation of sulfide XVI with hydrogen
peroxide. Oxidation to sulfone XVII proceeds with g r e a t e r difficulty [61]. Only the sulfone of 4H-thiopy-
ran, which is apparently isomerized under these conditions to the sulfone of 2H-thiopyran [61, 68], could
a r is e initially as a result of debromination of sulfone XVI.
The synthesis of 2H-thiopyran &S-dioxides from dipropargyl sulfone by the action of secondary
amines is of great interest [71]:
/C H2"-C~-CH R2NH R2N'~CH3 CH3,~NR2
SOz ,- +
~ CH~"C-~CH S02 SO2
Under the same conditions, dipropargyl sulfoxides form products of the addition of the secondary
amines, which are not cyelized [71].

1009
 2 H - T h i o p y r a n S,S-dioxides a r e a l s o f o r m e d in the c y c l i z a t i o n of allylsulfonyl e n a m i n e s under the
influence of t r i e t h y l a m i n e and subsequent deamination at 220 ~ of cyclization product XVIII [69~ 70, 72-76].
R. 502 R2 R SO2 R2 R. SO~ R2

C ~CH

XVlll

R,R2=H, alkyl; R'= atky], aryl

C e r t a i n difficulties have a r i s e n in the solution of the p r o b l e m of the position of the double bond in the
t h i o p y r a n ring [61, 67, 68]. In this connection, the s y n t h e s i s and s p e c t r a l c h a r a c t e r i s t i c s of 3 - p h e n y l - 2 H -
t h i o p y r a n S,S-dioxide (XIX), in the ring of which the position of the double bonds was p r e d e t e r m i n e d by the
s t r u c t u r e of the s t a r t i n g diketone [69], s e e m e d of g r e a t interest:
j-S~ CH3COO No SO2 I. Na B H4 ~SOZ
CO
C6"H5 C~ 3
CO CH3COOH ~
CsH 5 0
2,85aloH3PO4 C6H
5 ~

XX XlX

The properties of su/~ones of 2H-thiopyrans [67, 68, 72, 73] have been studied most completely. The
high lability of the hydrogen atoms of the a-methylene group, as attested to by their complete deuterium
exchange in the a b s e n c e of b a s i c c a t a l y s t s [77], was established. S,S-Dioxide anions a r e f o r m e d On t r e a t -
ment of sulfones of 2 H - t h i o p y r a n s with sodium or sodium methoxide in DMSO [72]. The PMR s p e c t r a c o n -
f i r m the benzoid c h a r a c t e r of the s y s t e m . . T h e d i r e c t o b s e r v a t i o n of an anion a t t e s t s to extensive ~r-elec-
t r o n delocalization [72 ]:
R~ R1

R2 R DM$ O R R

Like a , f l - u n s a t u r a t e d a c y c l i c sulfones, the sulfones of 2 H - t h i o p y r a n s add weakly basic nucleophiles

on refluxing in c h l o r o f o r m o r benzene [67, 68, 70].
XR
HXR

XR=(C2Hs)2N; NHC4H9-n ; HNC6HH ; morpholino;

pyrrolidino; s (C2H5)2; S Cell5 ; SC6H4CH3 -p ;S C6H4Br

Despite the obvious lability of the hydrogen a t o m s of 2 H - t h i o p y r a n S, S-dioxides, the action of diazo-
m e t h a n e does not r e s u l t in alkylation in the 2 - p o s i t i o n but r a t h e r in addition of the r e a g e n t to give 1 - p y r a -
zoline XXI, which is i s o m e r i z e d to 2 - p y r a z o l i n e XXII on refluxing in methanol [73].
N:N N--NH

SO2~I-~ ~ ether ~.so2.J ~

XXlll XlX XXI XXlt

The f o r m a t i o n of 1 - p y r a z o l i n e XXI suggests i s o m e r i z a t i o n of sulfone XIX to 5 - p h e n y l - 2 H - t h i o p y r a n

S,S-dioxide (XXIII) [73]. It was found that this s o r t of i s o m e r i z a t i o n is o b s e r v e d when a methanol solution
of sulfone XIX is s i m p l y s t o r e d . As a r e s u l t , the p o s s i b i l i t y of a t t a c k by dipolar r e a g e n t CH2N2 at the "end"
of the diene s y s t e m of sulfone XXIII, which is a p p a r e n t l y m o r e r e a c t i v e than sulfone XIX, a p p e a r s .
Condensation of sulfone XIX and 3 - p h e n y l - 6 - m e t h y l - 2 H - t h i o p y r a n S,S-dioxide (XXIV) with 1 - m e t h y l -
4 - b r o m o p y r i d i n i u m iodide gives compounds of the XXV type [76].
BP R1 F~!

ri 'f c'H -
X IX ~XX IV CH 3 C6H 5 C6H 5
xl_.~_ R~:H ; _XXIV
_ F~1 = CH 3 XXV

1010
 The sulfones of 2 H - t h i o p y r a n s a r e r e d u c e d to the c o r r e s p o n d i n g sulfones of thiacyclohexane b y c a t a -
lytic hydrogenation on palladium [69], and the sulfo g r o u p s a r e a l s o r e d u c e d on nickel [71].

CH3OH
R =C6H5 ~ I~l=R ; RI =CH 3 , R= p[peridino, N(CH3)2, mor]3hol~no

Reaction with Dichlorocarbene

This r e a c t i o n of d i h y d r o p y r a n (or dihydrothiopyran) has g e n e r a t e d a g r e a t deal of i n t e r e s t in c o n n e c -
tion with the ability of the r e s u l t i n g adducts to undergo c o n v e r s i o n to an oxepine on refluxing in quinoline
[78-80]:

~ :ccL2 ~CC~z t~ ~ cL

X = O~S

In c o n t r a s t to A2-dihydrothiopyran, A3-dihydrothiopyran f o r m s 2 - and 4 - d i e h l o r o m e t h y l d i h y d r o t h i o -

p y r a n s [80]:

:CC( 2 ~ CL2

A s i m i l a r d i f f e r e n c e with r e s p e c t to d i c h l o r o c a r b e n e is m a n i f e s t e d by 4H- and 2 H - b e n z o t h i o p y r a n s

[81]. The 3p o r b i t a l s of the sulfur a t o m in A2-dihydrothiopyran and 4 H - b e n z o t h i o p y r a n a p p a r e n t l y i n t e r a c t
with the ~r bond and a c t i v a t e it; this p r o m o t e s addition of d i c h l o r o c a r b e n e [80]. T h i s notion is c o n f i r m e d by
the ability of 4 - r n e t h o x y - 2 H - b e n z o t h i o p y r a n , in which the double bond is p o l a r i z e d due to p-Tr conjugation
of the f r e e e l e c t r o n p a i r s of oxygen and the r bond, to give an adduct with d i c h l o r 0 c a r b e n e [77]. D i m r o t h
has extended this r e a c t i o n to p y r a n s and t h i o p y r a n s [82]. It was found that 4 H - t h i o p y r a n is capable of a d d -
tug d i c h l o r o c a r b e n e at one and two double bonds to give m o n o - and diadducts. In addition, the r e a c t i o n m i x -
t u r e contains 4 - d i c h l o r o m e t h y l - 4 H - t h i o p y r a n .
CHCl2

The p o s s i b i l i t y of the f o r m a t i o n of a c a r b a n i o n that undergoes attack by d i c h l o r o c a r b e n e evidently shows

up under b a s i c c a t a l y s i s conditions due to splitting out of a p r o t o n in the 4 - p o s i t i o n .

fB
H CHC[2

The f o r m a t i o n of d i c h l o r o m e t h y l - s u b s t i t u t e d compounds in the r e a c t i o n of d i c h l o r o c a r b e n e with 2H-

benzothiopyr~n and A3-dihydrothiopyrsn can be s i m i l a r l y explained [81].
2 , 4 , 6 - T r i p h e n y l - 4 H - p y r a n adds d i c h l o r o c a r b e n e only at one double bond [82]. An a t t e m p t to a c c o m -
plish c o n v e r s i o n of the monoadducts of p y r a n and t h i o p y r a n to a n oxepine and a thiepine in analogy with the
p y r a n adduct was u n s u c c e s s f u l [82].

Isomerization and Other Transformations of Thiopyrans

When a solution of 2 , 4 , 6 - t r i p h e n y l : 4 - b e n z y l - 4 H - t h i o p y r a n (X-XVI) in hexane is subjected to UV i r r a -
diation in a nitrogen a t m o s p h e r e it is i s o m e r i z e d to 2 , 4 , 6 - t r i p h e n y l - 2 - b e n z y l - 2 H - t h i o p y r a n (XXVII) [21,
22, 83]. The s t r u c t u r e of i s o m e r XXVII is c o n f i r m e d by c o n v e r s i o n to 1 , 3 , 5 - t r i p h e n y l - 3 - b e n z y l p e n t a n e by
desulfuration o v e r Raney nickel. T e t r a p h e n y l b e n z e n e is f o r m e d when 2 H - t h i o p y r a n XXVII is heated with
sodium ethylene glycoxide.

1011
 C6H5 C H2C6H5 C6H5

C6H5~C6H 5 -- *"#' . C 6H5~~ S / ~ c 6CHzC6H5

H5
XXVI XXVII

2,4,6-Triphenyl-4-benzyl- and 2,6-diphenyl-4- (p-tolyl)-4-ben~yl-4H-pyrans are similarly iso-

m e r g e d [83, 84].
The c o n v e r s i o n of 2 , 4 , 6 - t r i p h e n y l - 4 - b e n z y l - 4 H - t h i o p y r a n and p y r a n by heating t o 90 ~ with 70% p e r -
cMoric acid is different in c h a r a c t e r . In this c a s e , two p a r a l l e l p r o c e s s e s - elimination of a benzyl group
to give 2 , 4 , 6 - t r i p h e n y l t h i a p y r y l i u m o r 2 , 4 , 6 - t r i p h e n y l p y r y l i u m p e r c h l o r a t e and a substituted naphthalene
and thioacetophenone - a r e o b s e r v e d [21, 22]. D i m r o t h p r o p o s e s the following m e c h a n i s m for the c o n v e r -
sion of 4 - b e n z y l - 4 H - t h i o p y r a n and p y r a n s to 1,3-diphenylnaphthalenes [21, 22]:

~ CHZ%H 5 ~' R~ RI_

~2 R2

215 B ,
- - A

~
N~ X ~ C i 4 #1 x RI X
--,. II il 2 ~ II z
CH2CR2 2C~ ~ v ~.- "f" CH3CR

, R R R
c X:O,5 XXXl

According to the data in [21, 22 ], 2 - b e n z y l - 2 H - p y r a n s and 2 - b e n z y l - 2 H - t h i o p y r a n s do not f o r m substituted

naphthalenes with p e r e h l o r i c acid.

Halogenation of Thiopyrans
2 H - T h i o p y r a n XXVII undergoes r a d i c a l substitution by the action of N - b r o m o s u c c i n i m i d e (NBS) in the
p r e s e n c e of benzoyl peroxide to give m o n o - o r d i b r o m o - s u b s t i t u t e d 2 H - t h i o p y r a n s , depending on the r e a -
gent r a t i o [23]. More than two b r o m i n e a t o m s cannot be introduced into the thiopyran molecule under t h e s e
conditions [23].
: C6H5
1:1 ~.~ B,"

jLC6H5 C6H5 -3" "CH2C6H5

': ' . r ~ BPN<

C6H ~ -S" "CHzC6HS

C6H5 1 3 Br"'C~BP

S i m i l a r b r o m i n a t i o n products a r e f o r m e d by the action of NBS on 4 - b e n z y l - 4 H - t h i o p y r a n (XXVI), but

the r e a c t i o n p r o c e e d s l e s s smoothly, and only 3 - b r o m o - 4 - b e n z y l - 4 H - t h i o p y r a n could be isolated p r e p a r a -
tively. The halogenation of 2 H - and 4 H - p y r a n s with NBS p r o c e e d s s i m i l a r l y [23].
The chlorination of 2 H - a n d 4 H - t h i o p y r a n s XXVI and XXVII with N - c h l o r o s u c c i n i m i d e (NCS) or
CCIsSO2C1 leads to a v e r y c o m p l e x m i x t u r e of r e a c t i o n products, in which 3 - c M o r o - 2 , 4 , 6 - t r i p h e n y l - 2 -
b e n z y l - 2 H - t h i o p y r a n was detected only by s p e c t r a l methods [23].
2 , 3 , 5 , 6 - T e t r a b r o m o t e t r a h y d r o t h i o p y r a n is f o r m e d in 75% yield by the action of a solution of b r o m i n e
in c h l o r o f o r m a t - 3 5 ~ on 4 H - t h i o p y r a n in the s a m e solvent. Under s i m i l a r conditions at - 4 0 ~ t h i a p y r y -
lium chloride is f o r m e d with chlorine. 4 H - T h i o p y r a n does not r e a c t with iodine under the s a m e conditions,
but the iodine c o l o r in the aqueous a c e t o n e solution v a n i s h e s in the c o u r s e of 1 h, and t h i o p y r y l i u m iodide
is f o r m e d . It should be noted that 4 H - t h i o p y r a n did not give a t h i a p y r y l i u m b r o m i d e with b r o m i n e in
aqueous a c e t o n e solutionl but the p r o d u c t of the addition of b r o m i n e and r e s i n i f i c a t i o n products w e r e
f o r m e d in s m a l l a m o u n t s [61].

Spectral Characteristics of Thiopyrans

T h e r e a r e only disconnected data on the e l e c t r o n i c and IR s p e c t r a of unsubstituted and substituted

1012
 TABLE 1. UV Spectra of Thiopyrans
Thiopyran k max, nm log
4H-Thiopyran [5, 6, 111 236-238, 278 3.7, 3.4
2 , 4 , 6 - T r i p h e n y l - 4 H - t h i o p y r a n [11, 13, 38, 60] 234 (235), 4.5 (4.46),
312 (350) 3.4 (3.20)
2 , 4 , 6 - T r i p h e n y l - 3 - m e t h y l - 4 H - t h i o p y r a n [60] 224, 310 4.2, 3.3
2 , 4 , 6 - T r i p h e n y I - 3 , 5 - d i m e t h y I - 4 H - t h i o p y r a n [60] 222, 2 82 4.3, 3.2
2 , 6 - D i p h c n y l - 3 , 5 - d i m e t h y l - 4 H - t h i o p y r a n [60] 220, 280 4.5, 3.7
2 , 3 , 5 , 6 - T e t r a p h e n y l - 4 H - t h i o p y r a n [60] 226,250-290 4.57, 4.25
2 , 4 , 6 - T r i p h e n y l - 4 - b e n z y l - 4 H - t h i o p y r a n [21, 23] 233,237 4.48, 4.45
2 , 4 , 4 , 6 - T e t r a p h e n y l - 4 H - t h i o p y r a n [13, 23 ] 235 4.2 9
2 , 4 , 6 - T r i p h e n y l - 4 - m e t h y l - 4 H - t h i o p y r a n [13] 235 4.4
2 H - T h i o p y r a n [10, 57] 231, 324 3.36, 3.29
3,5-Diphenyl-2 H - T h i o p y r a n [31, 32 ] 270, 304 4.49, 3.69
2 , 4 , 6 - T r iphenyl-2-methyl-2 H-thiopyran [13] 257, 347 4.32, 3.75

2H- and 4H-thiopyrans in the literature [5, 6, ii, 13, 38, 51, 57, 60]. The electronic spectrum of unsub-
stituted 4H-thiopyran contains kma x bands at 236-238 nm (log e 3.7) and 278 nm (log 5 3.4) [5, 6, ii]. The
following bands are presented for the most thoroughly studied compound, 2,4,6-triphenyl-4H-thiopyran:
235 nm (log ~ 4.46), 350 nm (log ~ 3.25) [13], 234 nm (log ~ 3.95), and 312 nm (log ~ 3.30) (in hexane) [60].
The second band undergoes a bathochrornic shift. Substituents in the 3- and 5-positions have the greatest
effect on the position of the bands in the electronic spectra of 4H-thiopyrans; substituents in the 4-position
have virtually no effect on the UV spectra [13, 23, 26, 38, 60] (Table i).
Judging from the data presented in [Ii, 57], the electronic spectrum of 2H-thiopyran differs only
slightly from the spectrum of 4H-thiopyran.
Two bands in the region of absorption of C-~C bonds are observed in the IR spectra of 2H- and 4H-
thiopyrans [5, 14, 15, 38]. A shift in the absorption bands in the spectrum of 2H-thiopyran (VC= C 1535,
1565 em -l) [Ii, 57] as compared with the IR spectrum of 4H-thiopyran [5, 6, ii] (~C=C 1600, 1640 cm -I)
in the longwave region is observed.
Resonance signals at 6 5.9 ppm (2-H, 6-H), 5.5 ppm (3-H, 5-H), and 2.8 ppm (4-H) are observed in
the PMR spectra of 4H-thiopyrans; signals at 5.59 ppm (4-, 5-, and 6-H), 5.10-5.60 ppm (3-H), and 3.00-
3.19 ppm (2-H) are observed in the spectra of 2H-thiopyrans [i0, 59, 82, 85, 86].

LITERATURE CITED
1. V. Meyer, Ber., 19, 628 (1886).
2. K. K r e k e l e r , B e r . , 19, 3266 (1886).
3. C. D. Nenitzescu, Organic C h e m i s t r y [Russian translation], Vol. 2, Inostr. Lit., Moscow (1963),
p. 684.
4. G. Suld and C. P r i c e , J. A m e r . Chem. Soc., 83, 1770 (1961).
5. J. Strating, J. Keiyer, E. Molenaar, and L. Brandsma, Angew. Chem., 7_44, 465 (1962).
6. J. Strating and E. Molenaar, Org. Prep. P r o c e d u r e s , 1, 21 (1969).
7. J. Degani, R. Fochi, and C. V[ncenzi, T e t r a h e d r o n Lett., 1167 (1963).
8. J. Degani, R. Fochi, and C. Vincenzi, Gazz. Chim. Itat., 94, 203, 451 (1964).
9. J. Degani and C. Vincenzi, Boll. Sci. Fac. Chim. Ind. Bologna, 23, 245 (1965).
10. J. Degani and R. Fochi, Gazz. Chim. Ital., 97, 397 (1967).
11. J. Degani and C. Vincenzi, Boll. Sci. Fac. Chim. Ind. Bologna, 25, 51 (1967).
12. J. Degani, R. Fochi, and C. Vincenzi, Boll. Sci. Fac. Chim. Ind. Bologna, 2 3 , 2 4 1 (1965).
13. G. Suld and C. P r i c e , J. A m e r . Chem. Soc., 84, 2090 (1962).
14. V . G . Kharchenko and V. I~ Zh. Organ. Khim., 7, 613 (1971).
15. V . G . Kharchenko, V. I. Kleimenova, and A. R. Yakoreva, Khim. Geterotsikl. Soedin., 900 (1970).
16. C. P r i c e and D. H. Follweiler, J. Org. Chem., 34, 3202 (1969).
17. C. P r i c e , M. Siskin, and C. Miao, J. Org. Chem., 36, 794 (1972).
18. A. Saffieddine, J. Rover, and J. Dreux, Bull. Soc. Chim. F r a n c e , 703 (1972).
19. J. R o v e r and J. Dreux, Bull. Soc. Chim. F r a n c e , 707 (1972).
20. O. Chalvet, C. Decoret, and J. Dreux, Bull. Soc. Chim. F r a n c e , 716 (1972).

1013
21. K. Dimroth, K. Wolf, and H. Kroke, Ann., 678, 183 (1964).
22. K. Dimroth, H. Krokr and K. Wolf, Ann., 678, 202 (1964).
23. U. E i s n e r and T. K r o s h n a m u r t y , J. o r g . Chem., 37, 150 (1972).
24 G. Suld and C. P r i c e , J. A m e r . Chem. Soc.; 8_44,2094 (1962).
25 C. P r i c e , M. Hori, and P. M. Polk, J. A m e r . Chem. Soc., 8__~5,2278 (1963).
26 M. Polk, M. Siskin, and C. P r i c e , J. A m e r . Chem. Soc., 91, 1206 (1969).
27 C. P r i c e , T. P a r a s a r a n , and T. V. L a k s h m i n a r a y a n , J. A m e r . Chem. Soc., 888, 1034 (1966).
28 C. P r i c e , I. F o l l w e i l e r , H. Pirelani, and M. Siskin, J. Org. Chem., 3_66, 791 (1971).
29 C. P r i c e and H. P r i e l a n i , J. Org. Chem., 3_~7,1718 (1972).
30 A. G. Hortmann, J. A m e r . Chem. Soc., 8_7, 4972 (1965).
31 A. G. H o r t m a l m and R. Z. H a r r i s , J. A m e r . Chem. Soc., 92, 1803 (1970).
32 A. G. H o r t m a n n and R. Z. H a r r i s , J. A m e r . Chem. Soc., 9_~3,2471 (1971).
33 V. G. Kharchenko, S. K. Klimenko, A. M. Plaksina, and A. R. Yakoreva, Zh. Organ. Khim., 2, 1122
(1966).
34. V. G. Kharehenko V. I. Kleimenova, N. M. Kupranets, N. P. Polikarpova, and A. R. Yakoreva, Zh.
Organ. Khim., 4, 2054 (1968).
35. V. G. Kharchenko S. K. Klimenko, V. I. Kleimenova, and N. M. Kupranets, Zh. Organ. Khim., 5, 1711
(1969).
36. V. G. Kharchenko N. M. Kupranets, V. I. Kleimenova, A. A. Rassudova, M. E. Stankevich, N. M.
Yartseva, and A. R. Yakoreva, Zh. Organ. Khim., 6, 1119 (1970).
37. V. G. Kharchenko M. E. Stankevich, A. R. Yakoreva, and E. G. Lelien-Fel'd, Khim. Geterotsikl.
Soedin., 422 (1971).
38. V. G. Kharchenko S. K. Klimenko, V. I. Kleimenova, N. M. Kupranets, and A. R. Yakoreva, Khim.
Geterotsikl. Soedin., No. 3, 73 (1971).
39. V. G. Kharchenko V. I. Kleimenova, and A. R. Yakoreva, Khim. Geterotsikl. Soedin., No. 3, 79 (1971).
40. V. G. Kharchenko, M. E. Stankevieh, A. R. Yakoreva, A. A. Rassudova, and N. M. Yartseva, Khim.
Geterotsikl. Soedin., 916 (1972).
41. V. G. Kharchenko, M. E. Stankevich, N. M. Kupranets, A. R. Yakoreva, V. I. Kleimenova, and S. K.
Klimenko, Zh. Organ. Khim., 8, 193 (1972).
42. E. Knoevenagel, Ann., 281, 25 (1894).
43. E. Knoevenagel, Ann., 303,223 (1898).
44. P. Rabe and F. Elze, Ann., 323, 83 (1902).
45. P. Rabe, Ann., 360,265 (1908).
46. M. N. Tilichenko, Ueh. Zap. SGU, Vyp. Khim., 7_ii,153 (1959).
47. V. G. Kharchenko and A. R. Yakoreva, USSR Author's Certificate No. 216747 (1968); Byul. izobret.,
No. 15, 38 (1968).
48 L. S. Pontecella and R. H. Schlessinger, J. Amer. Chem. Soc., 9_O0,4190 (1968).
49 R. H. Schlessinger and A. G. Schultz, J. Amer. Chem. Soe., 90, 1676 (1968).
50 I. M. Hoffmann and R. H. Schlessinger, J. Amer. Chem. Soe., 91, 3953 (1969).
51 M. P. Cava and G. E. M. Husbands, J. Amer. Chem. Soc., 91, 3952 (1969).
52 A. I. Chechak and C. Robenson, US Patent No. 3125571 (1964); Chem~ Abstr~ 61, 5702 (1964).
53 A. I. Chechak and C. D. Robenson, US Patent No. 3184516 (1965); Ref. Zh. Khim., 12N437P (1967).
54 C. E. C r e m e r and A. V. Subbaratnam, Chem. Commun., 33 (1967).
55 K. A. Latff, M. A. R a z z a g , B. K. Adhikari, and M. M. Eunus, J. Indian Chem. Soc., 3 6 , 2 0 9 (1959).
56 R. Kalisch, A. E. Smith, and E. J. Smithy, T e t r a h e d r o n Lett., 2241 (1971),
57 L. B r a n d s m a and P. J. W. Schuiyl, Rec. T r a y . Chim., 88, 30 (1969).
58 P. J. W. Schuiyl, H. J. T. Bos, and L. B r a n d s m a , Rec. T r a v . Chim., 88, 597 (1969).
59. D. S c h u i y l - L a r o s , P. J. W. Schuiyl, and L. B r a n d s m a , Rec. T r a y . Chim., 91, 785 (1972).
60. E. N. K h a r l a m o v a , E. N. G u r ' y a n o v a , and V. G. Kharchenko, Zh. Strukt. Khim., 12, 637 (1971).
61. E. Molenaar and J. Strating, T e t r a h e d r o n Left., 2941 (1965).
62. V. G. Kharchenko, N. M. Y a r t s e v a , and A. A. R a s s u d o v a , Zh. Organ. Khim., 6, 1513 (1970).
63. V. G. Kharchenko, S. K. Klimenko, and T. I. Krupina, Zh. Organ. Khim., 3, 1344 (1967).
64. V. G. Kharchenko, S. K. Klimenko, and T. I. Krupina, Khim. G e t e r o t s i k l . Soedin., No. 3, 76 (1971).
65. J. Degani, R. Fochi, and C. Vincenzi, Boll. Sci. Fac. Chim. Ind. Bologna, 23, 21 (1965).
66. J. Degani, R. Fochi, and G. Spunta, Boll. Sei. Fac. Chim. Ind. Bologna, 23, 243 (1965).
67. E. Molenaar and J. Strating, R e e . T r a y . Chim~, 86, 436 (1967).
68. E. Molenaar and J. Strating, Rec. T r a v . Chim., 86, 1047 (1967).

1014
69. J. Rossi and G. Pagani, Tetrahedron Lett., 2120 (1966).
70. G. Pagani, Gazz. Chim. Ital., 97~ 1518 (1967).
71. L. Skattebl, B. Boulette, and S. Solomen, J. Org. Chem., 33, 548 (1968).
72. S. Bradamante, A. Mangia, and G. Pagani, Tetrahedron Lett., 3381 (1970).
73. S. Bradamante, S. ]YIaiorana, A. Mangia, and G. Pagani, Tetrahedron Left., 2971 (1969).
74. S. Maiorana and G. Pagani, Chim. Ind. (Milano), 4_88, 1195 (1966).
75. S. Bradamante, S. Maiorana, and G. Pagani, J. Chem. Soc., Perkin I, 282 (1972).
76. G. Pagani and S. Maiorana, Chem. Ind. (Milano), 53,259 (1971).
77. W.E. Parham and D. E. Weetmann, J. Org. Chem., 34, 56 (1969).
78. E.E. Sehweizer and W. E. Parham, J. Amer. Chem. Soe., 82, 4085 (1960).
79. W.E. Parham and E. E. Sehweizer, J. Org. Chem., 24, 1733 (1959).
80. W.E. Parham, L. Christensen, S. H. Groen, and R. M. Dodson, J. Org. Chem., 29, 2211 (1964).
81. W.E. Parham and R. Konces, J. Amer. Chem. Soe., 83, 4034 (1961).
82. K. Dimroth, W. Kunzebach, and M. Soyno, Ber., 99, 2351 (1966).
83. K. Dimroth, Angew. Chem., 72, 331 (1960).
84. M. Nguven, K. Cuong, and F. Francoise, Comptes Rend., C, 271, 1626 (1970).
85. J. Degani, L. Lunarri, and F. Taddei, Boll. Sci. Fac. Chim. Ind. Bologna, 2__33,133 (1965).
86. L. Dalgaard and S. Lawesson, Tetrahedron Lett., 2051 (1972).

1015
CONDENSATION OF SALICYLNITRILE WITH SOME
a-HALO CARBONYL COMPOUNDS

F. A. Trofimov, G. F. Lelyak, UDC 547.728 : 542.953

L. I. Shevchenko, and A. N. Grinev

3-Aminobenzofuran derivatives were obtained by condensation of salicylnitrile and 5 - b r o m o -

salicylnitrile with ce-monochloroacetic acid derivatives and ~ - h a l o ketones.

In connection with the interest in the synthesis of h e t e r o c y c l i c analogs of anthranilic acid [1], we
studied the condensation of salicylnitrile (I) and 5 - b r o m o s a l i c y l n i t r i l e (II) with the methyl e s t e r and amide
of ~ - m o n o c h l o r o a c e t i c acid, chloroacetone, and bromoacetophenone. The reaction was c a r r i e d out by heat-
ing the reagents in d i m e t h y l f o r m ~mide (DMFA) o r in d i o x a n e - D M F A in the p r e s e n c e o f anhydrous potassium
carbonate; this p r o c e d u r e gave the previously inacessible 3 - a m i n o b e n z o f u r a n derivatives (III-VII). Two of
them - I i I and V I - w e r e obtained in the f o r m of t h e i r acetyl derivatives.

~Y'-o. ...c.~coR,-- l ~-oc.~cor, ~-~.o~.cor,j ~'~\o~'-coR'

,,. v., m-vu

I R=H; I1 R=Br; IlI R=H, R'=OCH3, R"=COCHz; IV R=Br, R'=OCH3, I~"=H;

V R=H, R'=NH2, I~"=H; VI R=H, R'=C6t-I5,R"=COCHs; VII t~=H, R'=CH3, t~"=H;
VIII R=H, R'=NH2

In one c a s e we w e r e able to isolate intermediate VIII, which m a k e s it possible to consider the p r o c e s s

to be a r e a c t i o n that p r o c e e d s through a step involving the f o r m a t i o n of a carbanion with subsequent intra-
m o l e c u l a r cyclization. Intermediate VIII is cyclized to 3-aminoberLzofuran derivative V in the p r e s e n c e of
sodium alkoxide in absolute alcohol. Hydrolysis of III gave 3 - a c e t a m i d o b e n z o f u r a n - 2 - c a r b o x y l i c acid (IX),
which was converted to 3 - a c e t a m i d o b e n z o f u r a n (X) by refluxing in DMFA.

NaOH ~ NHCOCH3 ~ / N HCOCPI3

I11 ~
"-O/ ~COOff

EXPERIMENTAL
The IR s p e c t r a of KBr pellets of the compound were r e c o r d e d with a UR-10 s p e c t r o m e t e r . The PMR
s p e c t r a of t r i f l u o r o a c e t i c acid solutions were r e c o r d e d with a V a r i a n ' T - 6 0 s p e c t r o m e t e r with hexamethyl-
disiloxane (HMDS) as the external standard.
Salicylnitrile (D. A 49.2-g (0.4 mole) sample of salicylaldehyde and 47.2 g (0.68 mole) of hydroxyl-
amine hydrochloride w e r e dissolved in 96 ml of d r y pyridine. A total of 60 ml (0.6 mole) of acetic a n h y -
dride was then added in portions while maintaing the t e m p e r a t u r e at 80-90 ~ after which the reaction m i x -
ture was heated on a w a t e r bath f o r 5 h, cooled, and poured over ice. The resulting solution was weakly
acidified with h y d r o c h l o r i c acid and extracted with ether. The e x t r a c t was dried with magnesium sulfate,

S c i e n t i f i c - R e s e a r c h Institute of Medicinal Radiology, A c a d e m y of Medical Sciences of the USSR.

S. Ordzhonikidze All-Union S c i e n t i f i c - R e s e a r c h Institute of P h a r m a c e u t i c a l C h e m i s t r y , Moscow. T r a n s -
lated f r o m Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1171-1173, September, 1974. Original
a r t i c l e submitted N o v e m b e r 5, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this pubfication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

1'016
 TABLE l . 3-Aminobenzofuran Derivatives
Corn IR s p e c t r u m c m "~ . . . . . Empirical Found % talc,, %
" , rt" o ~. . . . ! ..... vrvlK s p e c t r u m , . . . . . . _' _ Yield, %
po_und _..R ........... " . _ rap: C I c=.o. N-H . . . . ppm formula ..... c ! H N c H

III H OCHz COCHz 146--147 5 ! 1620. t680 3320 2,7, 3,83s'}" C~2Ift NO4
! 62,2 i 5,0 6,04 61.8 4.7 6,0 63
i 17 5 7,0--7,7 m '
IV Br OCHa II 149--150 ] 1630, 1680 3360, 3470, 4,0c, 7 , 1 - - 7 , 8 m CtoHsBrNOz 44,3 3,1 -- 44,4 2,9 40
V H NH2 H 159" ] 1630. 1660 3190, 3340, -- I C9It8N202 61,5 4,6 61.4 4.6 84
v , . c0H~ coo., 145 'i ,%1620,.90 3~5 - c,7.,3N03 73,2 4,9 _ 73,l 4,7 2O

VII H CIt3 H 153--154 1635 3190. 3390. 2.6c. 7 - - 8 m CIctt9NO2 68.5 7.3 -- 68,6 7,5 42
I 3420

From benzene- methanol.

t s is s i n g l e t a n d m is m u l t i p l e t .

Q
~q
and the e t h e r was r e m o v e d by distillation to give 23 g (50%) of nitrile I with mp 94-95 ~ (from b e n z e n e - h e x -
ane) (rap 95 ~ [2]).
5 - B r o m o s a l i c y l n i t r i l e (ii). T h i s compound was s i m i l a r l y obtained f r o m 5 - b r o m o s a l i c y l a l d e h y d e . The
yield of nitrile II with mp 158-159 ~ (from b e n z e n e - h e x a n e ) (rap 158-159 ~ [3]) was 78%.
3 - A m i n o b e n z o f u r a n D e r i v a t i v e s (III, IV, VI, and VII). A m i x t u r e of 0.01 mole of nitriles I o r II, 0.01
m o l e of anhydrous p o t a s s i u m carbonate, and 0.01 mole of s - h a l o c a r b o n y l compound in 30 ml of d r y DMFA
w a s refluxed for 45 min. The inorganic p r e c i p i t a t e was r e m o v e d by filtration, and the f i l t r a t e was v a c u u m
e v a p o r a t e d . The r e s i d u e was r e c r y s t a l l i z e d f r o m b e n z e n e - h e x a n e . Acetyl d e r i v a t i v e s III and VI w e r e ob-
tained by t r e a t m e n t of the r e a c t i o n m i x t u r e with acetic anhydride at 20 ~ f o r 3 h. Data on III, IV, VI, and
VII a r e p r e s e n t e d in T a b l e 1.
2 - C y a n o p h e n o x y a c e t a m i d e (VIII). A m i x t u r e of 11.9 g (0.1 mole) of nitrile I, 9.4 g (0.1 m o l e ) o f m o n o -
e h l o r o a c e t a m i d e , and 14 g (0.1 mole) of anhydrous p o t a s s i u m c a r b o n a t e was refluxed in 150 m l of absolute
alcohol f o r 3 h. The inorganic p r e c i p i t a t e w a s s e p a r a t e d , and the solution was e v a p o r a t e d . The yield of
VIII with mp 181-182 ~ was 11 g (62%). Found, %: C 61.3; H 4.8. CgHsN202. Calculated, %: C 61.4; H 4.6.
IR s p e c t r u m : 1705 (C~O), 2229 c m -I (C--N).
3 - A m i n o b e n z o f u r a n - 2 - c a r b o x a m i d e (V). A m i x t u r e of 5.7 g (0.037 mole) of a m i d e VIII and 0.2 g of
sodium ethoxide in 55 m l of absolute alcohol w a s refluxed for 1 h, a f t e r which the solvent was r e m o v e d by
distillation (Table 1).
3 - A c e t a m i d o b e n z o f u r a n - 2 - c a r b o x y l i c Acid (IX). A 2 . 4 - g (0.01 mole) s a m p l e of HI was added to a s o l u -
tion of 0.8 g (0.02 mole) of sodium hydroxide in 25 m l of 50% aqueous methanol, and the m i x t u r e was allowed
to stand at 20 ~ f o r 1.5 h. It was then diluted with w a t e r and acidified with h y d r o c h l o r i c acid. The p r e c i p i -
t a t e was r e m o v e d by f i l t r a t i o n and washed ~vith w a t e r to give 2 g (90%) of IX with mp 210~ (decomp., f r o m
aqueous alcohol). Found, %: C 60.1; II 4.3; N 6.4. CIIHgNO4. Calculated, %: C 60.0; H 4.1; N 6.4.
3-.Aeetamidobenzofuran ( X ) . A solution of 1 g (0.004 mole) of IX in DMFA was refluxed f o r 3 h, a f t e r
which the solvent was r e m o v e d by distillation, and the r e s i d u e was worked up to give 0.25 g (31%) of X with
m p 175-175.5 ~ (from b e n z e n e - h e p t a n e ) . Found, %:C 68.6; H 5.4; N 7.8. Ci0HgNO2. Calculated, %: C 68.6;
H 5.2; N 8.O.

LITERATURE CITED

1. V. I. Shvedov, V. K. Ryzhkova, and A. N. Grinev, Khim. G e t e r o t s i k l . Soedin., 459 (1967).

2. E. Beckmann, B e r . , 2.~6, 2623 (1_893).
3. K. A u w e r s and A. I. Walker, B e r . , 31, 3042 (1898).

1018
INTRODUCTION OF NEW SUBSTITUENTS
INTO SOME AROMATIC CATIONS

S. V . K r i v u n , V. I. Dulenko, UDC 547.814' 818.9'751 : 543.422.4

S. V . S a y a p i n a , N. S. S e m e n o v ,
Yu. A. Nikolyukin, a n d S. N. B a r a n o v

D i v e r s e substituents in the 2- and 6-positions of p y r y l i u m and s e l e n a p y r y l i u m s a l t s do not

have a substantial effect on the yields in the p y r y l a t i o n of dimethylaniline and 1 - m e t h y l i n -
dole. The c y c l o p r o p e n y l a t i o n and t r i p y l a t i o n of t h e s e compounds u n d e r conditions s i m i l a r
to those in the p y r y l a t i o n r e a c t i o n w e r e studied; this study m a k e s it possible to c o m p a r e
these three reactions.

T h e r e a r e an e x t r e m e l y l a r g e n u m b e r of methods f o r the introduction of substituents into the ring of

p y r y l i u m s a l t s and o t h e r h e t e r o a r o m a t i c cations (for example, see [1]). The p y r y l a t i o n r e a c t i o n [2, 3] opens
up b r o a d p o s s i b i l i t i e s for t r a n s f o r m a t i o n s of this s o r t . We have investigated this r e a c t i o n in the c a s e of the
r e a c t i o n of s o m e 2,6-di(alkyl, a r y l ) - s u b s t i t u t e d p y r y l i u m s a l t s with 1 - m e t h y l i n d o l e and dimethylaniline. It
w a s found that the r e a c t i o n is g e n e r a l in c h a r a c t e r and m a k e s it possible to widely v a r y the substituents in
the 2- and 6 - p o s i t i o n s of the p y r y l i u m cations. The r e a c t i o n p r o c e e d s through the i n t e r m e d i a t e f o r m a t i o n
of a 4 - s u b s t i t u t e d 4 H - p y r a n with subsequent dehydrogenation by the s t a r t i n g p y r y l i u m salt [2] v i a t h e s c h e m e

R R

R R R~ "~0/ ~R R/'<O/'R R \R
X-

A comparison of the yields of final products (see Table 1) shows that the snbstituents of the starting
p y r y l i u m s a l t do not have a s u b s t a n t i a l effect on the reaction, although dimethylaniline is p y r y l a t e d to a
s o m e w h a t l e s s e r extent than methylindole when t h e r e a r e e l e c t r o n - d o n o r substituents in the a r o m a t i c c a -
tion. We w e r e unable to isolate 2 , 6 - d i m e t h y l - 4 - ( p - d i m e t h y l a m i n o p h e n y l ) p y r y l i u m p e r c h l o r a t e , probably
b e c a u s e of the f o r m a t i o n of a m i x t u r e of this salt with its d i p e r c h l o r a t e (salt f o r m a t i o n at the d i m e t h y l -
a m i n o group). This was indirectly c o n f i r m e d by the fact that the d i p e r c h l o r a t e of the 2 , 6 - d i - t e r t - b u t y l - 4 -
( p - d i m e t h y l a m i n o p h e n y l ) p y r y l i u m salt was identified in the r e c r y s t a l l i z a t i o n of it f r o m acetic acid in the
p r e s e n c e of HC1Q. 2 , 6 - D i p h e n y l t h i a p y r y l i u m p e r c h l o r a t e s i m i l a r l y undergoes thiapyrylation [4]. We
a s c e r t a i n e d that 2 , 6 - d i p h e n y l s e l e n a p y r y l i u m p e r c h l o r a t e a l s o r e a d i l y r e a c t s with 1-methylindole and di-
methylaniline to give s e l e n a p y r y l i u m s a l t s when m i x t u r e s of the r e a g e n t s a r e heated slightly (see T a b l e 1).
Similar r e s u l t s w e r e obtained f o r nonbenzoid a r o m a t i c s y s t e m s - c y c l o p r o p e n y l i u m and t r o p y l i u m
s a l t s . The r e a c t i o n of the t r i p h e n y l c y c l o p r o p e n y l i u m cation with a r o m a t i c compounds was d e s c r i b e d in [5].
However, the t e t r a s u b s t i t u t e d c y c l o p r o p e n e s obtained could not be c o n v e r t e d to new c y c l o p r o p e n y l i n m salts.
It might be a s s u m e d that the use of the disubstituted c y c l o p r o p e n y l i u m cation in this r e a c t i o n would lead to
t r i s u b s t i t u t e d c y c l o p r o p e n y l i u m s a l t s with a new substituent c o r r e s p o n d i n g to the nucleophile used. E x -
c e s s s t a r t i n g c y c l o p r o p e n y l i u m ion (in which c a s e the r e a c t i o n p r o c e e d s in one step) o r even t r i t y l p e r -
c h l o r a t e , which r e a c t s with the r e s u l t i n g cyclopropene, m a y s e r v e as h y d r i d e - i o n a c c e p t o r s in this case.
In fact, r e a c t i o n of dimethylaniline with diphenylcyclopropenylium p e r c h l o r a t e in a c e t o n i t r i l e gives 1 , 2 - d i -

Donetsk Physical-Organic Chemistry Branch, Institute of Physical Chemistry, Academy of Sciences

of the Ukrainian SSR. Translated from Khimiya Geterotsiklicheskikh Soedlnenii, No. 9, pp. 1174-1177,
September, 1974. Original article submitted August 8, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 17th Sn'eet, New York, N. }7. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

1019
b9

TABLE 1. Characteristics of the Compounds Obtained

Compound (-pyryltum Empirical form- Found, % :alc., % IR spectrum ~ y l i u m l__m,..ri
r i n ~ Yield,
perchlorate) ula : tN I z 8a---- 8b ........ :19b L%

2, 6 - Dimethyl-4 - (I - m eth yl- 262 CI~HI6C1,NOs 1( 56,9 1 [6,5j - 1670 m 1570 s 1445 inf 84
3-indolyl)
2,6 - Di-tert - b utyl<4- ( l - 286 C~2H28CI'NO5 -- 62,6 i 8,41 - 1650 s [570 s 1430 s 92
methyl-3-indolyl)
2,6-Di-tert-butyl-4-(p- 202 C2,Ha0CINO5 -- 61,2 i 8,61 1555 inf 1430 s 65
dimethylaminophenyl) ~.6,2 1655s
2,6- DKp-bromophenu 360 C25H~oBr~CINOs 26,4
!6,4 ~ 49,2 i 5,8! 1650 s 1550 s 1410 w 85
( p- methyl-3- indolyb
2 6- Di(p-bromophenvl) -4 - 316 C26HIsBr2CINOs 25,7
25,7a 50,4 s,71 .~5,8 1660 m [540m 1415 s 85
'(p- dimethylarkinophemyl)
2~6-Di(p-methoxyphenyl)-4- 258 C~sH24CINO7 -- 64,4 6,81 1630 m I545 s 1415 m 85
(1- methyl-3-indolyl)
2, 6- Di(p- methoxyphenyD -4 - 312 C~TH~6ChNO7 -- 63,3 6,91 -- 1630 m 1420 m 55
( p- dimethytaminophenyl)
2,6-Di(m-hTdroxvphenyl)-4- 304 C26H~oCINO7 -- 63,2 <2t -- 1635 s [545 s 1415.m 98
(1-methyl-3-indolyl)
2,6-Di(m-hydroxyphenyl)-4- 370 C2sH~CI'NO7 -- 62,2 7,31 [~ 1650m [555 inf 1425 s 84
(p- dimethylaminophenyl)
2,6- Di(a- thienvl) -4 - ( l - 292 C2~HIeCINOsS~ 13,4 -o 55,8 7.51 1640 s [560 s 1425, s 95
methyl-3-indolyl)
2,6-Di(a-thtenyl)-4-(p- di- 308 C21HIsCI,NOsS2 13,7 b 54,4 7,7] :3,81 1645 s [545 s 1420' s 95
methylaminophenyl)
2,6-Diphenvl-4- (1- methyl- 247 C~6H2oCINO4Se 15,2 c 59,5 6,81 5,1 1640 s 1545 s 1420 s 70
8-indolyl)selena
2,6-Diphenyl-4-(p-dimethyL 253 C25H~CINO4Se 15,6c 58,3 G9i t5,4 !630 m t570 m [425 m 65
aminophenyl) selena

az = Br. bz = S. cz = Se. dThe characteristic frequencies were numbered in accordance with the Wilson
system.
p h e n y l - 3 - ( p - d i m e t h y l a m i n o p h e n y l ) c y c l o p r o p e n e . The l a t t e r can be c o n v e r t e d to a c y c l o p r o p e n y l i u m p e r -
c h l o r a t e by m e a n s of t r i p h e n y l m e t h y l p e r c h i o r a t e .

N(CH3)2 l!
~ {cnp~

ff
/s(c~p~

+ _
~.(cN~)2

"~
9 6 5 6 5 6 5 6 5 6 5 6 5,-
clo; no7

D i p h e n y l c y c l o p r o p e n y l i u m p e r e h l o r a t e r e a c t s with 1 - m e t h y l i n d o l e to give a m i x t u r e of indolyl-substituted

c y c l o p r o p e n y l i u m s a l t s and cyclopropene. The l a t t e r is c o n v e r t e d to the cation b y splitting out of a hydride
ion by the action of t r i t y l p e r c h l o r a t e . It is c l e a r that the splitting out of a hydride ion f r o m the i n t e r m e -
diate indolylcyclopropene in the c y c l o p r o p e n y ! a t i o n of indole is r e a l i z e d by e x c e s s s t a r t i n g diphenylcyclo-
p r o p e n y l i u m ion b e c a u s e of the g r e a t e r e l e c t r o n - d o n o r c h a r a c t e r of indole as c o m p a r e d with d i m e t h y l a n i -
line. At the s a m e t i m e , a l m o s t c o m p l e t e t r o p y l a t i o n of indole o c c u r s in the r e a c t i o n of t r i p y l i u m p e r c h l o -
r a t e with 1-methylindole. This indicates the g r e a t e r electrophilic c h a r a c t e r of the t r o p y l i u m cation as
c o m p a r e d with the c y c l o p r o p e n y l i u m cation. Thus, the e l e c t r o p h i l i c i t y d e c r e a s e s in the following o r d e r :
h e t e r o a r o m a t i c cations (pyrylium, t h i a p y r y l i u m , and s e l e n a p y r y l i u m salts), t r o p y l i u m cation, and c y c l o p r o -
penylium cation.
1 , 2 - D i p h e n y l - 3 - ( 1 - m e t h y l - 3 - i n d o l y l ) c y c l o p r o p e n y l i u m p e r c h l o r a t e is a l s o obtained by r e a c t i o n of di-
phenylcyclopropenone with 1 - m e t h y l i n d o l e in the p r e s e n c e of POCI~.
The intense bands at 1600-1630 and 1400-1500 c m -1 and e t h e r bands (according to [6]) in the IR s p e c -
t r a of h e t e r o a r o m a t i c cations c o n f i r m the s t r u c t u r e of the h e t e r o c y c l e s (Table 1). The indolyl- and p - d i -
m e t h y l a m i n o p h e n y l c y c l o p r o p e n y l i u m p e r c h l o r a t e s a r e c h a r a c t e r i z e d by IR bands at 3130-3145 and 1410-
1430 c m -I (according to [7, 8]). A n u m b e r of bands at 1610, 1515, 1450, and 1100 e m - I c o n f i r m the p r e s -
ence of a r o m a t i c and indole substituents and the CIO~ anion. A c o m p a r i s o n of the IR s p e c t r a of unsubsti-
tuted [9] and indolyl-substituted t r o p y l i u m cations m a k e s it p o s s i b l e to isolate the m o s t c h a r a c t e r i s t i c
bands p e c u l i a r to t h e s e compounds (650, 980, 1040, 1500, and 3900 cm-1). In c o n t r a s t to the unsubstituted
t r o p y l i u m ion, the l a s t two bands show up weakly in the s p e c t r u m of the indolyl-substituted tropyliurn
perchlorate.

EXPERIMENTAL
The IR s p e c t r a of K B r pellets of the compounds w e r e r e c o r d e d with a UR-20 s p e c t r o m e t e r . The py-
r y l i u m s a l t s w e r e obtained by the methods in [10, 11], while the diphenylcyclopropenylium and t r o p y l i u m
p e r c h l o r a t e s w e r e obtained by the methods in [12, 13], r e s p e c t i v e l y .
P y r y l a t i o n of A r o m a t i c and H e t e r o c y c l i c Compounds by 2 , 6 - D i s u b s t i t u t e d P y r y l i u m Salts. A m i x t u r e
of 0.01 m o l e of the p y r y l i u m s a l t and 0.075 mole of dimethylaniline o r 1-methylindole in 10-15 m l of d r y
d i m e t h y l f o r m a m i d e (DMFA) was refluxed f o r 3 0 min. It was then cooled, and the p r e c i p i t a t e d c r y s t a l s w e r e
s e p a r a t e d , washed with ether, d r i e d , and r e c r y s t a l l i z e d f r o m acetic acid o r n i t r o m e t h a n e (see Table 1).
1 , 2 - D i p h e n y l - 3 - ( p - d i m e t h y l a m i n o p h e n y l ) c y c l o p r o p e n y l i u m P e r c h l o r a t e . A m i x t u r e of 2.9 g" (0.01
mole) of diphenylcyclopropenylium p e r c h l o r a t e and 1.2 g (0.01 mole) of dimethylaniline in 15 m l of a c e t o n i -
t r i l e w a s refluxed f o r 30 rain. E t h e r (100 ml) was added, and the m i x t u r e was allowed to stand overnight.
The p r e c i p i t a t e d c r y s t a l s w e r e s e p a r a t e d , washed with ether, and d r i e d to give 3.0 g (73%) of a product
with m p 180 ~ ( n i t r o m e t h a n e - e t h y l acetate). Found, %: 66.9; H 5.4; C1 8.4; N 3.3. C23H22CINO4. Calculated,
%: C 67.1; H 5.3; C1 8.6; N 3.4.
1 , 2 - D i p h e n y l - 3 - ( p - d i m e t h y l a m i n o p h e n y l ) c y c l o p r o p e n e . The c y e l o p r o p e n y l i u m p e r c h l o r a t e obtained
a b o v e was t r e a t e d in alcohol with a s m a l l amount of a m m o n i a , ' a f t e r which the m i x t u r e was diluted with
w a t e r , and the final product was isolated. The yield of product with mp 115 ~ (from alcohol) was quantitative.
Found, %: C 88.6; H 6.8; N 4.4. C23H21N. Calculated, %: C 88.7; H 6.7; N 4.5.
1 , 2 - D i p h e n y l - 3 - (p-dimethylaminophenyl) c y c l o p r o p e n y l i u m P e r c h l o r a t e . A m i x t u r e of 0.62 g (0.002
mole) of 1 , 2 - d i p h e n y l - 3 - ( p - d i m e t h y l a m i n o p h e n y l ) c y c l o p r o p e n e and 0.68 g (0.002 mole) of t r i b y l p e r c h l o r a t e
in 7 m l of g l a c i a l acetic acid was r e f l u x e d f o r 15 rain, a f t e r which it was cooled, and the r e s u l t i n g c r y s t a l s
w e r e s e p a r a t e d , washed with e t h e r , and d r i e d to give 0.61 g (74%) of a product with m p 265 ~ (from n i t r o -
methane). Found, %: C 67.1; H 4.9; C1 8.5; N 3.3. C23H2~CINO4. Calculated, %: C 67.4; H 4.9; C1 8.6; N 3.4.

1021
 1,2-Diphenyl-3- (1-methyl-3- indolyl) cyclopropenylium Perchlorate. A solution of 0.58 g (0.002 mole)
of diphenylcyclopropenylium perchlorate and 0:13 g (0.001 mole) of 1-methylindole in 10 ml of dry acetoni-
trile was refluxed for 30 rain, af t e r which it was diluted with 30 ml of ether, and the resulting crystals were
separated, washed with ether, and dried to give 0.22 g (52%) of product. 1,2-Diphenyl-3-(1-methyl-3-in-
dolyl)cyclopropene with mp 57 ~ (from hexane) was isolated from the filtrate. Found, %: C 89.5; H 6.1;
N 4.2. C24H19N. Calculated, %: C 89.7; H 5.9; N 4.4. The latter was converted in the usual way with trityl
perchlorate to an indolyl-substituted cyclopropenylium perchlorate in 20% yield of product with mp 239 ~
(nitromethane-ether) was 72%. Found, %: C 68.5; H 4.5; C18.2. C24HlsC1NO4. Calculated, %: C 68.6;
H 4.3; C18.5.
1-Methyl-3-indolyltropylium Perchlorate. This compound was similarly obtained by cyclopropenyla-
tion from 1-methylindole and tropylium perchlorate. When ether was added, the final product with mp 224-
225 ~ (nitromethane-ether) was isolated in 93% yield. Found, %: C 60.4; H 5.0; C111.0; N 4.5. C16H14C104.
Calculated, %: C 60.1; H 4.4; C111.1; N 4.4.

LITERATURE CITED
1. A . T . Balaban, W. Sehroth, and G. Fischer, Advances in Heterocyclic Chemistry, 10,241 (1969).
2. S.V. Krivun, Dokl. Akad. Nauk SSSR, 180, 615 (1968).
3. S.V. Krivun, G. N. Dorofeenko, and A. S. Kovalevskii, Khim. Geterotsikl. Soedin., 733 (1970).
4. S.V. Krivun, Khim. Geterotsikl. Soedin., 14 (1971).
5. B. Fiihlisch and P. Btirgle, Ann., 701, 58 (1967).
6. A . T . Balaban, J. Mateescu, and M. Ellian, Tetrahedron, 1__88,1083 (1962).
7. D. Farnum and M. Burr, J. Amer. Chem. Soc., 82, 2651 (1960).
8. R. Breslov, J. Amer. Chem. Soc., 8_4; 3168 (1962).
9. W . E . Doering and J. H. Knox, J. Amer. Chem. Soc., 7_~6,3203 (1954).
10. V . V . Mezheritskii and G. N. Dorofeenko, Khim. Geterotsikl. Soedin., No. 2,232 (1970).
11. G . I . Zhungietu and G. V. Lazur'evskii, Zh. Vsesoyuzn. Khim. Obshchestva, 1_3, 597 (1968).
12. R. Breslov, J. Lockhart, and H. Chang, J. Amer. Chem. Soc., 8__33,2375 (1961).
13. D . N . Kursanov and M. E. Vol'pin, Dokl. Akad. Nauk SSSR, 113, 339 (1957).

1022
ALKYLATION AND SOME PHYSICOCHEMICAL
CHARACTERISTICS OF 6,7- AND 7,8-
DIHYDROXYC OUMARINS

V. A. Zagorevskii, Z. D. Kirsanova, UDC 547.814.1 : 542.953 : 543.422.25.4

I, V. Persianova, and D. A, Zykov

The lower s e l e c t i v i t y of the m e t h y l a t i o n of 4 - m e t h y l - 7 , 8 - d i h y d r o x y c o u m a r i n as c o m p a r e d

with the m e t h y l a t i o n of 6 , 7 - d i h y d r o x y c o u m a r i n s is explained by m e a n s of the pK a values
and data f r o m the PMR and IR s p e c t r a by the slight difference in the acidity of the hydroxyl
g r o u p s in the 7- and 8-positions.

The alkylation of eseuletin, i.e., 6 , 7 - d i h y d r o x y c o u m a r m (Ia), and 4 - m e t h y l - 6 , 7 - d i h y d r o x y c o u m a r i n

(Ha) p r o c e e d s p r i m a r i l y at the oxygen a t o m in the 7- o r 6-position, depending on whether 1 o r 2 m o l e s of
alkali, r e s p e c t i v e l y , is used {1, 2]. This is explained by the fact that m a i n l y the monophenoxide ion is
f o r m e d under the infiuence of 1 mole of alkali due to the m o r e acidic hydroxyt g r o u p in the 7-position; how-
e v e r , ff t h e r e is sufficient alkali for c o n v e r s i o n of both hydroxyl g r o u p s to anions, the m o r e basic (and in
this c a s e m o r e nucleophilic) anion in the 6-position is p r i m a r i l y alkylated.
We have c a r r i e d out the m e t h y l a t i o n of 4 - m e t h y l - 7 , 8 - d i h y d r o x y c o u m a r i n {4-methyldaphnetin) (Ilia)
with dimethyl sulfate and the m e t h y l a t i o n of Ia, Ha, and lIIa with diazomethane.
To f a c i l i t a t e the identification of the products of m e t h y l a t i o n of IIIa, we synthesized its 7- and 8-
m o n o m e t h y l e t h e r s (IIIb, c, r e s p e c t i v e l y ) . Compound IIIb was obtained by a known method [3]. The synthe-
sis of IIIc was a c c o m p l i s h e d by a new method, inasmuch as the methods d e s c r i b e d in the l i t e r a t u r e a r e
e i t h e r too c o m p l e x o r lead to one of the i s o m e r i c e t h e r s of insufficiently definite s t r u c t u r e [4, 5]. We ob-
tained IIIc f r o m the a c c e s s i b l e 4 - m e t h y l - 7 - h y d r o x y - 8 - a c e t y l c o u m a r i n [6] (IV) via the following s c h e m e :
CP~3 Clf~ H~~
C~HsCH2C[ / ~ I. NaOH,H2(J2
I10 O K2CO3 C~HsCH~.O 0 "2. HCI -
C6HsCH.,O- --~ ~ ,.u
COCH~ COCH3 OH
IV V V!
CH~ CHa
[CH~)~SO4
K;CO3
C6HsCH20 "HO O
OCH3 OCH3 ~-
Yl! !11 I

The i n t e r m e d i a t e s W-VII) have not been d e s c r i b e d in the l i t e r a t u r e . Substance IIIe differs f r o m IIYa with
r e s p e c t to its IR s p e c t r u m , pK a value, and c h r o m a t o g r a p h y on p a p e r and Sflufol.
The r e s u l t s of the m e t h y i a t i o n of HIa in the p r e s e n c e of i mole of NaOH p r o v e d to be s o m e w h a t unex-
pected: a m i x t u r e of a p p r o x i m a t e l y equal amounts of i s o m e r i c e t h e r s IIib, c (in yields of 9.1 and 13.1%,
r e s p e c t i v e l y , t o g e t h e r with 7.9% IIId) was f o r m e d . The yields of e t h e r s IIIb, c (7.1 and 13.8%) a l s o differed
only slightly in the p r e s e n c e of 2 m o l e s of NaOH, and it was e v e n m o r e difficult to evaluate the r e l a t i v e r e -

Institute of P h a r m a c o l o g y , A c a d e m y of Medical Sciences of the USSR, Moscow. T r a n s l a t e d f r o m

K h i m i y a G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 9, pp. 1178-1184, S e p t e m b e r , 1974. Original a r t i c l e sub-
m i t t e d N o v e m b e r 27, 1973.

9 Plenum Publishing Corporation, 227 West 17th Street, New York, N_ Y. t O0l I. No part o f thi~ publication may be reproduced,
stored in a retrieval a3atem, or transmitted, in any form oY by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without w~itten permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

1023
 TABLE 1. pK a Values and Data f r o m the IR Spectra of
Hydroxycoumarins
Corn- pKa in IR spectra
pound 70% alcoho~ recording conditions ~OH" C 1TI'I 'vc~ o, ClTI"1

Xab 9,22 C
VIlIa~ 9,35 CHCI3 ,c=10 -3M,d=lcm 3600, narrow
XIa" 10,40
IXa 10,56 CHCI3, c=lO-3M, d=l cm 3602, narrow 1723
Ia 8,60
IIa 8,76
tc 8.96
Iie 8,90 CCI4, c~lO-4M, d=5 cm 3550,narrow 11733,inflect.1752
Ib 10,40
lib 10,57 CCI4, c=lO-4Md, d=5 crn 3570,narrow 1742and1731, doublet
with equally in-
t ealse c o m -
XIIab 9,00
Ilia 9.15 CHCI3, c=lO SM, d : l am [3552.
broad;shoulder " [17p~
r
at3615 [
IIIc 8,99 CCla, c=10-4~ded=5 CI"n 3518, narrow i 17~4
lllb 10,02 CC14, c=lO-4M.,d=5em [3565 11749

aThe standard e r r o r in the determination was no m o r e than 0.06

pK a units in all c a s e s .
bCompounds Xa, XIa, and XIIa a r e , r e s p e c t i v e l y , 7 - h y d r o x y - , 6-
hydroxy-, and 7 , 8 - d i h y d r o x y c o u m a r i n s .
CIn CC14 solution (c 10 -4 M, d = 5 em), vOH 3600 c m -1.
dWhen c = 10 -3 M, the indicated f r e q u e n c i e s do not change.
e w h e n c = 10 -3 M, the f r e q u e n c i e s a r e 3560 and 1748 c m -1,
respectively.

a c t i v i t i e s of the 7- and 8-phenoxide ions in this c a s e in view of the fact that a considerable portion of the
starting m a t e r i a l is converted to the diether (21.6%), and it is not known which m o n o e t h e r is its p r e c u r s o r ,

R'r R~
I

OR
I,II a-d II[ a-d
I R"=H; II,III R ' = C H a ; | - I I | a R = R ' = H ; b R = H , R'=CH3; c R=CH3,
R'=H; d R=R'=CH 3

The r e s u l t s of the methylation of Ia and IIa under the same conditions as those in the p r e p a r a t i o n of
IIIa (the yields of the r e a c t i o n products in all of these e x p e r i m e n t s were determined by means of the PMR
spectra) a r e in a g r e e m e n t with e a r l i e r data obtained when t h e r e a c t i o n products w e r e analyzed by paper
c h r o m a t o g r a p h y [1, 2]. Thus, the following compounds (yields in percent given) a r e f o r m e d in the m e t h y l a -
tion of Ia and IIa with 1 mole o f alkali: ]b 40.2, Ic 4.6, I d 5.4, I]b 20.6, Hc 2.6, and IId 2.4. When 2 m o l e s
o f a l k a l i a r e used, the following compounds a r e f o r m e d (yields in p e r c e n t given): Ib 6.6, Ic 36.3, Id 13.2,
]2b 6.2, IIc 31.2, and lid 13. M o r e o v e r e t h e e r r o r s i n t h e d e t e r m i n a t i o n a r e such that they do not affect the
conclusions r e g a r d i n g the p r i m a r y direction of alkylation (see the e x p e r i m e n t a l section).
In o r d e r to attempt to explain the indicated behavior of IIIa in alkylation reactions we determined the
ionization constants of IIIa and its i s o m e r i c e t h e r s IIib and IIIc and c o m p a r e d them with the ionization con-
stants of Ia and IIa and t h e i r m o n o e t h e r s (Table 1). An examination of the PKa values makes it possible to
conclude that the 7 - h y d r o x y derivatives with a methoxy g r o u p in the 6- o r 8-position a r e s t r o n g e r acids
than the 6 - h y d r o x y - o r 8-hydroxy derivatives with a 7-CH30 group. This c o r r e s p o n d s to the difference in
the acidity between 7- and 6 - m o n o h y d r o x y c o u m a r i n s , and the experimentally found pK a values of o-dLhy-
d r o x y c o u m a r i n s , consequently, a r e related to the 7-OH group. The second ionization constant is not d e t e r -
mined by p o t e n t i o m e t r y in an aqueous alcohol medium; as in p y r o c a t e c h o l [7], it possibly c o r r e s p o n d s to
pK a -> 12. The 4 - m e t h y l - s u b s t i t u t e d compounds have higher n u m e r i c a l pK a values than the c o r r e s p o n d i n g
4-unsubstituted h y d r o x y c o u m a r i n s : on the a v e r a g e , the difference in the pK a values of the c o r r e s p o n d i n g
h y d r o x y derivatives is 0.15. Compound llIb is a s t r o n g e r acid than IIb, which may be explained by the elec-

1024
t r o n - a c c e p t o r effect of the r i n g - e s t e r group. The introduction of CH30 o r HO groups into the 6- (or 8-)
position of 4 - m e t h y l - 7 - h y d r o x y c o u m a r i n (VIIIa) intensitifes the acidity of the hydroxyl group in the 7 - p o s i -
tion, and the effect of the 6-OH group in the esculetin s e r i e s is s t r o n g e r than the effect of the 6-OCH 3 group,
but the r e v e r s e tendency exists in the dephnetin s e r i e s : the pK a of IIIa is 9.15, while the pK a of Ilic is
8.99. It is true that the e r r o r s in the m e a s u r e m e n t s m a y level out this small yet appreciable difference. It
m a y be a s s u m e d that the CI-I30 g r o u p in 8-methoxy derivative IIIc is partially r e m o v e d f r o m conjugation
with the benzene ring as a consequence of s t e r i c hindrance (which is o b s e r v e d in m o l e c u l a r models). How-
ever, the p r e s e n c e of a CH30 group in the 7-position of the 4 - m e t h y l - 6 - h y d r o x y c o u m a r i n (Ha) molecule
does not change the pK a value. In the benzene s e r i e s , the introduction of a methoxy group into the ortho
position relative to the phenolic OH group also does not change the pK a value, but the p r e s e n c e of an ortho
hydroxyl group i n c r e a s e s the acidity. One m a y t h e r e f o r e , with a c e r t a i n degree of caution, a s s u m e that
4 - m e t h y l - 8 - h y d r o x y c o u m a r i n , the ionization constant of which has not been determined (because of the low
a c c e s s i b i l i t y of this substance o r its 4-unsubstituted homolog), is close in acidity to liIb (pK a ~ 10). Thus,
the l e s s - e x p r e s s e d selectivity of the alkylation of Ilia as c o m p a r e d with Ia and IIa in the p r e s e n c e of 1 o r 2
m o l e s of alkali should be explained by the s m a l l e r differences in the acidities of the hydroxyl groups in the
7- and 8-positions. This is also in a g r e e m e n t with the r e s u l t s of methylation by diazomethane: the yields
of Ilib and liIc a r e 8.7 and 6.5%, r e s p e c t i v e l y (IIId 1.5%), while Ic and IIc a r e not f o r m e d at all under these
conditions, and the yields of Ib and lib a r e 10.8 and 12%, r e s p e c t i v e l y (Ib 3.4% and lid 2.4%).

As in the case of p y r o c a t e c h o l monoether [8, 9], the p r e s e n c e of i n t r a m o l e c u l a r hydrogen bonding was

o b s e r v e d in a study of the IR s p e c t r a (in CHCI3 and CCI~) of monoether derivatives of II and IIL The intra-
m o l e c u l a r hydrogen bond in m o n o e t h e r s IIb, c and IIib,c is c h a r a c t e r i z e d by an e n e r g y that c o r r e s p o n d s to a
band shift of 30-80 c m -1 in CC14 o r CHC13 solutions if it is supposed that the free hydroxyl groups of the
m o n o e t h e r s should have a p p r o x i m a t e l y the same stretching vibration frequencies, i.e., ~3600 cm -1, as
m o n o h y d r o x y c o u m a r i n s (for example, Villa and IXa).
The hydrogen bond in 7-hydroxy derivatives IIc and IIIc is s t r o n g e r than in 6 (8)-hydroxy derivatives
IIb and liIb, inasmuch as lic and IIIc a r e r e l a t i v e l y s t r o n g e r acids, and the oxygen atoms of the CH30 groups
in IIc and IIIc b e a r r e l a t i v e l y higher e l e c t r o n densities than in IIb and IIIb. The hydrogen bond is s t r o n g e r
in liic than in lic; this m a y be a s s o c i a t e d with the high e l e c t r o n density on the oxygen atom of the methoxy
g r o u p of liIc, confirming our assumption of r e m o v a l of this group f r o m conjugation with the benzene ring.
The f r e q u e n c y of the OH group in 8-hydroxy derivative Ilib is somewhat lower than in 6 - h y d r o x y derivative
lib, and this c o r r e s p o n d s to the higher acidity of IIIb. However, it is difficult to sufficiently a c c u r a t e l y
e s t i m a t e the relative e l e c t r o n densities on the c a r b o n a t o m s in the CH30 groups of lib and IIib. On the
b a s i s of indirect data, namely, f r o m the pK a values of 7 - h y d r o x y derivatives IIc and liIc, it can be stated
that t h e r e should notbe a substantial difference in the e l e c t r o n - d o n o r c h a r a c t e r of the oxygen atoms of these
g r o u p s with r e s p e c t to the proton. It follows f r o m q u a n t u m - c h e m i c a l calculations* by the simple Hiiekel
method with Pullman p a r a m e t e r s [10], without introduction of an auxiliary inductive p a r a m e t e r , that the
residual c h a r g e on the oxygen atoms of the 6-OH and 7-OH groups of Ia is 1.9319 and 1.9222, respectively,
as c o m p a r e d with 1.9105 and 1.8987 for 6,7-dimethoxycoumarin, 1.9320 and 1.8986 for Ib, and 1.9104 and
1.9224, r e s p e c t i v e l y , f o r Ic. All of these values a r e in a g r e e m e n t with the ionization constants and the IR
s p e c t r a in the region of the stretching vibrations of OH groups. However, in the 7 , 8 - d i h y d r o x y e o u m a r i n
s e r i e s the q u a n t u m - c h e m i c a l calculations by the indicated method frequently do not c o r r e s p o n d to these
e x p e r i m e n t a l data, apparently mainly because the inductive effect of the h e t e r o a t o m s and the stei'ic f a c t o r s
w e r e not taken into account in the calculations. We note that the oxygen atom of the heteroring, as was
a s s u m e d f o r 7 , 8 - d i h y d r o x y - o r 7 - m e t h o x y - S - h y d r o x y c h r o m o n e s [11], r a t h e r than that of the CHuG group
m a y participate in the f o r m a t i o n of an i n t r a m o l e c u l a r hydrogen bond in Ilib. The test with FeCI 3 s e r v e s as
a confirmation of the fact that in compounds of the Ilia, b type t h e r e is a possibility f o r coordination of the
proton of the 8-OH group with the h e t e r o c y c l i c O atom. In concentrated alcohol solutions, 7 - e t h e r IIIb gives
a g r e e n c o l o r a t i o n with FeC13. In c o n t r a s t to this, esculetin m o n o e t h e r s of the Ib, c and IIb, c type do not
give a c o l o r r e a c t i o n with FeC13.

The i n t r a m o l e c u l a r hydrogen bonds in m o n o e t h e r s IIb, c and [lib, e and also in Ilia and VliIa-IXa a r e
disrupted in t e t r a h y d r o f u r a n (THF) solution, and the stretching vibrations of the OH groups in the IR s p e c -
t r a (c 0.1 M) a p p e a r as b r o a d bands at 3200-3230 cm -1 f o r lib, c; iIIb, e; Ilia; and VIIIa; and at 3263 c m -I
f o r IXa. The i n t r a m o l e c u l a r hydrogen bonds of compounds of the indicated type a r e evidently completely
disrupted in aqueous and alcohol solutions and t h e r e f o r e do not affect the ionization constants under these

* The calculations w e r e made by M. E. P e r e l ' s o n , to whom the authors e x p r s s their gratitude.

1025
conditions. As in THF, p r i m a r i l y i n t e r m o l e c u l a r hydrogen bonds a r e f o r m e d in the c r y s t a l l i n e state. F o r
example, the IR s p e c t r a of Ic, Ha, Ilia, IIIb, IXa, and VliIa a r e c h a r a c t e r i z e d by b r o a d POH bands at 3333,
3280, 3100-3450, 3200-3445 (and 3550), 3330, and 3150 c m -1, r e s p e c t i v e l y . Of the s p e c t r a l c h a r a c t e r i s t i c s
of m o n o e t h e r s II and HI we also note the higher values of the f r e q u e n c i e s of the stretching v i b r a t i o n s of the
C = O group in the III s e r i e s as c o m p a r e d with li.

EXPERIMENTAL*
L e n i n g r a d ,,slow" p a p e r i m p r e g n a t e d with 0.1 M sodium b o r a t e solution was used f o r p a p e r c h r o m a -
t o g r a p h y by the method in [12]; the s y s t e m f o r ascending c h r o m a t o g r a p h y was butanol s a t u r a t e d with w a t e r ,
and the c h r o m a t o g r a m s w e r e developed with UV light. Genuine individual s u b s t a n c e s o r t h e i r a r t i f i c i a l
m i x t u r e s w e r e used in all c a s e s f o r monitoring.
The yields of r e a c t i o n products w e r e d e t e r m i n e d f r o m the PMR s p e c t r a with a V a r i a n T - 6 0 s p e c -
trometer. A genuine s a m p l e of N ~ m e t h y l - N - p h e n y l b e n z e n e s u l f o n a m i d e with m p 78.5-79.5 ~ s e r v e d a s the
reference compound. The CH30 groups w e r e identified by the addition of genuine s a m p l e s of the e t h e r s in
m o d e l and working e x p e r i m e n t s .
The acid d i s s o c i a t i o n c o n s t a n t s w e r e d e t e r m i n e d p o t e n t i o m e t r i e a l l y in 70% ethanol (by volume). The
solution c o n c e n t r a t i o n s f o r t i t r a t i o n w e r e 1 9 10 -3 M, and the pH values w e r e m e a s u r e d with a PHM-26
pH-meter.
Methylation of 4 - M e t h y l - 7 , 8 - d i h y d r o x y c o u m a r i n (IIIa). A) A total of 1.89 g (15 mmole) of dimethyl
sulfate was added in t h r e e portions in the c o u r s e of 3 h with s t i r r i n g at 0 ~ to a solution of 0.96 g (5 mmole)
of liIa and 0.6 g (15 m m o l e ) of NaOH in 8 m l of w a t e r , a~d the m i x t u r e vms s t i r r e d f o r another hour and
f i l t e r e d to give 0.35 g of the known diether. (IIId) with mp 131.5-133 ~ [9]. The alkaline f i l t r a t e was acidified
to give 0.43 g of a p r e c i p i t a t e containing (according to p a p e r c h r o m a t o g r a p h y ) liIc with R f 0.47, liIa (at the
s t a r t ) , and t r a c e s of IIId with Rf 0.91. The p r e c i p i t a t e was t r e a t e d with 50 ml of hot toluene, and the
toluene e x t r a c t was cooled and filtered. The f i l t r a t e was e v a p o r a t e d to o n e - t h i r d of its original volume
and allowed to stand to give 0.1 g (10%) of IIIc with mp 156-157.5 ~ containing t r a c e s of Ilia (no m o r e than
0.5%). The Ilic obtained in this m a n n e r was identical to a genuine s a m p l e .
B) A 0.96-g s a m p l e of IIIa was m e t h y l a t e d by m e a n s of dimethyl sulfate in acetone containing K2CO3 by
the method in [10]. The c r u d e product, which, a c c o r d i n g to p a p e r c h r o m a t o g r a p h y , contained both m o n o -
e t h e r s , a diether, and the s t a r t i n g substance, was t r e a t e d with 5% NaOH, and the m i x t u r e was f i l t e r e d to
give 0.22 g of Ilid. The alkaline f i l t r a t e was acidified to give 0.45 g of a p r e c i p i t a t e , which was t r e a t e d
with toluene a s d e s c r i b e d a b o v e to give 5% of 1Ili) with rap 155-156.5 ~ containing t r a c e s of IIIc and IIt~; IIIb
d e p r e s s e d the melting point of a genuine s a m p l e of IIIe and was identical to a genuine s a m p l e of IIIb ob-
tained by the method in [9].
C) A 1.89-g (15 mmole) s a m p l e of dimethyl sulfate was added to a solution of 2.88 g (15 mmole) of
IIIa and 0.6 g (15 mmole) of NaOH in 180 m l of alcohol, and the m i x t u r e was s t i r r e d at 20 ~ for 5 h and
allowed to stand f o r ~ 16 h. It w a s then acidified (with r e s p e c t to Congo red) with HC1, and the liquid w a s
r e m o v e d c o m p l e t e l y by v a c u u m distillation. The d r y r e s i d u e was t r e a t e d with 10 m l of w a t e r , and the m i x -
t u r e was allowed to stand at 4 ~ f o r ~ 2 0 h. The resulting p r e c i p i t a t e was r e m o v e d by filtration, washed
with 5 m l of w a t e r , and v a c u u m d r i e d o v e r P20~ to give 3.04 g of product (product A). The aqueous f i l t r a t e
was e x t r a c t e d with dichloroethane (five 1 0 - m l portions) and methylene chloride (five 1 0 - m l portions). The
c o m b i n e d organic solutions w e r e washed with w a t e r (two 1 0 - m l portions) and v a c u u m e v a p o r a t e d (near the
end with the addition of two 1 0 - m l portions of CC14). The r e s i d u e was v a c u u m dried o v e r P205 to give
0.30 g of product (product B, a s e m i e r y s t a l l i n e m a s s ; the m o n o e t h e r content in all of the e x p e r i m e n t s was
0.2-5.3%, while the d i e t h e r content was 2.4-7.1%). All of the aqueous solutions w e r e v a c u u m e v a p o r a t e d to
d r y n e s s , and the r e s i d u e was v a c u u m dried o v e r P205 and e x t r a c t e d with methylene chloride (three 3 0 - m l
portions) by refluxing each t i m e f o r 15 min. C a r b o n t e t r a c h l o r i d e (two 5 - m l portions) was added, and the
solvents w e r e r e m o v e d c o m p l e t e l y by v a c u u m distillation (product C r e m a i n e d in the flask; the e t h e r s and
s t a r t i n g m a t e r i a l s w e r e a b s e n t in this and subsequent e x p e r i m e n t s ) .

* T h e a u t h o r s thank V. S. T r o R s k a y a f o r r e c o r d i n g the tK s p e c t r a .

1026
 T A B L E 2. R e s u l t s of M e t h y l a t i o n of D i h y d r o x y c o u m a r i n s
Reaction I Yields of ethers, a %
--i ........ !- ~0verall. . . . . . . . . ~1 . . . . . ~er-a-l-IF--T---1 ]overall
conditions Ib ~e Id yield, ,Ib nc I lld yield,]ulblIHelH1dlyield

ImoleNaOH, ! L
lm'o!e (CHa)2SO4, 40,2 : 4,6 5,4 50,2 20,6 2,62,4 25,6 9,l :13,1 7.91 30.1
alcohol 20~ N 2!0h i
L I
2moleNaOH, I.
k
1mole (CHa)~SO~. 6,6 36.3 13,2: 56,1 6,2 31,2 .13,0 50,4 7,1 13,8 21,6i 42,5
alcohol20o, N 20 h
: 1
i

DMFA + ether 10,8 0b 3,4 14,2 12 0b 2,4 14,4 8,7 6,5 1 , 5 16,7

a T h e y i e l d s of e t h e r s in m i x t u r e s of A a n d C a r e p r e s e n t e d in
t h e e x p e r i m e n t s c a r r i e d out w i t h a l k a l i .
b T h i s c o m p o u n d a l s o w a s not d e t e c t e d by p a p e r c h r o m a t o g r a p h y .

PMR spectrum in pyridine-benzene (1:3),* 6, ppm: 1.9 (m, 4-CH3),~ 2.9 (s, CH3 reference), 3.5 (s,
OCH3 Hid), 3.6 (s, 7-OCH3 Illb), 3.75 (s, 8-OCHa llie), 3.8 (s, OCHa Hid). The yields of the ethers are given
in Table 2. Unchanged IIIa (56.4%) was recovered.
D) A 15-mmole sample of Illa was methylated in the presence of 30 mmole of NaOH as in the preced-
ing experiment. See Table 2 for the yields of ethers. Unchanged lila (35.6%) was recovered.
E) An ether solution of diazomethane (13.2 mmole) was added at +3 ~ to a solution of 0.84 g (4.4
mmole) of IHa in 4 ml of DMFA, and the mixture was held at 3~ for 30 rain and allowed to stand at 20~for
~16 h. It was then vacuum evaporated (near the end with two 10-ml portions of CC14), and the residue was
vacuum dried over P205 (see Table 2). Unchanged Ilia (65.3%) was recovered.
Methylation of 4-Methyl-6,7-dihydroxycoumarin (Ila). A) A 15-mmole sample of Ha was methylated
with dimethyl sulfate in alcohol in the presence of 15 mmole of NaOH in analogy with Ilia. PMR spectrum
of solution i [pyridine-benzene (1:2)], 6, ppm: 3.6 (s, 6-OCH3 Ilc and IId), 3.45 (s, 7-OCH3 llb and lld).
The assignment was made by means of 4-methyl-6-methoxy-7-trideuteromethoxycoumarinobtained by
methylation by means of CDal of a genuine sample of IIc in CDaOD solution. Pyridine (I ml) and 0.6 ml of
C~H5SO2CI were added to i ml of a pyridine solution of products A and C, and the mixture was heated at
60-80 ~ for 4 h (solution 2). PMR spectrum of solution 2, 6, ppm: 3.9 (unresolved OCH3 signals lid), 3.65
(unresolved OCH3 signals of benzene sulfonates Ilb and IIc), 3.2 (s, CH3 reference), and 2.2-2.4 (In, 4-CH3).
The yield of Ild was determined by analysis of solution 2, while the yields of lib and IIc were determined by
analysis of solution 1 (Table 2). Unchanged Ha (74.3%) was recovered.
B) A 15-mmole sample of Ilia was methylated in the presence of 30 mmole of NaOH in analogy with
Ilia (Table 2). Unchanged Ila (34.9%) was recovered.
C) A 4.4-mmole sample of IIa was methylated with diazometh~ne as in the case of Ilia (Table 2).
Unchanged IIa (77.0%) was recovered.
Methylation of 6,7-Dihydroxycoumarin (In). A) A 15-mmole sample of Ia was methylated in the p r e s -
ence of 15 mmole of NaOH in analogy with Ilia (Table 2).
B) A 15-mmole sample of la was methyiated in the presence of 30 mmole of NaOH in analogy with
Ilia (Table 2).
C) A 4.4-mmole sample of Ia was methylated with diazomethane as in the case of IIIa (Table 2).

Because of the systematic e r r o r in the integration, the reproducibility of the measurements was
~ 2 % . T h e e r r o r i n the d e t e r m i n a t i o n of the y i e l d s of t h e e t h e r s w i t h r e s p e c t to the l e a s t i n t e n s e PMR
s i g n a l w a s - 20% a s c o m p a r e d w i t h ~ 3 % f o r the m o s t i n t e n s e s i g n a l . In e x p e r i m e n t s i n v o l v i n g the m e t h y l -
a t i o n of Ha w i t h 1 a n d 2 m o l e s of NaOH, t h r e e c o n t r o l a n a l y s e s e a c h of g e n u i n e m i x t u r e s of the a p p r o p r i a t e
c o m p o s i t i o n w e r e m a d e . T h e a v e r a g e d e v i a t i o n i n the d e t e r m i n a t i o n s in the s t a n d a r d m i x t u r e s w e r e a s

* O t h e r s o l v e n t s a r e l e s s s u i t a b l e b e c a u s e of the low s o l u b i l i t i e s of t h e i n v e s t i g a t e d s u b s t a n c e s in t h e m ,
a n d in p y r i d i n e a l o n e the p r o t o n s of a l l of the CH30 g r o u p s g i v e a n u n r e s o l v e d s i g n a l a t 4 ppm.
t T h e following a b b r e v i a t i o n s a r e u s e d h e r e a n d s u b s e q u e n t l y : s is s i n g l e t , d is doublet, t is t r i p l e t , q is
q u a r t e t , a n d m is m u l t i p l e t .

1027
follows (in percent): f o r ilb - 0 . 8 and - 1 . 4 , f o r IIc +23 and +10, and f o r IId - 3 4 and - 2 7 ) . An additional
a n a l y s i s w a s a l s o m a d e in the d e t e r m i n a t i o n of IId in control e x p e r i m e n t s with 1 and 2 m o l e s of NaOH. F o r
2 . 2 a n d 5.9% I I d , IIa w a s t a k e n in a m o u n t s c o r r e s p o n d i n g to the p e r c e n t a g e s of m o n o e t h e r s and IIa in the
control m i x t u r e . The deviations in the d e t e r m i n a t i o n s w e r e as follows (in p e r c e n t ) : - 1 6 . 7 and - 6 . 6 in the
a n a l y s i s of the m i x t u r e in pyridine and - 5 3 . 4 and - 1 6 . 3 , r e s p e c t i v e l y , a f t e r benzenesulfonation (the a v e -
r a g e deviation of ~30% in the d e t e r m i n a t i o n of IId is, consequently, a s y s t e m a t i c e r r o r and it can be t a k e n
into account).
4 - M e t h y l - 7 - b e n z y l o x y - 8 - a c e t y l c o u m a r i n (V). A m i x t u r e of 7.64 g (35 mmole) of pure 4 - m e t h y l - 7 - h y -
d o r x y - 8 - a c e t y l c o u m a r i n (IV) [6] with m p 168-169 ~ 8.9 g (70 mmole) of benzyl chloride, and 12.09 g (88
mmole) of anhydrous K2CO3 in absolute a c e t o n e was r e f l u x e d f o r 40 h. The acetone was r e m o v e d by d i s -
tillation, 10% NaOH was added to the residue, and the alkaline m i x t u r e was e x t r a c t e d with dichloroethane.
The organic l a y e r was e v a p o r a t e d , and the r e s i d u e was t r e a t e d with p e t r o l e u m e t h e r and e t h e r to give 5.8 g
(54%~ a c c o r d i n g to c h r o m a t o g r a p h i c data, the product did not contain impurities) of V with mp 140-141 ~
(from alcohol). Found, %: C 73.9; H 5.4. C19HI~O4. Calculated, %: C 74.0; H 5.2.
4 - M e t h y l - 7 - b e n z y l o x y - 8 - h y d r o x y c o u m a r i n (VI). A 1.39-g s a m p l e of c o u m a r i n V was oxidized by the
Dakin method [3], and the r e a c t i o n m i x t u r e was acidified with h y d r o c h l o r i c acid and e x t r a c t e d with d i c h l o r o -
ethane. The organic l a y e r was e v a p o r a t e d p a r t i a l l y , e t h e r was added to the residue, and 0.82 g (64.6%) of
VI with m p 183-184 ~ (from alcohol) was r e m o v e d by filtration. Found, %: C 72.4; H 5.0. Cl~H1404. C a l -
culated, %: C 72.3; H 5.0.
4 - M e t h y l - 7 - b e n z y l o x y - 8 - m e t h o x y c o u m a r i n (VII). A 1.13-g s a m p l e of c o u m a r i n VI was m e t h y l a t e d
with dimethyl sulfate in the p r e s e n c e of K2CO3 in absolute acetone by refluxing the m i x t u r e f o r 7 h. The
solvent was r e m o v e d by distillation, 5% NaOH was added, and the m i x t u r e was e x t r a c t e d with c h l o r o f o r m .
The organic l a y e r was e v a p o r a t e d to give i.13 g (95%) of VII with mp 141-142 ~ (from alcohol). Found, %:
C 72.9; H 5.5. C18Ht~O4. Calculated, %: C 73.0; H 5.4.
4 - M e t h y l - 7 - h y d r o x y - 8 - m e t h o x y c o u m a r i n (Illc). A 0.89-g s a m p l e of VII was debenzylated in alcohol
o v e r P d / B a S O 4 to give 0.58 g (94%) of IIIc with mp 162-163 ~ (the product was t r e a t e d with e t h e r and then
r e c r y s t a l l i z e d f r o m benzene); a m i x t u r e of the product with i s o m e r IIIb (mp 160 ~ had m p 120-122 ~ C h r o -
m a t o g r a p h y of IIIc on p a p e r g a v e a spot with R f 0.50 that f l u o r e s c e s in UV light. I s o m e r i c IIIb f o r m e d a
b r o w n spot with R / 0.40 that did not f l u o r e s c e . The R f values of IIIc and IIIb on Silufol w e r e 0.63 and 0.53
(ethyl acetate), 0.~0 and 0.37 [ethyl a c e t a t e - c h l o r o f o r m (1 : 1)], and 0.55 and 0.42 [ethyl a c e t a t e - c h l o r o f o r m
(2 : 1)], r e s p e c t i v e l y . According to the l i t e r a t u r e data, IIIc has mp 163 ~ [4] and IIIb has mp 160-161 ~ [3].

LITERATURE CITED
1. V . A . Z a g o r e v s k i i and Z. D. Sovzenko, Zh. Obshch. Khim., 34, 3987 (1964).
2. V . A . Z a g o r e v s k i i and Z. D. Sovzenko, Zh. Organ. Khim., t , 380 (1965).
3. V . K . Ahluwalia, V. N. Gupta, C. L. Rustagi, and T. R. Seshadri, J. Sei. Ind. R e s . (India), 19B, 345
(1960); Chem. A b s t r . , 55, 5478h (1961).
4. C. Antonello, Gazz. Chim. Ital., 88, 415 (1958):
5. R . D . D e s a i and J. V. Parghi, J. Indian Chem. Soc., 33, 661 (1956).
6. V . V . K o r s h a k and N. G. Matveeva, Izv. Akad. Nauk SSSR, Otd. Khim. Nauk, 547 (1953).
7. A. A l b e r t and E. Serjeant, Ionization Constants of Acids and B a s e s , Methuen (1962).
8. V . S . Korobkov, in: Hydrogen Bonding [in Russian], Nauka, Moscow (1964), p. 185.
9. M. Tichy, in:: Advances in Organic C h e m i s t r y : Methods and R e s u l t s (edited by A. A. R a p h a e l et al.),
W i l e y - I n t e r s c i e n c e (1966).
10. B. P u l l m a n and A. Pullman, Quantum B i o c h e m i s t r y , Wiley (1963).
11. I s h w a r - D a s s , N. N a r a s i m h a c h a r i , and T. R. Seshadri, P r o c . Indian Acad. Sci., 37A, 599 (1953).
12. R . D . D e s a i and J. V. P a r g h i , J. Indian Chem. Soc., 33, 661 (1956).

1028
COMPETITIVE METHYLATION OF SOME PHENOLIC
COMPOUNDS

Z . D. K i r s a n o v a , V. A. Zagorevskii, UDC 547.813.814 : 542.953 : 543.422.6

and D. A. Zykov

The c o m p e t i t i v e m e t h y l a t i o n of a m i x t u r e of 6 - h y d r o x y - 4 - m e t h y l c o u m a r i n and of 7 - h y d r o x y -
4 - m e t h y l e o u m a r i n and also of o t h e r compounds of phenolic nature has been studied. It had
ben shown that in the p r e s e n c e of 1 m o l e of alkali, m e t h y l a t i o n of the m o r e acidic hydroxyl
t a k e s place at the oxygen atom, and with 2 m o l e s of alkali, the s t r o n g e r conjugated b a s e
reacts.

In a preceding c o m m u n i c a t i o n we r e p o r t e d a study of the s e l e c t i v e alkylation of d i h y d r o x y c o u m a r i n s

in which the c o n v e r s i o n of o n e - the m o r e acidic - hydroxy g r o u p into the conjugate b a s e e x e r t s a con-
s i d e r a b l e influence on the acidity of the o t h e r hydroxyl. In the c h e m i s t r y of phenolic compounds, including
the flavonoids, the n e c e s s i t y not only for the s e l e c t i v e alkylation of hydroxy groups interacting strongly o r
f e e b l y with one another, but also f o r the p e r f o r m a n c e of s e l e c t i v e i n t e r m o l e c u l a r alkylation frequently
arises.
We have p e r f o r m e d the methylation with dimethyl sulfate of a m i x t u r e of 6 - h y d r o x y - 4 - m e t h y l c o u m a -
r i n (Ia) and 7 - h y d r o x y - 4 - m e t h y l c o u m a r i n (IIa) in the p r e s e n c e of 1 and 2 m o l e s of NaOH. As can be s e e n
f r o m T a b l e 1, in the second c a s e the 6 - e t h e r (lb), and in the f i r s t c a s e the 7 - e t h e r (IIb), is f o r m e d p r e -
dominantly, i.e., in g e n e r a l the s a m e situation is o b s e r v e d as in the alkylation of 6 , 7 - d i h y d r o x y c o u m a r i n s .
However, the s e l e c t i v e c o m p e t i t i v e alkylation of m o n o h y d r o x y d e r i v a t i v e s is l e s s well defined. This can be
explained by the s m a l l e r difference in acidities [1] between the two OH groups in compounds (In) and (IIa).
In fact, pK a (In) - PKa (Ha) = 1 0 . 5 6 - 9.35 = 1.21, and pK a [6-OH in 6 , 7 - d i h y d r o x y - 4 - m e t h y l c o u m a r i n
(IHa)] - pK a [7-OH in (IIIa)]= 12 - 8.76 = 3.24, the l a t t e r difference actually being even g r e a t e r , since the
second ionization constant of (IIIa) c o r r e s p o n d s to PKa >- 12. In the c a s e of phenol (IVa) and p - n i t r o p h e n o l
(Va) [their methyl e t h e r s being (IVb) and (Vb), r e s p e c t i v e l y ] , f o r which ApK a = 2.83, the s e l e c t i v i t y of
m e t h y l a t i o n in the p r e s e n c e of NaOH proved to be higher (see T a b l e 1). The r e p l a c e m e n t of NaOH did not
lead to qualitatively different r e s u l t s .
It is g e n e r a l l y c o n s i d e r e d [2, 3] that compounds of the type of 2 - a c y l p h e n o l s , such as 2 - h y d r o x y -
benzaldehyde o r 2 - h y d r o x y a c e t o p h e n o n e (Via), a r e c o n s i d e r a b l y m o r e difficult to alkylate than the c o r r e s -
ponding p a r a i s o m e r s (VIIa), since in o r t h o - s u b s t i t u t e d compounds the hydroxyl takes p a r t in the f o r m a t i o n
of a strong i n t r a m o l e c u l a r hydrogen bond. This bond is not b r o k e n even under the influence of such s o l -
vents as w a t e r and alcohols, as follows i m m e d i a t e l y f r o m the values of the ionization constants of t h e s e
a c y l p h e n o l s , w h i c h w e r e d e t e r m i n e d in aqueous solutions [for example, according to handbook l i t e r a t u r e
the pK a values f o r (Via) and (VIIa) a r e 11.86 and 8.05, r e s p e c t i v e l y ] . * Such ideas have also been extended
to the c a s e of the 1 - a c y l - 2 , 4 - d i h y d r o x y b e n z e n e s , including compounds of the type of the 5 , 7 - d i h y d r o x y -
c h r o m o n e s : it is g e n e r a l l y a s s u m e d that a p a r a hydroxyl a l k y l a t e s m o r e easily than an ortho hydroxyl.
However, no sufficiently c l e a r delimitation has been made between the r e a c t i o n s of alkylation in alkaline

*We m a y note that the c h e m i c a l shift (12.3 ppm) of the proton of the hydroxy group in ( V i a ) s c a r c e l y
c h a n g e s w i t h a v a r i a t i o n in the c o n c e n t r a t i o n of the solutions in methanol f r o m 4.0 to 0.4 M.

Institute of P h a r m a c o l o g y , A c a d e m y of Medical Sciences of the USSR, Moscow. T r a n s l a t e d f r o m

K h i m i y a G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 9, pp. 1185-1188, S e p t e m b e r , 1974. Original a r t i c l e sub-
mitted N o v e m b e r 27, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

1029
 TABLE 1. Results of the Competitive Methylation of Mixtures of
Monohydroxy derivatives

Mixture of 1 g_-ion
. . . . . .
of HO-
.......................
' '
A _ .......
2 _g .-ions of HO-
...............
- Base yield of ethers, %
substances
-----
~total~--~ . . . . re~tive %............ tot al* relative r

Ia+lla NaOH 90 [ 18,5b; 81,5lib 98 70 Ib; 30 IIb

IVa+Va ]NaOH 76 ! 0 IVo; 100Vb 67 88,2IVb; 11,8Vb
1Va+Va !LiOH 77 i 26 IVb; 74Vb 97 85 IVb;15 Vb
Vla+Vlla ~NaOH 74 9VIb; 91 Vllb 95 51 Vlb;49 VIIb
VIa+VIIa i (CH3),NOH 82 ; ]6VIb; 84Vllb 90 58 VIb;42 Vllb

* In all c a s e s , the total yields a r e given on the m i x t u r e s of crude

e t h e r s , calculated to 1 mole of phenol.
t The relative yields w e r e determined by means of GLC.

log~ media and methylation with diazomethane. There is no

3,'~176
doubt that an ortho hydroxyl participating in a chelate hy-
4,2 drogen bond should r e a c t with diazomethane m o r e slowly
2; ~-...
r : "%: than a para hydroxy group. When, however, the r e a c t i o n
.~176
3,8 was p e r f o r m e d with a c e t y l - 2 , 4 - d i h y d r o x y b e n z e n e s in an

3,4
',:: alkaline medium, only alkylation in the p r e s e n c e of a weak
base o r of 1 mole of alkali was considered. Thus, r e c e n t l y
3,2 %
t" a method has been proposed f o r the selective methyaltion
of the 4-OH group in 2,4-dihydroxybenzophenone based on
2~8
the p e r f o r m a n c e of alkylation in a weakly alkaline m e d i -
I um (pH 7.4-7.8) [4].
2,6
z,4 However, the question is justified as to what the
\
2,2 % relative r e a c t i v i t i e s of the o- and p - a c y l h y d r o x y b e n z e n e s
. . . . . . . . . . . s will be when they a r e p r e s e n t c o m p l e t e l y in the f o r m of
ZOO 220 240 260 280 300 320 340 360 380 400 ,~20 lilY]
the conjugate b a s e s . It is natural to a s s u m e that the dif-
Fig. 1. UV s p e c t r a (e 1 9 10-4-1 9 10 -5 m): ference in t h e i r ionization constants in itself should not
1) (Via) (in ethanol), k m a x 2 5 2 , 3 2 6 nm (log affect the relative r a t e s of alkylation, s i n c e as a result of
3.98, 3.55); 2) (Via) in (59% ethanol + 100 the t r a n s f o r m a t i o n of these phenols into phenoxides the
m o l e s of NaOH), k m a x 230-232, 360-365 nm i n t r a m o l e c u l a r hydrogen bond in the ortho i s o m e r s c e a s e s
(log e 4.22, 3.81); 3) (Via) [in 59% ethanol + to exist. Consequently, the reactivity of the o - and p - p h e n -
100 m o l e s of (CH3)aNOH], Xmax 224-228, oxide ions with r e s p e c t to an alkylating agent should d e -
360-365 nm (log ~ 4.38, 3.88). pend on the c o r r e s p o n d i n g nucleophilicity of these anions.
It is true that, according to a widespread opinion [5], the
Na salts of 2 - a c e t y l h y d r o x y b e n z e n e s have the chelate type of s t r u c t u r e through the coordination of the m e t -
al with the carbonyl oxygen. But, a c c o r d i n g to our r e s u l t s , the UV s p e c t r a of the sodium and t e t r a m e t h y l -
a m m o n i u m salts of (Via) in 59% ethanol a r e identical (see Fig. 1, which, f o r c o m p a r i s o n , also gives the
s p e c t r u m of o-hydroxyacetophenone in a neutral medium}, which is evidence against the specific role of
sodium in the phenoxide of o-hydroxyacetophenone. Since the phenoxides of the alkali m e t a l s (Li, Na, K,
Cs) in etlmnolic solutions a r e p r e s e n t in the ionized state in the f o r m of separated ion p a i r s [6],* it must
be c o n s i d e r e d that the sodium and a m m o n i u m phenoxides of (Via) in aqueous ethanol also exist as separated
ion p a i r s .
By the competitive methylation of the sodium and t e t r a m e t h y l a m m o n i n m phenoxides of (Via) and
(VIIa) it was shown that the nucleophilicities of these two anions a r e a p p r o x i m a t e l y the s a m e (see Table 1).
If, however, 1 mole of alkali was used f o r a mixture of the two phenols in an amount of i mole each, the
phenoxide f o r m e d f r o m the m o r e acidic p - i s o m e r is alkylated predominantly. The same conclusions can
obviously be used in estimating the direction of the alkylation of the compounds of the type of the a c y l - 2 , 4 -
dihydroxybenzenes, including c h r o m o n e s with hydroxy g r o u p s in positions 3, 5, and 7.

* The UV s p e c t r a f o r phenoxides in ethanol and DMFA a r e different: in the f i r s t c a s e there a r e s e p a r a t e d

ion p a i r s , and the phenoxide ion is a s s o c i a t e d with solvent m o l e c u l e s , and in the second case, u n s e p a r a t e d
ions p a i r s predominate [6].

1030
 EXPERIMENTAL
GLC was performed on a Kbrom-2 instrument. Chromosorbs G, 60/80 mesh, and W, 80/60 mesh,
were used as supports, and the stationary phases were poly(tetramethylene suceinate) and silicone polymer.
The retention times of the second substances with respect to the first were: (Ib, lib) (1.08; 200~ (IVb, Vb)
(2.16; 165~ (Vib, VI!b) (1.36; 185~ The error in the determination amounted to ~0.5-2%.
Methylation of a Mixture of 6-Hydroxy- and 7-Hydroxy-4-methylcoumarins (In and Ha). a) With
stirring, a solution containing 0.44 g (2.5 mmole) each of (In) and (lie) in 6 ml of DMSO was added to a solu-
tion of 0.i g (2.5 mmole) of NaOH in 1.5 ml of water, and the mixture was cooled to 0~ and then with
stirring 0.33 g (2.6 mmole) of dimethyl sulfate was added dropwise, and the resulting mixture was stirred
at 0~ for 6 h and was left at 0~ for ~16 h. After this, 10% NaOH was added, and the product was ex-
tracted with dichloroethane, giving 0.43 g of a mixture of (ib) and (IIb) (see Table I).
b) A mixture of 2.5 mmole each of (Ia) and (lie) was methylated with 2.6 mmole of dimethyl sulfate
in the presence of 5 mmole of NaOH as described above. This gave 0.47 g of a mixture of (Ib) and (lib).
Methylation of a Mixture of Phenol (IVa) and p-Nitrophenol (va). a) With stirring, a solution of 0.94 g
(0.01 mole) of (IVa) and 1.38 g (0.01 mole) of (va) in 12 ml of DMSO and then (at 20~ 1.39 g (0.011 mole) of
dimethyl sulfate were added to a solution of 0.4 g (0.01 mole) of NaOH in 3 ml of water, and the mixture
was stirred for 6 h. After the addition of 10% NaOH, it was extracted with petroleum ether (bp -< 50~ or
diethyl ether. The organic layer was washed with water and dried, and the solvent was distilled off in a
rotating flask without the application of vacuum, giving 1.16 g of (Vb).
b) A mixture of 0.01 mole each of (IVa) and (Va) was methylated with 0.011 mole of dimethyl sulfate
in the presence of 0.02 mole of NaOH as described above. This gave 0.75 g of a mixture of (IVb) and (Vb),
c) With stirring, a solution of 0.94 g (0.01 mole) of (IVa} and 1.38 g (0.01 mole) of (Va) in 24 ml of
DMSO and then (at 20~ 1.39 g (0.011 mole) of dimethyl sulfate were added to a solution of LiOH formed
by the addition of 0.07 g (0.01 g-atom) of lithium to 6 ml of water. After 75 h (20~ 2 N KOH was added,
and extraction with ether yielded 1.07 g of a mixture of IVb and Vb.

d) A mixture of 0.01 mole of IVa and Va was methylated with 0.011 mole of dimethyl sulfate in the
presence of 0.02 mole of LiOH as described above, yielding I.i g of a mixture of IVa and Va.

Methylation of a Mixture of o- and p-Hydroxyacetophenones (Via) and (VIIa). a) With stirring, a solu-
tion of 0.34 g (2.5 mmole) each of (Via) and (vIIa) in i0 ml of DMSO, followed by 0.34 g (2.7 mmole) of di-
methyl sulfate, was added to a solution of 0.i g (2.5 mmole) of NaOH in 10 ml of water, and the mixture
was stirred for 1 h and was left for ~16 h (20~ after which NaOH was added and the products were ex-
tracted with ether, giving 0.28 g of a mixture of (vIb) and (vIIb).
b) A mixture of 2.5 mmole each of (Via) and (VIIa) was methylated with 2.7 mmole of dimethyl sul-
fate in the presence of 5 mmole of NaOH as described above, giving 0.36 g of a mixture of (VIb) and (VIib).
c) To 2.5 ml of aqueous solution of tetramethylammoninm hydroxide (2.5 mmole) were added 7.5 ml
of water and a solution of 0.34 g (2.5 nunole) each of (Via) and (Vile) in 10 ml of DMSO and 0.34 g (2.7
mrnole) of dimethyl sulfate, and the reaction mixture was stirred for 1 h and left for ~16 h (20~ after
which 0.31 g of a mixture of (VIb) and (VIIb) was isolated as in the preceding experiment.
d) A mixture of 2.5 mmole each of (Via) and (VIIa) was methylated with 2.7 mmole of dimethyl sul-
fate in the presence of 5 ml of the same base (5 mmole) with the addition of 5 ml of water as described
above. This gave 0.34 g of a mixture of (VIb) and (VIib).

LITERATURE CITED
i. V.A. Zagorevskii, Z. D. Kirsanova, I. V. Persianova, and D. A. Zykov, Khim. Geterotsikl. Soedin.,
1178 (1974).
2. G. Wagner and M. B~hrn, Pharmazie, 17, 670 (1962).
3. H.D. Sadekov, V. I. Minkin~ and A. E. Lutskii, Usp. Khim., 39,380 (1970).
4. E. Boboli, J. Kamionska, and L. Malasnicki, Roczn. Chem., 42,243 (1968).
5. A.E. Chiehibiban,The Basic Principles of Organic Chemistry [in Russian], Vol. 2, GKHI, Moscow
(1958), p. 393.
6. H.E. Zaugg and A. D. Schaefer, J. Amer. Chem. Soc., 87, 1857 (1965).

1031
 STEREOCHEMISTRY OF HETEROCYCLES
XXXIII.* ANALYSIS OF THE IR SPECTRA OF STEREOISOMERIC
SUBSTITUTED 1,3-DIOXANES BY MEANS OF A COMPUTER

G . N. V o s t r o v , A. I. Gren', UDC 547.841 : 543.422.4 : 541.634

A. V. Bogat-skii, I. B. Gernega,
V. P. Teptya, and Yu. P. Adler

The p o s s i b i l i t y of the use of the method of c o r r e l a t i o n pleiads f o r the isolation of the a b -

s o r p t i o n r e g i o n s in the IR s p e c t r a of substituted 1 , 3 - d i o x a n s s in which the c h a r a c t e r i s t i c
a b s o r p t i o n bands f o r the individual s t e r e o i s o m e r s of the s u b s t a n c e s a p p e a r was studied.
It is shown that the configurations of the investigated compounds can be d e t e r m i n e d on
the b a s i s of the c h a r a c t e r i s t i c a b s o r p t i o n bands by instructing a c o m p u t e r to distinguish
forms.

The c h a r a c t e r i s t i c a b s o r p t i o n bands of the cis o r t r a n s i s o m e r s in the IR s p e c t r a of s t e r e o i s o m e r i c

substituted 1,3-dioxanes [2] a r e found at 600-700 c m -1. It has been found to be i m p o s s i b l e to find r e g u l a r
changes in the IR s p e c t r a of g e o m e t r i c a l i s o m e r s in the s h o r t w a v e region when the usual methods of s p e c -
t r a l a n a l y s i s a r e used.
The p r e s e n t c o m m u n i c a t i o n is devoted to a study of the p o s s i b i l i t y of the use of the t h e o r y of r e c o g -
nition of f o r m s by m e a n s of a c o m p u t e r f o r the a n a l y s i s of the IR s p e c t r a of cis and tr~ns i s o m e r s of sub-
stituted 1,3-dioxanes and f o r finding the m o s t i n f o r m a t i v e a b s o r p t i o n bands for the individual s t e r e o i s o m e r s .
We think that the m a t h e m a t i c a l a p p a r a t u s of this method m a y p r o v e to be useful in investigations of this s o r t .
The s e t of a b s o r p t i o n bands in the IR s p e c t r a of t h e s e compounds was used as the s t a r t i n g information
r e g a r d i n g the eis and t r a n s i s o m e r s of 2 , 5 - d i a l k y l - , 2 , 5 , 5 - t r i a l k y l - , 4 , 5 - d i a l k y l - , and 2 , 5 - d i a l k y l - 5 - a l k o x y -
a l k y l - l , 3 - d i o x a n e s , the configurations of which w e r e p r o v e d p r e v i o u s l y by PMR s p e c t r o s c o p y (for example,
s e e [3]}.
In the f i r s t step we evaluated the i n f o r m a t i v e c h a r a c t e r of the e l e m e n t s of this d e s c r i p t i o n in o r d e r
to s e l e c t the wave n u m b e r s containing the g r e a t e s t amount of i n f o r m a t i o n r e g a r d i n g the m o l e c u l a r con-
figuration. We s i m u l t a n e o u s l y investigated the c o r r e l a t i o n r e l a t i o n s h i p s between the m o s t informative a b -
s o r p t i o n bands. We used the method of c o r r e l a t i o n pleiads [4] to evaluate the c o r r e l a t i o n dependences b e -
tween the wave n u m b e r s and the g r o u p i n g s of the l a t t e r . This m a d e it p o s s i b l e to isolate groups of wave
n u m b e r s that a r e i n t i m a t e l y c o r r e l a t e d with one a n o t h e r o r a r e not c o r r e l a t e d by a r e close in value. The
e x i s t e n c e of groups of the f i r s t type can be explained by the f a c t that in the s e r i e s of substituted 1 , 3 - d i -
oxanes u n d e r c o n s i d e r a t i o n t h e s e bands have an identical tendency to undergo change a s a function of the
type of i s o m e r . The e x i s t e n c e of the second g r o u p follows f r o m the a s s u m p t i o n that the a b s o r p t i o n bands
of the individual e l e m e n t s of the s t r u c t u r e a r e shifted on passing f r o m one compound to another. In both
c a s e s , each such g r o u p of wave n u m b e r s can be r e p r e s e n t e d by one wave number.
The p r i m a r y i n f o r m a t i o n on the i n f o r m a t i v e c h a r a c t e r of the individual a b s o r p t i o n bands was r e p r e -
sented a s a m a t r i x with a b s o r p t i o n bands with spacings of 10-12 c m -1 c o r r e s p o n d i n g to its columns and in-

See [1] f o r c o m m u n i c a t i o n XXXII.

I. I. Mechnikov Odessa State University. Odessa Polytechnic Institute. T r a n s l a t e d f r o m Khimiya

G e t e r o t s i k l i c h e s k i k h Seedinenii, No. 9, pp. 1189-1195, S e p t e m b e r , 1974. Original a r t i c l e submitted Sep-
t e m b e r 24, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, meehanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15.00.

1032
dividual compounds c o r r e s p o n d i n g to its rows. The entire absorption region was thus broken down into 50
intervals. In this c a s e , all of the a b s o r p t i o n bands p r e s e n t in the s p e c t r u m f o r c o n c r e t e compounds were
r e c o r d e d in the c o r r e s p o n d i n g intervals, while the remaining intervals w e r e filled with z e r o s .
Let us now imagine that a c e r t a i n set of r a n d o m values x is fixed. We will isolate the m a x i m u m and
m i n i m u m values, and we will divide the interval between them into k parts. We next c o n s t r u c t k v e c t o r s
Yl = (Yn . . . . . YlN) and Yk = (3~kl. . . . . YkN), which c o r r e s p o n d to these intervals. F o r this, we will take x 1 as the
f i r s t component of that v e c t o r in the interval of which it lies, and~we will set the f i r s t components of the
remaining v e c t o r s equal to z e r o . We then deal with the remaining r a n d o m x values in the s a m e way.
We note that the c o r r e l a t i v e c h a r a c t e r of r a n d o m values Yt . . . . . Yk will be close to z e r o in the gen-
eral case.
An analysis of the m a t r i x of the c o r r e l a t i v e c h a r a c t e r of the absorption bands showed that p r e c i s e l y
the adjacent a b s o r p t i o n bands p r a c t i c a l l y do not c o r r e l a t e . This is not difficult to understand if one takes
into account the fact that a b s o r p t i o n bands of this s o r t a r e m o s t frequently a shifting of c e r t a i n vibrations
a s s o c i a t e d with the a p p e a r a n c e in the molecule of some new s t r u c t u r a l element. Hence, a r t i f i c i a l b r e a k -
down of the entire a b s o r p t i o n region into n a r r o w intervals m a y distort the picture. To eliminate this, we
used the method indicated above to isolate the a b s o r p t i o n regions c o r r e s p o n d i n g to the c o r r e l a t e d intervals,
which a r e also c o r r e l a t e d wave numbers.
The set of c o r r e l a t e d signs of the groups will give a simplified d e s c r i p t i o n of the objects under in-
vestigation, in this c a s e the cis and t r a n s i s o m e r s of 2,5-substituted 1,3-dioxanes, with minimal l o s s e s of
information.

To evaluate the informative c h a r a c t e r of the indexes (the wave numbers) of the i s o m e r s we use the
following e x p r e s s i o n s :

s(i>= ~=i
Ip,~l; R(/)= ~j=1p , j , i=(1 .... ,n) (I-)

where Pij is the coefficient of correlation between the i-th and j-th wave numbers, and n is the n u m b e r of
indices [4, 5]. Those w a v e numbers that are the form of the group with a high level of correlation in ab-
solute magnitude are isolated in the first expression as the most informative wave numbers. Indices, the
corresponding groups of which contain frequencies that are correlated in pairs primarily with positive
correlation coefficients, are preferred in the second expression. These groups are m o r e uniform from
the point of view of the character of the linear dependence between them. The S(i) and R(i) functions can
be considered to be a m e a s u r e of the informational value of the i-th wave numbers. The results of treat-
ment of the m a t r i x of the starting data and the S(i) and R(i) values a r e p r e s e n t e d in Table 1.

In c o n f o r m i t y with the algorithm f o r a r r a n g e m e n t of the indices in the o r d e r of d e c r e a s i n g i n f o r m a -

tive c h a r a c t e r , the index f o r which S(i) takes on the g r e a t e s t value is isolated first. The R m a t r i x was
then converted by using the e x p r e s s i o n of partial c o r r e l a t i o n [6] in o r d e r to eliminate the effect of the
isolated index on the preceding spacing. This operation was repeated until all of the indices had been
thoroughly a r r a n g e d . By virtue of the fact that the effect of the previously isolated indices is eliminated
in each spacing, the S(i) and R(i) functions a r e not monotonically d e c r e a s i n g functions.
It is apparent f r o m Table 1 that the a b s o r p t i o n bands at 470-480, 1380-1390, 1180-1190, 1260-1270,
570-580, and 660-670 c m -1 b e a r the g r e a t e s t information r e g a r d i n g the affiliation of the sample with the
cis o r t r a n s s e r i e s . The absorption bands at 1000-1170 c m -I, which, however, according to the data in [7],
a r e c h a r a c t e r i s t i c f o r the 1,3-dioxane ring, a r e of somewhat l e s s e r informational value. The e x p r e s s i o n
f o r the determination of R(i) isolates the a b s o r p t i o n bands at 1100-1110, 585-595, 1120-1130, 1150-1160,
and 1380-1390 cm -1 as the m o s t informative bands.

The methods of the t h e o r y of graphs, in p a r t i c u l a r , the a l g o r i t h m f o r the isolation of the m a x i m u m

full and empty subgraphs by means of a Minsk-32 computer, w e r e used to c o n s t r u c t the groups of wave
n u m b e r s [8]. A prelLminary analysis of the data in Table 2 indicates that the starting set of f r e q u e n c i e s
p r a c t i c a l l y does not contain groups of intimately c o r r e l a t e d indices.
Those indices for which Pi] - 0.5 w e r e c o n s i d e r d as intimately c o r r e l a t e d indices. This threshold
was selected a r b i t r a r i l y to a c o n s i d e r a b l e degree, inasmuch as the groups of indices for which Pij < 0.5
also can be used as informative groups, but the e r r o r in d i s c r i m i n a t i o n due to l o s s e s of information during

1033
 T A B L E 1. R e s u l t s of A r r a n g e m e n t of the A b s o r p t i o n B a n d s of the
IR S p e c t r a i n the O r d e r of D e c r e a s i n g I n f o r m a t i o n a l V a l u e f o r
2,5-Dialkyl-1,3-dioxanes
Frequency No. of s(o Frequency range No. of
range for 8(9 bands for R(9 bands n(0

470--479 i 50 20,56 1100--II10 6,8

660---670 40 11,42 585--595 5,2
540--550 45 10,94 I190---1200 4.13
1030--1040 26 tl,53 11.20--1130 2,97
1410-1420 4 11,28 489--490 2,68
850--840 36 10,48 1240--1250 1,89
11'20---1130 21 10,47 t140--1150 2,08
12Z5---1240 12 10,65 1470--1480 1,95
970--980 30 10,08 1380--1390 1,61
lllO--ll20 22 9,66 1t50--1160 1,74
1190--1200 15 10,01 1460--1470 1,66
640--660 41 9,96 95(I--960 1,28
500-.~520 48 1~09 660--67O 1,28
580--590 10,53 530--540 1,08
1140--1150 11,27 1260--1270 1,38
1390.---1400 12,08 1290--1310 1,15
570--580 13,99 780-750 0,8
1380--1390 15,55 1150--1170 0,91
1450--1460 12,46 919--920 0,98
1260--1270 14,49 1010~1020 0,66
1180--1190 16 14,82 550--570 0,58
1240--1250 11 13,07 520--530 0.51
1210--1220 13 12,20 1370--1380 0,55
1040--1050 25 3,55 699--700 0,44

T A B L E 2. G r o u p i n g of the A b s o r p t i o n B a n d s a s a F u n c t i o n of
the C o e f f i c i e n t of P a i r C o r r e l a t i o n b e t w e e n T h e m

Group No. Frequency groups

Intimately correlated
1385--t400, 1380--1385, 1370--1380
690--700, 670--680, 660--670, 640--660
Weakly correlated
1470--1480, 1450--1470, i450--1460, 1420--1440
1290--1310, 1260--1270
1250--1260, 1240--1250, 1220--I~40, 121C--1220
1200--1210, 1190--1200, i180--1190, 1170--1180
1160--1170, 1.150--1160, 1,140--1150, 1120--1130
Ii10--1120
6 1100--1140, 1060--1080, 1040--1050
7 t039--1040, 1020--1030
8 1010--1020, 990--1010, 970--980
9 960--970, 940--960, 910--930
10 860--880, 830--850, 730--830
ll 590--600, 570--599, 550 570
12 540--550, 530--540, 520--530
13 500~520, 480--500, 470--480

r e m o v a l of s o m e of the i n d i c e s f r o m the g r o u p is c o n s i d e r a b l y l a r g e r in t h i s c a s e (Table 3). We note that

t h e c o r r e l a t i o n m a t r i x w a s a l m o s t d e v o i d of s t r o n g l y c o r r e l a t e d i n d i c e s . T h i s c a n be e x p l a i n e d b y the f a c t
t h a t the c o r r e l a t i o n w a s m a d e b e t w e e n i n d i v i d u a l a b s o r p t i o n b a n d s of the c o r r e l a t e d wave n u m b e r r a t h e r
t h a n b e t w e e n the a b s o r p t i o n b a n d s due to a s t r i c t l y d e t e r m i n e d f o r m of v i b r a t i o n s of a n y s t r u c t u r a l e l e -
m e n t o r bond. T h e r i g o r o u s a s s i g n m e n t of the c o r r e l a t e d a b s o r p t i o n b a n d s in the IR s p e c t r a of the i n v e s -
t i g a t e d s u b s t a n c e s w o u l d n a t u r a l l y l e a d to b e t t e r r e s u l t s i n d i s c r i m i n a t i o n . H o w e v e r , t h i s s o r t of a s s i g n -
m e n t b y c a l c u l a t i o n of the v i b r a t i o n s is a s y e t d i f f i c u l t .

Two g r o u p s of i n t i m a t e l y c o r r e l a t e d i n d i c e s w e r e i s o l a t e d . T h e c o e f f i c i e n t of the c o r r e l a t i o n b e -
t w e e n e a c h p a i r of w a v e n u m b e r s is g r e a t e r o r e q u a l to 0.7 in the f i r s t g r o u p a n d g r e a t e r o r e q u a l to 0.5 i n
the s e c o n d . T h e c o r r e l a t e d i n d i c e s a s f u n c t i o n s of t h e i r e l e m e n t s c a n be b r o u g h t into l l n e w i t h e a c h of the
g r o u p s . F o r t h i s , one c a n , f o r e x a m p l e , u s e r e g r e s s i o n a n a l y s i s .

It is a p p a r e n t f r o m T a b l e 2 t h a t t h e r e a r e a c o n s i d e r a b l e n u m b e r of g r o u p s , the c o r r e l a t i o n w i t h i n
w h i c h is l e s s t h a n o r e q u a l to 0.2. T h i s is not d i f f i c u l t to u n d e r s t a n d if one t a k e s into a c c o u n t the fact t h a t

1034
 T A B L E 3. R e s u l t s of D i s c r i m i n a t i o n of the C o n f i g u r a t i o n s of S u b s t i t u t e d 1 , 3 - D i o x a n e s
Error in d i s c r i m i n a t i o n of t h e c o n f i g u r a t i o n of c o m p o u n d s f o r
v a r i o u s a l g o r i t h m s (in %)
2,4,5-trialkyl- a n d 2,5-dial-
Algorithms 2,4,5-trialkyl- 1,3-dioxanes koxyatkyl-l,3-dioxanes

complete set minimal set: complete set minimal set:

of f r e q u e n c i e s 15 f r e q u e n c i e s of f r e q u e n c i e s 15 f r e q u e n c i e s

M e t h o d of p o t e n t i a l f u n c t i o n s 16.3 17 25 30
Albega 23 31 10 20
Linear programming 33 40 40 50

T A B L E 4. A r r a n g e m e n t of t h e A b s o r p t i o n R e g i o n s in O r d e r of
Decreasing Informative Character
2,4,5-Trialkyl-l,3- 2,5-A lkoxyalkyl-l,3- !2,4,5-Trialkyl- and 2.5-dial-
dioxanes dioxanes ikyl-5- alkoxyalkyl-l,3-dioxane
No. of w ave number No. of wave number No. of ~ave number
bands region bands region bands region
]
47 510--520 48 53'3--510 42 600~20
46 520--549 45 54'0--560 1410--1420
40 650--670 4'2 600--620 14 1290--1210
29 990--1010 ~, 630--640 5'50--560
5O 470--480 1,14,0--1150 690--700
31 96O--970 40 650--670 36 830--840
5 1390--[400 14 1190--1200 32 940--950
48 500--510 37 800--820 19 i150--1160
3O 680--690 32 940--950 17 l!60--1170
42 60-0--620 7 1360--1370 11 t240--I556

d e f o r m a t i o n v i b r a t i o n s of m e t h y l a n d m e t h y l e n e g r o u p s a p p e a r a t 1370-1400 c m -1, w h i l e t h e d i f f e r e n c e s b e -
t w e e n t h e i s o m e r s r e d u c e to a c h a n g e in t h e o r i e n t a t i o n of one of t h e s u b s t i t u e n t s in the 5 - p o s i t i o n of t h e
1,3-dioxane ring.
T h e a b s o r p t i o n a t 4 0 0 - 7 0 0 c m -1 is due to t h e s k e l e t a l v i b r a t i o n s , w h i c h a r e a p p a r e n t l y a l s o s e n s i t i v e
to a c h a n g e in t h e t h r e e - d i m e n s i o n a l s t r u c t u r e of the m o l e c u l e . T h e l a t t e r is d i r e c t l y a s s o c i a t e d w i t h t h e
a x i a l o r e q u a t o r i a l o r i e n t a t i o n of t h e a l k y l g r o u p in t h e 1 , 3 - d i o x a n e r i n g . T h e w a v e n u m b e r s of t h e a b s o r p -
t i o n b a n d s in t h e o t h e r r e g i o n s of t h e IR s p e c t r a a r e w e a k l y c o r r e l a t e d {Table 2). It is c h a r a c t e r i s t i c t h a t
a l l of t h e a b s o r p t i o n b a n d s a t 1000-1200 c m - l , i . e . , the " f i n g e r p r i n t r e g i o n , " w h i c h is not s u i t a b l e enough
for the identification of organic substances, are related to them. In addition, the absorption bands observed
in this region of the IR spectra are, according to the data in [2, 7], characteristic for 1,3-dioxane systems
and are less subject to the effect or are not additive to the effect of a change in the vibrational coordinates
of other atoms or groups of atoms of the molecules.
The above reasoning is also in good agreement with the data of the quantitative algorithm for mini-
mization of the descriptions. In this variant for the selection of the most informative wave numbers, the
informative character of the wave numbers is evaluated by means of the following expression:
PI f>2

~ (2)
w h e r e ~i is the s t a n d a r d d e v i a t i o n of t h e w a v e n u m b e r f r o m t h e a v e r a g e v a l u e in b o t h c l a s s e s , i.e., in t h e
i s o m e r s , s i m u l t a n e o u s l y o-il a n d o-i2 a r e t h e s t a n d a r d d e v i a t i o n s of the w a v e n u m b e r s f r o m t h e a v e r a g e in
t h e c i s a n d t r a n s i s o m e r s , r e s p e c t i v e l y , a n d P1 a n d 1)2 a r e the p r o b a b i l i t i e s of t h e c l a s s e s . In t h i s c a s e ,
w e h a v e a s s u m e d t h a t P1 = 1)2 = 0.5. T h e i n f o r m a t i v e c h a r a c t e r of t h e g r o u p s of w a v e n u m b e r s c a n a l s o
be evaluated from the following expression:
k P2
P1

1035
where I R], I R1], and I R2] are the determinants Of the m a t r i c e s of c o r r e l a t i o n of the wave numbers of the
cis and t r a n s i s o m e r s in the entire set of compounds and for each c l a s s s e p a r a t e l y . The informative c h a r a c -
t e r of the wave n u m b e r was calculated in each spacing of the operation of the algorittu~a f r o m formula (2),
and that wave n u m b e r for which I ~ i ) r e a c h e s a m a x i m u m was selected. Its effect was eliminated by means
of a partial c o r r e l a t i o n by the method d e s c r i b e d in [6], and the next wave number was selected in the s a m e
m a n n e r in the set of remaining wave numbers. This operation was c a r r i e d out until all of the elements of
the description w e r e completely a r r a n g e d . The r e s u l t s of the t r e a t m e n t of the blocks of starting informa-
tion a r e presented in Table 4. As seen f r o m this table, the a b s o r p t i o n bands at 570-670, 820-860, 960-980,
1100-1200, and 12 80-1380 cm -1 a r e informative in the sense of the configurational a s s i g n m e n t of the in-
vestigated compounds to the cis or t r a n s s e r i e s . One is easily convinced that the set of wave n u m b e r s p r e -
sented here, which a r e the most informative, a r e in s a t i s f a c t o r y a g r e e m e n t with the data in Table 1. How-
ever, this method gives too b r o a d intervals of wave numbers (100 c m -1) in which one should seek the s p e c -
t r a l indices of the individual s t e r e o i s o m e r s . In this connection, it is less suitable in this f o r m for the solu-
tion of the problem at band. In addition, the application of the quantitative algorithm of minimization of the
description to the analysis of the IR s p e c t r a of s t e r e o i s o m e r i c 4,5-substituted 1,3-dioxanes [9] gives n a r -
r o w e r absorption regions (see Table 4). This s a m e r e s u l t was obtained by joint analysis of the IR s p e c t r a
of 2,5- and 4,5-substituted 1,3-dioxanes.

Having at our disposal data on the most informative c h a r a c t e r of the individual absorption bands in
the IR s p e c t r a of cis and t r a n s - s u b s t i t u t e d 1,3-dioxanes, we set out to a s c e r t a i n the possibility of the r e c -
ognition of cis and t r a n s i s o m e r s by means of a c o m p u t e r [10]. F o r this, we had to select a certain algo-
r i t h m from the r e l a t i v e l y large n u m b e r of a l g o r i t h m s that a r e used in the recognition of f o r m s by means
of a computer. Considering the fact that t h e r e a r e no s t r i c t l y defined r e c o m m e n d a t i o n s with r e s p e c t to the
use of one o r another a l g o r i t h m f o r the solution of a c o n c r e t e problem, especially for the solution of our
problem, we selected the method of potential functions [11], "Albega" [10], and linear p r o g r a m m i n g [12].
E a c h of these a l g o r i t h m s is c h a r a c t e r i z e d by a c e r t a i n m e a s u r e of allowance for the topology of the sets.
The instructional sequence consisted of 22 2,5-substituted 1,3-dioxanes, while the examining s e -
quence consisted of 10 such 1,3-dioxanes. The instruction was a c c o m p l i s h e d both with the complete set
and with the set of the m o s t informative wave numbers obtained as a r e s u l t of minimization. The r e s u l t s
of an analysis of the examining sequence a r e presented in Table 3. It is apparent f r o m Table 3 that the
e r r o r in recognition of the configurations of the s t e r e o i s o m e r i c substituted 1,3-dioxanes depends on the
a l g o r i t h m used. The use of the "Albega" algorithm gives the best r e s u l t s for the v a r i o u s substituted 1,3-
dioxanes. This can be explained by the fact that it is p r e c i s e l y this a l g o r i t h m that best takes into account
the topology of the sets of cis and t r a n s i s o m e r s .

The r e s u l t s of the examination indicate that the highest a c c u r a c y in the configurational a s s i g n m e n t of

the individual s t e r e o i s o m e r s to the cis o r t r a n s s e r i e s by means of a computer is achieved when the c o m -
plete set of a b s o r p t i o n bands is used a s the starting data. The e r r o r in recognition in this c a s e ranges
f r o m 10 to 30%. As seen f r o m Table 3, the recognition of the s t e r e o i s o m e r s only with r e s p e c t to 15 of the
most informative wave numbers gives p o o r e r r e s u l t s . At f i r s t glance, this c o n t r a d i c t s the a b o v e - s t a t e d
concepts regarding the set of the m o s t informative bands, but this is r e a l l y not so. In fact, first, a c o m -
plete analysis of a s p e c t r u m is always m o r e informative than an analysis of its parts; second, the m o s t in-
f o r m a t i v e bands a r e nonequivalent with r e s p e c t to t h e i r own s p e c t r u m (reduction of the n u m b e r of them m a y
give b e t t e r results); third, the deviations in the c o u r s e of the examination with r e s p e c t to all of the bands
and with r e s p e c t to the most informative bands a r e small within the limits of the possibilities of this m e t h -
od. The fact that the indicated bands a r e the m o s t informative ones does not r a i s e any doubts and is addi-
tionally c o n f i r m e d by the fact that the inclusion in the examination sequence of wave n u m b e r s o b s e r v e d in a
m i x t u r e of i s o m e r s leads to the a s s i g n m e n t by the c o m p u t e r of s u b s t a n c e s s i m u l t a n e o u s l y to both c l a s s e s
(i.e., to the cis and t r a n s s e r i e s simultaneously), as should be expected.

LITERATURE CITED
i. A.V. Bogat-skii, Yu. Yu. Samitov, S. A. Petrash, A. L Gren', M. Bartok, and G. Bozoki-Bartok, Zh.
Organ. Khim. (1974, in press).
2. A.I. Gren', in: Problems in Stereochemistry [in Russian], Vol. 2, Izd. Kievskogo Univ. (1972), p. 76.
3. A.V. Bogat-skii, A. I. Gren,, Yu. Yu. Samitov, L. M. Krinitskaya, L. N. Vostrova, V. N. Somchin-
skaya, V. P. Mamontov, and T. I. Davidenko, Khim. Geterotsikl. Soedin., 582 (1971).
4. N.V. Terent'ev, Vestn. LGU, No. 9, 137 (1959).

1036
 5. G . N . Vostrov,and Yu. V. Rublev, in: Scientific-Technical Information [in Russian], Series 2, No. 4,
Izd. VINITI (1973), p. 8.
6. G. K r a m e r , Methods of Mathematical Statistics [Russian translation], Nauka, Moscow (1948), p. 310.
7. K. Ledwoch, Z. Anal. Chem., 197, 323 (1962).
8. A . A . Zykov, Theory of Finite Graphs [in Russian], Novosibirsk (1969).
9. A . V . Bogat-skii, Yu. Yu. Samitov, A. I. Gren', and S. G. Soboleva, Khim. Geterotsikl. Soedin., 893
(1971).
i0. G.N. Vostrov, I. B. Gernega, M. L. Varlamov, and G. A. Manakin, in: Methods and Systems for the
Treatment of Experimental Information [in Russian], Kiev (1972), p. 31
11. M.A. Aizerman, ]~. M. Braverman, and L. L Rozono6r, Methods of Potential Functions in the Theory
of Computer Instruction [in Russian], Nauka, Moscow (1970).
12. Yu. V. Devingtal', Izv. Akado Nauk SSSR, Ser. Tekhn. Kibernetika, No. 1, 162 (1968).

1037
RESEARCH IN T H E CHEMISTRY OF PHENOXAZINES
IX.* PREPARATION OF AMINO DERIVATIVES OF 7-HYDROXY-3-
PHE NOXAZ INONE

T . S. V i k t o r o v a , G. B. Afanas'eva, UDC 547.867.6.7

I. Ya. Postovskii, and L. V. Ivanova

Reaction of 7 - a c e t o x y - o r 7 - e t h o x y - 3 - p h e n o x a z i n o n e with a m i n e s gave 2- and 7 - a m i n o d e -

r i v a t i v e s of 3-phenoxazinone.

Amino d e r i v a t i v e s of phenoxazines have d i v e r s e kinds of physiological activity [2, 3]. B e c a u s e of the

a b s e n c e of a p r a c t i c a b l e method of p r e p a r a t i o n in this direction, amino d e r i v a t i v e s of 3-phenoxazinone have
not b e e n studied.
It has b e e n shown that 7 - h y d r o x y - 3 - p h e n o x a z i n o n e {resorufin) (D undergoes a smooth nucleophilic
substitution r e a c t i o n with thiophenols to give 2 , 8 - d i ( a r y l t h i o ) d e r i v a t i v e s [4]. A s i m i l a r r e a c t i o n of I with
a m i n e s might have been expected. However, by v i r t u e of its a p p r e c i a b l e acidity {PKa 6.85}, r e s o r u f i n r e -
a c t s with a m i n e s to give only salts, which a r e r e a d i l y d e c o m p o s e d during r e c r y s t a l l i z a t i o n . In the c a s e of
a s t r o n g e r a c i d - 2 , 4 , 6 , 8 - t e t r a b r o m o r e s o r ' u f i n (IV) [5] (pK a 2.16} - s a l t s can be isolated in p u r e f o r m .
Thus, IV r e a c t s with m o r p h o l i n e to give b r i g h t - g r e e n salt V, the e l e c t r o n i c s p e c t r u m of an alcohol solution
of which contains the m a x i m u m of the anion of 2 , 4 , 6 , 8 - t e t r a b r o m o r e s o r u f i n (Xma x 608 nm).
Amino d e r i v a t i v e s of r e s o r u f i n w e r e obtained f r o m 7 - a c e t o x y - (II) [5] and 7 - e t h o x y - 3 - p h e n o x a z i n o n e
(HI} [6] with subsequent r e m o v a l of the p r o t e c t i v e group.
Compound II r e a c t s r e a d i l y with a r o m a t i c a m i n e s (pK a 1-5) on refluxing in alcohol solution in the
p r e s e n c e of the a m i n e h y d r o c h l o r i d e s to give 2 - m o n o s u b s t i t u t e d d e r i v a t i v e s IVa-e. E n t r y of the a m i n e s
into the 2 - p o s i t i o n was p r e v i o u s l y c o n f i r m e d in the c a s e of the r e a c t i o n [1] of 3-phenoxazinone with
ammonia.

-- . ', .- ~. ~! j.

li i: "
I II "~l a - r
i \"

C2f150 O O C?HsO
/ ~""~.," XO/" ~"~--"'<O /~'N ~'~v""~'O@"'~"O i

III IX X~/ X-XI i

91, 1
,, I

c ~ . ~ o ~ o ~%J% ,,o~ - < . o ~ - ~ o

VIII XII v I I a-(~

VI, VII a R = H , b R = B r , C R = O C H 3. d R=CH~. (~ R=NO2; X x = O ; xl X=CI~I~

* See [1] f o r c o m m u n i c a t i o n VIII.

S. M. K i r o v Polytechnic Institute, Severdlovsk. T r a n s l a t e d f r o m K h i m i y a G e t e r o t s i k l i c h e s k i k h

Soedinenii, No. 9, pp. 1196-1199, S e p t e m b e r , 1974. Original a r t i c l e s u b m i t t e d N o v e m b e r 5, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, iV. ]I. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the publisher for $15. 00.

1038
 TABLE 1

Found, % Calc., %
Com- Empirical ~max, nm Y~:ld,
R' rap, ~
pound formula C H N C I1 N
(I~ e)

Via OCOCHa "NIIC6Its 246.--248a (:2ol

l t4NzO4 69,5 4,3 7,9 69,4 4,1 8,i 446 (4,38) 60
Vlb OCOCHa NHC6H4Br 263.--265 b C2ol1LaBrN~O4 56,7 3,0 -- 56,9 3,1 450 (4,08) 70
580 (3,91)
VIc OCOCt Ia NI tCJ~4OCI Ia 214--216 b (;2tttz~N2Os 67,2 4,3 7, I 67,2 4,3 7,5 442 (4,39) 65
580 (4,37)
vId OCOCtIa NHCGH4CH3 200--202 a C21HIoN204 69,9 4,3 7,7 70,2 4,5 7,8 440 (4,34) 60
578 (4,13)
Vie OCOCHa NHCsH4NO2 >asoc C2olI~3,NaC~ 61,3 3,5 10,5 61,5 3,4 10,8 462 -- 80
Vlla OH Nt IC~H5 >300 b CI8t112'N~03c 71,2 4,2 9,0 71,2 4,0 9,3 472 (4,46) 80
574 (4,02)
Vllb OH NHC6tI4Br >300 c CIsHu BrN203 f 56,7 3,0 -- 56,4 2,9 472 (4,31) 85
VIIe OH NHC6H4OCI t3 264--266 a CIgIII4N~O4 g 68,2 4,1 8,5 68,3 4,2 8,4 466 (4,39) 80
578 (4,24)
Vlld OH N HC6tt4CH3 282---284 a CjgItI4N~O3:h 71,6 4,6 9,0 71,8 4,4 8,9 468 (4,42) 80
Vile OH NHC6H4NO2 >35O F ClsHnN3Os 62,1 3,3 12,6 62,0 3,2 12,1 466 -- 85
VIII OC~H5 NHCsHs 207--209b C2ot'I16N2Oai 72,5 5,1 -- 72,4 4,9 468 (4,52) 60
IX OCzHs N (CH2CH2) O 223--225 b CjsHI~N~O4j 66,7 5,7 9,0 66,4 5,6 8,6 460 (4,4) 30
X N (CH2CH2) O tt >300 b CloHl4N2Osk 68,2 5,3 10,4 68,2 5,0 10,0 556 (4,65) 40
XI N (CH2CH2) CH2 It 246--248 d CI7HI6N2031 72,7 5,8 10,6 73,0 5,8 10,0 580 (5,0) 30
XII OH N (CH~CH2) O 260--262 d CI6HI4N204 -- 9,2 -- 9,4 472 (4,75) 22

aFrom isoamyl alcohol, bFrom butanol. CFrom dimethylformamide, dFrom ethanol, epK a 7.62 0.03.
fFound, %: Br 20.8. Calculated, %: B r 2 0 . 8 . p K a 7 . 5 8 0 . 0 2 . g p K a 7 . 7 4 0 . 0 2 . h p K a 7 . 9 5 * 0 . 0 1 .
iRf 0.718. JRf 0.354. kRf 0.182. IRf 0.218.

r
The r e s u l t i n g 2 - a m i n o - 3 - p h e n o x a z i n o n e was also obtained by an independent method f r o m 0-aminophenol
[7]. Saponification of the a c e t o x y g r o u p in V I a - e with sodium ethoxide gives 2 - a r y l a m i n o r e s o r u f i n s V I I a - e ,
which a r e d a r k - g r a y c r y s t a l l i n e s u b s t a n c e s that d i s s o l v e in alkali to give violet solutions. The pK a values
of u a r e higher than the pK a value of r e s o r u f i n (Table 1), i.e., the introduction of a r y l a m i n o g r o u p s
into the 2 - p o s i t i o n of the r e s o r u f i n molecule hinders a c i d - b a s e ionization of the hydroxyl group.
T r a n s a c y l a t i o n leading to r e s o r u f i n and the c o r r e s p o n d i n g a c e t y l a m i n e o c c u r s in the r e a c t i o n of II
with s t r o n g e r a m i n e s (pK a 8-11). Thus, p u r e r e s o r u f i n was isolated in the r e a c t i o n of II with morpholine.
Like 3-phenoxazinone, IT[ r e a c t s with a r o m a t i c a m i n e s to give 2 - s u b s t i t u t e d d e r i v a t i v e s (for example,
Viii). The r e a c t i o n of III with m o r p h o l i n e and piperidine p r o c e e d s p e c u l i a r l y . In the c a s e o f m o r p h o l i n e , a
m i x t u r e of two products (IX-X), which differ in c o l o r and R f values (Table 1}, is f o r m e d . In addition to en-
t r y of morpholine into the quinoid ring (IX), the ethoxy g r o u p u n d e r g o e s nucleophilic substitution by m o r p h o -
line to give X (the e l e c t r o p h i l i c i t y of the 7-position of the phenoxazinone m o l e c u l e was p r e v i o u s l y c o n f i r m e d
by c a l c u l a t i o n s by the Htiekel MO method [8]). The l a t t e r r e a c t i o n b e c o m e s the dominant one in the r e a c t i o n
of III with a s t r o n g e r a m i n e - piperidine. 7 - P i p e r i d i n o - 3 - p h e n o x a z i n o n e (XI) is the p r i m a r y product in this
c a s e . The i s o m e r with an amino g r o u p in the 2 - p o s i t i o n could not be isolated, although its p r e s e n c e in v e r y
s m a l l amounts can be a s s u m e d f r o m t h i n - l a y e r c h r o m a t o g r a p h y (TLC) of the r e a c t i o n m i x t u r e .
In c o n t r a s t to the a c e t o x y group, the ethoxy g r o u p is saponified in acidic media. Thus, 2 - m o r p h o l i n o -
r e s o r u f i n (XII) w a s obtained by heating IX in 75% H~SO4.

EXPERIMENTAL
The electronic spectra of alcohol solutions of the compounds were recorded with an SF-10 speetro-
photometer. The ionization constants were measured spectrophotometrically with an SF-4 spectrophotome-
ter by the method in [9].
2,4,6,8-Tetrabromoresorufin Morpholine Salt (V). A 1.5-ml sample of morpholine was added to 0.5 g
(1 mmole) of 2,4,6,8-tetrabromoresorufin in 15 ml of alcohol, and the mixture was heated on a water bath
for 3 h. The resulting green precipitate was removed by filtration, washed with alcohol, and crystallized
from dimethylformamide (DMFA} to give 0,4 g (75%) of V. Found, %: C 3].8; H 2.1; N 4.7. CIoHI2N204Br 4.
Calculated, %: C 31.3; H 1.8; N 4.6.
Compounds VIa-e. A l-ml sample of the amine was added to 3.9 mmole and II and 0.77 mmole of
the amine hydrochloride in 25 ml of alcohol, and the mixture was refluxed for 30 rain. It was then cooled,
and the c r y s t a l s that p r e c i p i t a t e d f r o m the brown solution w e r e r e m o v e d by f i l t r a t i o n and washed with a l -
cohol to give 0.6 g of product (Table 1).
Compounds V I I a - e . A 1 . 4 - m m o l e s a m p l e of VI was added to a solution of sodium ethoxide (0.3 g of
sodium in 30 m l of alcohol), and the mixture was refluxed on a water bath for 15 rain. The precipitated
sodium s a l t of VII w a s r e m o v e d by f i l t r a t i o n and t r e a t e d with dilute h y d r o c h l o r i c acid. The p r e c i p i t a t e
w a s a g a i n r e m o v e d by f i l t r a t i o n and washed with w a t e r and alcohol to give 0.4 g of product (Table 1).
2 - P h e n y l a m i n o - 7 - e t h o x y - 3 - p h e n o x a z i n o n e (Viii). Aniline (2 ml) was added to 0.35 g (1.5 mmole) of
III in 10 ml of alcohol, and the m i x t u r e was refluxed f o r 10 h. The p r e c i p i t a t e that f o r m e d on cooling was
r e m o v e d by f i l t r a t i o n and w a s h e d with alcohol and e t h e r to give 0.2 g of product {Table 1).
2 - M o r p h o l i n o - 7 - e t h o x y - 3 - p h e n o x a z i n o n e (IX) and 7 - M o r p h o l i n o - 3 - p h e n o x a z i n o n e (AT). Morpholine (4
ml) and 0.2 g (1.6 m m o l e ) of m o r p h o l i n e h y d r o c h l o r i d e w e r e added to 1 g (4 m m o l e ) of III in 25 m l of a l c o -
hol, a f t e r which the m i x t u r e was refluxed for 16 h. The m i x t u r e was cooled, and the r e s u l t i n g p r e c i p i t a t e
was r e m o v e d by filtration, w a s h e d with alcohol, dried, and c h r o m a t o g r a p h e d with b e n z e n e - e t h e r (3 : 1) in
a c o l u m n filled with a l u m i n u m oxide (activity III). The f i r s t d a r k - y e l l o w f r a c t i o n was c o l l e c t e d and e v a p o -
r a t e d to give 0.3 g of IX. The second violet f r a c t i o n w a s collected and e v a p o r a t e d to give 0.3 g of X (Table
1). E a c h compound was subjected to c r y s t a l l i z a t i o n .
7 - P i p e r i d i n o - 3 - p h e n o x a z i n o n e (XI). P i p e r i d i n e (1.5 ml) and 0.2 g (1.6 mmole) of piperidine h y d r o -
chloride w e r e added to 0.5 g (2 m m o l e ) of HI in 15 m l of alcohol, and the m i x t u r e was refluxed f o r 16 h. It
was then cooled, and the solvent w a s e v a p o r a t e d . The r e s u l t i n g p r e c i p i t a t e w a s r e m o v e d by filtration,
w a s h e d with alcohol, and dried. It was then c h r o m a t o g r a p h e d with a column filled with a c t i v i t y III a l u m i -
num oxide with elution by a n h y d r o u s c h l o r o f o r m to give a violet fraction. The solvent was evaporated, and
the r e s i d u e was c r y s t a l l i z e d to give 0.15 g of product (Table 1).

1040
 2-Morpholino-7-hydroxy-3-phenoxazinone (XII). A 0.5-g (1.6 mmole) sample of IX was dissolved in
10 mi of 75% sulfuric acid, and the solution was heated carefully on a water bath for 15 min. :It was then
cooled, treated with 20 ml of water, and neutralized to pH 3 with sodium carbonate. The resulting p r e -
cipitate was removed by filtration and washed with water to give 0.1 g of product.

LITERATURE CITED
1, I. Ya. Postovskii, K. I. pashkevich, and G. B. Afanas,eva, Khim. Geterotsikl. Soedin., 464 (1974).
2. L. F. Larionov, The Chemotherapy of Malignant Tumors [in Russian], Moscow (1962), p. 206.
3. N. Gerber and M. Lechavalur, Biochem., 3, 398 (1964).
4. G. B. Afanas,eva, T. S. Viktorova, K. I. Pashkevich, and I. Ya. Postovskii, Khim. Geterotsikl.
Soedin., 348 (1974).
5o R. Nietzki, A. Dietze, and H. M~ickler, Ber., 22, 3024 (1889).
6. E.Ruzicka,and J. Jurina, Monatsh., 97, 129 (1966).
7. A. Osman and I. Bassiouni, J. Amer. Chem. Soc., 82, 1607 (1960).
8. K. I. Pashkevich, G. B. Afanas'eva, E. G. Kovalev, and I. Ya. Postovskii, Khim. Geterotsikl. Soedin.,
1316 (1970).
9. A. Albert and E. Serjeant, Ionization Constants of Acids and Bases, Methuen (1962).

1041
KINETICS OF THE ALKALINE HYDROLYSIS OF
3-SULFOLANOL PHENYL ETHERS

T. F.. B e z m e n o v a , A. F. Rekasheva, UDC 541.127.12 : 547.733 : 542.938

T. S. L u t s k i i , and R. A. Dorofeeva

A s c h e m e f o r the elimination of a r y l o x y groups via an E l c B m e c h a n i s m is p r o p o s e d on the

b a s i s of data on the kinetics of the alkaline h y d r o l y s i s of 3-sulfolanol phenyl e t h e r s in H~O
and D20.

U n d e r the influence of basic c a t a l y s t s , 3-sulfolanol e t h e r s r e a d i l y split out alcohol to give 2 - s u l f o l i n e

o r r e a c t with nucleophilic r e a g e n t s with exchange of alkoxy o r a r y l o x y groups [1]. It has been shown in the
c a s e of 3 - m e t h o x y s u l f o l a n e [2] that the introduction of an alkoxy g r o u p into the sulfolane m o l e c u l e r a i s e s
the lability of the h y d r o g e n a t o m s of the methylene g r o u p in the 2 - p o s i t i o n . T h e i r isotopic exchange with
D20 r e a c h e s e q u i l i b r i u m at 20-25~ in 0.006 N alkali solution a f t e r 30-40 min. In this c a s e , the r a t e of
isotopic exchange is c o n s i d e r a b l y higher than the r a t e of elimination. T h e s e data m a k e it possible to p r o -
pose the i n t e r m e d i a t e f o r m a t i o n of c a r b a n i o n s ( E l c B m e c h a n i s m ) , which has been e s t a b l i s h e d f o r m a n y
e l i m i n a t i o n and c l e a v a g e - a d d i t i o n r e a c t i o n s (for example, see [3-5]), f o r the elimination and substitution
r e a c t i o n s of fl-substituted d e r i v a t i v e s of sulfolane.
The r e s u l t s of a n investigation of the kinetics of the alkaline h y d r o l y s i s of 3-sulfolanol phenyl e t h e r s
(Ia-f), which c o n f i r m this a s s u m p t i o n , a r e p r e s e n t e d below.
The h y d r o l y s i s of all of the investigated e t h e r s in e x c e s s alkali is d e s c r i b e d by a f i r s t - o r d e r kinetic
equation (Fig. 1). The f i r s t - o r d e r r e a c t i o n with r e s p e c t to the e t h e r is c o n f i r m e d by the c o n s t a n c y of the
o b s e r v e d r a t e constants when the s t a r t i n g c o n c e n t r a t i o n of e t h e r s I changes. The f i r s t - o r d e r r a t e constant
is l i n e a r l y r e l a t e d to the a c t i v i t y of the OH- ions (Fig. 2). Thus, the kinetic equation of the r e a c t i o n has
the f o r m

d[I]
dt = k2[l][aoH-].

The a c t i v a t i o n p a r a m e t e r s of the h y d r o l y s i s , which a r e p r e s e n t e d in T a b l e 1 t o g e t h e r with the r a t e c o n -

stants, w e r e found f r o m the t e m p e r a t u r e dependence of the r e a c t i o n r a t e at 30, 40, and 50~
A c o m p a r i s o n of the k 2 values f o r v a r i o u s e t h e r s I shows that e l e c t r o n - a c c e p t o r substituents in the
p a r a position of the phenyl ring a c c e l e r a t e the reaction, while e l e c t r o n - d o n o r substituents in this position
inhibit it. The k 2 values s a t i s f y the H a m m e t t equation with ~P substituent constants [6].. log k = - 1 . 3 0 1 0 +
1.27 ~P (1: = 0.942; s = 0.036).
I n a s m u c h as the magnitude of the kinetic isotope effect m a y s e r v e a s one of the c r i t e r i a of a c a r b a n -
ion m e c h a n i s m [3, 7, 8], we c a r r i e d out two p a r a l l e l s e r i e s of e x p e r i m e n t s with e t h e r Ia in D20 and H20
with c a t a l y s i s by NaOH in 50% d i o x a n e - w a t e r solutions. At 30 ~ k2(H) = 0.0436, k2(D ) = 0.072 l i t e r , m o l e -1 9
sec -1, and k H / k D = 0.61. The o b s e r v e d a c c e l e r a t i o n of the r e a c t i o n in D20 is in a g r e e m e n t with the r e -
sults of calculations [3] f r o m the shift in the protolytic equilibria on passing f r o m H20 to D20 (from 0.3 to
0.8), with the values of the isotope effect in the e l i m i n a t i o n of a phenoxy g r o u p f r o m a 2 - p h e n o x y e t h y l s u l -
fonium s a l t (0.66) and a sulfoxide (0.78) [3], and also with the values o b s e r v e d in the elimination of a

Institute of the C h e m i s t r y of H i g h - M o l e c u l a r - W e i g h t Compounds, A c a d e m y of Sciences of the

Ukrainian SSR, Kiev. T r a n s l a t e d f r o m K h i m i y a G e t e r o t s i k l i c h e s k i k h Soedinenii, No. 9, pp. 1200-1203,
S e p t e m b e r , 1974. Original a r t i c l e s u b m i t t e d October 31, 1972; r e v i s i o n submitted October 24, 1973.

9 76 Plenum Publishing Corporation, 22 7 West 17th Street, New York, N. Y. 10011. No part o f this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording or otherwise, without written permission o f the publisher. A copy o f this article is available from the pub6sher for $15.00.

104 2
 kl. 10a. t ~ , ~
5 ~ 3