Directed metalation of pyridinesulphonamides. Synthesis of pyridine-fused isothiazoles and 1,2-oxathioles

4-Lithio-N-t-butylpyridine-3-sulphonamide reacted with benzophenone and carbon dioxide respectively to give the corresponding intermediates which on appropriate treatment gave isothiazolo[5,4-c]pyridin-3-one 1,1-dioxides. Metalation of 2- and 4-(N,N-dialkylaminosulphonyl)pyridines with lithium diisopropylamide (LDA) gave anions which reacted with benzophenone to give carbinols which thermally cyclised to 1,2-oxathiolo[3,4-b]pyridine and 1,2-oxathiolo[4,3-c]pyridine respectively.     

Investigation of heterocycles containing nitrogen or sulfur. 47. Reactions of 1,2-dioxo-3a-alkyl-4,7-dichloroxazolidino [3,2-f]pyrido[2,3-b]-1,4-thiazines with saturated cyclic amines. synthesis and structure of derivatives of 1,2-dihydrothiazolo[5,4-b]pyridine

It has been established spectroscopically that 1-N-oxalamides of 2-acyl-5-chloro-1,2-dihydrothiazolo[5,4-b] pyridine are formed in the reaction of 4,7-dichloroxazolidino[3,2-f]pyrido[2,3-b]-1,4-thiazines with morpholine, piperidine and pyrrolidine. The products are a mixture of amide conformers in solution. The reaction intermediate 2-(1-chloro-2-oxobutylthio)-3-pyrrolidinooxamoyl-6-chloropyridine has been isolated and characterized. A proposed reaction scheme is presented.For Communication 46 see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1125–1132, August, 1993.     

Heterocyclic synthesis with 3-cyano-2(1H)pyridinethione: Synthesis of 3-oxo-2,3-dihydroisothiazolo[5,4-b]pyridine and related compounds

Summary 3-Carbethoxy-4,6-diphenyl-2-pyrridine sulfonamide (5), can be cyclized to 3-oxo-2,3-dihydro-4,6-diphenylisothiazolo[5,4-b]pyridine-1,1-dioxide (2). Oxidation of pyridinethione6 with Cl₂/H₂O gave the sulfonyl chloride derivative7, which can be ammonolyzed to 3-amino-4,6-diphenylisothiazolo[5,4-b]pyridine-1,1-dioxide (8), and 3-cyano-4,6-diphenylpyridine-2-sulfonamide (9). Hydrolysis of6 gave 3-carboxamido-2(1H)pyridinethione (12) which can be oxidized with iodine to 3-oxo-4,6-diphenyl-2,3-dihydroisothiazolo[5,4-b]pyridine (13). 3-Methyl-4,6-diphenylisothiazolo[5,4-b]pyridine-1,1-dioxide (17) was also prepared from6.

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Heterocyclensynthese mit 3-Cyano-2(1H)pyridinthion: Synthese von 3-Oxo-2,3-dihydroisothiazolo-[5,4-b]pyridin und verwandten Verbindungen

Zusammenfassung 3-Carbethoxy-4,6-diphenyl-2-pyridinsulfonamid (5) kann zu 3-Oxo-2,3-dihydro-4,6-diphenylisothiazolo[5,4-b]pyridin-1,1-dioxid (2) cyclisiert werden. Die Oxidation des Pyridinthions6 mit Cl₂/H₂O ergab das Sulfonylchlorid-Derivat7, das mit Ammoniak zu 3-Amino-4,6-diphenylisothiazolo[5,4-b]pyridin-1,1-dioxid (8) und 3-Cyano-4,6-diphenylpyridin-2-sulfonamid (9) umgesetzt werden kann. Die Hydrolyse von6 ergab 3-Carboxamido-2(1H)pyridinthion (12), das mit Jod zu 3-Oxo-4,6-diphenyl-2,3-dihydroisothiazolo[5,4-b]pyridin (13) oxidiert wurde. 3-Methyl-4,6-diphenyl-isothiazolo[5,4-b]pyridin-1,1-dioxid (17) wurde ebenfalls aus6 hergestellt.

     

Azaindole derivatives. 62. Synthesis and transformations of condensed three-ring systems that include a 5-azaindoline fragment

The reaction of 7-carbamoyl- and 7-cyano-6-chloro-5-azaindolines with hydrazine leads to the formation of pyrrolo[2,3-d]pyrazolo[5,4-b]pyridine, whereas the reaction of 7-carbamoyl-5-azaindolines with dimethylformamide diethylacetal gives pyrrolo[1,2-c]pyrido]4,3-d]pyrimidines — two new heterocyclic systems. The chemical properties of the synthesized compounds, including cleavage of the pyrimidine ring under the influence of nucleophilic agents, were studied.See [1] for communication 61.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1370–1373, October, 1982.     

Synthesis of 2-aryl-6-carbethoxythiazolo[4,5-c]pyridine and 7-chloro-2-phenylthiazolo[5,4-c]pyridine

Starting from readily available 2-aryl-5-formyl-4-mehtylthiazole, 2-aryl-6-carbethoxythiazolo[4,5-c]pyridine was prepared. β-(2-Phenylthiazol-4-yl)acrylic acid was converted to the corresponding azide (VI). Cyclization of compound VI afforded 2-phenylthiazolo[5,4-c]pyridin-7(6H)one. Reaction of the latter with phosphorous oxychloride gave 7-chloro-2-phenylthiazolo[5,4-c]pyridine.     

Reaction of dichloroketene and sulfenc with N,N-disubstituted 2-aminomethylene-1 -indanones. Synthesis of indeno[ 1,2-b ] pyran and lndeno[2,l-e] -1,2-oxathiin derivatives

The 1,4-cycloaddition of dichloroketene to N,N-disubstituted 2-aminomethylcnc-l-indanones afforded N,N-disubstituted 4-ainino-3,3-dichloro-3,4-dihydro-2-oxoindeno[1,2-b ]pyrans only in the case of full or partial aromatic N-substitution. The diphenylamino adduct gave 3-chloro-4-diphenylamino-2-oxoindeno[ 1,2-b]pyran by dehydrochlorination with DBN. The 1,4-cycloaddition with sulfene occurred only in the case of 2-diethylaininomethylene-1-indanone to give 4-diethylamino-3,4-dihydroindeno[2, 1-e]-1,2-oxathiin 2,2-dioxide, a derivative of a new hetero-cyclic system.     

Reaction of ketenes with N,N-disubstituted α-aminomethyleneketones. XVII. Synthesis of 2H-[1]benzothiepino[5,4-b]pyran derivatives

1,4-Cycloaddition of dichloroketene to a number of N,N-disubstituted (E)-4-amino methylene-3,4-dihydro-[1]benzothiepin-5(2H)-ones gave in excellent yield N,N-disubstituted 4-amino-3,3-dichloro-3,4,5,6-tetrahydro-2H-[1]benzothiepino[5,4-b]pyran-2-ones III, which are derivatives of the 2H-[1]benzothiepino[5,4-b]pyran system. Dehydrochlorination of III with DBN afforded N,N-disubstituted 4-amino-3-chloro-5,6-dihydro-2H-[1]-benzothiepino[5,4-b]pyran-2-ones, generally in excellent yield.     

SYNTHESIS OF BENZO[1,2-b: 5,4-b′]- DIFURANYL-TRIAZOLES, -OXADIAZOLES, -THIAZOLIDINONES, -THIADIAZOLES,AND THE USE OF DNA IN EVALUATION OF THEIR BIOLOGICAL ACTIVITY

Benzo[1,2-b:5,4-b′]difuran-2-carbohydrazides 5a, b were reacted with aryl or alkyl isothiocyanates to give the corresponding thiosemicarbazides 6a–h. Cyclization of the substituted thiosemicarbazides with sodium hydroxide led to the formation of benzo[1,2-b:5,4-b′]difuranyl-1,3,4-triazoles 7a–f. Desulfurization of thiosemicarbazides by mercuric oxide gave benzo[1,2-b:5,4-b′]difuranyl-1,3,4-oxadiazoles 8a–f. Treatment of thiosemicarbazides with ethyl bromoacetate or α-bromopropionic acid yielded benzo[1,2-b:5,4-b′]difuranyl-carbonyl-hydrazono-4-thiazolidinones 9a–f and 10a–f, respectively. Furthermore, the reaction of the thiosemicarbazides with phosphorus oxychloride gave benzo[1,2-b:5,4-b′]difuranyl-1,3,4-thiadiazoles 11a–f. Some compounds in this study were biologically evaluated for their ability to bind to DNA.     

On the amination of pyrimido[5,4-e]1,2,4-triazines in liquid ammonia

When dissolved in liquid ammonia 5-chloro-1,2-dihydropyrimido[5,4-e]-1,2,4-triazine ( 1 ) and 5-methoxy-pyrimido[5,4e]-1,2,4-triazine ( 4 ) quickly convert into 5-aminopyrimido[5,4-e]-1,2,4-triazine ( 2 ). When 2 is kept in liquid ammonia containing an excess of potassium permanganate, 3,5-diaminopyrimido[5,4-e]-1,2,4-triazine ( 5 ) is formed.     

Investigation of nitrogen-and sulfur-containing heterocycles

Reaction of 4-chloro-5-hydroxy-6-aminopyrimidine and its 2-methyl derivatives with -chloroacetoacetic ester gave the corresponding 4-chloro-6-carbethoxy-8H-pyrimido-[5,4-b][1,4]oxazines, which were converted to 4-aminopyrimidooxazines by reaction with amines.See [1] for communication XXVIII.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1694–1696, December, 1973. Original article submitted.     

Convenient and Practical Synthesis of 6-Chloro-2-(chloromethyl)-thiazolo[5,4-b]pyridine

A high-yielding and practical synthesis of 6-chloro-2-(chloromethyl)-thiazolo[5,4-b]pyridine starting from 2-amino-5-chloropyridine has been accomplished in a sequence of five steps.     

Synthesis of some 2-(heteroarylamino)benzimidazoles and their cyclization with phosgene

2-(Benzimidazol-2-ylamino)pyridine (4a) , 2-(benzimidazol-2-ylamino)pyrazine (4b) , and 2-(benzimidazol-2-ylamino)thiazole (4c) underwent a ring-closure reaction on treatment with phosgene affording 6H-pyrimido-[1′,2′:5,4][1,3,5]triazino[1,2-a]benzimidazol-6-one (1a) , 6H-pyrazino[1′,2′:5,4][1,3,5]triazino[1,2-a]benzimidazol-6-one (1b) , and 5H-thiazolo[2′,3′:4,5][1,3,5]triazino[1,2-a]benzimidazol-5-one (1c) respectively. The structure of these hitherto unknown heterocyclic systems was confirmed by their ir and mass spectra.     

A Novel,Degraded Polyketidic Lactone,Leptosphaerolide, and Its Likely Diketone Precursor,Leptosphaerodione. Isolation from Cultures of the Marine Ascomycete Leptosphaeria oraemaris (LINDER)

Acetone extraction of cultures of the marine ascomycete Leptosphaeria oraemaris (LINDER) on cornmeal disk gave the novel polyketide derivative leptosphaerolide ( = (+)-7-[(1E)-l,3-dimethylpent-1-enyl]-10-hydroxy-3-methoxybenzo[1,2-b:5,4-c′]dipyran-2(9H)-one; (4+)-8) besides the o-dihydroquinone 3-[(1E)-1,3-dimethylpent-1-euyl]-8,10-dihydroxy-7-methoxy-8-(2-oxopropyl)-1H-naphtho[2,3-c]pyran-9(8H)-one ( 1 ) as a 10:9 mixture of epimers. retro-Aldol reaction of 1 gave leptosphaerodione ( = (?)-3-[(1E)-1,3-dimethylpent-1-enyl]-10-hydroxy-7-methoxy-1H-naphtho[2,3-c]pyran-8,9(8H)-dione; (?)-6) which was also present in small amounts in the extracts and which gave 1 on reaction with acetone. It is thus likely that 1 is an artefact of the extraction by acetone. Biogenetically (+)-8 might derive from (?)-6 via an unusual oxidation with loss of CO₂.     

Properties of 8-Cyano-5-phenyl-7-trifluoromethyl-2,3-dihydroimidazo[1,2-a]pyridines

The alkylation, acylation, halogenation, nitration, oxidation, and hydrolysis reactions of 8-cyano-5-phenyl-7-trifluoromethyl-2,3-dihydroimidazo[1,2-a]pyridine have been studied. It was found that the 6-halo derivatives add alcohol to give covalent solvates. X-ray analysis has been carried out on one of the solvates (6-chloro-8-cyano-7-ethoxy-5-phenyl-7-trifluoromethyl-1,2,3,7-tetrahydroimidazo[1,2-a]pyridine) as well as on 8-cyano-5-phenyl-7-trifluoromethyl-2,3-dihydroimidazo[1,2-a]pyridine trifluoroacetate.     

The reaction of 2-acetoacetamidopyridines with phosgene. A route to novel 3-Acetyl-2-chloro-4H-pyrido[ 1,2-a] pyrimidin-4-ones

2-(Acetoacetamido)pyridine, 1 , and its 5-methyl derivative, 2 , with phosgene, gave 3-acetyl-2-chloro-4H-pyrido[1,2-a]pyrimidin- 4 -one, 5 , and 3-acetyl-2-chloro-7-methyl-4H-pyrido[1,2-a]-pyrimidin-4-one, 6 , respectively. The structures of these compounds followed from their elemental analyses, and interpretations of their uv, ir, pmr, and X-ray spectra. An alternative route to 5 and 6 , which sought first to react 1 and 2 with methyl - and benzyl chloroformates, was unsuccessful, and led, instead, to elimination of the acetoacetyl group with concomitant formation of the carbamate derivatives, 10 and 11 .     

Etude des conditions d'accés aux 6H-, 7H- et 11H-pyrimidino-[4,5-a], [4,5-b], [5,4-a] [5,4-b] et [5,4-c]carbazoles. 1

The synthesis of dihydropyrimidinocarbazoles 12,15 and 18 was achieved by cyclization of tetrahydrocarbazolones with triformamidomethane. The oxidation with potassium permanaganate of dihydropyrimidinocarbazoles gave the pyrimidinocarbazoles 13,16 and 19. The application of the Sandemeyer reaction to amiononitrocarbazoles gave cyanonitrocarbazoles which could be reduced to aminocyanocarbazoles 1 and 7. Intramolecular cyclization of the carbazoles 1 and 7 afforded 3,4-dilhydro-4-oxo-6H-pyrimidino[5,4-b]carbazole 2 and 1,2-dighydro-1-oxo-6H-pyrimidino[5,4-b]carbazole 10 was obtained by cyclization of quinazolinyl hydrazone 9 with hydrochloric acid and acetic acid. The structure of the derivatives was determined by ¹H-nmr and the Overhauser effect.     

Heterocycles containing nitrogen and sulfur. Part 49. Synthesis of derivatives of new heterocyclic systems: 1,2-Dioxocyclopenta(hexa)[g]oxazolidino-[3,2-f] pyrimido[4,5-b][1,4]thiazine, 1,2-dioxocyclopenta(hexa)-[g] imidazolidino[3,2-f]pyrimido[4,5-b][1,4]thiazine, and 1,2-oxazino[5,4-g]pyrimidino[4,5-b][1,4]thiazine

The reaction of 4-methoxy-5-amino-6-mercaptopyrimidine with 2-oxo-1-chlorocyclopentyl(hexyl)glyoxalate esters gave derivatives of the previously unknown tetracyclic systems 1,2-dioxocyclopenta (hexa)[g]oxazolidino[3,2-f]pyrimido[4,5-b][1,4]thiazines, which are transformed by ammonium acetate into derivatives of 1,2-dioxocyclopenta(hexa) [g]imidazolidino[3,2-f]pyrimido[4,5-b]-[1,4] thiazines. Derivatives of the new tricyclic 1-oxazino [5,4-g]pyrimido[4,5-b][1,4]thiazine system were obrtained by reaction of 6-carbethoxy-7-acetylpyrimido [4,5-b] [1,4] thiazines with hydroxylamine.     

Synthesis of pyrido[1,2-a]benzimidazoles by cyclizative condensation of 2-halopyridines and 1,2-benzenediamines. Scope and mechanism of the reaction

The scope and mechanism of acid-catalyzed cyclizative condensation of 2-halopyridines with 1,2-benzene-diamines has been explored. The reaction requires a 2-halopyridine which is activated toward nucleophilic substitution. Evidence in favor of a mechanism involving pyridine ring opening is presented. Of three substituted 1,2-benzenediamines which were examined, the 4-nitro compound gave a single cyclization product whereas 4-chloro and 4-methy 1-derivatives gave isomeric mixtures. The structure of the product from 2-chloro-5-nitropyridine and 4-nitro-1,2-benzenediamine is shown to be 2,8-dinitropyrido[1,2-a]benz-imidazole.     

Bridgehead nitrogen heterocycles. VI. The reaction of 1-amino- and 1,2-diaminopyridinium salts with β-dicarbonyl compounds

1,2-Diaminopyridinium iodide underwent reaction with ethyl acetoacetate to form 1,4-dihydro-2-methyl-4-oxopyrido[1,2-a]pyrimidin-1-ium iodide, and with acetyl acetone it gave 2,4-dimethylpyrido[1,2-a]pyrimidin-5-ium iodide. Though 2-acetylcyclohexanone gave the corresponding 5-methyl-1,2,3,4-tetrahydropyrido[1,2-a]quinazolin-11-ium iodide, no reaction was observed with 2,6-dimethyl-3,5-heptanedione, 1-benzoylacetone, 1,3-diphenyl-1,3-propanedione and its p-methoxyphenyl derivative. However, 1-aminopyridinium iodide and acetyl acetone in the presence of base gave 3-acetyl-2-methylpyrazolo[1,5-a]pyridine and 1-amino-2-methylpyridinium iodide yielded the corresponding 3-acetyl-2,7-dimethylpyrazolo[1,5-a]pyridine. With ethyl acetoacetate, the latter salt formed 3-ethoxycarbonyl-2,7-dimethylpyrazolo[1,5-a]pyridine but with 2,6-dimethyl substituents in the pyridine ring no condensation occurred. Reaction of 1-amino-2-methylpyridinium iodide with benzaldehyde gave N-benzalimino-2-methylpyridinium iodide which, on treatment with base, resulted in the formation of 2-picoline and benzonitrile, providing a convenient method of deamination.     

The reaction of 2-hetarylacetonitriles with heterocyclic haloaldehydes

The reaction of 4-oxo-3,4-dihydroquinazolyl-and benzimidazolylacetonitriles with 2-chloro-2-quinolinecarbaldehydes and 1-aryl-5-chloro-3-methyl-1H-pyrazole-4-carbaldehydes gave the corresponding 3-(2-chloro-3-quinolyl)-2-(4-oxo-3,4-dihydro-2-quinazolyl)-2-propenenitriles and 3-(1-aryl-5-chloro-3-methyl-1H-4-pyrazolyl)-2-hetaryl-2-propenenitriles. Intramolecular cyclization of these compounds gives 15-oxo-15H-benzo[6,7][1,8]naphthyridino[2,1-b]quinazoline-6-carbonitriles, 1-aryl-3-methyl-11-oxo-1,11-dihydropyrazolo[4′,3′:5,6]pyrido[2,1-b]quinazoline-5-carbonitriles, and 1-aryl-3-methyl-1H-benzo[4,5]imidazo[1,2-a]pyrazolo[4,3-e]pyridine-5-carbonitriles.