A New Route to Partially Hydrogenated Thiazolo[3,2-a]pyridine

Partially hydrogenated thiazolo[3,2-a]pyridines have been synthesized by the interaction of functionally substituted ammonium di- and tetrahydropyridine-2-thiolates with bromocyclohexanone. The structure of 6,8-dicyano-3-hydroxy-5-oxo-1,3-tetramethylene-2,3,4,5,6,7-hexahydrospiro[thiazolo[3,2-a]pyridine-7,1'-(4'-methylcyclohexane)] has been determined by X-ray crystallography.     

Pyrolysis and photolysis processes of pyran and thiopyran derivatives

Summary Pyrolysis and photolysis of 2-amino-3,5-dicyano-6-phenyl-4H-pyran (1) afford HNCO, acrylonitrile, cinnamonitrile, and 2-hydroxy-3,5-dicyano-6-phenylpyridine. Pyrolysis of 2-carboxyimino-3,5-dicyano-6-phenyl-4H-pyran (2) gives HCN, acrylonitrile, cinnamonitrile and 2-hydroxy-3,5-dicyano-6-phenylpyridine. Furthermore, both pyrolysis and photolysis of 2,6-diamino-3,5-dicyanothiopyran (3a) gives rise to HNCS, acrylonitrile and 6-amino-3,5-dicyano-6-mercaptopyridin. Moreover, comparative studies of pyrolysis and photolysis of 2,6-dicyano-4-arylthiopyran derivatives3b–d revealed similar results. The similarity of products obtained from pyrolysis and photolysis and the mechanistic implications of these data are discussed.

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Pyrolyse- und Photolyseprozesse von Pyran- und Thiopyranderivaten

Zusammenfassung Pyrolyse und Photolyse von 2-Amino-3,5-dicyano-6-phenyl-4H-pyran (1) ergeben HNCO, Acrylnitril, Zimtsäurenitril und 2-Hydroxy-3,5-dicyano-6-phenyl pyridin. Durch Pyrolyse von 2-Carboximino-3,5-dicyano-6-phenyl-4H-pyran (2) entstehen HCN, Acrylnitril, Zimtsäurenitril und 2-Hydroxy-3,5-dicyano-6-phenylpyridin. Weiters resultieren sowohl Photolyse als auch Pyrolyse von 2,6-Diamino-3,5-dicyanithiopyran (3a) in der Bildung von HNCS, Acrylnitril und 6-Amino-3,5-dicyano-6-mercaptopyridin. Vergleichende Untersuchungen zur Pyrolyse und Photolyse von 2,6-Dicyano-4-arylthiopyranderivaten (3b–d) lieferten vergleichbare Ergebnisse. Die Ähnlichkeit der Resultate von Pyrolyse und Photolyse sowie die sich daraus ergebenden mechanistischen Implikationen werden diskutiert.

     

Reaction of 2,6-dibutylaminohepta-2,5-dien-4-one with malononitrile

Malononitrile reacted with the title compound to give 6-amino-5-cyano-2-(3,3-dicyano-2-methylallylidene-4-methyl-2H-pyran (3). Treatment of 3 with hot 80% sulfuric acid yielded 4,7-dimethyl-56-hydroxy-2(1H)quinolone. With concentrated aqueous sodium hydroxide, 3 gave 5-amino-3,6-dicyano-4,7-dimethyl-2(1H)quinolone and 5-amino-6-carbamoyl-3-cyano-4,7-dimethyl-2(1H)quinolone. The reaction of 3 with hydrochloric in acetic acid gave a mixture of 6-amino-3,7-dicyano-2,8-dimethyl-4-quinolizone and 3-cyano-4-methyl-6-(3,3-dicyano-2-methylallyl)-2-pyrone. Compound 3 also reacted with methylamine, butylamine and piperidine to give 8-amino-5-cyano-4-methyl-2-pyridone, 6-bulylamino-5-cyano-4-methyl-2-pyridone and 5-eyano-4-methyl-6-piperidino-2-pyridone respectively.     

Reaction of α-cyanoacrylic acid catalyzed by tertiary amines

The action of pyridine on a-cyanoacrylic add leads to the rapid and quantitative formation of 2,4-dicyano-4-pentenoic add. In the presence of excess p-nitro-benzaldehyde, 1-hydroxy-1-p-nitrophenyl-2-cyano-2-butene is formed in this reaction in addition to 2,4-dicyano-4-pentenoic add.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 11, pp. 2644–2646, November, 1989.     

Reaction of 5,5-dialkyl-2-halo-6-hydroxy-5,6-dihydro-1H-pyridine-3,4,4-tricarbonitriles with Morpholine

5,5-Dialkyl-2-halo-6-hydroxy-5,6-dihydro-1H-pyridine-3,4,4-tricarbonitriles reacted with morpholine in aprotic solvent to give the corresponding 3,3-dialkyl-4,5-dicyano-6-halo-2-morpholino-1,2,3,4-tetrahydropyridine-4-carboxamides, while analogous reaction in amphiprotic solvent resulted in the formation of 8,8-dialkyl-3-halo-6-oxo-2,7-diazabicyclo[3.2.1]oct-3-ene-4,5-dicarbonitriles.     

Cyclisation of Ortho -Cyclohexenyl Phenols via Epoxidation #

A number of ortho -cyclohexenyl phenols 2(a–i) have been cyclised by treatment with one equivalent of m-chloroper-oxybenzoic acid in refluxing benzene for 4 h to furnish linearly fused 1-hydroxy-1,2,3,4,4a,9a-hexahydrodibenzofurans 3(a–i) (70–80%) and bicyclic 3-hydroxy-1,3-ethanochromans 4(a–f) (10–20%). Products 3(a–i) were oxidised with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (excess) in refluxing dry xylene for 6 h to give 2,3-dihydrodibenzofuran-1 (2H)-ones 6(a–i) (85–95%).

     

Synthesis and crystal structure of 5-amino-4,6-dicyano-3-dicyanomethylene-1, 8,8-trimethyl-2-azabicyclo[2.2.2]oct-5-ene

5-Amino-4,6-dicyano-3-dicyanomethylene-1,8,8-trimethyl-2-azabicyclo[2.2.2]oct-5-ene has been synthesized. The molecular and crystal structure of this compound has been determined.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 169–172, January, 1996.     

Synthesis and structure of novel 2-amino-l,3-dicyano-4-cyclopropyl-6-aryl-1,3-cyclohexadienes

The reaction of arylmethylenedicyanoacetates with 1,1-dicyano-2-cyclopropylpropene was studied and found to give 2-amino-1,3-dicyano-4-cyclopropyl-6-aryl-1,3-cyclohexadienes. The structure of 2-amino-6-(2-nitrophenyl)-1,3-dicyano-4-cyclopropyl-1,3-cyclohexadiene was corroborated by means of X-ray analysis.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 355–358, February, 1993.     

Synthesis of 4-Amino-3,5-dicyano-arylpyrazoles,Part 2: Isolation and Characterization of By-Products

Reaction of (dicyanomethylidene-hydrazino)benzoic acids with chloroacetonitrile, under basic conditions, gave cyanomethyl-3-(7-amino-3,5-dicyano-1H-pyrazolo[4,3-d]pyrimidin-1-yl-benzoates and para-substituted cyanomethyl benzoates, in addition to the expected cyanomethyl 3-(4-amino-3,5-dicyano-1H-pyrazol-1-yl)-benzoates.     

A novel three-component reaction of 1, 1-dicyano-2-(trifluoromethyl)ethylenes,primary arylamines,and ketones

1, 1-Dicyano-2, 2-bis(trifluoromethyl)ethylene and 3, 3-dicyano-2-(trifluoromethyl)acrylates react with primary arylamines in the presence of ketones to form 1, 1-aryl-1, 4-dihydropyridme derivatives under mild conditions. The mechanism of this three-component reaction includes the formation of Schiffs bases as intermediates. 1, 4-Dihydropyridine derivatives, which are the products of three-component heterocyclization, were also obtained by reaction the corresponding Schiffs bases with 1, 1-dicyano-2-(trifluoromethyl)ethylenes.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 552–559, March, 1993.For preliminary communication see Ref. 1.     

Cobalt Porphyrazines with Heterocyclic Substituents

Reactions of 4,5-diaminophthalodinitrile with thionyl chloride, sodium nitrite in concentrated sulfuric acid, and phenanthrenequinone gave, respectively, 5,6-dicyano-2,1,3-benzothiadiazole, 5,6-dicyano- 1H-benzotriazole, and 6,7-dicyano-2,3-(9,10-phenanthro)quinoxaline, from which the corresponding cobalt porphyrazines were prepared. The effect of the heterocyclic moiety on the physicochemical and spectral properties of porphyrazines was elucidated.     

Highly diastereoselective multicomponent synthesis of polysubstituted 2-hydroxy-2-trifluoromethylpiperidineswith four and five stereogenic centers

The Michael–Mannich cascade cyclization of cyano olefins, ethyl 4,4,4-trifluoro-3-oxobutanoate, aromatic aldehydes and ammonium acetate provides convenient stereoselective formation of ethyl 5,5-dicyano-4,6-diaryl-2-hydroxy-2-(trifluoromethyl)piperidine-3-carboxylates with fourstereogenic centers and dialkyl 4,6-diaryl-5-cyano-2-hydroxy-2-(trifluoromethyl)piperidine-3,5-dicarboxylates with five stereogenic centers. Ammonium acetate plays dual role, acting as a base and as a nitrogen source.     

The Mannich reaction in the synthesis of N,S-containing heterocycles 8. Aminomethylation of 3,5-dicyano-6-oxo-1,4,5,6-tetrahydropyridine-2-thiolates as a method for the synthesis of new functionally substituted 3,7-diazabicyclo[3.3.1]nonane derivatives

Aminomethylation of 3,5-dicyano-6-oxo-1,4,5,6-tetrahydropyridine-2-thiolates upon treatment with primary amines and excess formaldehyde leads to 3,7-diazabicyclo[3.3.1]nonane derivatives. N-Methylmorpholinium 4-(2-chlorophenyl)-3,5-dicyano-6-oxo-1,4,5,6-tetrahydropyridine-2-thiolate was obtained by the reaction of (E)-3-(2-chlorophenyl)-2-cyanoprop-2-enethioamide with 1-cyanoacetyl-3,5-dimethylpyrazole and N-methylmorpholine in acetone in quantitative yield. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2397–2400, December, 2007.     

Synthesis and cytotoxic activity of heterocyclization products of 1,1-dicyano-2-hetaryl-2-trifluoromethylethylenes

Methods for the synthesis of novel fluorinated compounds by reaction of 1,1-dicyano-2-hetaryl-2-trifluoromethylethylenes with a variety of nitrogen heterocycles have been developed. Cyctotoxicity of the obtained organofluorine heterocycles were studied in vitro at the U.S. National Cancer Institute (NCI) in the framework of the International Program for Development of Effective Antitumor Drugs. Cytotoxic activity in the series of fluorinated pyrazolo[1,5-a]pyrimidines has been observed for the first time, this strongly depending on the nature and position of the substituents.     

Structural reassignment of the alleged 6-hydroxy-1,2,4-triazine-3,5-(2H,4H)dione

The reaction of 6-amino-1,2,4-triazine-3,5-(2H,4H)clione with sodium hydroxide or nitrous acid has been shown to give 5-hydroxy-1,2,4-triazole-3-carboxylic acid instead of 6-hydroxy-1,2,4-triazine-3,5-(2H,4H)dione as reported in the literature. The triazolecarboxylic acid was also obtained from the aminotriazine and hydrochloric acid.     

4-Hydroxy-2-quinolones. 194*. 1-Hydroxy-3-oxo-6,7-dihydro-3H,5H-pyrido[3,2,1-<Emphasis Type="Italic">ij</Emphasis>]quinoline-2-carboxylic acid alkylamides. Synthesis,structure, and biological properties

Modified methods are proposed for the preparation of the ethyl ester and alkylamides of 1-hydroxy-3-oxo-6,7-dihydro-3H,5H-pyrido[3,2,1-ij]quinoline-2-carboxylic acid. A comparative analysis has been carried out of the steric structure and diuretic activity of the synthesized compounds and the previously studied, and closely structurally related, 1-hydroxy-3-oxo-5,6-dihydro-3H-pyrrolo-[3,2,1-ij]quinoline-2-carboxamides.     

Synthesis,alkylation, and molecular and crystal structure ofN-methylmorpholinium 6-amino-3,5-dicyano-1,4-dihydropyridine-4-spirocyclohexane-2-thiolate

The reaction of cyano(cyclohexylidene)thioacetamide with cyanothioacetamide or malononitrile andN-methylmorpholine yieldsN-methylmorpholinium 6-amino-3,5-dicyano-1,4-dihydropyridine-4-spirocyclohexane-2-thiolate. Its structure was established based on the results of alkylation and X-ray structural analysis.Deceased.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2535–2540, October, 1996.     

Synthesis and Alkylation of N-Methylmorpholinium 4-Aryl-3,5-dicyano-6-oxo-1,4,5,6-tetrahydro-2-pyridinethiolates. Molecular and Crystal Structure of 4,5-trans-3,5-Dicyano-4-(2-methoxyphenyl)-2-methylthio-6-oxo-1,4,5,6-tetrahydropyridine

The reaction of aromatic aldehydes with cyanothioacetamide and ethyl cyanoacetate in the presence of N-methylmorpholine gives N-methylmorpholinium 4-aryl-3,5-dicyano-6-oxo-1,4,5,6-tetrahydro-2-pyridinethiolates, which are used in the synthesis of substituted 2-alkylthiotetrahydropyridines. X-ray diffraction analysis was used to study the structure of 4,5-trans-3,5-dicyano-4-(2-methoxyphenyl)-2-methylthio-6-oxo-1,4,5,6-tetrahydropyridine.     

Ring transformations of 4H-pyrans. Pyridines from 2-amino-4H-pyrans

Ring transformations of 4H-pyrans into pyridines are reported. Treatment of 2-amino-4,6-diaryl-3,5-dicyano-4H-pyrans (I) with nitrosylsulfuric acid brings about their transformation into 3,5-dicyano-4,6-diaryl-2-pyridones (VI) which can also be obtained from α-benzoylcinnamonitriles (IX) and cyanoacetamide. Similarly, 2-amino-4,6-diaryl-5-carbethoxy-3-cyano-4H-pyrans (II) lead to 4,6-diaryl-5-carbethoxy-3-cyano-2-pyridones (VII). Treatment of both series of pyrans with sulfuric acid results in the formation of the corresponding 3,4-dihydro-2-pyridones (IV and V). Reaction of pyrans II with ammonium acetate in acetic acid yields 2-amino-4,6-diaryl-5-carbethoxy-3-cyanopyridines (XII). Pyrans I undergo an entirely different type of reaction upon treatment with this reagent leading to 2,4,6-triaryl-3,5-dicyano-1,4-dihydropyridines (XV).     

4,4-Dialkyl-substituted N-Methylmorpholinium 3,5-Dicyano-6-oxo-1,4,5,6-tetrahydropyridine-2-thiolates and Some of Their Properties

4,4-Dialkyl-substituted N-methylmorpholinium 3,5-dicyano-6-oxo-1,4,5,6-tetrahydropyridine-2-thiolates were synthesized by the condensation of 2-alkyl-2-cyanoethyl crotonates with cyanothioacetamide and N-methylmorpholine. They were used for the production of substituted 2-alkylthio-1,4,5,6-tetrahydropyridines, 2-acetylthio-1,4,5,6,-tetrahydropyridine, 6-hydrazino-1,4,5,6-tetrahydropyridine, and 2,3,4,5,6,7-hexahydrothiazolo[3,2-a]pyridine. The structure of 6-bromo-3-bromomethyl-6,8-dicyano-7,7-dimethyl-2,3,4,5,6,7-hexahydrothiazolo[3,2-a]pyridine was proved by X-ray crystallographic analysis.