Aliphatic aldehydes in synthesis of 4-alkyl-5-carbamoyl-3-cyano-6-methylpyridine-2(1H)-thiones

Condensation of isovaleric or acetic aldehydes with cyanothioacetamide and acetoacetamide leads to formation of 4-isobutyl(methyl)-5-carbamoyl-3-cyano-6-methylpyridine-2(1H)-thiones. By alkylation of 5-carbamoyl-3-cyano-4,6-dimethylpyridine-2(1H)-thione with 4-methoxyphenacyl bromide, 5-carbamoyl-3-cyano-4,6-dimethyl-2-(4-methoxybenzoyl)methylthiopyridine has been obtained.Lugansk T. G. Shevchenko State Pedagogical Institute, Lugansk 348011, Ukraine. N. D. Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 117913, Russia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 228–229, February, 1999.     

Synthesis of 3-cyano-3-ethoxycarbonyl-4-methyl-6-phenylpyridine-2(1H)-thione and its alkylation

The condensation of acetaldehyde with cyanothioacetamide and ethyl benzoylacetate in the presence of N-methylmorpholine leads to the formation of 3-cyano-5-ethoxycarbonyl-4-methyl-6-phenylpyridine-2(1H)-thione. Alkylation of the last afforded the corresponding substituted 2-alkythiopyridines.T. G. Shevchenko Lugansk State Pedagogical Institute, Lugansk 348011, Ukraine. N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences (RAN),Moscow 117913, Russia.Translated from Khimiya Geterotsklicheskh Soedinenii, No. 12, pp. 1645–1646, December, 1999.     

Investigation of the stereochemistry of the [3.3]-sigmatropic rearrangement of the sp-isomer of 2-allylthio-5-acetyl-6-methyl-4-(2-nitrophenyl)-3-cyano-1,4-dihydropyridine

The reaction of the syn-periplanar conformer (the sp-isomer) of morpholinium 5-acetyl-6-methyl-4-(2-nitrophenyl)-3-cyano-1,4-dihydropyridine-2-thiolate with allyl bromide proceeds regio- and stereoselectively with the formation of the sp-isomer of the substituted 2-allylthio-1,4-dihydropyridine. The [3.3]-sigmatropic rearrangement of the last leads to the sp-isomer of 3,4-trans-3-allyl-5-acetyl-6-methyl-4-(2-nitrophenyl)-3-cyano-1,2,3,4-tetrahydropyridine-2(1H)-thione.Deceased.A. N. Nesmeyanov Institute of Hetero-organic Compounds, Russian Academy of Sciences (RAN), Moscow 117813. N. D. Zelinskii Institute of Organic Chemistry, RAN, Moscow 117913. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 643–652, May, 1997.     

Synthesis of 6-methyl-5-phenylcarbamoyl-3,4-dihydropyridinespiro-4-cyclohexane-2(1H)-thione and its derivatives

3-Cyano-6-methyl-5-phenylcarbamoyl-3,4-dihydropyridinespiro-4-cyclohexane-2(1H)-thione was obtained by the condensation of acetoacetic acid anilide with cyclohexylidenecyanothioacetamide. Substituted 2-alkylthio-1,4-dihydropyridines and 3-amino-2-(4-chlorobenzoyl)-6-methyl-5-phenylcarbamoyl-4,7-dihydrothieno[2,3-b]pyridinespiro-4-cyclohexane were synthesized from it. T. G. Shevchenko Lugansk State Pedagogical Institute, Lugansk 348011, Ukraine N. D. Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 117913. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1533–1535, November, 1997.     

Synthesis and alkylation of 3-cyano-4-isobutyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-2-thiol

By reaction of isovaleric aldehyde with cyanothioacetamide and cyclohexane-1,3-dione, 3-cyano-4-isobutyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-1-thiol has been obtained, and subsequently used in synthesis of the corresponding substituted 2-alkylthiohexahydroquinolines.Lugansk T. G. Shevchenko State Pedagogical Institute, Lugansk 348011, Ukraine. N. D. Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 117913, Russia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 230–231, February, 1999.     

Synthesis of 2,6-diamino-3,5-dicyano-4-ethyl-4H-thiopyran and its recyclization to 6-amino-3,5-dicyano-4-ethylpyridine-2(1H)-thione

The triple condensation of propionaldehyde, malononitrile, and cyanothioacetamide gives 2,6-diamino-3,5-dicyano-4-ethyl-4H-thiopyran, which recyclizes to give 6-amino-3, 5-dicyano-4-ethylpyridine-2(1H)-thione. This thione was used to synthesize substituted 2-alkylthiopyridines and the corresponding thieno[2,3-b]pyridines.T. G. Shevchenko Lugansk State Pedagogical Institute, 348011 Lugansk. N. D. Zelinski Institute of Organic Chemistry, Russian Academy of Sciences, 117913 Moscow. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1099–1103, August, 1996. Original article submitted May 13, 1996.     

Synthesis of N-methylmorpholinium 6-oxo-3,5-dicyano-1,4,5,6-tetrahydro-4-(spirocyclopentane)pyridine-2-thiolate with the Michael reaction

N-Methylmorpholinium 6-oxo-3,5-dicyano-1,4,5,6-tetrahydro-4-(spirocyclopentane)pyridine-2-thiolate was obtained by reaction of cyclopentylidenecyanoacetic ester with cyanothioacetamide or cyclopentylidenecyanothioacetamide with cyanoacetic ester in the presence of N-methylmorpholine; it is used in synthesis of substituted 2-alkylthiotetrahydropyridines, 5-oxo-6,8-dicyano-2,3,6,7-tetrahydro-(5H)-7-(spirocyclopentane)-thiazolo[3,2-a]pyridine, 5-allyl-2-methylthio-3,5-dicyano-4,5-dihydro-4-(spirocyclo-pentane)pyridin-6(1H)-one, and 3-amino-6-oxo-5-cyano-4,5-dihydro-4-(spirocyclopentane)-2H-pyrazolo[5,4-b]pyridin-6(7H)-one. T. G. Shevchenko Lugansk State Pedagogical Institute, Lugansk 348011, Ukraine, N. D. Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 117913, Russia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 208–212, February, 1998.     

Synthesis and transformations of 6-amino-3,5-dicyano-4ethylpyridine-2(1H)-thione

The condensation of propionaldehyde with cyanothioacetamide gives 6-amino-3,5-dicyano-4-ethylpyridine-2(1H)-thione, which was used to obtain substituted 2-alkylthiopyridines, 2-ethylthio-6- ethylaminopyridine, and pyrazolo[3,4-b]pyridine.T. G. Shevchenko Lugansk State Pedagogical Institute, 348011 Lugansk. N. D. Zelinskii Institute of Organic Chemistry, Russian Academy of Science, 117913 Moscow. Translated from Khimiya Geterotsklicheskikh Soedinenii, No. 8, pp. 1094–1098, August, 1996. Original article submitted March 4, 1996; revision submitted July 1, 1996.     

Convenient method for synthesis of functionally substituted hexahydroquinolines. Molecular and crystal structure of 4-isopropyl-7,7-dimethyl-5-oxo-3-cyano-2-cyanomethylthio-1,4,5,6,7,8-hexahydroquinoline

We have obtained 2-alkylthio-7,7-dimethyl-5-oxo-4-ethyl(isopropyl)-3-cyano-1,4,5,6,7,8-hexahydroquinolines by reaction of 5,5-dimethylcyclohexane-1,3-dione, propionic (or isobutyric) aldehyde, cyanothioacetamide, and alkyl halides. We have established the structure of 4-isopropyl-7,7-dimethyl-5-oxo-3-cyano-2-cyanomethylthio-1,4,5,6,7,8-hexahydroquinoline by x-ray diffraction.T. G. Shevchenko Lugansk State Pedagogical Institute, Lugansk 348011. A. N. Nesmeyanov Institute of Heteroorganic Compounds, Russian Academy of Sciences, Moscow 117813. N. D. Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 117913. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 785–792, June, 1997.     

Synthesis and properties of N-methylmorpholinium 6-methyl-4-(4-pyridyl)-5-phenylcarbamoyl-3-cyano-1,4-dihydropyridine-2-thiolate

Condensation of acetoacetic acid anilide, 4-pyridyl aldehyde, cyanothioacetamide and N-methylmorpholine gave N-methylmorpholinium 6-methyl-4-(4-pyridyl)-5-phenylcarbamoyl-3-cyano-1,4-dihydropyridine-2-thiolate from which were obtained the corresponding substituted pyridinethiones, 2-alkylthio-1,4-dihydropyridines and 3-amino-2-benzoyl-6-methyl-4-(4-pyridyl)-5-phenylcarbamoylthieno[2,3-b]pyridine.T. G. Shevchenko Lugansk Pedagogical Institute, Lugansk 348011. N. D. Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 117913. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 672–675, May, 1997.     

Michael reaction in synthesis of 6-amino-4-(4-butoxyphenyl)-3,5-dicyanopyridine-2(1H)-thione

The reaction of 4-butoxybenzalcyanoacetic ester with cyanothioacetamide yielded 6-amino-4-(4-butoxyphenyl)-3,5-dicyanopyridine-2(1H)-thione, also synthesized by recyclization of 2,6-diamino-4-(4-butoxyphenyl)-3,5-dicyano-4H-thiopyran and condensation of 4-butyoxybenzaldehyde with a two-fold excess of cyanothioacetamide. Substituted 2-alkylthiopyridines and thieno[2,3-b]pyridines were obtained with the indicated pyridinethione. T. G. Shevchenko Lugansk State Pedagogical Institute, Lugansk 348011. Ukraine, N. D. Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 117913, Russia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 213–219, February, 1998.     

Synthesis of 4-alkyl-3-cyano-5,6,7,8-tetrahydroquinoline-2(1H)-thiones and their derivatives

4-Alkyl-3-cyano-5,6,7,8-tetrahydroquinoline-2(1H)-thiones, used in synthesis of substituted 2-alkylthioquinolines and thieno[2,3-b]pyridines, were obtained by condensation of cyanothioacetamide, aliphatic aldehydes, and morpholinocyclohexene.T. G. Shevchenko Lugansk State Pedagogical Institute, Lugansk 348011 Ukraine. N. D. Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 117913 Russia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 81–85, January, 1998.     

Synthesis and chemical properties of 8-aryl-7-acyl-1-6-dimethyl-6-hydroxy-4-cyano-5,6,7,8-tetrahydro-3(2H)-isoquinolinones and isoquinolinethiones

8-Aryl-7-acetyl-1, 6-dimethyl-6-hydroxy-4-cyano-5, 6, 7, 8-tetrahydro-3(2H)-isoquinolinones and -isoquinolinethiones and their sodium salts were obtained by the reaction of cyanoacetamide and cyanothioacetamide with 3-aryl-2, 4-diacetyl-5-methyl-5-hydroxycyclohexanonesinbasicrnedium. 8-Aryl-7-acetyl-6-methoxycarbonyl-1, 6-dimethyl-4-cyano-5, 6, 7, 8-tetrahydro-3(2H)-isoquinolinones were obtained by the reaction of acetyl chloride and the above isoquinolinone sodium salts. The reaction of iodoacetamide and the above isoquinolinethione sodium salts yielded 8-aryl-7-acetyl-3-carbamoylmethylthio-1, 6-dimethyl-4-cyano-5, 6, 7, 8-tetra-hydroisoquinolines, which were cyclized into 1-amino-6-aryl-7-acetyl-2-carbamoyl-5, 8-dimethyl-8-hydroxy-6, 7, 8, 9-tetrahydrothiophene[2,3-c]isoquinolines in basic medium.     

Synthesis and properties of N-methylmorpholinium 4aryl-6-methyl-5-phenylcarbamoyl-3cyano-1,4dihydropyridine-2-thiolates. Molecular and crystalline structure of 2allylthio-6-methyl-5-phenylcarbamoyl-4-(2chlorophenyl)-3-cyano-1,4-dihydropyridine

By the condensation of an aromatic aldehyde, the anilide of acetoacetic acid, cyanothioacetamide, and Nmethylmorpholine, substituted N-methylmorpholinium 1,4-dihydropyridine-2-thiolates have been synthesized and subsequently used in the synthesis of the corresponding thiones, 2-alkylthiopyridines, thieno[2, 3b]pyridines, and disulfides. X-ray diffraction has been used to establish the structure of 2-allylthio-6-methyl-5phenylcarbamoyl-4-(2-chlorophenyl)-3-cyano-1, 4-dihydropyridine.T. G. Shevchenko Lugansk State Pedagogical Institute, Lugansk 348011. A. N. Nesmeyanov Institute of Heteroorganic Compounds, Russian Academy of Sciences, Moscow 117813. N. D. Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 117913. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1243–1251, September, 1996. Original article submitted May 13, 1996.     

Synthesis of 3-cyano-5-ethoxycarbonyl-4-isobutyl-6-methyl-3,4-dihydropyridine-2(1H)-thione by three-component condensation

Condensation of isovaleraldehyde with cyanothioacetamide and ethyl acetoacetate (or its enamine) gives 3-cyano-5-ethoxycarbonyl-4-isobutyl-6-methyl-3,4-dihydropyridine-2(1H)-thione. This compound was used in the synthesis of substituted 1,4-dihydropyridin-2-yl sulfides. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 166–168, January, 1999.     

Synthesis and alkylation of 6-methyl-5-phenylcarbamoyl-3-cyano-4-ethylpyridine-2(1H)thione

By condensation of the anilide of acetoacetic acid, propionaldehyde, and cyanothioacetamide, 6-methyl-5-phenylcarbamoyl-3-cyano-4-ethylpyridine-2(IH)thione has been obtained. In an alkaline medium, this compound is alkylated, forming the corresponding substituted 2-pyridyl sulfides. From these pyridines, substituted thienoj2,3-blpyridines have been synthesized through the Thorpe-Ziegler reaction.T. G. Shevchenko Lugansk Pedagogical Institute, Lugansk 348011. N. D. Zelinskii Institute of Organic Chemistry, Moscow 117913. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1232–1234, September, 1996. Original article submitted May 13, 1996.     

Synthesis and Crystal Structure of 5-Amino-4-cyano-8-isobutyl-7-isopropyl-6-thiocarbamoyl-2-azabicyclo[2.2.2]oct-5-en-3-thione

5-Amino-4-cyano-8-isobutyl-7-isopropyl-6-thiocarbamoyl-2-azabicyclo[2.2.2]oct-5-en-3-thione was synthesized by the condensation of isovaleryl aldehyde with cyanothioacetamide. The structure of the product was established by X-ray crystallography.     

Propanal in the Syntheses of Alkyl-substituted 3-Cyano-2-piperidone, 3-Cyano-2,5,6,7-tetrahydropyrindin-2(1H)-one, and 3-Cyanopyridine-2(1H)-thione

Condensation of propanal with cyanothioacetamide and morpholine gave 3-cyano-4-ethyl-5-methyl-6-morpholino-2-piperidone, the structure of which was studied by X-ray analysis. Reaction of propanal with cyanothioacetamides and cycloalkanone enamines gave 3-cyano-4-ethyl-2,5,6,7-tetrahydropyrindin-2(1H)-one and 3-cyano-4-ethyl-5,6-hexamethylenepyridine-2(1H)-thione. The latter was used for the preparation of substituted 2-benzyloxycarbonylmethylthiopyridine and 3-amino-2-benzyloxycarbonylthieno[2,3-b]pyridine. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1053–1059, July, 2005.     

Synthesis, Structure, and Some Properties of Substituted 3-Carbethoxy(methoxy)-5-cyano-1,2,3,4-tetrahydrospirocyclohexane-4-pyridine-2-thiones

The condensation of cyclohexylidenemalononitrile or cyclohexylidenecyanoacetic ester with thioamidoethyl(methyl)malonate in the presence of sodium ethylate gave 6-amino-3-carbethoxy-5-cyano-4-spirocyclohexane-1,2,3,4-tetrahydropyridine-2-thione and 3-carbethoxy(methoxy)-5-cyano-6-oxo-4-spirocyclohexanepiperidine-2-thiones which were used in the synthesis of the corresponding substituted 2-alkylthiotetrahydropyridines. 5-Carbethoxy-3-cyano-3-methyl-6-methylthio-4-spiro-cyclohexane-3,4-dihydropyridine-2(1H)-one was studied by X-ray crystallography.     

Synthesis and reactions of 3-acetyl-6-methyl-2-(methylthio)pyridine

A reaction of methyllithium with 3-cyano-6-methylpyridine-2(1 H)-thione followed by alkylation of the resulting 3-acetylpyridinethione, or a direct reaction of methyllithium with 3-cyano-6-methyl-2-(methylthio)pyridine, afforded 3-acetyl-6-methyl-2-(methylthio)pyridine. The ketone obtained was examined in bromination reactions under various conditions. Bromi-nation in methanol or chloroform, proceeding through the formation of sulfonium bromides, gave substituted 3-(bromoacetyl)pyridine. A reaction of 3-acetyl-6-methyl-2-(methyl-thio)pyridine with N-bromosuccinimide in CCl4 afforded N-(pyridinesulfenyl)succinimide. The bromo ketone was used for the synthesis of various heterocyclic compounds.