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.     

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 properties of 5-acetyl-3-cyano-4-isobutyl-6-methyl-3,4-dihydropyridine-2(1H)-thione

Condensation of isovaleric aldehyde with cyanothioacetamide and acetylacetone or its enamine produces 5-acetyl-3-cyano-4-isobutyl-6-methyl-3,4-dihydropyridine-2(1H)-thione, from which 5-acetyl-3-cyano-4-isobutyl-6-methylpyridine-2(1H)-thione and the corresponding substituted 2-alkylthio-1,4-dihydropyridines are prepared. T. G. Shevchenko Lugansk State Pedagogical Institute, Lugansk 348011, Ukraine; e-mail: kgb@lgpi.lugansk.ua; N. D. Zelinskii Institute of Organic Chemistry of the Russian Academy of Sciences, Moscow 117913, Russia; Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 516–519, April, 1999.     

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-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.     

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 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.     

Molecular and crystal structure of 1-methylmorpholinium 6-methyl-4-phenyl-3-cyano-5-ethoxycarbonyl-1,4-dihydro-2-pyridineselenolate

The structure of 1-methylmorpholinium 6-methyl-4-phenyl-3-cyano-5-ethoxycarbonyl-1,4-dihydro-2-pyridineselenolate was studied using x-ray diffraction analysis. It was found that the 1,4-dihydropyridine ring has a boat conformation, and the plane of the pseudoaxial phenyl substituent is perpendicular to the bottom of this boat. In the anion, the C–Se bond length, which is 1.882(2) Å, indicates that the negative charge is formally located on the Se atom. The anions and cations of the salt in the crystal are linked by intermolecular hydrogen bonds.A. N. Nesmeyanov Institute of Heteroorganic Compounds, Russian Academy of Sciences, Moscow 117813, Russia. T. G. Shevchenko Lugansk State Pedagogical Institute, Lugansk 348011, Ukraine. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 785–789, June, 1998.     

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 6-oxo-3,5-dicyano-1,4,5,6tetrahydrospiro-(4′-r-cyclohexane-1′,4-pyridine)-2thiols and -selenols

By the interaction of a 4-R-cyclohe.xylidenecyanoacetic ester with cyanothio(seleno)acetainide, 6-oxo-3, 5dicyano-1, 4, 5, 6-tetrahydrospiro-(4-R-cyclohexane-1 ', 4-pyridine)-2-thiols and -selenols have been obtained; these have also been synthesized from a cyclohexytidenecyanothioacetamide and cyanoacetic ester. These thiols and selenols have been used to prepare the corresponding disulfides, diselenides, and spiro systems, including the fragments alkylthio(seleno)tetrahydropyridine, thieno[2, 3-bjpyridine, and 2, 3-dihydrothiazolopyridine.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. 9 pp. 1235–1242, September, 1996. Original article submitted May 13, 1996.     

Synthesis of N-methylmorpholinium 6-methyl-4-(2-thienyl)-5-phenylcarbamoyl-3-cyano-1,4-dihydropyridine-2-thiolate and its reaction with various functionally substituted methyl halides

Condensation of the anilide of acetoacetic acid, thiophene aldehyde, cyanothioacetamide and N-methyl-morpholine gave N-methylmorpholinium 6-methyl-4-(2-thienyl)-5-phenylcarbamoyl-3-cyano-1,4-dihydropyridine-2-thiolate which reacted with various halides ZCH₂Hal or H₂NCOCH(Ph)Cl to give substituted 2-ZCH₂-thio or 2-H₂NCOCH(Ph)-thio-1,4-dihydropyridines.     

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.     

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.     

Benzimidazole condensed ring systems. 5. Studies on the Synthesis of Pyrimido[1,6-α]benzimidazole-1,3(2H,5H)-diones

The reaction of ethyl 1H-benzimidazole-2-acetate (1) with methyl or ethyl isocyantes 2a,b resulted in excellent yields of the respective 2-methyl- or 2-ethylpyrimido[1,6-a]benzimidazole-1,3(2H,5H)-diones 3a,b , while the reaction of 1 with phenyl isocyanate (2c) gave, unexpectedly, ethyl 2-(1-phenylcarbamoyl-1H,3H-benzimidazol-2-ylidene)-2-phenylcarbamoylacetate (4). Alkylation of 3 with trimethyl or triethyl phosphates 5a,b led to the 5-methyl or 5-ethyl derivatives 6a-d . Chlorination of 6 with sulfuryl chloride afforded the 4-chloro derivatives 7a-d.     

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.     

Ring transformation of 5-amino (or acylamino)-6-hydroxy (or benzoyloxy)methylpyrimidin-4(3H)-ones into 1H-imidazoles

Treatment of 5-acylamino-6-hydroxy (or benzoyloxy)methyl-3-phenylpyrimidin-4(3H)-one 5,10 with 5% aqueous sodium hydroxide in ethanol gave 2-alkyl-5-hydroxymethyl-4-phenylcarbamoyl-1H-imidazoles 7,11 . Oxidation of 5-amino-6-benzoyloxymethyl-3-phenylpyrimidin-4(3H)-one 9 in the presence of copper( II ) chloride in alcohol gave 2-alkoxy-5-alkoxymethyl-4-phenylcarbamoyl-1H-imidazoles 12a,b accompanied by 5-amino-6-alkoxymethyl-3-phenylpyrimidin-4(3H)-ones 13a,b.     

Synthesis and Crystal Structure of 3-Carbamoyl-6-methyl-5-phenylcarbamoyl-2-thioxo-1,2,3,4-tetrahydropyridine-4-spirocyclohexane

3-Carbamoyl-6-methyl-5-phenylcarbamoyl-2-thioxo-1,2,3,4-tetrahydropyridine-4-spirocyclohexane has been synthesized by the condensation of cyclohexylidenecyanothioacetamide with acetoacetanilide and piperidine. The structure of the product was established by X-ray structural analysis.     

Aliphatic aldehydes in the synthesis of condensed 4-alkyl(cycloalkyl)-2-amino-3-cyano-4H-pyrans

Substituted 4-alkyl(cycloalkyl)-2-amino-3-cyano-4H-pyrans have been obtained from the reaction of aliphatic aldehydes with malononitrile and some other CH acids in the presence of N-methylmorpholine. T. G. Shevchenko Lugansk State Pedagogical University, Lugansk 348011, Ukraine. N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 117813, Russia; Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, 1363–1366, October, 1999.     

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.     

New methods for the synthesis of alkyl-substituted 6-oxo-3-cyano-1,4,5,6-tetrahydropyridine-2-thiolates and their derivatives

Condensation of formaldehyde or acetaldehyde with cyanothioacetamide and cyanoacetic ester in the presence of organic bases afforded 6-oxo-3,5-dicyano-4-R-1,4,5,6-tetrahydropyridine-2-thiolates (R=H, CH₃), which were utilized in the synthesis of substituted 2-alkylthiopyridones and thieno[2,3-b]pyridone. 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. 10, pp. 1381–1383, October, 1998.