The recyclization of 2,6-diamino-4-aryl-4H-thiopyran-3,5-dicarbonitrile in boiling ethanol in the presence of a tertiary amine furnished ammonium 6-amino-4-aryl-3,5-dicyanopyridine-2-thiolates [1] or ammonium 6-amino-4-aryl-3,5-dicyano-1,4-dihydropyridine-2-thiolates[2]. The use in this reaction at all other equal conditions of aqueous ethanol resulted in the formation of 4-aryl-6-hydroxy-2-thioxo-1,2-dihydropyridine-3,5-dicarbonitriles [3]. The application of ethanol as solvent and secondary amine piperidine as catalysts gave rise to 6-amino-4-aryl-2-thioxo-1,2-dihydropyridine-3,5-dicarbonitriles [4]. At the same time with use in this recyclization of primary amines (aniline and hydrazine) as catalysts 2-amino-4-phenyl-6-phenylaminopyridine-3,5-dicarbonitriles and 2,6-dihydrazinyl-4-phenylpyridine-3,5-dicarbonitriles were respectively obtained [5].It was shown for the fi rst time that the recyclization of 2,6-diamino-4-phenyl-4H-thiopyran-3,5-dicarbonitrile (I) in boiling ethylene glycol monomethyl ether in the presence of double excess of benzylamine gave 2,6-bis(benzylamino)-4-phenylpyridine-3,5-dicarbonitrile (II). The mechanism of the discovered recyclization and its application limits are under investigation.2,6-Diamino-4-phenyl-4H-thiopyran-3,5-dicarbonitrile (I) was prepared as described in [1]. 2,6-Bis(benzylamino)-4-phenylpyridine-3,5-dicarbonitrile (II).A mixture of 0.3 g (1.2 mmol) of thiopyran I and 0.26 ml (2.4 mmol) of benzylamine in 5 ml of ethylene glycol monomethyl ether was boiled for 5 h. On cooling to 20°C the reaction mixture was treated with 10% hydrochloric acid till pH 2 and left standing in the cold. After 3 days the precipitate in the form of red crystals was fi ltered off and washed with ethanol and hexane. Yield 0.2 g (43%), mp 247-250°C, possesses fl uorescence under UV irradiation. IR spectrum, ν, cm -1 : 3310 (NH), 2200 sh (C≡N). 1 H NMR spectrum, δ, ppm: 4.51 d (4H, 2CH 2 , J 5.9 Hz), 7.19-7.23 m (10H, 2Ph), 7.48-7.54 m (5H, Ph), 8.21 t (2H, 2NH, J 5.9 Hz). Mass spectrum, m/z (I rel , %): 415 (59.4) [M] + , 324 (26.0) [M -PhCH 2 ] + , 219 (4.3), 165 (2.3), 106 (39.6) [PhCH 2 NH 2 ] + , 91 (100) [PhCH 2 ] + , 65 (10.0). Found, %: C 77.98; H 5.00; N 17.02. C 27 H 21 N 5 . Calculated, %: C 78.05; H 5.09; N 16.86. 1 H NMR spectrum was registered on a spectrometer Bruker Avance II-400 (400.13 MHz) in DMSO-d 6 , internal reference TMS. Mass spectrum was measured on an instrument MKh-1321, electron impact ionization (70 eV). IR spectrum was registered on a FIR-spectrometer Spectrum One (Perkin Elmer) from mulls in mineral oil. The reaction progress was monitored and the purity of compound II was checked by TLC on Silufol UV-254 plates, eluent acetone-hexane, 3:5, development in iodine vaor and under UV irradiation. The melting point was measured on a Köffl er heating block.
Three-component reaction of 2,6-diamino-4-aryl-3,5-dicyano-4H-thiopyrans, acetoacetanilides, and alkylating reagents proceeds via cross-recyclization of thiopyrans to form 6-alkylthio-4-aryl-N-aryl-2-methyl-5-cyanonicotinamides, 3-imino-6-methyl-2-(4-methoxybenzoyl)-4-(3,4-dimethoxyphenyl)-N-phenyl-2,3-dihydrothieno[2,3-b]pyridine-5-carboxamide, and 3-amino-6-methyl-4-(3,4-dimethoxyphenyl)-2-(4-oxo-4H-pyrido[1,2-a]-pyrimidin-2-yl)-N-phenylthieno[2,3-b]pyridine-5-carboxamide.Search for biologically active nicotinamide derivatives is a promising to develop herbicides [1, 2] and drugs for Alzheimer's disease treatment [3,4].Studies on preparation of functionally substituted nicotinamide derivatives [5][6][7][8] showed that cross-recyclization of 2,6-diamino-4-aryl-3,5-dicyano-4H-thiopyrans Ia-Ic with acetoacetanilides IIa and IIb in refluxing ethanol in the presence of an equimolar quantity of triethylamine followed by addition of the alkylating reagent IIIa-IIIe afforded new nicotinamide derivatives such as 6-alkylthio-4,N-diaryl-2-Apparently, the reaction pathway included opening of the thiopyran ring to form intermediate VI that was further transformed into arylmethylidenecyanothioacetamide VIII via malononitrile VII elimination [9][10][11]. The Michael addition of acetoacetanilide II to arylmethylidenecyanothioacetamide VIII led to formation of the corresponding labile adduct IX, which underwent intramolecular heterocyclization to give the substituted pyridine X. The latter was subject to regioselective alkylation at the sulfur atom to form the corresponding thioethers IVa-IVg, in accordance with fundamentals of 2-mercaptopyridine chemistry [12,13]. At the same time, the cross-recyclization of thiopyran Ia, acetoacetanilide IIa, and 4-methoxyphenacylchloride IIIa yielded unknown 3-imino-6-methyl-2-(4-methoxybenzoyl)-4- (3,4-dimethoxyphenyl)-N-phenyl-2,3-dihydrothieno[2,3-b]pyridine-5-carboxamide V instead of the expected thioether XI, due to rapid intramolecular cyclization of intermediate XI.Noteworthily, formation of the substituted thieno[2,3-b]pyridines of that type generally does not stop at the stage of the imine V formation due to spontaneous transformation of the latter into the amine [14][15][16]. That reaction pathway was realized when 4-oxo-2-chloromethyl-4H-pyrido[1,2-a]pyrimidine IIId was used as an alkylating agent. As a result, 3-amino-6-methyl-4-(3,4-dimethoxyphenyl)-2-(4-oxo-4Н-pyrido [1,2-a]pyrimidin-2-yl)-N-phenylthieno[2,3-b]pyridine-5-carboxamide VI was obtained.
Recyclization of 4-Alkyl(aryl)-2,6-diamino-3,5-dicyano-4H-thiopyrans with 2-Aminoethanol and (2-Furyl)methylamine. -Title reaction leading to pyridines (III) occurs through C-S cleavage, nucleophilic attack by amines (II), heterocyclization, and oxidative dehydrogenation. -(DYACHENKO*, V. D.; RYLSKAYA, T. A.; Chem. Heterocycl. Compd. (N. Y., NY, U. S.) 49 (2013) 6, 897-901, http://dx.doi.org/10.1007/s10593-013-1323-0 ; Taras Shevchenko Lugansk Natl. Univ., Lugansk 91011, Ukraine; Eng.) -R. Langenstrassen 12-141
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