Synthesis, Structure, and Electrochemical Characteristics of 4-Aryl-2-carbamoylmethylthio-5-ethoxycarbonyl-1,4-dihydropyridine-3-carboxylic Acid Nitriles

We have obtained 4-aryl-2-carbamoylmethylthio-5-ethoxycarbonyl-1,4-dihydropyridine-3-carboxylic acid nitriles by S-alkylation of the corresponding 2-thioxo-1,2,3,4-tetrahydropyridine-3-carboxylic acid nitrile by iodoacetamide or one-pot multicomponent synthesis methods: condensation of 2-arylidene-acetoacetic acid ethyl ester, 2-cyanothioacetamide, piperidine, and iodoacetamide; acetoacetic acid ethyl ester, 3-aryl-2-cyanothioacrylamide, piperidine, and iodoacetamide; acetoacetic acid ethyl ester, an aromatic aldehyde, 2-cyanothioacetamide, piperidine, and iodoacetamide. We have carried out a comparative analysis of the capability of 2-alkylthio-4-aryl-5-ethoxycarbonyl-1,4-dihydropyridine-3-carboxylic acid nitriles for electrochemical oxidation as a function of the electronic properties of the aryl substituent in the 4 position of the heterocycle and the 2-alkylthio substituent. X-ray diffraction data indicate the existence of a hydrogen bond between the C=O of the 2-carbamoylmethylthio substituent and the NH of the hydrogenated heterocycle, which explains the more facile oxidation of the studied compounds compared with 2-methylthio-substituted 1,4-dihydropyridines.