Multicomponent synthesis of substituted N-aryl-4-aryl(3-pyridinyl-5-cyano)-6-(3,4-dihydroxybenzoylmethylsulphanyl)-2-methylnicotinamides, 6-allyl(carbamoylmethyl)sulphanyl-N-(4-chlorophenyl)-3-cyano-4-hetaryl-2-methyl-1,4-dihydronicotinamides and their antiradical and membrane-stabilizations properties

V. D. Dyachenko, O. O. Gonchar, I. V. Dyachenko

Abstract


The multicomponent condensation of aromatic aldehydes, acetoacetanilides, cyanothioacetamide, alkylating agents and morpholine in ethanol at 20°C was first synthesized to formation of substituted 4-aryl-N-aryl(3-pyridinyl)-5-cyano-6-(3,4-dihydroxybenzoylmethylsulphanyl)-2-methylnicotinamides, 6-allylsulphanyl-N-(4-chlorophenyl)-5-cyano-2-methyl-4-(3-pyridinyl)-1,4-dihydronicotinamide and 6-carbamoylmethylsulphanyl-N-(4-chlorophenyl)- 5-cyano-2-methyl-4-(4-pyridinyl)-1,4-dihydronicotinamide. In the first step Knoevenagel reaction produces the alkene which is then reacted with a Michael anilide acetoacetate to form the corresponding adduct. Last reaction conditions chemoselectively intramolecularly cyclized to substituted morpholinium tetrahydropyridinthiolate. Elimination of the water the latter leads to the formation of salt, the arises capable aromatization and alkylation of 3,4-dihydroxyphenacylbromide. Introduction this condensation as alkylating reagent allylbromide or α-chloroacetamide ends form the corresponding 1,4-dihydronicotinamide. The structure of the synthesized compounds was proved by IR-, 1H NMR- and chromatommas-spectrometry. Synthesized substances tested for anti-radical and membrane-stabilizing action. Revealed their high antiradical activity at a concentration of 10-1-10-3 mol/L compared with nicotinamide.


Keywords


multicomponent synthesis; acetoacetanilides; aromatic aldehydes; cyanothioacetamide; alkyl halides; Knoevenagel condensation; Michael reaction; nicotinamide; 1,4-dihydronicotinamide; antiradical and membranestabilization properties

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DOI: https://doi.org/10.24959/ophcj.15.827

Abbreviated key title: Ž. org. farm. hìm.

ISSN 2518-1548 (Online), ISSN 2308-8303 (Print)