Synthesis, characterization, antimicrobial evaluation and docking studies of 3-(5-(2-oxido-2-(4-substituted phenyl)-ureido-benzo[d][1,3,2]dioxaphosphol)-5-yl-1h-tetrazol-1-yl) thiophene-2-carboxamides and carbamoyl thiophene-1h-tetrazolyl-dioxaphosphol-(morpholine/piperidine/4-methyl piperizine)-carboxamides

Abstract

A series of compounds, 3-(5-(2-oxido-2-(4-substitutedphenyl)-ureido-benzo[d][1,3,2]dioxaphosphol)-5-yl-1H-tetrazol-1-yl)thiophene-2-carboxamides (9a-f), were synthesized through the condensation of 3-(5-(3,4-dihydroxyphenyl)-1H-tetrazol-1-yl)thiophene-2-carboxamide (7) with 4-substituted phenyl-carbamido-phosphoric acid dichlorides (8a-f). Similarly, carbamoyl thiophene-1H-tetrazolyl-dioxaphosphol morpholine/piperidine/4-methylpiperazine-carboxamides (9g-i) were obtained by condensing compound (7) with morpholinyl-, piperidinyl-, or N-methylpiperazinyl-carbamido-phosphoric acid dichlorides (8g-i). Hydrolysis of 3-(5-(3,4-dimethoxyphenyl)-1H-tetrazol-1-yl) thiophene-2-carboxamide (6) produced the key intermediate (7). Compound (6) was synthesized via the reaction of 3-((3, 4-dimethoxybenzylidene) amino) thiophene-2-carboxamide (5) with sodium azide in tetrahydrofuran. Intermediate (5), in turn, was prepared by condensing 3-aminothiophene-2-carboxamide (3) with 3, 4-dimethoxybenzaldehyde (4) in the presence of a few drops of acetic acid. The starting compound (3) was obtained from the condensation of 2-cyanoacetamide (1) and 1,4-dithiane-2,5-diol (2) using trace amounts of triethylamine in ethanol. The structures of the synthesized compounds (9a-i) were confirmed through IR, ¹H NMR, ¹³C NMR, mass spectrometry, and elemental analysis. The synthesized molecules were further subjected to biological evaluation and molecular docking studies, and the findings are presented in this article.