Synthesis, Antimicrobial Activity, and Molecular Docking of Phenylcarbamate Derivatives Containing a Heterocyclic Fragment

The condensation of o-phenylenediamine with 2- and 4-aminobenzoic acids in 65% polyphosphoric acid at 180–190°C for 4 h or in boiling o-xylene in the presence of tetrabutoxytitanium gave 2-(2 or 4-amino­phenyl)-1H-benzimidazoles, and acylation of the latter with methyl chloroformate in the presence of triethylamine afforded the corresponding benzimidazoles containing a carbamate moiety. The condensation of o-phenylenediamine and 4-nitrobenzene-1,2-diamine with glycolic acid in 70–75% polyphosphoric acid at 130°C for 4 h produced 81% of 1H-benzimidazol-2-ylmethanol and 84% of 5-nitro-1H-benzaimidazol-2-ylmethanol which were reacted with phenyl isocyanate in tetrahydrofuran at 27–30°C for 3.5 h to obtain the corresponding benzimidazol-2-ylmethyl phenylcarbamates in 84–86% yields. With the goal of finding most promising antimicrobial agents, the synthesized 2-substituted benzimidazole derivatives, as well as previously reported carbamate derivatives of pyridazine and N-allyl derivatives of 2-(morpholin-4-yl)ethyl and 2-(pyridin-2-yl)ethyl phenylcarbamates, were subjected to molecular docking study using glucosamine-6-phosphate synthase as the target protein.