Syntheses and antimicrobial activities of 1-(3-benzyl-4-oxo-3H-quinazolin-2-yl)-4-(substituted)thiosemicarbazide derivatives

Abstract

A series of 1-(3-benzyl-4-oxo-3H-quinazolin-2-yl)-4-(substituted) thiosemicarbazides (AS1–AS10) were obtained by the reaction of 2-hydrazino-3-benzyl quinazolin-4(3H)-one (6) with different dithiocarbamic acid methyl ester derivatives. The key intermediate, 3-benzyl-2-thioxo-2,3-dihydro-1H-quinazolin-4-one (4), was obtained by the reaction of benzyl amine (1) with carbon disulphide and sodium hydroxide in dimethyl sulphoxide to give sodium dithiocarbamate, which was methylated with dimethyl sulphate to yield the dithiocarbamic acid methyl ester (2) and condensation with methyl anthranilate (3) in ethanol yielded the desired compound (4) via the thiourea intermediate. The SH group of compound (4) was methylated in the favourable nucleophilic displacement reaction with hydrazine hydrate, which afforded 2-hydrazino-3-benzyl-3H-quinazolin-4-one (6). The IR, and 1H- and 13C-NMR spectra of these compounds showed the presence of peaks due to thiosemicarbazides, carbonyl (C=O), NH and aryl groups. The molecular ion peaks of the quinazolin-4-one moiety (m/z 144) were observed in all the mass spectra of the compounds AS1–AS10. Elemental (C, H, N) analysis satisfactorily confirmed purity and elemental composition of the synthesized compounds. All the synthesized compounds were screened for their antimicrobial activity against selective gram positive and gram negative bacteria by agar dilution method. In the present study, compounds AS8 and AS9 emerged as the most active compounds of the series.