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