Synthesis of asymmetrically substituted aminohalogenobenzimidazoles

Abstract

2-Fluoroacetanilide (1) upon treatment with HNO₃–H₂SO, at –5 to 0 °C gave 6-fluoro-4-nitroacetanilide (3) whereas at –20 to –10 °C the product was 6-fluoro-3,4-dinitroacetanilide (5). Although the formation of compound (5) could be accounted for by a conventional nitration mechanism, the fact that (3) could not be nitrated to give (5) and that (5) was formed at a lower temperature than was (3) suggested that the reaction might proceed via an ipsoδ intermediate (2). Deacetylation of (5) followed by reduction and condensation with formic acid in the presence of HCl gave 6(5)-fluoro-5(6)formylaminobenzimidazole (11), 5(6)-amino-6(5)-fluorobenzimidazole (12) and 5-amino-4-chloro6-fluorobenzimidazole (13). Reduction of (5) with tin followed by condensation with acetic acid gave 5(6)-amino-6(5)-fluoro-2-methylbenzimidazole (14). Concomitant reduction and cyclisation of 6-chloro-2,4-dinitroaniline with formic acid and HCl gave a mixture of 7(4)-chloro-5(6)-formylaminobenzimidazole (15) and 5-amino-4,7-dichlorobenzimidazole (16).