Synthesis and reactions of brominated 2-nitroimidazoles
Various approaches to the synthesis of the hitherto-unknown 4(5)-bromo-2-nitroimidazole (5) are reported. Direct bromination of 2-nitroimidazole with N-bromosuccinimide gave the unreported 4,5-dibromo-2-nitroimidazole (10) in quantitative yield, but this could not be selectively debrominated to give compound (5). While 1-methyl-2-nitroimidazole readily gave 4-bromo-1-methyl-2-nitroimidazole (15) on bromination, this could not be demethylated to give (5), and bromination of various other N-protected 2-nitroimidazoles was also unsuccessful. Lithiation of 4-bromo-1-tritylimidazole (21) followed by quenching with propyl nitrate gave (after detritylation and methylation) a mixture of a dimer (28) and compound (15), indicating that the desired product (5) is produced in this reaction although it can only be isolated in derivatized form. The proposed route for formation of the dimer suggests a general reaction between 1-alkyl-4-bromo-2-nitroimidazoles and strong C- and N-nucleophiles, resulting in substitution at the 5-position.