Nucleophilic substitution studies on nitroimidazoles, and applications to the synthesis of biologically active compounds

Article abstract of DOI:10.1002/jhet.5570370120

The rationalization of the synthesis of substituted analogs of megazol, a biologically active 5-nitroimidazole at position 4 of the imidazole ring, had led to the study of intermediate steps. The methylation by diazomethane of 2,4-(5)dihalogeno-5-(4)nitroimidazole is regioselective leading to 2,4- dihalogeno-1-methyl-5-nitroimidazole 2. On this compound 2, hard nucleophiles such as cyanide, methoxide or hydride anions react only with the halogen at the 2 position; whereas soft nucleophiles such as amine, thiol or trifluoromethyl anion from an organocopper species react only with the halogen at position 4 in the intermediate 3b or compound 4b.