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

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 postion 4 in the intermediate 3b or compound 4b.