2-Hydroxylaminoimidazoles--unstable intermediates in the reduction of 2-nitroimidazoles.

An unstable 2-hydroxylaminoimidazole (2-hydroxylamino-1-methylimidazole) was prepared by the reaction of 2-fluoro-1-methylimidazole with hydroxylamine. This substance was sufficiently stable (half-life of 1-2 days) in acid solutions to be observed and characterized by NMR spectroscopy; decomposition at neutrality was, however, rapid (half-life of 1-10 min). Radiochemical and electrochemical reduction experiments were carried out at pH 4 and pH 7 with 2-nitro-1-methylimidazole and misonidazole [1-(3'-methoxy-2'-hydroxypropyl)-2-nitroimidazole]. A four electron stoichiometry was found in every case. The pH 4 reduced product was identified as the 2-hydroxylamino derivative (greater than 80% yield). The pH 7 reduced solutions, on the other hand, showed no aromatic 1H NMR signals, suggesting that a simple imidazole ring was no longer present. A shift to pH 7 of the hydroxylamine produced at pH 4, however, resulted in very similar NMR spectra. The conclusion, therefore, is that the hydroxylamine was produced initially on reduction of the nitroimidazole, but it was not stable.