Reductive fragmentation of 2-nitroimidazoles: amines and aldehydes

Glyoxal has been identified as a product in the fragmentation of reduced 2-nitroimidazole radiosensitizers. Quantitative analysis of glyoxal as its bis (2,4-dinitrophenylhydrazone) derivative shows that it is formed in good yield (9-23%) in a variety of 2-nitroimidazoles. In addition to glyoxal a second as-yet-unidentified carbonyl compound, and a series of amines are formed when reduced 2-nitromidazoles fragment in the presence of water. One of the amines derived from misonidazole is identified as 1-amino-3-methoxypropan-2-ol, the product of extensive ring cleavage. Radiation chemical reduction of the 2-nitromidazoles proceeds with the consumption of 3 electrons for each molecule reduced. This could imply that a radical disproportionation or dimerization step is involved in the reductive degradation of 2-nitroimidazoles.