Tautomerism and reactivity in heterocyclic N-oxides. A spectroscopic and theoretical study of benzimidazole N-oxide derivatives (N-hydroxybenzimidazoles)

The tautomeric forms of benzimidazole N-oxide derivatives in solution were studied using nuclear magnetic resonance (NMR) techniques. Further insight into the molecular structures was provided by theoretical calculations using density functional theory (DFT). In the gas phase the N-hydroxy tautomer was more stable than the N-oxide, whereas in solution the stabilization of one form or the other depended on hydrogen bond formation involving the N-hydroxy/N-oxide moiety. Derivative 4 (n-butyl-5-nitrobenzimidazole-2-carboxamide 3-oxide), having a 2-carboxamide moiety, was the only compound studied present as a mixture of tautomers, the N-oxide being the predominant one. This was assigned to the formation of an internal hydrogen bond between the N-oxide group and the amide hydrogen atom. The tautomeric form present in the solid state was studied for derivative 1 (ethyl-5-nitrobenzimidazole-2-carboxylate 3-oxide) and was conclusively assigned by X-ray diffraction techniques to the N-hydroxy tautomer. In the cry...