Unusual rate-limiting proton transfer in the acid-catalysed reactions of N-nitroso compounds

Abstract

For both N-methyl-N-nitrosoaniline and N-nitrosodiphenylamine, the catalytic effect of halide ion, thiocyanate ion, and thiourea in the denitrosation reaction in acid solution disappears at high nucleophile concentrations. This suggests a change to an earlier rate-limiting step. The data, including the variation of rate constant with acidity, are quantitatively in accord with a reaction mechanism involving protonation of the nitrosamine followed by nucleophilic attack, either stage being rate limiting, depending on the reactivity and concentration of the nucleophile. The kinetic solvent isotope effect kH2O/kD2O decreases from 1.59 at 0.43M-thiourea to 0.71 at 0.015M-thiourea, which is consistent with a change from general acid catalysis at high [nucleophile] to specific hydrogen ion catalysis at low [nucleophile]. Substituent effects at the amino-nitrogen atom and also in the 4-position of a phenyl substituent are very small, the largest effect being a three-fold reduction in rate constant effected by a 4-NO2 group. These results are in accord with the known dipolar nature of nitrosamines. There is a close analogy between this system and the acid-catalysed cleavage reaction of carbamate derivatives. A similar mechanism is proposed involving a pre-association of the reactants forming a hydrogen-bonded intermediate.