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 k_H2O/k_D2O 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.