Kinetics and mechanism of the nitrosation of thioproline: evidence of the existence of two reaction paths

Abstract

The kinetics of N-nitrosation of thioproline have been studied under a variety of experimental conditions. The experimental rate equation obtained in the absence of nucleophiles suggests that under these conditions nitrosation initially takes place at the sulphur atom, the nitroso group subsequently being transferred to the nitrogen atom. The fact that a primary isotope effect and general base catalysis are observed, together with the experimental rate equation, implies that the rearrangement is intramolecular, and that the rate-controlling step is the loss of a proton from the nitrogen atom of the S-nitrosated intermediate. Cl^–, Br^–, SCN^–, and thiourea all catalyse the rection via the formation of the corresponding nitrosyl compounds, which react directly with the unprotonated thioproline nitrogen atom in both the negatively charged and neutral forms of the amino acid. The observed rate constants for these reactions are discussed in terms of the nitrosating agent and the substrate. In the case of Br^– and Cl^– the plot of reaction rate against concentration of catalyst levels off at high values of the latter, showing that the protonated N-nitrosamine intermediate is in the steady state. The characteristics of the curve, which provide a measure of the susceptibility of the nitrosamine to nucleophiles, show that this is much less than that of aromatic amines of similar basicity.