THE NITROSATION OF AMINO-ACIDS

With a view to clarifying analogies and differences between the mechanisms involved in the nitrosation of amino acids and secondary amines, we studied the kinetics of the nitrosation of five imino acids (azetidine-2-carboxylic acid, pyrrolidine-2-carboxylic acid, piperidine-2-carboxylic acid, piperidine-3-carboxylic acid, and piperidine-4-carboxylic acid) and of the ethyl esters of three of them. Reaction kinetics were determined by the initial rate method, by spectrophotometric monitoring of the concentration of nitroso amino acid formed. The presence of the -COO- group in the amino acids opens a new mechanistic route for the nitrosation of the secondary amino group: a nitrosyl carboxylate formed initially acts as an internal nitrosating agent, resulting in intramolecular migration of -N = O from the carboxylate group to the secondary amino group. The observed order of the alpha-, beta-, and gamma-amino acids as regards the ease of N-nitrosation by this route is explained in terms of the relative energies of (a) the equatorial and axial orientations of the C-ring-C-carboxyl bond, and (b) the chair and boat forms of the piperidine ring. (C) 1994 John Wiley & Sons, Inc.