N-nitroso compounds. Part 2. The synthesis of N-nitrosoclonidine and its decomposition in aqueous acidic media

Abstract

Clonidine, a 2-arylaminoimidazoline, undergoes nitrosation in aqueous nitrous acid to form N-nitrosoclonidine. ¹H NMR spectroscopy reveals that the nitroso group resides on one of the imidazoline nitrogen atoms. N-Nitrosoclonidine decomposes in aqueous acidic media to form quantitatively clonidine and nitrous acid. The reaction is acid catalysed and involves rate-limiting protonation of the substrate, as revealed by a solvent deuterium isotope effect, k₂^H/K₂^D, of 1.2 and the independence of the rate of denitrosation upon the presence of Cl^– or SCN^–. The Brønsted α exponent for general acid catalysis is 0.5. The mechanism is contrasted to that for analogous 2-arylimidazolines. which suffer acid-catalysed hydrolysis via a rapid pre-equilibrium protonation of the substrate followed by rate-limiting attack of the nucleophile to effect denitrosation or amidine hydrolysis. The present results are interpreted in terms of a protonation of the imidazoline nitroso nitrogen of N-nitrosoclonidine which results in an intermediate that decomposes by loss of the nitroso group.