Kinetics and mechanism of the formation and decomposition of N-nitrosoamides and related compounds

Abstract

Kinetic studies of the nitrosation reactions of ethyl N-ethylcarbamate, N,N′-dimethylurea, and 2-imidazolidone have shown that all are subject to primary solvent isotope effects and to general base catalysis with bases of pK_a in the range 0.6–4.6. Both these features are indicative of a slow proton transfer. The characteristics of this proton transfer and the reactivity of the substrate depend to a large extent on the nature of the substrate: for ethyl N-ethylcarbamate the Brønsted plot is linear (β= 0.34) and the solvent isotope effect is 5.5; for N,N′-dimethylurea the curved Brønsted plot suggests that the reaction with acetate ion is diffusion-controlled, and the isotope effect is 3.2 in the absence of added base and 1.1 when the reaction is catalysed by acetate; for 2-imidazolidone the slightly curved graph of reaction rate against base concentration shows the proton donor to be an intermediate in the steady state, and the solvent isotope effects for the uncatalysed and acetate-catalysed reactions are 2.9 and 1.4, respectively. These facts suggest that the protonated intermediate has a near-zero pK_a value. Complementary studies of the denitrosation of N-nitroso-N-methylurea, N-nitroso-N,N′-dimethylurea, and N-nitroso-2-imidazolidone have shown that the rate-controlling step of each of these reactions is protonation of the substrate. These data, together with those from the nitrosation experiments, imply a pK_a of ca.–12 for the nitroso-amide. The discrepancy between the two results suggests that nitrosation initially takes place at the oxygen atom; this is followed first by a slow proton transfer and subsequently by a fast internal rearrangement to produce the thermodynamically more stable N-nitroso-amide.