Evidence for the formation of nitrenium ions in the acid-catalysed solvolysis of mutagenic N-acetoxy-N-alkoxybenzamides

Abstract

In aqueous acetonitrile, N-acetoxy-N-alkoxybenzamides undergo acid-catalysed solvolysis by the AAl1 mechanism to give acetic acid and nitrenium ions. This is indicated by an inverse dependence of the acid-independent rate constant, kH, upon the activity of water, a solvent kinetic isotope effect of 0.44 and positive ΔS‡ values. In addition, relief of steric compression at the nitrogen enhances the rate of solvolysis. Hammett correlations with σ+ substituent constants were found for the rates of solvolysis of para-substituted-N-acetoxy-N-butoxybenzamides and N-acetoxy-N-(para-substituted benzyloxy) benzamides. This fact and the low ρ-values of –1.35 and –1.56, respectively, are indicative of a strong build-up of positive charge in the transition state which has both nitrenium ion and oxonium ion character and is in accordance with computed molecular-orbital properties of N-alkoxynitrenium ions. Greater levels of mutagenicity have been measured for those compounds which are more readily solvolysed to nitrenium ions.