EVIDENCE FOR THE FORMATION OF NITRENIUM IONS IN THE ACID-CATALYZED SOLVOLYSIS OF MUTAGENIC N-ACETOXY-N-ALKOXYBENZAMIDES

In aqueous acetonitrile, N-acetoxy-N-alkoxybenzamides undergo acid-catalysed solvolysis by the A(Al)1 mechanism to give acetic acid and nitrenium ions. This is indicated by an inverse dependence of the acid-independent rate constant, k(H), upon the activity of water, a solvent kinetic isotope effect of 0.44 and positive DELTA-S double-ended dagger values. In addition, relief of steric compression at the nitrogen enhances the rate of solvolysis. Hammett correlations with sigma+ 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 rho-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.