In aqueous acetonitrile, N-acetoxy-N-alkoxybenzamides undergo acid-catalysed solvolysis by the A,,1 mechanism t o give acetic acid and nitrenium ions. This is indicated by an inverse dependence of the acid-independent rate constant, k, , upon the activity of water, a solvent kinetic isotope effect of 0.44 and positive AS* values. In addition, relief of steric compression at the nitrogen enhances the rate of solvolysis. Hammett correlations with 0' substituent constants were found for the rates of solvolysis of para-substituted-N-acetoxy-N-butoxybenzamides and N-acetoxy-N-(parasubstituted benzyloxy) benzamides. This fact and the low p-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 molecularorbital properties of N-alkoxynitrenium ions. Greater levels of mutagenicity have been measured for those compounds which are more readily solvolysed to nitrenium ions.* Errors in Tables 2, 3 and 5 are based upon the standard deviations in the slope and intercept. Temperatures were accurate to within 0.7 K. Weighted least-squares fits taking into account all experimental inaccuracies gave smaller errors in the slope and intercept.
N-Methylaniline reacts bimolecularly with mutagenic N-acetoxy-N-alkoxybenzamides and the resultant N-alkoxy-N-(N-methylanilino) benzamides undergo a novel, concerted rearrangement to alkylbenzoates and 1 -methyl-I -phenyldiazene which dimerizes to 1,4-dimethyl-I ,4-diphenyltetrazene.
N-Acetoxy-N-alkoxybenzamides (1) are a new class of chemicalmutagens. 1 * 2 , 3 They are analogous to the ultimate carcinogens derived from the metabolism of the aromatic amines (2), namely N-acetoxy-N-arylamines (3) or their sulfate esters, both of which have been widely implicated in the mutation of nucleic acids.4 These metabolites are believed to react with DNA, nucleotides and model aromatic amines by either an s N 1 or an sN2 process and evidence for both modes of reaction has recently emerged. Certainly, s N 1 reactivity has been found under solvolytic conditions and here an electrophilic, resonance-stabilised arylnitrenium ion (4) is generated.' However, both Boche and Novak have recently reported bimolecular reactions for model aromatic amine metabolites.6
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