Hydrolysis of N-(Sulfonatooxy)-p-acetotoluidide: Solution Chemistry of Models for Carcinogenic Metabolites of Aromatic Amides

Article abstract of DOI:10.1021/jo00205a006

The hydrolysis reactions of the title compound, a model for the carcinogenic metabolites of polycyclic aromatic amides, were investigated over the pH range 1.0-8.0 by UV spectroscopic methods, product analyses, HPLC, and 1H NMR.This compound is unique among the N-(sulfonatooxy)acetanilides that have been studied to date in that over most of the pH range examined it exhibits non-first-order reaction kinetics.Product analyses indicate that, like the other N-(sulfonatooxy)acetanilides, the hydrolysis of this compound involves N-O bond cleavage, and the kinetics of the N-O bond cleavage process are consistent with a mechanism that includes generation of nitrenium ion-sulfate ion pairs.Four transient species, 9-12, were generated in sufficient quantity to be detected during the hydrolysis reaction.On the basis of isolated decomposition products and kinetic and spectral data obtained during the course of the hydrolysis reaction, the intermediate 9 was identified as 4-hydroxy-4-methylcyclohexa-2,5-dien-1-one N-acetylimine, while 10 and 11 were identified as the isomeric cis- and trans-N-acetyl-2-amino-5,6-dihydroxy-5-methylcyclohexa-1,3-dienes.These species are analogous to materials isolated by Gassman and Granrud from the methanolysis reactions of the methanesulfonate ester of N-hydroxy-p-acetotoluidide.The fourth intermediate, 12, has been tentatively identified as 4-(sulfonatooxy)-4-methylcyclohexa-2,5-dien-1-one.The pH dependence of the hydrolysis reactions of 9 and 10 have also been thoroughly investigated.Both are subject to acid catalysis of hydrolysis and give rise to a number of products.