MECHANISM OF THE REACTION OF CARBON AND NITROGEN NUCLEOPHILES WITH THE MODEL CARCINOGENS O-PIVALOYL-N-ARYLHYDROXYLAMINES - COMPETING SN2 SUBSTITUTION AND SN1 SOLVOLYSIS

The reaction of N,N-dimethylaniline (4) and aniline (5) with the O-pivaloyl-N-arylhydroxylamines (1a-f) in MeOH exhibits second-order kinetics and generates products of nucleophilic attack on the nitrogen of the hydroxylamine derivative. The characteristics of this reaction are not consistent with a nitrene or SET mechanism, an S(N)1 reaction with rate-limiting attack of the nucleophile, or nucleophile-assisted ionization. The only mechanism consistent with the available data, including substituent effects (rho+ almost-equal-to -3.0), cyclic voltammetry results, and product identifications, is an S(N)2 process. This reaction occurs in competition with an S(N)1 solvolysis that shows significant substituent dependence (rho+ = - 8.5). The reaction of 1 with 5 generates products of nucleophilic attack by both carbon (8, 9) and nitrogen (10). Competitive attack by carbon apparently occurs because of transition-state stabilization caused by the incipient C-N bond. The successful competition of the S(N)2 reactions with S(N)1 solvolysis for the esters 1a and 1b, which are similar in reactivity to the putative carcinogens 2a-c, indicates that certain adducts isolated from in vivo experiments, including 3, may be formed via S(N)2 mechanisms.