Reactivity and selectivity of nitrenium ions derived from ester derivatives of carcinogenic N-(4-biphenylyl)hydroxylamine and the corresponding hydroxamic acid

Article abstract of DOI:10.1021/ja00074a010

N-Acetyl-N-(sulfonatooxy)-4-aminobiphenyl (1a) and N-(4-biphenylyl)-O-pivaloylhydroxylamine (1c) decompose in 5% CH₃CN/H₂O, μ = 0.5 M, at 20°C via rate-limiting N-O bond heterolysis to generate the nitrenium ion intermediates 2a and 2b, respectively. Addition of Cl^- (≤0.5 M) or N₃^- (≤0.05 M) causes a marked decrease in the yields of all hydrolysis products derived from 1a and 1c, except the rearrangement products 10a and 11, without any change in the hydrolysis rate constants. At 0.5 M Cl^- more than 75% of the trappable hydrolysis products of 1a are replaced by the chloro adduct 7a without any observable change in the hydrolysis rate constant, and at 0.025 M N₃^- 96% of the trappable hydrolysis products of 1a are replaced by the azide adduct 8a, again, without an observable change in the hydrolysis rate constant. Similar results are obtained for 1c. The nucleophile/solvent selectivity ratios, k_cl/k_s and k_az/k_s, are 7.4 ± 0.3 M^-1 and (1.02 ± 0.04) × 10³ M^-1, respectively, for 2a. For 2b k/_cl/k_s is 15.7 ± 0.8 M^-1 and k_az/k_s is (2.9 ± 0.2) × 10³ M^-1. If k_az is at the diffusion controlled limit of 5 × 10⁹ M^-1 s^-1, k_s for 2a is 4.9 × 10₆ s^-1, and k_s for 2b is 1.7 × 10⁶ s^-1. Both of these ions are considerably less labile to solvent attack than 1-phenylethyl or cumyl carbocations with a 4-phenyl substituent. Surprisingly, 2a and 2b differ in their reactivity to solvent by only a factor of 3, while the estimated rate constants for their generation from starting materials with identical leaving groups differ by a factor of 10⁶. This phenomenon is similar to the situation previously observed by Richard for 1-aryl2,2,2-trifluoroethyl and 1-arylethyl carbocations and may be due to similar factors. A detailed mechanism for the hydrolysis of 1a and 1c, which is consistent with all available experimental data, is presented. The implications of these results for the mechanisms of chemical carcinogenesis by N-arylhydroxylamine derivatives are discussed.