Involvement of Free Nitrenium Ions, Ion Pairs, and Preassociation Trapping in the Reactions of Ester Derivatives of N-Arylhydroxylamines and N-Arylhydroxamic Acids in Aqueous Solution

Article abstract of DOI:10.1021/jo00130a034

Rate and product yield data for the decomposition of the ester derivatives of N-arylhydroxylamines and N-arylhydroxamic acids 1a-i in aqueous solution in the presence of N3^- support a mechanistic scheme (Scheme 5) in which the trapping by N3^- changes from trapping of the free ion, to trapping of an ion pair, to a preassociation process as the ion becomes more reactive.When the rate constant for trapping of the free ion by solvent, k_s, < ca. 10⁸ s^-1, trapping by both N3^- and solvent occurs almost exclusively at the free ion.When 10⁸ s^-1 < ca. k_s < ca. 10¹⁰ s^-1, a change in the mechanism occurs, and trapping of the ion pair by both solvent and N3^- becomes important.In this range of reactivity there is also evidence, based on the apparent magnitude of k_az', the rate constant for N3^- trapping of the ion pair, that some of the reaction with N3^- occurs through a preassociation process.When k_s > ca. 10¹⁰ s^-1 essentially all of the observed N3^- trapping occurs by a preassociation process because N3^-, which cannot react with the ion pair faster than the diffusion limit, can no longer compete with solvent for the ion pair.This progression in trapping mechanisms as the ion becomes more reactive with solvent is apparently an important factor in determining the carcinogenic potential of aromatic amines and amides which are metabolized into sulfuric and carboxylic acid esters of N-arylhydroxylamines and N-arylhydroxamic acids.Nitrenium ions which undergo slow reactions with solvent are selectively trapped by biologically relevant nucleophiles such as 2'-deoxyguanosine.As the rate constant for reaction with solvent increases, the nitrenium ion is no longer capable of undergoing selective trapping by nonsolvent nucleophiles because these reactions are limited by diffusion, but solvent trapping is not.