Reaction of amine nucleophiles with a disulphide (2,2′-dinitro-5,5′-dithiodibenzoic acid): nucleophilic attack, general base catalysis, and the reverse reaction

Abstract

Secondary and primary amines react with a disulphide (Ellman's reagent, 2,2′-dinitro-5,5′-dithiodibenzoic acid) in a reaction which is not base catalysed. The primary amines possess a Brønsted β_nuc of +0.45 consistent with only partial bond development between N and S in the transition state. Proton transfer to yield the stable sulphenamide occurs in a fast step after N–S bond formation has occurred. Tertiary amines catalyse the disulphide cleavage and possess a high Brønsted β(+0.8) and trimethylamine has a solvent deuterium isotope effect (k_Me3N/k_Me3N 1.72) consistent with the general base catalysed attack of water. The normally more efficient nucleophilic attack would yield NNN-trialkylsulphenamides which, together with the thiolate anion co-product, is in unfavourable equilibrium with the reactions; steric hindrance also contributes to the inefficiency of the nucleophilic mechanism.