The chemistry of nitroso-compounds. Part V. Encounter control for the nitrosation of indoles in dilute acid

Abstract

Rates of nitrosation of 1,2-dimethyl-, 2-phenyl-, 2-methyl-, 2-methyl-5-nitro-, 5-cyano-, 5-nitro-, and 1-methyl-5-nitro-indole in dilute aqueous acid under various conditions are reported. Reaction to form the 3-nitroso-product may be brought about by various reagents, including nitrous anhydride, the nitrous acidium ion, and nitrosyl chloride, depending on the conditions. Examination of kinetic hydrogen isotope effects and chloride ion catalysis shows that these reactions follow the expected A–S_E2 pathway characteristic of aromatic electrophilic substitution, but that the rate-limiting step depends on the basicity of the substrate. For basic compounds (pK_A–3·5) either formation of the reagent (in the case of nitrous anhydride) or diffusion of the reactants is rate limiting: molecular rate coefficients for the reaction of nitrosyl chloride with the neutral substrate are of the order of 10¹⁰ l mol^–1 min^–1 at 0 °C. For less basic compounds (pK_A⩽–6·0), proton expulsion from the Wheland-type intermediate is slow as is usual for aromatic nitrosation. Generally, indole compounds are much more reactive than aromatic amines (diazotisation) towards these nitrosating agents, and this suggests that nitrosation of the former may involve initial substitution of the heterocyclic N atom, with rearrangement to the 3-nitroso-product.