Heteroaromatic hydrogen exchange reactions. Part 9. Acid catalysed decarboxylation of indole-3-carboxylic acids

Abstract

Rates of acid catalysed decarboxylation in both H₂O and D₂O at 25° are reported for indole-3-carboxylic acid and its 2-methyl and 5-chloro-derivatives, and for indole-3-carboxylic acid in aqueous pyridine buffers at 60°. The experimental data are shown to fit well with the kinetic expression (Rate ={a+b[L₃O⁺]/(1 +c[L₃O⁺])}[Substrate]) obtained for the decarboxylation of other aromatic and heteroaromatic acids, consistent with an A–S_E2 mechanism involving a zwitterionic intermediate. Evaluation of the parameters b and c gives solvent deuterium isotope effects for reaction via both the neutral substrate and the carboxylate anion, from which primary isotope effects for proton transfer from the solvent to the substrate can be assessed. These primary isotope effects are remarkably similar (2.23–2.72), for all three indole-3-carboxylic acids. Further, comparison with decarboxylation data for azulene-1-carboxylic acid, and with other results for the protonation of indole compounds, shows there is no systematic variation in the solvent isotope effect for proton transfer (all of which lie in the limited range 2.23–2.87) over a reactivity span of ca. 10⁶. This implies that primary isotope effects are little influenced by substrate reactivity and, inter alia, by the symmetry of the transition state for proton transfer.