Heteroaromatic hydrogen exchange reactions. Part IV. Base-catalysed protodetritiation of 3-3H1-indoles in aqueous sodium hydroxide

Abstract

Rates of protodetritiation in aqueous NaOH at 25 °C are reported for eight indoles labelled at the 3-position. Both the catalytic effect of high [NaOH] and substituent effects on the rate are consistent with an S_E2 mechanism involving rate-limiting reaction between the indole anion and H₂O. The electrophilic nature of the reaction is demonstrated particularly by the large rate accelerations induced by 2-alkyl substituents, which can be attributed to extensive hyperconjugation in the neutral transition state. Values of the dissociation constant (K_E) for amino-hydrogen ionization obtained from the kinetic data are also reported. Various structure–reactivity relationships for the data are examined. The Brønsted relationship based on K_E values is unsatisfactory with an exponent in excess of the theoretical limit (β = 1·1). This arises from extensive charge delocalization accompanying attack at the 3-position, and a sensible Brønsted correlation can only be obtained with a parameter that directly measures the reactivity of this site. The application of H_ acidity functions to kinetic data is also discussed.