Heteroaromatic hydrogen exchange reactions. Part VI. Isotope effect for the acid-catalysed exchange of some 3-2H1- and 3-3H1-indoles

Abstract

Rates of deuterium and tritium displacement at 25 °C from the 3-position of indole, 5-methoxyindole, and 5-cyanoindole are reported for various aqueous acetic acid buffer solutions, together with data for indole in aqueous pyridine buffers and for indole and 5-cyanoindole in dilute HCl. Deuterium is displaced more readily than tritium throughout, and the incidence of general acid catalysis suggests a common A–SE2 exchange mechanism. Isotopic rate ratios computed from the experimental data for this pathway are substantial (kH/kD= 4·5–6·3) and show little systematic variation with the reactivity of either the substrate or the acid catalyst. Comparison with earlier data shows that the indole substrates are not exceptional in this respect and the size of the kinetic isotope effect appears to be an insensitive, if not unsatisfactory, index of transition state symmetry for aromatic hydrogen exchange reactions. Bronsted exponents for H3O+– and HOAc- catalysed exchange of these indoles are β= 0·67 and β= 0·75, respectively. Both are significantly larger than the Bronsted exponent obtained by the variation of the acid catalyst for exchange of 2-methylindole.