Rates of decarboxylation of the radical cations of indol-3-ylacetic acids and comparison with indolizin-1-ylacetic acids

Abstract

The radical cations of indol-3-ylacetic acid and derivatives were found to eliminate CO₂ to yield skatolyl radicals with rates in the range ca. 10² to >10⁵ s^-1, strongly dependent on substitution. For the radical cations substituted at nitrogen, the rate of decarboxylation did not vary with pH 4–7.5, but for those unsubstituted at nitrogen, deprotonation caused the rate of decarboxylation to decrease with increasing pH. The rate of decarboxylation of the radical cations exhibited a strong dependence on the respective reduction potentials, with a 100 mV increase in reduction potential corresponding to a ca. tenfold increase in the rate of decarboxylation. Methylation at the side-chain α-position increased the rate of decarboxylation >sixfold, but insertion of a methylene group, as in 3-indol-3-ylpropionic acid or tryptophan, completely inhibited decarboxylation. In contrast, indolizin-1-ylacetic acids, which are isomers of indolylacetic acids in which the heterocyclic nitrogen is the bridgehead, did not decarboxylate on one-electron oxidation.