The decarboxylation of some heterocyclic acetic acids. Part II. Direct and indirect evidence for the zwitterionic mechanism

Abstract

Macroscopic and model pK_a values for the 2- and 4-pyridylacetic acids in aqueous propan-2-ol have been measured and used to evaluate the microscopic pK_a values as a function of solvent composition. From these are calculated the mole fractions of neutral from and zwitterion present, which in conjunction with the observed decarboxylation rate allows this to be re-expressed in terms of these sub-species (as k_N and k_Z respectively). The smoothness of the relation between k_Z and solvent composition, and the contrast in this respect with k_N, are used as evidence that decarboxylation goes through the zwitterion. Similar calculations applied to some of the heterocyclic acetic acids previously examined show that k_Z, but not k_N, is a linear or slightly curved function of Perrin's nuclear σ constants; this and other evidence is interpreted in favour of the zwitterionic route for the whole range of heterocycles examined. A refinement of the theory implicates tautomeric ratio, which has been measured for some heterocyclic acetates, as a further influence on decarboxylation rate. The β-keto-acids are discussed in the light of these results: it is concluded that they also are probably decarboxylated by the zwitterionic mechanism.