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

Abstract

Macroscopic and model pKa values for the 2- and 4-pyridylacetic acids in aqueous propan-2-ol have been measured and used to evaluate the microscopic pKa 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 kN and kZ respectively). The smoothness of the relation between kZ and solvent composition, and the contrast in this respect with kN, are used as evidence that decarboxylation goes through the zwitterion. Similar calculations applied to some of the heterocyclic acetic acids previously examined show that kZ, but not kN, 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.