General approach to measurements of pKa differences by 13C NMR spectroscopy

Abstract

The method of measuring very small isotope effects on pK_a values using NMR spectroscopy has been adapted for wider use in comparative pK_a studies in mixtures of organic compounds. The method is illustrated initially on simple linear and branched monocarboxylic acids and on a mixture of methyladipic acids as examples of dicarboxylic acids. All measurements were performed by ¹³C NMR spectroscopy. In the case of propionic and valeric acid with close pK_a values their relative order as determined by the new technique was found to depend on the composition of the mixture. The method does not require pH measurements and opens a whole array of new applications in studies of acid–base equilibria.