Acidity in methanol–water

Abstract

The different factors influencing acidity of solutes in methanol–water (acidity of the solute, basicity and dielectric constant of the solvent, and specific solute–solvent interactions) are discussed. General thermodynamic models and preferential solvation models are used to establish linear relationships between the acidity p K values of a family of compounds in any methanol–water mixture and the p K values of the compounds in water. The parameters (slope and intercept) of the relationships are related with solvent composition for the most common families of compounds (phenols, carboxylic acids, amines and pyridine derivatives). These equations allow accurate calculation of the p K values of any member of these families at any methanol–water mixture from the p K value of the compound in water, or conversely estimation of the p K value in water from p K values measured in methanol–water mixtures. Some examples of prediction, including chromatographic retention of acid–base compounds, are presented.