Simple methods for the estimation of ionization constants of substituted pyridine N-oxides in polar aprotic solvents and water

Abstract

A direct method for the determination of the pK a values of acids conjugated to substituted pyridine N-oxides has been proposed which is based on the pH measurement of the solution of the basic salt. It has been experimentally shown that the method is reliable when applied to N-oxides of not too low basicity (pK a >5). Correlation has been performed between the pK a values in aqueous and aprotic media solutions which shows the great influence of the solvation effect on the acid-base equilibria. The good correlation between the pK a values in aqueous and non-aqueous solutions enables the pK a values in water to be estimated with sufficient accuracy, even in the cases when the experimental limitations make the determination impossible which is shown on the basis of selected examples.