Comparisons of pKa and log P values of some carboxylic and phosphonic acids: synthesis and measurement.

Abstract

The changes in the physiochemical properties accompanying the substitution of a phosphonic acid group for a carboxylic acid group on various heterocyclic platforms was determined. A series of low molecular weight heterocyclic carboxylic and phosphonic acids was prepared, and the acid dissociation content (pKa) and log P values were measured potentiometrically. These values were compared to those of substituted benzene phosphonic acids, carboxylic acids, sulfonamides, and tetrazoles. The carboxylic acids included 3 pyrazoles, an imidazole, a triazole, 2 pyrimidines, and 6 aryl compounds. The phosphonic acids included a triazole, 2 pyrazoles, 4 pyrimidines, a thiophene, and 6 aryl compounds. Most of the compounds synthesized had adequate water solubility, although a simple methyl substituent in 2 series had a great effect, completely changing the properties. Log P values for the synthesized carboxylic and phosphonic acid compounds were below 2, and pK1 values for the heterocyclic phosphonic acids were generally 2 to 3 log units lower than for the heterocyclic carboxylic acids.