Substituent effects on partition coefficients of barbituric acids

Article abstract of DOI:10.1002/jps.2600771105

Precise partition coefficients in 1-octanol-water at 25°C were determined for three 2-thiobarbituric acids and 14 barbituric acids with a wider range of substituents. The experimental log P values (log P(exp)) of barbituric acids were correlated with the carbon number and the branching effect of the C₅ substituent(s) by linear regression analysis. The carbon number term makes a major contribution to the partition coefficients. The contribution of the polar effect of the C₅ substituents was insignificant in contrast to a previous report. Hydrophobic constants (π) were determined for allyl, phenyl, and chloro-substituents, and these emperical π values gave much closer predicted calculated log P (log P(calc)) values when applied to the reported log P(exp) values.