Substituent effects on partition coefficients of barbituric acids.

Abstract

Precise partition coefficients in 1-octanol-water at 25 degrees C were determined for three 2-thiobarbituric acids and 14 barbituric acids with a wider range of substituents. The experimental log P values (log Pexp) 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 (pi) were determined for allyl, phenyl, and chloro-substituents, and these empirical pi values gave much closer predicted calculated log P (log Pcalc) values when applied to the reported log Pexp values.