Analysis and prediction of partition coefficients of meta- and para-disubstituted benzenes in terms of substituent effects.

The hydrophobic substituent parameter for a system of meta- and para-disubstituted benzenes, XC6H4Y, defined as pi X/PhY = log PXC6H4Y - log PC6H5Y, where P is the octanol-water partition coefficient and X and Y are variable and fixed substituents, respectively, varies from one system to another, according to the variation in substituent effects on the hydrogen bonding association of substituents with solvents. Using parameters from monosubstituted benzenes, pi X/PhH as the reference, the pi X values were analyzed by such relations as pi X/PhY = a pi X/PhH + rho Y sigma X + rho X sigma Y, where rho Y and rho X are susceptibilities of the relative hydrogen bonding association of substituents Y and X with two partitioning solvents to the electronic effect of X and Y, respectively. For substituents incapable of hydrogen bonding such as alkyl and halogen, the rho value is 0. The parameter a is a constant congruent to 1. The relationship was applied in calculating log P values of disubstituted benzenes.