Hydrophobicity Parameters Determined by Reversed-Phase Liquid Chromatography. XI. Prediction of log P Values for Phenyl N-Methyl and Phenyl N, N-Dimethylcarbamates

Capacity factors, k', for m- and p-substituted phenyl N-methyl (2) and phenyl N,N-dimethyl (3) carbamates were measured on an octadecyl silica column using methanol-buffer (pH 7.4) mixtures as the mobile phase. The relationship between logP (P : 1-octanol-water partition coefficient) and log k' was studied as a function of the mobile phase composition. An eluent containing 50% MeOH gave good but separate log k'-log P linearities for (2) and (3). As the methanol concentration in the mobile phase was decreased, the correlation became more complicated due to the intervention of hydrogen-bond effects. In a water-rich eluent, the log k' values for the combined data set of (2) and (3) were found to be expressed by a correlation equation of the type, log k'=a logP + ρσ°+ h A HB A + h AM HB AM + const., where σ° represents the Hammett type electronic substituent constant. HB A and HB AM are indicator variables for hydrogen-accepting substituents and compounds (2) (amphiprotics), respectively. As expected, the log k w approach failed to give reliable log P values due to the strongly hydrogen-accepting property of the fixed substituents.