Hydrogen-bond basicity of solutes in hydroxylic solvents from octanol-water partition coefficients

Hydrogen-bond acceptor strengths of numerous bases can be extracted from octanol-water partition coefficients after subtraction of a hydrophobic-cavity term proportional to the molecular volume of the solutes. A stepwise correlation analysis is carried out to compare these basicities in hydroxylic solvents with the pK(x)(HB) hydrogen-bonding basicity scale determined for the 1: 1 association of 4-fluorophenol in carbon tetrachloride. Within a family of bases, hydrogen-bond acceptor ability in hydroxylic solvents is found to be predicted by the pK(x)(HB) scale and the overall basicity of bifunctional and trifunctional solutes is precisely calculated by an exact summation SigmapK(x)(HB) of the strengths of the individual basic sites. Plots of octanol-water partition coefficients against SigmapK(x)(HB) present classical family-dependent relationships separating the amines, pyridines and ethers from the other bases. This separation can be accounted for by a simple multiplicative term lambda restoring the additivity of the basicity strengths. Careful dissection of the overall basicities of bifunctional compounds into their individual components reveals the considerable levelling effect of the hydroxylic solvents on die relative strengths of the different basic groups present in the same solute. A two-parameter equation involving the molecular volume and the corrected summation for all basic sites SigmalambdapK(x)(HB) is proposed to predict partitioning between octanol and water. Significant deviations from the equation are found when one of the basic centres of the solute is hindered by bulky substituents. Copyright (C) 2002 John Wiley Sons, Ltd.