Hydrophobicity Parameters Determined by Reversed-Phase Liquid Chromatography. V. Relationship between the Capacity Factor and the Octanol-Water Partition Coefficient for Simple Heteroaromatic Compounds and Their Ester Derivatives.

Abstract

The log k' (k' : capacity factor) values of various heteroaromatic compounds were measured by reversed-phase high performance liquid chromatography (RPLC) using a Capcell pack C18 column and methanol-water eluents, and the relationship with the log P values (P : 1-octanol-water partition coefficient) was examined as a function of the mobile phase composition. Furans having nonhydrogen-bonding or weakly hydrogen-accepting substituents exhibited a good linear relationship at 50% MeOH concentration. Amphiprotic sibstituents, CONHR, showed an acceleration effect (less retained than nonhydrogen-bonders and hydrogen-acceptors under the condition of equivalent log P), as is often observed in heterocyclic systems. The relationship was more complicated at other methanol contents, due to different retention behavior demonstrated by the ester-type substituents, CO2R and CONR2 (ester effect), To gain more insight into this ester effect, the retention behavior of ester derivatives of various heteroaromatics such as furan, benzofuran, N-Me pyrrole and indole was also studied. The factors affecting the log P-log k' relationship were discussed, and the optimum RPLC condition for predicting the log P value was described.