Abstract
Our previous study on the relationship between the logarithm of 1-octanol/water prtition coefficient (log P) by the shake-flask method and the logarithm of the capacity factor (log k') by reversed-phase liquid chromatography for monosubstituted pyrazines (2PR) has been extended to the 2-chloro-6-substituted pyrazine series (6PR) and also to other reversed-phase high-performance liquid chromatographic conditions. Analyses have shown that 6PR behave similarly to 2PR. The influences of stationary and mobile phases were studied using several commercially available reversed-phase columns, and various organic modifiers. The results, from any combination of the stationary phases and the modifiers examined, have presented analogous trends to those previously observed : (1) The log P-log k' relationship becomes more complicated as the concentration of organic modifier in the mobile phase decreases due to the intervention of the electronic interactions and the retardation effect ascribed to ester and amide substituents. (2) Amphiprotic substituents usually exhibit an acceleration effect and should be treated separately. Practical conditions to be used for predicting the log P values are proposed.
