Hydrophobicity Parameter of Diazines (1) Analysis and Prediction of Partition Coefficients of Monosubstituted Diazines

The octanol/water partition coefficient (P) of a number of monosubstituted diazines was measured. The composition of the π value of substituents, the increment in the logP value accompanied with the introduction of substituents, was examined in terms of physicochemical substituent parameters and correlation analysis. The diazine‐π value of substituents was generally higher than the pyridine‐π value of corresponding substituents, indicating that the intramolecular electronic interactions between the ring‐N atoms and substituent are more pronounced than those in substituted pyridines in governing the logP value of the molecule. Except for 2‐substituted pyrimidines, the π value of substituents in each series of monosubstituted diazines was in general nicely correlated with the π value of the corresponding substituents in substituted pyridines along with electronic parameter terms representing “bidirectional” electronic effects on the relative solvation of the ring‐N atom(s) and the hydrogen‐bondable substituents with partitioning solvents according to the procedure proposed previously for the analysis of the π value in disubstituted benzenes and monosubstituted pyridines. Keeping in mind that 2‐pyrimidines substituted by hydrogen‐bondable groups sometimes behave as outliers, the correlations were believed to be usable for prediction of logP value of monosubstituted diazines.