ChemInform Abstract: Hydrophobicity and Structure of 1,2,4-Triazole Derivatives Bearing 1-Carbamoyl and 3-Sulfonyl Groups

Various 3-sulfonyl-1,2,4-triazole-1-carboxamides (5a–h) were synthesized and their hydrophobicities were evaluated from their retention time in reversed-phase HPLC chromatography. Although the compounds have rather complex structures, a good linear relationship was observed between log k′ of these compounds derived from the retention time of HPLC and log PH for water–hexadecane partition coefficients of related alcohols. In regards with the rotation about the O2S–C(ester part) single bond, the preference for a gauche conformer relative to the anti form was revealed by both X-ray structural analysis of 5a and calculations at the AM1 level. In this conformation, substituents are arrayed to have the largest separation between the hydrophilic and hydrophobic parts. This can be rationalized as the primary reason for the good linearity.