ALKYL SUBSTITUENT EFFECTS ON THE NEUTRAL HYDROLYSIS OF 1-ACYL-(3-SUBSTITUTED)-1,2,4-TRIAZOLES IN HIGHLY AQUEOUS REACTION MEDIA - THE IMPORTANCE OF SOLVATION

The importance of solvation in determining substituent effects of alkyl groups has been assessed in a quantitative study of the medium effects of ethanol and 1-propanol on the neutral hydrolysis of 18 1-acyl-(3-substituted)-1,2,4-triazoles in highly aqueous solutions. The dependence of the pseudo-first-order rate constants for hydrolysis on the molality of added cosolvent is analyzed in terms of pairwise Gibbs function interaction parameters and individual group contributions to the overall medium effect. It is found that the alkyl substituent effects depend on the presence of the cosolvent and that this medium dependence is different for different alkyl groups. In addition, the effect is sensitive to the position of the substituent and the overall hydrophobicity of the substrate. Alkyl substituent effects have also been examined for the acid-catalyzed hydrolysis of a series of 1-acyl-(3-substituted)-1,2,4-triazoles. The solvation dependence of alkyl substituent effects is discussed in terms of changes in hydration of the substrate during the activation process.