AN ANALYSIS OF COMPLEX ALKYL-SUBSTITUENT EFFECTS IN THE WATER-CATALYZED HYDROLYSIS OF 1-ACYL-1,2,4-TRIAZOLES

Article abstract of DOI:10.1002/recl.19881070316

Pseudo-first-order rate constants and thermodynamic activation parameters have been determined for the water-catalyzed hydrolysis of the 1-acyl-1,2,4-triazoles 1-9 in water and in aqueous acetonitrile .The reaction occurs via water-catlalyzed nucleophilic attack of water at the amide carbonyl group.Variation of the alkyl group in the acyl part of the substrate led to the sequence of reactivities (in water): R= t-Bu > i-Pr > Et > Me > n-Pr > s-Bu > i-Pent > neo-Pent.This complex behaviour strogly suggest the operation of a composite steric effect most likely involving contributions from conformational preference (SE1), change of coordination number at carbonyl carbon (SE2), steric repulsion between O² and the alkyl group (SE3), and steric inhibition of solvation (SE4)> Modelling of the relative rates in water in terms of the expanded branching equation gave satisfactory results.Two pssible transition states are proposed for the neutral hydrolysis, one involving intramolecular hydrogen bonding between the second water molecule and N² of the 1,2,4-triazole ring .The different sequence of reactivities for neutral hydrolysis in aqueous acetonitrile as well as the rates for hydroxide-ion-catalyzed hydrolysis in water (B_Ac2 machanism) support the analysis of substituent effects.