Kinetics of hydrolysis of fenclorac.

The kinetics of hydrolysis of fenclorac were studied to determine its stability in aqueous solution at different pH's and temperatures. For this study, a stability-specific liquid chromatographic assay method was developed to separate fenclorac from its hydrolysis product, alpha-hydroxy-3-chloro-4-cyclohexylbenzeneacetic acid. The k-pH profile in the 0-12 pH range in various buffer solutions shows that fenclorac is stable in its undissociated form in strongly acidic media and is unstable in neutral and alkaline media. The instability of fenclorac in aqueous solution is proportional to the degree of ionization of the carboxyl group in the 1-4 pH range and is independent of pH above 4. The rate-determining step in the mechanism of hydrolysis of fenclorac involves ionization of the carbon-chlorine bond. The ionization is catalyzed by an intramolecular necleophilic attack on the alpha-carbon by the dissociated carboxyl group, resulting in the formation of an unstable intermediate, a three-membered ring lactone. This unstable intermediate rapidly hydrolyzes to the final hydrolysis product. This mechanism is supported by experimental evidence such as the medium effect, positive salt effect, common ion effect, and substituent effect. Arrhenius parameters for the hydrolysis of fenclorac and its 3-nitro substituted analog were obtained.