Alkyl Substituted Beta-Keto Acids: Molecular Structure and Decarboxylation Kinetics in Aqueous Solution and on the Surface of Metal Oxides

Four beta-keto acids proposed as intermediates in the mechanism of a metal oxide catalyzed decarboxylative cross-ketonization reaction from a mixture of acetic and isobutyric acids have been prepared by organic synthesis and isolated in a crystalline state. Structures have been analyzed by single-crystal X-ray diffraction. First order rate constants have been measured and compared at the temperature range 23–53 °C for the decarboxylation of beta-keto acids in solution as well as adsorbed on the surface of metal oxide catalysts, monoclinic ZrO₂, and anatase TiO₂, undoped and doped with KOH. The reactivity of the four acids in solution arranged from a low to high rate constant correlates with the increasing length of the C–C bond caused by the presence of alkyl groups at the α position. It is for the first time that the behavior of the beta-keto acid intermediate in the decarboxylative ketonization mechanism has been studied on the surface of metal oxide catalysts. In addition to decarboxylation as the major direction, the retro-condensation reaction is also observed as a minor path. The decarboxylation rate extrapolated to industrial scale operating temperatures is above the global rate of the catalytic decarboxylative ketonization, which points to the condensation as the slowest step. Still, decarboxylation is a kinetically significant step of the reaction mechanism for the decarboxylative cross-ketonization of a mixture of two acids. This conclusion is supported by a remarkable dependence of the decarboxylation rate constant on the symmetry of the ketone product and the type of the catalyst used. Namely, beta-keto acids leading to symmetrical ketones decompose faster with ZrO₂ catalysts while decarboxylation of the other two acids leading to unsymmetrical ketones is faster with KOH-TiO₂. This result is in agreement with the previously reported trend of the cross-selectivity according to which ZrO₂ favors the formation of symmetrical ketones, whereas KOH-TiO₂ favors the unsymmetrical ketone. A proposed explanation for this unusual sensitivity of the cross-selectivity to the catalyst choice may involve the entropy increase through the randomization process by the alpha proton exchange between a pair of neighboring carboxylates on the surface, one of which is enolized.