Distinguishing Enolic and Carbonyl Components in the Mechanism of Carboxylic Acid Ketonization on Monoclinic Zirconia

This study contributes toward understanding the mechanism of catalytic formation of mixed ketones in an attempt to improve their selectivity vs symmetrical ketones. A pulsed microreactor placed inside a gas chromatograph–mass spectrometer instrument was used to identify the source of carbonyl group and quantify its distribution among products of zirconia-catalyzed cross-ketonization reaction of a mixture of carboxylic acids, with the carbonyl group of one of the acids selectively labeled by ¹³C. A concept of enolic and carbonyl components in the ketonization mechanism was introduced to distinguish the sources of alkyl and acyl groups, respectively. The least branched acid was found to be the predominant source of CO₂, the essential byproduct of ketonization. Thus the least branched acid is the preferred source of the alkyl group of the cross-ketone product, while the most branched acid provides the acyl group. Increased branching at the α carbon next to the carbonyl group decreased the reactivity of both the enolic and the carbonyl components. Following a pseudo first order kinetic analysis, the relative reaction rates for a common enolic component with a pair of different carbonyl components were measured by the method of competing reactions to obtain mechanistic insights. The distinction between two possible paths in the cross-ketonization mechanism was characterized quantitatively by assessing the difference in activation energies; the results obtained were explained by the steric effect of substituents. On the basis of detailed kinetic analysis, the rate-limiting step most likely occurs after the enolic component activation