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

Abstract

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.

Cross-selectivity in the catalytic ketonization of carboxylic acids

“…For this reason, cross-reaction becomes a valuable method in the study of the ketonization mechanism. In our previous work on the ketonization mechanism we proposed enolization of carboxylic acids on zirconia [19] and were able to analyze separately the effect of substituents on the reaction rates of the enolic and the carbonyl component [20]. Accordingly, in two competing reactions of a common enolic component with two different carbonyl components, a faster reaction rate is observed for a less substituted carbonyl component ( Table 1).…”

“…In general, a higher degree of branching at the alpha-position decreases the carboxylic acid reactivity in the ketonization reaction [15,20]. The role of the catalyst, the molar ratio of two acids, and the process conditions affecting the cross-selectivity have not been sufficiently studied.…”

“…We have recently suggested naming their sources as the carbonyl and enolic components, respectively by analogy with the aldol condensation [20]. However, unlike the aldol condensation or the Tishchenko reaction in which two cross-products can form, there is only one cross-product possible in the carboxylic acids ketonization reaction (Scheme 1).…”

“…However, unlike the aldol condensation or the Tishchenko reaction in which two cross-products can form, there is only one cross-product possible in the carboxylic acids ketonization reaction (Scheme 1). It has been shown that two different mechanistic pathways exist, and they both lead to the same cross-product [20]. Among two possible combinations for the construction of the crossketone, the preferred one is that utilizing the alkyl group from the less branched acid and the acyl group from the more branched acid.…”

“…Among two possible combinations for the construction of the crossketone, the preferred one is that utilizing the alkyl group from the less branched acid and the acyl group from the more branched acid. Mechanistically, it may occur through the preferred enolization of the less branched acid and its subsequent condensation with the more branched carbonyl component to a beta-ketoacid followed by the loss of CO 2 from the enolic component in the decarboxylation step [20].…”