(509cj) Effect of Reactant Identity and Acid-Site Strength on Acid-Catalyzed Aldol Reactions

Aldol condensation is an important reaction to build new C-C bonds between two carbonyl containing compounds, while the aldol intermediate has also been observed to undergo a side reaction that produces an alkene and a carboxylic acid.¹ Our previous computational work has found that the aldol condensation reactions between aliphatic ketones and benzaldehyde on solid acids proceed through an E1 dehydration mechanism after the aldol intermediate is tautomerized into the enol form, while the fission reactions similarly feature a carbocation transition state. In this work, we build on these results and systematically examine how reactant identity and acid-site strength influence the relative reactivity of condensation versus fission pathways. Dispersion-corrected, periodic density-functional theory calculations were used to model how these reactions occur on a model Al/SiO₂ surface, a sulfonic acid-functionalized SiO₂ surface, and various Al-exchanged zeolites. The reactants examined include a series of para-substituted benzaldehydes with both electron withdrawing and donating groups, as well as non-aromatic and conjugated open-chain aldehydes. We found that while the activation energies for fission roughly scale with the proton affinity of the aldehydes, dehydration shows much more subtle variations, leading to a pronounced difference in predicted product selectivity. These results provide further insights into the nature of active species in the aldol reactions and the various factors determining their chemo-selectivity.

(1) Ponnuru, K.; Manayil, J. C.; Cho, H. J.; Fan, W.; Wilson, K.; Jentoft, F. C. Intraparticle Diffusional versus Site Effects on Reaction Pathways in Liquid-Phase Cross Aldol Reactions. ChemPhysChem 2018, 19, 386–401.