(101a) Effects of Lewis Acidity and Confinement on Aldol Reactions of Aldehydes in Zeotypes

Forming carbon-carbon (C-C) bonds is vital in organic synthesis and aldol reactions have attracted widespread interest for converting renewable biomass-derived substrates into alternative fuels, fine chemicals, and pharmaceuticals. Molecular sieves and zeotypes containing framework Lewis acid sites are promising catalysts for selective C-C coupling between carbonyl-containing moieties, including aldehydes lacking α-­C‑H bonds (e.g., formaldehyde, benzaldehyde) and enolizable substrates. Isolated metal heteroatoms and lattice oxygens in these materials function cooperatively as acid-base pairs to generate bound enolates that readily attack the activated carbonyl molecules. However, tailoring the catalytic performance of acid-base adducts for a given reaction requires fundamentally understanding the properties of these active sites as well as their interactions with reacting molecules and intermediates.

Here, the Claisen-Schmidt condensation of benzaldehyde and propionaldehyde was used as a probe reaction to examine the intrinsic activity of Ti-, Zr-, Sn-, and Hf-containing zeotypes by considering the influence of Lewis acidity along with the confining reaction environment on apparent rate constants, product site time yields (STY), and activation barriers. Experimental evidence revealed that initial rates of enolization at 393 K follow a pseudo-second-order dependence over large-pore *BEA (~7 Å) zeotypes with differences in STYs for α-methyl cinnamaldehyde (α-MCA), the cross-condensation product, that correlate with measured adsorption enthalpies for pyridine (Zr > Hf > Sn > Ti) as a proxy of functional Lewis acid strength (Figure 1). When Lewis sites are confined within medium‑pore MFI (~6 Å) zeotypes, initial rates of ­cross-aldol condensation exceed those for self‑condensation of propionaldehyde, indicating that selection of pore size and benzaldehyde/propionaldehyde ratios can be used to steer product selectivity.