(119g) Controlling Chemoselectivity in Aldol Reactions with Solid Catalysts

Aldol condensation has proven to be an important carbon-carbon bond forming reaction in organic synthesis.^[1] The aldol condensation consists of the formation of a β-hydroxy carbonyl compound in the first step, followed by a dehydration as the second step resulting in an α,β-unsaturated derivative. The fission of aldol products resulting in an olefin and a carboxylic acid has garnered attention recently as a potentially useful reaction for the sustainable production of isobutene from acetone.^{[2, 3]} Although this pathway has been reported long time ago for acetone self-condensation in the vapor phase,^[4] and for cross-aldol reactions involving aromatic aldehydes in the liquid phase,^{[5, 6]} the mechanistic details for the formation of fission products are still unclear. The fission products are reported to form via a free radical intermediate as a subsequent reaction to dehydration in the vapor phase.^[3] On the other hand, in the liquid phase, this reaction was shown to proceed via a carbocation intermediate as a parallel reaction to the dehydration.^[5] The objective of this investigation is thus to understand the reaction mechanism of the fission pathway and to identify the factors that govern chemoselectivity towards fission products in heterogeneously catalyzed cross aldol reactions.

The aldol condensations between five different para-substituted benzaldehyde derivatives (4-nitrobenzaldehyde, 4-methoxybenzaldehyde, 4-bromobenzaldehyde, 4-methylbenzaldehyde, and benzaldehyde) and several aliphatic ketones were investigated in liquid phase reactions at temperatures between 80 and 140 °C. A kinetic model was developed for the aldol reaction between benzaldehyde and 3-pentanone with propyl sulfonic-acid (PrSO₃H) functionalized mesoporous silica (PrSO₃H/MCM-41) to estimate the reaction orders and the rate constants. Additionally, activation energies and pre-exponential factors were calculated via Arrhenius analysis. The proton form of zeolites including BEA, MOR and FAU were used to investigate possible influence of pore confinement on chemoselectivity. Benzenesulfonic acid and phosphoric acid served as homogeneous benchmark catalysts and were used to investigate the effect of acid strength.

Reaction of various ketones with benzaldehyde revealed that ketones with more highly substituted alpha carbon atoms resulted in higher fission product yields. 2,4-Dimethyl-3-pentanone has only one H in the alpha position, which eliminates the possibility for the dehydration pathway upon reaction with benzaldehyde. The resulting high fission products yields (~80%) observed in the reaction at near complete conversion suggest that fission products directly form from the aldol addition product.

In comparison with benzenesulfonic acid, the weaker phosphoric acid catalyst gave a higher fission product selectivity, at the expense of condensation products . This result indicates that acid strength of the catalyst affects the transition states of the fission and the condensation pathways differently. Higher temperatures always resulted in higher fission products owing to the high activation energy of the fission pathway estimated from the kinetic model. Selectivities seen with microporous solids varied significantly as a function of framework type, suggesting a strong influence of confining the size or mobility of species involved in the reaction pathway.

In conclusion, aldol condensation and fission selectivity can be controlled by a combination of catalyst pore architecture, acid strength and reaction conditions.

References:

[1] R. Mahrwald, D. Evans, Modern aldol reactions, Wiley Online Library, 2004.

[2] J. Sun, R. A. Baylon, C. Liu, D. Mei, K. J. Martin, P. Venkitasubramanian, Y. Wang J Am Chem Soc. 2016, 138, 507-517.

[3] S. Herrmann, E. Iglesia Journal of Catalysis. 2018, 360, 66-80.

[4] D. V. N. Hardy Journal of the Chemical Society (Resumed). 1938, 464-468.

[5] G. W. Kabalka, D. Tejedor, N.-S. Li, R. R. Malladi, S. Trotman The Journal of Organic Chemistry. 1998, 63, 6438-6439.

[6] K. Ponnuru, J. C. Manayil, H. J. Cho, W. Fan, K. Wilson, F. C. Jentoft ChemPhysChem. 2018, 19, 386-401.