Benzaldehydes self-aldol reactions

This mixed aldol will succeed because one of the components, benzaldehyde, is a good acceptor of nucleophiles, yet has no cc-hydrogen atoms. Although it is possible for acetone to undergo self-condensation, the mixed aldol reaction is much more favorable. 

Liquid phase aldol condensation reaction between heptanal and benzaldehyde is studied over two series of oxynitride catalysts aluminium phosphate oxynitrides AlPON and mixed aluminium gallium phosphate oxynitrides AlGaPON , with increasing nitrogen contents (0-14 wt.% for AlPON and 0 - 16 wt. % for AlGaPON ). The main products are jasminaldehyde and 2-pentyl-2-nonenal. Jasminaldehyde is formed via the cross-aldol condensation reaction between heptanal and benzaldehyde and 2-pentyl-2-nonenal is formed via the self-condensation reaction of heptanal. 

Nolen et al. also reported the self-condensation reaction of butyraldehyde and the cross-aldol condensation of benzaldehyde with acetone (Figs. 9.58 and 9.59) at 250°C. The butyraldehyde self-condensation produced a number of products, including 2-ethyl-2-hexenal, 2-butyl-2-butenal, and 2-ethyUiexanal. The results from the condensation of butyraldehyde indicate that a 40% yield of 2 -ethyl-2 -hexenal is achieved before the formation of by-products becomes dominant. In addition, investigations of the back reaction show that a substantial quantity of butyraldehyde is formed when 2-ethyl-2-hexenal is subjected to water at 250°C. The condensation reaction of benzaldehyde with acetone produced a 15% yield of trans-4-phenyl-3-buten-2-one in 5 h and very small quantities of trans,trans-dibenzylidene acetone during this same period of time. The authors suggest that the low yield could be a result of equilibrium limitations. 

Scheme 1.10 Cross-aldol reaction of benzaldehyde and heptanal (top) and self-condensation of...

Cross-aldol condensations have been performed with alkaline earth metal oxide, as base catalysts. A limitation of the cross-aldol condensation reactions is the formation of by-products throught the self-condensation of the carbonyl compounds, resulting in low selectivities for the cross-aldol condensation product. Thus, the cross-condensation of heptanal with benzaldehyde, which leads to jasminaldehyde (a-M-amylcinnamaldehyde), with a violet scent, has been performed with various solid base catalysts/13,541 particularly MgO, which gave excellent conversions of heptanal (97 %) at 398 K in the absence of a solvent (but the selectivity to jasminaldehyde was only 43 %). A low selectivity was also reported (40 %) for the cross-aldol condensation of acetaldehyde and heptanal catalysed by MgO.[55]... 

This reaction proceeds well because the benzaldehyde has no a-protons and cannot form an enolate ion. Therefore, there is no chance of benzaldehyde undergoing self-condensation. It can only act as the electrophile for another enolate ion. However, what is to stop the ethanal undergoing an Aldol addition with itself as already described. 

We showed, over two different series of Al(Ga)PON oxynitrides catalysts, that the nitridation of phosphate precursors has a positive effect on the selectivity to jasminaldehyde for the mixed aldol condensation reaction of heptanal with benzaldehyde. The influence of nitridation on the product distribution was interpreted in terms of changes in the relative density of acid and basic sites on the catalyst surface. Decreasing the acidity and increasing the basicity through nitridation enhances the simultaneous activation of benzaldeyde and heptanal and favors the cross condensation reaction between those two aldehydes, rather than the self-condensation of heptanal. 

The self-condensation of butanal involves a single compound, but it is also possible to convert one ketone or aldehyde to an enolate anion, and it wiU react with a different ketone or aldehyde. This is called a mixed aldol condensation. If acetone (2) is treated with aqueous NaOH in the presence of another carbonyl molecule, such as benzaldehyde (25), enolate (26) is formed in situ. This enolate anion may react with itself (with another molecule of 2 in a selfcondensation reaction), but it may also react with aldehyde 25 via acyl addition to give alkoxide 28. Mild hydrolysis gives the mixed aldol product, 26. There is a competition for the reaction of 27 with either 2 or 25, so at least two products are possible in the reaction 28 and the self-condensation product. Note... 

Because LDA is a non-nudeophilic base, it should react with a ketone to give an enolate anion. In an actual experiment, 2-pentanone (32) reacts first with LDA to form the enolate anion (not shown) and then with benzaldehyde (25) to form the aldol alkoxide product (also not shown). Subsequent mild acid hydrolysis gives 33 in 80% yield. Virtually no self-condensation of 32 is observed in this experiment, which suggests that the reaction is largely irreversible. Assume that 2-pentanone reacts with LDA to give enolate anion 34 (the two resonance forms are 34A and 34B). As in all of these reactions, the carbanion form of the enolate 34A is the nucleophile. To account for the observed lack of self-condensation, the equilibrium for this acid-base reaction must be pushed toward 34 (the reasons for this will be discussed in Section 22.4.2). If this statement is correct, it means that 32 has been converted almost entirely to 34, so there is little or no 43 available to react. Therefore, a different carbonyl compound may be added in a second chemical step to give 35. This is an overstatement of the facts, but it is a useful assumption that explains the results. Note that benzaldehyde is used, which has no a-protons and cannot form an enolate anion. 

What does all of this mean The reaction of 2-pentanone with LDA in THF at -78°C constitutes typical kinetic control conditions. Therefore, formation of the kinetic enolate and subsequent reaction with benzaldehyde to give 34 is predictable based on the kinetic versus thermodynamic control arguments. In various experiments, the reaction with an unsymmetrical ketone under what are termed thermodynamic conditions leads to products derived from the more substituted (thermodynamic) enolate anion. Thermodynamic control conditions typically use a base such as sodium methoxide or sodium amide in an alcohol solvent at reflux. The yields of this reaction are not always good, as when 2-butanone (37) reacts with NaOEt in ethanol for 1 day. Self-condensation at the more substituted carbon occurs to give the dehydrated aldol product 38 in 14% yield. Note that the second step uses aqueous acid and, under these conditions, elimination of water occurs. 

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