Benzaldehyde cross-aldol reaction

On the other hand, a remarkable difference between catalysis by Y and 13 zeolites has been found for the Claisen-Sohmidt condensation of acetophenone and benzaldehyde (Table 5). When the cross aldolic reaction is carried out in the presence of HY, together with the expected trans and ois chalcones 5, the 3,3-diphenylpropiophenone 6 is also formed, this product being not detected on 13 zeolites. A likely explanation for the absence of 6 using zeolite beta is that the crystalline structure of this zeolite exerte a spatial constraint making difficult the formation of a big size molecule like 6, especially in the smaller channel. Similar effects due steno limitations on 6 catalysis have been found for the formation of multi-branched products during the cracking of alkanes (ref 8). 

An Aldol reaction is used to link two molecules of the same aldehyde or ketone, however, it is also possible to link two different carbonyl compounds. This is called a crossed Aldol reaction. For example, benzaldehyde and ethanal can be linked in the presence... 

When one carbonyl compound has no a hydrogens, a crossed aldol reaction often leads to one product. Two common carbonyl compounds with no a hydrogens used for this purpose are formaldehyde (CH2=0) and benzaldehyde (C HsCHO). 

Crossed aldol reaction between benzaldehyde and CH2(COOEt)2... 

Although we might not have been able to make predictions concerning the relative rates of the Cannizzaro and the aldol reactions, we could have predicted that the crossed aldol reaction would proceed faster than the reaction between two molecules of acetophenone. Both aldol reactions would involve the same intermediate carbanion (VII), but benzaldehyde would be expected to be a better acceptor molecule than acetophenone (see p. 155). 

Fluoroacetonitrile condenses with carbon disulfide in an interesting aldol-type reaction (Scheme 3.14). The carbanion for ethyl fluoroacetate reacts readily with benzaldehyde in a cross-aldol reaction to give the fluorinated alcohol. a-Fluorinated carbonyl compounds are often very toxic materials because biologically they are converted into fluoroacetate, which is toxic to the Krebs cycle. Thus, extreme care is needed during the use of these compounds. 

Draw the product of the crossed aldol reaction between benzaldehyde and 3-pentanone and the product formed by its base-catalyzed dehydration. 

Crossed aldol reactions can also be performed with benzaldehyde. 

FIGURE 19.91 The crossed aldol reaction of tert-h xXy methyl ketone and benzaldehyde can give only two products. Benzaldehyde has no a hydrogens and cannot form an enolate. 

In the real world of practical organic synthesis, one rarely needs to do a simple aldol condensation between two identical aldehydes or two identical ketones. Far more common is the necessity to do a crossed aldol between two different aldehydes, two different ketones, or an aldehyde and a ketone. As noted earlier, there are difficulties in doing crossed aldol reactions. Suppose, for example, that we want to condense 2-pentanone with benzaldehyde. Benzaldehyde has no a hydrogen, so no enolate can be formed from it. Some version of the Claisen-Schmidt reaction (p. 984) seems feasible. But 2-pentanone can form two enolates, and the first problem to solve is the specific formation of one or the other enolate (Fig. 19.127). 

Flosal is an a,f)-unsaturated aldehyde made by a crossed aldol reaction between benzaldehyde (CsHgCHO) and heptanal (CH3CH2CH2CH2CH2CH2CHO), followed by dehydration. Draw a stepwise mechanism for the following reaction that prepares flosal. 

As we learned in Section 23.3, the a hydrogens between two carbonyl groups are especially acidic, and so they are more readily removed than other a H atoms. As a result, the P-dicarbonyl compound always becomes the enolate component of the aldol reaction. Figure 24.2 shows the steps for the crossed aldol reaction between diethyl malonate and benzaldehyde. In this type of crossed aldol reaction, the initial P-hydroxy carbonyl compound always loses water to form the highly conjugated product. 

Aldolase antibodies 38C2 and 33F12 generated by immunization with diketone 1 are capable of accelerating more than 100 different aldol reactions [4, 8, 11, 15, 16]. Some examples of cross-aldol reactions are shown in Table 6.1. For cross-aldol reactions, a variety of ketones are accepted as donors, including aliphatic open-chain ketones (for example acetone to pentanone), aliphatic cyclic ketones (cyclopentanone to cycloheptanone), functionalized open-chain ketones (hydroxyacetone, dihydroxyacetone, fluoroacetone), and functionalized cyclic ketones (2-hydroxycyclohexanone). As with the donors, the antibodies also accept different kinds of aldehyde substrate, for example benzaldehyde derivatives 8-10, a,j5-unsaturated aldehyde 11, and aliphatic aldehydes 12 and 13 with products as indicated in Table 6.1. 

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

Recently, cross-aldol condensation of benzaldehyde with n-heptaldehyde to give jasminaldehyde (Scheme 13) has been reported a mesoporous molecular sieve Al-MCM-41 with supported MgO was the catalyst. The reactions were carried out in a stirred autoclave reactor with a molar benzaldehyde/heptanal ratio of 10 at 373-448 K (236). The results show that Al-MCM-41 is catalytically active, and its activity is significantly increased by the deposition of MgO (Table V). Increasing the amount of deposited MgO on Al-MCM-41 decreases the surface area but enhances the catalyst basicity. The basicity is well correlated with the catalytic activity, although the selectivity to jasminaldehyde is not the selectivity is essentially independent of temperature, pressure, time of the reaction, and conversion. 

Cyclocitral (540) behaves as a nucleophile towards benzaldehyde and in the presence of sodium hydroxide the fused pyran-2-oI (541) is formed through an aldol (Scheme 202) (81JHC549). However, when sodium ethoxide is used as the catalyst, the pyran-2-one is produced. It is proposed that oxidation arises through a crossed Cannizzaro reaction with benzaldehyde (and much benzyl alcohol is observed in support of this idea), followed by a carbanion attack on more benzaldehyde and subsequent cyclization. 

Asymmetric aldolreactions.1 The acetal (2) obtained by reaction of benzaldehyde with D-( — )-l (available from Aldrich) reacts with the ketone 3 to give the two possible crossed aldols in the ratio 16 1. The products can be converted into optically active /i-hydroxy ketones in three steps. 

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]... 

Crossed aldol condensations between aliphatic aldehydes on the one hand and benzaldehyde or cinnamic aldehyde or their derivatives on the other also are possible. The reaction components can even be mixed together. The aldol adducts are formed without chemo-... 

Crossed aldol condensations between aliphatic aldehydes on the one hand and benzaldehyde or cinnamic aldehyde or their derivatives on the other also are possible. The reaction components can even be mixed together. The aldol adducts are formed without chemoselectivity, as a mixture of isomers, but their formations are reversible. The Elcb elimination to an a,/3-unsaturated carbonyl compound is fast only if the newly created C=C double bond is conjugated to an aromatic system or to another C=C double bond already present in the substrate. This effect is due to product-development control. All the starting materials thus react in this way via the most reactive aldol adduct. 

A potentially valuable example of a crossed Claisen condensation was described by Tanabe and Mu-kaiyama in 1986. It arose from their earlier work on titanium(IV) ditriflate [dichlorobis(trifluorometh-anesulfonato)titanium(IV)] and triethylamine as a catalytic promoter of the simple Claisen reaction. The reaction was run in the presence of benzaldehyde, added to observe the aldol reaction, but the propionate anion added to the carbonyl group of another ester molecule in preference (equation 11). The same result was observed in a Dieckmann reaction dimethyl adipate, TiCh (OTf) (1.5 equiv.) and triethylamine... 

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. 

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. 

There are certainly cases when we want a crossed-aldol condensation between two reactive partners that have an enolizable position, as in 3-pentanone with cyclopentanone. If 3-pentanone and benzaldehyde, which has no enolizable protons, can lead to three products, what will happen in this new case If an aldol condensation occurs under thermodynamic conditions. 3-pentanone reacts with sodium ethoxide to give enolate 120. This enolate can condense with either unenolized 3-pentanone (to produce 126) or with unenolized cyclopentanone (to produce 128). Both of these ketones are symmetrical, and there is no opportunity for additional enolates, which would further complicate the reaction (see below). The pAa of 3-pentanone and cyclopentanone are not... 

Scandium triflate-catalyzed aldol reactions of silyl enol ethers with aldehyde were successfully carried out in micellar systems and encapsulating systems. While the reactions proceeded sluggishly in water alone, strong enhancement of the reactivity was observed in the presence of a small amount of a surfactant. The effect of surfactant was attributed to the stabiMzation of enol silyl ether by it. Versatile carbon-carbon bondforming reactions proceeded in water without using any organic solvents. Cross-linked Sc-containing dendrimers were also found to be effective and the catalyst can be readily recycled without any appreciable loss of catalytic activity.Aldol reaction of 1-phenyl-l-(trimethylsilyloxy) ethylene and benzaldehyde was also conducted in a gel medium of fluoroalkyl end-capped 2-acrylamido-2-methylpropanesulfonic acid polymer. A nanostmctured, polymer-supported Sc(III) catalyst (NP-Sc) functions in water at ambient temperature and can be efficiently recycled. It also affords stereoselectivities different from isotropic solution and solid-state scandium catalysts in Mukaiyama aldol and Mannich-type reactions. 

Aromatic ketones bearing a-hydrogens give aldol reaction products readily, but in this case the aldol product spontaneously loses water to form the unsaturated ketone. When benzaldehyde is used in the crossed-aldol condensation the final product is the unsaturated aldehyde or ketone. Conjugation of the double bond with the aromatic ring is the reason for the spontaneous dehydration (Scheme 3.13). 

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