Aldol reaction mixed/crossed

The aldol reaction as formulated above involves two molecules of the starting substrate. However, by a consideration of the mechanism, one can see that different carbonyl compounds might be used as nucleophile or electrophile. This would be termed a mixed aldol reaction or crossed aldol reaction. However, if one merely reacted, say, two aldehydes together under basic conditions, one would get a... 

Mixed aldol reactions may be broadly classified as the reaction between two different aldehydes or ketones, or the reaction of an aldehyde with a ketone. Apart from the concomitant self-condensation, not less than two possible crossed products can be envisaged. Such reactions are therefore only prepara-tively useful either if appropriate structural conditions are present, or if certain experimental conditions are used to effect a directed aldol condensation. 

Significant for cross-aldol reactions, when an aldehyde was mixed with (S)-proline in a reaction solvent, the dimer (the self-aldol product) was the predominant initial product. Formation of the trimer typically requires extended reaction time (as described above). Thus, it is possible to perform controlled cross-aldol reactions, wherein the donor aldehyde and the acceptor aldehyde are different. In order to obtain a cross-aldol product in good yield, it was often required that the donor aldehyde be slowly added into the mixture of the acceptor aldehyde and (S)-proline in a solvent to prevent the formation of the self-aldol product of the donor aldehyde. The outcome of these reactions depends on the aldehydes used for the reactions. Slow addition conditions can sometimes be avoided through the use of excess equivalents of donor or acceptor aldehyde - that is, the use of 5-10 equiv. of acceptor aldehyde or donor aldehyde. In general, aldehydes that easily form self-aldol products cannot be used as the acceptor aldehydes in... 

This reaction works well even if the electrophilic partner is an enolizable aldehyde. In this example, an unsymmetrical ketone (blocked on one side by an aromatic ring) as the enol partner reacts in excellent yield with a very enolizable aldehyde. This is the first complete aldol reaction we have shown you using a specific enol equivalent notice the important point that it is done in two steps— first, form the specific enol equivalent (here, the lithium enolate) then add the electrophile. Contrast the crossed aldols earlier in the chapter, where enolizable component, base, and electrophile were all mixed together in one step. 

These silyl enol ethers are probably the best way of carrying out crossed aldol reactions with an aldehyde as the enol partner. An example is the reaction of the enol of the not very enolizable iso-butyraldehyde with the very enolizable 3-phenylpropanal. Mixing the two aldehydes and adding base would of course lead to an orgy of self-condensation and cross-couplings. 

Mixed or crossed aldol condensation Aldol condensations between different carbonyl reactants are called crossed (or mixed) reactions. Crossed aldol condensation works well if one carbonyl compound has no a-hydrogen(s). For example, acetone reacts with furfural in a crossed-aldol reaction to give the corresponding a,P-unsaturated ketone 3.15. 

An aldol reaction between two different carbonyl compounds is called a crossed aldol or mixed aldol reaction. 

Crossed aldol reaction (Section 24.2) An aldol reaction in which the two reacting carbonyl compounds are different. A crossed aldol reaction is also called a mixed aldol reaction. 

Reaction between Two Different Aldehydes. In the most general case, this will produce a mixture of four products (eight, if the alkenes are counted). However, if one aldehyde does not have an a hydrogen, only two aldols are possible, and in many cases the crossed product is the main one. The crossed-aldol reaction is often called the Claisen-Schmidt reaction. The crossed aldol is readily accomplished using amide bases in aprotic solvent. The first aldehyde is treated with LDA in THF at —78°C, for example, to form the enolate anion. Subsequent treatment with a second aldehyde leads to the mixed aldol product. The crossed aldol of two aldehydes has been done using potassium ferf-butoxide and Ti(OBu)4. ... 

Aldol reactions between two different carbonyl compounds are called mixed or crossed aldol reactions. With aqueous bases, these reactions are of little synthetic value if both reactants have a-hydrogens because they afford mixtures of products. However, under carefully controlled conditions, it is possible to condense ketones with aldehydes in the presence of dilute sodium hydroxide to furnish P-hydroxyke-tones, provided that the aldehyde is added slowly to the ketone. 

The aldol examples shown above are described as self -condensations because they involve the reaction of a single carbonyl compound acting as both the nucleophile and the electrophile. The reaction of two different carbonyls presents a problem of c/icmose/ecftVify Which carbonyl will act as the nucleophile, and which will act as the electrophile Mixing two ketones in the presence of a mild base, for example, could give a mixture of four aldol products two cross-condensations and two self-condensations. Since acetone and 3-pentanone have similar reactivities, we would expect all possible combinations to occur. 

The experiment presented in this section is an example of a mixed-or crossed-aldol condensation. This term describes cases in which two different carbonyl compounds are the reactants. Such reactions are synthetically practical under certain circumstances, selectively producing a single major condensation product. For example, a ketone may preferentially condense with an aldehyde rather than undergoing self-addition with another molecule of itself (Scheme 18.3). This is because the carbonyl carbon atom of ketones is sterically and electronically not as susceptible to nucleophilic attack as is that of aldehydes. The aldehydic partner in such a reaction generally has no a-hydrogen atoms, so that it is unable to undergo an aldol reaction. 

Until now, we have focused on symmetrical aldol reactions, that is, aldol reactions that occur between two identical parmers. In this section, we explore crossed aldol, or mixed aldol, reactions, which are aldol reactions that can occur between different parmers. As an example, consider what happens when a mixture of acetaldehyde and propionaldehyde is treated with a base. Under these circumstances, four possible aldol products can be formed (Figure 22.3). The... 

Crossed aldol, or mixed aldol, reactions are aldol reactions that occur between different partners and are only efficient if one partner lacks a protons or if a directed aldol addition is performed. 

In a mixed aldol reaction involving acetaldehyde and aeetone, only two of the four possible products are observed. Cross out the two products that are unfavorable, and explain your reasoning. (Hint For each product, identify if acetone or acetaldehyde served as the electrophile and nucleophile.)... 

Another example of cross-aldol condensation is the reaction between citral and acetone, which yields pseudoionone, an intermediate in the production of vitamin A. Noda et a/.[56] working at 398 K with a 1 1 molar ratio of reagents and 2 wt % of catalyst, obtained high conversions (98 %) with selectivities to pseudoionone close to 70 % with CaO and an Al-Mg mixed oxide catalyst these pseudoionone yields are greater than those reported for the homogeneous reaction. MgO exhibited poor activity, and under these conditions only 20 % citral conversion was obtained after 4 h in a batch reactor. Nevertheless, Climent et a/./571 working with 16 wt % MgO as a catalyst, a molar ratio of acetone to citral close to 3 and at 333 K, achieved 99 % conversion and 68 % selectivity to pseudoionone after 1 h. 

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. 

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. 

The preceding reaction is called a mixed aldol addition or a crossed aldol addition. The four products have similar physical properties, making them difficult to separate. Consequently, a mixed aldol addition that forms four products is not a synthetically useful reaction. 

The reaction described for ethyl butanoate is a self-condensation, but as with the aldol condensation, Claisen condensation of two different esters can result in a mixture of products under thermodynamic control conditions. The reaction of two different esters is called the crossed-Claisen (or a mixed Claisen) condensation. A generalized reaction involving RC02Et and RlC02Et can lead to at least four different condensation... 

Crossed (mixed) aldol condensation (Section 19.7) An aldol condensation between two different carbonyl compounds. This reaction is not very useful unless strategies are employed to limit the number of possible products. 

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