Aldol reactions Claisen-Schmidt reaction

Claisen-Schmidt reaction (Section 18.10) A mixed aldol condensation in which an aromatic aldehyde reacts with an enolizable aldehyde or ketone. 

The Claisen-Schmidt reaction (Figure 11-17) produces an a,P-unsaturated aldehyde or ketone, the general structure of which is shown in Figure 11-18. The Claisen-Schmidt reaction is a crossed aldol condensation. 

The intramolecular carbon-carbon bond-forming reactions considered in this section are based on the aldol condensation (see Section 5.18.2, p. 799), the Claisen-Schmidt reaction (see Section 6.12.2, p. 1032), the Claisen ester condensation (see Section 5.14.3, p. 736), and the Claisen reaction (see Section 6.12.2, p. 1032). Since these carbonyl addition reactions are reversible, the methods of synthesis are most successful for the formation of the thermodynamically stable five- and six-membered ring systems. The preparation of the starting materials for some of these cyclisation reactions further illustrates the utility of the Michael reaction (see Section, 5.11.6, p. 681). 

The aldol condensation of ketones with aryl aldehydes to form a,p-unsaturated derivatives is called the Claisen-Schmidt reaction ° . ... 

The reaction of an aldehyde with a ketone employing sodium hydroxide as the base is an example of a mixed aldol condensation reaction, the Claisen-Schmidt reaction. Dibenzalacetone is readily prepared by condensation of acetone with two equivalents of benzaldehyde. The aldehyde carbonyl is more reactive than that of the ketone and therefore reacts rapidly with the anion of the ketone to give a /3-hydroxyketone, which easily undergoes base-catalyzed dehydration. Depending on the relative quantities of the reactants, the reaction can give either mono- or dibenzalacetone. 

The Claisen-Schmidt Reaction. When aromatic aldehydes are treated with aliphatic ketones in the presence of base, three reactions might be expected a Cannizzaro reaction of the aromatic aldehyde an aldol-type reaction of the ketone or a crossed aldol reaction between the ketone and the aromatic aldehyde. In either of the last two possibilities dehydration might also occur. Undoubtedly all these reactions will take place in strong base, but by employing about 10 per cent aqueous sodium hydroxide, good yields are often obtained of j3-unsaturated carbonyl conipounds derived from a crossed aldol reaction between the aldehyde and the ketone. This reaction, generally called a Claisen-Schmidt reaction, can be illustrated by the synthesis of benzalacetophenone.16... 

Subsequent elimination of water from the aldol product leads to a,6-unsaturated carbonyl compounds, for example, in the Claisen-Schmidt reaction (reference 142). 

There are numerous examples where the concept of supported ILs has been applied to specific chemical reactions. Examples include hydrogenation [57, 61, 62], hydroamination [24, 43, 63], aUyUc substitution [47], hydroformylation [64], carbonylation [64, 65], and carboxylation [66] reactions as well as partial oxidation of alcohols [67], the Claisen-Schmidt reaction [68], Mukaiyama aldol reaction [69], Michael reaction [70], and many more [71]. The concept is readily applied to reactions in which the bulk fluid is a gas, a Hquid, or a two-phase mixture of gas and liquid. Organometallic complexes, metal clusters, and supported functional groups have been employed as the catalyticaUy active function F. Characteristic features of some selected reaction systems are summarized in the following, focusing on two typical reaction systems involving liquid bulk fluids. 

The cross-aldol addition of a ketone to an aldehyde (Claisen-Schmidt reaction) is profitably carried out by using the silyl enol ether of the ketone in an organic solvent in the presence of TiCh (Mukaiyama reaction) [2], but this protocol is not suitable for acid-sensitive substrates. High pressure may be employed in place of the catalyst, but longer reaction times are required [4]. 

Ba(OH)2 is known to cattdyze several base-catalyzed organic reactions in the solid form, Of the reactions, aldol condensation is the most common. In recent years, several organic reactions besides aldol condensation have been found to be effectively catalyzed by Ba(OH)2. These reactions are the Claisen-Schmidt reaction, esterification of acid chlorides, Williamson s ether synthesis, benzil-benzilic acid rearrangement, the synthesis of A -pyrazolines by the reaction of a,/3-unsaturated ketone with PhNHNHz Wittig-Homer reaction, and Michael addition. For these reactions, the Ba(OH)2 catalyst prepared from Ba(0H)2-8H20 by cidcination at 473 K shows the highest activity. 

Ba.se Catalyzed. Depending on the nature of the hydrocarbon groups attached to the carbonyl, ketones can either undergo self-condensation, or condense with other activated reagents, in the presence of base. Name reactions which describe these conditions include the aldol reaction, the Darzens-Claisen condensation, the Claisen-Schmidt condensation, and the Michael reaction. 

A different situation is found in the case of crossed aldol reactions, which are also called Claisen-Schmidt reactions. Here the problem arises, that generally a mixture of products might be obtained. 

Benzilic acid rearrangement Benzoin reaction (condensation) Blanc chloromethylation reaction Bouveault-Blanc reduction Bucherer hydantoin synthesis Bucherer reaction Cannizzaro reaction Claisen aldol condensation Claisen condensation Claisen-Schmidt reaction. Clemmensen reduction Darzens glycidic ester condensation Diazoamino-aminoazo rearrangement Dieckmann reaction Diels-Alder reaction Doebner reaction Erlenmeyer azlactone synthesis Fischer indole synthesis. ... 

Crossed aldol condensations, where both aldehydes (or other suitable carbonyl compounds) have a-H atoms, are not normally of any preparative value as a mixture of four different products can result. Crossed aldol reactions can be of synthetic utility, where one aldehyde has no a-H, however, and can thus act only as a carbanion acceptor. An example is the Claisen-Schmidt condensation of aromatic aldehydes (98) with simple aliphatic aldehydes or (usually methyl) ketones in the presence of 10% aqueous KOH (dehydration always takes place subsequent to the initial carbanion addition under these conditions) ... 

The activated Ba(OH)2 was used as a basic catalyst for the Claisen-Schmidt (CS) condensation of a variety of ketones and aromatic aldehydes (288). The reactions were performed in ethanol as solvent at reflux temperature. Excellent yields of the condensation products were obtained (80-100%) within 1 h in a batch reactor. Reaction rates and yields were generally higher than those reported for alkali metal hydroxides as catalysts. Neither the Cannizaro reaction nor self-aldol condensation of the ketone was observed, a result that was attributed to the catalyst s being more nucleophilic than basic. Thus, better selectivity to the condensation product was observed than in homogeneous catalysis under similar conditions. It was found that the reaction takes place on the catalyst surface, and when the reactants were small ketones, the rate-determining step was found to be the surface reaction, whereas with sterically hindered ketones the adsorption process was rate determining. 

There are numerous examples of both acid- and base-catalyzed mixed aldol condensations involving aromatic aldehydes. The reaction is sometimes referred to as the Claisen-Schmidt condensation. Scheme 2.2 presents some representative examples. 

Reaction between two different aldehydes. In the most general case, this will produce a mixture of four products (eight, if the olefins 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. 

---