Claisen-Schmidt reaction with aromatic aldehydes

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... 

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) ... 

In this reaction, the starting materials are usually prepared by the Claisen-Schmidt Condensation between aromatic aldehydes and methyl azidoacetate for example, upon treatment with 4 eq. ethyl azidoacetate and sodium methoxide in methanol, the corresponding azidocinnamic ester was prepared from 2-0-(T-methyl)hexyl-5-bromo 2-hydroxylbenzaldehyde. On the other hand, the thermal decomposition is usually carried out in refluxing xylene,yielding indole derivatives of highly regiospecificity." ... 

Claisen-Schmidt reaction. Aromatic aldehydes condense with aliphatic or mixed alkyl-aryl ketones in the presence of aqueous alkali to form ap-unsaturated ketones ... 

The above are examples of the Claisen - Schmidt reaction. The formation of p-nitrostyrenes by reaction of nitroalkanes with aromatic aldehydes in the presence of aqueous alkali may be included under the Claisen- hmidt condensation ... 

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

A retrosynthetic analysis of a,/J-unsaturated ketones leading to various methods of synthesis is outlined in Section 5.18.2, p. 798. These methods are equally applicable to aromatic aldehydes. Aromatic aldehydes condense with aliphatic or mixed alkyl aryl ketones in the presence of aqueous alkali to form a,[i-unsaturated ketones (the Claisen-Schmidt reaction). 

Claisen-Schmidt reaction The cross condensation reaction of an aromatic aldehyde with a simple aliphatic aldehyde or ketone with 10% KOH to yield the dehydrated product, i.e. an a,P-unsaturated arenone. 

Similar transformations can be obtained in the reactions of acetone with aromatic aldehydes, the classic Claisen-Schmidt reaction. These reactions invariably give the a,p-unsaturated ketone products. Either the mono- or bis-condensation product may be obtained by suitable adjustment of the reaction conditions (equation 45 and 46). 46... 

There are many examples of both acid- and base-catalyzed condensation reactions involving aromatic aldehydes. The name Claisen-Schmidt condensation is associated with this type of mixed aldol reaction. Entries 7-10 in Scheme 2.1 are a few of the hundreds of examples of this reaction that have been recorded. 

Claisen-Schmidt reaction of acetophenones with aromatic aldehydes in presence of cationic surfactants such as cetylammonium compounds, CTACl, CTABr, (CTA)2S04 and CTAOH in mild alkaline conditions give chalcones, which on cyclisation give flavanols (Scheme 51). 

The most efficient variant of this combination is based on reaction of an enolizable ketone with a non-enolizable aldehyde, so that self-condensation of the latter cannot occur. Several examples of this type of combination in aldol reactions are given in Scheme 1.2. Usually in situ elimination occurs, so a,j5-unsaturated ketones result, in particular when aromatic aldehydes are condensed with ketones ( Claisen-Schmidt reaction ) [18-21]. 

The condensation of aliphatic aldehydes with acetone to give methyl vinyl ketone derivatives is rather common. The reaction can be carried out to the ketol stage (equations 39 and 40),or under conditions that lead to the a,3-unsaturated ketone (equations 41 and 42). 42 3y adjusting the stoichiometry, bis-condensation products can often be obtained in excellent yield (equations 43 and 44). 44 Similar transformations can be obtained in the reactions of acetone with aromatic aldehydes, the classic Claisen-Schmidt reaction. These reactions invariably give the a,p-unsaturated ketone products. Either the mono- or bis-condensation product may be obtained by suitable adjustment of the reaction conditions (equation 45 and 46). 46... 

E)-Chalcones 4 were prepared via Claisen-Schmidt condensation of methyl ketones with different aromatic aldehydes. Cycloaddition reaction of 4 with thiourea yielded the eorresponding thioxypyrimidine 5 derivatives. Compounds 5 were condensed with chloroacetic acid to yield thiazolopyrimidine 6. Also thione 5 were also condensed, in one pot reaction, with chloroacetic acid and aromatic aldehyde to yield arylmethylene derivatives 7 which could also be prepared directly by condensation of 5 with aromatic aldehydes (Scheme 2) [14-20]. 

Claisen-Schmidt condensation org chem A reaction employed for preparation of unsaturated aldehydes and ketones by condensation of aromatic aldehydes with aliphatic aldehydes or ketones in the presence of sodium hydroxide. klas-on jshmit kand-on sa-shon ... 

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. 

If there are two carbonyl compounds present, then a cross condensation might occur, but usually it is of little synthetic value as there are four possible products. However, if one of the carbonyl compounds lacks an a-hydrogen, then the reaction might prove useful, because this compound cannot form the enol intermediate. An example is the Claisen-Schmidt condensation involving an aromatic aldehyde, e.g. benzaldehyde, with a simple aldehyde or ketone,... 

Aldol addition and condensation reactions involving two different carbonyl compounds are called mixed aldol reactions. To be useful as a method for synthesis there must be some basis for controlling which carbonyl component serves as the electrophile and which acts as the enolate precursor. One of the most general mixed aldol condensations involves the use of aromatic aldehydes with alkyl ketones or aldehydes. 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. Aromatic aldehydes are incapable of enolization and cannot function as the nucleophilic component. Furthermore, dehydration is especially favorable because the resulting enone is conjugated with the aromatic ring. 

Dilute sodium hydroxide was used as a condensing ent by J. G. Schmidt and the method was applied by Claisen and collaborators to the s3mthesis (Claisen reaction) of aromatic ketonic esters, e.g. benzylidene acetone and di-benzylidene acetone from benzaldehyde and acetone. An alternative method was the use of an aromatic aldehyde or ketone with acetoacetic ester in presence of hydrogen chloride. Benzoylacetic ester, CgHgCO CHe-COOCoHs, was obtained by condensing benzoic and acetic esters in presence of sodium ethoxide, and j8-diketones by condensing ketones and acid esters, e.g. acetyl-acetone CHaCO-CHaCOCHg."... 

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