Claisen-Schmidt condensation examples

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) ... 

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. 

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-Schmidt condensation ... 

Aldol and related condensation reactions such as Knoevenagel and Claisen-Schmidt condensations are also widely used in the fine chemicals and specialty chemicals, e.g. flavors and fragrances, industries. Activated hydrotalcites have been employed as solid bases in many of these syntheses. Pertinent examples include the aldol condensation of acetone and citral [107, 108], the first step in the synthesis of ionones, and the Claisen-Schmidt condensation of substituted 2-hydroxyacetophenones with substituted benzaldehydes [109], the synthetic... 

As discussed in a previous section, metal oxides represent an important class of materials exhibiting a broad range of properties from insulators to semiconductors and conductors and have found applications as diverse as electronics, cosmetics and catalysts. Metal oxides have been widely used in many valuable heterogeneous catalytic reactions. Typical metal oxide-catalyzed reactions, including alkane oxidation, biodiesel production, methanol adsorption and decomposition, destructive adsorption of chlorocarbons and warfare agents, olefin metathesis and the Claisen-Schmidt condensation will be briefly discussed as examples of metal oxide-catalyzed reactions. 

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,... 

Hydrotalcite-derived materials also show good performances in analogous reactions, such as the Claisen-Schmidt condensation of substituted 2-hydroxyacetophe-nones with substituted benzaldehydes, the synthetic route to flavonoids and the condensation of 2,4-dimethoxyacetophenone with p-anisaldehyde to synthesize Vesidryl, a diuretic drug [270]. Another similar class of reactions in which HT-based materials give good results are Knoevenagel condensations [271]. An example is the synthesis of citronitrile, a perfumery compound with a citrus-like odor, which can be prepared by HT-catalyzed condensation of benzylacetone with ethyl cyanoacetate, followed by hydrolysis and decarboxylation (Figure 2.42b) [272]. 

The trivial name of the reaction was applied by Wurtz in 1872, and stems from the trivial name of the dimer resulting from the acid-catalyzed self-reaction of acetaldehyde (equation 1). In time, the term came to be applied to the analogous self-condensation reactions of ketones, the first known example of which was the acid-mediated dimerization of acetone, discovered in 1838. The first use of a base as a catalyst for the aldol reaction was in the reaction of furfural with acetaldehyde or acetone (equation 2). This example also illustrates the first example of a mixed aldol reaction, a process that came to be known as the Claisen-Schmidt condensation. ... 

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. 

Aldot condensations between a ketone acting as methylene compound and an aldehyde are termed C laiscn-Schmidt condensations [9]. Therefore. Claisen-Schmidt condensations between acetophenone and bcn/aldchyde derivatives allow u.p-unsaturated ketones called chalconcs (Figure 14) 1110, 182, 256-258]. Chalcones are flavonoids of numerous applications as pesticides, phoioproiector in plastics, solar creams, food additives and many biological activities [Pg.98]

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." ... 

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. 

Another example is the enhancement of the reaction rate for the Claisen-Schmidt condensation of benzaldehy-des with acetophenone by using either sodium butyl monoglycol sulfate or the sodium salts of aromatic sulfonic acids as hydrotropes (32). Solvents such as N, A -dimethylformamide, tetrahydrofuran and alcohols are generally used in these preparations. However, by introducing hydrotrope solutions as the reactive media, the use of expensive organic solvents can be avoided. 

The crossed aldol examples shown in Table 19.1 involve aldehydes as both reactants. A ketone can be used as one reactant, however, because ketones do not self-condense appreciably due to steric hindrance in the aldol adchtion stage. The following are examples of crossed aldol condensations where one reactant is a ketone. Reactions such as these are sometimes called Claisen—Schmidt condensations. Schmidt discovered and Claisen developed this type of aldol reaction in the late 1800s. 

There have been many other investigations of the applications of LDO catalysts to Claisen-Schmidt condensation (540). For example, with activated MgAl-COs-LDH as catalyst, benezaldehyde and 2-hydroxylacetophenone react at 50°C to give the desired compounds (2-hydroxychalcone and flavanone) at 80% conversion and 78% selectivity (541). As another example, the condensation of citral and acetone produces an intermediate that can be finally transformed to chemically useful ionones (542,543). The use of calcined LDH results in 70% selectivity at about 95% conversion. In addition, Dumitriu et al. (544) and Suzuki... 

While catalyst 22/23 has been known to be valuable in other C-C bond-forming strategies, for example, 1,3-dipolar cycloaddition [149], hetero-Diels-Alder reaction [150], Friedel-Crafts-type alkylation [151], double-Michael reaction [152], [2,3]-Wittig rearrangement [153], and Claisen-Schmidt condensation [154], only references are given here. 

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. 

Scheme 7.4 presents some representative examples of Claisen-Schmidt reactions. Entries 1 and 2 are typical base-catalyzed condensations at methyl groups. Entry 3 illustrates the use of a cyclic ketone, and reaction occurs at the methylene group, where dehydration is possible. The stereochemistry presumably places the furan ring trans to the carbonyl group for maximum conjugation. Entry 4 shows the use of phthalaldehyde to effect a cyclization. Entry 5 illustrates the preference for condensation at the more-substituted position under acidic conditions. 

Purpose, The synthetically useful aldol reaction is investigated as a method of forming carbon-carbon bonds. It is a general reaction of aldehydes that may also be extended to ketones. The specific case outlined in this experiment is known as the Claisen-Schmidt reaction. Experiments [A3a] and [FI] provide other examples of the aldol condensation. 

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). 

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]. 

Illustrative examples of the condensation of aromatic aldehydes /ith enolizable ketones ( Claisen-Schmidt reaction ). 

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