Ketones Claisen condensation with esters

The carbanions derived from acylthiophenes have been condensed with aldehydes,and, through the Claisen condensation with esters, thienylsubstituted -diketones have been obtained. 2-Thenoyl trifluoroacetone, first prepared by Reid and Calvin through the Claisen condensation of 2-acetylthiophene with ethyl trifluoracetate, has become an extremely useful chelating agent for the extraction of numerous elements from strongly acidic solutions, The tautomeric form which dominates in aqueous solution is the ketone hy-drate. Other thiophenes have also proved useful for analytical purposes. ... 

If only a single electron-withdrawing substituent is present, as with simple ketones, esters, and nitriles, the formation of alkyl derivatives in high yield requires careful control of reaction conditions. Use of bases that are strong enough to effect only partial conversion of the substrate to its anion can result in aldol-condensation reactions with ketones and Claisen condensations with esters (see Chapter 2 for discussion of these reactions). This problem can be partially avoided by use of very strong bases such as the amide, hydride, or triphenylmethyl anions. 

In a reaction related to the mixed Claisen condensation nonenolizable esters are used as acylatmg agents for ketone enolates Ketones (via their enolates) are converted to p keto esters by reaction with diethyl carbonate... 

Mixed Claisen-like reactions can also be carried out between an ester and a ketone, resulting in the synthesis of a jS-diketone. The reaction works best when the ester component has no a hydrogens and thus can t act as the nucleophilic donor. For example, ethyl formate gives high yields in mixed Claisen condensations with ketones. 

The biosynthesis of the polyketide moiety is thought to involve the condensation of coenzyme A esters of acetic acid with malonyl coenzyme A to give thiol esters of 3-keto acids. Further Claisen condensations with malonyl coenzyme A add further ketone units, leading to 3,5-diketo, 3,5,7-triketo acids and so on as their thiol esters. Intramolecular condensations subsequently afford heterocyclic or aromatic structures (Scheme 275). 

Methyl ethyl ketone can be made to undergo the Claisen condensation with a given ester to yield either of two products, depending upon experimental conditions, (a) What are these two products (b) How could you tell quickly and simply which product you had obtained Note Use ethyl benzoate as the ester.)... 

We know what the disconnection must be, since we have been given one starting material. This looks like an enolate alkylation, and we need to use a specific enolate to stop the ketone self-condensing. The best enolate equivalent will be one that is not too basic, to avoid competing ehmination. The simplest solution is probably to use a keto-ester, easily made by Claisen condensation with diuethyl carbonate. After alkylation, the ester group is removed by decarboxylation. 

Although mixed Claisen condensations between esters are usually not selective, they can be so with certain substrates (nonenohzable esters, intramolecular versions, ketones). 

Claisen condensation Condensation of an ester with another ester, a ketone or a nitrile in the presence of sodium ethoxide, sodium or sodamidc, with the elimination of an alcohol. The result is the formation of a / -ketonic ester, ketone, or nitrile respectively, e.g. 

This preparation was discovered independently by Geuther (1863) and by Frankland and Duppa (1865). The reaction was subsequently investigated in detail and so w idely extended by Claisen that it has become solely a specific example of the more general process known as the Claisen Condensation. Claisen showed that an ester under the influence of sodium ethoxide would not only condense with itself (as in the preparation of ethyl acetoacetate), but also with (i) another ester, (ii) a ketone, if of formula RCHgCOR, (iii) a nitrile, if of formula RCH CN, in each case with the elimination of alcohol. Examples of these modifications are ... 

The Claisen condensation of an aliphatic ester and a thiazolic ester gives after acidic hydrolysis a thiazolylketone (56). For example, the Claisen condensation of ethyl 4-methyl-5-thiazolecarboxylate with ethyl acetate followed by acid hydrolysis gives methyl 4-methyl-5-thiazolyl ketone in 16% yield. 

The sequence begins with a Claisen condensation of ethyl pentanoate to give a p keto ester The ester is hydrolyzed and the resulting p keto acid decarboxylates to yield the desired ketone... 

Esters, like aldehydes and ketones, are weakly acidic. When an ester with an a- hydrogen is treated with 1 equivalent of a base such as sodium ethoxide, a reversible carbonyl condensation reaction occurs to yield a /3-keto ester. For example, ethyl acetate yields ethyl acetoacetate on base treatment. This reaction between two ester molecules is known as the Claisen condensation reaction. (We ll use ethyl esters, abbreviated "Et," for consistency, but other esters will also work.)... 

The mixed Claisen condensation of two different esters is similar to the mixed aldol condensation of two different aldehydes or ketones (Section 23.5). Mixed Claisen reactions are successful only when one of the two ester components has no a hydrogens and thus can t form an enolate ion. For example, ethyl benzoate and ethyl formate can t form enolate ions and thus can t serve as donors. They can, however, act as the electrophilic acceptor components in reactions with other ester anions to give mixed /3-keto ester products. 

Carboxylic esters can be treated with ketones to give p-diketones in a reaction that is essentially the same as 10-118. The reaction is so similar that it is sometimes also called the Claisen condensation, though this usage is unfortunate. A fairly strong base, such as sodium amide or sodium hydride, is required. Yields can be increased by the catalytic addition of crown ethers. Esters of formic acid (R H) give P-keto aldehydes. Ethyl carbonate gives P-keto esters. 

In the presence of a strong base, the ot carbon of a carboxylic ester can condense with the carbonyl carbon of an aldehyde or ketone to give a P-hydroxy ester, which may or may not be dehydrated to the a,P-unsaturated ester. This reaction is sometimes called the Claisen reaction,an unfortunate usage since that name is more firmly connected to 10-118. In a modem example of how the reaction is used, addition of tert-butyl acetate to LDA in hexane at -78°C gives the lithium salt of ferf-butyl acetate, " (12-21) an enolate anion. Subsequent reaction a ketone provides a simple rapid alternative to the Reformatsky reaction (16-31) as a means of preparing P-hydroxy erf-butyl esters. It is also possible for the a carbon of an aldehyde or ketone to add to the carbonyl carbon of a carboxylic ester, but this is a different reaction (10-119) involving nucleophilic substitution and not addition to a C=0 bond. It can, however, be a side reaction if the aldehyde or ketone has an a hydrogen. 

Claisen condensation org chem 1. Condensation, in the presence of sodium ethox-ide, of esters or of esters and ketones to form p-dicarbonyl compounds. 2. Condensation of arylaldehydes and acylphenones with esters or ketones In the presence of sodium ethoxide to yield unsaturated esters. Also known as Claisen reaction. klas-3n kand-on sa-shon ... 

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