Ketones Claisen condensation with

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 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. ... 

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. 

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 addition to crossed aldol additions and crossed Claisen condensations, a ketone can undergo a crossed condensation with an ester. If both the ketone and the ester have a-hydrogens, then LDA is used to form the needed enolate ion and the other carbonyl compound is added slowly to the enolate ion to minimize the chance of its forming an enolate ion and reacting with another molecule of its parent ester. 

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 basic principle of polyketide assembly is highly related to that of fatty acid biosynthesis [14, 16]. In both biosynthetic systems, an acyl-primed ketosynthase (KS) catalyzes chain extension by decarboxylative Claisen condensation with malonate activated by its attachment to coenzyme A or an acyl carrier protein (ACP) via a thioester bond (Scheme 2.2). hi fatty acid synthases (FASs), the resulting ketone is rednced to the corresponding alcohol by a ketore-ductase (KR), dehydrated by action of a dehydratase (DH) to give the alkene with snbseqnent donble-bond reduction by an enoyl rednctase (ER) yielding the saturated system (cf. Section 3.2). The latter can then be transferred onto the KS domain and enter the next cycle of chain extension and complete rednction. This homologation process facilitates the assembly of long-chain satnrated fatty acids, for example, palmitic acid, after seven cycles, which will ultimately be released from the catalytic system by saponification of the... 

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 ... 

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 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. 

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... 

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... 

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. 

Acetylisothiazoles have been prepared by ketonic hydrolysis of the jS-ketoesters derived from the Claisen condensation on 5-ethoxycar-bonylisothiazoles. 5-Acetyl-3-methylisothiazole is also obtained from the reaction of 5-cyano-3-methylisothiazole with methylmagnesium iodide. ... 

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. 

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