Ethyl acetate Claisen condensation

The preparation of benzoylacctone Is another example of the acylation of a ketone (acetophenone) by ethyl acetate to a p diketone (Claisen condensation compare preceding Section) ... 

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. 

FIGURE 21 1 The mechanism of the Claisen condensation of ethyl acetate... 

On treatment with alkoxide bases, esters undergo self-condensation to give a p-keto ester and an alcohol. Ethyl acetate, for exanple, undergoes a Claisen condensation on treatment with sodium ethoxide to give a p-keto ester known by its common nane ethyl ace-toacetate (also called acetoacetic ester) ... 

Ethyl acetoacetate (acetoacetic ester), available by the Claisen condensation of ethyl acetate, has properties that make it a useful starting material for the preparation of ketones. These properties are... 

Claisen condensation of propionitrile with ethyl acetate in the presence of sodium ethoxide gives the cyanobutanone, 119. 

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.)... 

An important group of acylation reactions involves esters, in which case the leaving group is alkoxy or aryloxy. The self-condensation of esters is known as the Claisen condensation.216 Ethyl acetoacetate, for example, is prepared by Claisen condensation of ethyl acetate. All of the steps in the mechanism are reversible, and a full equivalent of base is needed to bring the reaction to completion. Ethyl acetoacetate is more acidic than any of the other species present and is converted to its conjugate base in the final step. The (3-ketoester product is obtained after neutralization. 

Benzoylacetone. — C6H5.CO.CH2.CO.CH3 is prepared in an analogous way from acetophenone and ethyl acetate according to the procedure of Claisen, Ber., 1905, 38, 695. The yield may be as much as 75 per cent of the theoretical. The cheaper converse method—action of sodamide on ethyl benzoate and acetone—also succeeds in this case, although it fails when sodium or sodium ethoxide is used as condensing agent. In general the use of sodamide is to be preferred in the synthesis of 1 3-diketones. 

The Claisen reaction (sometimes Claisen condensation) is formally the base-catalysed reaction between two molecules of ester to give a P-ketoester. Thus, from two molecules of ethyl acetate the product is ethyl acetoacetate. 

The enolate anion attacks the carbonyl carbon of a second molecule of ester and gives a P-ketoester. Thus, the Claisen condensation is a nucleophilic acyl substitution reaction. Eor example, two molecules of ethyl acetate condense together to form the enolate of ethyl acetoacetate, which upon addition of an acid produces ethyl acetoacetate (P-ketoester). 

Acetoacetic Ester can be prepared by the condensation of ethyl acetate, called the Acetoacetic Ester Condensation Reaction, a Claisen Condensation-. 

The acylation of ketones with esters an example of the Claisen condensation is generally effected with a basic reagent, such as sodium ethoxide, sodium, sodamide or sodium hy dride. Thus acetone and ethyl acetate condense in the presence of sodium ethoxide to yield acetylacetone ... 

Claisen condensation of ethyl quinuclidine-2-carboxylate (73) with ethyl acetate yields ethyl j8-oxo-j8-(2-quinuclidyl)propionate (84). This was transformed into j8-amino-j3-(2-quinuclidyl)propionic acid (85)108 and 2-acetylquinuclidine (86).43... 

By analogy, the chemical Claisen condensation using the enolate anion from diethyl malonate in Figure 2.10 proceeds much more favourably than that using the enolate from ethyl acetate. The same acetoacetic acid product can be formed in the malonate condensation by hydrolysis of the acylated malonate intermediate and decarboxylation of the gem-diacid. 

Diethyl 2-phenylmalonate is prepared by a mixed Claisen condensation between ethyl phenyl-acetate and diethyl carbonate. 

Synthesis of substituted acetic acids via acetoacetic ester Acetoacetic ester, an ester formed by the self-condensation of ethyl acetate via a Claisen condensation, has the following structure ... 

In both these last two examples, a very strong base is used in the form of LDA such that the enolate ion is formed quantitatively (from ethyl acetate and acetone respectively). This avoids the possibility of self-Claisen condensation and limits the reaction to the crossed Claisen condensation. 

The reaction of 2-methyl-4-carbethoxyoxazole (114) with ethyl acetate under basic conditions had been reported to result in the product of alkylation on the methyl group of 124 which was thought to exist in the enol form 125 (49). On reinvestigation of the reaction it was revealed that the product was actually that of Claisen condensation (126) which existed in the enol form 127 (75). The close... 

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