Ethyl acetoacetate from Claisen reaction

This reaction was first reported by Geuther in 1863 and subsequently studied by Claisen. It is a self-condensation of ester in the presence of alkali alkoxide in alcohol to form /3-keto esters (e.g. ethyl acetoacetate from ethyl acetate) and is generally known as acetoacetic ester condensation. This reaction was extensively explored by McElvain in 1930s. In general, it is carried out under basic conditions (e.g., NaOEt) to generate /3-keto-esters from aliphatic carboxylic acid esters. 

This Reaction should be carefully distinguished from the Claisen Conden-tation, which is the condensation of an ester, under the influence of sodium ethoxide, with (i) another ester, (ii) a ketone, or (iii) a nitrile, with the elimination of alcohol. For details of this condensation, see Ethyl Acetoacetate, p. 264. 

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. 

However, the reaction is not quite that simple, and to understand and utilize the Claisen reaction we have to consider pAT values again. Loss of ethoxide from the addition anion is not really favourable, since ethoxide is not a particularly good leaving group. This is because ethoxide is a strong base, the conjugate base of a weak acid (see Section 6.1.4). So far then, the reaction will be reversible. What makes it actually proceed further is the fact that ethoxide is a strong base, and able to ionize acids. The ethyl acetoacetate prodnct is a 1,3-dicarbonyl componnd and has relatively acidic protons on the methylene between the two carbonyls (see Section 10.1). With... 

This anion will not be produced from a B-ketoester that has no hydrogens on the carbon between the two carbonyl groups. Such B-ketoesters would result from the Claisen condensation of an ester having only one a hydrogen. Since our problem uses ethyl acetate, the B ketoester anion is formed. This anion, like the enolate anion, is nucleophilic enough to attack the partially positively charged carbonyl carbon of an ester. Here, 0-acylation is much less thermodynamically stable than is C-acylation. Hence, the reaction of the B-ketoester anion with the ester (using ethyl acetoacetate and ethyl acetate as in our problem) is ... 

Claisen reaction is a carbonyl condensation that occurs between two ester components and gives a p-keto ester product. The reaction has a mechanism similar to that of the aldol reaction. The difference from aldol condensation is the expulsion of an alkoxide ion from the tetrahedral intermediate of the initial Claisen adduct. This adduct is not stable and expels the ethoxide ion to give the new carbonyl compound ethyl acetoacetate (p-keto ester). Claisen products can be easily hydrolyzed and decarboxylated (Figure 1.19). There are also many examples of retro-Claisen... 

In this section, we examine the formation of an enolate anion from one ester, followed by the nucleophilic acyl substitution of the enolate anion at the carbonyl carbon of another ester. One of the first of these reactions discovered was the Claisen condensation, named after its discoverer, German chemist Ludwig Qaisen (1851—1930). We illustrate a Claisen condensation by the reaction between two molecules of ethyl acetate in the presence of sodium ethoxide, followed by acidification, to give ethyl acetoacetate (note that, in this and many of the equations that follow, we abbreviate the ethyl group as Et) ... 

The Claisen condensation is a carbon-carbon bond-forming reaction that is useful for synthesizing j8-keto esters. In Chapter 18 we saw how j8-keto esters are useful in synthesis. In a Qaisai condensation, the enolate of one ester molecule adds to the carbonyl group of another, resulting in an acyl substitution reaction that forms a j8-keto ester and an alcohol molecule. The alcohol molecule that is formed derives from the alkoxyl group of the ester. A classic example is the Claisen condensation by which ethyl acetoacetate (acetoacetic ester) can be synthesized. 

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