Esters, like aldehydes and ketones, enolize in base to produce a small equilibrium concentration of the corresponding enolate anion. As in the aldol condensation, this enolate anion can function as a nucleophile towards the carbonyl carbon of another mole of ester, and the result is the formation of a bond between the a-carbon of one mole of ester and the carbonyl of a second, to give a tetrahedral intermediate, as shown below for ethyl acetate. Expulsion of ethoxide from this intermediate re-forms the carbonyl and generates the condensation product, ethyl acetoacetate. This condensation reaction between two moles of an ester is called the Claisen condensation.

It is also possible to utilize two different esters in a Claisen-type condensation reaction (a mixed Claisen condensation). In order to minimize self-condensations, generally one reactant is chosen which has no a-hydrogens, and that reactant is maintained in large excess over the second reactant (which will have a-hydrogens and can form the enolate anion). An example of this is the synthesis shown below. This b-keto ester can be prepared by elimination of ethoxide from the tetrahedral intermediate formed by the addition of ethoxide anion to the ketone carbonyl. Splitting this tetrahedral intermediate between the a-carbon of the ester portion of the molecule and the tetrahedral center, it is evident that it can be prepared by the condensation of the enol of ethyl acetate and ethyl benzoate, as shown below.

The b-keto esters which are formed in a Claisen condensation are stable in base, but readily decarboxylate in acid solution to give simple ketones.

The decarboxylation reaction involves the hydrolysis of the ester to generate a b-keto carboxylic acid. These can undergo acid-catalyzed decarboxylation by the mechanism shown above to give the intermediate enol, which rapidly converts to the corresponding ketone. If the Claisen condensation involved the reaction of two moles of the same ester, the product formed will be a symmetrical ketone and the Claisen condensation is an excellent method for the preparation of symmetrical ketones. If a mixed Claisen condensation was utilized, more complex, asymmetrical ketones can be prepared.

As an example of the use of a Claisen condensation in synthesis, consider the preparation of 2,6-dimethyl-4-heptanone. This molecule is a symmetrical ketone. We can make these by the decarboxylation of b-keto acid in aqueous acid. The required b-keto acid, in turn can be prepared by the Claisen condensation of two moles of ethyl 3-methylbutanoate in the presence of ethoxide anion. Remember, to determine the structure of the required ester, simply add ethoxide to the ketone carbonyl to form the tetrahedral intermediate, shown on the right, and split the compound at the bond between the tetrahedral center and the a-carbon of the ester portion of the molecule. The complete synthesis is shown below.