15.26 : エステルからβ-ケトエステルへ: クライゼン縮合の概要

Regular Claisen condensation is the reaction when identical ester molecules bearing two α hydrogens combine to generate a β-keto ester—a molecule comprising a keto group β to the ester group.

Claisen condensations require nonaqueous alkoxide bases to initiate the reaction by deprotonating the α hydrogen of the ester and producing the nucleophilic enolate.

The base employed is specific and must be identical to the alkoxy group of the starting ester molecule.  

For instance, Claisen condensation of an ethyl ester—promoted by an ethoxide base—produces the desired β-keto ester in decent yields.

If, instead, a methoxide base is used, nucleophilic addition at the carbonyl carbon of the ester takes place, rather than deprotonation of the α hydrogen, to give a transesterification product.

Also, the use of hydroxide bases is forbidden, as it results in irreversible hydrolysis of esters to carboxylate ions.

In summary, Claisen condensation is a nucleophilic acyl substitution reaction wherein a nucleophilic ester enolate reacts with another ester molecule to produce a β-ketoester.