15.26:
Esters to β-Ketoesters: Claisen Condensation Overview
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.
15.26:
Esters to β-Ketoesters: Claisen Condensation Overview
Regular Claisen condensation is a base-promoted reaction involving identical esters with two α hydrogens, condensing to produce β-ketoesters. It is a nucleophilic acyl substitution reaction wherein one of the ester molecules, upon deprotonation by the base, forms a nucleophilic enolate ion, while the other molecule serves as an electrophile.
The condensation reaction requires specific nonaqueous bases, such as alkoxide, which must be similar to the alkoxy group of the ester molecule. The use of different alkoxide ions often leads to the transesterification product. Also, the use of hydroxide bases is avoided as they result in irreversible hydrolysis of the esters to carboxylate ions.
