Claisen Condensation
The Claisen Condensation is an important carbon-carbon bond forming reaction that produces a 1,3-dicarbonyl compound from an ester and another carbonyl compound. The intramolecular variant of the reaction is known as the Dieckmann Condensation. The reaction is performed under basic conditions, usually using the alkoxide form of the alcohol component of the ester to avoid transesterification.
The reaction usually involves the reaction of two molecules of the same ester to avoid forming a mixture of different condensation products. An ester and a different carbonyl compound can be used however, particularly when the ester does not possess an enolizable hydrogen atom α to the carbonyl. This variant is known as the Crossed Claisen Condensation.
The mechanism involves formation of the enolate of the compound that will react with the ester as a nucleophile. The enolate is formed via deprotonation of a hydrogen atom α to the carbonyl. The enolate then attacks the carbonyl carbon of the ester, and the tetrahedral intermediate undergoes elimination of alkoxide.
The driving force of the reaction is the deprotonation of the resulting 1,3-dicarbonyl compound condensation product. Hydrogen atoms that are α to two carbonyl carbon atoms are significantly more acidic than either the alcohol or the starting materials and essentially all of the 1,3-dicarbonyl product will be deprotonated in solution. For example, the pKa of ethyl acetoacetate (shown above) is 11, whereas the pKa of ethanol is 16.
The Claisen Condensation differs from the Aldol Condensation because the Aldol Condensation forms an intermediate β-hydroxy carbonyl compound which undergoes elimination to form an α,β-unsaturated carbonyl compound. In the Claisen Condensation however, the resulting tetrahedral intermediate is a hemiketal which can eliminate alkoxide to form the ketone.