Claisen Condensation

The Claisen condensation (different from  Claisen rearrangement) is a C-C bond forming reaction that occurs between two esters or one ester and another carbonyl compound in the presence of a strong base (like sodium ethoxide), resulting in a β-keto ester or a β-diketone.  It is named after Rainer Ludwig Claisen (German Chemist), who first published his work on the reaction in 1881.

The base used must not interfere with the reaction by undergoing nucleophilic substitution or addition with a carbonyl carbon. For this reason, the conjugate sodium alkoxide base of the alcohol formed (like sodium ethoxide if ethanol is formed) is often used, since the alkoxide is regenerated. In some cases LDA (lithium diisopropylamide) a non nucleophilic base is used (e.g. mixed claisen condensation)

The alkoxy portion of the ester must be a relatively good leaving group. Methyl and ethyl esters, which yields methoxide and ethoxide, respectively, are commonly used.

The driving force is the formation of the stabilized anion of the β-keto ester. If two different esters are used, an essentially statistical mixture of all four products is generally obtained, and the preparation does not have high synthetic utility.

However, if one of the ester partners has enolizable α-hydrogens and the other does not (e.g., aromatic esters or carbonates), the mixed reaction (or crossed Claisen) can be synthetically useful. If ketones or nitriles are used as the donor in this condensation reaction, a β-diketone or a β-ketonitrile is obtained, respectively.

The use of stronger bases (like sodium amide or sodium hydride) instead of sodium ethoxide, often increases the yield.

Mixed Claisen Condensation (Reaction between enolizable ester or ketone and a nonenolizable ester)

Intramolecular Claisen Condensation (Reaction where a molecule with two ester groups reacts intramolecularly, forming a cyclic β-keto ester.  This is also called as Dieckmann Condensation)