Claisen condensation

Claisen Condensation

The Claisen condensation is a fundamental carbon-carbon bond-forming reaction in organic chemistry. It involves the reaction of two esters or one ester and another carbonyl compound in the presence of a strong base to form a β-keto ester or a β-diketone. This reaction is named after the German chemist Ludwig Claisen, who first reported it in 1887.

Mechanism

The Claisen condensation proceeds through several key steps:

1. Deprotonation: A strong base, typically an alkoxide ion, deprotonates the α-hydrogen of the ester to form an enolate ion. This step is crucial as it generates the nucleophile needed for the subsequent reaction.
2. Nucleophilic Attack: The enolate ion attacks the carbonyl carbon of another ester molecule, forming a tetrahedral intermediate.
3. Elimination: The tetrahedral intermediate collapses, expelling an alkoxide ion and forming a β-keto ester or β-diketone.
4. Protonation: The alkoxide ion is protonated by the solvent or another source, regenerating the base and completing the reaction.

Conditions and Variations

The Claisen condensation requires a strong base, such as sodium ethoxide or sodium hydride, and is typically carried out in an anhydrous solvent like ethanol or THF. The reaction is sensitive to the nature of the ester and the base used.

There are several variations of the Claisen condensation:

• Crossed Claisen Condensation: Involves two different esters or an ester and a ketone. Care must be taken to avoid self-condensation.
• Dieckmann Condensation: An intramolecular version of the Claisen condensation, where a diester forms a cyclic β-keto ester.

Applications

The Claisen condensation is widely used in organic synthesis to construct complex molecules. It is particularly useful in the synthesis of β-keto esters, which are valuable intermediates in the synthesis of pharmaceuticals, agrochemicals, and natural products.

Also see

• Aldol reaction
• Dieckmann condensation
• Enolate chemistry
• Carbonyl chemistry