Claisen Condensation
Claisen condensation is an important organic reaction where an ester containing an alpha (α) hydrogen reacts with a strong base such as sodium ethoxide (C₂H₅ONa). This results in the formation of a β-keto ester.
The reaction can occur in two ways:
- Simple Claisen Condensation – between identical ester molecules.
- Crossed (Mixed) Claisen Condensation – between different esters or between an ester and a ketone.
Mechanism of Claisen Condensation
The mechanism involves the following key steps:
- Formation of Enolate Ion: The base abstracts an α-hydrogen from the ester, generating a strong nucleophilic enolate ion.
- Nucleophilic Attack: The enolate attacks the carbonyl carbon of another ester molecule, forming an intermediate oxonium ion.
- Elimination: The intermediate loses an ethoxide ion to form a β-keto ester.
- Enolate Stabilization: The β-keto ester is acidic due to the active methylene group and forms a stable enolate with excess strong base.
- Acidification: The reaction mixture is acidified to regenerate the β-keto ester.
Because the first three steps are reversible, excess sodium ethoxide is required to push the reaction forward by stabilizing the enolate form.
Important Note
Esters with only one α-hydrogen cannot undergo Claisen condensation using normal bases because the β-keto ester formed cannot convert into its enolate ion. However, very strong bases like triphenylmethyl sodium can force such reactions to occur.
Applications of Claisen Condensation
Claisen and crossed Claisen condensations are widely used to synthesize:
- Vitamins
- Alkaloids
- Terpenes
- Sex hormones
- Flavones
Crossed Claisen condensation usually gives mixtures unless one ester lacks α-hydrogens. Common esters that lack α-hydrogens and act as good carbanion acceptors include:
- Ethyl benzoate
- Ethyl formate
- Ethyl oxalate
- Ethyl carbonate
Crossed Claisen Condensation Examples
1. With Ethyl Benzoate
Used to produce aromatic β-keto esters with synthetic importance.
2. With Ethyl Formate
A useful method to introduce a formyl group into the product.
3. With Diethyl Oxalate
Produces oxalyl derivatives that eliminate CO to form malonic ester derivatives. These are important in the synthesis of dibasic acids and α-keto acids.
4. With Diethyl Carbonate
Forms malonic ester derivatives which can be further transformed into various useful organic compounds.
Ethyl Acetoacetate (EAA)
One of the most important β-keto esters obtained through Claisen condensation. It undergoes easy alkylation followed by hydrolysis to yield a wide range of ketones, acids, and heterocyclic compounds.
Dieckmann Reaction
When Claisen condensation occurs intramolecularly in a diester containing 6–8 carbon atoms, it forms a cyclic β-keto ester. This special type of intramolecular reaction is called the Dieckmann condensation.
Difference Between Aldol and Claisen Condensation
The key difference is:
- Aldol: No group is eliminated.
- Claisen: An ethoxide (C₂H₅O⁻) leaving group is eliminated.
This makes Claisen condensation suitable for forming β-keto esters rather than β-hydroxy compounds.
Detailed Notes:
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