Claisen reactions are the ester analogue of an aldol reaction except that in the Claisen reaction, an ester undergoes self-condensation instead of an aldehyde (aldol). An intramolecular Claisen reaction is also called a Dieckmann condensation.
Claisen condensation is the formation of a beta-keto ester from an ester and a base. A beta-keto ester is an ester that has a ketone on the beta carbon. The Claisen reaction is the ester analogue of the aldol condensation. An ester is used to make a beta-keto ester by formation of a C−C bond between the alpha carbon of one molecule and the carbonyl carbon of another molecule. The product of the reaction is the original ester with an acyl group added.
Claisen Condensation Reaction
In Claisen condensation, an alpha,beta-keto ester forms through the formation of a single carbon bond (C−C) between the alpha carbon of one ester molecule and the carbonyl carbon of another ester molecule.
In a practical crossed Claisen condensation, an ester or ketone enolate mixes with an ester that cannot form an enolate, an anion formed when the alpha hydrogen is removed as a hydrogen ion.
Crossed Claisen Reaction
In a crossed Claisen reaction, acetone and methyl benzoate react with sodium methoxide and then with acid to form 1-phenylbutane-1,3-dione, a beta-diketone. Acetone can form an enolate, but methyl benzoate cannot.
A directed Claisen condensation is a reaction in which an ester is treated with lithium diisopropylamide (LDA) or another strong base, followed by the addition of a second ester. The directed Claisen reaction involves the treatment of an ester with LDA followed by the addition of a second ester in a two-step process, just like in directed aldol condensation.
Intramolecular Claisen condensation (or Dieckmann condensation) is a reaction in which an ester is deprotonated at the alpha carbon, generating an enolate, which undergoes an intramolecular nucleophilic attack, yielding a cyclic enol. The enol is protonated with an acid to re-form the beta-keto ester. An enol is a compound with a C=C bond and a hydroxyl (OH) group.
The intramolecular Claisen condensation involves a diester that will cyclize to form five- or six-membered rings. The Dieckmann condensation reaction is named for German chemist Walter Dieckmann.
Intramolecular Claisen Condensation
In an intramolecular Claisen condensation, also known as a Dieckmann condensation, an ester is deprotonated at the alpha carbon, generating an enolate that undergoes nucleophilic attack, yielding a cyclic enol. The enol is protonated with an acid to re-form the beta-keto ester.
All Claisen condensations are reversible reactions that favor the reactant until the end of the mechanism, when the second alpha hydrogen is temporarily removed. Therefore, there must be at least 2 alpha protons for the reaction to proceed.
