Everything about The Claisen Condensation totally explained
The
Claisen condensation (not to be confused with the
Claisen rearrangement) is a
carbon-carbon bond forming
reaction that occurs between two
esters or one ester and another
carbonyl compound in the presence of a
strong base, resulting in a β-keto ester or a β-di
ketone. It is named after
Rainer Ludwig Claisen, who first published his work on the reaction in
1881
.
Requirements
At least one of the reagents must be enolizable (have an
α-proton and be able to undergo
deprotonation to form the
enolate anion). There are a number of different combinations of enolizable and nonenolizable carbonyl compounds that form a few different
types of Claisen condensations.
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 (for example sodium ethoxide if
ethanol is formed) is often used, since the alkoxide is regenerated. In mixed Claisen condensations, a
non-nucleophilic base such as
lithium diisopropylamide, or LDA, may be used, since only one compound is enolizable. LDA can't be used in the classic Claisen or Dieckmann condensations, since virtually all ester will be converted to ester enolate and condensation won't occur.
The alkoxy portion of the ester must be a good
leaving group.
Methyl and
ethyl esters, which yield the methoxy and ethoxy leaving groups, respectively, are usually used.
Types
The classic Claisen condensation, where only one enolizable ester is used.
The mixed (or "crossed") Claisen condensation, where an enolizable ester or ketone and a nonenolizable ester are used.
The
Dieckmann condensation, where a molecule with two ester groups reacts
intramolecularly, forming a
cyclic β-keto ester. In this case, the ring formed must not be
strained, usually a 5- or 6-membered ring.
Mechanism
In the first step, the ester with the α-proton is deprotonated by the base, resulting in the enolate anion, made relatively stable by the
delocalization of
electrons. Then, the carbonyl carbon of the other ester undergoes nucleophilic attack by the α-carbon of the enolate. The alkoxy group leaves (resulting in regeneration of the alkoxide), and aqueous
acid (for example
sulfuric or
phosphoric acid) is added to
neutralize the base and any enolate still present. The newly-formed β-keto ester or β-diketone is then isolated.
Stobbe condensation
The
Stobbe condensation is a modification specific for the diethyl
ester of
succinic acid requiring less strong bases . An example is its reaction with
benzophenone :
reaction mechanism which explains the formation of both an ester group and a
carboxylic acid group is centered around a
lactone intermediate (
5):
Further Information
Get more info on 'Claisen Condensation'.
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