Claisen condensation

Claisen condensation
The overall reaction of the classic Claisen condensation.

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-diketone[1]. It is named after Rainer Ludwig Claisen, who first published his work on the reaction in 1881 [2][3][4].



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 (e.g. 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 is not commonly used in the classic Claisen or Dieckmann condensations due to enolization of the electrophilic ester.

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.


Claisen ethyl acetate.png
The classic Claisen condensation, where only one enolizable ester is used.

Mixed claisen example.png
The mixed (or "crossed") Claisen condensation, where an enolizable ester or ketone and a nonenolizable ester are used.

Dieckmann example.png
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 chain or ring.


Claisen condensation mech.png

In the first step of the mechanism, an α-proton is removed by a strong base, resulting in the formation of an enolate anion, which is made relatively stable by the delocalization of electrons. Next, the carbonyl carbon of the (other) ester is nucleophilically attacked by the enolate anion. The alkoxy group is then eliminated (resulting in (re)generation of the alkoxide), and the alkoxide removes the newly-formed doubly α-proton to form a new, highly resonance-stabilized enolate anion. Aqueous acid (e.g. sulfuric acid or phosphoric acid) is added in the final step to neutralize the enolate and any base still present. The newly-formed β-keto ester or β-diketone is then isolated. Note that the reaction requires a stoichiometric amount of base as the removal of the doubly α-proton thermodynamically drives the otherwise endergonic reaction. That is, Claisen condensation does not work with substrates having only one α-hydrogen because of the driving force effect of deprotonation of the β-keto ester in the last step.

Stobbe condensation

The Stobbe condensation [5] is a modification specific for the diethyl ester of succinic acid requiring less strong bases [6]. An example is its reaction with benzophenone [7]:

Stobbe condensation

A reaction mechanism which explains the formation of both an ester group and a carboxylic acid group is centered around a lactone intermediate (5):

Stobbe condensation mechanism

See also


  1. ^ Carey, Francis A. (2006). Organic Chemistry (Sixth ed.). New York, NY: McGraw-Hill. ISBN 0-07-111562-5. 
  2. ^ Claisen, L., and A. Claparede. Ber. Deut. Chem. Ges., 1881, 14, 2460.
  3. ^ Claisen, L. Ber. Deut. Chem. Ges., 1887, 20, 655.
  4. ^ Hauser, C. R.; Hudson, Jr., B. E. Org. React. 1942, 1.
  5. ^ Hans Stobbe, Ann., 308, 89 (1899).
  6. ^ March, Jerry (1985), Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (3rd ed.), New York: Wiley, ISBN 0-471-85472-7 
  7. ^ Organic Syntheses, Coll. Vol. 4, p.132 (1963); Vol. 30, p.18 (1950).

External links

Wikimedia Foundation. 2010.

Look at other dictionaries:

  • Condensation reaction — The condensation of two amino acids to form a peptide bond (red) with expulsion of water (blue) A condensation reaction is a chemical reaction in which two molecules or moieties (functional groups) combine to form one single molecule, together… …   Wikipedia

  • Claisen rearrangement — The Claisen rearrangement (not to be confused with the Claisen condensation) is a powerful carbon carbon bond forming chemical reaction discovered by Rainer Ludwig Claisen. The heating of an allyl vinyl ether will initiate a [3,3] sigmatropic… …   Wikipedia

  • Condensation acyloïne — La condensation acyloïne est une réaction réductive de couple entre deux esters carboxyliques, utilisant du sodium métallique et menant à une α hydroxycétone, ou acyloïne[1],[2],[3] …   Wikipédia en Français

  • Condensation (Homonymie) — Cette page d’homonymie répertorie les différents sujets et articles partageant un même nom. En physique, la condensation est soit une transition de phase, d un gaz vers un état condensé (liquide ou solide), soit le passage de la matière à l état… …   Wikipédia en Français

  • Condensation de Claisen — La condensation de Claisen (à ne pas confondre avec le réarrangement de Claisen) est une réaction omniprésente en milieu biologique. C est une réaction formant une liaison carbone carbone à partir de deux esters (ou deux thioesters par exemple)… …   Wikipédia en Français

  • Condensation (homonymie) — Cette page d’homonymie répertorie les différents sujets et articles partageant un même nom. En physique : la condensation, une transition de phase, d un gaz vers un état condensé (liquide ou solide), condensat de Bose Einstein ;… …   Wikipédia en Français

  • condensation — 1. Making more solid or dense. 2. The change of a gas to a liquid, or of a liquid to a solid. 3. In psychoanalysis, an unconscious mental process in which one symbol stands for a number of others. 4 …   Medical dictionary

  • Rainer Ludwig Claisen — (January 14, 1851 ndash; January 5, 1930) was a famous German chemist best known for his work with condensations of carbonyls and sigmatropic rearrangements. He was born in Cologne as the son of a jurist and studied chemistry at the university of …   Wikipedia

  • Aldol condensation — An aldol condensation is an organic reaction in which an enol or an enolate ion reacts with a carbonyl compound to form a β hydroxyaldehyde or β hydroxyketone, followed by a dehydration to give a conjugated enone. Aldol condensations are… …   Wikipedia

  • Dieckmann condensation — The Dieckmann condensation is the intramolecular chemical reaction of diesters with base to give β ketoesters.[1][2][3][4][5] It is named after the German chemist Walter Dieckmann (1869–1925). The equivalent intermolecular reaction is the Claisen …   Wikipedia

Share the article and excerpts

Direct link
Do a right-click on the link above
and select “Copy Link”

We are using cookies for the best presentation of our site. Continuing to use this site, you agree with this.