Claisen Condensation Mechanism

What is Claisen Condensation?

The Claisen condensation reaction is an organic coupling reaction that results in the formation of a C-C bond between either a single ester and one carbonyl compound or between two esters. The reaction proceeds when a strong base is present and the product of the reaction is a beta-keto ester or a beta-diketone.

The reaction is named after its discoverer, the German chemist Rainer Ludwig Claisen. An illustration of this reaction is provided below. The mechanism of the Claisen condensation reaction proceeds with the removal of an alpha proton through the action of a strong base to result in the formation of an enolate ion.

Claisen Condensation

  • The Claisen condensation reaction requires that a minimum of one reagent must have an alpha proton and can form an enolate anion upon deprotonation.
  • The reaction also requires the base to avoid participating in nucleophilic substitution reactions or nucleophilic addition with a carbon belonging to the carbonyl functional group.
  • An ideal base for this reaction is the sodium alkoxide which is the conjugate base of the alcohol to be formed since it is regenerated.
  • Another requirement is that the alkoxy part of the ester must behave as a good leaving group, as in the case of ethyl and methyl esters.

It can be noted that when different esters undergo a Claisen condensation reaction, a mixture of four different products is obtained. The yield of the reaction can be improved with the usage of a very strong base, such as NaOH.

Mechanism of Claisen Condensation

Step 1

The strong base removes an alpha proton. This results in the generation of the enolate ion. This enolate anion is relatively stable due to the delocalization of the negative charge (electrons). Given below is the reaction which leads to the formation of the enolate anion.

Claisen Condensation Mechanism Step 1

Step 2

The carbonyl carbon belonging to the second ester reactant is now the target of a nucleophilic attack from the enolate anion. This leads to the elimination of the alkoxy group and the regeneration of the conjugate base of the alcohol. This alkoxide ion removes the doubly alpha proton which is formed, giving rise to a new enolate anion which is now resonance stabilized. The formation of this new enolate ion is illustrated below.

Claisen Condensation Mechanism Step 2

Step 3

Now, an aqueous acid (phosphoric acid or sulphuric acid, for example) is added to neutralize the negative charge on the enolate anion as well as any base which is still present. This leads to the formation of a beta-diketone or a beta-keto ester, which is immediately isolated. The leaving group is removed. The final step of the Claisen condensation mechanism can be illustrated as follows:

Claisen Condensation Mechanism Step 3

Thus, the ester (or carbonyl compound and ester) reactants are converted into beta-keto esters or beta-diketones. The Claisen condensation reaction has been modified into several variations, which are discussed in the next subsection.

Variations

Some important variations of this organic coupling reaction are listed below.

  • The classic version of the Claisen condensation reaction involves a reaction between two molecules of an ester-containing compound where the ester is enolizable.
  • The Dieckmann condensation reaction involves the intramolecular reactions of two ester groups belonging to the same molecule. The reaction yields a beta-keto ester which has a cyclic structure.
  • When an enolizable ester/ketone is used with a non-enolizable ester, the resulting reaction is known as the crossed Claisen condensation.
  • Another modification of this reaction is the Stobbe condensation reaction, which can proceed with relatively weaker bases. It generally involves the use of a diethyl ester prepared from succinic acid.

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Frequently Asked Questions – FAQs

What is the Claisen-Schmidt condensation reaction?

The Claisen-Schmidt condensation reaction is an organic reaction in which a ketone or an aldehyde holding an α-hydrogen reacts with an aromatic carbonyl compound which does not have any α-hydrogens. This reaction is named after the chemists J.G. Schmidt and Rainer Ludwig Claisen. It can be noted that dibenzalacetone can be synthesized with the help of this reaction.

What is the primary difference between Aldol condensation and Claisen condensation?

The Claisen condensation reaction is closely related to the aldol condensation reaction since both of them are organic condensation reactions involve the addition of enolates to organic compounds. However, the aldol condensation reaction involves the addition of enolates to ketones or aldehydes whereas Claisen condensation involves the addition of enolates to esters.

What are the key requirements for the Claisen condensation reaction?

The Claisen condensation reaction requires at least one of the reagents used to be enolizable. Therefore, they must have an α-proton which can be deprotonated for the formation of the enolate ion. Another key requirement for this organic reaction is that the base used must not undergo nucleophilic addition or nucleophilic substitution and hinder the reaction.

What are the different types of Claisen condensations?

Some important types of the Claisen condensation reaction are listed below.

  • The ‘classic’ Claisen condensation reaction which features the self-condensation of two molecules that contain an enolizable ester.
  • The ‘crossed’ Claisen condensation reaction (also known as mixed Claisen condensation), where one of the molecules is an enolizable ester and the other is a ketone or a non-enolizable ester.
  • The Dieckmann condensation reaction, in which a molecule featuring two ester groups undergoes an intramolecular reaction.

What is the mechanism of the Claisen condensation reaction?

First, an α-proton is removed by the highly basic environment, facilitating the formation of an enolate ion. This enolate ion is stabilized by the delocalization of electrons. Then, the carbonyl carbon belonging to the second ester undergoes a nucleophilic attack from the enolate ion. The subsequent elimination of the alkoxy group results in the formation of a new enolate that is stabilized by resonance. The enolate is now neutralized via the addition of a suitable acid, after which the beta-keto ester or the beta-diketone can be isolated.

What are the products formed in Claisen reactions?

The desirable products of Claisen condensations are usually β-ketoesters. They are known to be very useful synthetic intermediates in the field of organic chemistry. In these reactions, an ester enolate reacts with another ester molecule to form the required products.

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