Claisen Condensation of esters

by James

Description: When esters are treated with strong base, an enolate can be formed. The resulting enolate can add to another ester, resulting in a substitution at the carbonyl carbon.
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Notes: The base for this process is usually the alkoxide of the ester (“alkoxide” is the conjugate base of an alcohol). Although not explicitly stated, it is safe to assume that there are more than two equivalents of the ester. The reaction between two esters is called the Claisen condensation. An intramolecular version that forms a ring is called the Dieckmann condensation.

Examples:

Notes: Examples 1 and 2 show typical Claisen condensations. Note how the base used is generally the alkoxide corresponding to the ester. That’s because use of hydroxide ion (HO–) would lead to hydrolysis of the ester, and the use of a different alkoxide would result in transesterification. It’s assumed that 2 equivalents of ester is used here. Example 3 shows formation of a ketone enolate followed by addition to the ester (still called a Claisen condensation.) Example 4 shows a crossed Claisen condensation using the bulky base litihum di-isopropyl amide (LDA) which irreversibly forms the enolate of the first ester; addition of the second ester results in condensation.

The fifth example shows the intramolecular version of this reaction which is called the Dieckmann reaction.

Mechanism:   Strong base removes a proton from the carbon adjacent to the ester carbonyl (Step 1, arrows A and B) forming the enolate, which attacks a second equivalent of ester in a 1,2-addition (Step 2, arrows C and D) forming a tetrahedral intermediate. Elimination of alkoxide (Step 3, arrows E and F) then results in the beta-keto ester product.

Notes:  Note that base is catalytic in this reaction.

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{ 5 comments… read them below or add one }

Nima Omid-Fard

Some of these are reversible right? (the ones which have only 1 alpha H?)

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Aleksey

I believe the reversibility depends on the type of base you are using and not the number of the alpha hydrogens.

Here are some common bases for the irreversible forms:
NaH, NaNH2, KH, LDA

Common reversible bases:
NaOEt, NaOMe

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padhiyar pankaj A.

is there any possibility of dickmann reaction if -NH- group present in molecule?
i think -NH- group give anion instead of -CH2-.

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Sandra

Since the b-keto ester has an acidic proton, does the reaction of ester with base need to be followed by a work-up step?

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Monika Kulak

Can you also go over the reformatsky reaction?

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