The Claisen Ester Condensation

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The Claisen Ester Condensation

Esters, like aldehydes and ketones, have acidic E-hydrogens. When an ester bearing an E-hydrogen is treated with a strong base, a condensation reaction takes place to yield a F-ketoester.

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The Claisen Ester Condensation

O R CH2 C + O R CH2 C O CH2 CH3 O CH2 CH3 O NaOCH2CH3 R CH2 C O CH C R a Fketoester + CH3 CH2 O H O CH2 CH3

NOTE: The alkoxide should match the alkyl group of the ester in order to avoid a competing transesterification.
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Claisen Ester Condensation -- Mechanism (Part One)

1) O CH3 C + _ .. :O .. OC2H5 fast _ : CH2 O C OC2H5
enolate ion

.. _ : O: CH2 C OC2H5

HO

C2H5

C2H5

2)

O CH3 C _ : CH2

acceptor OC2H5 slow O C OC2H5

.. _ :O: CH3 C OC2H5 O OC2H5

CH2 C

donor

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Claisen Ester Condensation -- Mechanism (Part Two)

3) .. _ :O : CH3 C OC2H5 O CH2 C OC2H5 fast

: O: CH3 C O CH2 C + _ .. :O .. OC2H5

C2H5

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The Key to Claisen Ester Condensations

The E-carbon of the donor attaches itself to the carbonyl carbon of the acceptor. The alkoxy group of the acceptor leaves to form a C=O bond.

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Example
O 2 CH3 CH CH3 CH3 CH CH3 CH3 E CH2 C O CH3 NaOCH 3

O CH2 C E CH CH

O C O CH3

CH3

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Another Example
O 2 E CH2 C NaOCH 3 O CH3 O CH2 C E CH O C O CH3

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Example of a Ring Formation

O E CH2 C (CH2)n O CH3 NaOCH3 O E CH C (CH2)n O CH3

CH2 C O

CH3

CH2

This reaction is known as the Dieckmann cyclization.

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Effect of Chain Length on the Rate of Ring Closure

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What if we mixed two different esters?

As in the case with the aldol condensation, if we mixed two different esters, the result would be a mixture of products. However, we can do this deliberately, in what is known as a crossed Claisen ester condensation.

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Crossed Claisen Condensation

In the crossed Claisen condensation, we choose one of the esters to be the acceptor. The acceptor does not have E-hydrogens. The other ester, the donor, does have E-hydrogens. It can react with base to form a nucleophilic enolate ion. With such an experimental design, the crossed Claisen condensation can be used successfully.

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Crossed Claisen Condensation -- An Example

O C O CH2 CH3

acceptor NaOCH2CH3 + O E CH3 C O CH2 CH3 donor C O E CH2 C O CH2 CH3 O

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Synthesize this:
O H C E CH O C O CH3

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