Chapter 21: Ester Enolates

Summary

• The Claisen condensation is the ester analogue of the Aldol condensation.
• Reagents : most commonly the base would be the alkoxide, R'O^-
• The reaction involves an ester enolate reacting with another molecule of the ester.
• Remember enolates are good nucleophiles and the ester carbonyl C are electrophilic.
• The products of these reactions are β-ketoesters which are important, useful synthetic intermediates.
• Note that the product is the original ester with an acyl group added i.e. an acylation reaction has occurred.
• A simple example of a Claisen condensation is the reaction of ethyl ethanoate which is shown below in two representations.

Try to identify the enolate portion and the carbonyl portion in the different representations

• Methanoate esters can not undergo Claisen self condensations. Why ? ANSWER

STUDY TIPS: Students often find this reaction difficult, probably because they are intimidated by it..... break it down into the component steps. Think of it as a nucleophile adding to the carbonyl of the ester as we saw in chapter 20 (review) Try to recognise the two units that came together and identify the nucleophilic (enolate) portion and the electrophilic (carbonyl) portion. The nucleophilic enolate will still contain the ester unit -CO2R. The electrophilic ester will have become a ketone C=O having lost it's -OR group. Recognise the products, the b-ketoester, as being from a Claisen reaction.

Related Reactions

• Dieckmann Condensation
• Acylation of Ketones
• Aldol Condensation of aldehydes and ketones

MECHANISM OF THE CLAISEN CONDENSATION
Step 1: First, an acid-base reaction. The alkoxide functions as a base and removes the acidic a-hydrogen giving the reactive ester enolate.
Step 2: The nucleophilic ester enolate attacks the carbonyl C of another ester in a nucleophilic substitution process giving the tetrahedral intermediate.
Step 3: The intermediate collapses, reforming the C=O, resulting in loss of the leaving group, the alkoxide, leading to the b-ketoester product.
Note that the reaction is drawn to completion by deprotonation of the active methylene in the product by the ethoxide. The salt typically precipitates and is recovered after acid work-up.

© Dr. Ian Hunt, Department of Chemistry