Ch. 22 - Condensation ChemistrySee all chapters
All Chapters
Ch. 1 - A Review of General Chemistry
Ch. 2 - Molecular Representations
Ch. 3 - Acids and Bases
Ch. 4 - Alkanes and Cycloalkanes
Ch. 5 - Chirality
Ch. 6 - Thermodynamics and Kinetics
Ch. 7 - Substitution Reactions
Ch. 8 - Elimination Reactions
Ch. 9 - Alkenes and Alkynes
Ch. 10 - Addition Reactions
Ch. 11 - Radical Reactions
Ch. 12 - Alcohols, Ethers, Epoxides and Thiols
Ch. 13 - Alcohols and Carbonyl Compounds
Ch. 14 - Synthetic Techniques
Ch. 15 - Analytical Techniques: IR, NMR, Mass Spect
Ch. 16 - Conjugated Systems
Ch. 17 - Aromaticity
Ch. 18 - Reactions of Aromatics: EAS and Beyond
Ch. 19 - Aldehydes and Ketones: Nucleophilic Addition
Ch. 20 - Carboxylic Acid Derivatives: NAS
Ch. 21 - Enolate Chemistry: Reactions at the Alpha-Carbon
Ch. 22 - Condensation Chemistry
Ch. 23 - Amines
Ch. 24 - Carbohydrates
Ch. 25 - Phenols
Ch. 26 - Amino Acids, Peptides, and Proteins
Johnny Betancourt

The Claisen condensation is a base-catalyzed reaction between an ester and another carbonyl compound producing a beta-keto ester or beta-diketone as the product.

Overview

In a Claisen condensation, just like in other condensation reactions, an enolate attacks the electrophilic carbonyl carbon of a second molecule. What differentiates it from other condensation reactions is that it involves two molecules, at least one of which is an ester.


Enolate formation

Enolate-formation-with-NaOEt

Enolate formation with NaOEt


So, how do we actually form an enolate? We have to deprotonate the alpha-carbon of a carbonyl by using a strong base like sodium ethoxide or sodium amide. Remember that alpha-carbons are much more acidic than standard sp3-hybridized carbons!


Claisen condensation

Enolate-attack-on-ester

Enolate attack on ester

Here we have the reaction between a ketone and ester. The stabilized anion (the enolate) attacks the electrophilic carbonyl through a nucleophilic acyl substitution mechanism and the alkoxide is eliminated. If our enolate were a ketone or aldehyde, we'd end up with a beta-diketone (two ketones separated by a carbon); if our enolate were an ester, we'd end up with a beta-keto ester (ketone and ester with a carbon between them). 

The reaction between a ketone and aldehyde (or any combination of those) is called an aldol condensation—so named because the nucleophilic addition forms an alcohol. 


Dieckmann condensation

The Dieckmann condensation is basically an intramolecular Claisen condensation that forms a cyclic beta-keto ester or beta-diketone. In this example, the 2 alpha-hydrogens in blue and green are entirely equivalent since the molecule is symmetrical. Dieckmann-condensation

Dieckmann condensation



Johnny Betancourt

Johnny got his start tutoring Organic in 2006 when he was a Teaching Assistant. He graduated in Chemistry from FIU and finished up his UF Doctor of Pharmacy last year. He now enjoys helping thousands of students crush mechanisms, while moonlighting as a clinical pharmacist on weekends.


Additional Problems
Fill in the missing reagents and conditions.
Predict the product when this compound undergoes a Claisen condensation. 
Complete the following reaction scheme.
Indicate the order in which these intermediates would appear during the conversion of  1 into 2. a) 1 → I → V → 2 b) 1 → II → I → IV → V → 2 c) 1 → III → I → IV → V → 2 d) 1 → III → I → V → 2 e) 1 → II → I → 2
Provide a mechanism for the following reaction.  
Provide an unambiguous structural formula for the condensation product expected when the compound below is treated with sodium ethoxide, then quenched with cold dilute aqueous acid.
Identify the base you would use for the following transformation. 
Predict the major product obtained when the following compound undergoes a Claisen condensation. 
Indicate the order in which these intermediates would appear during the conversion of 1 into 2. a) 1 → V → III → I → 2 b) 1 → V → II → I → 2 c) 1 → II → I → 2 d) 1 → IV → 2 + I → 2 e) 1 → III → V → 2 + I → 2
Predict the product(s) for the following reaction.
Draw the product for the following Claisen reaction.
Complete the following reaction supplying the missing product and showing correct regio- and stereochemistry where applicable. If a racemic or diastereomeric mixture forms show all stereoisomers; if no reaction takes place, write N.R.
What would be the major product of this reaction sequence?
What is the starting material that will yield this compound upon treatment with CH3CH2ONa in CH3CH2OH?
What is the product of this reaction?
What compound would be produced by this reaction?
Which compound, when treated with NaOCH 3 followed by neutralization with aqueous acid, will produce this β-diketone?
Draw the product for the following Claisen reaction.
What is the product of the following reaction?
Show the product of the following self-Claisen condensation
Show your understanding of the following reaction by showing the full arrow pushing mechanism including all resonance forms and predicting the product.
Show your understanding of the reaction given below by showing the full arrow pushing mechanism, including ALL RESONANCE FORMS and predicting the products. 
Provide a detailed mechanism for the following transformation.