Theory and Defination :


The Benzoin Condensation is a coupling reaction between two aldehydes that allows the preparation of α-hydroxyketones.The homocoupling of benzaldehyde gives the parent benzoin.The first methods were only suitable for the conversion of aromatic aldehydes.
The modifications of the benzoin condensation include the use of acylsilanes as well as imine derivatives in place of one aldehyde partner.

General Reaction :


 <img src="benzoin-condensation.jpg" alt="aldehydes to α-hydroxyketones Benzoin Condensation mechanism"/>
e.g.

 <img src="benzoin-condensation.jpg" alt="aldehydes to α-hydroxyketones Benzoin Condensation mechanism"/>

Mechanism :



Addition of the cyanide ion to create a cyanohydrin effects an umpolung of the normal carbonyl charge affinity, and the electrophilic aldehyde carbon becomes nucleophilic after deprotonation: A thiazolium salt may also be used as the catalyst in this reaction (we will see Stetter Reaction in upcoming posts ).

 <img src="benzoin-condensation.jpg" alt="aldehydes to α-hydroxyketones Benzoin Condensation mechanism"/>


A strong base is now able to deprotonate at the former carbonyl C-atom:

 <img src="benzoin-condensation.jpg" alt="aldehydes to α-hydroxyketones Benzoin Condensation mechanism"/>


A second equivalent of aldehyde reacts with this carbanion; elimination of the catalyst regenerates the carbonyl compound at the end of the reaction:.
 <img src="benzoin-condensation.jpg" alt="aldehydes to α-hydroxyketones Benzoin Condensation mechanism"/>
 <img src="benzoin-condensation.jpg" alt="aldehydes to α-hydroxyketones Benzoin Condensation mechanism"/>


Application and Example :


The reaction can be extended to aliphatic aldehydes with base catalysis in the presence of thiazolium salts; the reaction mechanism is essentially the same. These compounds are important in the synthesis of heterocyclic compounds. The addition is also possible withenones; for instance methyl vinyl ketone is a reagent in the Stetter reaction.
In biochemistry, the coenzyme thiamine is responsible for biosynthesis of acyloin-like compounds. This coenzyme also contains a thiazolium moiety, which on deprotonation becomes a nucleophilic carbene. In one study, a custom-designed N-heterocyclic carbene (NHC, the framework is related to thiazolium salts) was found to facilitate anenantioselective intramolecular benzoin condensation.

 <img src="benzoin-condensation.jpg" alt="aldehydes to α-hydroxyketones Benzoin Condensation mechanism"/>


This finding was confirmed in another study with a slightly modified NHC using DBU as the base instead of potassium tert-butoxide.


 <img src="benzoin-condensation.jpg" alt="aldehydes to α-hydroxyketones Benzoin Condensation mechanism"/>