Benzoin Condenstation Reaction

The benzoin addition is an addition reaction involving two aldehydes. The reaction generally occurs between aromatic aldehydes or glyoxals. The reaction produces an acyloin. In the classic application benzaldehyde is converted to benzoin

1. NAMED REACTIONS IN ORGANIC SYNTHESIS: Benzoin Condensation By PRUTHVIRAJ K PRUTHVIRAJ K, MSc

2. Benzoin Condensation. Upon treating certain (but not all) aromatic aldehydes or glyoxals ( α - keto aldehydes) with cyanide ion (CN-), benzoins ( α - hydroxy -ketones or acyloins ) are produced in a reaction called the benzoin condensation . The reverse process is called the retro-benzoin condensation , and it is frequently used for the preparation of ketones. The condensation involves the addition of one molecule of aldehyde to the C=O group of another. One of the aldehydes serves as the donor and the other serves as the acceptor. Some aldehydes can only be donors ( e.g. p dimethylaminobenzaldehyde ) or acceptors, so they are not able to self-condense, while other aldehydes ( benzaldehyde ) can perform both functions and are capable of self-condensation. Certain thiazolium salts can also catalyze the reaction in the presence of a mild base. his version of the benzoin condensation is more synthetically useful than the original procedure because it works with enolizable and non- enolizable aldehydes and asymmetric catalysts may be used. Aliphatic aldehydes can also be used and mixtures of aliphatic and aromatic aldehydes give mixed benzoins . Recently, it was also shown that thiazolium -ion based organic ionic liquids (OILs) promote the benzoin condensation in the presence of small amounts of triethylamine.12 The stereoselective synthesis of benzoins has been achieved using chiral thiazolium salts as catalysts. PRUTHVIRAJ K, MSc

3. Mechanism All the steps of the cyanide ion catalyzed benzoin condensation are completely reversible, and the widely accepted mechanism involves the loss of the aldehydic proton in the key step. This deprotonation is possible due to the increased acidity of this C-H bond caused by the electron-withdrawing effect of the CN group. The cyanide ion is a very specific catalyst of the reaction. Cyanide is a good nucleophile, a good leaving group, and its electronwithdrawing effect enhances the acidity of the aldehyde hydrogen. PRUTHVIRAJ K, MSc

4. PRUTHVIRAJ K, MSc

5. Synthetic applications A. Miyashita and co-workers have developed a new method for the synthesis of ketones based on the concept that the benzoin condensation is reversible ( retro-benzoin condensation ) and affords the most stable product. When α - benzylbenzoin was treated with KCN in DMF, the C-C bond was cleaved, resulting in the formation of deoxybenzoin and benzaldehyde . This method of synthesizing ketones has been applied to several α -substituted benzoins , and the corresponding ketones were formed in good yields. The authors also realized, based on the known analogy between the chemical behavior of the C=O double bond of ketones and the C=N double bond of nitrogen-containing heteroarenes , that a cyanide ion catalyzed retro-benzoin condensation of α - hydroxybenzylheteroarenes would also be possible The retro-benzoin condensation methodology was used to synthesize 2-substituted quinazolines in good overall yield from 2,4-dichloroquinazoline. 2-Substituted quinazolines are obtained by substitution of 2-chloroquinazoline with nucleophiles, though it is difficult to prepare the starting 2-chloroquinazoline. These results indicate that the aroyl group, which may be introduced onto nitrogen-containing heteroarenes at the α -position, can be used as a protecting group. Later it can be easily removed by conversion to an α - hydroxybenzyl group, followed by a retro-benzoin condensation . PRUTHVIRAJ K, MSc

6. In the laboratory of K. Suzuki, a catalytic crossed aldehyde-ketone benzoin condensation was developed and applied to the synthesis of stereochemically defined functionalized preanthraquinones . PRUTHVIRAJ K, MSc

7. REFERENCES STRATEGIC APPLICATIONS OF NAMED REACTIONS IN ORGANIC SYNTHESIS By- Laszlo Kurti and Barbara Czako REACTIONS, REARRANGEMNTS AND REAGENTS By- S N Sanyal PRUTHVIRAJ K, MSc