Retro-benzoin condensation

Treatment of a-phenylquinazolin-4-ylmethanols 4 with potassium cyanide in dimethylform-amide results in C—C bond cleavage to give quinazolines 5 and ketones 6. This reaction proceeds through a retro-benzoin condensation in which the N3 —C4 double bond of quinazolines behaves like a carbonyl group. 

Upon treating certain (but not all) aromatic aldehydes or glyoxals (a-keto aldehydes) with cyanide ion (CN ), benzoins (a-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=0 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. This 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. The stereoselective synthesis of benzoins has been achieved using chiral thiazolium salts as catalysts. 

Benzoin and retro-benzoin condensation Reaction of aldehydes to form a-hydroxy ketones in the presence of a nucleophilic catalyst (e.g. cyanide ion). 54... 

Miyashita, A., Suzuki, Y., Okumura, Y., Iwamoto, K.-l., Higashino, T. Carbon-carbon bond cleavage of -substituted benzoins by retro-benzoin condensation a new method of synthesizing ketones. Chem. Pharm. Bull. 1998, 46, 6-11. 

Methylquinazolin-4(3//)-one was obtained in over 62% yield by reacting the phosphorane (25) with sodium hydride in methyl cyanide. The phos-phorane was readily formed from anthranilamide and prop-2-ynyltriphenyl-phosphonium bromide. When anthranilamide was fused with benzoin and a trace of acid at 150°C, it gave 2-phenylquinazolin-4(3H)-one together with o-iV-(a-benzoyl benzyl)aminobenzamide. The latter was cyclized, with ethyl orthoformate, to l-(a-benzoylbenzyl)quinazolin-4-one. If anthranilamide and benzoin were boiled in benzene with azeotropic removal of water, then the Schiff base (26) was formed. This gave 2-phenylquinazolin-4(3Jf/)-one and benzoic acid on heating alone at 150°C or with ethyl orthoformate. The mechanism of this reaction is not clear unless a retro-benzoin condensation and oxidation are occurring. 

Retro-benzoin condensation. KCN promotes C-C bond cleavage in benzoins, and... 

Recently, there has heen some work dealing with the cross-henzoin condensation to afford nonsymmetrical products chemoselectively. In this case, the Breslow intermediate has to he formed predominantly with only one of the aldehydes and react selectively with the other one. Kuhl and Glorius have succeeded in this area developing a selective hydro gmiethylation of aldehydes.With a different approach, it is also possible to use hindered ortho-substituted aldehydes to inhibit the retro-benzoin reaction and the attack of the As an extension, the cross-benzoin reaction has been... 

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