Cannizzaro's Reaction

The Cannizzaro reaction, named after its discoverer Stanislao Cannizzaro, is a chemical reaction that involves the base-induced disproportionation of two molecules of a non-enolizable aldehyde to give a primary alcohol and a carboxylic acid

1. NAMED REACTIONS IN ORGANIC SYNTHESIS: CANNIZZARO REACTION By PRUTHVIRAJ K

2. CANNIZZARO REACTION When reacted with concentrated NaOH (50 wt %) or other strong bases (e.g., alkoxides ), aliphatic and aromatic aldehydes with no α-hydrogen undergo an intermolecular hydride-transfer reaction known as the Cannizzaro reaction . In this disproportionation reaction, one molecule of aldehyde oxidizes another to the corresponding carboxylic acid and is reduced to the corresponding primary alcohol in a maximum 50% yield. If the aldehyde has α- hydrogens , the aldol reaction will take place faster than the Cannizzaro reaction . Alternatively, high yields of alcohol can be obtained from almost any aldehyde when the reaction is performed in the presence of an excess of formaldehyde. This process is called the crossed Cannizzaro reaction . α- Keto aldehydes undergo an intramolecular Cannizzaro reaction . This method, however, has been rendered obsolete by the emergence of hydride reducing agents in 1946. In the presence of an appropriate Lewis acid catalyst, the intramolecular Cannizzaro reaction takes place with stereocontrol , yielding synthetically useful α- hydroxy esters directly from readily available glyoxals under neutral conditions.It has also been shown that the reaction rates are enhanced significantly when the Cannizzaro reaction is performed under solvent-free conditions. PRUTHVIRAJ K, MSc, CHEM MASTER

3. Mechanism A variety of mechanisms have been proposed for this reaction, but the generally accepted mechanism of the Cannizzaro reaction involves a hydride transfer. First, OH- adds across the carbonyl group, and the resulting species is deprotonated under the applied basic conditions to give the corresponding dianion . This dianion facilitates the ability of the aldehydic hydrogen to leave as a hydride ion. This leaving hydride ion attacks another aldehyde molecule in the rate-determining step (RDS) to afford the alkoxide of a primary alcohol, which gets protonated by the solvent (H 2 O). By running the reaction in the presence of D 2 O, it was shown that the reducing hydride ion came from another aldehyde and not the reaction medium, since the resulting primary alcohol did not contain a deuterium. Ashby and co-workers using resolved ESR spectra demonstrated that substituted benzaldehyde radical anions were formed in the reactions of substituted benzaldehydes with either NaOH or KO t - Bu. This observation suggested that the reaction proceeded by a single-electron transfer (SET) mechanism. PRUTHVIRAJ K, MSc, CHEM MASTER

4. Mechanism: Reaction View PRUTHVIRAJ K, MSc, CHEM MASTER

5. Synthetic applications. J. Rebek et al. synthesized novel dibenzoheptalene bislactones via a double intramolecular Cannizzaro reaction for condensation polymerization and remote catalysis studies. These bislactones are chiral, atropisomeric molecules During the large-scale, high-yield, one-pot synthesis of 4-chloro-3-( hydroxymethyl )pyridine , a starting material for the preparation of several polyfunctionalized molecules that can be linked to cephalosporines , M. Penso and co-workers utilized the combination of direct regioselective lithiation / formylation and crossed- Cannizzaro reduction of 4-chloropyridine PRUTHVIRAJ K, MSc, CHEM MASTER

6. -THANK YOU- PRUTHVIRAJ K, MSc, CHEM MASTER