In the Cannizzaro reaction

Aldehydes can react through a hydride transfer as in the Cannizzaro reaction. 

Cannizzaro Reaction. In the Cannizzaro reaction (19-60) aldehydes without an a hydrogen are reduced to alcohols. 

Heavy water, DzO, has often been used in a rather similar way. Thus in the Cannizzaro reaction of benzaldehyde (p. 216),... 

Suitable dialdehydes can also undergo intramolecular hydride transfer, as in the Cannizzaro reaction of ethan- 1,2-dial (55, glyoxal ) — hydroxyethanoate ( glycollate, 56) anion,... 

In the Cannizzaro reaction [110, 111] two aldehyde functionalities disproportionate into the corresponding hydroxyl and carboxyl functions, either as separate compounds or as an ester (Scheme 20.25). The reaction conditions needed are rather harsh, except when R1 or R2 is a phenyl group. Typically, an excess of so-... 

One obvious candidate for an electrophilic but non-enolisable compound is formaldehyde CH2=0 but it is simply too electrophilic to be well controlled. A trivial example is its reaction with acetaldehyde and hydroxide ion. The first aldol gives the expected product 43 but a second gives 44 and a third follows. Now hydroxide adds to another molecule of formaldehyde and delivers a hydride ion 45 in the Cannizzaro reaction (the other product is formate ion HCO2-) to give pentaerythritol 46, a useful compound in polymer chemistry for cross-linking but not much use to us. We need to moderate the unruly behaviour of this useful one-carbon electrophile. 

Our mechanism does not explain this result but small amounts of radicals are formed in many reactions in which the products are actually formed by simple ionic processes. Detection of a species in a reaction mixture does not prove that it is an intermediate. Only a few chemists believe that radicals are involved in the Cannizzaro reaction. Most believe the mechanism we have given. 

The mechanisin of alcohol oxidation with NAD has several analoge in laboratory chemistry A base removes the O-TC proton from the alcohol and Keaerates an allcoxide ion, which expels a hydride ion leaving group as in the Cannizzaro reaction tSection 19.13>> The nucleophilic hydride ion dacn adds to the Cs=C-C=N part of NAD in a conjugate addition reaction, much the same as water adds to the C=C-C=0 part of the tt,p-unsaturated acyl CoA in step 2. 

In the Cannizzaro reaction (62), which involves self-condensation of aldehydes that have no a-hydrogen atoms, the nucleophile is represented best as a hydride ion in the Prins reaction (26), the nucleophile is an olefin in the aldol condensation (63) and reaction of methyl acetate with formaldehyde (62), the nucleophile is a methylene group a- to a... 

In F, benzyl alcohol is the hydrogen-rich product from hydride transfer to benzaldehyde in the Cannizzaro reaction the hydrogen-deficient species is benzoic acid. Hydride transfer to the carbonium ion derived from benzyl alcohol also results in the formation of toluene, an even more reduced species. As shov n in Equations 11 and 12, these Cannizzaro-like transformations are essentially redox type, at least in respect to hydrogen balance. 

Problem 19.14 In the case of some aldehydes there is evidence that intermediate II is the hydride donor in the Cannizzaro reactions, (a) How would II be formed from I ... 

Ashby, E. C., Coleman, D. T., Ill, Gamasa, M. P. Evidence supporting a single-electron-transfer path in the Cannizzaro reaction. Tetrahedron Lett. 1983, 24, 851-854. 

In the Cannizzaro reaction, the hydride ion that is being used to effect this reduction may come from an aldehyde that lacks an a-hydrogen atom, e.g. methanal or benzaldehyde. The receiving molecule may be a second molecule of the same aldehyde or a different one. The reaction requires a strong base, and the rate law is found to depend on the square of the concentration of the aldehyde and either the concentration or the square of the concentration of the base used. Overall a carboxylate anion and an alcohol are formed from two molecules of the aldehyde(s). The reaction may occur intramolecularly, i.e. a-ketoaldehydes give the a-hydroxycarboxylic acids on treatment with hydroxide ions. A variation of this process is called the Tollens reaction. In this case, a ketone or aldehyde that contains an a-hydrogen is treated with formaldehyde in the presence of Ca(OH)2. 

The factors leading to isoracemisation can lead to misinterpretation of isotope-ex-change experiments. The lack of exchange of the proton with solvent protons is classical evidence for hydride transfer in the Cannizzaro reaction and Meerwein-Pondorff-Verley reduction and in the rearrangements involved in steroid biosynthesis. For some time the lack of deuterium exchange in the glyoxalase reaction was attributed to a hydride-transfer mechanism (Eqn. 64). 

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