Reactions under water cities.

The Cannizzaro reaction (1) was mentioned in an older textbook that I’ve been reading (2). It turns out that my not having heard of the Cannizzaro before, and the 1961 publication date of the textbook didn’t mean I had found an Atlantis, (there is, in fact, even a Wikipedia entry on this reaction), but I still found it interesting enough to dig further.

The Cannizarro is a disproportionate, hydride transfer reaction. One molecule of reactant reduces another, itself becoming oxidized, and the result is that two different products are formed, ergo benzaldehyde:


Scheme 1
The synthetic utility is limited by the 50% maximum possible yield. Also, since the aldol reaction is faster, the Cannizzaro won’t occur where there are enolizable hydrogens.

To determine whether the hydride source for benzaldehyde reduction was another molecule of benzaldehyde or water, the reaction was carried out in D2O by (3), who found that deuterium was not incorporated into benzyl alcohol. Accordingly, the mechanism involves three steps, OH- nucleophilic addition, rate limiting, carbon-to-carbon hydride shift, and a rapid proton transfer.

Scheme 2
A hydride shift occurs instead of alkoxide nucleophilic addition.

The proposed mechanism agrees with the rate expression


and a DFT study of the reaction (4) which found the phenyl groups were able to reasonably position such as to avoid crowding each other, and the end products were very stable (exothermic, -36.28 kcal/mol).

The mechanism can be rationalized by considering the two opposing properties of the carbonyl group. On one hand, the electronegativity of oxygen polarizes the electron distribution (~2.5 debye), placing a partial positive charge on the carbonyl carbon and making it susceptible to nucleophilic attack. On the other hand, the carbonyl C=O has a large bond energy of 730 kJ/mol, compared to C=C 614 kJ/mol, and C=N 615 kJ/mol. In fact, the π-bond is stronger than the σ-bond (C-O 360 kJ/mol). The strength of the bond works to oppose the loss of C=O. So while attack of the oxygen anion of intermediate 1 on PhCHO seems reasonable, the resultant ether can’t convert to form C=O; instead, the hydride anion is released in order to form benzoic acid, a carbonyl containing compound.

In application, the Cannizzaro reaction has narrow synthetic utility, but should be remembered as source of byproducts whenever compounds containing aldehydes are treated with OH-/RO- bases.

(1) Cannizzaro, S. (1853). "Ueber den der Benzoësäure entsprechenden Alkohol". Liebigs Annalen 88: 129–130
(2) Peter Sykes, “A Guidebook to Mechanism in Organic Chemistry” 4th Ed.
(3) FREDENHAGEN AND BONHOEFFER, 2. phys. Chem., A181, 379 (1938).
(4) Yamabe, S. 2009, 7, 951