What Is Cannizzaro Dispropotionation?
The Cannizzaro reaction is a classic example of a disproportionation reaction within organic chemistry. Disproportionation occurs when two identical molecules react in such a way that one undergoes oxidation while the other undergoes reduction. Specifically, aldehydes lacking α-hydrogens undergo bimolecular autooxidation-reduction reactions under alkaline conditions to form carboxylic acids and alcohols. α-Ketoaldehydes lacking α'-hydrogens can undergo intramolecular Cannizzaro reactions, producing α-hydroxy acids in high yields. In addition, commonly used aromatic aldehydes and formaldehyde can undergo a cross-Cannizzaro reaction, with formaldehyde acting as a reducing agent.
- Reagents: Concentrated aqueous solution of a strong base (typically NaOH or KOH).
- Reactants:
a) Aldehydes lacking alpha-hydrogen atoms (non-enolizable aldehydes).
b) Common examples: Formaldehyde (HCHO), aromatic aldehydes (e.g., benzaldehydes), aldehydes with quaternary alpha-carbons (e.g., trimethylacetaldehyde). - Products: Carboxylic acids and primary alcohols.
- Reaction Type: Disproportionation, redox reaction.
- Experimental Tips:
a) Aldehydes possessing α-hydrogens (e.g., acetaldehyde, propionaldehyde) typically undergo aldol condensation under basic conditions instead of the Cannizzaro reaction.
b) This reaction can be carried out under Lewis acidic conditions. For example, using a magnesium bromide-triethylamine system allows the reaction to proceed under mild conditions (room temperature). Using a Yb(OTf)3-SeO2 system allows the oxidation of acetophenone and the intramolecular Cannizzaro reaction to proceed in tandem.
c) Microwave irradiation can enhance the reaction rate while providing high yields. Solvent-free conditions can also enhance the reaction rate.
d) Use of solid-supported hydroxides or hydrotalcites to facilitate catalyst separation and recycling.
Fig 1. Cannizzaro dispropotionation and its mechanism. [1]
Mechanism of the Cannizzaro Reaction
- The hydroxide ion acts as a nucleophile, attacking the electrophilic carbonyl carbon of the first aldehyde molecule. This forms a tetrahedral intermediate, a hydride donor species formally known as an alkoxide adduct.
- This highly nucleophilic alkoxide adduct then acts as a hydride donor. It attacks the carbonyl carbon of a second molecule of the same aldehyde. This concerted step transfers a hydride ion from the adduct to the carbonyl carbon of the second aldehyde, resulting the carboxylate anion and the alkoxide anion of the primary alcohol, respectively.
- The alkoxide ion is rapidly protonated by water (or the solvent) to yield the final primary alcohol product. The carboxylate ion can be acidified to yield the free carboxylic acid.
Application Examples of the Cannizzaro Reaction
- Example 1: 1-Naphthaldehyde can be subjected to the Cannizzaro reaction using KOH under alkaline, solvent-free conditions. The aldehyde and base are mixed and heated for 30 minutes, then cooled and diluted with water. Solid 1-naphthol is isolated by extraction with ether, and 1-naphthoic acid is precipitated by acidification. [2]
- Example 2: Sud, Abhishek et al. described a novel reaction involving the in situ redox conversion of glyoxylate esters to glycine, termed the intramolecular Aza-Cannizzaro reaction. [3]
Fig 2. Synthetic examples via Cannizzaro reaction.
Related Products
References
- Jie Jack Li. Name Reactions-A Collection of Detailed Mechanisms and Synthetic Applications, Sixth Edition, 2021, 70-72.
- Dicks, Andrew P. Green Chemistry Letters and Reviews, 2009, 2(2), 87-100.
- Sud, Abhishek, et al. Tetrahedron Letters, 2017, 58(19), 1891-1894.
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