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The Cannizzaro reaction is an example of an organic disproportionation or dismutation reaction in which an aldehyde lacking alpha hydrogens oxidizes and reduces itself to become a carboxylic acid molecule and an alcohol molecule. The reaction is catalyzed by strong bases such as sodium or potassium hydroxide, although some organic alkoxides can also be used as catalysts.
This reaction was discovered and characterized by the Italian chemist Stanislao Cannizzaro in 1853, and has the particularity that it involves the migration of a hydride group from one aldehyde molecule to the carbonyl of another aldehyde molecule, effectively reducing the second while the first it oxidizes.
Cannizzaro reaction substrates
An important condition for the Cannizzaro reaction to occur is that the reacting aldehyde does not have alpha hydrogens. In fact, Cannizzaro discovered the reaction using benzaldehyde, an aromatic aldehyde consisting of a formyl group attached directly to a benzene ring (so the alpha carbon belongs to the ring).
This limitation is mainly due to the fact that the reaction is catalyzed by a strong base. If it has alpha hydrogens, it is much more probable that the base starts off said hydrogen, leading to the enolate and another series of possible products, rather than the Cannizzaro reaction.
It should also be mentioned that, although the reaction is formally classified as a disproportionation (meaning that a compound oxidizes and reduces itself), the Cannizzaro reaction can also be carried out in a crosswise fashion, reacting two different aldehydes in such a way that one of them reduces the other.
This is important from the point of view of reaction yields. Yields are limited to 50% in the case of disproportionation, since two reactant molecules are needed for every different product molecule.
Reaction mechanism
There are two accepted mechanisms for the Cannizzaro reaction. Both are very similar and involve hydride ion migration, but differ in the kinetics they follow. Which of the two mechanisms the reaction follows will depend on the concentration of the base. These mechanisms are presented below:
Mechanism of the Cannizzaro reaction at low base concentration
Step 1: Nucleophilic attack of the base on the carbonyl carbon
The carbonyl carbon of aldehydes is always a good substrate for nucleophilic attack; hydroxide groups, in addition to being good bases, are also good nucleophiles.
Step 2: Migration of hydride ion to the second aldehyde molecule
This is the stage that characterizes the Cannizzaro reaction. In this step, one of the three lone pairs of electrons on the negative oxygen atom closes the double bond with carbon again. However, for this to happen, one of the other three bonds must necessarily be broken, otherwise carbon would violate the octet rule. If you break the bond with the OH group, then you go back to the beginning. This, in fact, occurs because the first reaction is reversible. The only other option is to break the bond with the hydrogen, which takes the pair of electrons in search of a positive center to attack. This center is provided by the carbonyl carbon of a second aldehyde molecule.
During this stage, the carbonyl carbon of the original aldehyde changes from having two bonds with oxygen to having three. Also, it loses a hydrogen bond. This means that this carbon is oxidized during this stage. On the other hand, the second carbonyl carbon that had a double bond with oxygen now has only one, while also ending up with an additional hydrogen. For this reason, this carbon is reduced during the second stage of the reaction.
Step 3: Protonation of the alkoxide
At the end of the second step of the reaction, a carboxylic acid molecule and an alkoxide ion are obtained. However, since carboxylic acids are much more acidic than alcohols, the alkoxide ion quickly deprotons the carboxylic acid to give the carboxylate ion and alcohol, which are the end products of the reaction.
Mechanism of the Cannizzaro reaction at high base concentration
In this case, the first step of the reaction is the same as in the previous case, ie the nucleophilic attack of the base on the carbonyl of the aldehyde. However, there is an additional step before the migration of the hydride group.
Step 1: Nucleophilic attack of the base on the carbonyl carbon
Step 2: Deprotonation of the hydroxyl group
When the concentration of the base is high enough, a second hydroxide ion from the base attacks the newly formed hydroxyl in step 1. This forms the dianion RCHO 2 -2 . The RCHO 2 dianion loses the hydride group more easily than the species of the previous mechanism.
Step 3: Migration of hydride group
This step is equivalent to deprotonation of the hydroxyl group, with the difference that instead of the neutral carboxylic acid, the carboxylate is formed directly. As in the previous case, an alkoxide is also formed.
Step 4: Protonation of the alkoxide
To give the final alcohol, the alkoxide ion formed in the previous step must be protonated. In this case, the hydrogen of the carboxylic acid is no longer available, so the alkoxide removes a proton from a water molecule that acts as a solvent, regenerating the second hydroxide molecule.
reaction kinetics
Since the mechanism varies with the concentration of the base, the kinetics of the reaction or its rate law also varies. When the base concentration is low, the reaction follows third-order kinetics (second with respect to aldehyde and first with respect to hydroxide), as shown by the following equation:
On the other hand, when the concentration of the base is high, in addition to acting as a reagent, the hydroxide also acts as a catalyst. For this reason, the reaction follows a second order kinetics with respect to hydroxide ions, and a global fourth order:
Applications of the Cannizzaro reaction
What makes the Cannizzaro reaction promising is that it occurs at room temperature and atmospheric pressure (i.e., at moderately low pressures on the order of 1 atmosphere), whereas many other synthetic reactions that give similar products require high temperatures or pressures. . Furthermore, it can generally be carried out using water as a solvent. Both characteristics make this reaction a cheaper way to reduce aldehydes to alcohols at an industrial level.
Some of the most important applications involve the synthesis of different glycols and polyols that are of great importance in the industry. Some are neopentyl glycol (2,2-dimethylpropane-1,3-diol), 2,2-bis(hydroxymethyl)propane-1,3-diol, and 2-ethyl-2-hydroxymethyl. These compounds are used as a base for the preparation of varnishes, plasticizers and emulsifiers, as well as substitutes for glycerin.
Examples of the Cannizzaro reaction
Benzaldehyde reaction:
Formaldehyde reaction:
Reaction of 2,2-dimethylpropanal:
References
- Carey, F., & Giuliano, R. (2014). Organic Chemistry (9th ed .). Madrid, Spain: McGraw-Hill Interamericana de España SL
- Smith, MB, & March, J. (2001). March’s Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 5th Edition (5th ed.). Hoboken, NJ: Wiley-Interscience.
- Reyez, D. (2015). Cannizzaro’s reaction . Retrieved from https://www.slideshare.net/DanielaReyes20/reaccin-de-cannizzaro
- Cannizzaro Reaction: Industrial Importance (nd). Retrieved from http://www.chemgapedia.de/vsengine/vlu/vsc/en/ch/2/vlu/oxidation_reduktion/red_cannizzaro.vlu/Page/vsc/en/ch/2/oc/reaktionen/formale_systematik/oxidation_reduktion/ reduktion/ersatz_o_n_durch_h/carbonsaeuren_und_derivate/cannizzaro/anwendung2.vscml.html
