The Cannizzaro reaction, named after its discoverer
Stanislao Cannizzaro
Stanislao Cannizzaro ( , also , ; 13 July 1826 – 10 May 1910) was an Italian chemist. He is famous for the Cannizzaro reaction and for his influential role in the atomic-weight deliberations of the Karlsruhe Congress in 1860.
Biograph ...
, is a
chemical reaction
A chemical reaction is a process that leads to the IUPAC nomenclature for organic transformations, chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the pos ...
which involves the
base-induced
disproportionation
In chemistry, disproportionation, sometimes called dismutation, is a redox reaction in which one compound of intermediate oxidation state converts to two compounds, one of higher and one of lower oxidation states. More generally, the term can b ...
of two molecules of a non-
enol
In organic chemistry, alkenols (shortened to enols) are a type of reactive structure or intermediate in organic chemistry that is represented as an alkene ( olefin) with a hydroxyl group attached to one end of the alkene double bond (). The t ...
izable
aldehyde
In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl grou ...
to give a
primary alcohol
A primary alcohol is an alcohol in which the hydroxy group is bonded to a primary carbon atom. It can also be defined as a molecule containing a “–CH2OH” group.
In contrast, a secondary alcohol has a formula “–CHROH” and a tertiary ...
and a
carboxylic acid
In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxylic ...
.
:
Cannizzaro first accomplished this transformation in 1853, when he obtained
benzyl alcohol
Benzyl alcohol is an aromatic alcohol with the formula C6H5CH2OH. The benzyl group is often abbreviated "Bn" (not to be confused with "Bz" which is used for benzoyl), thus benzyl alcohol is denoted as BnOH. Benzyl alcohol is a colorless liquid w ...
and
potassium benzoate
Potassium benzoate (E212), the potassium salt of benzoic acid, is a food preservative that inhibits the growth of mold, yeast and some bacteria. It works best in low- pH products, below 4.5, where it exists as benzoic acid.
Acidic foods and bev ...
from the treatment of benzaldehyde with
potash
Potash () includes various mined and manufactured salts that contain potassium in water-soluble form. (potassium carbonate). More typically, the reaction would be conducted with
sodium hydroxide
Sodium hydroxide, also known as lye and caustic soda, is an inorganic compound with the formula NaOH. It is a white solid ionic compound consisting of sodium cations and hydroxide anions .
Sodium hydroxide is a highly caustic base and alkali ...
or
potassium hydroxide
Potassium hydroxide is an inorganic compound with the formula K OH, and is commonly called caustic potash.
Along with sodium hydroxide (NaOH), KOH is a prototypical strong base. It has many industrial and niche applications, most of which exp ...
, giving the sodium or potassium
carboxylate
In organic chemistry, a carboxylate is the conjugate base of a carboxylic acid, (or ). It is an ion with negative charge.
Carboxylate salts are salts that have the general formula , where M is a metal and ''n'' is 1, 2,...; ''carboxylat ...
salt of the carboxylic-acid product:
:2 C
6H
5CHO + KOH → C
6H
5CH
2OH + C
6H
5COOK
The process is a
redox
Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate (chemistry), substrate change. Oxidation is the loss of Electron, electrons or an increase in the oxidation state, while reduction ...
reaction involving transfer of a
hydride
In chemistry, a hydride is formally the anion of hydrogen( H−). The term is applied loosely. At one extreme, all compounds containing covalently bound H atoms are called hydrides: water (H2O) is a hydride of oxygen, ammonia is a hydride of ...
from one substrate molecule to the other: one aldehyde is oxidized to form the acid, the other is reduced to form the alcohol.
Mechanism
The reaction involves a
nucleophilic acyl substitution
Nucleophilic acyl substitution describe a class of substitution reactions involving nucleophiles and acyl compounds. In this type of reaction, a nucleophile – such as an alcohol, amine, or enolate – displaces the leaving group of an acyl deriv ...
on an aldehyde, with the
leaving group In chemistry, a leaving group is defined by the IUPAC as an atom or group of atoms that detaches from the main or residual part of a substrate during a reaction or elementary step of a reaction. However, in common usage, the term is often limited t ...
concurrently attacking another aldehyde in the second step. First, hydroxide attacks a carbonyl. The resulting
tetrahedral intermediate
A tetrahedral intermediate is a reaction intermediate in which the bond arrangement around an initially double-bonded carbon atom has been transformed from trigonal to tetrahedral. Tetrahedral intermediates result from nucleophilic addition to a ...
then collapses, re-forming the carbonyl and transferring
hydride
In chemistry, a hydride is formally the anion of hydrogen( H−). The term is applied loosely. At one extreme, all compounds containing covalently bound H atoms are called hydrides: water (H2O) is a hydride of oxygen, ammonia is a hydride of ...
to attack another carbonyl. In the final step of the reaction, the acid and alkoxide ions formed exchange a proton.
In the presence of a very high concentration of base, the aldehyde first forms a doubly charged anion from which a hydride ion is transferred to the second molecule of aldehyde to form carboxylate and alkoxide ions. Subsequently, the alkoxide ion acquires a proton from the solvent.
![C-R startAnimGif](https://upload.wikimedia.org/wikipedia/commons/b/b2/C-R_startAnimGif.gif)
![Cannizzaro reaction mechanism](https://upload.wikimedia.org/wikipedia/commons/d/d6/Cannizzaro_reaction_mechanism.svg)
Overall, the reaction follows third-order kinetics. It is second order in aldehyde and first order in base:
::: rate = k
CHOsup>2
−">H−At very high base a second path (k') becomes important that is second order in base:
::: rate = k
CHOsup>2
−">H− + k'
CHOsup>2
−">H−sup>2
The k' pathway implicates a reaction between the doubly charged anion (RCHO
22−) and the aldehyde. The direct transfer of hydride ion is evident from the observation that the recovered alcohol does not contain any deuterium attached to the α-carbon when the reaction is performed in the presence of D
2O.
Scope
Due to the strongly
alkaline
In chemistry, an alkali (; from ar, القلوي, al-qaly, lit=ashes of the saltwort) is a base (chemistry), basic, ionic compound, ionic salt (chemistry), salt of an alkali metal or an alkaline earth metal. An alkali can also be defined as ...
reaction conditions, aldehydes that have alpha hydrogen atom(s) instead undergo deprotonation there, leading to
enolate
In organic chemistry, enolates are organic anions derived from the deprotonation of carbonyl () compounds. Rarely isolated, they are widely used as reagents in the synthesis of organic compounds.
Bonding and structure
Enolate anions are electr ...
s and possible
aldol reaction
The aldol reaction is a means of forming carbon–carbon bonds in organic chemistry.
Discovered independently by the Russian chemist Alexander Borodin in 1869 and by the French chemist Charles-Adolphe Wurtz in 1872, the reaction combines two carb ...
s. Under ideal conditions the reaction produces 50% of both the alcohol and the carboxylic acid (it takes two aldehydes to produce one acid and one alcohol). This can be economically viable if the products can be separated and both have a value; the commercial conversion of
furfural into
furfuryl alcohol
Furfuryl alcohol is an organic compound containing a furan substituted with a hydroxymethyl group. It is a colorless liquid, but aged samples appear amber. It possesses a faint odor of burning and a bitter taste. It is miscible with but unstable ...
and
2-furoic acid is an example of this.
Alternatively, higher yields of one product (usually the alcohol) can be achieved in the crossed Cannizzaro reaction, in which a sacrificial aldehyde is used in combination with a more valuable chemical. In this variation, the reductant is
formaldehyde
Formaldehyde ( , ) (systematic name methanal) is a naturally occurring organic compound with the formula and structure . The pure compound is a pungent, colourless gas that polymerises spontaneously into paraformaldehyde (refer to section F ...
, which is oxidized to
sodium formate
Sodium formate, HCOONa, is the sodium salt of formic acid, HCOOH. It usually appears as a white deliquescent powder.
Preparation
For commercial use, sodium formate is produced by absorbing carbon monoxide under pressure in solid sodium hydroxide ...
and the other aldehyde chemical is reduced to the alcohol. Thus, the yield of the valuable chemical is high, although the
atom economy
Atom economy (atom efficiency/percentage) is the conversion efficiency of a chemical process in terms of all atoms involved and the desired products produced. The simplest definition was introduced by Barry Trost in 1991 and is equal to the ratio ...
can be low. The final stage in the synthesis of
pentaerythritol
Pentaerythritol is an organic compound with the formula C(CH2OH)4. Classified as a polyol, it is a white solid. Pentaerythritol is a building block for the synthesis and production of explosives, plastics, paints, appliances, cosmetics, and many o ...
is an example.
![Pentaerythrit](https://upload.wikimedia.org/wikipedia/commons/7/7a/Pentaerythrit.svg)
A solvent-free reaction has been reported involving grinding liquid 2-chlorobenzaldehyde with
potassium hydroxide
Potassium hydroxide is an inorganic compound with the formula K OH, and is commonly called caustic potash.
Along with sodium hydroxide (NaOH), KOH is a prototypical strong base. It has many industrial and niche applications, most of which exp ...
in a
mortar and pestle
Mortar and pestle is a set of two simple tools used from the Stone Age to the present day to prepare ingredients or substances by crushing and grinding them into a fine paste or powder in the kitchen, laboratory, and pharmacy. The ''mortar'' () ...
:
Variations
In the
Tishchenko reaction The Tishchenko reaction is an organic chemical reaction that involves disproportionation of an aldehyde in the presence of an alkoxide. The reaction is named after Russian organic chemist Vyacheslav Tishchenko, who discovered that aluminium alkoxi ...
, the base used is an
alkoxide
In chemistry, an alkoxide is the conjugate base of an alcohol and therefore consists of an organic group bonded to a negatively charged oxygen atom. They are written as , where R is the organic substituent. Alkoxides are strong bases and, whe ...
rather than hydroxide, and the product is an
ester
In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ar ...
rather than the separate alcohol and carboxylate groups. After the nucleophilic base attacks an aldehyde, the resulting new oxygen anion attacks another aldehyde to give a hemiacetal linkage between two of the formerly aldehyde-containing reactants rather than undergoing tetrahedral collapse. Eventually tetrahedral collapse does occur, giving the stable ester product.
:
![Tishchenko reaction](https://upload.wikimedia.org/wikipedia/commons/7/7c/Tishchenko_reaction.svg)
Certain
ketone
In organic chemistry, a ketone is a functional group with the structure R–C(=O)–R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group –C(=O)– (which contains a carbon-oxygen double bo ...
s can undergo a Cannizzaro-type reaction, transferring one of their two carbon groups rather than the hydride that would be present on an aldehyde.
See also
*
Meerwein–Ponndorf–Verley reduction
The Meerwein–Ponndorf–Verley (MPV) reduction in organic chemistry is the reduction of ketones and aldehydes to their corresponding alcohols utilizing aluminium alkoxide catalysis in the presence of a sacrificial alcohol. The advantages of the ...
*
Oppenauer oxidation
Oppenauer oxidation, named after , is a gentle method for selectively oxidizing secondary alcohols to ketones.
The reaction is the opposite Meerwein–Ponndorf–Verley reduction. The alcohol is oxidized with aluminium isopropoxide in excess ...
References
{{Organic reactions
Organic redox reactions
Name reactions