The benzoin addition is an

addition reaction In organic chemistry, an addition reaction is, in simplest terms, an organic reaction where two or more molecules combine to form a larger one (the adduct).. Addition reactions are limited to chemical compounds that have multiple bonds, such as ...

involving two

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 gro ...

s. The reaction generally occurs between

aromatic In chemistry, aromaticity is a chemical property of cyclic ( ring-shaped), ''typically'' planar (flat) molecular structures with pi bonds in resonance (those containing delocalized electrons) that gives increased stability compared to satur ...

aldehydes or glyoxals, and results in formation of an

acyloin Acyloins or α-hydroxy ketones are a class of organic compounds which all possess a hydroxy group adjacent to a ketone group. The name acyloin is derived from the fact that they are formally derived from reductive coupling of carboxylic acyl grou ...

. In the classic example, benzaldehyde is converted to benzoin. The benzoin condensation was first reported in 1832 by

Justus von Liebig Justus Freiherr von Liebig (12 May 1803 – 20 April 1873) was a German scientist who made major contributions to agricultural and biological chemistry, and is considered one of the principal founders of organic chemistry. As a professor at t ...

and

Friedrich Wöhler Friedrich Wöhler () FRS(For) HonFRSE (31 July 180023 September 1882) was a German chemist known for his work in inorganic chemistry, being the first to isolate the chemical elements beryllium and yttrium in pure metallic form. He was the firs ...

during their research on bitter almond oil. The catalytic version of the reaction involving cyanide was developed by

Nikolay Zinin Nikolay Nikolaevich Zinin (russian: link=no, Никола́й Никола́евич Зи́нин; 25 August 1812, in Shusha – 18 February 1880, in Saint Petersburg) was a Russian organic chemist. Life He studied at the University of Kazan where ...

in the late 1830s. Benzoin condensation reaction

Reaction mechanism

The reaction is

catalyzed Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...

nucleophiles In chemistry, a nucleophile is a chemical species that forms bonds by donating an electron pair. All molecules and ions with a free pair of electrons or at least one pi bond can act as nucleophiles. Because nucleophiles donate electrons, they are ...

such as a

cyanide Cyanide is a naturally occurring, rapidly acting, toxic chemical that can exist in many different forms. In chemistry, a cyanide () is a chemical compound that contains a functional group. This group, known as the cyano group, consists of ...

or an

N-heterocyclic carbene A persistent carbene (also known as stable carbene) is a type of carbene demonstrating particular stability. The best-known examples and by far largest subgroup are the ''N''-heterocyclic carbenes (NHC) (sometimes called Arduengo carbenes), for ex ...

(usually thiazolium salts). The

reaction mechanism In chemistry, a reaction mechanism is the step by step sequence of elementary reactions by which overall chemical change occurs. A chemical mechanism is a theoretical conjecture that tries to describe in detail what takes place at each stage of ...

was proposed in 1903 by

A. J. Lapworth Arthur Lapworth FRS (10 October 1872 – 5 April 1941) was a Scottish chemist. He was born in Galashiels, Scotland, the son of geologist Charles Lapworth, and educated at St Andrew's and King Edward's School, Birmingham. He graduated in chemist ...

. In the first step in this reaction, the cyanide anion (as

sodium cyanide Sodium cyanide is a poisonous compound with the formula Na C N. It is a white, water-soluble solid. Cyanide has a high affinity for metals, which leads to the high toxicity of this salt. Its main application, in gold mining, also exploits its hi ...

) reacts with the aldehyde in a

nucleophilic addition In organic chemistry, a nucleophilic addition reaction is an addition reaction where a chemical compound with an electrophilic double or triple bond reacts with a nucleophile, such that the double or triple bond is broken. Nucleophilic additions di ...

. Rearrangement of the intermediate results in polarity reversal of the

carbonyl In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups. A compound containing a ...

group, which then adds to the second carbonyl group in a second nucleophilic addition.

Proton A proton is a stable subatomic particle, symbol , H+, or 1H+ with a positive electric charge of +1 ''e'' elementary charge. Its mass is slightly less than that of a neutron and 1,836 times the mass of an electron (the proton–electron mass ...

transfer and elimination of the cyanide ion affords benzoin as the product. This is a

reversible reaction A reversible reaction is a reaction in which the conversion of reactants to products and the conversion of products to reactants occur simultaneously. : \mathit aA + \mathit bB \mathit cC + \mathit dD A and B can react to form C and D or, in the ...

, which means that the distribution of products is determined by the relative

thermodynamic stability In chemistry, chemical stability is the thermodynamic stability of a chemical system. Thermodynamic stability occurs when a system is in its lowest energy state, or in chemical equilibrium with its environment. This may be a dynamic equilibriu ...

of the products and starting material. Benzoin mechanism

In this reaction, one aldehyde donates a proton and one aldehyde accepts a proton. Some aldehydes can only donate protons, such as 4-dimethylaminobenzaldehyde whereas benzaldehyde is both a proton acceptor and donor. In this way it is possible to synthesise mixed benzoins, i.e. products with different groups on each half of the product. However, care should be taken to match a proton donating aldehyde with a proton accepting aldehyde to avoid undesired homo-dimerization.

Scope

The reaction can be extended to

aliphatic In organic chemistry, hydrocarbons ( compounds composed solely of carbon and hydrogen) are divided into two classes: aromatic compounds and aliphatic compounds (; G. ''aleiphar'', fat, oil). Aliphatic compounds can be saturated, like hexane, or ...

aldehydes with base catalysis in the presence of

thiazolium salt Thiazole, or 1,3-thiazole, is a heterocyclic compound that contains both sulfur and nitrogen. The term 'thiazole' also refers to a large family of derivatives. Thiazole itself is a pale yellow liquid with a pyridine-like odor and the molecular for ...

s; the reaction mechanism is essentially the same. These compounds are important in the synthesis of

heterocyclic compounds A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different elements as members of its ring(s). Heterocyclic chemistry is the branch of organic chemistry dealing with the synthesis, properties, and ...

. The analogous 1,4-addition of an aldehyde to an enone is called the

Stetter reaction The Stetter reaction is a reaction used in organic chemistry to form carbon-carbon bonds through a 1,4-addition reaction utilizing a nucleophilic catalyst.Stetter, H. ''Angew. Chem. Int. Ed.'' 1976, ''15'', 639. While the related 1,2-addition re ...

. In

biochemistry Biochemistry or biological chemistry is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology and ...

, the

coenzyme A cofactor is a non-protein chemical compound or metallic ion that is required for an enzyme's role as a catalyst (a catalyst is a substance that increases the rate of a chemical reaction). Cofactors can be considered "helper molecules" that ass ...

thiamine Thiamine, also known as thiamin and vitamin B1, is a vitamin, an essential micronutrient, that cannot be made in the body. It is found in food and commercially synthesized to be a dietary supplement or medication. Phosphorylated forms of thi ...

is responsible for biosynthesis of acyloin-like compounds utilizing the benzoin addition. This coenzyme also contains a thiazolium moiety, which on

deprotonation Deprotonation (or dehydronation) is the removal (transfer) of a proton (or hydron, or hydrogen cation), (H+) from a Brønsted–Lowry acid in an acid–base reaction.Henry Jakubowski, Biochemistry Online Chapter 2A3, https://employees.csbsju.ed ...

becomes a nucleophilic carbene. The asymmetric version of this reaction has been performed by utilizing chiral thiazolium and triazolium salts. Triazolium salts were found to give greater enantiomeric excess than thiazolium salts. An example is shown below. Since the products of the reaction are thermodynamically controlled, the Retro Benzoin Addition can be synthetically useful. If a benzoin or acyloin can be synthesized by another method, then they can be converted into the component

ketones 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 bon ...

using cyanide or thiazolium catalysts. The reaction mechanism is the same as above, but it occurs in the reverse direction. This can allow the access of ketones otherwise difficult to produce.

References

External links

{{Organic reactions Addition reactions

Reaction mechanism

Scope

See also

References

External links