The
benzoin condensation is a reaction (often called a
condensation reactionA condensation reaction is a chemical reaction in which two molecules or moieties combine to form one single molecule, together with the loss of a small molecule. When this small molecule is water, it is known as a dehydration reaction; other possible small molecules lost are hydrogen chloride,...
, for historical reasons) between two aromatic
aldehydeAn aldehyde is an organic compound containing a terminal carbonyl group. This functional group, which consists of a carbon atom bonded to a hydrogen atom and double-bonded to an oxygen atom , is called the aldehyde group...
s, particularly
benzaldehydeBenzaldehyde is an organic compound consisting of a benzene ring with a formyl substituent. It is the simplest aromatic aldehyde and one of the most industrially useful. This colorless liquid has a characteristic pleasant almond-like odor...
. The reaction is
catalyzedCatalysis is the process in which the rate of a chemical reaction is either increased or decreased by means of a chemical substance known as a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. The catalyst may participate...
by a
nucleophileIn chemistry, a nucleophile is a reagent that forms a chemical bond to its reaction partner by donating both bonding electrons. Because nucleophiles donate electrons, they are by definition Lewis bases . All molecules or ions with a free pair of electrons can act as nucleophiles...
such as the
cyanideA cyanide is any chemical compound that contains the cyano group , which consists of a carbon atom triple-bonded to a nitrogen atom. Inorganic cyanides are hydrogen cyanide salts in which cyanide is generally the anion CN
-. Organic compounds that have a -C≡N functional group bonded to...
anion or an
N-heterocyclic carbeneA persistent carbene is a type of carbene demonstrating particular stability despite also being a reactive intermediate. The instability in these carbenes involves reactivity with substrates, or dimerisation...
. The reaction product is an aromatic
acyloinAcyloins are a class of organic compounds in organic chemistry sharing a common functional group consisting of a hydroxyl group placed on the α-position of a carbonyl group.- Synthesis of acyloins :...
with
benzoinBenzoin is an organic compound consisting of an ethylene bridge flanked by phenyl groups and with hydroxyl and ketone functional groups. It appears as off-white crystals, with a light camphor odor. Benzoin is synthesized from benzaldehyde in the benzoin condensation.Benzoin is not a constituent of...
as the parent compound. An early version of the reaction was developed in 1832 by
Justus von LiebigJustus von Liebig was a German chemist who made major contributions to agricultural and biological chemistry, and worked on the organization of organic chemistry. As a professor, he devised the modern laboratory-oriented teaching method, and for such innovations, he is regarded as one of the...
and Friederich Woehler during their research on
bitter almond oilThe Almond is a species of tree native to the Middle East. Almond is also the name of the edible and widely cultivated nut of this tree...
. The catalytic version of the reaction was developed by
Nikolay ZininNikolay Nikolaevich Zinin was a Russian organic chemist.-Life:He studied at the University of Kazan where he graduated in mathematics but he started teaching chemistry in 1835. To improve his skills he was asked to study in Europe for some time, which he did between 1838 and 1841...
in the late 1830s, and the
reaction mechanismIn chemistry, a reaction mechanism is the step by step sequence of elementary reactions by which overall chemical change occurs .Although only the net chemical change is directly observable for most chemical reactions, experiments can often be designed that suggest the possible sequence of steps in...
for this
organic reactionOrganic reactions are chemical reactions involving organic compounds. The basic organic chemistry reaction types are addition reactions, elimination reactions, substitution reactions, pericyclic reactions, rearrangement reactions and redox reactions. In organic synthesis, organic reactions are used...
was proposed in 1903 by
A. J. LapworthArthur Lapworth was a Scottish chemist born in Galashiels, Scotland, son of Charles Lapworth geologist. He was a pioneer of the field of physical organic chemistry. The Lapworth reaction is named after him...
.
In the first step in this reaction, the cyanide anion (as sodium cyanide) reacts with the aldehyde in a
nucleophilic additionIn organic chemistry, a nucleophilic addition reaction is an addition reaction where in a chemical compound a π bond is removed by the creation of two new covalent bonds by the addition of a nucleophile....
.
The
benzoin condensation is a reaction (often called a
condensation reactionA condensation reaction is a chemical reaction in which two molecules or moieties combine to form one single molecule, together with the loss of a small molecule. When this small molecule is water, it is known as a dehydration reaction; other possible small molecules lost are hydrogen chloride,...
, for historical reasons) between two aromatic
aldehydeAn aldehyde is an organic compound containing a terminal carbonyl group. This functional group, which consists of a carbon atom bonded to a hydrogen atom and double-bonded to an oxygen atom , is called the aldehyde group...
s, particularly
benzaldehydeBenzaldehyde is an organic compound consisting of a benzene ring with a formyl substituent. It is the simplest aromatic aldehyde and one of the most industrially useful. This colorless liquid has a characteristic pleasant almond-like odor...
. The reaction is
catalyzedCatalysis is the process in which the rate of a chemical reaction is either increased or decreased by means of a chemical substance known as a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. The catalyst may participate...
by a
nucleophileIn chemistry, a nucleophile is a reagent that forms a chemical bond to its reaction partner by donating both bonding electrons. Because nucleophiles donate electrons, they are by definition Lewis bases . All molecules or ions with a free pair of electrons can act as nucleophiles...
such as the
cyanideA cyanide is any chemical compound that contains the cyano group , which consists of a carbon atom triple-bonded to a nitrogen atom. Inorganic cyanides are hydrogen cyanide salts in which cyanide is generally the anion CN
-. Organic compounds that have a -C≡N functional group bonded to...
anion or an
N-heterocyclic carbeneA persistent carbene is a type of carbene demonstrating particular stability despite also being a reactive intermediate. The instability in these carbenes involves reactivity with substrates, or dimerisation...
. The reaction product is an aromatic
acyloinAcyloins are a class of organic compounds in organic chemistry sharing a common functional group consisting of a hydroxyl group placed on the α-position of a carbonyl group.- Synthesis of acyloins :...
with
benzoinBenzoin is an organic compound consisting of an ethylene bridge flanked by phenyl groups and with hydroxyl and ketone functional groups. It appears as off-white crystals, with a light camphor odor. Benzoin is synthesized from benzaldehyde in the benzoin condensation.Benzoin is not a constituent of...
as the parent compound. An early version of the reaction was developed in 1832 by
Justus von LiebigJustus von Liebig was a German chemist who made major contributions to agricultural and biological chemistry, and worked on the organization of organic chemistry. As a professor, he devised the modern laboratory-oriented teaching method, and for such innovations, he is regarded as one of the...
and Friederich Woehler during their research on
bitter almond oilThe Almond is a species of tree native to the Middle East. Almond is also the name of the edible and widely cultivated nut of this tree...
. The catalytic version of the reaction was developed by
Nikolay ZininNikolay Nikolaevich Zinin was a Russian organic chemist.-Life:He studied at the University of Kazan where he graduated in mathematics but he started teaching chemistry in 1835. To improve his skills he was asked to study in Europe for some time, which he did between 1838 and 1841...
in the late 1830s, and the
reaction mechanismIn chemistry, a reaction mechanism is the step by step sequence of elementary reactions by which overall chemical change occurs .Although only the net chemical change is directly observable for most chemical reactions, experiments can often be designed that suggest the possible sequence of steps in...
for this
organic reactionOrganic reactions are chemical reactions involving organic compounds. The basic organic chemistry reaction types are addition reactions, elimination reactions, substitution reactions, pericyclic reactions, rearrangement reactions and redox reactions. In organic synthesis, organic reactions are used...
was proposed in 1903 by
A. J. LapworthArthur Lapworth was a Scottish chemist born in Galashiels, Scotland, son of Charles Lapworth geologist. He was a pioneer of the field of physical organic chemistry. The Lapworth reaction is named after him...
.
Reaction mechanism
In the first step in this reaction, the cyanide anion (as sodium cyanide) reacts with the aldehyde in a
nucleophilic additionIn organic chemistry, a nucleophilic addition reaction is an addition reaction where in a chemical compound a π bond is removed by the creation of two new covalent bonds by the addition of a nucleophile....
. Rearrangement of the intermediate results in
polarity reversalUmpolung or polarity inversion in organic chemistry is the chemical modification of a functional group with the aim of the reversal of polarity of that group. This modification allows secondary reactions of this functional group that would otherwise not be possible. The concept was introduced by...
of the
carbonylIn organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom : C=O.The term carbonyl can also refer to carbon monoxide as a ligand in an inorganic or organometallic complex In organic chemistry, a carbonyl group is a functional group...
group, which then adds to the second carbonyl group in a second nucleophilic addition.
ProtonHydrogen ion is recommended by IUPAC as a general term for all ions of hydrogen and its isotopes. Depending on the charge of the ion, two different classes can be distinguished:-Cation :...
transfer and elimination of the cyanide ion affords benzoin as the product. This is a
reversible reactionA reversible reaction is a chemical reaction that results in an equilibrium mixture of reactants and products. For a reaction involving two reactants and two products this can be expressed symbolically as...
.
The cyanide ion serves three different purposes in the course of this reaction. It acts as a
nucleophileIn chemistry, a nucleophile is a reagent that forms a chemical bond to its reaction partner by donating both bonding electrons. Because nucleophiles donate electrons, they are by definition Lewis bases . All molecules or ions with a free pair of electrons can act as nucleophiles...
, facilitates proton abstraction, and is also the
leaving groupIn chemistry, a leaving group is a molecular fragment that departs with a pair of electrons in heterolytic bond cleavage. Leaving groups can be anions or neutral molecules. Common anionic leaving groups are halides such as Cl-, Br-, and I-, and sulfonate esters,...
in the final step. The benzoin condensation is in effect a dimerization and not a condensation because a small molecule like water is not released in this reaction. For this reason the reaction is also called a
benzoin addition. In this reaction, the two aldehydes serve different purposes; one aldehyde donates a proton and one aldehyde accepts a proton. 4-Dimethylaminobenzaldehyde is an efficient proton donor while 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.
Scope
The reaction can be extended to
aliphaticIn organic chemistry, compounds composed of carbon and hydrogen are divided into two classes: aromatic compounds, which contain benzene rings or similar rings of atoms, and aliphatic compounds , which do not contain aromatic rings.
Aliphatic compounds can be cyclic, like cyclohexane, or...
aldehydes with
baseIn chemistry, a base is most commonly thought of as an aqueous substance that can accept hydrogen ions. Bases are also the oxides or hydroxides of metals. A soluble base is also often referred to as an alkali if hydroxide ions are involved. This refers to the Brønsted-Lowry theory of acids and bases...
catalysis in the presence of thiazolium salts; the reaction mechanism is essentially the same. These compounds are important in the synthesis of heterocyclic compounds. The addition is also possible with
enoneAn enone is an unsaturated chemical compound or functional group consisting of a conjugated system of an alkene and a ketone. The simplest enone is methyl vinyl ketone or CH2=CHCOCH3....
s; for instance
methyl vinyl ketoneMethyl vinyl ketone is a reactive organic compound classified as an enone. It is a colorless, flammable, highly toxic liquid with a pungent odor...
is a reagent in the
Stetter reactionThe Stetter reaction is an organic reaction involving the nucleophile catalyzed conjugate addition of an aldehyde to a Michael acceptor such as an enone . The reaction product is a 1,4-dicarbonyl compound...
.
In
biochemistryBiochemistry is the study of the chemical processes in living organisms. It deals with the structure and function of cellular components such as proteins, carbohydrates, lipids, nucleic acids and other biomolecules....
, the coenzyme
thiamineThiamine or thiamin, sometimes called aneurin, is a water-soluble vitamin of the B complex , whose phosphate derivatives are involved in many cellular processes. The best characterized form is thiamine diphosphate , a coenzyme in the catabolism of sugars and amino acids...
is responsible for biosynthesis of acyloin-like compounds. This coenzyme also contains a thiazolium moiety, which on
deprotonationDeprotonation is a chemistry term that refers to the removal of a proton from a molecule, forming the conjugate base. The relative ability for a molecule to give up a proton is measured by a pKa value. A low pKa value indicates that the compound is acidic and will easily...
becomes a nucleophilic carbene.
In one study, a custom-designed
N-heterocyclic carbeneA persistent carbene is a type of carbene demonstrating particular stability despite also being a reactive intermediate. The instability in these carbenes involves reactivity with substrates, or dimerisation...
(NHC, the framework is related to thiazolium salts) was found to facilitate an enantioselective
intramolecularIntramolecular in chemistry describes a process or characteristic limited within the structure of a single molecule; a property or phenomenon limited to the extent of a single molecule.- Examples :...
benzoin condensation (
Scheme 2).
This finding was confirmed in another study with a slightly modified NHC using
DBU1,8-Diazabicyclo[5.4.0]undec-7-ene, or more commonly DBU, is a chemical compound and belongs to the class of amidine compounds. It is used in organic synthesis as a catalyst and complexing ligand and non-nucleophilic base....
as the base instead of
potassium tert-butoxidePotassium tert-butoxide is the chemical compound with the formula
3COK. This colourless solid is a strong base useful in organic synthesis. It exists as a tetrameric cubane-like cluster...
(
Scheme 3).