Benzoin condensation
The
Benzoin condensation is a
condensation reaction between two
aromatic aldehydes, especially
benzaldehyde that is
catalyzed by a
cyanide [Main text & image German Wiki original]. The reaction product is an aromatic
acyloin with
benzoin as the parent compound
[Benzoin Roger Adams and C. S. Marvel Organic Syntheses, Coll. Vol. 1, p.94 (1941); Vol. 1, p.33 (1921) Article]. The
reaction mechanism for this
organic reaction was already proposed in 1903 by
A. J. Lapworth [CXXII.â€"Reactions involving the addition of hydrogen cyanide to carbon compounds. Part II. Cyanohydrins regarded as complex acids Arthur Lapworth, Journal of the Chemical Society, Transactions, 1904, 85, 1206 - 1214 Abstract].
 |
Scheme 1. Benzoin condensation reaction mechanism |
In the first step in this reaction the cyanide ion (as sodium cyanide) reacts with the aldehyde in a
nucleophilic addition.
Umpolung reverses the
polarity of the carbonyl group and the rearranged intermediate adds to the second carbonyl group in a second nucleophilic addition.
Proton transfer and elimination of the cyanide ion affords the benzoin. This is a
reversible reaction.The cyanide ion is a very specific
catalyst and serves three different purposes in the course of the reaction. It acts as a
nucleophile, it facilitates proton abstraction in the umpolung by its
inductive effect and it is also the
leaving group 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. Both aldehydes have a different purpose. One aldehyde donates a proton and one aldehyde accepts a proton. 4-dimethylaminobenzaldehyde is an efficient proton donor while benzaldehyde is both a proton and a donor. In this way it is possible to synthesise asymmetric benzoins.
The reaction can be extended to
aliphatic aldehydes with
base catalysis in the presence of
thiazolium salts. The reaction mechanism is essentially the same. The corresponding product is called an
acyloin. These compounds are important in the synthesis of
heterocyclic compounds. The addition is also possible with
enones for instance
methyl vinyl ketone in the
Stetter reaction.
In
biochemistry, the
coenzyme Thiamine is responsible for biosynthesis of acyloine-like compounds. This coenzyme also contains a thiazolium moiety.In one study a custom designed
N-Heterocyclic Carbene (NHC, the framework is related to thiazolium salts) was found to be able to bring about an
enantioselective intramolecular benzoin condensation (
scheme 2)
[Asymmetric Intramolecular Crossed-Benzoin Reactions by N-Heterocyclic Carbene Catalysis Dieter Enders, Oliver Niemeier, Tim Balensiefer Angewandte Chemie International Edition Volume 45, Issue 9 , Pages 1463 - 1467 2006 Abstract ].
|
Scheme 2. Intramolecular benzoin condensation |
This finding was confirmed in another study
[Catalytic Enantioselective Crossed Aldehyde-Ketone Benzoin Cyclization Hiroshi Takikawa , Yoshifumi Hachisu, Jeffrey W. Bode, Keisuke Suzuki Angewandte Chemie International Edition Volume 45, Issue 21 , Pages 3492 - 3494 2006 Abstract] with a slightly modified NHC and a
DBU base instead of
potassium tert-butoxide |
Scheme 3. Intramolecular benzoin condensation |
