The Benzoin Condensation

Although the benzoin condensation proceeds rapidly and produces benzoin in high yield when
catalyzed by cyanide, we will not perform the reaction with this catalyst. Cyanide is extremely
toxic and accidental exposure to even small amounts can have serious consequences. Cyanide is
not readily absorbed through the skin, but any small cut or break in the skin can lead to accidental
exposure. In solid form, it may also be inhaled in the form of dust or small particles.
A number of biochemical reactions bear a close resemblance to the benzoin condensation but are
not catalyzed by the highly toxic cyanide ion. In the 1960s it was found that that vitamin B1,
thiamine hydrochloride, in the form of the coenzyme thiamine pyrophosphate, can function in a
manner completely analogous to cyanide ion in promoting reactions like the benzoin
condensation. The resonance stabilized conjugate base of the thiazolium ion, thiamine, and the
resonance stabilized carbanion that it forms are the key to the reaction. Like the cyanide ion, the
thiazolium ion has just the right balance of nucleophilicity, ability to stabilize the intermediate
anion, and good leaving group qualities.
H3C N NH2
N
H
S
CH 2
N +
Cl -
CH 3
OH
HO -
H3C N NH2
N
C -
S
CH 2
N +
Cl -
thiamine hydrochloride thiamine (a nucleophile)
Note that one of the carbons in the 5-membered ring is a carbanion; this will attack benzaldehyde
in much the same way cyanide does, resulting in a carbanion at the benzyl position of
benzaldehyde. It is thiamine we will use as a catalyst for the benzoin condensation. We will
form the thiamine in situ by adding thiamine hydrochloride and NaOH to our reaction mixture.
The importance of thiamine is evident in that it is a vitamin, an essential substance that must be
provided in the diet to prevent beriberi, a nervous system disease.
CH 3
OH
2