Benzoin condensation

The Benzoin condensation is a condensation reaction between two aromatic aldehydes, especially benzaldehyde that is catalyzed by a cyanide. The reaction product is an aromatic acyloin with benzoin as the parent compound ^[1]. The reaction mechanism for this organic reaction was already proposed in 1903 by A. J. Lapworth ^[2].

Additional recommended knowledge

Correct Test Weight Handling Guide: 12 Practical Tips

Don't let static charges disrupt your weighing accuracy

Weighing the right way

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.

Scope

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) ^[3].

This finding was confirmed in another study ^[4] with a slightly modified NHC and a DBU base instead of potassium tert-butoxide

References

1. ^ Benzoin Roger Adams and C. S. Marvel Organic Syntheses, Coll. Vol. 1, p.94 (1941); Vol. 1, p.33 (1921) Article
2. ^ CXXII. — 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. doi:10.1039/CT9048501206
3. ^ D. Enders, O. Niemeier and T. Balensiefer (2006). "Asymmetric Intramolecular Crossed-Benzoin Reactions by N-Heterocyclic Carbene Catalysis". Angewandte Chemie International Edition 45 (9): 1463-1467. doi:10.1002/anie.200503885.
4. ^ H. Takikawa, Y. Hachisu, J. W. Bode and K. Suzuki (2006). "Catalytic Enantioselective Crossed Aldehyde-Ketone Benzoin Cyclization". Angewandte Chemie International Edition 45 (21): 3492-3494. doi:10.1002/anie.200600268.