- Benzoin condensation
The benzoin condensation is a
condensation reaction between twoaromatic aldehyde s, particularlybenzaldehyde . The reaction is catalyzed by anucleophile such as thecyanide anion or an N-heterocyclic carbene. The reaction product is an aromaticacyloin withbenzoin as the parent compound. ["Benzoin" Roger Adams and C. S. MarvelOrganic Syntheses , Coll. Vol. 1, p.94 (1941); Vol. 1, p.33 (1921) [http://www.orgsyn.org/orgsyn/prep.asp?prep=cv1p0094 Article] ] An early version of the reaction was developed in 1832 byJustus von Liebig and Friederich Woehler during their research on bitter almond oil. [cite journal
title = Untersuchungen über das Radikal der Benzoesäure
author = Wöhler, Liebig
journal = Annalen der Pharmacie
volume = 3
issue = 3
pages = 249–282
year = 1832
url =
doi = 10.1002/jlac.18320030302 ] The catalytic version of the reaction was developed byNikolay Zinin in the late 1830s, [cite journal
title = Beiträge zur Kenntniss einiger Verbindungen aus der Benzoylreihe
author = N. Zinin
journal = Annalen der Pharmacie
volume = 31
issue = 3
pages = 329–332
year = 1839
url =
doi = 10.1002/jlac.18390310312 ] [cite journal
title = Ueber einige Zersetzungsprodukte des Bittermandelöls
author = N. Zinin
journal = Annalen der Pharmacie
volume = 34
issue = 2
pages = 186–192
year = 1840
url =
doi = 10.1002/jlac.18400340205 ] and thereaction mechanism for thisorganic reaction was proposed in 1903 by A. J. Lapworth. ["CXXII. — Reactions involving the addition ofhydrogen 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]Reaction mechanism
In the first step in this reaction, the cyanide anion (as sodium cyanide) reacts with the aldehyde in a
nucleophilic addition . Rearrangement of the intermediate results in polarity reversal of thecarbonyl group, which then adds to the second carbonyl group in a second nucleophilic addition. Proton transfer and elimination of the cyanide ion affords benzoin as the product. This is areversible reaction .The cyanide ion serves three different purposes in the course of this reaction. It acts as a
nucleophile , facilitates proton abstraction, and is also theleaving group in the final step. The benzoin condensation is in effect adimerization 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.cope
The reaction can be extended to aliphatic aldehydes with base catalysis in the presence of
thiazolium salt s; the reaction mechanism is essentially the same. These compounds are important in the synthesis ofheterocyclic compounds . The addition is also possible withenone s; for instancemethyl vinyl ketone is a reagent in theStetter reaction .In
biochemistry , thecoenzyme thiamine is responsible for biosynthesis of acyloin-like compounds. This coenzyme also contains a thiazolium moiety, which ondeprotonation becomes a nucleophilic carbene.In one study, a custom-designed N-heterocyclic carbene (NHC, the framework is related to thiazolium salts) was found to facilitate an
enantioselective intramolecular benzoin condensation ("Scheme 2"). [cite journal | author = D. Enders, O. Niemeier and T. Balensiefer | title = Asymmetric Intramolecular Crossed-Benzoin Reactions by N-Heterocyclic Carbene Catalysis | year = 2006 | journal =Angewandte Chemie International Edition | volume = 45 | issue = 9 | pages = 1463–1467 | doi = 10.1002/anie.200503885 ]This finding was confirmed in another study with a slightly modified NHC using DBU as the base instead of
potassium tert-butoxide ("Scheme 3"). [cite journal | author = H. Takikawa, Y. Hachisu, J. W. Bode and K. Suzuki | title = Catalytic Enantioselective Crossed Aldehyde-Ketone Benzoin Cyclization | year = 2006 | journal =Angewandte Chemie International Edition | volume = 45 | issue = 21 | pages = 3492–3494 | doi = 10.1002/anie.200600268 ]References
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