Debus–Radziszewski imidazole synthesis explained

The Debus–Radziszewski imidazole synthesis is a multi-component reaction used for the synthesis of imidazoles from a 1,2-dicarbonyl, an aldehyde, and ammonia or a primary amine. The method is used commercially to produce several imidazoles.^[1] The process is an example of a multicomponent reaction.

The reaction can be viewed as occurring in two stages. In the first stage, the dicarbonyl and two ammonia molecules condense with the two carbonyl groups to give a diimine:

In the second stage, this diimine condenses with the aldehyde:

However, the actual reaction mechanism is not certain.^{[2] [3]}

This reaction is named after Heinrich Debus^[4] and .^[5]

A modification of this general method, where one equivalent of ammonia is replaced by an amine, affords N-substituted imidazoles in good yields.^[3]

This reaction has been applied to the synthesis of a range of 1,3-dialkylimidazolium ionic liquids by using various readily available alkylamines.^[6]

Notes and References

1. Ebel, K., Koehler, H., Gamer, A. O., & Jäckh, R. "Imidazole and Derivatives." In Ullmann’s Encyclopedia of Industrial Chemistry; 2002 Wiley-VCH,
2. Microwave-Mediated Synthesis of Lophine: Developing a Mechanism To Explain a Product . R. David . Crouch . Jessica L. . Howard . Jennifer L. . Zile . Kathryn H. . Barker . J. Chem. Educ. . 2006 . 83 . 11 . 1658–1660 . 10.1021/ed083p1658 .
3. Efficient library synthesis of imidazoles using a multicomponent reaction and microwave irradiation . E. . Gelens . F. J. J. . De Kanter . R. F. . Schmitz . L. A. J. M. . Sliedregt . B. J. . Van Steen . Chris G. . Kruse . R. . Leurs . M. B. . Groen . R. V. A. . Orru . Molecular Diversity . 10 . 17–22 . 2006 . 10.1007/s11030-006-8695-3 .
4. Ueber die Einwirkung des Ammoniaks auf Glyoxal . . 10.1002/jlac.18581070209 . 1858 . Debus . Heinrich . 107 . 2 . 199–208.
5. Ueber Glyoxalin und seine Homologe . . 10.1002/cber.188201502245 . 1882 . Radzisewski . Br. . 15 . 2 . 2706–2708.
6. One-pot synthesis of symmetric imidazolium ionic liquids N,N-disubstituted with long alkyl chains . Giacomo . Damilano . Demian . Kalebić . Koen . Binnemans . Wim . Dehaen. RSC Adv. . 2020 . 10 . 21071-21081 . 10.1039/D0RA03358H . 9054310 .