Imidazoles tetra-substituted synthesis

Acke DRJ, Orru RVA, Stevens CV (2006) Continuous synthesis of tri- and tetra-substituted imidazoles via a multicomponent reaction under microreactor conditions. QSAR Comb Sci 25 474-483 Antes J, Tuercke T, Marioth E, Lechner F, Scholz M, Schntirer F, Krause HH, Lobbecke S (2001) In Matlosz M, Ehrfeld W, Baselt JP (eds) IMRET 5 Proceedings of the Fifth International Conference on Microreaction Technology. Springer Berlin New York Heidelberg, pp 446 153 Barrow D, Cefai J, Taylor S (1999) Shrinking to fit. Chem Ind 15 591-594 Bradley D (1999) Chemical Reduction. Eur Chem 1 17-20 Chambers RD, Spink RCH (1999) Microreactors for Elemental Flourine. Chem Comm 10 883-884... 

Allthough this SPS route averted some of the problems inherent to the synthesis of substituted imidazoles via condensation approaches, the value of the synthesized libraries of compounds is of a limited interest for the histamine receptor research field. First, there is only a limited number of glyoxals, one of the four reaction components, available as precursor. Secondly, only tri- and tetra-substituted imidazoles can be prepared via this method. And finally, the linker (H0-C(=0)-(CH2)2-), a pharmacophore not common to histaminergic ligands, remains present in the final product. 

Safari J, Gandomi-Ravandi S, Akbari Z (2013) Sonochemical synthesis of 1,2,4,5-tetra-substituted imidazoles using nanocrystalline MgAl O as an effective catalyst. J Adv Res... 

The synthesis of tri- and tetra-substituted imidazoles catalyzed by unfunctionalized SBA-15 and witii 2,2,2-trifluo-roethanol (TFE) (SBA-15/TFE) was performed by Rostamnia et al. [97]. It seems that SBA-15 shows no acceptable reactivity in the course of this acid-catalyzed multicomponent reaction between aldehyde, amine, and ammonium acetate with benzil (20% yield in 30 min). However, the yield of imidazole increased when the medium of reaction changed from ethanol to TFE (45% yield in 30 min) (Figure 7). 

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