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Molecular Diversity

, Volume 10, Issue 1, pp 17–22 | Cite as

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
Full-length paper

Abstract

Optimization of Radziszewski's four-component reaction employing a microwave-assisted protocol, led to a small library of 48 imidazoles with a success rate of 65% (conversion > 45%). All three diversity points of the four-component reaction were varied. Aromatic and aliphatic inputs were successfully implemented and mono-, di-, tri- and tetrasubstituted imidazoles with various substitution patterns were synthesized. Furthermore, unsymmetrical diketones could successfully be used which improved the intrinsic diversity of the method significantly. If the unsymmetrical diketone 1,2-phenylpropanedione (R1 and R2) was used two regioisomers were formed. Depending on the type of amine (R4) and aldehyde (R3) applied, regioselectivity was modest to good. Based on these results, a reaction mechanism is proposed.

Keywords

imidazoles multicomponent reaction microwave diversity library synthesis combinatorial chemistry 

Abbreviations:

MW

microwave

MCR

multicomponent reaction

EWG

electron withdrawing group

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Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  • E. Gelens
    • 1
  • F. J. J. De Kanter
    • 1
  • R. F. Schmitz
    • 1
  • L. A. J. M. Sliedregt
    • 2
  • B. J. Van Steen
    • 2
  • Chris G. Kruse
    • 2
  • R. Leurs
    • 1
  • M. B. Groen
    • 1
  • R. V. A. Orru
    • 1
  1. 1.Department of Chemistry, Faculty of Exact SciencesVrije UniversiteitAmsterdamThe Netherlands
  2. 2.Solvay Pharmaceuticals Research LaboratoriesWeespThe Netherlands

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