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Efficient library synthesis of imidazoles using a multicomponent reaction and microwave irradiation

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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.

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Abbreviations

MW:

microwave

MCR:

multicomponent reaction

EWG:

electron withdrawing group

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Exact Sciences, Vrije Universiteit, De Boelelaan 1083, 1081 HV, Amsterdam, The Netherlands

    E. Gelens, F. J. J. De Kanter, R. F. Schmitz, R. Leurs, M. B. Groen & R. V. A. Orru

  2. Solvay Pharmaceuticals Research Laboratories, Weesp, The Netherlands

    L. A. J. M. Sliedregt, B. J. Van Steen & Chris G. Kruse

Authors
  1. E. Gelens
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  2. F. J. J. De Kanter
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  3. R. F. Schmitz
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  4. L. A. J. M. Sliedregt
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  5. B. J. Van Steen
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  6. Chris G. Kruse
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  7. R. Leurs
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  8. M. B. Groen
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  9. R. V. A. Orru
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Corresponding author

Correspondence to R. V. A. Orru.

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Gelens, E., Kanter, F.J.J.D., Schmitz, R.F. et al. Efficient library synthesis of imidazoles using a multicomponent reaction and microwave irradiation. Mol Divers 10, 17–22 (2006). https://doi.org/10.1007/s11030-006-8695-3

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  • DOI: https://doi.org/10.1007/s11030-006-8695-3

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