Efficient library synthesis of imidazoles using a multicomponent reaction and microwave irradiation |
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| Authors: | 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 |
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| Institution: | (1) Department of Chemistry, Faculty of Exact Sciences, Vrije Universiteit, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands;(2) Solvay Pharmaceuticals Research Laboratories, Weesp, The Netherlands |
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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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| Keywords: | imidazoles multicomponent reaction microwave diversity library synthesis combinatorial chemistry |
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