Efficient library synthesis of imidazoles using a multicomponent reaction and microwave irradiation.
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.
Gelens
E
E
Department of Chemistry, Faculty of Exact Sciences, Vrije Universiteit, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands.
De Kanter
F J J
FJ
Schmitz
R F
RF
Sliedregt
L A J M
LA
Van Steen
B J
BJ
Kruse
Chris G
CG
Leurs
R
R
Groen
M B
MB
Orru
R V A
RV
D000447:Aldehydes / Q000138:chemical synthesis* / Q000528:radiation effects; D020650:Combinatorial Chemistry Techniques; D007093:Imidazoles / Q000138:chemical synthesis*; D007659:Ketones / Q000138:chemical synthesis / Q000737:chemistry* / Q000528:radiation effects; D008872:Microwaves; D015394:Molecular Structure
D000447:Aldehydes; D007093:Imidazoles; D007659:Ketones