title: Efficient library synthesis of imidazoles using a multicomponent reaction and microwave irradiation.
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.
authors.affiliation: Department of Chemistry, Faculty of Exact Sciences, Vrije Universiteit, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Gelens
authors.forename: F J J
authors.initials: FJ
authors.lastname: De Kanter
authors.forename: R F
authors.initials: RF
authors.lastname: Schmitz
authors.forename: L A J M
authors.initials: LA
authors.lastname: Sliedregt
authors.forename: B J
authors.initials: BJ
authors.lastname: Van Steen
authors.forename: Chris G
authors.initials: CG
authors.lastname: Kruse
authors.forename: R
authors.initials: R
authors.lastname: Leurs
authors.forename: M B
authors.initials: MB
authors.lastname: Groen
authors.forename: R V A
authors.initials: RV
authors.lastname: Orru
mesh_terms: 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
chemical_list: D000447:Aldehydes; D007093:Imidazoles; D007659:Ketones