A resource-efficient and highly flexible procedure for a three-component synthesis of 2-imidazolines.
A multicomponent reaction between alpha-acidic isonitriles, primary amines, and carbonyl compounds was studied using 14 different solvents. Depending on the isocyanide that was used, optimal yields for the three-component synthesis of 2H-2-imidazolines were observed in different solvents. The solvents could be used as purchased, and in situ preformation of the imine was not required. By selecting the appropriate solvent, it was possible to considerably expand the range of compatible isocyanides toward less alpha-acidic isocyanides. Further process simplification was achieved by performing the reaction at higher concentrations and avoiding purification by column chromatography, resulting in a fast, easy to perform, and resource-efficient protocol for this three-component reaction.
Elders
Niels
N
Department of Organic and Inorganic Chemistry, Faculty of Sciences, Vrije Universiteit Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands.
Schmitz
Rob F
RF
de Kanter
Frans J J
FJ
Ruijter
Eelco
E
Groen
Marinus B
MB
Orru
Romano V A
RV
D000588:Amines / Q000737:chemistry; D002625:Chemistry, Organic / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002845:Chromatography / Q000379:methods; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry*; D048288:Imidazolines / Q000737:chemistry; D008956:Models, Chemical; D008968:Molecular Conformation; D015394:Molecular Structure; D009570:Nitriles / Q000737:chemistry; D012997:Solvents / Q000737:chemistry
D000588:Amines; D007093:Imidazoles; D048288:Imidazolines; D009570:Nitriles; D012997:Solvents; C017424:2-imidazoline