Multicomponent synthesis of 2-imidazolines.
[reaction: see text] A multicomponent reaction (MCR) between amines, aldehydes, and isocyanides bearing an acidic alpha-proton gives easy access to a diverse range of highly substituted 2-imidazolines. The limitations of the methodology seem to be determined by the reactivity of the isocyanide and by the steric bulk on the in situ generated imine rather than by the presence of additional functional groups on the imine. Less reactive isocyanides, for example p-nitrobenzyl isocyanide 25a, react successfully with amines and aldehydes, using a catalytic amount of silver(I) acetate. Some of the resulting p-nitrophenyl-substituted 2-imidazolines undergo air oxidation to the corresponding imidazoles. Differences in reactivity of the employed isocyanides are explained with use of DFT calculations. Difficult reactions with ketones instead of aldehydes as the oxo-compound in this MCR are promoted by silver(I) acetate as well.
Bon
Robin S
RS
Department of Chemistry, Faculty of Sciences, Vrije Universiteit Amsterdam, De Boelelaan 1083, 1081 HV, Amsterdam, The Netherlands.
van Vliet
Bart
B
Sprenkels
Nanda E
NE
Schmitz
Rob F
RF
de Kanter
Frans J J
FJ
Stevens
Christian V
CV
Swart
Marcel
M
Bickelhaupt
F Matthias
FM
Groen
Marinus B
MB
Orru
Romano V A
RV