Metal-Templated Macrocycle Synthesis in an Ionic Liquid: A Comparison With Reaction in Protic Solvents

Metal-directed macrocyclization reactions of [Cu(diamine)2]2+ (diamine = ethane-, propane-, and trans-cyclohexane-1,2-diamine, and propane-1,3-diamine) and [Co(ethane-1,2-diamine)3]3+ with formaldehyde and a nitroalkane carbon acid were examined for the first time in an ionic liquid solvent (1-butyl-3-methylimidazolium tetrafluoroborate), and compared with outcomes in molecular solvents. Products were identical and overall yields similar in ionic liquid and protic solvents. However, two important advantages were defined with the ionic liquid solvent: first, macrocycles form almost exclusively, rather than the mixture of macrocyclic and acyclic products formed in protic solvents; second, larger ring (16- vs. 14-membered) macrocycles form in much higher yield in ionic liquid.