Being structurally simple, symmetrical, and polyfunctional, cyclen has been widely investigated.

Illustrative is the reaction of the deprotonated tosylamides with ditosylates:[2] The resulting macrocycle can be deprotected with strong acid.

High dilution conditions result in a low reaction rate penalty and this disadvantage is removed in an alternative procedure starting from triethylenetetraamine and dithiooxamide to a bisamidine – also a bis(imidazoline) – followed by reduction and ring expansion with DIBAL.

[5][6] With a 12-membered ring, it tends to bind to four contiguous sites on octaheral metal centers.

In contrast the larger cyclam ligand tens to form attach to four coplanar sites.