PREPARATION AND STRUCTURAL-PROPERTIES OF LARGE-CAVITY PERAZA MACROCYCLES CONTAINING PYRIDINE, PHENANTHROLINE, OR PIPERAZINE SUBCYCLIC UNITS

Ten large peraza macrocycles containing either two pyridine, two phenanthroline, or three, four, or six piperazine subcyclic groups have been prepared. Those containing pyridine or phenanthroline were prepared by reacting either 2,6-pyridinedicarbaldehyde or its dimethyl ketone analogue or 1,10-phenanthroline-2,9-dicarbaldehyde with the appropriate bisprimary amine to form the cyclic tetraSchiff base. Those macrocycles containing the piperazine units were prepared by the reaction of a crablike piperazine-containing bis(alpha-chloro amide) (formed from piperazine and 2 mol of chloroacetyl chloride) and piperazine to give tetrapiperazinoperaza-24-crown-8-tetramide, the 2:2 cyclization product, and hexapiperazinoperaza-36-crown-12-hexamide, the 3:3 cyclization product. The macrocyclic hexamide was fully reduced to form the hexapiperazino-36-crown-12 ligand. The reaction of equimolar amounts of the crablike piperazine-containing bis(alpha-chloro amide) and benzylamine gave N,N',N"-tribenzyltripiperazinoperaza-27-crown-9-hexamide. The structures of one of the diphenanthrolinoperaza-crowns and of the tetrapiperazinoperaza-24-crown-8-tetramide were determined by an X-ray crystallographic procedure. The diphenanthrolino-crowns contained water molecules as shown by their combustion analyses. These water molecules were replaced by solvent molecules as shown by two molecules of dimethylformamide in the solid-state structure of one phenanthrolino-crown. The dipyridinoperaza-crown formed a highly protonated ligand at neutral pH.