Compounds of amine-substituted cyclic amines: synthesis and structures

Cyclic tetra-amines with amine substituents on the central carbon atom of C-3 ring segments are readily prepared by reduction of nitro-substituted aza-macrocycles, formed by reactions of metal-ion amine compounds with formaldehyde and a nitro-alkane. Reactions of bis-(ethane-1,2-diamine)-copper(II) or -nickel(II) cations with formaldehyde and nitroethane form the trans (anti) and cis (syn) isomers of (6,13-dimethyl-6,13-di-nitro-1,4,8,11-tetra-azacyclotetradecane)-copper(II) or -nickel(II)) cations, which are readily reduced to form the trans and cis-6,13-diamino cations, from which the trans- and cis-amine substituted cyclic tetra-amines can be isolated. Similar reactions for the (3,7-diaza-nonane-1,9-diamine)-copper(II) or -nickel(II) cations lead to 6-methyl-1,4,8,11-tetra-azacyclotetradecane-6-amine. Amine-substituted cyclic tetra-amines with different ring sizes or alkyl substituents can similarly be prepared by using different diamines or alkyl-nitro compounds. This review is primarily about compounds formed by trans-6,13-diamino and 6-amino-1,4,8,11-tetraazacyclotetradecanes with d-transition-metal ions. The amines react with transition-metal ions in much the same manner as 1,4,8,11-tetraazacyclotetradecane (cyclam), forming compounds with isomeric configurations arising from the four chiral nitrogen centres of coordinated cyclam, the cis- or trans-configurations of the amine substituents and a form of geometrical isomerism arising from the relationship between the chiral coordinated cyclam configuration and the orientation of the substituents. The amine-substituted cyclams coordinate by the four cyclam nitrogen atoms, in planar or folded arrangements, and also by one or both of the amine substituents. Non-coordinated amine substituents can be protonated. The amine substituents can be modified by methylation, amide formation and reaction with aldehydes to form imines. The imines formed with functionalised aldehydes can be reduced to form variously functionalised secondary amine substituents. This all leads to complex coordination chemistry and X-ray crystallographic structure determinations have been critical in understanding the configurations present. Structures in the Cambridge Crystallographic Data Base of all relevant compounds are listed.