Metal complexes with macrocyclic ligands,XVII. Synthesis of two key intermediates for the preparation of mono-N-functionalized tetraazamacrocycles and their metal complexes

With a modification of the cyclization procedure of Richman & Atkins [8] the two macrocycles 1,4,7-tritosyl-11-benzyl-1,4,7,11-tetraazacyclotetradecane ( 8 ) and 1,7,11-tritosyl-4-trityl-1,4,7,11-tetraazacyclotetradecane ( 15 ) were prepared. After selective cleavage of the benzyl and trityl group, respectively, one obtains the two key products 1,4,7-tritosyl-11-benzyl-1,4,7,11-tetraazacyclotetradecane ( 9 ) and 1,7,11-tritosyl-4-trityl-1,4,7,11-tetraazacyclotetradecane ( 16 ) which have three N-atoms protected by tosyl groups and one accessible for further reactions. To test some of the possibilities we have alkylated 9 and 16 with iodoacetamide, 1-tosyl-aziridine and acrylonitrile. After detosylation with HBr in glacial acetic acid in the presence of phenol mono-N-functionalized tetraazamacrocycles were thus obtained. The advantage of this synthesis is that the cyclization which is the most difficult step of the whole procedure, has to be done only once, regardless of the nature of the pendant arm. In addition a large number of derivatives can be prepared by varying the alkylation component. With Ni²⁺, Cu²⁺ and Zn²⁺ metal complexes of these new ligands were prepared and their IR. and VIS. spectra studied. In the case of the carbamoyl derivatives 12, 14 and 18 the Cu²⁺-complexes exist in two forms. Whereas at low pH the carboxamide group of the pendant arm is probably not bound to the metal ion, at high pH after deprotonation it coordinates in one of the axial positions.