3-Hydroxypropylation of tetraazamacrocycles and its effect on the stability of divalent metal complexes

Abstract

Reaction of trimethylene oxide (oxetane) with 1,4,7,10-tetraazacyclododecane (cyclen) or 1,4,8,11-tetraazacyclotetradecane (cyclam) in an autoclave at ca. 150°C has been used to develop syntheses for new pendant 3-hydroxypropyl macrocycles. Tetrakis(3-hydroxypropyl)-cyclen and -cyclam can be formed quantitatively if a 4:1 ratio of trimethylene oxide/macrocycle is employed, and 1-(3-hydroxypropyl)cyclen, 1,4-bis(3-hydroxypropyl)cyclen and 1-(3-hydroxypropyl)cyclam can be isolated in reasonable yield following simple separation procedures if a lower ratio is used. The protonation constants for these ligands and the formation constants for their Co(II), Cu(II), Zn(II), Cd(II) and Pb(II) complexes have been determined by potentiometric titration and are reported. There is a decrease in both the ligand basicity and the stability of the metal complexes with increasing extent of 3-hydroxypropylation, which is attributed to the presence of intramolecular hydrogen bonds between the pendant hydroxyl groups and ring amines, similar to those known to exist in the solid state.