Simple and high yielding regioselective synthesis of 1,4,8-tri(carbamoylmethyl)-1,4,8,11-tetraazacyclotetradecane hydroiodide

Near quantitative synthesis of 1,4,8-tris(carbamoylmethyl)-1,4,8,11-tetraaz acyclotetradecane hydroiodide (1) has been achieved by reacting the parent macrocycle 1,4,8,11-tetraazacyclotetradecane (cyclam) with iodoacetamide in acetone in the presence of diisopsopylethylamine as a base. The reaction s tops at the trisubstituted stage even in the presence of a large excess of the reactants. This process represents the first example of a solubility co ntrolled regioselective synthesis of a polyazamacrocyclic complexing agent; the driving force is the exceptionally low solubility of 1 in the reaction medium. 1 was hydrolyzed in acidic medium to the corresponding acetate der ivative 1,4,8-tris(carboxylmethyl)-1,4,8,11-tetraazacyclotetradecane (2) in high yield. (C) 1998 Elsevier Science Ltd. All rights reserved.