I. Lazar, Simple and high yielding regioselective synthesis of 1,4,8-tri(carbamoylmethyl)-1,4,8,11-tetraazacyclotetradecane hydroiodide, TETRAHEDR L, 40(2), 1999, pp. 381-382
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.