Synthesis of ester derivatives of 1,4,7-triazacyclononane-1,4,7-tris(methylenephosphonic acid) and 1,4,7-triazacyclononane-1,4,7-tris(methyleneethylphosphinic acid)

Two methods have been developed for the synthesis of new 1,4,7-triazacyclononanetris(methylenephosphonic acid) (3-6, 8-11) and -tris(methyleneethylphosphinic acid) (7, 12) ester derivatives. The first procedure includes the synthesis of 2 in anhydrous THF which can then be used as a useful synthetic intermediate for several new derivatives of 1,4,7-triazacyclononane (1).In the second procedure, compound 1 and dialkyl phosphite or ethyl ethylphosphinate are reacted with paraformaldehyde in refluxing benzene yielding the corresponding esters in good to excellent yield. New macrocyclic complexing agents 8-12 have been prepared by either basic (8-11) or acidic (12) hydrolysis of the corresponding ester derivatives, or directly from the starting macrocycle 12. Side reactions decreasing the yield and purity of the products are also discussed.