T~wuhedron Lam. Vol. 36, No 51, pp. 9269-9272, 199.5 Elsevier Saence Ltd Prmtai tn Great Britain 0040-403Y/YS $9.50+0.00 0040-4039 (9.5)02009-8 A General Synthesis of Mono- and Disubstituted 1,4,7-Triazacyclononanes Zoltan Kovacs and A Dean Sherry* Depanment of Chemistry. Unncrslty of Texas at Dallas, P 0 Box 830688. Ekhardson. Texas 750X7-0688 Abstract I.J.7-Tnalac!clononalle reacts sclcct~vel~ vtth 2-(t-butoxycarbonyloxyimtno)- and 2-(benz~lox~carbon~lo~~tm~no)-2-phen~laceton~tr~le to gne I.&dlprotected dertvatives which could be comerted to mono and dlsubstltuted trla/acyclononanes Numerous derivatives of triazacyclononane contarntng more than one type of functionalized side-chain have appeared in the recent literature ’ The synthetic routes to these derivatives usually involve either reacting the amine in excess and isolating a monoprotected derivative, protecting via N-formylation,’ or selective detosylation ’ Interest in the coordination chemistry of these compounds ranges from models of protein active sites to centers for molecular recognition We have an interest in using these systems for monitoring free Mg’- concentrations by “P NMR in brological tissues ’ Thus, it is important for our work to not only introduce a variety of different coordinating srde-chain groups to fine tune the Mg2’ binding constant but also to prepare such ligands in large quantities for ultimate use irr VIVO Recently we reported a general. high yield synthesis of I .7-disubstituted 1,4,7,10-tetraaza- cyclododecanes through the 1.7-biscarbamate dertvatrves ’ Regioselective diprotection was achieved by reacting the tetramine with different chloroformates m acid solution (pH-2-3) Unfortunately, when the selective protection of triazacyclononane was attempted under these conditions, a mixture of products were obtained Several other reagents used for the prepat-ation of carbamates were tried We have found that the free triamme reacts with exactly two equivalents of 7-(t-butoxvcarbonyloxyimino)-2-phenylacetonitrile (BOC- ON)6 and 2-(benzyloxycarbonylo\cyimino)-2-phen~lacetonltrile (Z-ON)’ in chloroform under anhydrous conditions to give high yields (>90%) of the diprotected dertvatives I and 3 (Scheme 1). At present the reason for the high selectivity is unclear When the reaction was run with one equivalent of the reagent a mixture of unreacted triamine. mono- and diprotected derivatives was isolated As the )1f>O