Carboxymethylation of cage amines: control of alkylation by metal ion coordination

Reactions between chloroacetate and both "free" and coordinated forms of the cage amine diaminosarcophagine (1,8-diamino-3,6,10,13,16,19-hexaazabicyclo[6.6.6]icosane) result in the introduction of between one and four pendent carboxymethyl substituents on the nitrogen atoms of the cage. While at least the first two steps in the reaction of the free ligand have been found to involve only the secondary nitrogen centers, in both the Cu(II) and Co(III) complexes alkylation occurs only at the primary (1,8) centers, the greater ease of achieving a higher degree of alkylation of the Cu(II) complex being attributed to the lower charge of this species causing a lesser reduction of the nucleophilicity of the uncoordinated primary nitrogen atoms. All the new ligands have been characterized by X-ray structure determinations of their Cu(II) or Co(III) complexes. In some cases, this has shown that the methods used to isolate the crystalline complexes result in lactamization of the ligand.