Regioselective N-Functionalization of Tetraazacycloalkanes

Bisaminal type compounds obtained by condensation of pyruvic aldehyde with the suitable open-chain tetraamine followed by cyclization with either dibromoethane or dibromopropane can be
regioselectively quaternized by a wide range of alkylating agents. Removal of the bisaminal bridge
yields the monosubstituted tetraazamacrocycle or bismacrocycle. Further functionalization allows
the preparation of bifunctional ligands or trisubstituted macrocycles. The structure of six compounds
was solved by X-ray diffraction, and the unexpected results are rationalized according to the
molecular modeling calculations.