Synthesis and characterization of various unsubstituted and mono-N-substituted tetraazamacrocycles

Abstract

Syntheses of tetraazamacrocycles have been carried out by using p-toluenesulfonyl chloride as protective group. The [14(ane) N4] and [15(ane) N4] were also obtained by the template synthesis. Mono-N-functionalization of tetraazamacrocycles was accomplished by reaction of a fivefold excess of the free macrocycles with 1 equivalent of a suitable alkylating or arylating reagent. The key point of the synthesis lies in the use of an excess of the macrocycle over the substituting reactants to reduce the formation of polysubstituted derivatives, and in the easy separation of the excess of unreacted macrocycle. All the products were characterized on the basis of spectral studies (1H and l3C NMR, including 2D NMR and NOE difference studies) and mass spectrometry. Keywords: tetraazamacrocycles, improved synthesis, protective group, N-tosylation, template synthesis, NOE difference spectroscopy.