Synthesis of nitrogen and sulfur macrocycles with cis exogenous oxygen and sulfur donor atoms

Abstract

A series of new N₄ and N₈ macrocycles has been prepared, that includes cis-exogenous O₂, S₂ and S/O atoms to allow chelation to a metal external to the macrocyclic ring. We found that thioamide units within the macrocycles were unstable to attack by secondary amines and thus alkylated precursors containing only tertiary amines could lead to exogenous-S₂ macrocycles. Cyclisation of alkylated tetraamine precursors with dimethyloxalate or dithiooxamide led to both N₄ and N₈ macrocycles via 1 + 1 and 2 + 2 cyclisation reactions with exogenous-O₂ or S₂ respectively. Alkylation of preformed exogenous-O₂ macrocycles was explored and led to alkyl substitution at the secondary amine nitrogens in the ring, however synthesis of these species was overall lower yielding than cyclisation using alkylated tetraamine precursors. Thionation of an exo-O₂ macrocycle using an analogue of Lawesson's Reagent led to formation of the analogous exogenous-S₂ and exogenous-O,S macrocycles. Related S₂N₂ macrocycles with exogenous-O₂ were prepared by a cyclisation route but could not be isolated free of larger ring analogues.