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.

Binuclear and trinuclear complexes of exoO2-cyclam

“…14 Apart from our early report of the trinuclear Cu(II) species (2) however, there has been little further study of this readilyprepared class of trinuclear molecules. We therefore report here the systematic synthesis and study of a series of seven new (homo and hetero) trinuclear complexes (3)(4)(5)(6)(7)(8)(9). These include the first examples of metals other than Cu(II) within the macrocyclic cavity, namely the Co(II) and Zn(II) trinuclear complexes 3 and 4.…”

“…We and others have previously reported the synthesis and characterization of cyclam-based macrocyclic ligands that incorporate cis-exogenous oxygen atoms (hereafter referred to as exoO 2 ) arranged for chelation to a metal atom external to the macrocyclic ring. 6- 8 These macrocycles incorporate an oxamide-based bis-bidentate linker with deprotonatable amides and are related to amino acid based ligands. 9 Although bis-amide macrocycles have been widely studied [10][11][12] generally as precursors to saturated macrocycles (by reduction), only a small minority of those reported contain cis amides and the use of exogenous binding groups as bidentate linkers has been seldom utilized for the formation of multinuclear systems in macrocyclic chemistry.…”

Synthesis and characterization of N2S2-tin macrocyclic complexes of Co(II), Ni(II), Cu(II) and Zn(II)

“…A number of mixed donor macrocycles have been reported (Richard et al, 2004;Ilhan et al, 2007;Lindoy et al, 2013) incorporating N 2 S 2 , O 3 N 2 , O 2 N 3 , or N 4 S 2 donor sets, and investigation of the effects of incorporating a soft sulfur donor into a ligand framework containing harder nitrogen atoms is of great interest (Adhikari et al, 1997;Danks et al, 1998;Tavacoli et al, 2003;Quintana and Roglans, 2005). Although sulfides are generally treated as poor ligands to transition metal centers , recent studies (Bottino et al, 1976;Bruce et al, 1996;White et al, 2005) have proved that macrocyclic sulfides readily bind to transition metal ions to form stable complexes. Template synthesis is the organization of an assembly of atoms with respect to one or more geometric loci to achieve a particular linking of atoms.…”