Synthesis, Characterization, and Copper(II) Chelates of 1,11-Dithia-4,8-diazacyclotetradecane

Abstract

Synthesis of 1,11-dithia-4,8-diazacyclotetradecane (L1), a constitutional isomer of the macrocyclic [14]aneN 2 S 2 series, is accompanied with reaction and method optimization. Chelation of L1 with copper(II) provided assessment of lattice packing, ring contortion, and evidence of conformational fluxionality in solution through two unique crystal structures: L1Cu(ClO4) 2 and [(L1Cu) 2 μ-Cl](ClO 4 ) 3 . Multiple synthetic approaches are presented, supplemented with reaction methodology and reagent screening to access [14]aneN 2 S 2 L1. Reductive alkylation of bis-tosyl-cystamine was integrated into the synthetic route, eliminating the use and isolation of volatile thiols and streamlining the synthetic scale-up. Late-stage cleavage of protecting sulfonamides was addressed using reductive N−S cleavage to furnish macrocyclic freebase L1.

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“…The Cu–N (2.03 Å), Cu–S (2.33 Å) and Cu–O (2.51 Å) bond distances are consistent with bond parameters for related copper( ii ) complexes (Table S2†). 44,46,49…”

“…2A and S2 †). 44,46,49 The corresponding copper(II)-cyclam complexes (3 and 4, Fig. 1) were also prepared using the same protocol employed for 1 and 2, with cyclam as the coordinating ligand.…”