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

Synthesis of 1,11-dithia-4,8-diazacyclotetradecane (L1), a constitutional isomer of the macrocyclic [14]­aneN2S2 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)2μ-Cl]­(ClO4)3. Multiple synthetic approaches are presented, supplemented with reaction methodology and reagent screening to access [14]­aneN2S2 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.