Synthesis of [2+2] Schiff base macrocycles by a solvent templating strategy and halogen bonding directed assembly

Schiff base imine condensations are a useful tool for macrocycle synthesis and applications within supramolecular chemistry. Here we address the mixtures of products that can arise from template free synthesis using dicarbonylheterocycles and diamines, and look to develop metal-free template methods for selective macrocycle formation. A range of alkyl α,ω-diamines were combined with phenanthroline and pyridine heterocyclic dicarbaldehydes under standard literature conditions. The reaction conditions were modified to demonstrate a relationship between choice of solvent and product equilibria. It was observed that benzene and toluene could shift a mixture of products and unreacted starting materials to form predominantly one imine product for a number of systems. Once the macrocyclic products had been characterized in selected solvents, iodinated halogen bonding guest molecules were added to direct macrocycle assemblies using non-covalent interactions. Studies to investigate host – guest suitability and halogen bond interactions were conducted, and it was found that tetraiodoethylene had an influence on the formation of a phenanthroline based macrocycle. Proof of concept experiments were performed to show the influence of the guest molecule, tetraiodoethylene, on the macrocyclic products formed under competitive dynamic combinatorial chemistry conditions.