High-Yielding Flow Synthesis of a Macrocyclic Molecular Hinge

Area of Science:

• Supramolecular Chemistry
• Organic Synthesis
• Materials Science

Background:

• Molecular machines often utilize modular components like axles and wheels.
• Existing molecular hinges primarily rely on dihedral rotations, not clamp-like mechanisms.
• There is a need for molecular hinges that mimic macroscopic hinged devices.

Purpose of the Study:

• To design and synthesize novel macrocyclic compounds that function as clamp-like molecular hinges.
• To develop a scalable and efficient synthetic route for these macrocycles.
• To explore the potential applications of these molecular hinges in advanced materials.

Main Methods:

• Synthesis of two isomeric macrocycles via a one-pot addition cyclization reaction.
• Characterization of macrocycle structures and conformational behavior using NMR spectroscopy.
• Development of a semicontinuous flow synthesis optimized for yield and selectivity.
• Investigation of guest encapsulation properties and chemical inertness.

Main Results:

• Two isomeric macrocycles with distinct open and closed clamp-like geometries were synthesized.
• The macrocycles interconvert freely in solution and can be produced on a multigram scale efficiently.
• A semicontinuous flow synthesis achieved high conversions (85-93%) and selectivity (>80%).
• The macrocycles possess sterically protected voids, demonstrating inertness to reactive species like fluoride ions.

Conclusions:

• The synthesized macrocycles represent a new class of molecular hinges with clamp-like functionality.
• The efficient and scalable synthesis facilitates their use in constructing complex molecular systems.
• These chemically inert hinges are promising building blocks for adaptive supramolecular receptors and flexible porous materials.