Defect-Engineered Metal-Organic Frameworks as Bioinspired Heterogeneous Catalysts for Amide Bond Formation.

Area of Science:

• Materials Science
• Organic Chemistry
• Catalysis

Background:

• Amide synthesis is crucial in medicinal chemistry but often relies on wasteful stoichiometric reagents.
• Current catalytic methods for amide coupling have limitations in scope and recyclability.
• Nature utilizes cooperative Lewis/Brønsted acid/base catalysis for amide bond formation, inspiring new synthetic strategies.

Purpose of the Study:

• To develop a recyclable heterogeneous catalyst for efficient amide bond formation.
• To address the limitations of existing stoichiometric and catalytic amide coupling methods.
• To explore defect engineering in metal-organic frameworks (MOFs) for enhanced catalytic activity.

Main Methods:

• Synthesized a defective metal-organic framework, MOF-808-py-Nox, by colocalizing Lewis acidic Zr sites with pyridine N-oxide.
• Utilized density functional theory (DFT) calculations to understand the catalytic mechanism.
• Tested the catalyst's performance in amide bond formation from various precursors and assessed its recyclability and suitability for continuous flow.

Main Results:

• MOF-808-py-Nox demonstrated broad functional group compatibility for synthesizing amides from amines and carboxylic acids, esters, or primary amides.
• DFT calculations indicated that a hydrogen-bonding network at defect sites facilitates amide bond formation.
• The catalyst was recycled at least five times without significant loss of activity, crystallinity, or porosity, and was effective in continuous flow.

Conclusions:

• Defect engineering in MOFs provides a viable strategy for creating highly active and recyclable heterogeneous catalysts.
• MOF-808-py-Nox offers a sustainable alternative for amide synthesis in medicinal chemistry and beyond.
• The defect engineering approach is generalizable for creating diverse MOF-based catalysts with colocalized active sites.