Scalable synthesis of multi-substituted aryl-phosphonates: Exploring the limits of isoretical expansion and the synthesis of new triazene-based phosphonates

Abstract

The development of novel multi-substituted aryl-phosphonate compounds offers promise as new building blocks for metal-organic frameworks (MOFs) materials with excellent properties in regards to porosity and gas sorption. We demonstrate the efficiency of the palladium-catalyzed Hirao cross-coupling reaction in the synthesis of substituted phosphonates; however, attempts to prepare derivatives with isoretical expansion through the cyclization of 4-(4′-bromophenyl)acetophenone resulted in an extremely low yield, with the isolation of the dimer intermediate. Ab initio calculations showed that while the trimerization of acetophenone is exothermic, that of 4-phenyl acetophenone is endothermic. By contrast, the cyclization of 4-(4′-bromophenyl)benzonitrile is exothermic and allows for the formation of the appropriate phosphonic acid. The benzonitrile methodology also allows for the formation of ortho methyl derivatives with high steric hindrance. All the multi-substituted aryl-phosphonate compounds reported herein can be prepared on a multi gram scale enabling researchers a wider range of building blocks for phosphonate MOFs.

Graphical Abstract

Keywords:

• Aryl-phosphonate
• coupling
• palladium
• catalyst

Additional information

Funding

Financial support was provided by the Air Force Institute of Technology Civilian Intuition Program (AFIT CIP) and the Reduce Industrial Carbon Emissions (RICE) research operations funded by the Welsh European Funding Office (WEFO) through the Welsh Government.