Toward a perfect organic catalyst for green synthesis

Posted 31 August 2017

Demelza Lyons and Reece Crocker, PhD students from the Nguyen Group, demonstrate that tropylium salts, which have been largely neglected in organic synthesis since their discovery in 1891, are ideal Lewis acid catalysts for safe and efficient production of synthetic precursors to pharmaceutical agents.

The Nguyen group at UNSW Chemistry report that the unique aromatic seven-membered ring structure of tropylium ion confers the perfect balance of stability and reactivity that good catalysts need. This study is featured on the current cover of Green Chemistry journal.

[Image: “Superchemist” holds a tropylium ion shield to protect the “carbonyl compound” on his chest. Artwork by Demelza Lyons.]

“Tropylium ion has the perfect combination of reactivity to promote reactions, and stability to entice its regeneration for further reaction cycles,” says team leader Dr Vinh Nguyen.

Unlike traditional Lewis acid catalysts, which are usually metal or transitional metal cations, this organic catalyst would not leave behind trace metals in the synthesized product.

The chemical transformation tested in this study, as proof-of-concept for the new role of tropylium ion, was batch and flow acetalisation reaction. This is a frequently employed step in the synthesis of many pharmaceutical reagents. The acetal functionality protects the carbonyl group in the intermediates and end products from other chemical reactions during lengthy synthetic sequences.

Tropylium salts are not only the safer alternative to metal ion catalysts, they are more efficient than traditional Lewis acids, and can be use in solvent-free settings to minimize the environmental impact of synthesis. Since these organic catalysts can be easily synthesised in the laboratory, there is a great potential to bring down production costs.

This is the first time that tropylium salts have been used as Lewis acid catalysts. Organic catalysts are largely considered unsuitable for this type of synthetic reaction because they are generally unstable compared to metal and transition metal cation catalysts.

“Other organic ions don’t have the same versatility as tropylium ion – to be stable and reactive at the same time,” says Nguyen.

The Nguyen group plan to explore the synthetic utilities of this organic catalyst beyond Lewis acid catalysis.

“This is a really simple project, but it opens up a whole new concept in organic chemistry,” says Nguyen.



This research was highlighted in Chemical & Engineering News by Stephen Ritter, and in the Green Chemistry blog.