Simple method converts fluorspar into fluorochemicals

A safer and more sustainable way of producing fluorination reagents directly from the mineral fluorspar could help the chemical industry overcome its reliance on hydrogen fluoride (Nature 2024, DOI: 10.1038/s41586-024-08125-1).

“Hydrogen fluoride is probably one of the most dangerous chemicals that you can manufacture,” says Véronique Gouverneur of the University of Oxford, who led the research. “The ambition is to transform the way fluorochemicals are produced.”

Fluorochemicals are widely used in products such as pharmaceuticals, refrigerants, and lithium-ion batteries, and all their fluorine atoms originate from fluorspar, the mineral form of calcium fluoride. The chemical industry treats fluorspar with concentrated sulfuric acid at temperatures above 300 °C to produce hydrogen fluoride (HF), which serves as the feedstock for other fluorinating reagents.

But making HF is energy intensive, and the chemical is highly toxic and difficult to handle—leaks have caused fatal accidents and environmental pollution incidents, for example. “The dream is to use fluorspar in any lab and prepare any fluorochemical from that rock so there’s no dependence on the complex supply chain for HF,” Gouverneur says.

Last year, Gouverneur’s team unveiled a mechanochemical method that converted fluorspar directly into a new phosphate-based reagent that could fluorinate a wide range of organic molecules (Science 2023, DOI: 10.1126/science.adi1557). But relatively few labs have access to the required mechanochemistry equipment, and the reagent was not suitable for making some fluoroarenes commonly found in pharmaceuticals and agrochemicals.

Now the team has developed a more accessible approach that can make conventional fluorinating reagents from fluorspar under very mild conditions. The researchers mix fluorspar with oxalic acid and a Lewis acid such as boric acid in water at 50 °C, forming calcium oxalate, which precipitates from solution and drives the reaction forward. Meanwhile, HF formed by the reaction is immediately captured by boron to form fluoroboric acid in 96% yield. As long as the fluorophilic Lewis acid is present, no free HF can be detected in the reaction mixtures.

Using silicon dioxide as the Lewis acid produced fluorosilicic acid, which could be converted into other fluorinating reagents, such as potassium fluoride or tetramethylammonium tert-amyl alcohol fluoride. The team used this range of reagents to fluorinate various arenes, producing molecules that can be used as building blocks in common drugs.

“This follow-up work is much more practical in terms of making what everybody uses already, without going through HF,” says Tobias Ritter, who works on fluorination chemistry at the Max Planck Institute for Kohlenforschung and was not involved in the research. “I think it’s fantastic.”

The researchers’ method even worked with a lower grade of fluorspar called metspar, which contains about 85–90% calcium fluoride. And Gouverneur points out that oxalic acid, a solid, not only is easier to handle than concentrated sulfuric acid but also offers a sustainability advantage because it can be produced from captured carbon dioxide or from biomass, whereas sulfuric acid is a by-product of fossil fuel extraction.

Gouverneur acknowledges that some applications, like glass etching, will still require HF, but she believes it should be possible to use alternative fluorinating reagents in most of the chemical reactions that currently use HF. In 2022, she cofounded a spin-off company called FluoRok to develop and scale up sustainable fluorochemical production from fluorspar.

“This has the potential to change the chemical industry, and I think it’s very likely that some sort of incarnation of this method will be used in the future,” Ritter says.