Fluorine-based compounds are everywhere—from life-saving pharmaceuticals and crop protection agents to high-performance materials like Teflon and refrigerants. Thanks to their unique chemical properties, which make them indispensable across various industries. But synthesizing these compounds has long been a challenge due to the hazardous and toxic fluorinating reagents.
Hydrogen fluoride (HF) is one such reagent that is effective and inexpensive, but its high toxicity and corrosive nature make it extremely difficult to handle. In a recent breakthrough, researchers led by Professor Toshiki Tajima from Shibaura Institute of Technology, Japan, have developed a groundbreaking method to safely and efficiently generate HF from simple and stable materials—unlocking a safer path to fluorination chemistry. The study, made available online on April 22, 2025, and was published in Volume 31, Issue 32 of the journal Chemistry – A European Journal on June 6, 2025, unveils a cation exchange method to safely generate HF on demand.
Cation exchange reactions are chemical processes where positively charged ions are swapped between a solid porous material (usually a resin) and a salt solution. In the current study, the researchers used Amberlyst 15DRY, a commercially available solid acid resin, as the cation exchange resin and potassium fluoride (KF) which is a stable and inexpensive salt. By combining these solids in acetonitrile, they triggered a cation exchange reaction, which resulted in the quantitative production of HF without any external hazards.
"In a single step of the cation exchange reaction, we only generated 69% of HF from KF. But by removing the HF after each run and repeating the reaction seven times, we achieved nearly complete HF production from KF conversion," explains Prof. Tajima.
Once the reaction was complete, HF was separated from the resin, and organic amines were added to the HF solution in a 1:3 ratio. HF was immediately captured by these organic amines to form stable amine-3HF complexes. The complexes were then isolated by evaporating the solvent under reduced pressure. Amine-3HF complexes commonly act as nucleophilic fluorinating agents, i.e.; these complexes donate fluoride ions (F⁻) to other molecules while replacing another negatively charged leaving group (nucleophile) from those molecules.
These fluorination reactions are especially valuable for various applications in industries.
"Various HF complexes can be derived from HF," notes Prof. Tajima. "These complexes act as fluorinating agents and could enable the synthesis of novel pharmaceuticals, functional materials, and even molecular probes."
What sets this study apart is that it eliminates the use of pressurized HF gas and corrosive liquid reagents, making the process safer and more aligned with green chemistry principles. Also, the method operates under ambient conditions with common laboratory reagents without the use of any special equipment, making it suitable for both laboratory and industrial scales. Moreover, the resin used for the cation exchange reaction was effectively reused for almost over 10 times, marking the efficiency and sustainability of the approach.
The study marks a significant milestone in fluorination chemistry, opening avenues for multiple applications across various industries. The new fluorinating agents generated through the complexation could open multiple avenues for unique applications in pharmaceuticals, agrochemicals, and material sciences, all while ensuring a simpler, safer, and sustainable process of fluorination.
