Green chemistry milestone: fluorine complexes from common fluoride salt
Researchers from Japan develop a safer method for the synthesis of fluoride complexes for electrochemical fluorination
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The reaction between KF and NBR in HFIP forms Bu4NF(HFIP)3 complex through ion exchange
Credit: Professor Toshiki Tajima from Shibaura Institute of Technology, Japan
Chemical synthesis lies at the heart of modern science and technology, enabling the creation of various pharmaceuticals, agrochemicals, and functional materials. While the demand for chemical synthesis grows with scientific advancements, it comes with the costs of environmental pollution and hazardous waste. To combat the same, researchers are now turning towards sustainable alternatives using green chemistry approaches.
One such chemical process which is in urgent need for greener alternatives is fluorination. Fluorine-based organic compounds find applications in a variety of industries, ranging from pharmaceuticals to electronics. These compounds are synthesized through the process of fluorination using different fluorinating agents like potassium fluoride (KF) and quaternary ammonium fluorides like tetrabutylammonium fluoride (Bu4NF). While these reagents are promising, their reactivity is often hindered due to low solubility (as in the case of KF) and high hygroscopicity (seen in Bu4NF). This calls for the development of novel fluorinating agents with suitable properties and better reactivity.
Against this backdrop, a team of researchers led by Professor Toshiki Tajima from Shibaura Institute of Technology, Japan, came up with an exciting solution. The team developed a new fluorinating quaternary ammonium complex by combining KF with tetrabutylammonium bromide (Bu4NBr). The newly formed quaternary ammonium tri(1,1,1,3,3,3-hexafluoroisopropanol)-coordinated fluoride (Bu4NF(HFIP)3) showed extremely low hygroscopicity and was found to be an excellent fluorinating reagent for electrochemical fluorination. The findings were made available online on April 29, 2025, and published in Volume 61, Issue 42 of Chemical Communications on May 25, 2025.
“KF is a safe, affordable fluorinating agent, but its poor solubility in organic solvents has limited its use. We had been exploring ways to make it more effective,” explains Prof. Tajima. “It all clicked only after we discovered it readily dissolves in HFIP."
To develop the fluorinating complex, the team started by dissolving KF in HFIP and Bu4NBr in dichloromethane, respectively. Once dissolved, both solutions were mixed together for 30 minutes and were then subjected to filtration and purification. The resultant product was a viscous and clear liquid of Bu4NF(HFIP)3. The chemical composition of the product was confirmed through NMR spectroscopy studies. Furthermore, the approach was also applied to other quaternary ammonium bromides for synthesis of different reagents.
The resultant products showed low hygroscopicity, which is favorable for a greater shelf life. Additionally, the synthesis only involved a basic ion exchange reaction using KF which makes the method simpler and inexpensive. Moreover, the method is also safer compared to other synthesis methods, making it a greener alternative for fluorination.
“The new fluorinating agent we developed in this study can have a range of applications in the synthesis of pharmaceuticals, agrochemicals, functional materials, molecular probes for PET inspection, and many more...” remarks Prof. Tajima.
Many industries use fluorinating agents for the synthesis of organofluorine compounds. Having a safer fluorinating reagent that is easier to handle could be a game-changer and is a significant milestone in the field of green chemistry. By overcoming the limitations of two different fluorinating reagents to form a novel fluorinating agent, the research has bridged a critical gap in the process of fluorination, opening avenues for sustainable and effective synthesis strategies.
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Reference
DOI: 10.1039/d5cc01341k
About Shibaura Institute of Technology (SIT), Japan
Shibaura Institute of Technology (SIT) is a private university with campuses in Tokyo and Saitama. Since the establishment of its predecessor, Tokyo Higher School of Industry and Commerce, in 1927, it has maintained “learning through practice” as its philosophy in the education of engineers. SIT was the only private science and engineering university selected for the Top Global University Project sponsored by the Ministry of Education, Culture, Sports, Science and Technology and had received support from the ministry for 10 years starting from the 2014 academic year. Its motto, “Nurturing engineers who learn from society and contribute to society,” reflects its mission of fostering scientists and engineers who can contribute to the sustainable growth of the world by exposing their over 9,500 students to culturally diverse environments, where they learn to cope, collaborate, and relate with fellow students from around the world.
Website: https://www.shibaura-it.ac.jp/en/
About Professor Toshiki Tajima from SIT, Japan
Dr. Toshiki Tajima is a Professor at the College of Engineering, Shibaura Institute of Technology, Japan. He earned his doctorate from the Interdisciplinary Graduate School of Science and Engineering, Tokyo Institute of Technology, and specializes in organic electrochemistry and synthesis. He has over 56 peer-reviewed publications and over 11 book chapters to his credit. His research mainly focuses on green chemistry, environmental chemistry, and sustainable sciences.
Journal
Chemical Communications
Method of Research
Experimental study
Subject of Research
Not applicable
Article Title
Facile synthesis of R4NF(HFIP)3 complexes from KF and their application to electrochemical fluorination
Hidden role of hydrogen - Unlocking the roar of heavy metal atom
Institute of Physical Chemistry of the Polish Academy of Sciences
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Bromine and hydrogen play unexpected roles in the dissociation dynamics of triazole anions. The findings provide new insights into the behavior of transient negative ions. Photo taken thanks to the ActiveZone fitness club. Photo courtesy: Grzegorz Krzyzewski
view moreCredit: Source IPC PAS, Grzegorz Krzyzewski
Hydrogen interactions play a crucial role in organic chemistry. The position of hydrogen in many molecules can completely change what happens to the other atoms in the rings. The international research team, led by Dr. Dariusz Piekarski from the Institute of Physical Chemistry, Polish Academy of Sciences, and Dr. Jaroslav Kočišek from the Czech Academy of Sciences, explored the role of hydrogen in the molecules under the hit with low-energy electrons, revealing mechanisms behind it. Their study helps us to understand how small changes in molecule structure affect the dynamics of the molecular target, i.e., particular breaking of it, which is important for both environmental cleanup and designing new materials. Let’s take a closer look at their studies.
Imidazoles and triazoles are essential chemical compounds used in many medicines, including drugs used to defeat various pathogen-induced infections and cancer. Besides these applications, both imidazoles and triazoles are used not only in humans but also to protect crops against fungi. However, despite their high effectiveness, they can easily end up in water or soil leading to environmental pollution and uncontrolled development of fungi resistant to fungicides. Removing these chemicals from the environment is far from easy for the high stability of the compounds. Therefore, novel ways to degrade imidazoles and triazoles are widely studied to improve and deeply understand the mechanisms that stand behind the bonds breaking in both compounds, especially in developing effective wastewater treatment. To control the structure of obtained molecules under the application of external stimuli the mechanistic insight for the detailed description on a molecular level is needed.
Recent study published in the prestigious Journal of the American Chemical Society (JACS) by international research team, led by Dr. Dariusz Piekarski from the Institute of Physical Chemistry, Polish Academy of Sciences and Dr. Jaroslav Kočišek from the Czech Academy of Sciences presents the significant advancement for molecular chemistry revealing the role of hydrogen and bromine in the dissociation dynamics of triazole anions. Researchers shows in details how to break these molecules is using low-energy electrons. How does it work?
When a compound like triazole captures one of these low-energy electrons, it forms a short-lived charged version of itself that finally breaks up. But not all triazoles undergo such a reaction in the same way. This process depends on the molecular structure, especially the position of hydrogen atoms. In the present study, researchers looked at two versions of a bromine-substituted triazole. Researchers employed dissociative electron attachment (DEA) to study the behavior of the specific site in two nearly identical molecules like 3-bromo-1H-1,2,4-triazole and 3-bromo-4H-1,2,4-triazole (4HBrT) that differ only in the position of one hydrogen atom, under the exposition to low-energy electrons.
By combining of the empirical studies with sophisticated theoretical calculations based on the potential energy surfaces, molecular dynamics, and analytic continuation methods they tracked the atoms position change and the lifetimes of transient negatively charged molecules with remarkable precision. Such combining of experiment with quantum chemistry shows that hydrogen position change has a direct influence on the molecule dynamics after an interaction with low-energy electrons, where even single electron induces subtle structural difference resulting in dramatic different molecular dynamics. This is how it works. Hydrogen position controls the character of the resonant states. While the singly occupied molecular orbital SOMO of 1HBrT is highly symmetric with a short lifetime against both dissociation of bromine or loss of electron, the 4HBrT SOMO state is asymmetric, resulting in induced dance of the bromine atom around the rest of the molecule.
Quantum chemical calculations show that bromine migrates more easily when the hydrogen is in the 4-position than an 80 times lighter hydrogen atom, forming a stable noncovalent complex around the triazole ring. The hydrogen position defines whether the bromine atom will move around a molecule or break away directly during a molecular breakup reaction. For 4HBrT, the dissociation of the bromine atom proceeds via a delayed mechanism, where the bromine forms temporarily weakly bonded species, stabilizing the transient negative ion and elongating its lifetime. This results in an intermediate metastable state before hydrogen bromide (HBr) is formed. In contrast, the 1HBrT, a different position of the H-atom facilitates easy and direct cleavage of the C–Br bond, allowing bromine to dissociate without interaction with the remaining triazole ring structure.
The research findings provide new insights into the behavior of transient negative ions and could have far-reaching implications for pharmaceutical development and environmental chemistry. They found that the bromine atom not only makes it easier for the molecule to grab an electron, but also helps stabilize different forms of the molecule, depending on where the hydrogen is placed in the ring via different timescale-lived resonant states called transient negative ions.
"Like two keys that at first glance look the same but open completely different doors, these nearly identical molecules behave in strikingly different ways," explains Dr. Dariusz Piekarski.
This "roaming" of bromine completely reverses the molecular breaking patterns, facilitating the release of hydrogen bromide HBr, whereas, in the 1H-form, the direct bromine dissociation dominates. This fundamental scientific achievement challenges conventional chemical knowledge in several ways, not only for the bromine orbiting around a molecule. More surprisingly, the bromine roaming happens in negative charge states prior to the electron auto-detachment process. Second, the study reveals that even a tiny shift in the position of the hydrogen atom can completely alter this reaction pathway. Third, it shows that Br- ions can form weak, noncovalent bonds around the triazole ring, creating a much more stable complex that holds the electrons much longer than expected.
"The idea that we can control the movement of heavy atoms through something as simple as placing hydrogen in a given position is exciting and offers new possibilities for chemical design," remarks Dr. Dariusz Piekarski.
Now, it is possible to steer halogenated molecular targets' breakups in desired directions just by positioning hydrogen atoms. These findings point out how even subtle structural differences can guide chemical reactions in unexpected directions. Their study opens new directions for controlled molecular manipulation in chemistry and material science, demonstrating the value of low-energy electron studies in probing dynamic molecular behavior. Demonstrated work enables describing a pathway to a more effective breakdown of stable, pollution-prone compounds in the environment and understanding of how drug-like molecules behave under certain conditions, which is crucial for drug design. Future studies will explore whether similar phenomena occur while induced with different radiation sources and in other halogenated compounds.
This work was supported by National Science Centre, Poland, Grant No. 2022/47/D/ST4/03286 and MEYS, OP JAK project CZ.02.01.01/00/22_008/0004558 “AMULET”.
Journal
Journal of the American Chemical Society
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