For the first time in the world, thiols and disulfides were converted into sulfonyl fluorides using SHC5® and KF, expanding "click chemistry" with high efficiency and low environmental impact. This green process, yielding only NaCl and KCl as byproducts, is expected to become the preferred method in chemical and industrial synthesis.
The concept of "click chemistry" is known for its high chemical selectivity, high yield, and rapid connection of molecules. Since its inception, click chemistry has demonstrated broad utility across various fields, including synthesis, materials science, chemical biology, and pharmaceutical development, garnering immense popularity.
However, sulfonyl fluoride is a key compound in the sulfur-fluorine exchange (SuFEx) click reaction, which links molecules together, and its synthesis initially required the use of SO2F2 gas or KHF2, both of which are highly toxic and difficult to handle. To achieve the safe and environmentally-friendly synthesis of sulfonyl fluoride, synthetic chemists have explored various chemical reaction processes.
In this study, it was developed for the first time in the world that sulfonyl fluoride can be efficiently synthesized by reacting the easily-handled and highly-reactive SHC5® and KF (potassium fluoride) with thiols or disulfides. This is a green synthetic process that produces only non-toxic sodium and potassium salts as by-products, resulting in minimal environmental impact.
This chemical reaction enabled the environmentally-friendly and tailor-made synthesis of a broad scope of sulfonyl fluorides containing aromatic, aliphatic, and heterocyclic groups.
The synthetic protocol is very simple, enabling the low-cost, scalable, and safe production of sulfonyl fluorides. This new method is expected to become the first choice for sulfonyl fluoride synthesis in both the chemical and industrial sectors.
"Developing new organic synthetic protocols to create useful compounds, such as pharmaceuticals, is a highly important research theme, particularly from the perspective of the Sustainable Development Goals (SDGs)," says corresponding authors of the study Masayuki Kirihara, Shinobu Takizawa, and Mohamed S. H. Salem. "Furthermore, developing reaction processes that consider the environmental impact of by-products is becoming increasingly important. We will continue to disseminate research from Japan that focuses on the green synthesis of useful compounds with ripple effects across various fields."
Fig. 1
A new, safe and low-cost synthetic reaction process for sulfonyl fluorides
Credit: Shinobu Takizawa
Fig. 2
An image expressing the value of the study: Liquid representing water resources with an organic synthesis reaction in a flask, emphasizing environmental sustainability.
Credit: Reprinted with permission from ACS Sustainable Chem. Eng. 2024, 12, 32, 12135-12142. Copyright 2024 American Chemical Society.
The article, "Green and Efficient Protocols for the Synthesis of Sulfonyl Fluorides Using Potassium Fluoride as the Sole Fluorine Source," was published in ACS Sustainable Chemistry & Engineering at DOI: https://doi.org/10.1021/acssuschemeng.4c03951.
