A joint research paper describing use of the flow method (see below) was published in the scientific journal Nature Communications* on January 7, 2025. The paper describes a study done by Central Glass in collaboration with Professor Aiichiro Nagaki and Associate Professor Kazuhiro Okamoto of Hokkaido University’s Faculty of Science. The study used a flow reactor to selectively cleave a single carbon-fluorine bond in a trifluoromethyl compound and convert it to a new functional group in just seconds.

Central Glass has an extensive history of developing organofluorine compounds, which have unique properties that enable a wide range of applications in areas such as pharmaceuticals, agrochemicals and functional materials. The difluoromethyl unit is known as a bioisostere of other functional groups (ether and thiol groups). Despite growing interest in the difluoromethyl unit for pharmaceutical and agrochemical applications, the scarcity of synthesis methods available for it required for a new method to enable quick and easy synthesis.

The study responded to this need by successfully developing a new reaction using the flow method (with a flow microreactor with microchannels as the reaction field). The reaction instantly generates an extremely unstable difluoromethyl anion species from a trifluoromethyl compound and converts only mono-selective fluorine atom of the trifluoromethyl group into a new functional group. In addition, the study achieved the world’s first successful observation of the active species. The method’s reaction time of up to just 6.3 seconds and compatibility with drugs and other biologically active substances make it promising for drug discovery applications. Practical applications for the method have also been demonstrated by the successful creation of a rapid and shortened process for synthesizing a drug molecule used to combat HIV.

Central Glass will continue researching and developing flow method applications while working to create new highly functional chemical products designed to improve lives around the world.

*A Nature-affiliated British journal of natural sciences that accepts submissions of only the highest level of scientific merit.

Summary

Title

Defluorinative Functionalization Approach led by Difluoromethyl Anion Chemistry

Authors

Central Glass Co., Ltd.
　Kensuke Muta　(Enrolled in Doctoral course, Graduate School of Science, Hokkaido University)

Graduate School of Science, Hokkaido University
　Kazuhiro Okamoto, Hiroki Nakayama, Shuto Wada, Aiichiro Nagaki

Journal

Nature Communications

DOI

10.1038/s41467-024-52842-0

Publication Date

January 7, 2025 (Online publication)

Contact Information

Central Glass Co., Ltd.
New-STEP Research Center
Phone: +81-49-246-3719