Reaction evolution of a solvate fluoride ionic liquid induced fluorination process probed by Raman spectroscopy

Abstract

Currently, about 30% of new approved drugs contained fluorine atoms and most of them are made through fluorination reactions using various kinds of fluorinating reagents. In the current work, we report a facile and more accessible way to probe the fluorination evolution at different stages using a newly developed fluorinating reagent (1-ethyl-3-methylimmidazolium fluoride-ethylene glycol, [C 2 C 1 im]F-EG). Benzyl bromide was converted to benzyl fluoride using this fluorinating reagent under mild conditions. A more accessible Raman method, compared to NMR, was used to probe the reaction process due to the products having their own characteristic Raman vibrational frequencies because of the formation of different C-X bonds. Thus the yield of the product at different time scales could be then quantified based on their relative intensities, providing a fresh insight into the fluorination process. This method could be applied in other reactions to reflect the important fluorination process, which methodologically reports a facile way to probe reaction processes. • A fluoride solvate ionic liquid was used as fluorinating reagent in a fluorination reaction. • Raman spectroscopy was exclusively used to quantitatively determine the reaction products. • The reaction rate was mainly reduced logarithmically with time. • Increasing complexing molecules, ethylene glycol, in the reagent can reduce the rate greatly.