Pharmaceutical industry, medical diagnostics, agrochemistry and material sciences are among many different fields which have benefited tremendously from the development of fluorine chemistry and unique properties of fluorinated compounds. In order to further develop this type of chemistry we expanded initial reactivity studies of imidazolium fluoride-based reagents. Among these, the least reactive but the most stable reagent, 1,3-bis(2,6-diisopropylphenyl)imidazolium dihydrogen trifluoride (ImH2F3), was successfully activated for fluorination of benzyl bromides. We tested poly(hydrogen fluoride) species activators from the literature and evaluated their compatibility with our reaction system. Besides potassium and caesium fluoride only sterically hindered base DIPEA enabled us quick and selective fluorination of benzylic substrates. Lithium and sodium fluoride proved to be inactive. Influence of added water, heating mode and reaction scale were studied. Water is detrimental for fluorination yield when DIPEA is used as an activator while potassium fluoride allows fluorination in acetonitrile / water solvent mixture. Higher reaction temperatures and shorter reaction times can be achieved using microwave heating. Careful concentration control or reduction of reaction time are crucial for reaction scale-up. After the optimization of reaction conditions benzyl fluorides were prepared in fair to excellent yields (56–95 %) from the corresponding benzyl bromides, iodides, mesylates and tosylates. Benzylic substrates with electron donating as well as electron accepting groups are compatible with the optimized reaction conditions. Benzyl chlorides are less reactive. However, good fluorination yields with benzyl chlorides can be achieved by using excess of both ImH2F3 reagent and DIPEA. Substrate scope was expanded with one example of aromatic fluorodenitration, preparations of acyl and sulfonyl fluorides and fluorination of an aliphatic iodide, a secondary mesylate and -bromocarbonyl compounds. ImH2F3 can also be used as a mild reagent for deprotection of silyl ethers. We have developed simple protocols for isolation of fluorinated product and spent reagent. The latter can be conveniently regenerated with hydrofluoric acid or anhydrous hydrogen fluoride without the use of organic solvents. Reactions involving interconversions of imidazolium salts can be easily monitored with ion chromatography. We showed that dihydrogen trifluoride anion can be activated to serve as a good source of nucleophilic fluoride. Dihydrogen trifluoride anion forms an air-stable nucleophilic fluoride reagent with imidazolium moiety, which is suitable for fluorination in wet organic solvents and can be recycled with hydrofluoric acid.
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