First application of ionic liquids in electrophilic fluorination of arenes; Selectfluor™ (F-TEDA-BF4) for “green” fluorination

Abstract

The NF fluorinating agent F-TEDA-BF₄ dication salt (Selectfluor™) 1 dissolves in imidazolium-based ionic liquids [emim][OTf] 7, [emim][BF₄] 8, [bmim][PF₆] 9 and [bmim][BF₄] 10 (assisted by sonication), providing a convenient medium for fluorination of arenes under essentially acid-free conditions in a simple set-up (no volatile solvent; simple extraction of the aromatics without aqueous work-up), from which the ionic liquid can be easily recycled and reused. Comparative studies in [emim][OTf] 7 with anisole as substrate show that 1 is superior to NFTh-BF₄ (Accufluor^®) 2 and that the N-fluoropyridinium salt NFPy-B₂F₇4 is least effective. The scope of the reaction has been surveyed. Substrate selectivity (k_mesitylene ∶ k_durene = 10) measured in competitive experiments in 7 is clearly indicative of a conventional polar mechanism. Substrate selectivity measured without the ionic liquid in MeCN solvent is also indicative of a polar mechanism but exhibits lower magnitude (k_mesitylene ∶ k_durene = 6). Addition of dicyclohexano-24-crown-8 to the fluorination reaction mixture (1 and anisole) in 7 reduced the conversion but did not change the isomer distribution. AM1 minimization was used to model the complexation of 1 with this crown. With reactive aromatics optimal fluorination yields in ionic liquids (using 1 equivalent of the NF reagent) are around 50% (higher for naphthalene). A key control experiment suggests that the free base (produced upon transfer-fluorination) could complex to unreacted 1 (generating a bulky dimer complex which may be ineffective for fluorine transfer) in competition to N-protonation.