Catalytic nucleophilic fluorination by an imidazolium ionic liquid possessing trialkylphosphine oxide functionality

•Enhanced rates of fluorination compared to conventional ionic liquids using CsF.•Cooperative effect of imidazolium and phosphine oxide groups facilitates fluorination.•Simple and quick procedure suitable for 18F-labeled compounds preparation.•Recyclability of the catalyst with no change in yield and purity of the products.

The synthesis of a new alkylmethylimidazolium ionic liquid wherein the alkyl group is functionalized with dihexylphosphine oxide moiety at the terminal position has been achieved in four steps from 1-methylimidazole. This hybrid ionic liquid effectively catalyzed the nucleophilic fluorination of primary alkyl mesylates under mild conditions using CsF as the fluoride source with a faster rate compared to butylmethylimidazolium mesylate. The hybrid catalyst was recycled 5 times without compromising the yield and purity of the product. The nucleophilic fluorination has been used for the synthesis of diethyl 2-(5-fluoropentyl)-2-methyl malonate, a precursor of 18F isotopomer of an apoptosis imaging agent and the protected form of O-(2′-fluoroethyl)-l-tyrosine, a 18F isotopomer of a tumor imaging agent.

Graphical abstractA remarkable rate acceleration observed in the nucleophilic fluorination catalyzed by a designer alkylmethylimidazolium ionic liquid tailed functionalized with dihexylphosphine oxide.Figure optionsDownload full-size imageDownload as PowerPoint slide