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.

A remarkable rate acceleration observed in the nucleophilic fluorination catalyzed by a designer alkylmethylimidazolium ionic liquid tailed functionalized with dihexylphosphine oxide.Figure optionsDownload as PowerPoint slide