Fluorine-18 Tracer Studies of Inorganic and Organic Electrophilic Fluorinating Agents

Abstract

<p> Fluorine-18 labelled F2, produced by the nuclear reaction, 18O(p,n)18F, and recovered from an oxygen-18 gas target, has been used to elucidate the mechanism for the formation of XeF+AsF6- from Xe, F2, and AsF5 under low temperature and dark conditions. Formation of XeF+AsF6- was confirmed by Raman spectroscopy. A method was designed to allow for the dilution of the 18F activity onto a pool of carrier 19F2 such that suitable quantities of low specific activity [18F]F2 could be produced for the mechanistic study of this reaction. Based on the 18F distributions within the products and unreacted [18F]F2 and AsF5, it was shown that an F2-AsF5 activated complex containing an electrophilic fluorine reacts with the weak electron donor, xenon gas, in a Lewis acid-base type reaction. The absence of random fluorine exchange within the activated complex indicated that a transient Fδ+ was responsible for the enhanced oxidizing ability of the F2-AsF5 complex, rather than the production of a formal "F+" or F· intermediate. Fluorine-18 investigations into the reaction of the F2-AsF5 activated complex with other possible electron donors have shown some 18F transfer with krypton gas. Attempts to establish the formation of KrF+ using 19F NMR spectroscopy have shown no evidence for the presence of the cation in the Kr/F2/AsF5 system. The systems Kr/F2/HF/SbF5 and OF2/F2/AsF5 were not seen to undergo a reaction.</p> <p> The results of such sensitive radiotracer experiments required a complete analysis of the composition of the target gas delivered from the 18O(p,n)18F oxygen gas target; the presence of reactive agents other than [18F]F2 could affect the distribution of activities in reaction mixtures. Oxygen difluoride, which was suspected as a possible side product of the double bombardment method, was identified as a constituent of the target gas by 19F NMR characterization. An analysis of the effect of the variation of irradiation parameters has concluded that the quantity of [18F]OF2 activity is independent of the production irradiation parameters and is most likely a consequence of the presence of small amounts of O2 within the target during the recovery irradiation.</p> <p> The application of CsSO4F as an electrophilic fluorinating agent has provided preliminary evidence for the flourination of biologically active aromatic amino acids. Cesium fluoroxysulphate was found to react with 3,4-dihydroxyphenylalanine (L-Dopa) in an CH3CN solution containing BF3 to produce a mixture 2-, 5-, and 6-fluoro-L-dopa. Fluorine-19 NMR spectroscopy was used to confirm the presence of the 2-, 5-, and 6-fluoro-isomers of fluorodopa in the reaction mixture.</p>