Ortho-[ 18 F]Fluoronitrobenzenes by no-carrier-added nucleophilic aromatic substitution with K[18F]F-K222 -: A comparative study

The scope of the nucleophilic aromatic ortho-fluorinations from the corresponding ortho-halonitrobenzene precursors (halo-to-fluoro substitutions) with no-carrier-added [F-18]fluoride ion as its activated K[F-18]F-K-222 complex has been evaluated via the radiosynthesis of ortho-[F-18]fuoronitro-benzene, chosen as a model reaction. The parameters studied include the influence of the leaving group in the ortho position of the phenyl ring (-Cl, -Br, -1), the quantity of precursor used, the type of activation (conventional heating or microwave irradiations), the solvent, the temperature and the reaction time. The iodo-precursor was completely unreactive and the bromo-precursor gave only low incorporation (< 10%) in the optimal conditions used (conventional heating at 145degreesC or microwave activation, 100 W for 120 s). Only the chloro-precursor was found reactive in the conditions described above and up to 70% yield was observed for the formation of ortho-[18 F]fluoronitrobenzene ([F-18]-1). In all the experiments, the unwanted ortho-[18F]fluoro-halobenzenes, potentially resulting from the nitro-to-fluoro substitution, could not be detected. These results will be applied for the radiosynthesis of 5-[F-18]fluoro-nitroquipazine, a potent radioligand for the imaging of the serotonin transporter with PET. Copyright (C) 2002 John Wiley Sons, Ltd.