Syntheses of meta-[18F]fluorobenzaldehyde and meta-[ 18F]fluorobenzylbromide from phenyl(3-Formylphenyl) iodonium salt precursors

Article abstract of DOI:10.1002/jlcr.1853

¹⁸F-labeled fluorobenzaldehydes and fluorobenzylbromides are useful synthons for the preparation of positron emission tomography radiopharmaceuticals. Although ortho- and para-[¹⁸F] fluorobenzaldehydes can easily be prepared with high yields, the corresponding meta-derivatives are more problematic. In order to improve the yield of meta-[¹⁸F]fluorobenzaldehyde, we used the corresponding diaryliodonium salt precursors, since diaryliodonium salts had already been used as precursors in the preparations of ¹⁸F-labeled electron-rich, as well as electron-deficient, aromatic rings. Diaryliodonium salts with different counter ions [PhIPhCHO]X (X = Cl, Br, OTs, OTf) were synthesized. ¹⁸F radiolabeling was performed using different bases at different temperatures in the presence of a radical scavenger, 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO). The best conversion (～80%) to meta-[¹⁸F] fluorobenzaldehyde was obtained using CsHCO₃ base at a reaction temperature of 110°C. To study iodonium salt counter ion effects on radiofluorination, each precursor was separately treated with Cs[ ¹⁸F]F/CsHCO₃ in DMF at 110°C for 5 min in the presence of TEMPO. Our observed reactivity order was OTs18F]fluorobenzaldehyde thus obtained was reduced to the corresponding alcohol with aqueous NaBH₄ at room temperature and then converted to meta-[¹⁸F]fluorobenzylbromide using triphenylphosphine dibromide. Formation of meta-[¹⁸F]fluorobenzylbromide was confirmed using high-performance liquid chromatography and the desired product was purified on a silica Sep-Pak plus cartridge. Copyright