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

✍ Scribed by Falguni Basuli; Haitao Wu; Gary L. Griffiths

• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: French
• Weight: 210 KB
• Volume: 54
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/jlcr.1853

✦ Synopsis

Abstract

^18^F‐labeled fluorobenzaldehydes and fluorobenzylbromides are useful synthons for the preparation of positron emission tomography radiopharmaceuticals. Although ortho‐ and para‐[^18^F]fluorobenzaldehydes can easily be prepared with high yields, the corresponding __meta‐__derivatives are more problematic. In order to improve the yield of meta‐[^18^F]fluorobenzaldehyde, we used the corresponding diaryliodonium salt precursors, since diaryliodonium salts had already been used as precursors in the preparations of ^18^F‐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. ^18^F 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‐[^18^F]fluorobenzaldehyde was obtained using CsHCO~3~ base at a reaction temperature of 110°C. To study iodonium salt counter ion effects on radiofluorination, each precursor was separately treated with Cs[^18^F]F/CsHCO~3~ in DMF at 110°C for 5 min in the presence of TEMPO. Our observed reactivity order was OTsMeta‐[^18^F]fluorobenzaldehyde thus obtained was reduced to the corresponding alcohol with aqueous NaBH~4~ at room temperature and then converted to meta‐[^18^F]fluorobenzylbromide using triphenylphosphine dibromide. Formation of meta‐[^18^F]fluorobenzylbromide was confirmed using high‐performance liquid chromatography and the desired product was purified on a silica Sep**‐**Pak^®^ plus cartridge. Published in 2011 by John Wiley & Sons, Ltd.