Nucleophilic aromatic substitution of activated cationic groups by 18F-labeled fluoride. A useful route to no-carrier-added (NCA) 18F-labeled aryl fluorides

A method is described for the rapid preparation of no-carrier-added (NCA) ¹⁸F-labeled aryl fluorides by treatment of the corresponding aryltrimethylammonium perchlorates with ¹⁸F-labeled fluoride in DMSO. The basic features of the ¹⁸F-for-⁺NMe₃ displacement process are evaluated as a function of the experimental variables and compared with related substitution routes to NCA ¹⁸F-labeled aryl fluorides. The relative nucleofugicity of the ammonium group in the nucleophilic substitution reactions surpasses that of the best neutral leaving groups, including NO₂ and F itself. In contrast, radiofluoride incorporation into aromatic rings $\text{via}$ other cationic substrates, such as aryldimethylsulfonium perchlorates, is prevented by the fast methyl group transfer from the starting compound to the nucleophiles present. The use of the ammonium function as a leaving group in nucleophilic substitutions by ¹⁸F^? may give access to the rapid preparation of novel NCA ¹⁸F-radiopharmaceuticals by facilitating the synthesis and the purification of their labeled precursors.