Microwave-induced nucleophilic [18F]fluorination on aromatic rings: Synthesis and effect of halogen on [18F]fluoride substitution of meta-halo (F, Cl, Br, I)-benzonitrile derivatives

The meta-halo-3-methylbenzonitrile derivatives (-F, -Cl, -Br, -I) were synthesized as model compounds to study reactivity towards aromatic nucleophilic substitution. A single-mode microwave system was incorporated into a commercial radiochemical synthetic module for 18F labeling. Labeling yields of 64% for fluoro-, 13% for bromo- and 9% for chloro-precursors were achieved in DMSO in <3 min. The observed order of reactivity of the leaving groups toward aromatic nucleophilic substitution was Fnot double greater-than signBr>Cl>>>I.