Nucleophilic substitution of nitro groups by [F]fluoride in methoxy-substituted ortho-nitrobenzaldehydes—A systematic study

As model reactions for the introduction of [¹⁸F]fluorine into aromatic amino acids, the replacement of NO₂ by [¹⁸F]fluoride ion in mono- to tetra-methoxy-substituted ortho-nitrobenzaldehydes was systematically investigated. Unexpectedly, the highly methoxylated precursors 2,3,4-trimethoxy-6-nitrobenzaldehyde and 2,3,4,5-tetramethoxy-6-nitrobenzaldehyde showed high maximum radiochemical yields (82% and 48% respectively). When the electrophilicity of the leaving group substituted carbon atom is expressed by its ¹³C NMR chemical shift a good correlation with the reaction rate at the beginning of the reaction (first min) was found (R² = 0.89), whereas the maximum radiochemical yields correlated much poorer with this electrophilicity parameter. This may be caused by side reactions becoming influencial in the further reaction course. As possible side reactions the demethylation of methoxy groups and intramolecular redox reactions could be detected by HPLC/MS.