Effect of aldehyde and methoxy substituents on nucleophilic aromatic substitution by [18F]fluoride

For a series of benzaldehydes only with a leaving group or with both a leaving group and a single methoxy substituent F-18-fluorination via nucleophilic aromatic substitution (SNAr) was studied in DMF and Me2SO. In general, the radiochemical yields were clearly higher in DMF than in Me2SO. In the fluorodehalogenation reaction (leaving group: halogen = Br, Cl), extremely low radiochemical yields were observed in Me2SO (<1%). By monitoring labeling reactions using HPLC, oxidation of the aldehyde function of the precursor was detected. Especially, 2-bromobenzaldehyde was oxidized fastest in Me2SO (within 3min reaction time, 90% of the precursor was consumed; radiochemical yield = 1.0 +/- 0.5%); however, in DMF oxidation was always kept at a low level during the entire reaction (<5% of the precursor was oxidized; radiochemical yield = 73.0 +/- 0.2%). In DMF, nitrobenzaldehydes with a methoxy substituent (methoxy group in meta-position to the nitro group) were labeled with good radiochemical yields (4-methoxy-2-nitrobenzaldehyde: 87 +/- 3%; 2-methoxy-4-nitrobenzaldehyde: 83 +/- 3%; 2-methoxy-6-nitrobenzaidehyde: 79 +/- 4%) comparable to the non-substituted nitrobenzaldehydes (2-nitrobenzaldehyde: 84 +/- 3%; 4-nitrobenzaldehyde: 81 +/- 5%). Moreover, for structurally similar compounds, radiochemical yields showed a good correlation with C-13-NMR ppm values of the aromatic carbon atom bearing the leaving group. (C) 2007 Elsevier B.V. All rights reserved.