Nucleophilic [18F]Fluorination and subsequent decarbonylation of methoxy‐substituted nitro‐ and halogen‐benzenes activated by one or two formyl groups

Abstract

AbstractAs model reactions for the introduction of 18F into protected aromatic amino acids, the replacement of NO2, Cl, Br and F by [18F]fluoride in 2‐isophthalaldehyde and 2‐terephthalaldehyde derivatives which model 18F‐DOPA and 18F‐tyrosine was investigated by comparing labelling yields and reaction rates with those of corresponding mono‐aldehyde compounds. All isophthalaldehydes showed maximum radiochemical yields (79 to 86%) at 140°C and in comparison with the corresponding mono‐aldehydes the reaction proceeded faster. At lower temperature the reaction already resulted in high yields, e.g. 2‐nitroisophthalaldehyde was labelled with a yield of 78% at 25°C after 7 min, whereas 2‐nitrobenzaldehyde only reached a yield of 1.7% under the same reaction conditions. The 18F/NO2 exchange in nitroterephthalaldehydes proceeded more slowly and with lower radiochemical yields when compared with corresponding isophthalaldehydes and monoaldehydes. The decarbonylation of 18F‐labelled aromatic dialdehydic compounds with 4 eq. of Wilkinson's catalyst at 150°C in benzonitrile resulted in high yields, e.g. 2‐[18F]fluoro‐5‐methoxyisophthalaldehyde and 4‐[18F]fluoro‐2‐methoxy‐5‐methylisophthalaldehyde were decarbonylated efficiently with yields of 67±3% and 72±2%, respectively. Copyright © 2010 John Wiley & Sons, Ltd.