CAN WE PREDICT REACTIVITY FOR AROMATIC NUCLEOPHILIC SUBSTITUTION WITH (1sFJFLUORIDE ION?

The correlation between the 1%-NMR chemical shift of the aromatic ring carbon bearing the leaving group and the yield of nucleophilic aromatic displacement with no-carrier-added [ 18Flfluoride ion was evaluated. In comparison of structurally analogous compounds (fluoro, nitro and trimethylammonium substituted benzaldehydes, benzophenones and benzonitriles), the 13C-NMR chemical shift of the reactive aryl ring carbon correlated quite well with the [18F]fluorination yield (r2 = 0.87) for most but not all ring structures. Compounds with trimethylammonium leaving groups or methyl ring substituents were found to not fit the proposed correlation. Kinetic studies indicated clearly different rates of reaction for these compounds, with much higher than expected reactivity for the ccompounds with the cationic leaving group. Competition experiments suggest that low reactivity of methylsubstituted rings may be due to conversion of [18F[fluoride to an unreactive form. Our results indicate that the correlation between [W'Jfluorination yields for nucleophilic aromatic substitution reactions and the 1% NMR chemical shift of the aryl ring carbon bearing the leaving group is applicable to numerous structurally analogous compounds, but cannot be simply generalized to aromatic rings with different leaving groups or ring substituents.