CAN WE PREDICT REACTIVITY FOR AROMATIC NUCLEOPHILIC-SUBSTITUTION WITH[F-18] FLUORIDE-ION

The correlation between the C-13-NMR chemical shift of the aromatic ri ng carbon bearing the leaving group and the yield of nucleophilic arom atic displacement with no-carrier-added [F-18]fluoride ion was evaluat ed. In comparison of structurally analogous compounds (fluoro, nitro a nd trimethylammonium substituted benzaldehydes, benzophenones and benz onitriles), the C-13-NMR chemical shift of the reactive aryl ring carb on correlated quite well with the [F-18]fluorination yield (r2 = 0.87) for most but not all ring structures. Compounds with trimethylammoniu m leaving groups or methyl ring substituents were found to not fit the proposed correlation. Kinetic studies indicated clearly different rat es of reaction for these compounds, with much higher than expected rea ctivity for the ccompounds with the cationic leaving group. Competitio n experiments suggest that low reactivity of methyl-substituted rings may be due to conversion of [F-18[fluoride to an unreactive form. Our results indicate that the correlation between [F-18]fluorination yield s for nucleophilic aromatic substitution reactions and the C-13 NMR ch emical shift of the aryl ring carbon bearing the leaving group is appl icable to numerous structurally analogous compounds, but cannot be sim ply generalized to aromatic rings with different leaving groups or rin g substituents.