1H-NMR showed complete conversion of the 3-nitro substrate 1 into the 3-fluoro substitution product 2 after 1.5 hours reflux with CsF in dry DMSO. We have succeeded in achieving the nucleophilic aromatic substitution of the nitro group in 3-nitro-pyridyl carboxylate 1 with fluoride anion, thus obtaining methyl 3-fluoropyridine-4-carboxylate ( 2, see Scheme 2) in 38 % yield. On this background, the development of new and efficient methods for the preparation of fluoroorganic compounds has got increased attention in recent years.
The C-F bond is stronger than the original C-H bond and fluorinated compounds are more resistant to metabolic degradation. The higher electronegativity of fluorine may also alter the physical and chemical properties of a molecule, and the higher polarizability due to the new C-F bond may give new possibilities for binding to the receptor. The incorporation of fluorine into organic molecules may change the solubility properties and enhance the lipophilicity and thus increase the rate of cell penetration and transport of a drug to an active site. Due to the minimal conformational effects, the fluorinated molecule generally also fits in the active site of the receptor and the fluorine atom is thus a suitable isosteric substitution of hydrogen. In general, the introduction of a fluorine atom in a molecule does not result in a considerable change in the size or the shape of the compound.
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