4fluoropyridines

4-fluoropyridines are a class of heteroaromatic compounds in which a single fluorine atom is substituted at the 4-position of the pyridine ring. The core is derived from pyridine (C5H5N) with formula C5H4FN for the unsubstituted derivative, and many additional 4-fluoropyridine derivatives exist with substituents at other positions. The fluorine substituent is small and highly electronegative, imparting an electron-withdrawing effect on the ring and modestly reducing the basicity of the pyridine nitrogen relative to unsubstituted pyridine.

Electrophilic and nucleophilic fluorination methods have been used to prepare 4-fluoropyridines, including direct fluorination of 4-substituted pyridines and halogen-exchange reactions starting from 4-chloro- or 4-bromo-pyridines with fluoride sources. Other routes include deoxyfluorination of 4-hydroxypyridine precursors and transition-metal-catalyzed fluorination. The 4-fluoro motif can influence properties relevant to drug design, such as metabolic stability, lipophilicity, and receptor-binding characteristics, making these compounds common building blocks in medicinal and agrochemical research.

Because the C–F bond in aryl fluorides is relatively strong, 4-fluoropyridines are often less reactive in subsequent substitutions than their non-fluorinated analogs, though specialized conditions can enable further functionalization. The skeleton also serves as a valuable ligand in coordination chemistry due to the pyridine nitrogen and the electron-withdrawing fluorine, which can modulate metal-ligand interactions. Commercial availability varies by substitution pattern, with the unsubstituted 4-fluoropyridine and several derivatives available from chemical suppliers.