4Halopyridines

4-Halopyridines are pyridine derivatives in which a halogen atom (fluorine, chlorine, bromine, or iodine) is substituted at the 4-position (para to the ring nitrogen). The 4-position halogen provides a versatile synthetic handle for bond formation, enabling nucleophilic substitution or transition‑metal–catalyzed cross-coupling. The pyridine nitrogen remains a defining feature, contributing to the ring’s basicity and reactivity, while the halogen substituent modulates reactivity and serves as a reactive site for further functionalization.

Reactivity and applications: The 4-halogen can be displaced by nucleophiles such as amines, thiols, or alkoxides in SNAr-type reactions to furnish 4-substituted pyridines. Rates depend on the leaving-group ability (I > Br > Cl > F) and on the nucleophile and conditions. In cross-coupling chemistry, 4-iodopyridines and 4-bromopyridines are common electrophiles in Suzuki–Miyaura, Negishi, and related couplings to form C–C bonds, while 4-chloro- and, less routinely, 4-fluoropyridines can participate under specialized catalysts to form C–N or C–C bonds. Because of their modularity, 4-halopyridines are valuable intermediates in pharmaceutical and agrochemical synthesis, enabling rapid construction of heterobiaryl motifs and other substituted pyridines. They also appear as starting points for coordination chemistry and can serve as building blocks in material science.

Synthesis and availability: 4-halopyridines are commercially available and can be prepared by electrophilic halogenation of pyridine derivatives. Their versatility as electrophiles in SNAr and cross-coupling reactions underpins their widespread use as building blocks in medicinal chemistry and related fields.