fluorination

Fluorination is the chemical process of introducing fluorine atoms into organic or inorganic substrates, often forming carbon–fluorine bonds. It is a key strategy in medicinal chemistry, agrochemistry, and materials science because fluorine can alter lipophilicity, metabolic stability, acidity, and bond strength. Fluorination is typically categorized as electrophilic, nucleophilic, or radical, depending on the fluorine source and mechanism.

Electrophilic fluorination uses electrophilic fluorinating agents such as Selectfluor, N-fluoro-N-sulfonylimide (NFSI), and related reagents to transfer a positively charged fluorine to electron-rich substrates (arenes, alkenes, carbonyls). Nucleophilic fluorination relies on fluoride nucleophiles (CsF, KF) in polar aprotic solvents or phase-transfer catalysts to form C–F bonds at carbon centers that can accommodate nucleophilic attack. Deoxyfluorination reagents such as DAST and Deoxo-Fluor convert alcohols into alkyl fluorides, replacing hydroxyl with fluorine. Radical fluorination methods use radical initiators to install fluorine under milder conditions for certain substrates.

Applications and significance include the widespread use of fluorinated motifs in pharmaceuticals and agrochemicals, where fluorination can increase metabolic stability, modify pKa, and adjust lipophilicity. Fluorinated polymers and materials, such as PTFE and related fluoropolymers, play important roles in industry. In radiochemistry, isotopic fluorination with fluorine-18 enables PET imaging tracers. Industrial fluorination often employs elemental fluorine gas or hydrogen fluoride derivatives under strict safety protocols.

Safety and environmental considerations are important: many fluorinating agents are highly reactive and corrosive, and hydrofluoric acid poses serious hazards. Some organofluorine compounds are persistent in the environment. Proper engineering controls, regulatory compliance, and ongoing development of greener reagents and catalytic methods are central to the field.