fluorinating

Fluorinating is the chemical process of introducing fluorine atoms into organic or inorganic substrates, typically to form carbon–fluorine bonds in organofluorine compounds. Fluorination can alter properties such as metabolic stability, polarity, and boiling points, and is widely used in pharmaceuticals, agrochemicals, and advanced materials. The term covers several distinct mechanistic approaches, including electrophilic fluorination, nucleophilic fluorination, and radical fluorination.

Electrophilic fluorination uses reagents that deliver a positively charged or electrophilic fluorine species. Common reagents include Selectfluor and N-fluorobenzenesulfonimide (NFSI), which can install fluorine onto activated substrates such as arenes or alkenes under relatively mild conditions. Nucleophilic fluorination relies on fluoride sources, such as CsF or tetra-n-butylammonium fluoride, often with phase-transfer catalysts or activators to promote substitution or to form organofluorides from suitable leaving groups. Radical fluorination employs radical intermediates to form C–F bonds, frequently under photoredox or radical-promoted conditions, enabling selective functionalization of C–H bonds or alkenes.

Reagents range from elemental fluorine gas and xenon difluoride to sulfur tetrafluoride and specialized organofluorinating agents. Each method has distinct substrate scope, reactivity, and safety considerations. Fluorination is challenging in some contexts due to the strength of the C–F bond and the high reactivity of fluorinating reagents, which can lead to over-fluorination or side reactions.

Applications of fluorination include enhancing the pharmacokinetic properties of drugs, labeling compounds for diagnostic imaging with fluorine-18, and producing materials with unique electronic or thermal attributes. Safety concerns, environmental impact, and the need for specialized equipment shape how fluorination is practiced in research and industry.