Organofluorine Chemistry - History

History

Organofluorine chemistry began in the 1800s with the development of organic chemistry as a whole. The first organofluorine compounds were prepared by metathesis reactions using antimony trifluoride as the F- source. The nonflammability and nontoxicity of the chlorofluorocarbons CCl₃F and CCl₂F₂ attracted industrial attention in the 1920s. In the 1930s, scientists at duPont discovered polytetrafluoroethylene. Subsequent major developments, especially in the US, benefited from expertise gained in the production of uranium hexafluoride. Starting in the late 1940’s, a series of electrophilic fluorinating methodologies were introduced, beginning with CoF₃. About this time, electrochemical fluorination ("electrofluorination") was announced, having been developed in the 1930s with the goal of generating highly stable perfluorinated materials compatible with uranium hexafluoride. These new methodologies allowed the synthesis of C-F bonds without using elemental fluorine and without relying on metathetical methods. In 1957, the anticancer activity of 5-fluorouracil was described. This report provided one of the first examples of rational design of drugs. This discovery sparked a surge of interest in fluorinated pharmaceuticals and agrichemicals. The discovery of the noble gas compounds, e.g. XeF₄, provided a host of new reagents starting in the early 1960’s. In the 1970s, fluorodeoxyglucose was established as a useful reagent in 18F positron emission tomography. In Nobel Prize-winning work, CFC’s were shown to contribute to the depletion of atmospheric ozone. This discovery alerted the world to the negative consequences of organofluorine compounds and motivated the development of new routes to organofluorine compounds. In 2002, the first C-F bond-forming enzyme, fluorinase, was reported.