Methoxyflurane - History

History

Further information: Drug development, Gaseous diffusion, Manhattan Project, Medicinal chemistry, and Organofluorine compounds

All of the currently used volatile anesthetic agents are organofluorine compounds. Aside from the synthesis of Freon (Thomas Midgley, Jr. and Charles F. Kettering, 1928) and the discovery of Teflon (Roy J. Plunkett, 1938), the field of organofluorine chemistry had not attracted a great deal of attention up to 1940 because of the extreme reactivity of elemental fluorine, which had to be produced in situ for use in chemical reactions. The development of organofluorine chemistry was a spin-off from the Manhattan Project, during which elemental fluorine was produced on an industrial scale for the first time.

The need for fluorine arose from the need to separate the isotope235U from 238U because the former, present in natural uranium at a concentration of less than 1% is fissile (capable of sustaining a nuclear chain reaction of nuclear fission with thermal neutrons), whereas the latter is not. Members of the MAUD Committee (especially Francis Simon and Nicholas Kurti) proposed the use of gaseous diffusion for isotope separation, since, according to Graham's law the rate of diffusion is inversely proportional to molecular mass. After an extensive search, uranium hexafluoride, UF₆, was determined to be the most suitable compound of uranium to be used for the gaseous diffusion process. Elemental fluorine is needed in the production of UF₆.

Significant obstacles had to be overcome in the handling of both fluorine and UF₆. Before the K-25 gaseous diffusion plant could be built, it was first necessary to develop non-reactive chemical compounds that could be used as coatings, lubricants and gaskets for the surfaces which would come into contact with the UF₆ gas (a highly reactive and corrosive substance). William T. Miller, professor of organic chemistry at Cornell University, was co-opted to develop such materials, because of his expertise in organofluorine chemistry. Miller and his team developed several novel non-reactive chlorofluorocarbon polymers that were used in this application.

Charles Suckling synthesized halothane in 1951. Halothane was the first organofluorine anesthetic agent to be introduced into clinical practice in 1956. Miller and his team continued to develop organofluorine chemistry after the end of World War II and methoxyflurane was synthesized in 1948.