musings on music and life

May 18, 2012

On flourine and organofluorine chemistry

Filed under: Chemistry, Uncategorized — Tags: , , — sankirnam @ 8:08 pm

Since I had a spare moment today, I thought I would briefly write about fluorine chemistry (especially organofluorine chemistry as it pertains to my research today).

For those not acquainted with it’s basic chemistry, fluorine is element 9 on the Periodic Table, and is the lightest member of the chemical family known as the halogens. Like all the halogens, in it’s elemental state it is diatomic, existing as molecules rather than individual atoms. However, fluorine was the last of the halogens to be isolated, due to its (dare I say obscene?) reactivity. Many people were seriously injured or even killed during attempts to isolate the element, and ultimately Henri Moissan succeeded in the late 19th century. He was later awarded the Nobel Prize for his efforts, and also probably for being the only person to isolate it without being maimed in the process. The weak F-F bond in elemental fluorine, combined with the very strong bonds other elements make with it, make the reactions of fluorine with almost anything extremely energetic.

Thus, for some time, fluorine chemistry, and organofluorine chemistry especially, were considered niche topics of little interest. Reactions of elemental fluorine with organic compounds were difficult to control, often catching fire or just going straight to tar. As most undergraduates learn, the introduction of fluorine into aromatic compounds is a little different from the other halogens. The fluorine atom cannot be introduced by a usual Sandmeyer reaction as is possible for other halogens or pseudohalogens (such as Cl, Br, I, or CN). Instead, the Balz-Schiemann reaction is required.

A few developments helped to spark interest in organofluorine chemistry. The realization that C-F bonds were among the strongest single bonds that carbon makes with other elements led to the discovery of several important inert compounds. One was CFC’s (chlorofluorocarbons). These were found to be extremely unreactive under even very harsh reaction conditions (CFC’s can even be used as solvents for such reactive compounds as SbF5!). They then found extensive use as solvents and especially refrigerants. They were made in multi-tonne quantities worldwide, until the work of the late Prof. F. S. Rowland (more about him later) showed that they were responsible for ozone depletion in the upper atmosphere. Prof. Rowland received the Nobel Prize in chemistry in 1995 for that very work.

Another important discovery was that of Teflon. Teflon is the polymer of tetrafluoroethylene, and so it only contains C-F bonds, making it very inert. The introduction of fluorine into organic molecules also tends to make them lipophilic, or hydrophobic, and so Teflon surfaces were found to be ideal for non-stick cooking ware. The discovery of Teflon was actually an accident (see here).

The Manhattan project sparked further interest in fluorine since it was discovered that the most convenient method of uranium enrichment was through separation of the two isotopes via UF6. UF6 is an extremely reactive, corrosive solid that has a low sublimation temperature, and so separation of the isotopes is done through careful gaseous diffusion. Materials that could handle UF6 were therefore sought, and most such materials were found to have to be fluorinated themselves in order to withstand the reactivity of UF6.

As one can see, fluorine chemistry offers a swath of compounds with extremely varying degrees of reactivity, from the most inert compounds known to man, to the most reactive and toxic compounds known (e.g. HF and fluoroacetate). HF (hydrogen fluoride or hydrofluoric acid when in solution) is an extremely versatile acid and fluorinating reagent, but is not used much in academic research due to difficulties involved with its handling. Prof. Olah (whom I talked about in detail earlier) made a significant contribution to the development of HF chemistry through the introduction of the reagent that now bears his name. Noble gas chemistry also falls under the umbrella of fluorine chemistry, since most of the oxidants required to access the higher oxidation states of Xe, Kr, or Ar are either F2 itself or are fluorinated.

Jumping to the modern day, there is a now a sudden renaissance in medicinal chemistry involving organofluorine compounds. As mentioned earlier, the C-F bond is one of the strongest carbon single bonds known. As such, C-F bonds are typically more difficult to degrade, making compounds containing such bonds longer lasting (as usual, exceptions exist). Dr. Prakash (who was initially a graduate student of Prof. Olah and is now a professor himself alongside Olah at USC) made a significant contribution to the development of modern organofluorine chemistry through the use of the reagent commonly called TMSCF3. The facile introduction of trifluoromethyl groups into organic compounds was a long-standing challenge in organic synthesis due to the instability of organometallic compounds containing CF3. The use of TMSCF3 provided a solution to this problem, and paved the way for numerous other methods for the introduction of trifluoromethyl or other perfluoroalkyl groups into organic molecules. Now, within 20 years, trifluoromethylation chemistry has become rather trivial, in my opinion. Several top-selling medications contain a trifluoromethyl group, including Celebrex and Prozac. The best-selling pharmaceutical in the world, Lipitor, is fluorinated, again highlighting the importance of fluorine in modern medicinal chemistry.

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