Methyl Hypofluorite


[36336-08-0]  · CH3FO  · Methyl Hypofluorite  · (MW 50.04)

(used for adding the elements of MeO and F across double bonds,1 for electrophilic methoxylation a to carbonyls,2 and as a tool for introducing the short lived 11C isotope for positron emission tomography (PET)3)

Physical Data: mp -142 °C; bp -33 °C (by extrapolation); 19F NMR +120 ppm (3JHF = 45 Hz); 1H NMR 4.51 ppm (3JHF = 45 Hz).

Handling, Storage, and Precautions: MeOF is an unstable substance and for all practical purposes has to be prepared in situ in solution and used soon after its formation. Neat solid and liquid MeOF can be unpredictably explosive at temperatures above -78 °C. The concentration of the reagent is determined iodometrically (MeOF + 2KI + H2O -> I2 + KF + MeOH + KOH). As with all hypofluorites, it may be toxic and should be treated accordingly. Use in a fume hood.

Addition to Alkenes.

Although MeOF has been a subject for several theoretical studies,4 it was synthesized only recently by passing relatively concentrated fluorine through methanol in the presence of acetonitrile.1 Unlike other hypofluorites such as Trifluoromethyl Hypofluorite or Acetyl Hypofluorite the fluorine in MeOF is nucleophilic, leaving the rest of the molecule (MeO) to act as a strong electrophile. This formally constitutes the previously unknown methoxylium ion. This is evident from the addition of MeOF to unsymmetrical alkenes such as styrene, which produces exclusively 1-fluoro-1-phenyl-2-methoxyethane (eq 1).1

Methoxylation of Ketones.

This unique electrophilic system was used to methoxylate ketones in their a-position in a fast and direct mode. It was found that the methoxylation is best when performed on methyl enol ethers.2 Since this reaction takes only a few seconds, and since it is relatively easy to make 11CH3OH (half life of the positron emitting 11C isotope is about 20 min), this method adds a new route (to the very few existing ones) for incorporating this isotope into organic molecules for PET studies (eq 2).3

It should be noted that addition of the elements of MeO and F can also be achieved when electrophilic fluorination reagents such as CF3OF,5 FClO3,6 or CsSO4F7 are reacted with alkenes in the presence of MeOH (eq 3). The same is true when XeF2/MeOH is employed, although in this case the intermediate MeOXeF was suggested (eq 4).8 In some of these reactions the fluorine acts as an electrophile, but in others most of the regioselectivity is lost.

Related Reagents.

Hypofluorous Acid.

1. (a) Kol, M.; Rozen, S.; Appelman, E. JACS 1991, 113, 2648. (b) Rozen, S.; Mishani, E.; Kol, M.; Ben-David, I. JOC 1994, 59, 4281.
2. Rozen, S.; Mishani, E; Kol, M. JACS 1992, 114, 7643.
3. McCarthy, T. J.; Bonasera, T. A.; Welch, M. J.; Rozen, S. CC 1993, 561.
4. See for example: Lee, I.; Cho, J. K.; Song, C. H. JCS(F2) 1988, 84, 1177.
5. Barton, D. H. R.; Hesse, R. H.; Jackman, G. P.; Pechet, M. M. JCS(P1) 1977, 2604.
6. Djuric, S. W.; Garland, R. B.; Nysted, L. N.; Pappo, R.; Plume, G.; Swenton, L. JOC 1987, 52, 978.
7. Stavber, S.; Zupan, M. JOC 1987, 52, 919.
8. Shellhamer, D. F.; Curtis, C. M.; Dunham, R. H.; Hollingsworth, D. R.; Ragains, M. L.; Richardson, R. E.; Heasley, V. L.; Shackelford, S. A.; Heasley, G. E. JOC 1985, 50, 2751.

Shlomo Rozen

Tel Aviv University, Israel

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