Hypofluorous Acid1

HOF
(HOF)

[14034-79-8]  · FHO  · Hypofluorous Acid  · (MW 36.01) (HOF.MeCN)

[147583-45-7]  · C2H4FNO  · Hypofluorous Acid-Acetonitrile  · (MW 77.07)

(the HOF.MeCN complex is used for tertiary hydroxylations,2 epoxidations,3 and oxidation of amines,4 alcohols and ketones,5 aromatics,6 and sulfides7)

Physical Data: mp -117 °C; bp -79 °C/1 mmHg; 19F NMR d +27.5 ppm (of the MeCN complex, -8.5 ppm).

Handling, Storage, and Precautions: HOF is a very unstable substance and of little use in synthetic chemistry. Neat liquid HOF can be unpredictably explosive at temperatures above -40 °C. Its acetonitrile complex is much more stable but nevertheless has to be prepared in situ and, for all practical purposes, has to be reacted soon after its formation. The concentration of the reagent is determined iodometrically (HOF + 2KI -> I2 + KF + KOH). Both forms of the hypofluorous acid may be toxic and should be treated accordingly. Use in a fume hood.

Epoxidation.

HOF was synthesized originally by Appelman,8 but it was hardly a useful synthetic reagent since it was difficult to make and could be generated only in very minute amounts. Still, it was demonstrated that it can react with a few unsaturated compounds.9 Recently, it was discovered that HOF can be prepared simply by passing Fluorine through aqueous Acetonitrile, thus forming a stabilized complex HOF.MeCN.3,10 Possessing a strong electrophilic oxygen, it is an excellent oxygen transfer agent which epoxidizes a wide variety of alkenes (eq 1),3a,c including very deactivated ones which cannot be directly epoxidized by any other method (eq 2).3b

Other Oxidations.

The electrophilic properties of the oxygen have been put to use for attacking the deactivated, relatively electron-rich, tertiary C-H bond, resulting in tertiary hydroxylation as demonstrated, for example, by 4-t-butylcyclohexanol acetate (eq 3).2 Being a strong oxidizer, HOF.MeCN can oxidize amines to the corresponding nitro derivatives (eq 4),4 alcohols to ketones (eq 5),5 and sulfides to sulfones.7 The reactions proceed at 0 °C, in a few minutes and usually in very good yields. On prolonging the reaction time and using an excess of reagent, ketones are also oxidized to the corresponding esters much faster than with the peroxy acids used in the conventional Baeyer-Villiger oxidation (eq 5).5 The reagent can also hydroxylate and otherwise oxidize many aromatic compounds (eq 6), although yields are moderate.6 It should be mentioned that Xenon(II) Fluoride/H2O form in situ HOXeF, which adds the elements of H and OF across some alkenes (eq 7).11


1. Appelman, E. H. ACR 1973, 6, 113.
2. Rozen, S.; Brand, M.; Kol, M. JACS 1989, 111, 8325.
3. (a) Rozen, S.; Kol, M. JOC 1990, 55, 5155. (b) Hung, M. H.; Smart, B. E.; Feiring, A. E.; Rozen, S. JOC 1991, 56, 3187. (c) Hung, M. H.; Rozen, S.; Feiring, A. E.; Resnick, P. R. JOC 1993, 58, 972.
4. (a) Kol, M.; Rozen, S. CC 1991, 567. (b) Rozen, S.; Kol, M. JOC 1992, 57, 7342.
5. Rozen, S.; Bareket, Y.; Kol, M. T 1993, 49, 8169.
6. Kol, M.; Rozen, S. JOC 1993, 58, 1593.
7. Rozen, S.; Bareket, Y. TL 1994, 35, 2099.
8. Studier, M. H.; Appelman, E. H. JACS 1971, 93, 2349.
9. (a) Migliorese, K. G.; Appelman, E. H.; Tsangaris, M. N. JOC 1979, 44, 1711. (b) Andrews, L. E.; Bonnett, R.; Appelman, E. H. T 1985, 41, 781.
10. Appelman, E. H.; Dunkelberg, O.; Kol, M. JFC 1992, 56, 199.
11. Shellhamer, D. F.; Carter, D. L.; Chiaco, M. C.; Harris, T. E.; Henderson, R. D.; Low, W. S. C.; Metcalf, B. T.; Willis, M. C.; Heasley, V. L.; Chapman, R. D. JCS(P2) 1991, 401.

Shlomo Rozen

Tel Aviv University, Israel



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