Sulfur Tetrafluoride1

SF4

[7783-60-0]  · F4S  · Sulfur Tetrafluoride  · (MW 108.07)

(fluorinating agent for many functional groups;1 can form other fluorinating agents1)

Physical Data: mp -121.0 °C; bp -38 °C; d (liq, -78 °C) 1.95 g cm-3, d (solid, -183 °C) 2.349 g cm-3.

Solubility: sol benzene.

Form Supplied in: colorless gas.

Handling, Storage, and Precautions: is about as toxic as phosgene. It is also a strong irritant and a corrosive agent that should be handled with utmost care in a well-ventilated fume hood. Sulfur tetrafluoride reacts violently with water. The reagent can be handled in a well-dried Pyrex glass apparatus up to about 30 °C with only nominal attack. Stainless steel, copper, and nickel are all inert to SF4 at both ordinary and elevated temperatures. First-aid treatment of hydrogen fluoride burns has been described.2 A reactor design for safe, routine handling of SF4 and HF is available.3

Introduction.

Sulfur tetrafluoride is one of the more common fluorinating agents. It converts hydroxyl, carbonyl, and carboxylic groups into mono-, di-, and trifluoromethyl groups, respectively (eq 1).

Fluorination of Alcohols.

Sulfur tetrafluoride is suitable for fluorination of alcohols in high yield, provided that the alcohols are roughly equal to or greater than tropolone in acidity (pKa = 6.42).1a Decomposition is often a problem during SF4 fluorination of aliphatic alcohols and various alternative fluorinating agents have been introduced, e.g. N,N-Diethylaminosulfur Trifluoride (DAST),4 SeF4-pyridine,5 and HF.amine (see Hydrogen Fluoride) reagents.6

(2-Furyl)methanol and 2-phenylethanol react with SF4 at -50 °C in the presence of Triethylamine or Pyridine in CH2Cl2 or cyclohexane to give (2-fluoromethyl)furan and 2-fluoro-1-phenylethane, respectively (eqs 2 and 3).7

Fluorination of vicinal diols such as ethanediol and 1,2-propanediol under mild conditions leads to the formation of 2-fluoro fluorosulfites, which are readily hydrolyzed to give the respective fluorohydrins (eqs 4 and 5).8 A different pattern is observed in the reaction of 3,3,3-trifluoro-1,2-propanediol with SF4 (eq 6).

Selective substitution of the hydroxyl group by fluorine can also be realized in the reactions of SF4 with 1,3- and 1,4-diols (eqs 7 and 8).9

Reaction of glycerol with SF4 in anhydrous HF under mild conditions leads unexpectedly to 3-fluoro-1,2-propylene sulfite (eq 9).10 Treatment of myo-inositol with SF4 and anhydrous HF yields a novel compound, the cyclic sulfite ester of 2b,3b-difluoro-7-oxabicyclo[2.2.1]heptane-5a,6a-diol (eq 10).11

Fluorination of Aldehydes and Ketones.

Aldehydes lacking a-hydrogens react with SF4 at high temperatures (150-200 °C) to afford gem-difluoride compounds (eq 11).1a Aldehydes possessing a-hydrogen atoms can be fluorinated by SF4 at lower temperatures (to prevent decomposition) and yields of the resulting difluorides are generally low (eq 12).1a

Fluorination of ketones by SF4 is exemplified as shown in eq 13.12 Either one or both carbonyl groups can be converted into difluoromethylene by the control of reaction temperature and time.

Aliphatic b-diketones react with SF4 to form the corresponding di- and tetrafluoro derivatives and also compounds containing double and triple carbon-carbon bonds (eq 14).13

Fluorination of Carboxylic Acids.

Aliphatic carboxylic acids react with SF4 at low temperature to give 1,1,1-trifluoroalkanes as well as the unexpected a,a,a,a-tetrafluoroalkyl ethers (eq 15).1b The yields of tetrafluoroalkyl ethers depend primarily on their stability in the reaction medium because they are subject to protolytic decomposition by HF (eq 16).

Sulfur tetrafluoride fluorination of aromatic carboxylic acids is the method of choice for introducing the trifluoromethyl substituent (eqs 17-19).1b,14

Preparation of Other Fluorinating Agents.

Sulfur tetrafluoride is used to prepare a very useful fluorinating agent, N,N-Diethylaminosulfur Trifluoride (DAST) (eq 20).1b

DAST is a convenient reagent to replace the hydroxyl group and carbonyl oxygen of aldehydes or ketones with one and two fluorine atoms, respectively.


1. (a) Boswell, G. A. Jr.; Ripka, W. C.; Scribner, R. M.; Tullock, C. W. OR 1974, 21, 1. (b) Wang, C.-L. J. OR 1985, 34, 319. (c) Dmowski, W. JFC 1986, 32, 255.
2. Finkel, A. J. Adv. Fluorine Chem. 1973, 7, 199.
3. Nickson, T. E. JFC 1991, 55, 169.
4. Middleton, W. J. JOC 1975, 40, 574.
5. Olah, G. A.; Nojima, M.; Kerekes, I. JACS 1974, 96, 925.
6. Olah, G. A., Welch, J. T.; Vankar, Y. D.; Nojima, M.; Kerekes, I.; Olah, J. A. JOC 1979, 44, 3872.
7. Janzen, A. F.; Marat, R. K. JFC 1988, 38, 205.
8. Burmakov, A. I.; Hassanein, S. M.; Kunshenko, B. V.; Alekseeva, L. A.; Yagupol'skii, L. M. JOU 1986, 22, 1146.
9. Hassanein, S. M.; Burmakov, A. I.; Bloshchitsa, F. A.; Yagupol'skii, L. M. JOU 1988, 24, 1473.
10. Hassanein, S. M.; Burmakov, A. I.; Bloshchitsa, F. A.; Yagupol'skii, L. M. JOU 1987, 23, 1003.
11. Coe, P. L.; Proctor, L. D.; Martin, J. A.; Thomas, W. A. JFC 1992, 58, 87.
12. Aleksandrov, A. M.; Sorochinskii, A. E.; Petrenko, A. E.; Kukhar', V. P. JOU 1988, 24, 131.
13. Stepanov, I. V.; Burmakov, A. I.; Kunshenko, B. V.; Alekseeva, L. A.; Yagupol'skii, L. M. JOU 1983, 19, 244.
14. Lyalin, V. V.; Grigorash, R. V.; Alekseeva, L. A.; Yagupol'skii, L. M. JOU 1984, 20, 769.

Chia-Lin J. Wang

Development Center for Biotechnology, Taipei, Taiwan



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