N-Bromosuccinimide-Hydrogen Fluoride


[128-08-5]  · C4H4BrNO2  · N-Bromosuccinimide-Hydrogen Fluoride  · (MW 177.99) (HF)

[7664-39-3]  · FH  · N-Bromosuccinimide-Hydrogen Fluoride  · (MW 20.01)

(reagent for the bromofluorination of alkenes and fluorination of dithioesters)

Alternate Name: NBS-HF.

Physical Data: NBS: mp 173-175 °C; d 2.098 g cm-3. HF: mp -83.1 °C; bp 19.54 °C; d 0.991 g cm-3.

Solubility: NBS: sol water, acetone, alcohol, acetic acid, ethyl acetate. HF: sol water, alcohol, benzene, pyridine; slightly sol ether.

Form Supplied in: NBS: off-white to yellow crystalline material; widely available. HF: widely available as aqueous solutions, or anhydrous solutions in pyridine (70% HF, 30% pyridine).

Handling, Storage, and Precautions: NBS: eye protection and rubber gloves should be worn when handling this material. This reagent should only be handled in a fume hood. Absorbed through the skin; high concentrations are destructive to mucous membranes and the tissues of upper respiratory systems. HF: eye protection and rubber gloves should be worn when handling this material. This reagent should only be handled in a fume hood. Corrosive, highly irritating, and poisonous. Should not be stored in glass containers; will etch glass. Causes severe burns, which may not be immediately apparent. Extremely destructive to mucous membranes and tissues of the upper respiratory system. Pyridine solutions are moisture sensitive.

Fluorination and Bromofluorination of Alkenes.

N-Bromosuccinimide used in conjunction with poly(hydrogen fluoride)/tertiary amine reagents bromofluorinates alkenes1 and polymeric alkenes (eq 1).2 In ether, using HF/pyridine, the products exhibit typical Markovnikov regioselectivity, with the bromide adding to the least substituted end of the alkene.3 Bromofluorination also occurs with NBS and liquid Hydrogen Fluoride, but these conditions are more harsh and are more difficult to carry out due to the need for low temperature and high pressure.4 The reaction is stereoselective, giving anti addition products (eq 2).3,5a This reaction can be done with HF supported on crosslinked poly(styrene-co-4-vinylpyridine) or poly-4-vinylpyridinium, and exhibits the same regio- and stereoselectivity as that with HF supported on pyridine.5 If Silver(I) Fluoride is added to the reaction after completion, vic-difluorides can be formed by exchange of the bromofluoroalkane to the difluoride.1 If any water is present, the vicinal halohydrin can also be formed.6

In the reaction of NBS-HF/pyridine, several factors influence the stereoselectivity.3,7 Normal anti selectivity results from the NBS-HF complex reacting with one face of the alkene, thus preventing fluoride ion from adding in a syn fashion. If the concentration of HF is increased, the complexing effects are lessened, and fluoride can add to the carbocation from either face.7 The reaction of 1-phenyl-4-t-butylcyclohexene demonstrates the selectivity, reacting to give two anti products, resulting from complexation on either face of the alkene (eq 3).3c In addition to concentration, the diastereoselectivity for bromofluorination of alkenes is dependent on solvent effects7 and alkene geometry.4,8

For large cyclic alkenic compounds containing an oxirane group, bromofluorination fails to give the expected a-bromo-b-fluoro compound, due to competing complexation with the oxirane ring. Instead, a mixture of bicyclic ethers substituted with bromine and fluorine is produced (eq 4).9

NBS-HF/pyridine or poly-4-vinylpyridinium reacts with diazoalkanes and diazo ketones to give the a,a-bromofluoroalkanes and ketones (eq 5).10 Hydrazones of aldehydes and ketones also react under these conditions, giving the gem-difluoro compounds, with the fluoride substituents replacing the hydrazone, in effect allowing the transformation of carbonyls to gem-difluoro compounds (eq 6).11

NBS-HF/pyridine has also been used for the fluorination of dithioesters of aromatic acids, which react to give trifluoromethyl substituted aromatic compounds (eq 7).12 This reaction can also be carried out on sulfides where one of the substituents is ArCF2, to give trifluoromethylaryl compounds.

1. (a) Bowers, A. JACS 1959, 81, 4107. (b) Olah, G. A.; Nojima, M.; Kerekes, I. S 1973, 780. (c) Gregorcic, A.; Zupan, M. CCC 1977, 42, 3192.
2. Asahi Chemical Industry Co., Ltd. Jpn. Patent 58 219 202, 1983 (CA 1984, 100, 217 907u).
3. (a) Zupan, M. JFC 1977, 9, 177. (b) Stavber, S.; Zupan, M. BCJ 1979, 52, 925. (c) Gregorcic, A.; Zupan, M. JOC 1984, 49, 333. (d) Zupan, M.; Pollack, A. JCS(P1) 1976, 971.
4. Mel'nikova, N. B.; Yasman, Y. B.; Boguslavskaya, L. S.; Kartashov, V. R. JOU 1980, 16, 1723.
5. (a) Gregorcic, A.; Zupan, M. JFC 1984, 24, 291. (b) Olah, G. A.; Li, X.-Y. SL 1990, 267.
6. Chi, D.-Y.; Kiesewetter, D. O.; Katzenellenbogen, J. A.; Kilbourn, M. R.; Welch, M. J. JFC 1986, 31, 99.
7. Hamman, S.; Beguin, C. G. JFC 1983, 23, 515.
8. Hamman, S.; Benaissa, T.; Beguin, C. G. JCR(S) 1992, 20.
9. Haufe, G.; Alvernhe, G.; Laurent, A. JFC 1990, 46, 83.
10. Olah, G. A.; Welch, J. A. S 1974, 896.
11. Prakash, S. G. K.; Reddy, V. P.; Li, X.-Y.; Olah, G. A. SL 1990, 594.
12. Hiyama, T.; Kuroboshi, M. Jpn. Patent 04 283 524, 1992 (CA 1993, 118, 168 804u).

Andrew K. Jones & Timothy E. Wilson

Emory University, Atlanta, GA, USA

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