Pyridinium Poly(hydrogen fluoride)1

(C5H5N.9HF; 30% pyridine, 70% HF by wt)

[32001-55-1]  · C5H14F9N  · Pyridinium Poly(hydrogen fluoride)  · (MW 259.20)

(convenient, less volatile form of anhydrous HF with enhanced nucleophilicity; substitutes F for secondary or tertiary hydroxy groups,2 other halides,3 or primary amine4 groups; adds HF to alkenes and alkynes;1d with halonium ion sources, halofluorinates alkenes and alkynes;1a,5 opens and adds HF to oxiranes (epoxides), aziridines, azirines, and cyclopropanes;1 oxidatively fluorinates when combined with electrolytic processes or PbIV compounds1c,e)

Alternate Names: Olah's reagent; hydrogen fluoride-pyridine

Physical Data: dissoc 55 °C; at 80-110 °C, liq phase is primarily py.5HF; at reflux (160-170 °C) the stoichiometry is py.3HF; low-temperature phase behavior and X-ray crystal structures for some phases are known.6

Solubility: sol CH2Cl2, MeCN, Et2O, THF, toluene, sulfolane.

Form Supplied in: light brown liquid in plastic bottles; H2O most likely impurity (from HF used); commercially available.

Preparative Method: condensation of anhydrous Hydrogen Fluoride into Pyridine at -78 °C, followed by gradual warming to rt; caution: highly exothermic.1d,e

Purification: best approach is to purify components (pyridine, HF) before mixing.7 HF can also be dried using Antimony(V) Fluoride,8 BiF5,8,9 high-pressure Fluorine,10 or electrolysis.

Handling, Storage, and Precautions: toxic, hygroscopic, corrosive. Moisture drastically inhibits fluorination activity. Compatible materials: polyethylene, fluoro polymers (FEP, PFA, PTFE). Hydrogen pressure may accumulate in metal HF storage containers. Avoid contact with glass. Sodium Fluoride, aq base, and CaCl2 are useful for neutralization and workup. Reagent contains a small equilibrium concentration of HF. Although the reduced HF vapor pressure in py.(HF)x reduces the potential for exposure, extreme care should be used in handling this material; handle only in a fume hood, wear safety goggles or a face shield, and wear appropriate impermeable clothing. Effects of exposure to HF are often delayed for several hours, but the burns are extremely painful and can be slow to heal. Exposure to py.(HF)x should be treated in the same way as for HF. Thus users and coworkers should be familiar with and be prepared to administer the proper first aid treatment.11

Substitution Reactions.

Fluorodehydroxylation.

Secondary and tertiary alcohols react with py.(HF)x to give alkyl fluorides. The tertiary compounds react quickly at temperatures as low as -70 °C, while rt is usually sufficient for secondary alcohols. This can provide significant regioselectivity as shown for reactions at the competitive sites in a steroid (eq 1).12 Primary alcohols require the addition of NaF for the substitution to occur. The probable SN2 mechanism of the reaction is illustrated by the lack of rearrangement upon fluorination of neopentyl alcohol (eq 2)2 (for alternative reagents, see fluoroalkylamine reagents (FAR), N,N-Diethylaminosulfur Trifluoride (DAST)).

Halogen Exchange.

No fluorination of tertiary alkyl halides occurs unless the halide is abstracted by an agent such as a nitronium salt (eq 3).3 Related R3N.3HF complexes are more effective for nucleophilic halide replacement.1c

Fluorodeamination.

Substitution of F for NH2 is achieved by an in situ diazotization-fluorinative dediazotization sequence. For example, a-fluorocarboxylic acids are obtained from a-amino acids, as shown for 2-aminobutanoic acid (eq 4).4 Retention of configuration is usually observed.

Addition Reactions.

Hydrofluorination of Alkenes and Alkynes.

Addition of HF takes place in Markovnikov fashion. Among alkenes, branched derivatives and cycloalkenes give higher yields (eq 5).1d,e As expected, gem-difluoro derivatives are obtained from alkynes (eq 6).1d THF is often used as a cosolvent since the starting materials are generally insoluble in py.(HF)x. The related melamine.(HF)x reagent is especially effective for hydrofluorination of unsaturated substrates and can be used repeatedly in pentane or CCl4 two-phase systems.1c

Halofluorination of Alkenes and Alkynes.

When these unsaturated compounds are combined with py.(HF)x and a source of halonium ion (e.g. N-halosuccinimides, N-haloacetamides, or 1,3-Dibromo-5,5-dimethylhydantoin (DBH)), addition of XF (X = Cl, Br, I) to the multiple bond is the result. Alkenes provide several potentially useful extensions from the initial 1,2-halofluoroalkane products.1a For example, addition of Silver(I) Fluoride to the initial product results in halogen exchange yielding vicinal difluorides without isolation of the intermediates. Similarly, reduction of the intermediates with a tin hydride reagent gives products corresponding to Markovnikov addition of HF to the starting alkene. Elimination reactions of the intermediates with base lead to vinyl fluorides. Alkene halofluorination was found to exhibit Markovnikov and anti-Markovnikov orientation in the case of 1-phenyl-4-t-butylcyclohexene.13

Bromofluorination of phenylacetylene using py.(HF)x and DBH in sulfolane (eq 7)5 gave a mixture of (Z) and (E) isomers but with good regio- and stereoselectivity.

Ring-Opening Fluorination.

The fluoride ion donor ability of py.(HF)x is shown by the cleavage of cyclopropane (eq 8),14 in which fluoride traps the primary cation before it can rearrange. Regioselective conversion of oxiranes to fluorohydrins has become an important process in the steroid field (eq 9).15 An iterative cyclization/ring opening approach has served in the conversion of a tetrachlorocyclohexanol to its tetrafluoro analog with complete regio- and stereoselectivity.16 In the case of aziridines the ring opening is regioselective in that fluoride becomes bound to the carbon best able to stabilize a positive charge, but the stereochemistry depends strongly on the starting material and the fluorinating agent.1c,e Substituted 1-azirines give difluorinated amines or a-fluoro ketones, depending on the substituents.1c,e

Oxidative Fluorination.

With py.(HF)x and stoichiometric amounts of PbIV, phenols are converted to difluorodienones (eq 10). Benzene reacts very slowly to give the same product.1b,c Similar reactions can be conducted using anodic oxidation in place of the lead compounds. In both situations, cations or radical cations are proposed as the initially generated species, which then react with fluoride. For these reactions, Triethylamine.3HF is used most often.

Related Reagents.

Several applications of Et3N.3HF and melamine.(HF)x have been mentioned above. In addition, 2,4,6-trimethylpyridine.(HF)x [45725-47-1] is useful since it is a commercially available solid melting at 90 °C. A polymer-supported agent containing about 35-40% HF, poly[4-vinylpyridinium poly(hydrogen fluoride)], is also available.17


1. (a) Mascaretti, O. A. Aldrichim. Acta 1993, 26, 47. (b) Wilkinson, J. A. CRV 1992, 92, 505. (c) Yoneda, N. T 1991, 47, 5329. (d) Olah, G. A.; Welch, J. T.; Vankar, Y. D.; Nojima, M.; Kerekes, I.; Olah, J. A. JOC 1979, 44, 3872. (e) Synthetic Fluorine Chemistry; Olah, G. A.; Chambers, R. D.; Prakash, G. K. S., Eds.; Wiley: New York, 1992; pp 163-204. (f) Fluorine: The First Hundred Years (1886-1986); Banks, R. E.; Sharp, D. W. A.; Tatlow, J. C., Eds.; Elsevier: New York, 1986; pp 377-381. (g) Fluorine in Bioorganic Chemistry; Welch, J. T.; Eswarakrishnan, S., Eds.; Wiley: New York, 1991.
2. Olah, G. A.; Welch, J. S 1974, 653.
3. Olah, G. A.; Shih, J. G.; Singh, B. P.; Gupta, B. G. B. S 1983, 713.
4. Olah, G. A.; Welch, J. S 1974, 652.
5. Eddarir, S.; Mestdagh, H.; Rolando, C. TL 1991, 32, 69.
6. Boenigk, D.; Mootz, D. JACS 1988, 110, 2135.
7. Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory Chemicals, 3rd ed.; Pergamon: New York, 1988; pp 267-268, 327.
8. Christe, K. O.; Schack, C. J.; Wilson, R. D. IC 1975, 14, 2224.
9. Christe, K. O.; Wilson, W. W.; Schack, C. J. JFC 1978, 11, 71.
10. Tolberg, W. E.; Rewick, R. T.; Stringham, R. S.; Hill, M. E. IC 1967, 6, 1156.
11. (a) Effects of Exposure to Toxic Gases-First Aid and Medical Treatment, 3rd ed.; Scornavacca, F.; Mossman, A., Eds.; Matheson: Secaucus, NJ, 1988. (b) Finkel, A. J. Adv. Fluorine Chem. 1973, 7, 199. (c) MacKinnon, M. A. Dermatol. Clinics 1988, 6, 67. (d) Dunn, B. J.; MacKinnon, M. A.; Knowlden, N. F.; Billmaier, D. J.; Derelanko, M. J.; Rusch, G. M.; Naas, D. J.; Dahlgren, R. R. J. Occup. Med. 1992, 34, 902. (e) AlliedSignal Inc., HF Products Group. Recommended Medical Treatment for Hydrofluoric Acid Exposure; AlliedSignal: Morristown, NJ, 1991.
12. Parish, E. J.; Schroepfer, G. J., Jr. JOC 1980, 45, 4034.
13. Gregorcic, A.; Zupan, M. JOC 1984, 49, 333.
14. Olah, G. A.; Nojima, M.; Kerekes, I. S 1973, 779.
15. Annen, K.; Hofmeister, H.; Laurent, H.; Wiechen, R. LA 1982, 966.
16. Duhamel, P.; Leblond, B.; Poirier, J.-M. CC 1993, 476.
17. Olah, G. A.; Li, X.-Y. SL 1990, 267.

Stefan P. Kotun

Ohmeda, The BOC Group, Murray Hill, NJ, USA



Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.