Tetrafluoroboric Acid

BF4H

[16872-11-0]  · BF4H  · Tetrafluoroboric Acid  · (MW 87.82) (HBF4.OMe2)

[67969-83-9]  · C2H7BF4O  · Tetrafluoroboric Acid Dimethyl Etherate  · (MW 133.90) (HBF4.OEt2)

[67969-82-8]  · C4H11BF4O  · Tetrafluoroboric Acid Diethyl Etherate  · (MW 161.96)

(strong acid with pKa = -0.441 and a noncoordinating counterion2)

Solubility: sol H2O, alcohols and ethers.

Form Supplied in: 48% aq solution; diethyl ether complex; dimethyl ether complex.

Purification: commercial 50% solutions can be concentrated by evaporation at 50-60 °C/5 mmHg to give a residue of 11 N total acidity. Water can also be removed by slow addition to ice-cold acetic anhydride (dangerously exothermic reaction: caution is advised!).3

Handling, Storage, and Precautions: storage in glass containers is not recommended, although dilute solutions can be used in glass containers over short periods. Poisonous: causes burns to eyes, skin, and mucous membranes and may be fatal if ingested. Use in a fume hood with safety goggles and chemically resistant gloves and clothing. Incompatible with cyanides and strong bases: decomposes to form HF.

General Considerations.

Tetrafluoroboric acid is a useful strong Brønsted acid with a nonnucleophilic counterion. Its solubility in polar organic solvents makes it a useful strong acid under nonaqueous conditions.

Preparation of Arenediazonium Tetrafluoroborates.

Arenediazonium salts can be precipitated as their tetrafluoroborate salts by addition of a cold solution of HBF4 to a solution of the initial arenediazonium chloride. 4-Methoxybenzenediazonium tetrafluoroborate is thus obtained in 94-98% yield. The arylamine can be diazotized with Sodium Nitrite in the presence of HBF4, and the diazonium fluoroborate then precipitates directly. 3-Nitroaniline, when treated in this manner, provides a 90-97% yield of 3-nitrobenzenediazonium tetrafluoroborate (eq 1).4 Diazotizations of arylamines and heteroarylamines in organic solvents can be conveniently conducted using HBF4.OEt2 and alkyl nitrites.5

Protecting-Group Manipulations.

A preparation of monoesters of glutamic and aspartic acids using HBF4.OEt2 as a catalyst has been developed. The diesters are generally side products when other acids are used, but HBF4.OEt2 appears to suppress the diesterification. Thus L-glutamic acid g-benzyl ester was obtained in 94% yield by treatment of the carboxylic acid in BnOH with the HBF4.OEt2 catalyst and a drying agent.6

When di-t-butyl carbonate is treated with DMAP.HBF4, water-soluble Boc-pyridinium tetrafluoroborate is formed.36 This reagent installs the Boc protecting group onto amino acids in aqueous NaOH. Thus L-proline is converted to its N-Boc derivative in nearly quantitative yield in 10 min.

Carbohydrate protection and deprotection reactions are amenable to HBF4 catalysis; aqueous HBF4 and HBF4.OEt2 are complementary in these applications. Transacetalization with benzaldehyde dimethyl acetal and ethereal HBF4 gives a monobenzylidene product without disturbing the isopropylidene and trityl groups of the substrate (eq 2). Aqueous HBF4 is useful in selective deprotection reactions, cleaving a trityl group in the presence of other acid-sensitive functionality (eq 3).7

Recently developed in solid-phase peptide synthesis is the use of HBF4/thioanisole/m-cresol as a general deprotection reagent. Most commonly used groups are cleaved from termini or side chain functionality under mild conditions (1 M HBF4, 4 °C, 30-60 min) in very high yields. Human glucagon (a 29 residue peptide) has been synthesized as a demonstration of the effectiveness of the method,8 which has been successful in both solid-phase and solution-phase syntheses.9

General Acid Catalysis.

HBF4 is a versatile acid catalyst which is applicable to many typical acid-catalyzed reactions. Some adducts obtained upon reaction of cyclopropyl phenyl sulfide anion with carbonyl compounds can be rearranged to cyclobutanones under the catalytic influence of HBF4 (eq 4), although different acids have been required for other substrates.10 Acid-catalyzed rearrangement of 2-cyclopropylphenyl phenyl ether or sulfide with HBF4 has been reported (eq 5).11

Acid-catalyzed oxidation of epoxides with HBF4.OMe2/DMSO results in the formation of a-hydroxy ketones (eq 6).12 This procedure in an acidic medium complements the a-hydroxylation of ketone enolates under strongly basic conditions.

An intramolecular alkylation of a diazomethyl ketone was achieved with catalysis by HBF4, providing an angularly fused cyclopentanone hydrofluorene (eq 7).13

Other catalytic applications of HBF4 include alkene isomerizations,14 alkylation of alcohols with diazoalkanes,15 preparations of substituted pyridines,16 hydrolysis of a-hydroxyketene or a-(methylthio)ketene thioacetals to a,b-unsaturated thioesters,17 and terpene formation from isoprenic precursors.18

Preparation of Annulated Triazolones.

Cyclization of the isocyanate in eq 8 in the presence of HBF4 affords an oxotriazolium tetrafluoroborate, which then rearranges to form a 1,5-heteroannulated 1,2-dihydro-2-phenyl-3H-1,2,4-triazol-3-one (eq 8).19

Carbenium Tetrafluoroborate Preparation.

4,6,8-Trimethylazulene is converted by ethereal HBF4 into 4,6,8-trimethylazulenium tetrafluoroborate.20 A convenient preparation of tropylium tetrafluoroborate employs HBF4 to precipitate the product from a solution of the double salt [C7H7]PCl6.[C7H7]Cl in ethanol (eq 9). An indefinitely stable, nonhygroscopic, and nonexplosive white solid is obtained, a distinct advantage of a fluoroborate salt.21

The formyl cation equivalent 1,3-benzodithiolylium tetrafluoroborate can be made in 94% yield by treatment of a dithioorthoformate with HBF4/Ac2O (eq 10).22 2-Deuterio-1,3-benzothiolylium tetrafluoroborate prepared by this method has been used to produce 1-deuterioaldehydes by homologation.23 An analogous preparation of a similar formyl cation equivalent, 1,3-dithiolan-2-ylium tetrafluoroborate, employs HBF4.OEt2 (eq 11) to provide the intermediate salt. Subsequent reaction with a silyl enol ether forms a masked 2-formylcyclohexanone in high yield (eq 11).

Ethynylfluorenylium dyes can be obtained by treatment of appropriate tertiary alcohols with HBF4 (eq 12).24

In addition to the aforementioned carbenium ions and diazonium ions, numerous other organic cations can be obtained as their fluoroborate salts by treatment of appropriate precursors with HBF4.25

Dimerization of Carbodiimides.

Treatment of alkyl carbodiimides with anhydrous HBF4.OEt2 in CH2Cl2 results in rapid dimerization to tetrafluoroborate salts in 95% yield (eq 13). Basification converts the salts to diazetidines.26 In the same work, aryl carbodiimides undergo a similar reaction, but substituted quinazolines are obtained.

Mercury(II) Oxide/Tetrafluoroboric Acid.

Yellow Mercury(II) Oxide is added to 48% aqueous HBF4 to yield, upon solvent removal, HgO.2HBF4 as a hygroscopic white solid.27 This reagent is useful in applications involving mercuration of alkenes, including diamination of alkenes and preparation of trans-cinnamyl ethers from allylbenzene.28 Alkylations of carboxylic acids29 and alcohols30 with alkyl halides are also facilitated by HgO.2HBF4. Mercury(II) oxide and HBF4 in alcohol effected mild solvolysis of 2-hydroxytrithioorthoesters to yield a-hydroxycarboxylic esters in high yield.31 See also Mercury(II) Oxide-Tetrafluoroboric Acid.

Preparation of a Useful Hypervalent Iodine Reagent.

When treated with HBF4.OMe2 at low temperatures, Iodosylbenzene reacts with silyl enol ethers to form a hypervalent iodine adduct capable of useful carbon-carbon bond formation reactions with alkenes (eq 14).32

Synthesis of Cationic Organometallic Complexes.

Tetrafluoroborate is frequently encountered as the counterion in cationic organometallic compounds; its lack of nucleophilic reactivity makes HBF4 and its etherates ideal reagents for delivery of protons without side reactions. The poorly coordinating conjugate base of HBF4 allows substrates greater opportunity to bind to metals in organometallic reactions requiring the presence of acids.33

Propargylium complexes of cobalt, obtained by treatment of propargylic alcohols with HBF4.OEt2, have been studied with regard to their selectivity as alkylating agents. N-Acetyl-3,4-dimethoxyphenethylamine undergoes selective aromatic substitution, whereas the unprotected amine undergoes N,N-dialkylation but not aromatic substitution (eq 15).34

Oxidation.

In a reaction proposed as a model for substrate reactions at metal-sulfur centers of enzymes, HBF4 apparently functions as an oxidizing agent in a two-electron oxidation of a ruthenium benzenedithiolate complex (eq 16).35


1. (a) Sudakova, T. N.; Krasnoshchekov, V. V. Zh. Neorg. Khim. 1978, 23, 1506. (b) Acidity relative to other strong acids: Bessiere, J. BSF 1969, 9, 3356.
2. Ellis, R.; Henderson, R. A.; Hills, A.; Hughes, D. L. JOM 1987, 333, C6.
3. (a) Lichtenberg, D. W.; Wojcicki, A. JOM 1975, 94, 311. (b) Wudl, F.; Kaplan, M. L. Inorg. Synth. 1979, 19, 27.
4. Roe, A. OR 1949, 5, 193. See also: (a) Starkey, E. B. OSC 1943, 2, 225. (b) Curtin, D. Y.; Ursprung, J. A. JOC 1956, 21, 1221. (c) Schiemann, G.; Winkelmuller, W. OSC 1943, 2, 299.
5. (a) Cohen, T.; Dietz, A. G., Jr.; Miser, J. R. JOC 1977, 42, 2053. (b) Allmann, R.; Debaerdemaeker, T.; Grehn, W. CB 1974, 107, 1555.
6. Albert, R.; Danklmaier, J.; Honig, H.; Kandolf, H. S 1987, 635.
7. Albert, R.; Dax, K.; Pleschko, R.; Stutz, A. E. Carbohydr. Res. 1985, 137, 282.
8. Akaji, K.; Yoshida, M.; Tatsumi, T.; Kimura, T.; Fujiwara, Y.; Kiso, Y. CC 1990, 288.
9. Kiso, Y.; Yoshida, M.; Tatsumi, T.; Kimura, T.; Fujiwara, Y.; Akaji, K. CPB 1989, 37, 3432.
10. Trost, B. M.; Keeley, D. E.; Arndt, H. C.; Bogdanowicz, M. J. JACS 1977, 99, 3088.
11. Shabarov, Y. S.; Pisanova, E. V.; Saginova, L. G. ZOR 1980, 16, 418 (CA 1981, 94, 3819a).
12. Tsuji, T. BCJ 1989, 62, 645.
13. Ray, C.; Saha, B.; Ghatak, U. R. SC 1991, 21, 1223.
14. Powell, J. W.; Whiting, M. C. Proc. Chem. Soc. 1960, 412.
15. (a) Neeman, M.; Johnson, W. S. OS 1961, 41, 9. (b) Brückner, R.; Peiseler, B. TL 1988, 29, 5233.
16. (a) Schulz, W.; Pracejus, H.; Oehme, G. J. Mol. Catal. 1991, 66, 29. (b) Kanemasa, S.; Asai, Y.; Tanaka, J. BCJ 1991, 64, 375.
17. Dieter, R. K.; Lin, Y. J.; Dieter, J. W. JOC 1984, 49, 3183.
18. Babin, D.; Fourneron, J.-D.; Julia, M. BSF(2) 1980, 588.
19. Gstasch, H.; Seil, P. S 1990, 1048.
20. (a) Hafner, K.; Pelster, H.; Schneider, J. LA 1961, 650, 62. (b) Hafner, K.; Pelster, H.; Patzelt, H. LA 1961, 650, 80.
21. Conrow, K. OS 1963, 43, 101.
22. Nakayama, J.; Fujiwara, K.; Hoshino, M. CL 1975, 1099.
23. Nakayama, J. BCJ 1982, 55, 2289.
24. Nakatsuji, S.; Nakazumi, H.; Fukuma, H.; Yahiro, T.; Nakashima, K.; Iyoda, M.; Akiyama, S. JCS(P1) 1991, 1881.
25. A few examples: (a) oxotriazolium: Gstasch, H.; Seil, P. S 1990, 1048. (b) pyridinium: Paley, M. S.; Meehan, E. J.; Smith, C. D.; Rosenberger, F. E.; Howard, S. C.; Harris, J. M. JOC 1989, 54, 3432. (c) pyridinium: Guibe-Jampel, E.; Wakselman, M. S 1977, 772. (d) tetrameric dication from 2-aminobenzaldehyde: Skuratowicz, J. S.; Madden, I. L.; Busch, D. H. IC 1977, 16, 1721. (e) tetrathiafulvenium: Wudl, F. JACS 1975, 97, 1962. Wudl, F.; Kaplan, M. L. Inorg. Synth. 1979, 19, 27. (f) sulfonium: LaRochelle, R. W.; Trost, B. M. JACS 1971, 93, 6077. (g) diazetidinium: Hartke, K.; Rossbach, F. AG(E) 1968, 7, 72.
26. Hartke, K.; Rossbach, F. AG(E) 1968, 7, 72.
27. Barluenga, J.; Alonso-Cires, L.; Asensio, G. S 1979, 962.
28. Barluenga, J.; Alonso-Cires, L.; Asensio, G. TL 1981, 22, 2239.
29. Barluenga, J.; Alonso-Cires, L.; Campos, P. J.; Asenio, G. S 1983, 649.
30. Barluenga, J.; Alonso-Cires, L.; Campos, P. J.; Asensio, G. T 1984, 40, 2563.
31. Scholz, D. SC 1982, 12, 527.
32. Zhdankin, V. V.; Tykwinski, R.; Caple, R.; Berglund, B.; Koz'min, A. S.; Zefirov, N. S. TL 1988, 29, 3703.
33. Ellis, R.; Henderson, R. A.; Hills, A.; Hughes, D. L. JOM 1987, 333, C6. Some other recent examples of the use of HBF4.OEt2 in synthesis and/or reactions of organometallics: (a) Field, J. S.; Haines, R. J.; Stewart, M. W.; Sundermeyer, J.; Woollam, S. F. JCS(D) 1993, 947. (b) Dawson, D. M.; Henderson, R. A.; Hills, A.; Hughes, D. L. JCS(D) 1992, 973. (c) Lemos, M. A. N. D. A.; Pombeiro, A. J. L.; Hughes, D. L.; Richards, R. L. JOM 1992, 434, C6. (d) Arliguie, T.; Chaudret, B.; Jalon, F. A.; Otero, A.; Lopez, J. A.; Lahoz, F. J. OM 1991, 10, 1888. (e) Bassner, S. L.; Sheridan, J. B.; Kelley, C.; Geoffroy, G. L. OM 1989, 8, 2121. For use of HBF4.OMe2: (a) Schrock, R. R.; Liu, A. H.; O'Regan, M. B.; Finch, W. C.; Payack, J. F. IC 1988, 27, 3574. (b) Blagg, J.; Davies, S. G.; Goodfellow, C. L.; Sutton, K. H. JCS(P1) 1987, 1805.
34. Gruselle, M.; Philomin, V.; Chaminant, F.; Jaouen, G.; Nicholas, K. M. JOM 1990, 399, 317.
35. Sellmann, D.; Binker, G.; Knoch, F. ZN(B) 1987, 42, 1298.
36. Guibe-Jampel, E.; Wakselman, M. S 1977, 772.

Gregory K. Friestad & Bruce P. Branchaud

University of Oregon, Eugene, OR, USA



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