Trifluoromethanesulfonic Anhydride

Used Chemicals

• Pyridinium p-Toluenesulfonate (= PPTS) [P0942]
• Triphenylphosphine Oxide [T0625]
• Trifluoromethanesulfonic Anhydride (=Tf₂O) [T1100]
• Pentafluorophenol [P0919]
• Triethylamine (= Et₃N) [T0424]
• Dichloromethane

Procedure

Under nitrogen atmosphere, triphenylphosphine oxide (1.057 g, 3.798 mmol) was dissolved in dichloromethane (20 mL) and cooled to 0 °C. Then trifluoromethanesulfonic anhydride anhydride (0.295 mL, 1.80 mmol) was added and stirred for 1 h. After confirming the formation of intermediate 1 by ³¹P-NMR, PPTS (0.452 g, 1.80 mmol) was added and the mixture was stirred for 30 min. After that, a solution of triethylamine (0.28 mL, 2.00 mmol) and pentafluorophenol (0.370 g, 2.00 mmol) in dichloromethane (5 mL) was added dropwise with a syringe to this solution. Then the mixture was warmed to room temperature and stirred for 1 h. After completion of the reaction, the mixture was diluted with dichloromethane (20 mL) and then 2 mol/L HCl (30 mL) was added to quench. The two layers were separated and the organic layer was washed with brine (20 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by silica gel chromatography (hexane:ethyl acetate = 9:1) to afford pentafluorophenyl p-toluenesulfonate as a yellow solid (540 mg, 88% yield).

Experimenter’s Comments

The reaction mixture was monitored by ¹H-NMR and ³¹P-NMR (CDCl₃).
Dichloromethane was used for the reaction after dehydration with molecular sieves and bubbling with nitrogen.

Analytical Data

Pentafluorophenyl p-Toluenesulfonate

¹H NMR (400 MHz, CDCl₃); δ 7.86 (d, J = 8.4 Hz, 2H), 7.42 (d, J = 8.2 Hz, 2H), 2.51(s, 3H).

Lead Reference

• Direct Synthesis of Sulfonamides and Activated Sulfonate esters From Sulfonic Acids
  • S. Caddick, J. D. Wilden, D. B. Judd, J. Am. Chem. Soc. 2004, 126, 1024.

Other Reference

• The Structure of Polymer-Supported Triphenylphosphine Ditriflate: A Potentially Useful Reagent in Organic Synthesis
  • M. J. Petersson, I. D. Jenkins, W. A. Loughlin, J. Org. Chem. 2008, 73, 4691.

Used Chemicals

• Trifluoromethanesulfonic Anhydride (= Tf₂O) [T1100]
• Triethylamine (= Et₃N) [T0424]
• 4-Bromobenzamide [B4216]
• Dichloromethane

Procedure

Tf₂O (0.32 mL, 2.0 mmol, 1.3 eq.) was slowly added to a solution of 4-bromobenzamide (300 mg, 1.5 mmol), and triethylamine (0.54 mL, 3.9 mmol, 2.6 eq.) in dichloromethane (3 mL) at 0 °C. The mixture was stirred at room temperature for 2 hours. Then additional triethylamine (1.1 mL, 7.8 mmol, 5.2 eq.) and Tf₂O (0.64 mL, 3.9 mmol, 2.6 eq.) were added at 0 °C and the mixture was stirred at r.t. for overnight. The reaction mixture was quenched with water (15 mL) and the aqueous layer was extracted with ethyl acetate (15 mL x 3). The combined organic layer was washed with 2 mol/L HCl aq. (15 mL), sat. NaHCO₃ aq. (15 mL), and brine (15 mL), dried over sodium sulfate and filtered. The solvent was removed under reduced pressure and the residue was purified by column chromatography (on silica gel, ethyl acetate:hexane = 1:8) to give 4-bromobenzonitrile a pale yellow solid (165 mg, 61% yield).

Experimenter’s Comments

The reaction mixture was monitored by UPLC.

Analytical Data

4-bromobenzonitrile

¹H NMR (400 MHz, CDCl₃); δ 7.64 (d, J = 8.4 Hz, 2H), 7.53 (d, J = 8.4 Hz, 2H).

Lead Reference

• A Practical Method for the Preparation of Nitriles from Primary Amides Under Non-Acidic Conditions
• D. S. Bose, B. Jayalakshmi, Synthesis 1999, 64.

References

• H. Geng, P.-Q. Huang, Tetrahedron 2015, 71, 3795.

References

• J. E. McMurry, W. J. Scott, Tetrahedron Lett. 1980, 21, 4313.
• H. J. Bestmann, K. Kumar, W. Schaper, Angew. Chem. Int. Ed. Engl. 1983, 22, 167.
• P. J. Stang, M. Hanack, L. R. Subramanian, Synthesis 1982, 85.