2,2,2-Trifluoroethyl Trifluoromethanesulfonate

Used Chemicals

• 4'-Hydroxyacetophenone [H0193]
• 2,2,2-Trifluoroethyl Triflate (= CF₃CH₂OTf) [T1604]
• Sodium Hydride (60%, dispersion in Paraffin Liquid) [S0481]
• DMF

Procedure

To a solution of 4'-hydroxyacetophenone (1.0 g, 7.34 mmol) in DMF (10 mL) was slowly added sodium hydride (353 mg, 8.38 mmol) at rt and the mixture was stirred for 10 min. CF₃CH₂OTf (1.27 mL, 8.38 mmol) was added to the reaction mixture and stirred overnight at 60 °C. The reaction mixture was diluted with ethyl acetate (100 mL) and washed with water (50 mL) and brine (50 mL), then the organic layer was 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 = 0:1 - 15:85) to give 4-(2,2,2-trifluoroethoxy)acetophenone as a pale yellow solid (1.2 g, 71%).

Experimenter’s Comments

The reaction mixture was monitored by UPLC.

Analytical Data

4-(2,2,2-trifluoroethoxy)acetophenone

¹H NMR (270 MHz, CDCl₃); δ 7.98 (d, 2H, J = 8.9 Hz), 6.99 (d, 2H, J = 8.9 Hz), 4.43 (q, 2H, J = 8.1 Hz), 2.59 (s, 3H).

Lead Reference

• Synthesis and Evaluation of Antiplasmodial Activity of 2,2,2-Trifluoroethoxychalcones and 2-Fluoroethoxy Chalcones against Plasmodium falciparum in Culture
• K. Devi, V. Rajendran, Ayushee, T. M. Rangarajan, P. R. Singh, C. P. Ghosh, M. Singh, Molecules 2018, 23, 1174.

References

• 2,2-difluoro-1-tosyloxyvinyllithium: a novel, effective reagent for the preparation of α-keto acids from carbonyl compounds
  • K. Tanaka, T. Nakai, N. Ishikawa, Tetrahedron Lett. 1978, 19, 4809.
• A one-pot synthesis of 2,2-difluorovinyl carbonyl compounds from 2,2,2,-trifluoroethyl p-toluenesulfonate via 2,2-difluorovinylboranes
  • J. Ichikawa, S. Hamada, T. Sonoda, H. Kobayashi, Tetrahedron Lett. 1992, 33, 337.

References

• A convenient preparation of arylthioynamines
  • T. Nakai, K. Tanaka, H. Setoi, N. Ishikawa, Bull. Chem. Soc. Jpn. 1977, 3069.
• New applications of organofluorine reagents in organic synthesis. III. A convenient synthetic method for acetylenic ethers and thioethers
  • K. Tanaka, S. Shiraishi, T. Nakai, N. Ishikawa, Tetrahedron Lett. 1978,19, 3103.
• Synthesis of 2,2,2-trifluoroethanesulfonic acid
  • C. Bunyagidj, H. Piotrowska, M. H. Aldridge, J. Org. Chem. 1981, 46, 3335.

References

• Synthesis of fluorine-containing amino acids
  • T. Tsushima, K. Kawada, S. Ishihara, N. Uchida, O. Shiratori, J. Higaki, M. Hirata, Tetrahedron 1988, 44, 5375.
• Reaction with phenols
  • Y. Morishita, Y. Sugimoto, H. Ishikawa, S. Hayashida, T. Okamoto, N. Hayashi, Synth. Met. 1991, 41, 1231.
  • H. Shigyo, S. Sato, K. Shibuya, Y. Takahashi, T. Yamaguchi, H. Sonoki, T. Ohta, Chem. Pharm. Bull. 1993, 41, 1573.