2,2,2-Trifluoroethyl p-Toluenesulfonate

• 4'-Hydroxyacetophenone [H0193]
• 2,2,2-Trifluoroethyl Tosylate (= CF₃CH₂OTs) [T1516]
• Sodium Hydride (60%, dispersion in Paraffin Liquid) [S0481]
• DMF

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. CF₃CH₂OTs (2.24 g, 8.38 mmol) was added to the reaction mixture and stirred overnight at 130 °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 (1.4 g, 82%).

The reaction mixture was monitored by UPLC.

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).

• 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.