trifluoromethyl benzoate

Chemical Properties

Trifluoromethyl benzoate (TFBz) is developed as a new shelf-stable trifluoromethoxylation reagent, which can be easily prepared from inexpensive starting materials using KF as the only fluorine source.

Preparation

To a 350-mL oven-dried sealed tube (I) equipped with a robust stir bar were added KF (65.4 g, 1125 mmol, 45 equiv) and 18-crown-6 (8.9 g, 33.75 mmol, 1.35 equiv) in the glove box. Tube (I) was removed out of glove box and 230 mL dry CH3CN was added under N2. To another 350-mL oven-dried sealed tube (II) equipped with a robust stir bar were added dried KF (2.18 g, 37.5 mmol, 1.5 equiv) and dried 18-crown-6 (9.91 g, 37.5 mmol, 1.5 equiv) in the glove box. Tube (II) was removed out of glove box and 100 mL dry THF was added under N2. Tube (I) was placed into dry-ice/acetone, and triphosgene (37.1 g, 125 mmol, 5 equiv) was added until the solution was frozen. Tube (I) was sealed. The mixture was warmed to room temperature and stirred for 1 h. Tube (II) was evacuated for 1-2 seconds before it was connected with tube (I) through a gas-tube and tube (I) was heated to 80 oC while tube (II) was cooled to -78 oC. The COF2 was transferred from tube (I) to tube (II) for 2 h. Then benzoyl bromide (4.63 g, 25 mmol, 1.0 equiv) was added to tube (II) at -78 oC under N2, then the solution was warmed to -30 oC and stirred for 2 h while the solution became very stick. Then soduim trifluoromethanesulfonate (8.6 g) was added at -78 oC under N2 and stirred for another 30 min at -30 oC. Tube (II) was warmed to room temperature and over-excess COF2 was absorbed by 10% NaOH (aq) carefully. The difluorophosgene dissolved in the reaction mixture in tube (II) was also completely removed by flowing N2 gas to the reaction mixture and absorbed by 10% NaOH (aq). The solvent was evaporated under vacuum. Et2O was added and the mixture was filtered through a pad of celite. The solvent was evaporated under vacuum and product was further purified by flash column chromatography using petroleum ether (30-60 oC) as eluent to give product 1a 3.31g as a colorless liquid. (Caution! COF2 was a toxic gas, so it should be handled in a well ventilated hood!) TFBz has been stored in the air at room temperature for 5 months without detectable decomposition. Moreover, a mixture of TFBz and water (1:2, v/v) can be stored at room temperature for at least 5 days without detectable decomposition. ^[1]Colorless liquid. 1H NMR (400 MHz, CDCl3) δ 8.08 (dd, J = 8.3, 1.2 Hz, 2H), 7.70 (t, J = 7.5 Hz, 1H), 7.53 (t, J = 7.9 Hz, 2H). 19F NMR (376 MHz, CDCl3) δ -57.71 (s, 3F). 13C NMR (126 MHz, CDCl3) δ 159.0, 135.1, 130.5, 128.9, 126.6 (q, J = 1.6 Hz), 119.9 (q, J = 265.4 Hz). MS (EI, m/z, %): 190 (M+ , 22), 105 (100), 77 (58); HRMS (EI) (m/z): [M]+ Calcd for C8H5F3O2, 190.0242; found, 190.0247.

References

[1] MIN ZHOU. Trifluoromethyl Benzoate: A Versatile Trifluoromethoxylation Reagent[J]. Journal of the American Chemical Society, 2018, 140 22: 6801-6805. DOI:10.1021/jacs.8b04000.