Simple synthesis of multi-halogenated alkenes from 2-bromo-2-chloro-1,1,1-trifluoroethane (halothane)

General information

1H NMR, 19F NMR and 13C NMR spectra were recorded on JEOL ECZ 400S spectrometers. Chemical shifts of 1H NMR are reported in ppm from tetramethylsilane (TMS) as an internal standard. Chemical shifts of 13C NMR are reported in ppm from the center line of a triplet at 77.16 ppm for deuteriochloroform. Chemical shifts of 19F NMR are reported in ppm from CFCl3 as an internal standard. All data are reported as follows: chemical shifts, relative integration value, multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, sep = septet, br = broad, brd = broad-doublet, m = multiplet), coupling constants (Hz). Mass spectra were obtained on JEOL JMS-700T spectrometer (EI).

Materials

All commercially available materials were used as received without further purification. All experiments were carried out under argon atmosphere in flame-dried glassware using standard inert techniques for introducing reagents and solvents unless otherwise noted.

Typical procedures for synthesis of multi-halogenated alkene

Ground KOH (5.0 mmol) was added to a solution of phenol (1.0 mmol) in DME (5.0 mL). The mixture was stirred for 1 h at room temperature, and then halothane (1.0 mmol) was added in small portions. The solution was heated to 80 °C, and the temperature was maintained for 4.5 h. The reaction mixture was quenched by addition of saturated aqueous NH4Cl (40 mL) at 0 °C and extracted with Et2O. The organic phase was dried over Na2SO4, filtered, and concentrated by evaporation under reduced pressure. The residue was purified by column chromatography to afford 2.

2-Bromo-2-chloro-1-fluoroethenyl phenyl ether (2a): Product 2a was purified by column chromatography (pentane only). 2a was obtained in 85% yield (212.7 mg) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.06–7.13 (2H, m), 7.16–7.23 (1H, m), 7.38 (2H, t, J = 7.7 Hz); 13C NMR (100 MHz, CDCl3) δ 80.5 (d, J = 61.8 Hz), 80.8 (d, J = 52.9 Hz), 116.53, 116.55, 125.2, 130.1, 152.3 (d, J = 288.1 Hz), 152.6 (d, J = 283.0 Hz), 153.9; 19F NMR (376 MHz, CDCl3) δ −80.5 (s, 1F), −80.6 (s, 1F); EIMS m/z: 250, 252 [M]+; HREIMS: [M]+ calcd for C8H5BrClFO, 249.9196, 251.9176; found, 249.9202, 251.9172.

(3-Chloro-4-fluoro-4-phenoxybut-3-en-1-yn-1-yl)trimethylsilane (7): To a solution of 2a (0.5 mmol), bis(triphenylphosphine)palladium dichloride (4 mol %), copper iodide (4 mol %) and triethylamine (0.75 mmol) in THF (2.5 mL) was added dropwise trimethylsislylacetylene (1.0 mmol) for 1 min at room temperature. The solution was stirred at rt until the Sonogashira coupling reaction was completed. The reaction mixture was filtered and concentrated under reduced pressure. The residue was purified by column chromatography (hexane only) to afford 7 in 80% yield (107.2 mg) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 0.127 and 0.239 (s, 9H), 7.06–7.14 (m, 2H), 7.16–7.22 (m, 1H), 7.32–7.41 (m, 2H); 13C NMR (100 MHz, CDCl3) δ −0.364, −0.259, 85.3 (d, J = 45.2 Hz), 85.6 (d, J = 53.5 Hz), 94.3 (d, J = 6.8 Hz), 94.8 (d, J = 2.7 Hz), 103.4 (d, J = 5.4 Hz), 104.1 (d, J = 8.1 Hz), 117.2, 117.3, 125.2, 125.3 130.0, 130.1, 153.6 (d, J = 1.9 Hz), 154.4 (d, J = 3.0 Hz), 158.1 (d, J = 292.6 Hz), 158.7 (d, J = 290.7 Hz); 19F NMR (376 MHz, CDCl3) δ −73.3 (s, 1F), −78.4 (s, 1F); EIMS m/z: 268, 270 [M]+; HREIMS: [M]+ calcd for C13H14ClFSi, 268.0486, 270.0457; found, 268.0490, 270.0452.

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