Carbon Tetrabromide

• 2-Phenylethyl Alcohol [P0084]
• Carbon Tetrabromide [T0038]
• Triphenylphosphine [T0519]
• Dichloromethane

To a mixture of 2-phenylethyl alcohol (0.196 mL, 1.64 mmol) and carbon tetrabromide (0.652 g, 1.96 mmol) in CH₂Cl₂ (8.2 mL) was added a solution of PPh₃ (0.644 g, 2.46 mmol) in CH₂Cl₂ (3.3 mL) at 0 ºC. The reaction mixture was stirred at room temperature for 1 h, concentrated under reduced pressure, and purified by silica gel column chromatography (hexane:ethyl acetate = 7:3) to give (2-bromoethyl)benzene (0.290 g, 96% yield) as a colorless liquid.

The reaction mixture was monitored by TLC (hexane:ethyl acetate = 4:1, Rf = 0.7).

¹H NMR (400 MHz, CDCl₃); δ 7.36-7.20 (m, 5H), 3.78 (t, 2H, J = 11.2 Hz), 3.17 (t, 2H, J = 11.2 Hz).

¹³C NMR (101 MHz, CDCl₃); δ 138.9, 128.6, 128.5, 126.9, 39.4, 32.9.

• Hexabromoacetone and ethyl tribromoacetate: a highly efficient reagent for bromination of alcohol
• P. Tongkate, W. Pluempanupat, W. Chavasiri, Tetrahedron Lett. 2008, 49, 1146.


Application
Bromination of Alcohols



References

• 1)Halo sugar nucleosides. III. Reactions for the chlorination and bromination of nucleoside hydroxyl groups
  • J. P. H. Verheyden , J. G. Moffatt, J. Org. Chem. 1972, 37, 2289.
• 2)General 1,5-diene synthesis involving overall allyl alcohol coupling with geometrical and positional control
  • E. Axelrod, G. M. Milne, E. E. V. Tamelen, J. Am. Chem. Soc. 1970, 92, 2139.


Application
Corey-Fuchs Alkyne Synthesis



Typical Procedure:
Carbon tetrabromide (34.67 g, 104.5 mmol) and anhydrous CH₂Cl₂ (175 mL) are added to a 500 mL round bottom flask equipped with a magnetic stir bar and septum under N₂ atmosphere. The reaction flask is cooled to 0 ℃ with an ice bath for 10 min. Triphenylphosphine (54.84 g, 209.1 mmol) is added in portions over 5 min, and the dark red solution is stirred at 0 ℃ for 30 min. 3,4-Dimethoxybenzaldehyde (17.37 g, 104.5 mmol) is added and the mixture is stirred at 0 ℃ for 1 h. A 1 : 1 mixture of H₂O : brine is added and the layers are separated. The aqueous layer is extracted with a 1 : 1 mixture of hexanes : CH₂Cl₂, and the combined organic layers are dried, filtered, and concentrated under reduced pressure. The crude material is chromatographed on SiO₂ (0-15% EtOAc/hexanes) to afford the dibromide 1 (29.37 g, Y. 88%) as a yellow oil.
Then, 1 (4.41 g, 13.79 mmol, 1.0 equiv) and THF (45 mL) are added to a 250 mL round bottom flask equipped with a magnetic stir bar and septum, and the reaction flask is cooled to -78 ℃ under N₂ atmosphere. 2.5M n-BuLi solution in hexane (11.6 mL) is added slowly via syringe and the reaction solution is stirred at -78 ℃ for 45 min and then at 0 ℃ for 45 min. The flask is recooled to -78 ℃, and freshly distilled methyl chloroformate (1.1 mL, 1.3 mmol, 1.0 equiv) is added slowly via syringe. The mixture is stirred at -78 ℃ for 10 min, then 0 ℃ for 1 h. Saturated aqueous NH₄Cl solution is added, and the layers are separated. The aqueous layer is extracted with Et₂O, and the combined organic layers are dried, filtered and concentrated under reduced pressure. The residue is chromatographed (SiO₂, 2-20% EtOAc / hexanes) to afford the desired alkyne 2 (2.83 g, Y. 93%) as a white solid.

References

• Total synthesis of (+)-Lithospermic acid by asymmetric intramolecular alkylation via catalytic C-H bond activation
  • S. J. O’Malley, K. L. Tan, A. Watzke, R. G. Bergman, J. A. Ellman, J. Am. Chem. Soc. 2005, 127, 13496.


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