3141-26-2

3,4-Dibromothiophene  is clear colorless to yellow liquid

3,4-Dibromothiphene is used in the synthesis of thiophene-estrogen receptor ligands which contain superagonist activities when involving luciferase in genes in human cells giving 2-3 times the activit y of estradiol. Also used in the synthesis of supercapacitors for use as charge storage applications.

1. Dissolve thiophene (185 mL, 2.3 mol) in chloroform at 0°C, stir and cool. Bromine (500 mL, 1560 g, 9.75 mol) was added dropwise for 5 hours. During the last 1 hour, stop cooling the reaction mixture and continue adding bromine. 2. The reaction mixture was stirred and heated to reflux for 5 h. After cooling to room temperature, the reaction was quenched with 3 M NaOH aqueous solution with vigorous stirring to consume excess bromine. The aqueous layer was separated and the organic phase was washed sequentially with water and acetone (150 mL) to remove residual water. 3. After drying the organic residue, it was dissolved in chloroform (1 L) at reflux. Upon cooling, tetrabromothiophene precipitated as colorless crystals (693 g, 75% yield). 4. Tetrabromothiophene (47 g, 0.12 mol) was dissolved in anhydrous ether (300 mL) and cooled to 0 °C. The solution was then dissolved in chloroform (1 L). A butyl lithium solution (150 mL, 0.24 mol, 1.6 M) in hexane was added dropwise over 80-90 minutes under argon protection. 5. After continued stirring for 20 minutes, ice water (250 mL) was carefully added. The organic phase was separated and the aqueous phase was extracted twice with ether, the organic extracts were combined, dried with anhydrous calcium chloride, and concentrated in vacuum. 6. The residue was distilled at 15 mmHg to give 3,4-dibromothiophene (22 g, 77% yield). 7. 3,4-dibromothiophene (72 g, 33 mL, 0.3 mol) was dissolved in anhydrous ethyl ether (120 mL) and cooled to -78 °C. The residue was dried over a period of time. Add a solution of nBuLi (206 mL, 0.33 mol, 1.6 M) and stir at -78 °C for 5 min. 8. Slowly add an anhydrous ether (120 mL) solution of DMF (35 mL, 33 g, 0.45 mol) pre-cooled to -78 °C to the reaction mixture. after 10 min, remove the cold bath and carefully add an aqueous solution of 6N HCl (150 mL) and warm up to 23 °C. 9. The aqueous phase was separated and the organic phase was washed with ether. The organic extracts were combined, washed with saturated aqueous sodium bicarbonate and the organic solvent was evaporated. 10. The residue was distilled twice under vacuum to give pure 3,4-dibromothiophene (40 g, 69% yield).

[1] Journal of Organic Chemistry, 2008, vol. 73, # 1, p. 323 - 326
[2] Synthesis, 1990, # 5, p. 403 - 405
[3] Synthesis, 1990, # 5, p. 403 - 405
[4] Chemistry - A European Journal, 2004, vol. 10, # 13, p. 3331 - 3340
[5] Tetrahedron Letters, 2004, vol. 45, # 17, p. 3405 - 3407