Chemical Properties
Colorless to yellow liquid
Uses
3-Bromothiophene-2-carboxaldehyde is an important raw material and intermediate used in organic synthesis, pharmaceuticals, agrochemicals and dyestuff.
Synthesis Reference(s)
Journal of Medicinal Chemistry, 34, p. 1805, 1991
DOI: 10.1021/jm00110a008
Synthesis
Diisopropylamine (51.6 kg, 509.9 mol, 1.0 eq.) and anhydrous tetrahydrofuran (THF) (385.0 kg) were added to a 1000 L autoclave under nitrogen protection. After cooling the system to 0-5 °C, n-butyllithium (BuLi) (131.4 kg, 463.8 mol, 1.0 eq.) was slowly added. After addition, stirring was continued at 0-5 °C for 30 min. Subsequently, a solution of 3-bromothiophene (75.0 kg, 460.0 mol, 1.0 eq.) in THF (20.0 kg) was added dropwise. After dropwise addition, stirring was continued at 0-5 °C for 30 min. Next, a solution of N,N-dimethylformamide (DMF) (35.3 kg, 473.3 mol, 1.0 eq.) in THF (10.0 kg) was slowly added dropwise. After completion of dropwise addition, stirring was maintained at 0-5 °C for 3 hours. Upon completion of the reaction, a 14% aqueous ammonium chloride (NH4Cl) solution (700.0 g) was slowly added dropwise at 0-5 °C. After addition, the reaction was stirred at 0-5 °C for 15 min and allowed to stand for 15 min. The organic phase was separated and stored temporarily in a clean PTFE drum. The aqueous phase was re-pumped into the reactor, methyl tertiary butyl ether (MTBE) (150.0 kg) was added, stirred for 15 min, and allowed to stand for 15 min before separating the phase and collecting the upper organic phase. All organic phases were combined and dried with anhydrous sodium sulfate (85.0 kg) for several hours until the moisture content was <1%. Filtration, the filter cake was washed with methyl tert-butyl ether (20 mL x 2), the filtrates were combined and concentrated under reduced pressure to remove the solvent to give 3-bromothiophene-2-carbaldehyde (93.8 kg, 100% yield).
References
[1] Patent: CN103172646, 2016, B. Location in patent: Paragraph 0101-0104
[2] European Journal of Organic Chemistry, 2016, vol. 2016, # 31, p. 5263 - 5273
[3] Macromolecules, 2013, vol. 46, # 6, p. 2078 - 2091
[4] Tetrahedron Letters, 2012, vol. 53, # 2, p. 166 - 169
[5] Journal of the American Chemical Society, 2014, vol. 136, # 19, p. 7132 - 7139
