Synthesis
The general procedure for the synthesis of 2-chloromethylthiophene from 2-thiophenemethanol was as follows: 2-thiophenemethanol (5,58 g, 509 mmol) and pyridine (60 g, 763 mmol) were dissolved in 600 mL of anhydrous dichloromethane at 0 °C, and thionyl chloride was added slowly and dropwise. The reaction mixture was stirred at 0°C for 1 hour, then brought to room temperature and continued to stir overnight. Upon completion of the reaction, the reaction was quenched by the addition of 500 mL of water. The organic layer was separated and the aqueous layer was extracted twice with 300 mL of dichloromethane. The organic layers were combined and washed sequentially with 600 mL of 5% aqueous sodium bicarbonate and 300 mL of brine. The organic layer was dried with anhydrous sodium sulfate and concentrated to give 40 g of 2-chloromethylthiophene (6) as an oil in 60% yield.
References
[1] European Journal of Medicinal Chemistry, 2001, vol. 36, # 11-12, p. 873 - 886
[2] European Journal of Pharmaceutical Sciences, 2002, vol. 16, # 1-2, p. 15 - 28
[3] European Journal of Organic Chemistry, 2014, vol. 2014, # 11, p. 2365 - 2370
[4] Tetrahedron, 1998, vol. 54, # 25, p. 6999 - 7012
[5] Synthetic Communications, 2005, vol. 35, # 15, p. 2079 - 2083
