Chemical Properties
Off-White to Pale Yellow Solid
Uses
4-Chloro-1H-imidazole (cas# 15965-31-8) is a compound useful in organic synthesis.
Synthesis
General procedure for the synthesis of 5-chloroimidazole from imidazole: Imidazole (10 g, 0.150 mol) and sodium hydroxide (29.4 g, 0.74 mol) were added to a reaction flask containing water (250 mL) and stirred vigorously for 15 min at room temperature. The reaction mixture was cooled to 10 °C and sodium hypochlorite (16.7 g, 0.225 mol) was added slowly, keeping the temperature at 10 °C during the addition. The reaction mixture was stirred at room temperature for 6 h. The progress of the reaction was monitored by thin layer chromatography (TLC). Upon completion of the reaction, the mixture was cooled to 10 °C and the pH was adjusted to 6-7 by slow addition of concentrated hydrochloric acid solution. extraction was carried out with dichloromethane (2 x 200 mL) with stirring for 10 min and the organic layer was separated, the organic layer was washed with saturated brine. The organic phase was dried with anhydrous sodium sulfate and concentrated under reduced pressure to remove the dichloromethane. The crude product obtained was purified by column chromatography on silica gel (230-400 mesh), and 5-chloroimidazole was obtained by using 10-35% ethyl acetate solution in petroleum ether as eluent. The product was a pale yellow solid in 52% yield with a melting point of 118-119°C. 1H NMR (400 MHz, DMSO-d6) δ 7.09 (s, 1H, ArH), 7.39 (s, 1H, ArH), 12.42 (s, 1H, NH); 13C NMR (300 MHz, DMSO-d6) δ 126.7, 128.2 140.2; LC/MS (ESI-MS) m/z 103.6 (M + 1).
References
[1] Journal of Organic Chemistry, 2012, vol. 77, # 13, p. 5823 - 5828
[2] European Journal of Medicinal Chemistry, 2014, vol. 71, p. 354 - 365
[3] Patent: US2012/252758, 2012, A1. Location in patent: Page/Page column 30
[4] Patent: US2012/202834, 2012, A1. Location in patent: Page/Page column 34
