Chemical Properties
Light yellow to light reddish yellow solid
Uses
4-Bromomethyl-2(1H)-quinolinone is a reagent used in the preparation of coumarins and 1-aza coumarins which has nti-microbial, anti-inflammatory, and analgesic activities.
Application
4-Bromomethyl-1,2-dihydroquinoline-2-one is used as an intermediate in Rebamipide, a gastroprotective agent used in the treatment of gastritis, gastroduodenal ulcers and mucosal protection.
Synthesis
The general procedure for the synthesis of bromomethyl quinolone from 4-bromo-3-oxo-N-phenylbutyramide is as follows: In a 5000L enameled reactor, 4000 kg of ethylene dichloride and 500 kg of bromoacetoacetanilide were added, and stirred thoroughly until homogeneous. At the same time, 1000 kg of ethylene dichloride and 1000 kg of phosphorus pentoxide were added to another 2000L reactor. The temperature of the two reactors was raised to the reflux temperature of dichloroethane, i.e., 83°C. After refluxing for 1 hr, the dichloroethane condensate from the 5000L reactor was distilled into the 2000L reactor, while the dichloroethane condensate distilled from dehydration in the 2000L reactor was transferred back to the 5000L reactor, making sure that the rate of distillation in the two reactors was synchronized. After the reaction lasted 12 hours, the reaction mixture was cooled to room temperature. The crude 4-bromomethylquinolone was isolated using a filter press and washed with dichloroethane for further purification. After separation, it was again passed through a filter press to give a wet product containing dichloroethane. Subsequently, the solvent was removed by vacuum drying, resulting in 442 kg of solid product in the form of a white powder. The yield of the process was 95.08% and the purity of the product was 99.67% (as determined by HPLC).
References
[1] Patent: CN105753781, 2016, A. Location in patent: Paragraph 0016; 0017
[2] Patent: US2008/139558, 2008, A1. Location in patent: Page/Page column 19
[3] European Journal of Medicinal Chemistry, 2008, vol. 43, # 10, p. 2178 - 2188
[4] Green Chemistry, 2016, vol. 18, # 7, p. 2201 - 2205
[5] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2016, vol. 55B, # 5, p. 637 - 642
