6-Bromoquinolin-4(1H)-one

187278-01-9

145369-94-4

General procedure for the synthesis of 6-bromo-4-hydroxyquinoline from 5-[(4-bromophenylamino)methylene]-2,2-dimethyl-1,3-dioxane-4,6-dione: First, Meldrum acid (1) (32.4 g, 225.0 mmol) was dissolved in trimethyl orthoformate (250 mL), stirred and heated to reflux for 3 h under nitrogen protection to obtain Intermediate 2. After the solution was cooled to about 50 °C, a solution of 4-bromoaniline (25.8 g, 150.0 mmol) in trimethyl orthoformate (80 mL) was slowly added dropwise. After the dropwise addition was completed, the reaction mixture was continued to be heated and refluxed for 2 hours. Upon completion of the reaction, the solvent was evaporated under reduced pressure, the residue was diluted with hexane, filtered, and the solid portion was washed with hexane and dried to afford the yellow solid Meldrum's acid derivative 3. Subsequently, compound 3 was slowly added in portions (~1.0 g each) to diphenyl ether (Ph2O, 500 mL) preheated to 245°C. The rate of addition needs to be carefully controlled to prevent violent gas release. The reaction mixture was heated at 250 °C with stirring for 15 min, then cooled to room temperature, diluted with hexane and filtered. The solids were washed sequentially with hexane and 30% ether/hexane mixture. The crude product was purified by silica gel column chromatography (eluent ratio 16:1 to 10:1 dichloromethane/methanol), resulting in a light brown solid 6-bromo-4-hydroxyquinoline (4) (24.6 g, 73% yield) with a melting point of 282-284 °C (literature value 282-284 °C). Its 1H NMR (DMSO-d6) data were as follows: δ 11.93 (broad single peak, 1H, NH), 8.17 (double peak, J=2.0 Hz, 1H, Ar-H), 7.96 (double double peak, J=7.5,6.0 Hz, 1H), 7.79 (double double peak, J=9.0,2.5 Hz, 1H, Ar-H), 7.53 (double peak, J= 8.5 Hz, 1H), 6.08 (double peak, J=2.5 Hz, 1H, Ar-H).