Hydrochloric Acid → 2-hydroxy-1H-quinolin-4-one

Into a 150 ml three neck flask, equipped with an agitator, a reflux condenser sealed on its upper end with a gas bubbler, a thermometer and an electric heating mantle were charged 16.3 g pure isatoic anhydride (M.W. 163) 10.1 g triethylamine (M.W. 101), 9.9 g methyl cyanoacetate (M.W. 99) and 2 ml DMF. The reaction mixture, under agitation, was kept at a temperature within the range of 25° to 30° C. for approximately 1 hour. During this period a constant evolution of gas was observed. The temperature of the reaction mixture was then elevated to and maintained at 78° to 80° C. for approximately 2 hours. At the end of this heating period the evolution of gas practically stopped and the reaction mixture turned into a slightly yellow, good stirrable oil. A minimum of water (approximately 40 ml) and the still hot oil were transferred to a 300 ml stainless steel autoclave, equipped with an anchor agitator, a pressure gauge, a thermocouple and a vent-valve. A charge of 14.7 g sodium hydroxide (MW 40) pellets was added to the reaction mixture and the autoclave was closed. The contents of the autoclave, under agitation, were heated to and maintained at a temperature in the range of 150° to 155° C. for 3 hours. The pressure in the autoclave reached 275 to 280 psig during the heating; after cooling to 50° to 60° C. hot water was added to the autoclave and approximately 600 ml of a brownish colored solution was removed therefrom and treated with 1 g activated charcoal at 60° C. A slightly yellowish colored solution which resulted was then acidified with concentrated hydrochloric acid to a pH of approximately 2. White, slightly creamy colored precipitate which formed was recovered by filtration; the precipitate was then reslurried in 200 ml water, refiltered and dried at 110° C. The yield was 14.17 g (87.9 percent of theory based upon the isatoic anhydride charged) 2,4-dihydroxyquinoline, melting point 350°-355° C. Examination of the product by infrared spectroscopy and nuclear magnetic resonance indicated that it was of high purity.

1. customsealed on its upper end with a gas bubbler
2. waitDuring this period a constant evolution of gas was observed
3. temperaturemaintained at 78° to 80° C. for approximately 2 hours
4. customequipped with an anchor agitator
5. additionwas added to the reaction mixture
6. customthe autoclave was closed
7. temperatureThe contents of the autoclave, under agitation, were heated to and
8. temperaturemaintained at a temperature in the range of 150° to 155° C. for 3 hours
9. customwas removed
10. additiontreated with 1 g
11. customat 60° C
12. customA slightly yellowish colored solution which resulted
13. customWhite, slightly creamy colored precipitate which formed
14. filtrationwas recovered by filtration
15. customdried at 110° C
16. additioncharged) 2,4-dihydroxyquinoline, melting point 350°-355° C

ORD record

ord-1ca23ad38c6c4b3b9c35e863fe34f56d

Source dataset

uspto-grants-1982_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04362876