反应详情

温度

2 °C

Sodium hypochlorite solution was prepared by first adding 40.2 kg (500 moles) of 50% sodium hydroxide solution to 50 kg of flaked ice in a jacketed vessel having external coolant; then adding 70 kg more ice and introducing 8.88 kg (125 moles) of chlorine gas below the surface, all with agitation. Temperature of the hypochlorite solution was -8° C. To the hypochlorite solution was added, portion wise, 17.04 kg (120.0 mole) of 98% purity 2-hydroxynicotinic acid. The temperature of the reaction mixture rose to 27° C. After stirring overnight, a sample was withdrawn and neutralized with 37% hydrochloric acid to give precipitate which when analyzed by 1HNMR showed 80:20 ratio of title compound to starting 2-hydroxynicotinic acid. A second solution of sodium hypochlorite prepared as above from 12 kg of 55% sodium hydroxide solution (152.4 mole), 33 kg of ice and 4.15 kg (58.5 mole) of chlorine was added to the reaction mixture and the mixture was stirred overnight at room temperature. 1HNMR analysis showed no starting material was present. Sodium bisulfite, 416 g (4.0 mole) was added and the mixture agitated for about 5 min. Eight liters of 2-isopropyl alcohol was added to reduce expected foaming. The reaction mixture was then mixed gradually with concentrated 37% hydrochloric and keeping the temperature generally at 15°-23° C. with good agitation. The temperature of the acidified mixture was then cooled to 2° C. and filtered. The filter cake was washed with 15 liters of cold water followed by 8 liters of acetone. The solids were dried for 2 days at 80° F. and pressed through an 18 mesh screen. The crystals were then dried further in a vacuum oven at 125° F. to give 18.81 kg (90.1% yield) of title compound. 1NMR analysis by the procedure of Example 3 showed only a trace of 3,5-dichloro-2-hydroxypyridine was present.

1. additionthen adding 70 kg more ice
2. customwas -8° C
3. customrose to 27° C
4. customa sample was withdrawn
5. customto give precipitate which when
6. additionwas added to the reaction mixture
7. stirringthe mixture was stirred overnight at room temperature
8. stirringthe mixture agitated for about 5 min
9. additionThe reaction mixture was then mixed gradually
10. concentrationwith concentrated 37% hydrochloric
11. customgenerally at 15°-23° C.
12. filtrationfiltered
13. washThe filter cake was washed with 15 liters of cold water
14. customThe solids were dried for 2 days at 80° F.
15. customThe crystals were then dried further in a vacuum oven at 125° F.