反应详情

温度

62.5 °C

In a 5-L cylindrical reactor, p-fluorophenylhydrazine HCl (400 g, 2.46 mol) was suspended in ethanol (2B) (1.2 kg; 1.5 L). The slurry was stirred and heated to 60-65° C. A solution of 4-cyclohexanone carboxylic acid ethyl ester (400 g, 2.35 mol) in ethanol (2B) (0.4 L) was added over 1 h. The reaction temperature may rise to reflux (78-82° C.). After addition, the suspension was stirred and heated at reflux for 1 h then cooled to 40-50° C. A 50% sodium hydroxide solution (470 g) was added over 30 min. The suspension was heated to reflux (80-82° C.). (This can cause evolution of ammonium gas during heating). After 1 h, the reaction mixture was distilled at atmospheric pressure to about 1.5 L, about half of its original volume, then cooled to 60-70° C. Water (2.5 L) was added. The mixtured was cooled to 30-40° C. before dilute HCl (0.333 L conc HCl+0.667 L water) was added over 20 min. The suspension was stirred at 20° C. for 1 h then filtered through a Buchner funnel. The solid product was washed with water (3×1 L) then dried under N2 overnight to give 534.5 g (97.5% yield) of off-white solid.

1. temperatureto reflux (78-82° C.)
2. additionAfter addition
3. stirringthe suspension was stirred
4. temperatureheated
5. temperatureat reflux for 1 h
6. temperaturethen cooled to 40-50° C
7. temperatureThe suspension was heated
8. temperatureto reflux (80-82° C.)
9. temperatureduring heating)
10. distillationthe reaction mixture was distilled at atmospheric pressure to about 1.5 L, about half of its original volume
11. temperaturecooled to 60-70° C
12. additionWater (2.5 L) was added
13. temperatureThe mixtured was cooled to 30-40° C. before dilute HCl (0.333 L conc HCl+0.667 L water)
14. additionwas added over 20 min
15. stirringThe suspension was stirred at 20° C. for 1 h
16. filtrationthen filtered through a Buchner funnel
17. washThe solid product was washed with water (3×1 L)
18. customthen dried under N2 overnight