反应详情

温度

90 °C

2-Chlorobenzaldehyde (70.3 g) was added to a mixture of acetone (294 ml) and an aqueous solution (1.4 L) of sodium hydroxide (22.0 g) and the mixture was stirred at room temperature for 5 hours. An excessive acetone was distilled off under reduced pressure, and the residue was combined with ethyl acetate (1.4 L) and extracted. The ethyl acetate layer was washed with brine and dried (anhydrous magnesium sulfate), and then ethyl acetate was distilled off under reduced pressure to obtain a crude 2-chlorobenzalacetone (94.6 g) as a yellow oil. This oil was employed in the next step without a further purification. A 20% solution of sodium ethoxide in ethanol (170.1 g) was combined with diethyl malonate (80.1 g) at room temperature (resulting in instantaneous precipitation), and then with a solution of a crude 2-chlorobenzalacetone (94.6 g) in ethanol (40 ml). The reaction mixture was stirred with heating at 90° C. for 2 hours, allowed to stand to cool, and then cooled on ice (1 hour). The precipitate was recovered by a filtration, washed successively with ethyl acetate and isopropyl ether to obtain a crude 6-(2-chlorophenyl)-2-hydroxy-4-oxo-2-cyclohexenene-1-carboxylic acid ethyl ester monosodium salt (151.0 g) as a pale yellow powder. This powder was combined with 2M sodium hydroxide (350 ml) and stirred with heating at 100° C. for 2 hours. After allowing to stand to cool, 2.5 M sulfuric acid (350 ml) was added over a period of 15 minutes, and the mixture was stirred with heating at 100° C. for 2 hours. After allowing to stand to cool, ethyl acetate (1.4 L) was added and extracted. The ethyl acetate layer was washed with brine, dried (anhydrous magnesium sulfate), and then ethyl acetate was distilled off under reduced pressure. The precipitated crystal was washed successively with ethyl acetate-isopropyl ether (1:4) and isopropyl ether to obtain 5-(2-chlorophenyl)cyclohexane-1,3-dione (82.1 g) as a colorless crystal.

1. distillationAn excessive acetone was distilled off under reduced pressure
2. extractionextracted
3. washThe ethyl acetate layer was washed with brine
4. dry with materialdried (anhydrous magnesium sulfate)
5. distillationethyl acetate was distilled off under reduced pressure
6. customto obtain a crude 2-chlorobenzalacetone (94.6 g) as a yellow oil
7. customThis oil was employed in the next step without a further purification
8. customwas combined with diethyl malonate (80.1 g) at room temperature
9. custom(resulting in instantaneous precipitation)
10. temperatureto cool
11. temperaturecooled on ice (1 hour)
12. filtrationThe precipitate was recovered by a filtration
13. washwashed successively with ethyl acetate and isopropyl ether
14. customto obtain a crude 6-(2-chlorophenyl)-2-hydroxy-4-oxo-2-cyclohexenene-1-carboxylic acid ethyl ester monosodium salt (151.0 g) as a pale yellow powder
15. stirringstirred
16. temperaturewith heating at 100° C. for 2 hours
17. temperatureto cool
18. stirringthe mixture was stirred
19. temperaturewith heating at 100° C. for 2 hours
20. temperatureto cool
21. extractionextracted
22. washThe ethyl acetate layer was washed with brine
23. dry with materialdried (anhydrous magnesium sulfate)
24. distillationethyl acetate was distilled off under reduced pressure
25. washThe precipitated crystal was washed successively with ethyl acetate-isopropyl ether (1:4) and isopropyl ether