تفاعل #489506

معادلة التفاعل

2,3-dihydro-1,4-benzodioxine-6-carbaldehyde

3-Chloroperoxybenzoic acid

→

2,3-dihydro-1,4-benzodioxin-6-ol

المردود 95.0%

المذيبات

dichloromethane

ظروف التفاعل

المعالجة

1. 1
   أخرىwas obtained
2. 2
   درجة الحرارةThe mixture was heated
3. 3
   درجة الحرارةto reflux at a rate of 8-10° C./h
4. 4
   درجة الحرارةheated
5. 5
   درجة الحرارةat reflux for a further 6 h
6. 6
   ترشيحThe resultant suspension was filtered through a 500 L Nutsche
7. 7
   ترشيحfilter
8. 8
   غسيلthe filter cake was washed with dichloromethane (391 kg)
9. 9
   غسيلThe filtrate and wash solution
10. 10
    أخرىwere transferred to a 2000 L reactor
11. 11
    workup.ADDITIONA 7% by weight aqueous solution of sodium bicarbonate (212.7 kg) was added
12. 12
    workup.STIRRINGthe mixture was stirred for 0.5 h
13. 13
    أخرىto separate over 0.5 h
14. 14
    أخرىThe aqueous layer was removed
15. 15
    تركيزThe organic phase was concentrated to dryness under reduced pressure at a temperature <30° C
16. 16
    workup.ADDITIONMethanol (116.1 kg) was added
17. 17
    درجة الحرارةthe resultant mixture was cooled to 0° C
18. 18
    workup.ADDITIONA 15.5% by weight aqueous solution of sodium hydroxide (234.3 kg) was added at a rate of 30-40 kg/h such that the mixture's temperature
19. 19
    درجة الحرارةwas maintained between 0-10° C
20. 20
    workup.STIRRINGThe mixture was stirred at this temperature for a further 2.25 h
21. 21
    workup.ADDITIONthe pH of the mixture was adjusted to 6-7 by the addition of 4 N hydrochloric acid (266.5 kg) such that the mixture's temperature
22. 22
    درجة الحرارةwas maintained between 0-10° C
23. 23
    درجة الحرارةto warm to ambient temperature
24. 24
    استخلاصwas extracted three times in total with methyl tert-butyl ether (145 kg
25. 25
    استخلاصfor each extraction)
26. 26
    workup.STIRRINGby stirring for 0.5 h
27. 27
    أخرىto separate for 0.5 h
28. 28
    غسيلThe combined organic extracts were washed three times in total with a 7% aqueous solution of sodium bicarbonate (212.7 kg for
29. 29
    غسيلeach wash)
30. 30
    workup.STIRRINGby stirring for 0.5 h
31. 31
    أخرىto separate for 0.5 h
32. 32
    أخرىremoving the aqueous phase
33. 33
    غسيلThe organic phase was then washed with a 30% by weight aqueous solution of sodium chloride (212.7 kg)
34. 34
    workup.STIRRINGby stirring for 0.5 h
35. 35
    أخرىto separate for 0.5 h
36. 36
    أخرىremoving the aqueous phase
37. 37
    تركيزThe organic phase was concentrated to dryness under reduced pressure at a temperature <45° C
38. 38
    workup.ADDITIONTetrahydrofuran (170 kg) was added
39. 39
    تركيزthe resultant solution concentrated to dryness under reduced pressure at a temperature <45° C
40. 40
    workup.ADDITIONFurther tetrahydrofuran (17.1 kg) was added
41. 41
    تركيزthe resultant solution concentrated to dryness under reduced pressure at a temperature <45° C
42. 42
    workup.ADDITIONTetrahydrofuran (122.5 kg) was added

الإجراء التجريبي

A 2000 L reactor was charged with dichloromethane (1303.4 kg) followed by 2,3-dihydro-1,4-benzodioxine-6-carbaldehyde (98.0 kg, 597 mol) and stirred until a homogeneous solution was obtained. 3-Chloroperoxybenzoic acid (144.3 kg, 836 mol) was added. The mixture was heated to reflux at a rate of 8-10° C./h, heated at reflux for a further 6 h and allowed to cool to 20° C. The resultant suspension was filtered through a 500 L Nutsche filter and the filter cake was washed with dichloromethane (391 kg). The filtrate and wash solution were transferred to a 2000 L reactor. A 7% by weight aqueous solution of sodium bicarbonate (212.7 kg) was added and the mixture was stirred for 0.5 h. The stirring was stopped and the phases were allowed to separate over 0.5 h. The aqueous layer was removed. The aqueous sodium bicarbonate washing procedure was repeated three times in total. The organic phase was concentrated to dryness under reduced pressure at a temperature <30° C. Methanol (116.1 kg) was added and the resultant mixture was cooled to 0° C. A 15.5% by weight aqueous solution of sodium hydroxide (234.3 kg) was added at a rate of 30-40 kg/h such that the mixture's temperature was maintained between 0-10° C. The mixture was stirred at this temperature for a further 2.25 h and the pH of the mixture was adjusted to 6-7 by the addition of 4 N hydrochloric acid (266.5 kg) such that the mixture's temperature was maintained between 0-10° C. The mixture was allowed to warm to ambient temperature and was extracted three times in total with methyl tert-butyl ether (145 kg for each extraction) by stirring for 0.5 h, stopping the stirring and allowing the phases to separate for 0.5 h. The combined organic extracts were washed three times in total with a 7% aqueous solution of sodium bicarbonate (212.7 kg for each wash) by stirring for 0.5 h, stopping the stirring, allowing the phases to separate for 0.5 h and removing the aqueous phase. The organic phase was then washed with a 30% by weight aqueous solution of sodium chloride (212.7 kg) by stirring for 0.5 h, stopping the stirring, allowing the phases to separate for 0.5 h and removing the aqueous phase. The organic phase was concentrated to dryness under reduced pressure at a temperature <45° C. Tetrahydrofuran (170 kg) was added and the resultant solution concentrated to dryness under reduced pressure at a temperature <45° C. Further tetrahydrofuran (17.1 kg) was added and the resultant solution concentrated to dryness under reduced pressure at a temperature <45° C. Tetrahydrofuran (122.5 kg) was added to afford a brown-red solution of 2,3-dihydro-1,4-benzodioxin-6-ol (86.3 kg, 95%) in tetrahydrofuran which was carried forward without further purification: purity (HPLC-UV at 220 nm) 95.7%.

المصدر