Hydrogen Peroxide → Fipronil

Temperature

12 °C

Trifluoroacetic acid (1660 g, 14.5 mol) was added to a stirred solution of 5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethylthiopyrazole (436 g, 1.03 mol) and boric acid (5 g, 0.08 mol) in a glass reactor at 12° C. Hydrogen peroxide (131.5 g of 35% w/w, 1.35 mol) was added over 2 hours whilst maintaining the temperature at 12° C., and the mixture kept at this temperature for a further 4-5 hours. When the transformation had reached 97-98%, or the amount of unwanted 5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethylsulphonylpyrazole reached 2% (as judged by HPLC analysis), sulphur dioxide was added to quench any remaining hydrogen peroxide, and the mixture maintained at 10-18° C. for 0.5 hour. Chlorobenzene (370 g) was added and the mixture placed under reduced pressure (from 0.17 to 0.04 atmosphere) and heated to 47-50° C. with azeotropic distillation. A homogeneous fraction containing recovered trifluoroacetic acid was obtained. During the distillation additional chlorobenzene (1625 g) was added continuously in order to maintain a constant volume. At the end of the azeotropic distillation the reactor contents were maintained at 47-50° C. under reduced pressure (0.04 atmosphere), and a homogeneous fraction of chlorobenzene distilled. After release of the vacuum, the reactor was heated to 40° C., ethanol (207 g) and chlorobenzene (235 g) added, and the mixture heated to 80° C. with stirring to give a solution. On cooling to 40° C. the product crystallised. The reactor was placed under progressively reduced pressure (from 0.13 to 0.03 atmosphere) and the ethanol distilled at 40° C. The vacuum was released and the mixture cooled to 5° C. during 3.5 hours and left for a further 0.5 hour. The product was filtered off, washed with cold chlorobenzene, then with cold aqueous ethanol, then with water, and dried in vacuo at 135° C. to give the title compound (407.5 g), in a typical yield of 89% and purity of 95.5%.

1. additionwas added
2. customto quench any remaining hydrogen peroxide
3. temperaturethe mixture maintained at 10-18° C. for 0.5 hour
4. additionChlorobenzene (370 g) was added
5. temperatureheated to 47-50° C. with azeotropic distillation
6. additionA homogeneous fraction containing
7. customrecovered trifluoroacetic acid
8. customwas obtained
9. temperatureto maintain a constant volume
10. distillationAt the end of the azeotropic distillation the reactor contents
11. temperaturewere maintained at 47-50° C. under reduced pressure (0.04 atmosphere)
12. distillationa homogeneous fraction of chlorobenzene distilled
13. temperatureAfter release of the vacuum, the reactor was heated to 40° C.
14. additionethanol (207 g) and chlorobenzene (235 g) added
15. temperaturethe mixture heated to 80° C.
16. customto give a solution
17. temperatureOn cooling to 40° C. the product
18. customcrystallised
19. distillationthe ethanol distilled at 40° C
20. temperaturethe mixture cooled to 5° C. during 3.5 hours
21. waitleft for a further 0.5 hour
22. filtrationThe product was filtered off
23. washwashed with cold chlorobenzene
24. dry with materialwith cold aqueous ethanol, then with water, and dried in vacuo at 135° C.

ORD record

ord-8d72eb35ffe34418a31d9172b0630027

Source dataset

uspto-grants-2003_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06620943B1