반응 #41926

반응 방정식

boron trichloride

4-fluorobenzonitrile

NaOH

gallium (III) chloride

4-bromoaniline

→

solid

수율 43.0%

(2-Amino-5-bromo-phenyl)-(4-fluoro-phenyl)-methanone

수율 43.0%

용매

dichloromethane

1,2-dichloroethane

반응 조건

후처리

1. 1
   기타In a reactor fitted with magnetic stir bar
2. 2
   기타rubber septum, thermometer, Hickmann-condenser, nitrogen-inlet and nitrogen-outlet connected to a washing bottle
3. 3
   workup.ADDITIONwere added at once and
4. 4
   온도This solution was cooled in ice
5. 5
   기타the temperature below 5° C
6. 6
   기타the temperature below −5° C
7. 7
   온도to warm to 20° C
8. 8
   기타The Hickmann-condenser was replaced by a normal reflux condenser
9. 9
   온도the reaction mixture was heated in an oil-bath (90° C.) over 1-2 h in order
10. 10
    workup.DISTILLATIONto distill off all the dichloromethane (a total of ca. 100 mL of distillate
11. 11
    기타was collected) until the reflux temperature of 80° C.
12. 12
    온도Refluxing
13. 13
    온도The reaction mixture was cooled in ice and hydrolyzed slowly with water (100 mL)
14. 14
    온도heated at 60-80° C. for 20-30 min. in order
15. 15
    온도The reaction mixture was cooled again
16. 16
    추출extracted twice with dichloromethane and water
17. 17
    기타The crude product was purified by chromatography with a heptane/ethyl acetate gradient from 100:0 to 80:20

실험 절차

In a reactor fitted with magnetic stir bar, rubber septum, thermometer, Hickmann-condenser, nitrogen-inlet and nitrogen-outlet connected to a washing bottle containing 30% NaOH, anhydrous beads of gallium (III) chloride (11.7 g, 66 mmol) were added at once and then dissolved by the addition of 1,2-dichloroethane (100 mL). This solution was cooled in ice, then 4-bromoaniline (9.5 g, 55 mmol) was added slowly while keeping the temperature below 5° C. Then the solution was cooled to −10° C., and a fresh 1 M solution of boron trichloride in dichloromethane (61 ml) was added via a syringe fitted with a teflon stop-cock while keeping the temperature below −5° C. Finally, 4-fluorobenzonitrile (6.7 g, 55 mmol) was added, and the mixture was allowed to warm to 20° C. The Hickmann-condenser was replaced by a normal reflux condenser, and the reaction mixture was heated in an oil-bath (90° C.) over 1-2 h in order to distill off all the dichloromethane (a total of ca. 100 mL of distillate was collected) until the reflux temperature of 80° C. was achieved. Refluxing was continued for 14 h. The reaction mixture was cooled in ice and hydrolyzed slowly with water (100 mL) and then heated at 60-80° C. for 20-30 min. in order to hydrolyze the imine. The reaction mixture was cooled again and then extracted twice with dichloromethane and water. The crude product was purified by chromatography with a heptane/ethyl acetate gradient from 100:0 to 80:20 to give a yellow solid (7 g, 43%). MS: m/z=294 (M).

출처