反応 #41926

反応方程式

boron trichloride

4-fluorobenzonitrile

NaOH

gallium (III) chloride

4-bromoaniline

→

solid

収率 43.0%

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

収率 43.0%

溶媒

dichloromethane

1,2-dichloroethane

反応条件

後処理

1. 1
   その他In a reactor fitted with magnetic stir bar
2. 2
   その他rubber septum, thermometer, Hickmann-condenser, nitrogen-inlet and nitrogen-outlet connected to a washing bottle
3. 3
   workup.ADDITIONwere added at once and
4. 4
   温度This solution was cooled in ice
5. 5
   その他the temperature below 5° C
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   その他the temperature below −5° C
7. 7
   温度to warm to 20° C
8. 8
   その他The Hickmann-condenser was replaced by a normal reflux condenser
9. 9
   温度the 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
    その他was collected) until the reflux temperature of 80° C.
12. 12
    温度Refluxing
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    温度The reaction mixture was cooled in ice and hydrolyzed slowly with water (100 mL)
14. 14
    温度heated at 60-80° C. for 20-30 min. in order
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    温度The reaction mixture was cooled again
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    抽出extracted twice with dichloromethane and water
17. 17
    その他The crude product was purified by chromatography with a heptane/ethyl acetate gradient from 100:0 to 80:20

実験手順

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).

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