反应详情

温度

-10 °C

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).

1. customIn a reactor fitted with magnetic stir bar
2. customrubber septum, thermometer, Hickmann-condenser, nitrogen-inlet and nitrogen-outlet connected to a washing bottle
3. additionwere added at once and
4. temperatureThis solution was cooled in ice
5. customthe temperature below 5° C
6. customthe temperature below −5° C
7. temperatureto warm to 20° C
8. customThe Hickmann-condenser was replaced by a normal reflux condenser
9. temperaturethe reaction mixture was heated in an oil-bath (90° C.) over 1-2 h in order
10. distillationto distill off all the dichloromethane (a total of ca. 100 mL of distillate
11. customwas collected) until the reflux temperature of 80° C.
12. temperatureRefluxing
13. temperatureThe reaction mixture was cooled in ice and hydrolyzed slowly with water (100 mL)
14. temperatureheated at 60-80° C. for 20-30 min. in order
15. temperatureThe reaction mixture was cooled again
16. extractionextracted twice with dichloromethane and water
17. customThe crude product was purified by chromatography with a heptane/ethyl acetate gradient from 100:0 to 80:20