反应详情

温度

35 °C

A 3-necked 3 L round bottomed flask equipped with overhead stirrer, temperature probe, and nitrogen inlet was charged with 100 grams (0.387 mol) of 2-(3,4-dichloro-phenylamino)-ethanethiol hydrochloride and 1 L of 2B-ethanol. To the resulting suspension was charged 76 grams (1.35 mol, 3.5 equivalents) of potassium hydroxide. The addition resulted in a temperature increase to approximately 35° C. This suspension was stirred at room temperature for 15-20 minutes, then cooled to 5-10° C. and treated with a solution of 59.1 grams (0.425 mol, 1.1 equivalents) of bromoacetic acid in 152 mL of 2B-ethanol. After stirring at room temperature for approximately 3 hours, the reaction mixture was concentrated under vacuum to a volume of approximately 225 mL. To this suspension was added 864 mL (9.15 mol, 23.6 equivalents) of acetic anhydride with no external cooling which resulted in a temperature increase to approximately 100° C. The flask was fitted with a condenser and receiving flask, and heated to 105-110° C. at which point distillate began to be collected. With continued heating, the internal temperature rose to 115° C., the reaction flask was refitted with a reflux condenser and the reaction mixture held at reflux for 1 hour. After allowing to cool to room temperature, the reaction mixture was poured into a 3-necked 5 L round bottomed flask containing 1700 mL of water and 864 mL of methylene chloride and stirred for 10-20 minutes at 20-25° C. The layers were separated and the organic layer was washed with 1 L of water then treated with 2 L of 10% aqueous sodium hydroxide which brought the pH to 9-10. The layers were separated, the organic layer was dried over magnesium sulfate, and concentrated atmospherically to a volume of approximately 200 mL. Displacement of the methylene chloride by isopropyl ether was accomplished by continuing to charge isopropyl ether and concentrating until an internal temperature of 68° C. was attained. The solution was then cooled to room temperature. Solids began to precipitate at 45° C. The resulting slurry was stirred at room temperature for two hours. The solids were collected by filtration, washed with isopropyl ether and vacuum dried at 45-50° C. to yield 57.5 grams (56.7% yield) of the title compound as a white solid, mp 81-83° C. 1H NMR (CDCl3) δ7.44 (d, J=8.7 Hz, 1H), 7.38 (d, J=2.5 Hz, 1H), 7.13 (d, J=2.5 Hz, 1H), 3.93 (t, J=11.5 Hz, 2H), 3.43 (s, 2H), 3.01 (t, J=11.5 Hz, 2H). 13C NMR (CDCl3) δ168.10, 143.04, 134.201, 132.25, 132.09, 129.42, 126.83, 53.32, 31.81, 27.86. HRMS (FAB) calcd for C10H9Cl2NOS: 261.9860; found: 261.9839.

1. customA 3-necked 3 L round bottomed flask equipped with overhead stirrer
2. additionThe addition
3. customresulted in a temperature
4. temperaturecooled to 5-10° C.
5. stirringAfter stirring at room temperature for approximately 3 hours
6. concentrationthe reaction mixture was concentrated under vacuum to a volume of approximately 225 mL
7. temperatureno external cooling which
8. customresulted in a temperature
9. temperatureincrease to approximately 100° C
10. customThe flask was fitted with a condenser
11. temperatureheated to 105-110° C. at which point distillate
12. customto be collected
13. temperatureWith continued heating
14. customrose to 115° C.
15. customthe reaction flask was refitted with a reflux condenser
16. temperatureat reflux for 1 hour
17. temperatureto cool to room temperature
18. additionthe reaction mixture was poured into a 3-necked 5 L round bottomed flask
19. additioncontaining 1700 mL of water and 864 mL of methylene chloride
20. stirringstirred for 10-20 minutes at 20-25° C
21. customThe layers were separated
22. washthe organic layer was washed with 1 L of water
23. additionthen treated with 2 L of 10% aqueous sodium hydroxide which
24. customThe layers were separated
25. dry with materialthe organic layer was dried over magnesium sulfate
26. concentrationconcentrated atmospherically to a volume of approximately 200 mL
27. additionto charge isopropyl ether
28. concentrationconcentrating until an internal temperature of 68° C.
29. temperatureThe solution was then cooled to room temperature
30. customto precipitate at 45° C
31. stirringThe resulting slurry was stirred at room temperature for two hours
32. filtrationThe solids were collected by filtration
33. washwashed with isopropyl ether and vacuum
34. customdried at 45-50° C.