反应详情

To stirred 90° C. polyphosphoric acid (125 g) was added 2,5-difluoro-benzoic acid (10.0 g, 6.32 mmol) and aniline (5.87 g 6.3 mmol) and the bath temperature raised to 180°-190° C. and held there for 1 hour. The heating bath was removed and the stirred mixture (sublimate above the solution) was treated cautiously with 50 mL of water. The mixture was stirred at 140°-155° C. for 1 hour, the heating bath removed, 45 mL of 3N HCl added, the mixture poured into 650 mL of water and filtered through a pad of Celite. The filtrate was basified with 15% sodium hydroxide and the mixture filtered through a pad of Celite. The Celite pad was washed well with methylene chloride, the methylene chloride dried (MgSO4), filtered and the solvent removed in vacuo. Purification by flash column chromatography (methylene chloride) followed by recrystallization twice from 50% ethanol (80 mL) yielded the aniline as a yellow solid (3.08 g, 21%); mp 101°-103° C. 1H--NMR (300 MHz, CDCl3): 4.27 (s, 2H, NH2) 6.63-6.67 (m, 2H, aromatic) 7.09-7.19 (m, 3H, aromatic) 7.68-7.71 (m, 2H, aromatic). MS (CI, CH4): 234 (M+1).

1. temperaturethe bath temperature raised to 180°-190° C.
2. customThe heating bath was removed
3. additionthe stirred mixture (sublimate above the solution) was treated cautiously with 50 mL of water
4. customthe heating bath removed
5. addition45 mL of 3N HCl added
6. additionthe mixture poured into 650 mL of water
7. filtrationfiltered through a pad of Celite
8. filtrationthe mixture filtered through a pad of Celite
9. washThe Celite pad was washed well with methylene chloride
10. dry with materialthe methylene chloride dried (MgSO4)
11. filtrationfiltered
12. customthe solvent removed in vacuo
13. customPurification by flash column chromatography (methylene chloride)
14. customfollowed by recrystallization twice from 50% ethanol (80 mL)