反应详情

To stirred 90° C. polyphosphoric acid (200 g) was added 14.29 g (10.2 mmol) of 2-fluorobenzoic acid and aniline (9.32 g 10.0 mmol) and the bath temperature raised to 180°-190° C. and held there for 1 hour. A solution was obtained at about 140° C. The heating bath was removed and the stirred mixture (sublimate above the solution) was treated cautiously with 80 mL of water. The mixture was stirred at 140°-155° C. for 1 hour, the heating bath removed, 66 mL of 3N HCl added, the mixture poured into 1L of water and filtered through a pad of Celite. The liltrate was basilled with 15% sodium hydroxide and the solid which formed on stirring was collected. The Celite pad was washed well with methylene chloride, the methylene chloride removed and the residue was combined with the solid obtained from basification of the aqueous phase. The combined material was dissolved in refluxing ethanol (175 mL), and treated hot with 125 mL of water. The brown solid obtaing on cooling was additionally recrystallized twice from ethyl acetate - hexane. Final purification by flash column chromatography (methylene chloride) yielded the aniline as a white solid (5.45 g, 25%); mp 128°-130° C. 1H-NMR (250 MHz, d6-DMSO): 6.32 (s, 2H, NH2) 6.60 (dd, 2H, J=8.6, 1.5 Hz, aromatic) 7.28-7.35 (m, 2H, aromatic) 7.40-7.60 (m, 4H, aromatic). MS (CI, CH4): 216 (M+1).

1. temperaturethe bath temperature raised to 180°-190° C.
2. customA solution was obtained at about 140° C
3. customThe heating bath was removed
4. additionthe stirred mixture (sublimate above the solution) was treated cautiously with 80 mL of water
5. customthe heating bath removed
6. addition66 mL of 3N HCl added
7. additionthe mixture poured into 1L of water
8. filtrationfiltered through a pad of Celite
9. customthe solid which formed
10. stirringon stirring
11. customwas collected
12. washThe Celite pad was washed well with methylene chloride
13. customthe methylene chloride removed
14. customobtained from basification of the aqueous phase
15. dissolutionThe combined material was dissolved
16. temperatureThe brown solid obtaing on cooling
17. customwas additionally recrystallized twice from ethyl acetate - hexane
18. customFinal purification by flash column chromatography (methylene chloride)