Aniline → 4'-Amino-2,3-difluorobenzophenone

HRID 865763Notes

Reaction equation

HRID 865763 reaction equation
[F:1][C:2]1[C:10]([F:11])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.[NH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>>[NH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:4](=[O:6])[C:3]2[CH:7]=[CH:8][CH:9]=[C:10]([F:11])[C:2]=2[F:1])=[CH:15][CH:14]=1

Participants

3

Reactant 2

HCID 6115AnilineHCID 3705902,3-Difluorobenzoic acid

Product 1

HCID 108235164'-Amino-2,3-difluorobenzophenoneYield 10%

Conditions

Temperature
90 °C

Procedure

To stirred polyphosphoric acid (125 g) heated to 90° C. was added 2,3-difluorobenzoic acid (10.00 g, 63.3 mmol) followed by aniline (5.72 g, 61.7 mmol). The reaction mixture was heated at 180°-185° C. for 1 hour (solid dissolved at 135° C.), then the oil bath was removed and distilled water (35 mL) was cautiously added in small portions through the condenser. The oil bath was returned, and the reaction mixture heated at 135°-145° C. for 1 hour. The oil bath was again removed, 3N HCl (55 mL) was added to the solution, the reaction mixture was then poured into water (750 mL) and stirred for one hour. The aqueous solution was filtered through Celite and the filtrate basified with 15% NaOH to a pH of 8. A green solid was collected by filtration and purified by flash column chromatography (methylene chloride). Trituration with hexane yielded the title benzophenone (1.43 g, 10%) as a yellow solid; mp 104°-106° C. 1H-NMR (250 MHz, d6-DMSO): 6.41 (s, 2H, NH2) 6.60 (d, 2H, J=8.7 Hz, aromatic) 7.22-7.37 (m, 2H, aromatic) 7.50 (d, 2H, J=8.6 Hz, aromatic) 7.53-7.64 (m, 1H, aromatic). MS (CI, CH4): 234 (M+1).

Workup

  1. temperatureThe reaction mixture was heated at 180°-185° C. for 1 hour
  2. dissolution(solid dissolved at 135° C.)
  3. customthe oil bath was removed
  4. distillationdistilled water (35 mL)
  5. additionwas cautiously added in small portions through the condenser
  6. temperaturethe reaction mixture heated at 135°-145° C. for 1 hour
  7. customThe oil bath was again removed
  8. addition3N HCl (55 mL) was added to the solution
  9. additionthe reaction mixture was then poured into water (750 mL)
  10. filtrationThe aqueous solution was filtered through Celite
  11. filtrationA green solid was collected by filtration
  12. custompurified by flash column chromatography (methylene chloride)

Sources & evidence

ORD record
ord-db967ebc58814947b70e9f79c895f2ce
Source dataset
uspto-grants-1996_10
Patent number
US05567735

Reaction notes

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