Aniline → 4-(Phenylamino)benzoic acid

HRID 1093589Notes

Reaction equation

HRID 1093589 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[C:9]1[CH:17]=[CH:16][C:12]([C:13]([OH:15])=[O:14])=[CH:11][CH:10]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[C:2]1([NH:1][C:9]2[CH:17]=[CH:16][C:12]([C:13]([OH:15])=[O:14])=[CH:11][CH:10]=2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 6115AnilineHCID 10796Cesium carbonateHCID 114644-Bromobenzoic acid

Product 1

HCID 2923314-(Phenylamino)benzoic acidYield 83.6%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 634876Binap, (A+-)-CatalystHCID 1140TolueneSolvent2×

Procedure

A mixture of BINAP (1.6 g, 0.00257 mole), palladium acetate (0.23 g, 0.001 mole) and toluene (30 mL) was degassed with argon for 15 minutes. This mixture was then added to a mixture of aniline (5.0 g, 0.0536 mole), 4-bromobenzoic acid (12.9 g, 0.0644 mole) and cesium carbonate (52.47 g, 0.161 mole) in toluene (30 mL) (previously degassed with argon for 15 minutes). The resulting mixture was heated at reflux for 22 hours. The reaction mixture was then concentrated under reduced pressure. The resulting residue was acidified with 10% HCl and the product was extracted with ethyl acetate. The ethyl acetate layer was washed with brine solution, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography using silica gel 60-120 mesh (15% ethyl acetate in hexane) to afford 9.55 g (83%) of 4-phenylamino-benzoic acid.

Workup

  1. customwas degassed with argon for 15 minutes
  2. custompreviously degassed with argon for 15 minutes)
  3. temperatureThe resulting mixture was heated
  4. temperatureat reflux for 22 hours
  5. concentrationThe reaction mixture was then concentrated under reduced pressure
  6. extractionthe product was extracted with ethyl acetate
  7. washThe ethyl acetate layer was washed with brine solution
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-3c82169165b1426ab0f2c868d4cb8389
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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