Toluene → 4-(4-Chlorophenoxy)-3,5-difluoroaniline

HRID 1669986Notes

Reaction equation

HRID 1669986 reaction equation
[Cl:1][C:2]1[CH:19]=[CH:18][C:5]([O:6][C:7]2[C:12]([F:13])=[CH:11][C:10]([N+:14]([O-])=O)=[CH:9][C:8]=2[F:17])=[CH:4][CH:3]=1.C1(C)C=CC=CC=1.C([O-])(=O)C.[NH4+]>[Fe].O>[Cl:1][C:2]1[CH:19]=[CH:18][C:5]([O:6][C:7]2[C:12]([F:13])=[CH:11][C:10]([NH2:14])=[CH:9][C:8]=2[F:17])=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 1140TolueneHCID 517165Ammonium AcetateHCID 469415962-(4-Chlorophenoxy)-1,3-difluoro-5-nitrobenzene

Product 1

HCID 529880694-(4-Chlorophenoxy)-3,5-difluoroanilineYield 114.2%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 962WaterSolvent

Procedure

A mixture of 4-(4-chlorophenoxy)-3,5-difluoronitrobenzene (10.6 g, 37 mmol), toluene (150 ml), H2O (150 ml), iron powder (6.9 g, 124 mmol), and ammonium acetate (9.3 g, 120 mmol) was heated to reflux with stirring for 2-3 hrs. After cooling to room temperature, the reaction mixture was filtered through Celite with thorough washing with H2O and EtOAc. The filtrate was transferred to a separatory funnel and the phases separated. The aqueous phase was further extracted with EtOAc (2×). The combined organic phases were washed with H2O (1×), sat'd NaCl (1×), dried over Na2SO4, and concentrated in vacuo to give 4-(4-chlorophenoxy)-3,5-difluoroaniline (10.8 g, 113%) which was used in the next step without further purification. 1H NMR (CDCl3): δ 3.81 (s, 2H), 6.27 (d, 2H, J=9.2 Hz), 6.85 (d, 2H, J=9.2 Hz), 7.21 (d, 2H, J=9.2 Hz).

Workup

  1. temperaturewas heated
  2. temperatureto reflux
  3. filtrationthe reaction mixture was filtered through Celite
  4. washwith thorough washing with H2O and EtOAc
  5. customThe filtrate was transferred to a separatory funnel
  6. customthe phases separated
  7. extractionThe aqueous phase was further extracted with EtOAc (2×)
  8. washThe combined organic phases were washed with H2O (1×), sat'd NaCl (1×)
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c851634278474f2893302d964bfda08f
Source dataset
uspto-grants-2011_08
Patent number
US07989661B2

Reaction notes

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