Sulfuric Acid → 3,4-Difluoro-2-(difluoromethoxy)aniline

HRID 1275929Notes

Reaction equation

HRID 1275929 reaction equation
S(=O)(=O)(O)O.[F:6][C:7]1[C:8]([O:17][CH:18]([F:20])[F:19])=[C:9]([N+:14]([O-])=O)[CH:10]=[CH:11][C:12]=1[F:13]>[Fe].O>[F:6][C:7]1[C:8]([O:17][CH:18]([F:19])[F:20])=[C:9]([CH:10]=[CH:11][C:12]=1[F:13])[NH2:14]

Participants

5

Reactant 2

HCID 1118Sulfuric AcidHCID 221180133-(Difluoromethoxy)-1,2-difluoro-4-nitro-benzene

Product 1

HCID 221180113,4-Difluoro-2-(difluoromethoxy)anilineYield 72.8%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 962WaterSolvent

Conditions

Temperature
95 °C

Procedure

Into a 200-ml four-necked flask provided with a reflux condenser, a thermometer and a stirrer were fed 7.0 g (0.125 mol) of an iron powder, 50 ml of water and 0.1 ml of 98% sulfuric acid. The resulting mixture was heated to 95° C. on an oil bath. Thereto was dropwise added, at 95 to 100° C. over 10 minutes, 11.3 g (0.05 mol) of the previously synthesized 3,4-difluoro-2-difluoromethoxy-nitrobenzene. The resulting mixture was stirred at the same temperature for 2.5 hours. Then, a Dean-Stark trap was fitted and the mixture was refluxed with heating, whereby an oily substance was separated as a fraction of azeotropic distillation with water. The aqueous layer was subjected to extraction with 100 ml of methylene chloride. The resulting methylene chloride layer was mixed with the oily substance. The resulting mixture was concentrated, and the resulting residue was subjected to vacuum distillation to obtain 7.1 g (yield: 72.8%) of 3,4-difluoro-2-difluoromethoxy-aniline (purity: 99.1%, boiling point: 76-78° C./6 mmHg).

Workup

  1. customInto a 200-ml four-necked flask provided with a reflux condenser
  2. additionThereto was dropwise added, at 95 to 100° C. over 10 minutes
  3. customThen, a Dean-Stark trap was fitted
  4. temperaturethe mixture was refluxed
  5. temperaturewith heating
  6. customwhereby an oily substance was separated as a fraction of azeotropic distillation with water
  7. extractionThe aqueous layer was subjected to extraction with 100 ml of methylene chloride
  8. additionThe resulting methylene chloride layer was mixed with the oily substance
  9. concentrationThe resulting mixture was concentrated
  10. distillationthe resulting residue was subjected to vacuum distillation

Sources & evidence

ORD record
ord-ff8e5457f53e4f71a831f514fc7c7aac
Source dataset
uspto-grants-2000_12
Patent number
US06162944

Reaction notes

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