Nitric Acid → 4,5-Difluoro-2-nitrophenol

HRID 1256020Notes

Reaction equation

HRID 1256020 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([OH:9])[CH:5]=[CH:6][C:7]=1[F:8].[N+:10]([O-])([OH:12])=[O:11].O.C(Cl)Cl>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.ClC(Cl)C>[F:8][C:7]1[C:2]([F:1])=[CH:3][C:4]([OH:9])=[C:5]([N+:10]([O-:12])=[O:11])[CH:6]=1

Participants

7

Reactant 4

HCID 944Nitric AcidHCID 962WaterHCID 6344DichloromethaneHCID 759273,4-Difluorophenol

Product 1

HCID 27741824,5-Difluoro-2-nitrophenolYield 30%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 63651,1-DichloroethaneSolvent

Procedure

A solution of 3,4-difluorophenol (5.0 g, 38.4 mmol) and tetrabutylammonium bromide (1.239 g, 3.8 mmol) in dichloroethane (30 mL) were added into a 250 mL round-bottomed flask. The mixture was stirred for 45 min before nitric acid (86 g, 96.09 mmol) (7%) was added. The reaction was stirred at RT for 14 h. Water (100 mL) and DCM (50 mL) was added. After stirring for another 10 min, the mixture was partitioned, and the aqueous layer was extracted with DCM (1×20 mL). The combined organic layer was dried (Na2SO4), and concentrated to give the crude product. The crude product was purified by chromatography on silica gel using EtOAc/hexance (0-50%, 30 min). Collected fractions were concentrated to give the title product (2.0 g, 30% yield).

Workup

  1. additionwas added
  2. stirringAfter stirring for another 10 min
  3. customthe mixture was partitioned
  4. extractionthe aqueous layer was extracted with DCM (1×20 mL)
  5. dry with materialThe combined organic layer was dried (Na2SO4)
  6. concentrationconcentrated
  7. customto give the crude product
  8. customThe crude product was purified by chromatography on silica gel
  9. customEtOAc/hexance (0-50%, 30 min)
  10. concentrationCollected fractions were concentrated

Sources & evidence

ORD record
ord-b6654557683143e9b93a9feba72a68a7
Source dataset
uspto-grants-2013_06
Patent number
US08461170B2

Reaction notes

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