p-Fluoronitrobenzene → 1,3-Difluoro-2-(4-nitrophenoxy)benzene

HRID 409057Notes

Reaction equation

HRID 409057 reaction equation
[H-].[Na+].F[C:4]1[CH:9]=[CH:8][C:7]([N+:10]([O-:12])=[O:11])=[CH:6][CH:5]=1.[F:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[C:15]=1[OH:21]>CN(C)C=O.O>[F:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[C:15]=1[O:21][C:4]1[CH:9]=[CH:8][C:7]([N+:10]([O-:12])=[O:11])=[CH:6][CH:5]=1

Participants

6

Reactant 3

HCID 9590p-FluoronitrobenzeneHCID 24758Sodium hydrideHCID 943922,6-Difluorophenol

Product 1

HCID 138436881,3-Difluoro-2-(4-nitrophenoxy)benzeneYield 80.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent3×

Conditions

Temperature
0 °C

Procedure

Into a 500-mL 4-necked round-bottom flask, was placed a solution of sodium hydride (4.05 g, 168.75 mmol, 1.70 equiv) in N,N-dimethylformamide (200 mL). A solution of 1-fluoro-4-nitrobenzene (14 g, 99.22 mmol, 1.00 equiv) in N,N-dimethylformamide (50 mL) was added dropwise with stirring at 0° C. over 20 min. The resulting solution was stirred for 2 hr at room temperature. Cu2Cl2 (9.83 g, 100.31 mmol, 1.01 equiv) was added and a solution of 2,6-difluorophenol (15.5 g, 119.15 mmol, 1.20 equiv) in N,N-dimethylformamide (50 mL) was added dropwise with stirring at 25° C. over 10 min. The resulting solution was stirred for 12 h at 100° C. in an oil bath, diluted with 500 mL of water and extracted with ethyl acetate. The combined organic layers were washed with water and brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was placed on a silica gel column and eluted with ethyl acetate/petroleum ether (1/8) to give 20 g (80%) of 1,3-difluoro-2-(4-nitrophenoxy)benzene as brown oil.

Workup

  1. customInto a 500-mL 4-necked round-bottom flask, was placed
  2. stirringThe resulting solution was stirred for 2 hr at room temperature
  3. stirringwith stirring at 25° C. over 10 min
  4. stirringThe resulting solution was stirred for 12 h at 100° C. in an oil bath
  5. extractionextracted with ethyl acetate
  6. washThe combined organic layers were washed with water and brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated under vacuum
  9. washeluted with ethyl acetate/petroleum ether (1/8)

Sources & evidence

ORD record
ord-3b18621192624507b45163b0e3607988
Source dataset
uspto-grants-2014_06
Patent number
US08759358B1

Reaction notes

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