Phenol → 4-Methoxy-1-nitro-2-phenoxybenzene

HRID 448383Notes

Reaction equation

HRID 448383 reaction equation
[H-].[Na+].[C:3]1([OH:9])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.I[C:11]1[CH:12]=[C:13]([O:20][CH3:21])[CH:14]=[CH:15][C:16]=1[N+:17]([O-:19])=[O:18]>N1C=CC=CC=1.[Cu](Br)Br>[CH3:21][O:20][C:13]1[CH:14]=[CH:15][C:16]([N+:17]([O-:19])=[O:18])=[C:11]([O:9][C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=2)[CH:12]=1

Participants

6

Reactant 3

HCID 996PhenolHCID 24758Sodium hydrideHCID 27334564-Nitro-3-iodoanisole

Product 1

HCID 583072504-Methoxy-1-nitro-2-phenoxybenzeneYield 64%

Reagents, catalysts & solvents 2

HCID 24611Copper bromide (CuBr2)CatalystHCID 1049PyridineSolvent

Procedure

A 60% dispersion of sodium hydride (0.86 g, 22 mmol) was added to a mixture of copper bromide (2.6 g, 17.9 mmol) and phenol (1.7 g, 17.9 mmol) in pyridine (300 mL). After the effervescence subsided, the mixture was heated to reflux for 30 minutes. 3-Iodo-4-nitroanisole (5.0 g, 17.9 mmol) was added and stirring proceeded under nitrogen for 20 hours. The mixture was cooled and the reaction was quenched with saturated ammonium chloride (1 mL). The mixture was evaporated in vacuo. The residue was dissolved in ethyl acetate (250 mL) and washed with dilute aqueous HCl (2×200 mL), saturated sodium carbonate (2×200 mL) and water (200 mL), and was evaporated in vacuo. The residue was purified by ISCO silica gel flash chromatography in hexanes-ethyl acetate gradient, eluting 2.8 g of the product at 7:3 hexanes-ethyl acetate, in 64% yield; 1H NMR (CDCl3) δ 3.78 (s, 3H), 6.43 (d, J=2.3 Hz, 1H), 6.68 (dd, J=9.2, J=2.3 Hz, 1H), 7.03-7.07 (m, 2H), 7.19 (t, J=7.3 Hz, 1H), 7.37-7.41 (m, 2H), 8.07 (d, J=9.2 Hz, 1H).

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 30 minutes
  3. temperatureThe mixture was cooled
  4. customthe reaction was quenched with saturated ammonium chloride (1 mL)
  5. customThe mixture was evaporated in vacuo
  6. dissolutionThe residue was dissolved in ethyl acetate (250 mL)
  7. washwashed with dilute aqueous HCl (2×200 mL), saturated sodium carbonate (2×200 mL) and water (200 mL)
  8. customwas evaporated in vacuo
  9. customThe residue was purified by ISCO silica gel flash chromatography in hexanes-ethyl acetate gradient
  10. washeluting 2.8 g of the product at 7:3 hexanes-ethyl acetate

Sources & evidence

ORD record
ord-5a118e78b6c842d58fa96ec98f1c6893
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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