Phenol → 4-Phenoxybenzonitrile

HRID 1884217Notes

Reaction equation

HRID 1884217 reaction equation
Br[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1.[C:10]1([OH:16])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C([O-])([O-])=O.[Cs+].[Cs+].C1(C(O)=O)C2C(=CC=CC=2)C=CC=1>C(OCC)(=O)C.C1(C)C=CC=CC=1>[O:16]([C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

7

Reactant 4

HCID 996PhenolHCID 68471-Naphthoic acidHCID 10796Cesium carbonateHCID 12162Benzonitrile, 4-bromo-

Product 1

HCID 1378214-PhenoxybenzonitrileYield 86%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateCatalystHCID 1140TolueneSolvent

Procedure

4-Bromobenzonitrile (2.5 mmol), phenol (3.5 or 5.0 mmol), Cs2CO3 (3.5 or 5.0 mmol), (CuOTf)2 PhH (0.0625 mmol, 5.0 mol % Cu), ethyl acetate (0.125 mmol, 5.0 mol %), 1-naphthoic acid (3.5 mmol), molecular sieves (625 mg) and toluene (1.5 mL) were added to an oven-dried test tube which was then sealed with a septum, purged with argon, and heated to 110 C. under argon until the aryl halide was consumed as determined by GC analysis. Upon cooling at room temperature, dichloromethane was added and the solvent was removed by filtration. The remaining molecular sieves were stirred with another portion of dichloromethane for 1 h at room temperature, and the solvent was removed by filtration. The combined organic phases were washed with 5% aqueous NaOH. The aqueous layer was then extracted three times with dichloromethane and the combined organic layers were washed with brine. The organic layer was dried over Mg2SO4 and concentrated under vacuum to give the crude product. Purification by flash column chromatography (3% EtOAc/hexane) gave the analytically pure product as a clear oil (405 mg, 86% yield). 1H NMR (300 MHz, CDCl3) δ 7.57 (d, J=8.7 Hz, 2 H), 7.40 (t, J=7.9 Hz, 2 H), 7.22 (t, J=7.6 Hz, 1 H), 7.05 (d, J=7.9 Hz, 2 H), 6.98 (d, J=8.8 Hz, 2 H); 13C NMR (75 MHz, CDCl3) δ 154.6, 133.9, 130.0, 124.9, 120.2, 118.6, 117.7, 105.6; IR (neat): 3068, 2226, 1586, 1483, 1245, 1165 cm−1.

Workup

  1. customwas then sealed with a septum
  2. custompurged with argon
  3. temperatureheated to 110 C
  4. customunder argon until the aryl halide was consumed
  5. additiondichloromethane was added
  6. customthe solvent was removed by filtration
  7. customthe solvent was removed by filtration
  8. washThe combined organic phases were washed with 5% aqueous NaOH
  9. extractionThe aqueous layer was then extracted three times with dichloromethane
  10. washthe combined organic layers were washed with brine
  11. dry with materialThe organic layer was dried over Mg2SO4
  12. concentrationconcentrated under vacuum
  13. customto give the crude product
  14. customPurification by flash column chromatography (3% EtOAc/hexane)

Sources & evidence

ORD record
ord-cb3657c41bcd4ac4a147fc2c18348841
Source dataset
uspto-grants-2004_07
Patent number
US06762329B2

Reaction notes

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