Hydrogen Bromide → 4-(4-Chlorophenoxy)phenol

HRID 273669Notes

Reaction equation

HRID 273669 reaction equation
COC1C=CC(O)=CC=1.[OH-].[K+].ClC1C=CC(I)=CC=1.[Cl:20][C:21]1[CH:35]=[CH:34][C:24]([O:25][C:26]2[CH:31]=[CH:30][C:29]([O:32]C)=[CH:28][CH:27]=2)=[CH:23][CH:22]=1.Br>C(O)C.[Cu].C(O)(=O)C.CC1C=CC(C)=CC=1>[Cl:20][C:21]1[CH:35]=[CH:34][C:24]([O:25][C:26]2[CH:31]=[CH:30][C:29]([OH:32])=[CH:28][CH:27]=2)=[CH:23][CH:22]=1

Participants

10

Reactant 5

HCID 260Hydrogen BromideHCID 90154-MethoxyphenolHCID 125101-Chloro-4-iodobenzeneHCID 14797Potassium HydroxideHCID 101054561-Chloro-4-(4-methoxyphenoxy)benzene

Product 1

HCID 123461204-(4-Chlorophenoxy)phenol

Reagents, catalysts & solvents 4

HCID 23978CopperCatalystHCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 7809P-XyleneSolvent

Procedure

The 4-(4-chlorophenoxy)phenol precurser was prepared as follows. A 1 L 3-necked flask equipped with a mechanical stirrer, a Dean-Stark trap carrying a reflux condenser, and a heating mantle, was charged with 4-methoxyphenol (35.9 g, 0.29 mol), 85 percent KOH (19.1 g, 0.29 mol) and p-xylene (350 mL), and the mixture was heated at reflux for 1 hour, thus removing the water of reaction azeotropically. The mixture was cooled, and 1-chloro-4-iodobenzene (69 g, 0.29 mol), copper powder (2.9 g, 46 mmol), and cuprous chloride (2.9 g, 29 mmol) were added and the mixture was heated at reflux for 20 hours. The reaction was monitored periodically by HPLC. Workup consisted of diluting the cooled mixture with Et2O (200 mL), filtration through a medium-fritted funnel, and concentration of the filtrate to leave a deep dark oily residue. This crude material, consisting primarily of 4-(4-chlorophenoxy)anisole, was treated with glacial acetic acid (275 mL) and 48 percent HBr (105 mL), and the mixture was heated at reflux for 24 hours. Workup consisted of partitioning the mixture between H2O (1.2 L) and CH2Cl2 (0.5 L), washing the organic phase with H2O (0.5 L), and concentration to leave a deep dark oil residue. This residue was taken up in ethanol (0.5 L) and treated with activated carbon (Norit; 50 g). Filtration through celite, and concentration of the filtrate gave the crude 4-(4-chlorophenoxy)phenol as a thick, red oil. Further purification of the product was achieved by chromatography on a column packed with flash-grade silica gel (6"×2" i.d.), eluting with CH2Cl2, to give after concentration a pinkish solid, which was subsequently recrystallized from hexane-EtOAc to give 31.4 g (49% yield) of the pure product as off-white prisms m.p. 85-86° C.

Workup

  1. customThe 4-(4-chlorophenoxy)phenol precurser was prepared
  2. customA 1 L 3-necked flask equipped with a mechanical stirrer
  3. temperaturethe mixture was heated
  4. temperatureat reflux for 1 hour
  5. customthus removing
  6. customthe water of reaction azeotropically
  7. temperatureThe mixture was cooled
  8. temperaturethe mixture was heated
  9. temperatureat reflux for 20 hours
  10. additionof diluting the cooled mixture
  11. filtrationwith Et2O (200 mL), filtration through a medium-fritted funnel
  12. customconcentration of the filtrate to leave a deep dark oily residue
  13. temperaturethe mixture was heated
  14. temperatureat reflux for 24 hours
  15. customof partitioning the mixture between H2O (1.2 L) and CH2Cl2 (0.5 L)
  16. washwashing the organic phase
  17. concentrationwith H2O (0.5 L), and concentration
  18. customto leave a deep dark oil residue
  19. additiontreated with activated carbon (Norit; 50 g)
  20. filtrationFiltration through celite, and concentration of the filtrate

Sources & evidence

ORD record
ord-444fab22196d4dae814e7cb084135576
Source dataset
uspto-grants-1995_02
Patent number
US05387353

Reaction notes

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