3-Chlorothiophenol → 4-Chlorophenyl-alpha-[(3-chlorophenyl)thiomethyl]acetic acid

HRID 2399778Notes

Reaction equation

HRID 2399778 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[CH2:14])[C:9]([O:11]CC)=[O:10])=[CH:4][CH:3]=1.[Cl:15][C:16]1[CH:17]=[C:18]([SH:22])[CH:19]=[CH:20][CH:21]=1>C(O)C.[O-]CC.[Na+]>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([CH2:14][S:22][C:18]2[CH:19]=[CH:20][CH:21]=[C:16]([Cl:15])[CH:17]=2)[C:9]([OH:11])=[O:10])=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 162573-ChlorothiophenolHCID 181005Benzeneacetic acid, 4-chloro-alpha-methylene-, ethyl ester

Product 1

HCID 193846964-Chlorophenyl-alpha-[(3-chlorophenyl)thiomethyl]acetic acidYield 81.2%

Reagents, catalysts & solvents 2

HCID 2723922Sodium ethoxideCatalystHCID 702EthanolSolvent

Procedure

A solution of the ethyl 4-chlorophenyl-α-methyleneacetate (4.2 g), m-chlorothiophenol (2.9 g) and sodium ethoxide (0.05 g) in ethanol (20 ml) was stirred at room temperature for 12 hours. The reaction mixture was concentrated under reduced pressure, followed by addition of water (150 ml) to the residue, and the mixture was extracted with ether (150 ml). The extract was washed two times with 15% aqueous sodium hydroxide, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. To the resulting residue were added 88% formic acid (20 ml) and methanesulfonic acid (2.1 ml), followed by heating at reflux for 8 hours. After cooling to room temperature, the mixture was poured into water (100 ml) and extracted with dichloromethane (150 ml). The aqueous layer was further washed with dichloromethane (50 ml), and the combined organic layer was dried over anhydrous magnesium sulfate and concentrated. The resulting residue was subjected to chromatography on silica gel to give 4-chlorophenyl-α-[(3-chlorophenyl)thiomethyl]-acetic acid (yield, 5.3 g), nD23.6, 1.5627

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionfollowed by addition of water (150 ml) to the residue
  3. extractionthe mixture was extracted with ether (150 ml)
  4. washThe extract was washed two times with 15% aqueous sodium hydroxide
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. additionTo the resulting residue were added 88% formic acid (20 ml) and methanesulfonic acid (2.1 ml)
  8. temperatureby heating
  9. temperatureat reflux for 8 hours
  10. additionthe mixture was poured into water (100 ml)
  11. extractionextracted with dichloromethane (150 ml)
  12. washThe aqueous layer was further washed with dichloromethane (50 ml)
  13. dry with materialthe combined organic layer was dried over anhydrous magnesium sulfate
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-7ddebfc6fe294e0cb6cb7a947d540cfe
Source dataset
uspto-grants-1995_09
Patent number
US05451607

Reaction notes

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