2-Mercaptobenzoic Acid → 2-(3,5-Dimethoxyphenylthio)benzyl alcohol

HRID 567877Notes

Reaction equation

HRID 567877 reaction equation
[C:1]([OH:10])(=O)[C:2]1[C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[SH:4].Cl[C:12]1[CH:13]=[C:14]([O:20][CH3:21])[CH:15]=[C:16]([O:18][CH3:19])[CH:17]=1.C(=O)([O-])[O-].[K+].[K+]>CN1CCCC1=O.[Cu].[Cu](I)I>[CH3:19][O:18][C:16]1[CH:17]=[C:12]([S:4][C:3]2[CH:5]=[CH:6][CH:7]=[CH:8][C:2]=2[CH2:1][OH:10])[CH:13]=[C:14]([O:20][CH3:21])[CH:15]=1

Participants

7

Reactant 3

HCID 54432-Mercaptobenzoic AcidHCID 11430Potassium CarbonateHCID 815021-Chloro-3,5-dimethoxybenzene

Product 1

HCID 118079672-(3,5-Dimethoxyphenylthio)benzyl alcoholYield 10%

Reagents, catalysts & solvents 3

HCID 23978CopperCatalystHCID 83717Copper iodideCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
190 °C

Procedure

Thiosalicylic acid (44 g), 5-chloro-1,3-dimethoxybenzene (49.2 g), potassium carbonate (78 g), copper (4.3 g) and copper iodide (4.3 g) were dissolved in N-methyl-2-pyrrolidone (390 ml) and the solution was stirred at 190° C. for ten hours. The reaction solution was partitioned between ethyl acetate and diluted hydrochloride and filtered, the organic layer was washed with diluted hydrochloride, water and saturated sodium chloride solution and dried over anhydrous magnesium sulfate and the solvent was evaporated in vacuo. To the residue was added anhydrous tetrahydrofuran (200 ml) and the mixture was dropped into a suspension of lithium aluminum hydride (16.24 g) in anhydrous tetrahydrofuran (100 ml) at 0° C. The reaction solution was stirred overnight at room temperature, saturated sodium chloride solution was added to the reaction solution until no more hydrogen was generated, after decantation the organic layer was evaporated in vacuo. The residue was purified by a silica gel column chromatography (developing solvent; hexane:ethyl acetate=3:1) to give 2-(3,5-dimethoxyphenylthio)benzyl alcohol (7.9 g; yield of 10%).

Workup

  1. customThe reaction solution was partitioned between ethyl acetate and diluted hydrochloride
  2. filtrationfiltered
  3. washthe organic layer was washed with diluted hydrochloride, water and saturated sodium chloride solution
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customthe solvent was evaporated in vacuo
  6. additionTo the residue was added anhydrous tetrahydrofuran (200 ml)
  7. additionthe mixture was dropped into a suspension of lithium aluminum hydride (16.24 g) in anhydrous tetrahydrofuran (100 ml) at 0° C
  8. stirringThe reaction solution was stirred overnight at room temperature
  9. additionsaturated sodium chloride solution was added to the reaction solution until no more hydrogen
  10. customafter decantation the organic layer was evaporated in vacuo
  11. customThe residue was purified by a silica gel column chromatography (developing solvent; hexane:ethyl acetate=3:1)

Sources & evidence

ORD record
ord-edda4a481e5c42cfb6bf6edec69b3004
Source dataset
uspto-grants-2001_01
Patent number
US06180659B2

Reaction notes

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