Ethanethiol → 4-Amino-5-chloro-2-hydroxybenzoic acid

HRID 2254606Notes

Reaction equation

HRID 2254606 reaction equation
[H-].[Na+].C(S)C.[NH2:6][C:7]1[C:15]([Cl:16])=[CH:14][C:10]([C:11]([OH:13])=[O:12])=[C:9]([O:17]C)[CH:8]=1>CN(C)C=O>[NH2:6][C:7]1[C:15]([Cl:16])=[CH:14][C:10]([C:11]([OH:13])=[O:12])=[C:9]([OH:17])[CH:8]=1

Participants

5

Reactant 3

HCID 6343EthanethiolHCID 24758Sodium hydrideHCID 816264-Amino-5-chloro-2-methoxybenzoic acid

Product 1

HCID 148832224-Amino-5-chloro-2-hydroxybenzoic acidYield 83.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A cooled (5° C.) suspension of 60% sodium hydride/oil dispersion (20 g, 0.5 mole) in anhydrous dimethylformamide (300 ml) under nitrogen was treated dropwise with ethyl mercaptan (18.7 g, 0.3 mole) while maintaining a temperature below 15° C., then stirred at room temperature for 15 minutes, cooled (5° C.), and treated in portions with 4-amino-5-chloro-2-methoxybenzoic acid (40.33 g, 0.2 mole). The mixture was heated to 105°±5° C. for 4 hours, cooled, and concentrated in vacuo to remove most of the dimethylformamide, then poured into water (500 ml). The aqueous solution was extracted with methylene chloride (2×150 ml), and ether (150 ml), acidified with concentrated HCl (55 ml), filtered, and the filter cake washed with water and dried in vacuo to provide 35.7 g of crude product. Crystallization of the product from tetrahydrofuran/hexane yielded 31.3 g (83%) of a white solid, mp 192° C.

Workup

  1. temperatureA cooled
  2. temperaturewhile maintaining a temperature below 15° C.
  3. temperaturecooled (5° C.)
  4. temperatureThe mixture was heated to 105°±5° C. for 4 hours
  5. temperaturecooled
  6. concentrationconcentrated in vacuo
  7. customto remove most of the dimethylformamide
  8. additionpoured into water (500 ml)
  9. extractionThe aqueous solution was extracted with methylene chloride (2×150 ml), and ether (150 ml)
  10. filtrationfiltered
  11. washthe filter cake washed with water
  12. customdried in vacuo
  13. customto provide 35.7 g of crude product
  14. customCrystallization of the product from tetrahydrofuran/hexane

Sources & evidence

ORD record
ord-019cbf71efaa40fba7fbf42ec6a3c222
Source dataset
uspto-grants-1993_08
Patent number
US05236931

Reaction notes

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