Hydrochloric Acid → 5-Nitro-1-benzothiophene

HRID 1935631Notes

Reaction equation

HRID 1935631 reaction equation
C(OC)(=O)[CH2:2][SH:3].C[O-].[Na+].Cl[C:11]1[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[CH:15][C:12]=1[CH:13]=O.[OH-].[Na+].Cl>CO.O>[N+:19]([C:16]1[CH:17]=[CH:18][C:11]2[S:3][CH:2]=[CH:13][C:12]=2[CH:15]=1)([O-:21])=[O:20]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 16907Methyl ThioglycolateHCID 729332-Chloro-5-nitrobenzaldehydeHCID 10942334Sodium Methoxide

Product 1

HCID 124140845-Nitro-1-benzothiopheneYield 81%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent3×HCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

Methyl thioglycolate (14.3 g, 135 mmol) in methanol (250 mL) at 40° C. is treated dropwise with 25% sodium methoxide in methanol (37 mL, 160 mmol) and the resulting mixture mechanically stirred at 50° C. for 30 min. 2-chloro-5-nitrobenzaldehyde in methanol (250 mL) is added in a steady stream to give a heavy precipitate which is heated at 50° C. for 1 h. Sodium hydroxide (50% aqueous, 15 mL) is added and heating continued for 2 h, then cooled to ice bath temperature and acidified with concentrated hydrochloric acid. An additional 200 mL of water is added during this process to facilitate stirring. The resulting solids are collected by filtration, washed with water, and dried in vacuo at 45° C. overnight. The dried solids are suspended in quinoline (120 mL), copper metal (7.2 g) is added and the mixture is heated at 190° C. for 2 hr. The mixture is allowed to cool, then poured onto 500 g of ice, 6 N hydrochloric acid (500 mL) is added and then extracted with of dichloromethane. The organic layers are combined and washed with 6 N hydrochloric acid, dried, and flash chromatographed on silica gel eluting with 10-40% ethyl acetate in heptane to give 16.2 g (81%) of the title compound. 1H NMR (CDCl3) δ8.75 (s, 1 H), 8.22 (dd, J=2.3, 10 Hz, 1 H), 8.0 (d, J=10 Hz, 1 H), 7.68 (d, J=6 Hz, 1 H), 7.53 (d, J=6 Hz, 1 H); MS (−ESI) m/z 221.8 (M−H)

Workup

  1. customto give a heavy precipitate which
  2. temperatureis heated at 50° C. for 1 h
  3. temperatureheating
  4. waitcontinued for 2 h
  5. temperaturecooled to ice bath temperature
  6. stirringto facilitate stirring
  7. filtrationThe resulting solids are collected by filtration
  8. washwashed with water
  9. customdried in vacuo at 45° C. overnight
  10. additioncopper metal (7.2 g) is added
  11. temperaturethe mixture is heated at 190° C. for 2 hr
  12. temperatureto cool
  13. additionpoured onto 500 g of ice, 6 N hydrochloric acid (500 mL)
  14. additionis added
  15. extractionextracted with of dichloromethane
  16. washwashed with 6 N hydrochloric acid
  17. customdried
  18. customflash chromatographed on silica gel eluting with 10-40% ethyl acetate in heptane

Sources & evidence

ORD record
ord-db76aacf68804b1e9c303ee4065fa91f
Source dataset
uspto-grants-2002_05
Patent number
US06387896B1

Reaction notes

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