Triethylamine → 2,5-Difluorothiobenzamide

HRID 1037478Notes

Reaction equation

HRID 1037478 reaction equation
[F:1][C:2]1[CH:9]=[CH:8][C:7]([F:10])=[CH:6][C:3]=1[C:4]#[N:5].[NH4+]=[S:12].C(N(CC)CC)C>N1C=CC=CC=1.O>[F:1][C:2]1[CH:9]=[CH:8][C:7]([F:10])=[CH:6][C:3]=1[C:4](=[S:12])[NH2:5]

Participants

5

Reactant 2

HCID 8471TriethylamineHCID 1235582,5-Difluorobenzonitrile

Product 1

HCID 227131172,5-DifluorothiobenzamideYield 99%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 1049PyridineSolvent

Conditions

Temperature
50 °C

Procedure

A stirred solution of 2,5-difluorobenzonitrile (25 g, 180 mmol) in pyridine (90 mL) was treated with 20 wt % ammonium sulfide in water (67.4 mL, 198 mmol) and triethylamine (27.4 mL, 198 mmol). The reaction mixture was stirred at 50° C. for 5 hr until the reaction was complete. After cooling to room temperature, the mixture was diluted with cold water and extracted with EtOAc. The organic layer was separated, then washed with H2O (×3), brine (×3), then dried over anhydrous Na2SO4, filtered, and evaporated under reduced pressure to give the crude product. Purification on silica gel column (20% EtOAc in hexanes) to afford 2,5-difluorobenzothioamide as yellow solid (31.0 g, 99%). 1H NMR (CDCl3, 300 MHz): δ 7.12 (m, 2H), 7.90 (br, 2H), 8.08 (m, 1H). LC/MS (uplc): MH+174.0, 0.64 min.

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionextracted with EtOAc
  3. customThe organic layer was separated
  4. washwashed with H2O (×3), brine (×3)
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. customto give the crude product
  9. customPurification on silica gel column (20% EtOAc in hexanes)

Sources & evidence

ORD record
ord-0aa4d8e5fb0246b9be5615aba4a62f0f
Source dataset
uspto-grants-2013_10
Patent number
US08546434B2

Reaction notes

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