Hydrochloric Acid → (3,5-Difluorophenyl)thiourea

HRID 9569

Reaction equation

HRID 9569 reaction equation
C(Cl)(=O)C1C=CC=CC=1.[S-:10][C:11]#[N:12].[NH4+].[F:14][C:15]1[CH:16]=[C:17]([CH:19]=[C:20]([F:22])[CH:21]=1)[NH2:18].[OH-].[Na+].Cl.[OH-].[NH4+]>CC(C)=O.O>[F:14][C:15]1[CH:16]=[C:17]([NH:18][C:11]([NH2:12])=[S:10])[CH:19]=[C:20]([F:22])[CH:21]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 7412Benzoyl chlorideHCID 14798Sodium HydroxideHCID 14923Ammonium HydroxideHCID 15666Ammonium thiocyanateHCID 965953,5-Difluoroaniline

Product 1

HCID 2783293(3,5-Difluorophenyl)thioureaYield 48.3%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolvent2×HCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

Benzoyl chloride (5.44 g, 38.73 mmol) was added to a stirred solution of ammonium thiocyanate (3.83 g, 50.35 mmol) in acetone (80 mL) at 30° C. The mixture was stirred at reflux for 30 minutes, then cooled to 50° C., and a solution of 3,5-difluoroaniline (5.00 g, 38.73 mmol) in acetone (10 mL) was added in one portion. The mixture was stirred at reflux for 30 minutes. A solution of NaOH (5.42 g, 135.54 mmol) in water (65 mL) was added, and the mixture was stirred at reflux for 20 minutes and then cooled to 20° C. Concentrated HCl was added to adjust the acidity to pH=5, and then the mixture was adjusted to slightly alkaline by the addition of conc. ammonium hydroxide. After 30 minutes, the mixture was cooled to 10° C. and extracted with EtOAc, and the combined organic layer was washed with brine, filtered, and concentrated to afford N-(3,5-difluorophenyl) thiourea (3.52 g, 48%). ret. time 1.73; m/z 189.0 (MH+); 1H NMR (400 MHz, MeOH-d4) δ 6.72 (m, 1H), 7.16 (m, 2H).

Workup

  1. temperatureat reflux for 30 minutes
  2. stirringThe mixture was stirred
  3. temperatureat reflux for 30 minutes
  4. stirringthe mixture was stirred
  5. temperatureat reflux for 20 minutes
  6. temperaturecooled to 20° C
  7. temperaturethe mixture was cooled to 10° C.
  8. extractionextracted with EtOAc
  9. washthe combined organic layer was washed with brine
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-0c0dac246ef34adebe28927fa5547233
Source dataset
uspto-grants-2006_08
Patent number
US07091228B2

Linked notes

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