Phosphorus sulfide (P2S5) → 5-(2-Chlorophenyl)-7-ethyl-1,3-dihydro-2H-thieno[2,3-e]-1,4-diazepine-2-thione

HRID 1291739Notes

Reaction equation

HRID 1291739 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:9]2[CH:18]=[C:17]([CH2:19][CH3:20])[S:16][C:10]=2[NH:11][C:12](=O)[CH2:13][N:14]=1.P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:22].C(=O)(O)[O-].[Na+]>C(Cl)(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:9]2[CH:18]=[C:17]([CH2:19][CH3:20])[S:16][C:10]=2[NH:11][C:12](=[S:22])[CH2:13][N:14]=1

Participants

5

Reactant 3

HCID 14817Phosphorus sulfide (P2S5)HCID 516892Sodium BicarbonateHCID 135624512Desmethylclotiazepam

Product 1

HCID 1356675755-(2-Chlorophenyl)-7-ethyl-1,3-dihydro-2H-thieno[2,3-e]-1,4-diazepine-2-thioneYield 99.7%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

5-(2-Chlorophenyl)-7-ethyl-1,3-dihydro-2H-thieno[2,3-e]-1,4-diazepin-2-one (40 g) was dissolved in chloroform (600 ml) and phosphorus pentasulfide (117 g) was added thereto with stirring. The mixture was refluxed for 3 hours. After the reaction, the reaction mixture was neutralized with saturated aqueous sodium bicarbonate, washed with water, and dried over anhydrous magnesium sulfate. The solvent was distilled away under reduced pressure and precipitated crystals were collected by filtration with diisopropyl ether and recrystallized from ethanol-chloroform to give 42 g of 5-(2-chlorophenyl)-7-ethyl-1,3-dihydro-2H-thieno[2,3-e]-1,4-diazepine-2-thione having a melting point of 198°-199° C. The thione compound obtained (42 g) was suspended in methanol (300 ml) and 100% hydrazine hydrate (19 ml) was added thereto under cooling. The mixture was stirred at room temperature for 2 hours. After the reaction, the precipitated crystals were collected by filtration and recrystallized from ethanol-dimethylformamide to give 34 g of 5-(2-chlorophenyl)-7-ethyl-1,3-dihydro-2H-thieno[2,3-e]-1,4-diazepine-2-hydrazine, melting point 214°-216° C. The hydrazone compound (20 g) was dissolved in chloroform (200 ml) and cyclohexylcarbonyl chloride (10 g) was added thereto with stirring. The mixture was stirred at room temperature for 1 hour. After the reaction, the reaction mixture was washed with a saturated aqueous solution of sodium bicarbonate and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue obtained was dissolved in toluene (200 ml) and acetic acid (5.4 ml) was added thereto. The mixture was refluxed for 3 hours. After the completion of the reaction, the reaction mixture was washed with a saturated aqueous solution of sodium bicarbonate and water, and dried over anhydrous magnesium sulfate. The mixture was concentrated under reduced pressure and the residue was purified by silica gel column chromatography. The objective fraction was concentrated under reduced pressure to give 15 g of 4-(2-chlorophenyl)-9-cyclohexyl-2-ethyl-6H-thieno[3,2-f]-[1,2,4]triazolo[4,3-a][1,4]diazepine, melting point 116°-119°πC.

Workup

  1. temperatureThe mixture was refluxed for 3 hours
  2. customAfter the reaction
  3. washwashed with water
  4. dry with materialdried over anhydrous magnesium sulfate
  5. distillationThe solvent was distilled away under reduced pressure
  6. customprecipitated crystals
  7. filtrationwere collected by filtration with diisopropyl ether
  8. customrecrystallized from ethanol-chloroform

Sources & evidence

ORD record
ord-a73030fbed31472a85348787d6177bf2
Source dataset
uspto-grants-1998_05
Patent number
US05753649

Reaction notes

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