Ammonia → Diazepam

HRID 1973062Notes

Reaction equation

HRID 1973062 reaction equation
C1N2CN3CN(C2)C[N:2]1C3.Cl[CH2:12][C:13]([N:15]([C:17]1[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][C:18]=1[C:19]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=O)[CH3:16])=[O:14].N>CO>[Cl:31][C:28]1[CH:29]=[CH:30][C:17]2[N:15]([CH3:16])[C:13](=[O:14])[CH2:12][N:2]=[C:19]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:18]=2[CH:27]=1

Participants

5

Reactant 3

HCID 222Ammonia3×HCID 4101HexamethylenetetramineHCID 80117N-(2-Benzoyl-4-chlorophenyl)-2-chloro-N-methylacetamide

Product 1

HCID 3016DiazepamYield 96.09%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of hexamethylenetetramine (17.5 g., 0.125 mol), methanol (135.5 ml) and 2(2-chloro-N-methylacetamido)-5-chlorobenzophenone (80.5 g., 0.25 mol) was saturated with ammonia. Heat the stirred mixture slowly to reflux with a steady stream of ammonia flowing through the mixture. During the course of the reaction ##STR5## was prepared. The product was not isolated. Hold at reflux for 6 hours. Stop the flow of ammonia and remove the solvent under vacuum. Take up the residue in a mixture of toluene (500 ml.) and hot water (500 ml). Separate the toluene phase and add to it, with stirring, 3N nitric acid (169 ml). The crystals which separate are filtered, wash with toluene (50 mls) and resuspended in a mixture of toluene (250 ml) and water (250 ml). Concentrated ammonia (30 ml) is added to pH 8. The toluene phase is separated, washed with water (250 ml) and then distilled to dryness in vacuo yielding 96.09% of 7-chloro-1-methyl-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one, melting point 125° to 127° C.

Workup

  1. temperatureHeat the stirred mixture slowly
  2. customDuring the course of the reaction ##STR5## was prepared
  3. customThe product was not isolated
  4. temperatureat reflux for 6 hours
  5. customremove the solvent under vacuum
  6. additionin a mixture of toluene (500 ml.) and hot water (500 ml)
  7. customSeparate the toluene phase
  8. additionadd to it
  9. customThe crystals which separate
  10. filtrationare filtered
  11. washwash with toluene (50 mls)
  12. additionresuspended in a mixture of toluene (250 ml) and water (250 ml)
  13. additionConcentrated ammonia (30 ml) is added to pH 8
  14. customThe toluene phase is separated
  15. washwashed with water (250 ml)
  16. distillationdistilled to dryness in vacuo

Sources & evidence

ORD record
ord-40ce6cb7fcb7438d9c403620b05cab91
Source dataset
uspto-grants-1976_12
Patent number
US03996209

Reaction notes

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