Ammonia → Nordiazepam

HRID 1973064

Reaction equation

HRID 1973064 reaction equation
C1N2CN3CN(C2)C[N:2]1C3.[OH-].[NH4+].Cl[CH2:14][C:15]([NH:17][C:18]1[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][C:19]=1[C:20]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=O)=[O:16].N>C(O)C>[Cl:32][C:29]1[CH:30]=[CH:31][C:18]2[NH:17][C:15](=[O:16])[CH2:14][N:2]=[C:20]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:19]=2[CH:28]=1

Participants

6

Reactant 4

HCID 222Ammonia2×HCID 4101HexamethylenetetramineHCID 14923Ammonium HydroxideHCID 776355-Chloro-2-(chloroacetamido)benzophenone

Product 1

HCID 2997NordiazepamYield 167%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of ethanol (1100 ml), hexamethylenetetramine (70.0 g., 0.5 mol), 26% ammonium hydroxide (58 ml) and 2-chloroacetamido-5-chlorobenzophenone (308.2 g., 1.0 mol) was stirred and slowly heated to reflux with ammonia bubbling into the mixture. Reflux was continued for 5 hours, the flow of ammonia was interrupted, and the reaction mixture distilled to dryness in vacuo. The residue was heated to reflux for 30 minutes in a mixture of toluene (500 mls) and water (500 mls) and then allowed to cool slowly to room temperature. The crystalline material was filtered, washed with toluene (100 mls) and hot water (2 × 250 mls) and dried to constant weight. The product, 7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one (226 g) obtained corresponded to a yield of 83.5%, melting point 210° C.

Workup

  1. temperatureslowly heated
  2. temperatureReflux
  3. distillationthe reaction mixture distilled to dryness in vacuo
  4. temperatureThe residue was heated
  5. temperatureto reflux for 30 minutes in a mixture of toluene (500 mls) and water (500 mls)
  6. filtrationThe crystalline material was filtered
  7. washwashed with toluene (100 mls) and hot water (2 × 250 mls)
  8. customdried to constant weight

Sources & evidence

ORD record
ord-2518b212b6f642098e18a46d46582765
Source dataset
uspto-grants-1976_12
Patent number
US03996209

Linked notes

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