Ammonia → Diazepam

HRID 1973063Notes

Reaction equation

HRID 1973063 reaction equation
C1N2CN3CN(C2)C[N:2]1C3.N.Cl[CH2:13][C:14]([N:16]([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)[CH3:17])=[O:15]>C(O)C>[Cl:32][C:29]1[CH:30]=[CH:31][C:18]2[N:16]([CH3:17])[C:14](=[O:15])[CH2:13][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

5

Reactant 3

HCID 222Ammonia2×HCID 4101HexamethylenetetramineHCID 80117N-(2-Benzoyl-4-chlorophenyl)-2-chloro-N-methylacetamide

Product 1

HCID 3016Diazepam

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
70 °C

Procedure

A mixture of ethanol (600 ml) and hexamethylenetetramine (39.1 g., 0.279 mol) was stirred and saturated with ammonia. With ammonia bubbling into the mixture it was slowly heated to reflux. Over a period of 41/2 hours, 2-(2-chloro-N-methylacetamido)-5-chlorobenzophenone (40 g., 0.124 mol) was added in increments yielding ##STR6## which was not isolated. Refluxing was continued for 2 hours longer. The reaction mixture was then distilled to dryness in vacuo at 50° C. The residue was stirred with toluene (250 ml), heated to reflux and heated with two increments of para-toluene sulfonic acid. Reflux was continued for one hour. After cooling to 70° C., the toluene was washed with hot water to remove soluble salts and distilled to dryness in vacuo. The residue was dissolved in hot ethanol (111 mol) and the solution cooled at -10° C. for one hour. The crystalline 7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one obtained was isolated and weighed 29 g., melting point 129° to 131° C. Concentration of the mother liquor by ca. 50% gave a second crop weighing 2.0 g. melting at 127° C.

Workup

  1. customyielding ##STR6## which
  2. customwas not isolated
  3. temperatureRefluxing
  4. distillationThe reaction mixture was then distilled to dryness in vacuo at 50° C
  5. temperatureheated
  6. temperatureto reflux
  7. temperatureheated with two increments of para-toluene sulfonic acid
  8. temperatureReflux
  9. waitwas continued for one hour
  10. washthe toluene was washed with hot water
  11. customto remove soluble salts
  12. distillationdistilled to dryness in vacuo
  13. temperaturethe solution cooled at -10° C. for one hour

Sources & evidence

ORD record
ord-bf7acc9231f34791ae9d3cbc5efb8063
Source dataset
uspto-grants-1976_12
Patent number
US03996209

Reaction notes

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