2-Hydroxyacetohydrazide → alpha-Hydroxytriazolam

HRID 596351Notes

Reaction equation

HRID 596351 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:11][C:10](=S)[CH2:9][N:8]=[C:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[Cl:19])[C:6]=2[CH:20]=1.[OH:21][CH2:22][C:23]([NH:25][NH2:26])=O>C(O)CCC>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[C:23]([CH2:22][OH:21])=[N:25][N:26]=[C:10]3[CH2:9][N:8]=[C:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[Cl:19])[C:6]=2[CH:20]=1

Participants

4

Reactant 2

HCID 3505362-HydroxyacetohydrazideHCID 8267037-chloro 5-(2-chlorophenyl)-1,3-dihydro-2H-(1,4)-benzodiazepine-2-thione

Product 1

HCID 1963alpha-Hydroxytriazolam

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

A solution of 1,3-dihydro-7-chloro-5-(o-chlorophenyl)-2H-1,4-benzodiazepine-2-thione (9.63 g., 0.03 mole) and hydroxy-acetic acid hydrazide (6.66 g.) in n-butyl alcohol (300 ml.) is refluxed for about 15 hours with a slow stream of nitrogen bubbling through the reaction mixture for the first hour. The mixture is then cooled and concentrated in vacuo and the resulting residue is suspended in water, treated with a little ether and crystallized. The solid is collected by filtration and dried in vacuo. Recrystallization of this material from methylene chloride-methanol gives 8-chloro-1-(hydroxymethyl)-6-(o-chlorophenyl)-4H-s-triazolo[4,3-a][1,4]benzodiazepine in three crops: 4.96 g. of melting point 239°-241° C., 1.58 g. of melting point 236°-239° C., and 0.365 g. of melting point 232°-236° C. The analytical sample has a melting point of 239.5°-241° C. Anal. calcd. for C17H12Cl2N4O: C, 56.84; H, 3.37; Cl, 19.74; N, 15.60. Found: C, 56.27; H, 3.28; Cl, 19.75; N, 15.55. Preparation 2 8-Chloro-1-(hydroxymethyl)-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine

Workup

  1. temperatureThe mixture is then cooled
  2. concentrationconcentrated in vacuo
  3. additiontreated with a little ether
  4. customcrystallized
  5. filtrationThe solid is collected by filtration
  6. customdried in vacuo
  7. customRecrystallization of this material from methylene chloride-methanol

Sources & evidence

ORD record
ord-110925dc63aa4b38be6253d683625cd7
Source dataset
uspto-grants-1977_03
Patent number
US04010177

Reaction notes

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