2-Chlorobenzaldehyde → 2-(o-Chlorophenyl)-2,3,5,6,7,8-hexahydro-3-(2-thienyl)-thiazolo[3,2-a][1,3]diazepin-3-ol

HRID 67237

Reaction equation

HRID 67237 reaction equation
[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH:6]=[O:7].[Cl:8][C:9]1[CH:16]=[CH:15][CH:14]=[CH:13][C:10]=1[CH:11]=O.[C-]#N.[K+].CS(Cl)(=O)=O.[NH:25]1[CH2:31][CH2:30][CH2:29][CH2:28][NH:27][C:26]1=[S:32]>CC(C)=O.O.C1(C)C=CC=CC=1.C(N(CC)CC)C.C(O)C>[Cl:8][C:9]1[CH:16]=[CH:15][CH:14]=[CH:13][C:10]=1[CH:11]1[S:32][C:26]2=[N:25][CH2:31][CH2:30][CH2:29][CH2:28][N:27]2[C:6]1([C:2]1[S:1][CH:5]=[CH:4][CH:3]=1)[OH:7]

Participants

11

Reactant 5

HCID 69962-ChlorobenzaldehydeHCID 73642-ThiophenecarboxaldehydeHCID 9032Potassium CyanideHCID 31297Methanesulfonyl chlorideHCID 7365891,3-Diazepane-2-thione

Product 1

HCID 130683092-(o-Chlorophenyl)-2,3,5,6,7,8-hexahydro-3-(2-thienyl)-thiazolo[3,2-a][1,3]diazepin-3-ol

Reagents, catalysts & solvents 5

HCID 180AcetoneSolventHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 1140TolueneSolvent2×HCID 8471TriethylamineSolvent

Procedure

A mixture of 9.2 ml. of 2-thiophenecarboxaldehyde, 11.3 ml. of o-chlorobenzaldehyde, 8 g. of potassium cyanide and 100 ml. of 65% ethanol is refluxed for 2 hours and then refrigerated. A 30 ml. portion of water is added, refrigeration is continued, the oil is separated by decantation, added to toluene, washed with water, dried and concentrated giving 12.7 g. of an oil. A 9.0 g. portion of this oil is mixed with 8.4 ml. of triethylamine and 100 ml. of toluene and stirred as a mixture of 2.4 ml. of methanesulfonyl chloride in 100 ml. of toluene is added. The mixture is stirred overnight then 100 ml. of water is added. The toluene layer is separated, washed with water, dried and concentrated, giving 10.6 g. of oily 2-thienyl α-hydroxy(2-chlorophenyl)ketone. This oil is combined with 3.9 g. of hexahydro-2H-1,3-diazepin-2-thione in 150 ml. of acetone and allowed to stand 48 hours. The solvent is removed, 100 ml. of water and 2 ml. of ammonium hydroxide are added and the aqueous layer is decanted. Ethanol is added, the mixture is cooled and the solid is collected, giving 3.4 g. of the desired product, m.p. 120°-122° C.

Workup

  1. additionA mixture of 9.2 ml
  2. customthe oil is separated by decantation
  3. additionadded to toluene
  4. washwashed with water
  5. customdried
  6. concentrationconcentrated
  7. customgiving 12.7 g
  8. additionportion of this oil is mixed with 8.4 ml
  9. customThe toluene layer is separated
  10. washwashed with water
  11. customdried
  12. concentrationconcentrated
  13. customgiving 10.6 g
  14. waitto stand 48 hours
  15. customThe solvent is removed
  16. additionof ammonium hydroxide are added
  17. customthe aqueous layer is decanted
  18. additionEthanol is added
  19. temperaturethe mixture is cooled
  20. customthe solid is collected
  21. customgiving 3.4 g

Sources & evidence

ORD record
ord-1ac4433c53b549cab3064718b77f2db4
Source dataset
uspto-grants-1982_08
Patent number
US04344954

Linked notes

Loading…