Acetaldehyde → 1-(4-chloro-2-fluorophenyl)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazole

HRID 1756271Notes

Reaction equation

HRID 1756271 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][NH2:9])=[C:4]([F:10])[CH:3]=1.[CH:11](=O)[CH3:12].[O-:14][C:15]#[N:16].[Na+]>C(O)(C)(C)C.O.O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:15](=[O:14])[NH:16][C:11]([CH3:12])=[N:9]2)=[C:4]([F:10])[CH:3]=1

Participants

6

Reactant 3

HCID 177AcetaldehydeHCID 517096Sodium CyanateHCID 2782934(4-Chloro-2-fluorophenyl)hydrazine

Product 1

HCID 1355016041-(4-chloro-2-fluorophenyl)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazole

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 714019492-Methylpropan-2-ol--water (1/1)Solvent2×

Conditions

Temperature
20 °C

Procedure

A stirring solution of 80.3 grams (0.500 mole) of 4-chloro-2-fluorophenylhydrazine in 180 ml of tert-butanol/water (88/12) is cooled to 0° to 5° C., and a solution of 23.4 grams (0.525 mole) of acetaldehyde in 50 grams of tert-butanol/water (88/12) is added dropwise during a 20 minute period. Upon completion of addition, the reaction mixture is stirred for five minutes, and a slurry of 39.8 grams (91.5% pure-0.560 mole-12% molar excess) of sodium cyanate in 90 grams of water is added in one portion. Additional water is used to wash any of the remaining slurry of sodium cyanate from its container into the reaction mixture. The reaction mixture is cooled to 0° to 5° C. and 39 3 grams (0.655 mole-5% equivalent excess, based on equivalents of sodium cyanate and its sodium carbonate impurity) of acetic acid is added dropwise during a 15 minute period. Upon completion of addition, the reaction mixture is stirred for about two hours during which time it is allowed to warm to about 20° C. Upon completion of the two hour stirring time, the reaction mixture is cooled to 10° C. and 321 grams (0.537 mole) of a 12.4% aqueous solution of sodium hypochlorite is added dropwise during a 40 minute period. Upon completion of addition, the reaction mixture is stirred for an additional 40 minutes. The tert-butanol/water medium is then distilled from the reaction mixture by slowly heating the reaction mixture to about 100° C. Upon completion of the distillation, the pot residue is filtered, washed with water and dried, yielding 1-(4-chloro-2-fluorophenyl)-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-one.

Workup

  1. additionUpon completion of addition
  2. washto wash any of the remaining slurry of sodium cyanate from its container into the reaction mixture
  3. temperatureThe reaction mixture is cooled to 0° to 5° C.
  4. addition39 3 grams (0.655 mole-5% equivalent excess, based on equivalents of sodium cyanate and its sodium carbonate impurity) of acetic acid is added dropwise during a 15 minute period
  5. additionUpon completion of addition
  6. stirringthe reaction mixture is stirred for about two hours during which time it
  7. stirringUpon completion of the two hour stirring time
  8. temperaturethe reaction mixture is cooled to 10° C.
  9. addition321 grams (0.537 mole) of a 12.4% aqueous solution of sodium hypochlorite is added dropwise during a 40 minute period
  10. additionUpon completion of addition
  11. stirringthe reaction mixture is stirred for an additional 40 minutes
  12. distillationThe tert-butanol/water medium is then distilled from the reaction mixture
  13. temperatureby slowly heating the reaction mixture to about 100° C
  14. distillationUpon completion of the distillation
  15. filtrationthe pot residue is filtered
  16. washwashed with water
  17. customdried

Sources & evidence

ORD record
ord-29a493fcca504000aca8e810ac443c4f
Source dataset
uspto-grants-1995_08
Patent number
US05440045

Reaction notes

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