Sulfuric Acid → 1-(2-Fluoro-4-chloro-5-bromophenyl)-3-methyl-4-(difluoromethyl)-1H-1,2,4-triazol-5(4H)-one

HRID 636836Notes

Reaction equation

HRID 636836 reaction equation
S(=O)(=O)(O)O.[Cl:6][C:7]1[CH:12]=[CH:11][C:10]([N:13]2[C:17](=[O:18])[N:16]([CH:19]([F:21])[F:20])[C:15]([CH3:22])=[N:14]2)=[C:9]([F:23])[CH:8]=1.[Br:24]Br>>[Cl:6][C:7]1[C:12]([Br:24])=[CH:11][C:10]([N:13]2[C:17](=[O:18])[N:16]([CH:19]([F:20])[F:21])[C:15]([CH3:22])=[N:14]2)=[C:9]([F:23])[CH:8]=1

Participants

4

Reactant 3

HCID 1118Sulfuric AcidHCID 24408BromineHCID 9882096Chloro Fluoro Triazolin-3-one

Product 1

HCID 212559541-(2-Fluoro-4-chloro-5-bromophenyl)-3-methyl-4-(difluoromethyl)-1H-1,2,4-triazol-5(4H)-oneYield 90.1%

Procedure

To a 250 mL roundbottom flask equipped with a mechanical stirrer and a thermometer was added 6 mL of 20% fuming sulfuric acid (oleum) (% wt/vol. triazole to solvent—23.3%), 1.4 grams (0.0051 mole—1.0 equiv.) of 1-(4-chloro-2-fluorophenyl)-4-difluoromethyl-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazole, and 0.85 gram (0.0053 mole—1.03 equiv.) of bromine crystals. The reaction mixture stirred at ambient temperature for two hours. After this time TLC analysis of the reaction mixture indicated that the reaction was almost complete. The reaction mixture was stirred at ambient temperature for an additional 16 hours. At the conclusion of this period a second TLC analysis of the reaction mixture indicated the reaction was essentially completed. The reaction mixture was poured into 300 grams of ice, and the resulting mixture was extracted with two 50 mL portions of methylene chloride. The organic extracts were combined and washed with an aqueous 10% potassium carbonate solution, an aqueous 5% sodium bisulfite solution, and an aqueous saturated sodium chloride solution. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure yielding a white solid, which was dried to a constant weight, yielding 1.6 grams of 1-(4-chloro-2-fluoro-5-bromophenyl)-4-difluoromethyl4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazole (90.1 % yield) . The NMR spectrum was consistent with the proposed structure.

Workup

  1. customTo a 250 mL roundbottom flask equipped with a mechanical stirrer
  2. stirringThe reaction mixture was stirred at ambient temperature for an additional 16 hours
  3. extractionthe resulting mixture was extracted with two 50 mL portions of methylene chloride
  4. washwashed with an aqueous 10% potassium carbonate solution
  5. dry with materialThe organic layer was dried with magnesium sulfate
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customyielding a white solid, which
  9. customwas dried to a constant weight

Sources & evidence

ORD record
ord-ed8d2daf9e134eda9818eea67eae4768
Source dataset
uspto-grants-2001_02
Patent number
US06194583B1

Reaction notes

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