Sulfuric Acid → 5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethoxyphenyl)pyrazole

HRID 1716617Notes

Reaction equation

HRID 1716617 reaction equation
S(=O)(=O)(O)O.[N:6]([O-])=O.[Na+].[Cl:10][C:11]1[CH:17]=[C:16]([O:18][C:19]([F:22])([F:21])[F:20])[CH:15]=[C:14]([Cl:23])[C:12]=1[NH2:13].[C:24]([CH:26]([CH2:32][C:33]#[N:34])C(OCC)=O)#[N:25]>C(O)(=O)C.ClCCl>[NH2:34][C:33]1[N:13]([C:12]2[C:11]([Cl:10])=[CH:17][C:16]([O:18][C:19]([F:22])([F:21])[F:20])=[CH:15][C:14]=2[Cl:23])[N:6]=[C:26]([C:24]#[N:25])[CH:32]=1

Participants

7

Reactant 4

HCID 1118Sulfuric AcidHCID 6882472,6-Dichloro-4-(trifluoromethoxy)anilineHCID 10725530Ethyl 2,3-DicyanopropionateHCID 23668193Sodium Nitrite

Product 1

HCID 183731495-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethoxyphenyl)pyrazoleYield 36.3%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolvent3×HCID 6344DichloromethaneSolvent

Conditions

Temperature
15 °C

Procedure

To sulphuric acid (18M, 54 ml) was added sodium nitrite (13.9 g, 201.2 mmol) and the solution was stirred at 15° C. for 1 h. To the solution was added acetic acid (200 ml), followed by 2,6-dichloro-4-(trifluoromethoxy)aniline (45.0 g, 182.9 mmol) in acetic acid (90 ml), ensuring the temperature of the solution did not rise above 20° C. After addition was complete, the mixture was heated at 50° C. for 1 h, cooled to room temperature and added dropwise to a solution of ethyl 2,3-dicyanopropanoate (Hainzl, D.; Cole, L. M.; Casida, J. E. Chemical Research in Toxicology (1998), 11(12), 1529-1535, 27.8 g, 182.9 mmol) in acetic acid (115 ml) and ice cold water (145 ml). The reaction mixture was then stirred overnight at room temperature. To the reaction mixture was added dichloromethane (500 ml) and the mixture was stirred for 10 min. The two phases were separated and the organic phase was washed with water (200 ml) and ammonia (0.88, 400 ml) was added dropwise, maintaining the temperature of the mixture below 10° C. This mixture was stirred overnight at room temperature and the organic phase was separated and concentrated in vacuo. The residue was re-crystallised from toluene/pentane [2:1] to give the titled compound (22.4 g).

Workup

  1. customdid not rise above 20° C
  2. additionAfter addition
  3. temperaturethe mixture was heated at 50° C. for 1 h
  4. temperaturecooled to room temperature
  5. stirringThe reaction mixture was then stirred overnight at room temperature
  6. stirringthe mixture was stirred for 10 min
  7. customThe two phases were separated
  8. washthe organic phase was washed with water (200 ml) and ammonia (0.88, 400 ml)
  9. additionwas added dropwise
  10. temperaturemaintaining the temperature of the mixture below 10° C
  11. stirringThis mixture was stirred overnight at room temperature
  12. customthe organic phase was separated
  13. concentrationconcentrated in vacuo
  14. customThe residue was re-crystallised from toluene/pentane [2:1]

Sources & evidence

ORD record
ord-4b6bf6c5ea994cb1a6c958ba83936d52
Source dataset
uspto-grants-2010_09
Patent number
US07803832B2

Reaction notes

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