Hydrochloric Acid → 3-Methyl-1-(2,4,6-trichlorophenyl)-1H-pyrazol-5-amine

HRID 612979

Reaction equation

HRID 612979 reaction equation
[Na].CC1ON=CC=1.ClC1C=C(Cl)C=C(Cl)C=1NN.Cl.[Cl:20][C:21]1[CH:26]=[C:25]([Cl:27])[CH:24]=[C:23]([Cl:28])[C:22]=1[NH:29][N:30]=[C:31]([CH3:35])[CH2:32][C:33]#[N:34].C[O-].[Na+]>CO.O.CCOCC>[NH2:34][C:33]1[N:29]([C:22]2[C:21]([Cl:20])=[CH:26][C:25]([Cl:27])=[CH:24][C:23]=2[Cl:28])[N:30]=[C:31]([CH3:35])[CH:32]=1

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 79234(2,4,6-Trichlorophenyl)hydrazineHCID 798335-MethylisoxazoleHCID 5360545Sodium2×HCID 10942334Sodium MethoxideHCID 865850181-Cyanoacetone-2,4,6-trichlorophenylhydrazone

Product 1

HCID 20600323-Methyl-1-(2,4,6-trichlorophenyl)-1H-pyrazol-5-amine

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent4×HCID 962WaterSolventHCID 3283Diethyl EtherSolvent

Procedure

To a solution of 0.51 g (22.0 mmol) of sodium in methanol was added 1.66 g (20.0 mmol) of 5-methylisoxazole. The reaction mixture as refluxed for 8 hours and then stirred overnight at room temperature. Then 4.23 g (20.0 mmol) of 2,4,6-trichlorophenylhydrazine was added and the reaction mixture was again refluxed for 4 hours. A second portion of sodium In methanol was added and reflux was continued for 24 hours. The reaction mixture was taken up with ether and dilute hydrogen chloride. The organic extracts were washed with dilute hydrogen chloride and brine, and then dried with magnesium sulfate and evaporated to give crystals, m.p. 132-134° C. Analysis of this material, particularly two CN bands in the IR spectrum at 2190 cm-1 and 2250 cm-1, revealed it to be a mixture of the cis- and trans-isomers of 1-cyanoacetone-2,4,6-trichlorophenylhydrazone. This material was suspended in methanol and treated with 10.0 mmol of sodium methoxide in 5 mL of methanol. After 5 minutes at room temperature, water was added to crystallize the product which was filtered off and washed well with water. After air drying, the product weighed 2.21 g (40%) and melted at 134.0-135.5° C. Despite the similarity in melting points, the latter material was distinctly different from the former, having an R1 of 0.67 vs. 0.78 for the intermediate on silica gel TLC plates developed with 1:1 hexane ethyl acetate and a distinctly different 300 MHz proton NMR spectrum.

Workup

  1. temperatureThe reaction mixture as refluxed for 8 hours
  2. temperaturethe reaction mixture was again refluxed for 4 hours
  3. temperaturereflux
  4. waitwas continued for 24 hours
  5. washThe organic extracts were washed with dilute hydrogen chloride and brine
  6. dry with materialdried with magnesium sulfate
  7. customevaporated
  8. customto give crystals, m.p. 132-134° C
  9. waitAfter 5 minutes at room temperature
  10. customto crystallize the product which
  11. filtrationwas filtered off
  12. washwashed well with water
  13. customAfter air drying

Sources & evidence

ORD record
ord-5371c3b5d71942d593e0134c9ac21e95
Source dataset
uspto-grants-1999_12
Patent number
US06005109

Linked notes

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