1,2-Dichlorobenzene → HCID 178424441, compound

HRID 1039553Notes

Reaction equation

HRID 1039553 reaction equation
[CH:1]1([C:4]2[CH:9]=[CH:8][CH:7]=[C:6]([CH3:10])[C:5]=2[OH:11])[CH2:3][CH2:2]1.ClC1C=CC=CC=1Cl.[OH-].[K+].[OH:22][C:23]1[CH:28]=[C:27]([Cl:29])[N:26]=[N:25][C:24]=1Cl>C(O)(C)(C)C>[Cl:29][C:27]1[N:26]=[N:25][C:24]([O:11][C:5]2[C:6]([CH3:10])=[CH:7][CH:8]=[CH:9][C:4]=2[CH:1]2[CH2:3][CH2:2]2)=[C:23]([OH:22])[CH:28]=1

Participants

6

Reactant 4

HCID 72391,2-DichlorobenzeneHCID 14797Potassium HydroxideHCID 229399512-Cyclopropyl-6-methylphenolHCID 178516198HCID 178516198, compound

Product 1

HCID 178424441HCID 178424441, compoundYield 52.2%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Procedure

To a mixture of 1.34 g (purity: 96.2%; 34.9 mmol) of 2-cyclopropyl-6-methylphenol and 1,2-dichlorobenzene (42.0 mL) was added 2.06 g (34.9 mmol) of 95% potassium hydroxide at room temperature. The resultant mixture was heated to 180° C. and subjected to azeotropic dehydration under reflux while stirring for one hour. To the resultant solution was added dropwise the preliminarily prepared solution of 3.07 g (purity: 96.0%; 17.8 mmol) of 4-hydroxy-3,6-dichloropyridazine in t-butanol (50.0 g) at 180° C. over 2 hours. (The t-butanol was distilled off simultaneously with the dropwise addition of the solution.) After stirring at 180° C. for another 2 hours, the reaction mixture was cooled to room temperature, and pure water was added to the cooled mixture and stirred at room temperature for 30 minutes, and then an organic phase was separated. 1,2-Dichlorobenzene was added to the resultant aqueous phase and stirred at room temperature for 30 minutes, and then an organic phase containing 2-cyclopropyl-6-methylphenol was separated, and then a 1 N aqueous hydrochloric acid solution and methanol were added to the resultant aqueous phase containing a potassium salt of 6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinol to obtain a uniform solution. The obtained solution was quantitatively determined by an HPLC internal standard analysis method, which showed that 2.57 g of 6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinol (yield: 52%) and 29 mg of 3-chloro-6-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinol (yield: 0.6%) were obtained.

Workup

  1. temperatureunder reflux
  2. distillation(The t-butanol was distilled off simultaneously with the dropwise addition of the solution
  3. stirring) After stirring at 180° C. for another 2 hours
  4. additionpure water was added to the cooled mixture
  5. stirringstirred at room temperature for 30 minutes
  6. customan organic phase was separated
  7. addition1,2-Dichlorobenzene was added to the resultant aqueous phase
  8. stirringstirred at room temperature for 30 minutes
  9. additionan organic phase containing 2-cyclopropyl-6-methylphenol
  10. customwas separated
  11. additiona 1 N aqueous hydrochloric acid solution and methanol were added to the resultant aqueous phase
  12. additioncontaining a potassium salt of 6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinol
  13. customto obtain a uniform solution

Sources & evidence

ORD record
ord-aef029fda74942fb93e9d73a3395ebbb
Source dataset
uspto-grants-2013_10
Patent number
US08552182B2

Reaction notes

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