1,2-Dichlorobenzene → HCID 178424441, compound

HRID 1039546Notes

Reaction equation

HRID 1039546 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-].[Na+].[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 14798Sodium HydroxideHCID 229399512-Cyclopropyl-6-methylphenolHCID 178516198HCID 178516198, compound

Product 1

HCID 178424441HCID 178424441, compoundYield 91%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Procedure

To a mixture of 12.8 g (86.4 mmol) of 2-cyclopropyl-6-methylphenol and 1,2-dichlorobenzene (78.3 mL) was added 3.64 g (86.4 mmol) of 95% sodium hydroxide at room temperature. The resultant mixture was heated to 180° C. and subjected to azeotropic dehydration under reflux while stirring for 30 minutes. To the resultant solution was added dropwise the preliminarily prepared solution of 5.00 g (purity: 95%; 28.8 mmol) of 4-hydroxy-3,6-dichloropyridazine in t-butanol (95.0 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 30 minutes, the reaction mixture was cooled to room temperature, and 78.7 g of pure water was added to the cooled mixture and stirred for 30 minutes, and an organic phase containing 2-cyclopropyl-6-methylphenol added in an excess amount was separated. 50.0 g of toluene was added to the resultant aqueous phase and stirred at room temperature for 30 minutes, and an organic phase containing 2-cyclopropyl-6-methylphenol was separated. This operation was repeated twice. Then, the resultant aqueous phase containing a sodium salt of 6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinol was added dropwise to a 4% aqueous hydrochloric acid solution at 0° C. to deposit solids, followed by filtration. The resultant solids were washed with pure water and dried under a reduced pressure, and dissolved in an organic solvent and quantitatively determined by an HPLC internal standard analysis method, which showed that 7.17 g of 6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinol (yield: 91%) and 43 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 30 minutes
  4. addition78.7 g of pure water was added to the cooled mixture
  5. stirringstirred for 30 minutes
  6. additionan organic phase containing 2-cyclopropyl-6-methylphenol
  7. additionadded in an excess amount
  8. customwas separated
  9. addition50.0 g of toluene was added to the resultant aqueous phase
  10. stirringstirred at room temperature for 30 minutes
  11. additionan organic phase containing 2-cyclopropyl-6-methylphenol
  12. customwas separated
  13. additionThen, the resultant aqueous phase containing a sodium salt of 6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinol
  14. additionwas added dropwise to a 4% aqueous hydrochloric acid solution at 0° C.
  15. filtrationfollowed by filtration
  16. washThe resultant solids were washed with pure water
  17. customdried under a reduced pressure
  18. dissolutiondissolved in an organic solvent

Sources & evidence

ORD record
ord-a66060c84b81400583d52b9e5068f1da
Source dataset
uspto-grants-2013_10
Patent number
US08552182B2

Reaction notes

Loading…