1,2-Dichlorobenzene → HCID 178424441, compound

Participants

Reaction Steps

To a mixture of 13.0 g (87.0 mmol) of 2-cyclopropyl-6-methylphenol and 1,2-dichlorobenzene (78.3 mL) was added 3.67 g (87.0 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: 95.7%; 29.0 mmol) of 4-hydroxy-3,6-dichloropyridazine in t-butanol (95.0 g) at 180° C. over 5 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 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 8.30 g of 6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinol (purity: 90.9%; yield: 94%) and 29 mg of 3-chloro-6-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinol (yield: 0.4%) were obtained.

Provenance & Evidence