4,6-二氯甲酚

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 88.5 g (0.5 mole) of 2,4-dichloro-6-methylphenol, 180 ml of dry xylene, 95 g (0.5 mole) of p-chloromethylbenzoyl chloride and 0.5 ml of pyridine were refluxed for 24 hours in a weak current of nitrogen with the exclusion of moisture. After cooling, the slightly turbid (pyridine hydrochloride), orange-colored solution was filtered free of a small amount of a blackish brown resin, and the filtrate was freed of xylene at diminished pressure. The residue (165 g=100%) crystallized after two days of standing to a light brown crystal mass, which was triturated in 200 ml of ice-cold petroleum ether and suction filtered. After drying, nearly colorless crystals were obtained with a melting point of 71°-73° C. Recrystallization from petroleum ether (1:10) yielded white needles melting at 74°-75° C.; no change in the melting point was brought about by repeated recrystallization. After cooling the slightly turbid (pyridine hydrochloride), orange-colored solution was filtered free of a small amount of a blackish brown resin The residue (165 g=100%) crystallized after two days was triturated in 200 ml of ice-cold petroleum ether suction filtered After drying nearly colorless crystals were obtained with a melting point of 71°-73° C Recrystallization from petroleum ether (1:10)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 88.5 g (0.5 mole) of 2,4-dichloro-6-methylphenol, 180 ml of dry xylene, 95 g (0.5 mole) of p-chloromethylbenzoyl chloride and 0.5 ml of pyridine were refluxed for 24 hours in a weak current of nitrogen with the exclusion of moisture. After cooling, the slightly turbid (pyridine hydrochloride), orange-colored solution was filtered free of a small amount of a blackish brown resin, and the filtrate was freed of xylene at diminished pressure. The residue (165 g=100%) crystallized after two days of standing to a light brown crystal mass, which was triturated in 200 ml of ice-cold petroleum ether and suction filtered. After drying, nearly colorless crystals were obtained with a melting point of 71°-73° C. Recrystallization from petroleum ether (1:10) yielded white needles melting at 74°-75° C.; no change in the melting point was brought about by repeated recrystallization. After cooling the slightly turbid (pyridine hydrochloride), orange-colored solution was filtered free of a small amount of a blackish brown resin The residue (165 g=100%) crystallized after two days was triturated in 200 ml of ice-cold petroleum ether suction filtered After drying nearly colorless crystals were obtained with a melting point of 71°-73° C Recrystallization from petroleum ether (1:10)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: By the same procedure as in Example 1, 60 g of sodium hydroxide is dissolved at 70° C. in 1.8 liters of ethylene glycol monomethyl ether and, by the addition of 265.6 g (1.5 moles) of 2,4-dichloro-6-methylphenol, a phenolate solution is prepared into which 92 g (0.5 mole) of cyanuric acid chloride is stirred at 70° over a period of 3 minutes, causing the temperature of the reaction mixture to rise to 81° C. After half an hour of refluxing, the product is separated as in Example 1. to rise to 81° C After half an hour of refluxing the product is separated as in Example 1

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: By the same procedure as in Example 1, 60 g of sodium hydroxide is dissolved at 70° C. in 1.8 liters of ethylene glycol monomethyl ether and, by the addition of 265.6 g (1.5 moles) of 2,4-dichloro-6-methylphenol, a phenolate solution is prepared into which 92 g (0.5 mole) of cyanuric acid chloride is stirred at 70° over a period of 3 minutes, causing the temperature of the reaction mixture to rise to 81° C. After half an hour of refluxing, the product is separated as in Example 1. to rise to 81° C After half an hour of refluxing the product is separated as in Example 1

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 2,4-dichloro-7-(1-ethylpropyl)-1-methyl-1H-benzimidazole (200 mg, 0.750 mmol), 2,4-dichloro-6-methylphenol (398 mg, 2.25 mmol), potassium carbonate (311 mg, 2.25 mmol) and 1-methyl-2-pyrrolidone (0.5 ml) was stirred at 120° C. for 12 h under nitrogen atmosphere. The mixture was diluted with water, extracted with ethyl acetate, and washed with brine. The organic layer was dried over magnesium sulfate, and concentrated in vacuo. The residue was purified by chromatography on silica gel with a 2-30% ethyl acetate/n-hexane gradient mixture and crystallized from methanol to afford the title compound as colorless crystals (109 mg, 36%). extracted with ethyl acetate washed with brine The organic layer was dried over magnesium sulfate concentrated in vacuo The residue was purified by chromatography on silica gel with a 2-30% ethyl acetate/n-hexane gradient mixture crystallized from methanol

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 88.5 g (0.5 mole) of 2,4-dichloro-6-methylphenol, 180 ml of dry xylene, 95 g (0.5 mole) of p-chloromethylbenzoyl chloride and 0.5 ml of pyridine were refluxed for 24 hours in a weak current of nitrogen with the exclusion of moisture. After cooling, the slightly turbid (pyridine hydrochloride), orange-colored solution was filtered free of a small amount of a blackish brown resin, and the filtrate was freed of xylene at diminished pressure. The residue (165 g=100%) crystallized after two days of standing to a light brown crystal mass, which was triturated in 200 ml of ice-cold petroleum ether and suction filtered. After drying, nearly colorless crystals were obtained with a melting point of 71°-73° C. Recrystallization from petroleum ether (1:10) yielded white needles melting at 74°-75° C.; no change in the melting point was brought about by repeated recrystallization. After cooling the slightly turbid (pyridine hydrochloride), orange-colored solution was filtered free of a small amount of a blackish brown resin The residue (165 g=100%) crystallized after two days was triturated in 200 ml of ice-cold petroleum ether suction filtered After drying nearly colorless crystals were obtained with a melting point of 71°-73° C Recrystallization from petroleum ether (1:10)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A suspension of 2-chloro-7-(3,5-diethyl-1H-pyrazol-1-yl)-1-methyl-1H-benzimidazole (92 mg, 0.318 mmol), 2,4-dichloro-6-methylphenol (114 mg, 0.643 mmol), potassium carbonate (89 mg, 0.643 mmol) in N,N-dimethylformamide (1.5 ml) was stirred at 90° C. for 5.5 days (2,4-dichloro-6-methylphenol and potassium carbonate were added in three equal portions each over 5.5 days). After cooling, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with water and brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by column chromatography on silica gel eluting with a 10-25% ethyl acetate/n-hexane gradient mixture to give 107 mg (0.249 mmol, 78.3%) of the title compound as an oil. The oil was crystallized from hexane to give 70 mg (51%) as a pale yellow crystal. were added in three equal portions each over 5.5 days) After cooling extracted with ethyl acetate The organic layer was washed with water and brine dried over sodium sulfate concentrated in vacuo The residue was purified by column chromatography on silica gel eluting with a 10-25% ethyl acetate/n-hexane gradient mixture

反应条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 2-chloro-7-(1-ethylpropyl)-1-methyl-4-(trifluoromethyl)-1H-benzimidazole (304 mg, 1.00 mmol), 4,6-dichloro-o-cresol (531 mg, 3.00 mmol), potassium carbonate (553 mg, 4.0 mmol) and N,N-dimethylformamide (5 ml) was heated at 110° C. for 48 h. Aqueous saturated sodium bicarbonate was added to the residue and extracted with ethyl acetate. The extracts were washed with water, dried over magnesium sulfate and concentrated in vacuo. The residue was purified by column chromatography on silica gel with a 10% ethyl acetate/n-hexane and recrystallization from diisopropylether/n-hexane to give 290 mg (0.65 mmol, 65%) of the title compound as a white powder. extracted with ethyl acetate The extracts were washed with water dried over magnesium sulfate concentrated in vacuo The residue was purified by column chromatography on silica gel with a 10% ethyl acetate/n-hexane and recrystallization from diisopropylether/n-hexane

反应条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of methyl 2-chloro-7-(1-ethylpropyl)-1-methyl-1H-benzimidazole-4-carboxylate (1.15 g, 3.90 mmol), 4,6-dichloro-o-cresol (2.07 g, 11.70 mmol), potassium carbonate (2.16 g, 15.60 mmol) and N,N-dimethylformamide (15 ml) was heated at 110° C. for 5 h. The residue was diluted with aqueous saturated sodium bicarbonate and extracted with ethyl acetate. The extracts were washed with water, dried over magnesium sulfate and concentrated in vacuo. The residue was purified by column chromatography on alumina with a 15% ethyl acetate/n-hexane to give 1.41 g (3.24 mmol, 83%) of the title compound as a white powder. extracted with ethyl acetate The extracts were washed with water dried over magnesium sulfate concentrated in vacuo The residue was purified by column chromatography on alumina with a 15% ethyl acetate/n-hexane

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 2,4-dichloro-7-(1-ethylpropyl)-1-methyl-1H-benzimidazole (5.5 g, 20.2 mmol), 2,4-dichloro-6-methylphenol (10 g, 56.5 mmol) and potassium carbonate (8.4 g, 60.8 mmol) in N,N-dimethylformamide (55 mL) was heated at 100° C. for 9 h. To the mixture was added 2,4-dichloro-6-methylphenol (5 g, 28.3 mmol) and potassium carbonate (4.2 g, 30.4 mmol) and heated at 100° C. for 16 h. Additional 2,4-dichloro-6-methylphenol (5 g, 28.3 mmol) and potassium carbonate (4.2 g, 30.4 mmol) were added and heated at 100° C. for 9 h. After cooling, the mixture was diluted with water and extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography on NH silica gel eluting with a 12.5% ethyl acetate/n-hexane. The resulting solids were recrystallized from a 10% ethyl acetate/n-hexane to give 5.3 g (64%) of the title compound as a colorless crystal. heated at 100° C. for 9 h After cooling extracted with ethyl acetate The extract was washed with brine dried over magnesium sulfate filtered concentrated in vacuo The residue was purified by column chromatography on NH silica gel eluting with a 12.5% ethyl acetate/n-hexane The resulting solids were recrystallized from a 10% ethyl acetate/n-hexane

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: By the same procedure as in Example 1, 60 g of sodium hydroxide is dissolved at 70° C. in 1.8 liters of ethylene glycol monomethyl ether and, by the addition of 265.6 g (1.5 moles) of 2,4-dichloro-6-methylphenol, a phenolate solution is prepared into which 92 g (0.5 mole) of cyanuric acid chloride is stirred at 70° over a period of 3 minutes, causing the temperature of the reaction mixture to rise to 81° C. After half an hour of refluxing, the product is separated as in Example 1. to rise to 81° C After half an hour of refluxing the product is separated as in Example 1