| 92% |
|
In the p-chlorophenylhydrazine hydrochloride prepared in Example 4, 8 times by weight of toluene was added and the mixture was stirred with p-chlorobenzene.The equivalent ratio of hydrazine hydrochloride was added alkali (potassium bicarbonate), 10percent by weight of water, heated to reflux, dehydrated to a water content of 190 pm, and the heating was stopped;After the temperature was lowered, 1.05 equivalent ratio of sodium alkoxide (sodium methoxide) was added to maintain the internal temperature based on the amount of p-chlorophenylhydrazine hydrochloride.At 70°CBased on the amount of p-chlorophenylhydrazine hydrochloride, 1.5 equivalent ratio of acrylate (methyl acrylate) was added and the temperature was increased to refluxAfter distillation, distill off the low-boilers to an internal temperature of about 85 °C to stop distillation. At this time, the content of p-chlorophenylhydrazine was determined by HPLC at 0.30percent;Reduce the internal temperature to 65°C, adjust the pH to 2, separate the organic phase, extract the aqueous phase with toluene, and combine the organic phases to obtainIntermediate pyrazolone in toluene solution. The synthesis process involved in this embodiment includes the following sequence steps:After the toluene solution prepared in Example 12 was distilled under reduced pressure to remove toluene, the amount of p-chlorophenylhydrazine hydrochloride was added.Into the 1.8 equivalent ratio of alkali (2:1:1 sodium hydroxide, barium hydroxide, calcium hydroxide) and 10 times the weight of water, heated to 80 ° C;Add 30percent hydrogen peroxide solution with stirring. The amount of hydrogen peroxide solution is controlled at 1.6 when calculated as p-chlorophenylhydrazine hydrochloride.Amount, after adding, heat 1.5 hours;The reaction was stopped by HPLC when the pyrazolone content was 0.4percent;The reaction solution was cooled to room temperature, the pH was adjusted to 1.8, suction filtration, washing with water, and drying to give 1-(4-chlorophenyl)-3-Pyrazol, its HPLC content 99.2percent, yield 92.0percent. |
| 76% |
|
At room temperature, 36.16 g (99percent, 0.2 mol) of p-chlorophenylhydrazine hydrochloride was mixed with 198.88g of methanol. Then 90 g (30percent, 0.5 mol) of 30 wtpercent methanol solution of sodium methoxide and 35.1g (98percent, 0.4 mol) of methyl acrylate were added dropwise at 60 °C for 1 hour. After heating to 65° C, the reaction was stirred for 6 hours. After liquid-phase detection, the main raw material of p-chlorophenylhydrazine hydrochloride peak disappeared and the reaction is complete; followed by distillation under reduced pressure,Steamed to ethanol-free flow and then continue to steam 0.5h, then 145g of water was added to dissolve 5.46g (99percent, 0.02mol) of ferric chloride hexahydrate. Heating to 65 °C air (air flow rate of 70L / min) oxidation 11h to detect by liquid 1- (4-chlorophenyl) pyrazolidin-3-one peak disappears, the reaction is complete; add 50g water at 45°C , Hydrochloric acid was added dropwise to pH = 2,the temperature was lowered to 30°C , and 30.2 g of 1- (4-chlorophenyl) -3-pyrazolol was obtained by filtration with the yield of 76percent with 97.9percent content. |
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