Disclosure of Invention
The invention aims to overcome the defects of the prior art and provides a preparation method of a prothioconazole sustained-release agent, which has the characteristics of self-assembly, strong water solubility and efficient and continuous administration and well solves the problems of cost and water solubility of a microcapsule suspending agent.
According to the invention, the prothioconazole and the polyethylene glycol are organically combined, the prothioconazole has good water solubility, and the prothioconazole can be sustainably released through the natural degradation of the polyethylene glycol, so that the slow release effect is achieved.
The invention provides the following technical scheme: a preparation method of a prothioconazole sustained-release agent comprises the following steps: dissolving prothioconazole in a solvent, adding polyethylene glycol methacrylate and a catalyst, heating for reaction, filtering to remove the catalyst after detection reaction is finished, adding petroleum ether into a crude product after desolventizing, stirring for dispersion, and filtering to obtain a product; the reaction formula is as follows:
preferably, in the step, the molecular weight distribution of the polyethylene glycol methacrylate is between 200 and 20000.
Preferably, in the step, the ratio of the molar weight of the polyethylene glycol methacrylate to the prothioconazole is 0.01-1: 1.
Preferably, in the step, the catalyst is neutral alumina or the like.
Preferably, in the step, the ratio of the molar amount of the catalyst to the prothioconazole is 0.01-5: 1.
Preferably, in the step, the solvent is one or more of DMF, acetonitrile, DMSO, dichloroethane, dichloromethane, diethyl ether and other common solvents.
Preferably, in the step, the ether solvent is one or more of diethyl ether, petroleum ether, ethylene glycol dimethyl ether and methyl tertiary ether.
Preferably, in the step, the reaction temperature is 70-160 ℃.
Preferably, in the step, the reaction time is 1-10 h.
Preferably, in the step, the detection method is HPLC detection; and determining the detection result by using the normalized percentage of the peak area.
The invention has the following beneficial effects:
1. the invention provides a preparation method of a prothioconazole sustained-release agent, which has simple process and lower cost;
2. the prothioconazole sustained-release agent prepared by the invention has good water solubility, can be applied in various administration modes, and has low pesticide residue;
3. the prothioconazole sustained-release agent prepared by the invention has the advantages of controllable release, environmental protection and the like.
Detailed Description
The invention is further illustrated by the following specific examples.
Example 1
Adding 0.1 mol of prothioconazole, 150 mL of DMF, 0.5 mol of polyethylene glycol methacrylate (average molecular weight 360) and 0.1 mol of neutral aluminum oxide into a 250 mL four-mouth bottle, stirring and heating to 100 ℃, reacting for 5 hours, and stopping the reaction when the content of the prothioconazole is less than 0.5% by HPLC (high performance liquid chromatography) detection; filtering to remove the catalyst, and removing the solvent under reduced pressure; and adding 200 g of diethyl ether into the crude product, stirring for dispersion, and filtering to obtain the prothioconazole sustained-release agent product with the yield of 85%.
30 g of a polyethylene glycol methacrylate (average molecular weight 360) graft copolymer of prothioconazole is added into 100 g of water, and the mixture is stirred for 10 minutes at normal temperature, so that the prothioconazole graft is completely dissolved. The comparative prothioconazole bulk drug has a solubility of 0.3 g/L in water at pH = 8.
A300 mg/L solution was prepared for soil spray test (laboratory data, 20 ℃), soil DT50 for 5-8 days, and decomposition product desulfurization-prothioconazole soil DT50 for 7-34 days. The soil DT50 of the prothioconazole bulk drug is compared for 0.07-1.3 days. Meanwhile, a field spraying test shows that the cucumber powdery mildew control agent has a good control effect on cucumber powdery mildew.
Example 2
Adding 0.5 mol of prothioconazole, 200 mL of DMF, 0.5 mol of polyethylene glycol methacrylate (average molecular weight 360) and 0.1 mol of neutral aluminum oxide into a 250 mL four-mouth bottle, stirring and heating to 100 ℃, reacting for 6 h, and stopping the reaction when the content of the prothioconazole is less than 0.5% by HPLC (high performance liquid chromatography) detection; filtering to remove the catalyst, and removing the solvent under reduced pressure; adding 250 g of diethyl ether into the crude product, stirring for dispersion, and filtering to obtain the prothioconazole sustained-release agent product with the yield of 91%.
30 g of a polyethylene glycol methacrylate (average molecular weight 360) graft copolymer of prothioconazole is added into 100 g of water, and the mixture is stirred for 10 minutes at normal temperature, so that the prothioconazole graft is completely dissolved. The comparative prothioconazole bulk drug has a solubility of 0.3 g/L in water at pH = 8.
A300 mg/L solution was prepared for soil spray tests (laboratory data, 20 ℃ C.), soil DT50 for 5-8 days and decomposition product desulfurization-prothioconazole soil DT50 for 7-34 days. Compared with soil DT50 of prothioconazole technical for 0.07-1.3 days. Meanwhile, a field spraying test shows that the cucumber powdery mildew control agent has a good control effect on cucumber powdery mildew.
Example 3
Adding 0.5 mol of prothioconazole raw drug, 200 mL of DMF, 0.5 mol of polyethylene glycol methacrylate (average molecular weight 360) and 0.5 mol of neutral aluminum oxide into a 250 mL four-mouth bottle, stirring and heating to 100 ℃, reacting for 6 hours, and stopping the reaction when the content of the prothioconazole raw drug is less than 0.5% by HPLC (high performance liquid chromatography) detection; filtering to remove the catalyst, and removing the solvent under reduced pressure; adding 250 g of diethyl ether into the crude product, stirring for dispersion, and filtering to obtain the prothioconazole sustained-release agent product with the yield of 95%.
30 g of a polyethylene glycol methacrylate (average molecular weight 360) graft copolymer of prothioconazole is added into 100 g of water, and the mixture is stirred for 10 minutes at normal temperature, so that the prothioconazole graft is completely dissolved. The comparative prothioconazole bulk drug has a solubility of 0.3 g/L in water at pH = 8.
A300 mg/L solution was prepared for soil spray test (laboratory data, 20 ℃), soil DT50 for 5-8 days, and decomposition product desulfurization-prothioconazole soil DT50 for 7-34 days. The soil DT50 of the prothioconazole bulk drug is compared for 0.07-1.3 days. Meanwhile, a field spraying test shows that the cucumber powdery mildew control agent has a good control effect on cucumber powdery mildew.
Example 4
Adding 0.1 mol of prothioconazole, 200 mL of DMF, 0.5 mol of polyethylene glycol methacrylate (average molecular weight 1000) and 0.1 mol of neutral aluminum oxide into a 250 mL four-mouth bottle, stirring and heating to 120 ℃, reacting for 8 hours, and stopping the reaction when the content of the prothioconazole is less than 0.5% by HPLC (high performance liquid chromatography) detection; filtering to remove the catalyst, and removing the solvent under reduced pressure; adding 250 g of diethyl ether into the crude product, stirring for dispersion, and filtering to obtain the prothioconazole sustained-release agent product with the yield of 81%.
10 g of a polyethylene glycol methacrylate (average molecular weight 360) graft copolymer of prothioconazole is taken, added into 100 g of water, stirred for 10 minutes at normal temperature, and the prothioconazole graft is completely dissolved. The comparative prothioconazole bulk drug has a solubility of 0.3 g/L in water at pH = 8.
A300 mg/L solution was prepared for soil spray test (laboratory data, 20 ℃), soil DT50 for 9-10 days, and decomposition product desulfurization-prothioconazole soil DT50 for 10-40 days. The soil DT50 of the prothioconazole bulk drug is compared for 0.07-1.3 days. Meanwhile, a field spraying test shows that the cucumber powdery mildew control agent has a good control effect on cucumber powdery mildew.
Example 5
Adding 0.1 mol of prothioconazole, 150 mL of DMF, 0.5 mol of polyethylene glycol methacrylate (average molecular weight 200) and 0.1 mol of neutral aluminum oxide into a 250 mL four-mouth bottle, stirring and heating to 100 ℃, reacting for 5 hours, and stopping the reaction when the content of the prothioconazole is less than 0.5% by HPLC (high performance liquid chromatography) detection; filtering to remove the catalyst, and removing the solvent under reduced pressure; and adding 200 g of diethyl ether into the crude product, stirring for dispersion, and filtering to obtain the prothioconazole sustained-release agent product with the yield of 89%.
40 g of a polyethylene glycol methacrylate (average molecular weight 200) graft copolymer of prothioconazole is taken, added into 100 g of water, stirred for 10 minutes at normal temperature, and the prothioconazole graft is completely dissolved. The comparative prothioconazole bulk drug has a solubility of 0.3 g/L in water at pH = 8.
A300 mg/L solution was prepared for soil spray test (laboratory data, 20 ℃), soil DT50 for 4-6 days, and decomposition product desulfurization-prothioconazole soil DT50 for 5-20 days. The soil DT50 of the prothioconazole bulk drug is compared for 0.07-1.3 days. Meanwhile, field spraying experiments show that the bactericidal composition has good control effect on cucumber powdery mildew.
Example 6
Adding 0.1 mol of prothioconazole, 150 mL of DMF, 0.5 mol of polyethylene glycol methacrylate (average molecular weight 360) and 0.1 mol of neutral aluminum oxide into a 250 mL four-mouth bottle, stirring and heating to 70 ℃, reacting for 10h, and stopping the reaction when the content of the prothioconazole is less than 0.5% by HPLC (high performance liquid chromatography) detection; filtering to remove the catalyst, and removing the solvent under reduced pressure; and adding 200 g of diethyl ether into the crude product, stirring for dispersion, and filtering to obtain the prothioconazole sustained-release agent product with the yield of 90%.
30 g of a polyethylene glycol methacrylate (average molecular weight 360) graft copolymer of prothioconazole is added into 100 g of water, and the mixture is stirred for 10 minutes at normal temperature, so that the prothioconazole graft is completely dissolved. The comparative prothioconazole bulk drug has a solubility of 0.3 g/L in water at pH = 8.
A300 mg/L solution was prepared for soil spray tests (laboratory data, 20 ℃ C.), soil DT50 for 5-8 days and decomposition product desulfurization-prothioconazole soil DT50 for 7-34 days. The soil DT50 of the prothioconazole bulk drug is compared for 0.07-1.3 days. Meanwhile, a field spraying test shows that the cucumber powdery mildew control agent has a good control effect on cucumber powdery mildew.
Example 7
Adding 0.1 mol of prothioconazole, 150 mL of DMF, 0.5 mol of polyethylene glycol methacrylate (average molecular weight 360) and 0.1 mol of neutral aluminum oxide into a 250 mL four-mouth bottle, stirring and heating to 160 ℃, reacting for 1h, and stopping the reaction when the content of the prothioconazole is less than 0.5% by HPLC (high performance liquid chromatography) detection; filtering to remove the catalyst, and removing the solvent under reduced pressure; and adding 200 g of diethyl ether into the crude product, stirring for dispersion, and filtering to obtain the prothioconazole sustained-release agent product with the yield of 73%.
30 g of a polyethylene glycol methacrylate (average molecular weight 360) graft copolymer of prothioconazole is added into 100 g of water, and the mixture is stirred for 10 minutes at normal temperature, so that the prothioconazole graft is completely dissolved. The solubility of the comparative prothioconazole technical in water with pH =8 was 0.3 g/L.
A300 mg/L solution was prepared for soil spray test (laboratory data, 20 ℃), soil DT50 for 5-8 days, and decomposition product desulfurization-prothioconazole soil DT50 for 7-34 days. Compared with soil DT50 of prothioconazole technical for 0.07-1.3 days. Meanwhile, a field spraying test shows that the cucumber powdery mildew control agent has a good control effect on cucumber powdery mildew.
Example 8
Adding 0.1 mol of prothioconazole, 150 mL of DMF, 0.5 mol of polyethylene glycol methacrylate (average molecular weight 360) and 0.1 mol of neutral aluminum oxide into a 250 mL four-mouth bottle, stirring and heating to 160 ℃, reacting for 10 hours, and stopping the reaction when the content of the prothioconazole is less than 0.5% by HPLC (high performance liquid chromatography) detection; filtering to remove the catalyst, and removing the solvent under reduced pressure; and adding 200 g of diethyl ether into the crude product, stirring for dispersion, and filtering to obtain the prothioconazole sustained-release agent product with the yield of 95%.
30 g of a polyethylene glycol methacrylate (average molecular weight 360) graft copolymer of prothioconazole is added into 100 g of water, and the mixture is stirred for 10 minutes at normal temperature, so that the prothioconazole graft is completely dissolved. The comparative prothioconazole bulk drug has a solubility of 0.3 g/L in water at pH = 8.
A300 mg/L solution was prepared for soil spray tests (laboratory data, 20 ℃ C.), soil DT50 for 5-8 days and decomposition product desulfurization-prothioconazole soil DT50 for 7-34 days. The soil DT50 of the prothioconazole bulk drug is compared for 0.07-1.3 days. Meanwhile, a field spraying test shows that the cucumber powdery mildew control agent has a good control effect on cucumber powdery mildew.
Example 9
Adding 0.1 mol of prothioconazole, 150 mL of DMF, 0.5 mol of polyethylene glycol methacrylate (average molecular weight 360) and 0.1 mol of neutral aluminum oxide into a 250 mL four-mouth bottle, stirring and heating to 70 ℃, reacting for 10h, and stopping the reaction when the content of the prothioconazole is less than 0.5% by HPLC (high performance liquid chromatography) detection; filtering to remove the catalyst, and removing the solvent under reduced pressure; and adding 200 g of petroleum ether into the crude product, stirring and dispersing, and filtering to obtain the prothioconazole sustained-release agent product with the yield of 88%.
30 g of a polyethylene glycol methacrylate (average molecular weight 360) graft copolymer of prothioconazole is added into 100 g of water, and the mixture is stirred for 10 minutes at normal temperature, so that the prothioconazole graft is completely dissolved. The comparative prothioconazole bulk drug has a solubility of 0.3 g/L in water at pH = 8.
A300 mg/L solution was prepared for soil spray test (laboratory data, 20 ℃), soil DT50 for 5-8 days, and decomposition product desulfurization-prothioconazole soil DT50 for 7-34 days. The soil DT50 of the prothioconazole bulk drug is compared for 0.07-1.3 days. Meanwhile, field spraying experiments show that the bactericidal composition has good control effect on cucumber powdery mildew.
Example 10
Adding 0.1 mol of prothioconazole, 150 mL of DMF, 0.5 mol of polyethylene glycol methacrylate (average molecular weight 360) and 0.1 mol of neutral aluminum oxide into a 250 mL four-mouth bottle, stirring and heating to 70 ℃, reacting for 10h, and stopping the reaction when the content of the prothioconazole is less than 0.5% by HPLC (high performance liquid chromatography) detection; filtering to remove the catalyst, and removing the solvent under reduced pressure; and adding 200 g of ethylene glycol dimethyl ether into the crude product, stirring and dispersing, and filtering to obtain the prothioconazole sustained-release agent product with the yield of 85%.
30 g of a polyethylene glycol methacrylate (average molecular weight 360) graft copolymer of prothioconazole is added into 100 g of water, and the mixture is stirred for 10 minutes at normal temperature, so that the prothioconazole graft is completely dissolved. The comparative prothioconazole bulk drug has a solubility of 0.3 g/L in water at pH = 8.
A300 mg/L solution was prepared for soil spray tests (laboratory data, 20 ℃ C.), soil DT50 for 5-8 days and decomposition product desulfurization-prothioconazole soil DT50 for 7-34 days. The soil DT50 of the prothioconazole bulk drug is compared for 0.07-1.3 days. Meanwhile, a field spraying test shows that the cucumber powdery mildew control agent has a good control effect on cucumber powdery mildew.