CN115322185A - Preparation method of topramezone - Google Patents
Preparation method of topramezone Download PDFInfo
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- CN115322185A CN115322185A CN202211256456.5A CN202211256456A CN115322185A CN 115322185 A CN115322185 A CN 115322185A CN 202211256456 A CN202211256456 A CN 202211256456A CN 115322185 A CN115322185 A CN 115322185A
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Abstract
The invention provides a preparation method of topramezone, and belongs to the field of topramezone preparation. The preparation method of topramezone comprises the following steps: preparing raw material liquid, performing first-stage reaction, performing second-stage reaction, performing third-stage reaction, performing fourth-stage reaction and performing post-treatment. Wherein, the preparation of the raw material liquid comprises: preparing a first raw material liquid and preparing a second raw material liquid. The preparation method of topramezone can effectively catalyze the reaction by adopting the catalyst loaded with non-noble metal active ingredients at the temperature of 80-100 ℃, so that the purity of the prepared topramezone can reach 99.791%, and the yield is 90.1-91.0%.
Description
Technical Field
The invention relates to the field of topramezone preparation, in particular to a preparation method of topramezone.
Background
Topramezone is a novel pyrazolone post-emergence foliar treatment herbicide developed by basf european corporation, and belongs to a triketone post-emergence foliar treatment agent. Its trade names are Convey, clio, bract and so on. Topramezone is mainly used for controlling weeds in corn fields, such as broadleaf weeds, grass weeds and the like.
Topramezone is in the Chinese market under the trade name baowen, which is defined as a herbicide for various types of corn fields, and has the advantage of high safety.
Topramezone is an organic heterocyclic selective systemic pre-emergence herbicide, is absorbed by plants in a mode of being absorbed by leaves, roots or seedlings, then is transported to meristems of the plants, and finally blocks the production of p-hydroxyphenylpyruvate dioxygenase (4-HPPL) in the meristems, thereby affecting the synthesis of plastid wakefulness and simultaneously inhibiting the synthesis of carotenoids. Finally, the plants can not normally synthesize the chloroplasts, so that the chlorophylls are oxidized and degraded, and the germinated weeds are whitened and die.
Topramezone has good control effect in sweet corn and popcorn fields, and can play a good role in controlling various weeds, such as goosegrass, ragweed, cyperus heterophyllus, green bristlegrass and the like. Meanwhile, the topramezone can be mixed with a plurality of other pesticides, so that a good control effect on other crop fields is realized.
U.S. patent 20030216580A1 discloses a synthesis method of topramezone, which adopts key intermediate 3- [ 3-bromo-2-methyl-6- (methylsulfonyl) phenyl ] -4, 5-dihydro-isoxazole, and performs carboxylation reaction on the key intermediate, 1-methyl-5-hydroxypyrazole and carbon monoxide in the presence of a catalyst to prepare topramezone. Wherein, the key intermediate 3- [ 3-bromo-2-methyl-6- (methylsulfonyl) phenyl ] -4, 5-dihydro isoxazole can be prepared by adopting 2, 3-dimethylaniline or 3-nitro-o-xylene as an initial reactant and adopting different methods. The synthesis principle of topramezone is as follows:
the inventor finds that in the existing technology for preparing topramezone by reacting 3- [ 3-bromo-2-methyl-6- (methylsulfonyl) phenyl ] -4, 5-dihydroisoxazole with 1-methyl-5-hydroxypyrazole, in order to ensure ideal product yield and purity index, precious metal catalysts (such as palladium catalysts and the like) are needed, and the precious metal catalysts are expensive, high in production cost and difficult to effectively recover. Meanwhile, the reaction can be smoothly carried out under the environment of higher pressure and temperature of more than 120 ℃, the production energy consumption is high, and the requirement on a reaction device is high. Further, in the technology for preparing topramezone in the prior art, the yield index of topramezone cannot be further improved while high-purity topramezone is obtained.
Disclosure of Invention
In order to solve the technical problems in the prior art, the invention provides the preparation method of topramezone, which can adopt a non-noble metal catalyst for effective catalysis, has mild reaction conditions, and reduces the production cost and energy consumption; and the ideal yield index can be obtained while the high-purity topramezone is obtained.
In order to solve the technical problems, the technical scheme adopted by the invention is as follows:
a preparation method of topramezone comprises the following steps: preparing raw material liquid, performing first-stage reaction, performing second-stage reaction, performing third-stage reaction, performing fourth-stage reaction and performing post-treatment.
The preparation of the raw material liquid comprises the steps of preparing a first raw material liquid and preparing a second raw material liquid.
The method for preparing the first raw material liquid comprises the steps of putting 3- [ 3-bromo-2-methyl-6- (methylsulfonyl) phenyl ] -4, 5-dihydro isoxazole and a first acid-binding agent into 1, 4-dioxane, and uniformly mixing to prepare the first raw material liquid;
in the preparation of the first raw material liquid, a first acid-binding agent is triethylamine;
in the preparation of the first raw material liquid, the ratio of parts by weight of 3- [ 3-bromo-2-methyl-6- (methylsulfonyl) phenyl ] -4, 5-dihydro isoxazole, the first acid-binding agent and 1, 4-dioxane is 25-25.
The method for preparing the second raw material liquid comprises the steps of putting a predetermined amount of 1-methyl-5-hydroxypyrazole and a second acid-binding agent into 1, 4-dioxane, and uniformly mixing to prepare a second raw material liquid;
in the preparation of the second raw material solution, the second acid-binding agent is sodium methoxide;
in the preparation of the second raw material liquid, the ratio of the 1-methyl-5-hydroxypyrazole to the second acid-binding agent to the 1, 4-dioxane by weight parts is 7.7-15.
Controlling carbon monoxide to continuously enter a first-stage reaction unit of the microchannel reactor filled with the catalyst, and keeping the pressure of the carbon monoxide in the first-stage reaction unit at 0.4-0.6MPa; meanwhile, controlling the first raw material liquid and the second raw material liquid to pass through the first-stage reaction unit at a preset flow rate to perform first-stage reaction; controlling the reaction temperature to be 80-85 ℃ and the reaction time to be 20-30min to prepare a first-stage reaction solution;
in the first-stage reaction, the flow rates of the first raw material liquid and the second raw material liquid are equal; the flow rates of the first raw material liquid and the second raw material liquid are 50-75ml/min;
in the first-stage reaction, the addition amount of the catalyst is 0.3-0.8wt% of the total mass of the first raw material liquid and the second raw material liquid.
The method of the second-stage reaction comprises the steps of controlling carbon monoxide to continuously enter a second-stage reaction unit of the microchannel reactor filled with the catalyst, and keeping the pressure of the carbon monoxide in the second-stage reaction unit at 0.5-0.7MPa; the first-stage reaction liquid passes through a second-stage reaction unit to carry out second-stage reaction; controlling the reaction temperature to be 85-90 ℃ and the reaction time to be 20-30min to prepare a secondary reaction liquid;
the addition amount of the catalyst in the secondary reaction is 0.3-0.8wt% of the mass of the primary reaction liquid;
in the second-stage reaction, the catalyst is the same as that of the first-stage reaction.
The three-stage reaction method comprises the steps of controlling carbon monoxide to continuously enter a three-stage reaction unit of the microchannel reactor filled with the catalyst, and keeping the pressure of the carbon monoxide in the three-stage reaction unit at 0.6-0.8MPa; meanwhile, the second-stage reaction liquid passes through a third-stage reaction unit to carry out a third-stage reaction; controlling the reaction temperature to be 90-95 ℃ and the reaction time to be 20-30min to prepare a third-stage reaction liquid;
in the third-stage reaction, the addition amount of the catalyst is 0.3-0.8wt% of the mass of the second-stage reaction liquid;
the catalyst in the third-stage reaction is the same as that in the first-stage reaction.
The method of the four-stage reaction comprises the steps of controlling carbon monoxide to continuously enter a four-stage reaction unit of the microchannel reactor filled with the catalyst, and keeping the pressure of the carbon monoxide in the four-stage reaction unit at 0.7-0.9MPa; meanwhile, the third-stage reaction liquid passes through a fourth-stage reaction unit to carry out a fourth-stage reaction; controlling the reaction temperature to be 95-100 ℃ and the reaction time to be 20-30min to prepare a four-stage reaction solution;
in the four-stage reaction, the addition amount of the catalyst is 0.3-0.8wt% of the mass of the three-stage reaction liquid;
the catalyst in the fourth-order reaction is the same as that of the first-order reaction.
The post-treatment method comprises the steps of mixing the four-stage reaction solution with deionized water with the volume of 0.4-0.8 time, uniformly stirring, and filtering to obtain a filtrate; then, under the temperature condition of 105-115 ℃, concentrating the filtrate to 35-45% of the original volume to prepare a concentrated solution; cooling the concentrated solution to 2-6 ℃, dropwise adding sulfuric acid until the pH value is 2.5-3.0, standing until no solid is separated out, filtering out the solid, washing the solid with deionized water, placing in a vacuum environment, and drying at 70-80 ℃ until the weight is unchanged to obtain topramezone;
in the post-treatment, the concentration of sulfuric acid is 20-25wt%.
In the first-stage reaction to the fourth-stage reaction, the preparation method of the adopted catalyst comprises the following steps: and (4) preprocessing and loading.
Completely soaking the activated carbon into absolute ethyl alcohol, performing ultrasonic dispersion for 20-50min, filtering out the activated carbon, putting the filtered activated carbon into deionized water, heating until the deionized water boils, performing heat preservation and reflux for 2-5h, and drying at 95-105 ℃ for 7-10h in a vacuum environment to obtain the pretreated activated carbon;
in the pretreatment, the ratio of the weight parts of the activated carbon to the weight parts of the deionized water is 1-8.
The loading method comprises the steps of putting nickel nitrate and cobalt nitrate into deionized water, adjusting the pH value to 7.5-8.0 by ammonia water, and preparing a negative carrier liquid; putting the pretreated activated carbon into a negative carrier liquid with the volume 2-5 times of the volume of the activated carbon, stirring for 12-16h, filtering out solids, placing the solids in a vacuum environment, drying at 105-115 ℃ until the weight is unchanged, and then carrying out reduction treatment in hydrogen at 350-400 ℃ for 3-5h to prepare a catalyst;
in the load, the concentration of nickel nitrate in the negative carrier liquid is 12-15wt%, and the concentration of cobalt nitrate is 6-10wt%;
in the load, the concentration of ammonia water is 22-25%.
Compared with the prior art, the invention has the beneficial effects that:
(1) The preparation method of topramezone comprises the steps of respectively preparing a first raw material solution and a second raw material solution; preparing a catalyst loaded with non-noble metal active ingredients; the first raw material liquid, the second raw material liquid and carbon monoxide are parallelly introduced into a microchannel reactor filled with a catalyst, and four-stage reaction is sequentially carried out; meanwhile, in the series-connected four-stage reaction process, the stepped reaction temperature and carbon monoxide pressure are set; the preparation method can effectively catalyze the reaction by adopting a non-noble metal catalyst, the purity of the prepared topramezone can reach 99.791%, the yield is 90.1-91.0%, and the content of single impurities (such as condensation acid and the like) can reach less than 0.077%.
(2) The preparation method of topramezone has mild reaction conditions, can realize smooth reaction at the temperature of 80-100 ℃, can reduce the production energy consumption, and can further improve the yield index of topramezone while obtaining high-purity topramezone.
(3) According to the preparation method of topramezone, the catalyst loaded with non-noble metal active ingredients is adopted, so that the reaction can be effectively catalyzed, noble metal catalysts (such as palladium catalysts and the like) are not required, the catalysts can be repeatedly recycled, and the production cost is effectively reduced.
(4) Compared with the existing topramezone production process, the preparation method of topramezone effectively shortens the reaction time, has high production efficiency, and further saves the production cost.
Drawings
FIG. 1 is a liquid chromatogram of topramezone prepared in example 1.
FIG. 2 is a liquid chromatogram of topramezone prepared in example 2.
FIG. 3 is a liquid chromatogram of topramezone prepared in example 3.
Detailed Description
In order to more clearly understand the technical features, objects, and effects of the present invention, specific embodiments of the present invention will now be described.
Example 1
A preparation method of topramezone comprises the following specific steps:
1. preparation of the stock solution
1) Preparing a first stock solution
Adding 3- [ 3-bromo-2-methyl-6- (methylsulfonyl) phenyl ] -4, 5-dihydro isoxazole and a first acid-binding agent into 1, 4-dioxane, and uniformly stirring to prepare a first raw material liquid.
Wherein the first acid-binding agent is triethylamine.
The weight ratio of the 3- [ 3-bromo-2-methyl-6- (methylsulfonyl) phenyl ] -4, 5-dihydroisoxazole, the first acid-binding agent and the 1, 4-dioxane is 25.
2) Preparing a second stock solution
And (3) adding a predetermined amount of 1-methyl-5-hydroxypyrazole and a second acid-binding agent into 1, 4-dioxane, and uniformly stirring to prepare a second raw material solution.
Wherein the second acid-binding agent is sodium methoxide.
The weight ratio of the 1-methyl-5-hydroxypyrazole to the second acid-binding agent to the 1, 4-dioxane is 7.7.
2. First order reaction
Controlling carbon monoxide to continuously enter a first-stage reaction unit of the microchannel reactor filled with the catalyst, and keeping the pressure of the carbon monoxide in the first-stage reaction unit at 0.6MPa; meanwhile, controlling the first raw material liquid and the second raw material liquid to be introduced into the first-stage reaction unit at a preset flow rate to carry out first-stage reaction; controlling the reaction temperature at 85 ℃ and the reaction time at 30min to prepare a first-stage reaction solution.
Wherein the flow rates of the first raw material liquid and the second raw material liquid are both 75ml/min.
The amount of the catalyst added was 0.8wt% of the total mass of the first raw material liquid and the second raw material liquid.
The catalyst is prepared by the following method:
1) Pretreatment of
Completely soaking activated carbon into absolute ethyl alcohol, performing ultrasonic dispersion for 50min, filtering out the activated carbon, putting the filtered activated carbon into deionized water, heating until the deionized water boils, performing heat preservation and reflux for 5h, and drying at 105 ℃ for 10h in a vacuum environment to obtain the pretreated activated carbon.
Wherein the weight part ratio of the activated carbon to the deionized water is 1.
2) Load(s)
Putting nickel nitrate and cobalt nitrate into deionized water, and adjusting the pH value to 7.8 by using ammonia water to prepare a negative carrier liquid; putting the pretreated activated carbon into negative carrier liquid with the volume 5 times that of the activated carbon, stirring for 16h, filtering out solids, placing the solids in a vacuum environment, drying at 115 ℃ until the weight is unchanged, and then carrying out reduction treatment for 5h in hydrogen at 400 ℃ to obtain the catalyst.
Wherein, the concentration of nickel nitrate in the negative carrier liquid is 15wt%, and the concentration of cobalt nitrate is 10wt%.
The concentration of ammonia was 24%.
3. Second order reaction
Controlling carbon monoxide to continuously enter a secondary reaction unit of the microchannel reactor filled with the catalyst, and keeping the pressure of the carbon monoxide in the secondary reaction unit at 0.7MPa; introducing the primary reaction liquid into a secondary reaction unit for secondary reaction; controlling the reaction temperature at 90 ℃ and the reaction time at 30min to prepare a secondary reaction solution.
The addition amount of the catalyst was 0.8wt% of the mass of the first-order reaction solution.
The catalyst in the second stage reaction is the same as the catalyst in the first stage reaction.
4. Three-stage reaction
Controlling carbon monoxide to continuously enter a three-stage reaction unit of the microchannel reactor filled with the catalyst, and keeping the pressure of the carbon monoxide in the three-stage reaction unit at 0.8MPa; meanwhile, introducing the second-stage reaction liquid into a third-stage reaction unit to carry out a third-stage reaction; controlling the reaction temperature at 95 ℃ and the reaction time at 30min to prepare a third-stage reaction solution.
The addition amount of the catalyst is 0.8wt% of the mass of the secondary reaction liquid.
The catalyst in the third stage reaction is the same as that in the first stage reaction.
5. Four-stage reaction
Controlling carbon monoxide to continuously enter a four-stage reaction unit of the microchannel reactor filled with the catalyst, and keeping the pressure of the carbon monoxide in the four-stage reaction unit at 0.9MPa; meanwhile, the third-stage reaction liquid passes through a fourth-stage reaction unit to carry out a fourth-stage reaction; controlling the reaction temperature at 100 ℃ and the reaction time at 30min to prepare a four-stage reaction solution.
The addition amount of the catalyst is 0.8wt% of the mass of the third-stage reaction liquid.
The catalyst in the fourth stage reaction is the same as the catalyst in the first stage reaction.
6. Post-treatment
Mixing the four-stage reaction solution with deionized water with 0.8 times of volume, stirring uniformly, and filtering to obtain a filtrate; then, concentrating the filtrate to 45% of the original volume at the temperature of 115 ℃ to prepare a concentrated solution; and (3) cooling the concentrated solution to 6 ℃, dropwise adding sulfuric acid until the pH value is 2.8, standing until no solid is separated out, filtering out the solid, washing the solid with deionized water, placing the solid in a vacuum environment, and drying at 80 ℃ until the weight of the solid is unchanged to obtain a solid product, namely the topramezone.
Wherein the concentration of sulfuric acid is 25wt%.
Through detection, the purity of the prepared topramezone is 99.145 percent, the yield is 90.1 percent, the content of single impurities (such as condensation acid and the like) is less than 0.316 percent, and a specific liquid chromatogram is shown in figure 1.
Example 2
A preparation method of topramezone comprises the following specific steps:
1. preparation of the stock solution
1) Preparing a first stock solution
3- [ 3-bromo-2-methyl-6- (methylsulfonyl) phenyl ] -4, 5-dihydroisoxazole and a first acid-binding agent in a predetermined amount are put into 1, 4-dioxane and stirred uniformly to prepare a first raw material liquid.
Wherein the first acid-binding agent is triethylamine.
The weight ratio of the 3- [ 3-bromo-2-methyl-6- (methylsulfonyl) phenyl ] -4, 5-dihydroisoxazole to the first acid-binding agent to the 1, 4-dioxane is 25.
2) Preparing a second stock solution
And (3) adding a predetermined amount of 1-methyl-5-hydroxypyrazole and a second acid-binding agent into 1, 4-dioxane, and uniformly stirring to prepare a second raw material solution.
Wherein the second acid-binding agent is sodium methoxide.
The weight ratio of the 1-methyl-5-hydroxypyrazole to the second acid-binding agent to the 1, 4-dioxane is 7.7.
2. First order reaction
Controlling carbon monoxide to continuously enter a first-stage reaction unit of the microchannel reactor filled with the catalyst, and keeping the pressure of the carbon monoxide in the first-stage reaction unit at 0.5MPa; meanwhile, controlling the first raw material liquid and the second raw material liquid to flow into a first-stage reaction unit at a preset flow rate, and carrying out a first-stage reaction; controlling the reaction temperature at 82 ℃ and the reaction time at 25min to prepare a first-stage reaction solution.
Wherein the flow rates of the first raw material liquid and the second raw material liquid are both 50ml/min.
The amount of the catalyst added was 0.5wt% based on the total mass of the first raw material liquid and the second raw material liquid.
The catalyst is prepared by the following method:
1) Pretreatment of
Completely soaking activated carbon into absolute ethyl alcohol, performing ultrasonic dispersion for 30min, filtering out the activated carbon, putting the filtered activated carbon into deionized water, heating until the deionized water boils, performing heat preservation and reflux for 3h, and drying at 100 ℃ for 8h in a vacuum environment to obtain the pretreated activated carbon.
Wherein the weight ratio of the activated carbon to the deionized water is 1.
2) Load(s)
Putting nickel nitrate and cobalt nitrate into deionized water, and adjusting the pH value to 8.0 by adopting ammonia water to prepare a negative carrier liquid; putting the pretreated activated carbon into negative carrier liquid with the volume 3 times that of the activated carbon, stirring for 14h, filtering out solids, placing the solids in a vacuum environment, drying at 110 ℃ until the weight is unchanged, and then carrying out reduction treatment in hydrogen at 360 ℃ for 4h to obtain the catalyst.
Wherein, the concentration of the nickel nitrate in the negative carrier liquid is 13wt%, and the concentration of the cobalt nitrate is 8wt%.
The concentration of ammonia was 25%.
3. Second order reaction
Controlling carbon monoxide to continuously enter a secondary reaction unit of the microchannel reactor filled with the catalyst, and keeping the pressure of the carbon monoxide in the secondary reaction unit at 0.6MPa; introducing the primary reaction liquid into a secondary reaction unit for secondary reaction; controlling the reaction temperature to 87 ℃ and the reaction time to 25min to prepare a secondary reaction solution.
The addition amount of the catalyst is 0.5wt% of the mass of the first-order reaction liquid.
The catalyst in the second stage reaction is the same as the catalyst in the first stage reaction.
4. Three-stage reaction
Controlling carbon monoxide to continuously enter a three-stage reaction unit of the microchannel reactor filled with the catalyst, and keeping the pressure of the carbon monoxide in the three-stage reaction unit at 0.7MPa; meanwhile, introducing the second-stage reaction liquid into a third-stage reaction unit to carry out a third-stage reaction; controlling the reaction temperature to be 92 ℃ and the reaction time to be 25min to prepare a third-stage reaction solution.
The addition amount of the catalyst is 0.5wt% of the mass of the second-stage reaction liquid.
The catalyst in the third stage reaction is the same as that in the first stage reaction.
5. Four-stage reaction
Controlling carbon monoxide to continuously enter a four-stage reaction unit of the microchannel reactor filled with the catalyst, and keeping the pressure of the carbon monoxide in the four-stage reaction unit at 0.8MPa; meanwhile, the tertiary reaction liquid passes through a quaternary reaction unit to carry out quaternary reaction; controlling the reaction temperature to 97 ℃ and the reaction time to 25min to prepare a four-stage reaction solution.
The addition amount of the catalyst is 0.5wt% of the mass of the tertiary reaction liquid.
The catalyst in the fourth stage reaction is the same as the catalyst in the first stage reaction.
6. Post-treatment
Mixing the four-stage reaction solution with deionized water with 0.6 volume times, stirring uniformly, and filtering to obtain a filtrate; then, under the temperature condition of 110 ℃, concentrating the filtrate to 40 percent of the original volume to prepare a concentrated solution; and (3) cooling the concentrated solution to 4 ℃, dropwise adding sulfuric acid until the pH value is 2.5, standing until no solid is separated out, filtering out the solid, washing the solid with deionized water, placing the washed solid in a vacuum environment, and drying at 75 ℃ until the weight of the dried solid is unchanged to obtain a solid product, namely the topramezone.
Wherein the concentration of sulfuric acid is 22wt%.
Through detection, the purity of the prepared topramezone is 99.784% (HPLC area normalization method), the yield is 91.0%, the content of single impurities (such as condensation acid and the like) is less than 0.077%, and a specific liquid chromatogram is shown in figure 2.
Example 3
A preparation method of topramezone comprises the following specific steps:
1. preparation of the stock solution
1) Preparing a first stock solution
3- [ 3-bromo-2-methyl-6- (methylsulfonyl) phenyl ] -4, 5-dihydroisoxazole and a first acid-binding agent in a predetermined amount are put into 1, 4-dioxane and stirred uniformly to prepare a first raw material liquid.
Wherein the first acid-binding agent is triethylamine.
The weight ratio of the 3- [ 3-bromo-2-methyl-6- (methylsulfonyl) phenyl ] -4, 5-dihydroisoxazole, the first acid-binding agent and the 1, 4-dioxane is 25.
2) Preparing a second stock solution
And (3) adding a predetermined amount of 1-methyl-5-hydroxypyrazole and a second acid-binding agent into 1, 4-dioxane, and uniformly stirring to prepare a second raw material solution.
Wherein the second acid-binding agent is sodium methoxide.
The weight ratio of the 1-methyl-5-hydroxypyrazole to the second acid-binding agent to the 1, 4-dioxane is 7.7.
2. First order reaction
Controlling carbon monoxide to continuously enter a first-stage reaction unit of the microchannel reactor filled with the catalyst, and keeping the pressure of the carbon monoxide in the first-stage reaction unit at 0.4MPa; meanwhile, controlling the first raw material liquid and the second raw material liquid to be introduced into the first-stage reaction unit at a preset flow rate to carry out first-stage reaction; controlling the reaction temperature at 80 ℃ and the reaction time at 20min to prepare a first-stage reaction solution.
Wherein the flow rates of the first raw material liquid and the second raw material liquid are 65ml/min.
The amount of the catalyst added was 0.3wt% based on the total mass of the first raw material liquid and the second raw material liquid.
The catalyst is prepared by the following method:
1) Pretreatment of
Completely soaking activated carbon into absolute ethyl alcohol, performing ultrasonic dispersion for 20min, filtering out the activated carbon, putting the filtered activated carbon into deionized water, heating until the deionized water boils, performing heat preservation and reflux for 2h, and drying at 95 ℃ for 7h in a vacuum environment to obtain the pretreated activated carbon.
Wherein the weight ratio of the activated carbon to the deionized water is 1.
2) Load(s)
Putting nickel nitrate and cobalt nitrate into deionized water, and adjusting the pH value to 7.5 by adopting ammonia water to prepare a negative carrier liquid; putting the pretreated activated carbon into a negative carrier liquid with the volume 2 times that of the activated carbon, stirring for 12 hours, filtering out solids, placing the solids in a vacuum environment, drying at 105 ℃ until the weight is unchanged, and then carrying out reduction treatment in hydrogen at 350 ℃ for 3 hours to obtain the catalyst.
Wherein, the concentration of the nickel nitrate in the negative carrier liquid is 12wt%, and the concentration of the cobalt nitrate is 6wt%.
The concentration of ammonia was 22%.
3. Second order reaction
Controlling carbon monoxide to continuously enter a secondary reaction unit of the microchannel reactor filled with the catalyst, and keeping the pressure of the carbon monoxide in the secondary reaction unit at 0.5MPa; introducing the primary reaction liquid into a secondary reaction unit for secondary reaction; controlling the reaction temperature at 85 ℃ and the reaction time at 20min to prepare a secondary reaction solution.
The addition amount of the catalyst is 0.3wt% of the mass of the first-order reaction liquid.
The catalyst in the second stage reaction is the same as the catalyst in the first stage reaction.
4. Three-stage reaction
Controlling carbon monoxide to continuously enter a three-stage reaction unit of the microchannel reactor filled with the catalyst, and keeping the pressure of the carbon monoxide in the three-stage reaction unit at 0.6MPa; meanwhile, introducing the second-stage reaction liquid into a third-stage reaction unit to carry out a third-stage reaction; controlling the reaction temperature at 90 ℃ and the reaction time at 20min to prepare a third-stage reaction solution.
The addition amount of the catalyst is 0.3wt% of the mass of the secondary reaction liquid.
The catalyst in the third stage reaction is the same as that in the first stage reaction.
5. Quaternary reaction
Controlling carbon monoxide to continuously enter a four-stage reaction unit of the microchannel reactor filled with the catalyst, and keeping the pressure of the carbon monoxide in the four-stage reaction unit at 0.7MPa; meanwhile, the tertiary reaction liquid passes through a quaternary reaction unit to carry out quaternary reaction; controlling the reaction temperature at 95 ℃ and the reaction time at 20min to prepare a four-stage reaction solution.
The addition amount of the catalyst is 0.3wt% of the mass of the third-stage reaction liquid.
The catalyst in the fourth stage reaction is the same as the catalyst in the first stage reaction.
6. Post-treatment
Mixing the four-stage reaction solution with deionized water with 0.4 times of volume, stirring uniformly, and filtering to obtain a filtrate; then, under the temperature condition of 105 ℃, concentrating the filtrate to 35% of the original volume to prepare a concentrated solution; and (3) cooling the concentrated solution to 2 ℃, dropwise adding sulfuric acid until the pH value is 3.0, standing until no solid is separated out, filtering out the solid, washing the solid with deionized water, placing the washed solid in a vacuum environment, and drying at 70 ℃ until the weight of the washed solid is unchanged to obtain a solid product, namely the topramezone.
Wherein the concentration of sulfuric acid is 20wt%.
Through detection, the purity of the prepared topramezone is 99.791 percent (HPLC area normalization method), the yield is 90.2 percent, the content of single impurities (such as condensation acid and the like) is less than 0.139 percent, and a specific liquid chromatogram is shown in figure 3.
Comparative example 1
The technical scheme of the embodiment 2 is adopted, and the difference is that: 1) In the step of preparing the raw material liquid, a second acid-binding agent is omitted; 2) In the step of preparing the raw material liquid, 3- [ 3-bromo-2-methyl-6- (methylsulfonyl) phenyl ] -4, 5-dihydroisoxazole, a first acid-binding agent, 1-methyl-5-hydroxypyrazole and 1, 4-dioxane are directly mixed to prepare the raw material liquid without adopting a mode of respectively preparing a first raw material liquid and a second raw material liquid; the flow rate of the raw material liquid in the first-stage reaction is 100ml/min; 3) In the preparation of the catalyst, nickel nitrate was omitted.
Wherein the weight parts ratio of the 3- [ 3-bromo-2-methyl-6- (methylsulfonyl) phenyl ] -4, 5-dihydro isoxazole, the first acid-binding agent, the 1-methyl-5-hydroxypyrazole and the 1, 4-dioxane is 25.
The topramezone prepared in comparative example 1 had a purity of 96.6% and a yield of 87.5%.
According to the invention, the specific acid-binding agent is added into each raw material solution to prepare the first raw material solution and the second raw material solution respectively, and then the first raw material solution and the second raw material solution are introduced into the microchannel reactor in parallel to carry out reaction, so that the reaction can be promoted, and the purity and yield of the final product topramezone can be promoted to be synchronously improved; meanwhile, the catalyst loaded with the nickel active component can effectively catalyze the reaction.
Comparative example 2
The technical scheme of the embodiment 2 is adopted, and the differences are that: omitting the step of preparing a raw material liquid, putting 3- [ 3-bromo-2-methyl-6- (methylsulfonyl) phenyl ] -4, 5-dihydro isoxazole, a first acid-binding agent, 1-methyl-5-hydroxypyrazole, a second acid-binding agent and 1, 4-dioxane into a fixed bed reactor filled with a catalyst, uniformly stirring, heating to 120 ℃, keeping the temperature, continuously introducing carbon monoxide, keeping the pressure of the carbon monoxide in the fixed bed reactor at 0.7-0.9MPa, and reacting for 10 hours to prepare a reaction liquid; and carrying out post-treatment on the reaction solution to obtain topramezone.
Wherein, the catalyst is the same as the catalyst in the embodiment 2.
The weight parts of the 3- [ 3-bromo-2-methyl-6- (methylsulfonyl) phenyl ] -4, 5-dihydroisoxazole, the first acid scavenger, the 1-methyl-5-hydroxypyrazole, the second acid scavenger, the catalyst, and the 1, 4-dioxane are 25.
Comparative example 2 produced topramezone with a purity of 96.0% and a yield of 86.7%.
It can be seen that the present invention adopts a mode of preparing the first raw material solution and the second raw material solution respectively; and a four-stage series microchannel reaction mode is adopted, and the stepped reaction temperature and the carbon monoxide pressure are set in the four-stage reaction, so that the reaction time can be effectively shortened, the reaction temperature can be reduced, and the purity and the yield of the topramezone can be synchronously improved.
All percentages used in the present invention are mass percentages unless otherwise indicated.
Finally, it should be noted that: although the present invention has been described in detail with reference to the foregoing embodiments, it will be apparent to those skilled in the art that modifications may be made to the embodiments described above, or equivalents may be substituted for elements thereof. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (4)
1. A preparation method of topramezone is characterized by comprising the following steps: preparing a raw material solution, performing primary reaction, secondary reaction, tertiary reaction, quaternary reaction and post-treatment;
the preparation raw material liquid comprises the following steps: preparing a first raw material liquid and a second raw material liquid;
the method for preparing the first raw material liquid comprises the steps of putting 3- [ 3-bromo-2-methyl-6- (methylsulfonyl) phenyl ] -4, 5-dihydro isoxazole and a first acid-binding agent into 1, 4-dioxane, and uniformly mixing to prepare the first raw material liquid;
in the preparation of the first raw material liquid, a first acid-binding agent is triethylamine;
the method for preparing the second raw material liquid comprises the steps of putting a predetermined amount of 1-methyl-5-hydroxypyrazole and a second acid-binding agent into 1, 4-dioxane, and uniformly mixing to prepare a second raw material liquid;
in the preparation of the second raw material solution, the second acid-binding agent is sodium methoxide;
the first-stage reaction method comprises the steps of continuously introducing carbon monoxide into a first-stage reaction unit of the microchannel reactor filled with the catalyst, and keeping the pressure of the carbon monoxide in the first-stage reaction unit at 0.4-0.6MPa; introducing the first raw material liquid and the second raw material liquid into a first-stage reaction unit at preset flow rates respectively to perform first-stage reaction; controlling the reaction temperature to be 80-85 ℃ and the reaction time to be 20-30min to prepare a first-stage reaction solution;
in the first-stage reaction, the flow rates of the first raw material liquid and the second raw material liquid are equal; the flow rates of the first raw material liquid and the second raw material liquid are 50-75ml/min;
continuously introducing carbon monoxide into a secondary reaction unit of the microchannel reactor filled with the catalyst, and keeping the pressure of the carbon monoxide in the secondary reaction unit at 0.5-0.7MPa; introducing the primary reaction liquid into a secondary reaction unit for secondary reaction; controlling the reaction temperature to be 85-90 ℃ and the reaction time to be 20-30min to prepare a secondary reaction solution;
the three-stage reaction method comprises the steps of continuously introducing carbon monoxide into a three-stage reaction unit of the microchannel reactor filled with the catalyst, and keeping the pressure of the carbon monoxide in the three-stage reaction unit at 0.6-0.8MPa; introducing the second-stage reaction liquid into a third-stage reaction unit to carry out a third-stage reaction; controlling the reaction temperature to be 90-95 ℃ and the reaction time to be 20-30min to prepare a third-stage reaction liquid;
the four-stage reaction method comprises the steps of continuously introducing carbon monoxide into a four-stage reaction unit of the microchannel reactor filled with the catalyst, and keeping the pressure of the carbon monoxide in the four-stage reaction unit at 0.7-0.9MPa; introducing the third-stage reaction liquid into a fourth-stage reaction unit to carry out a fourth-stage reaction; controlling the reaction temperature to be 95-100 ℃ and the reaction time to be 20-30min to prepare a four-stage reaction solution;
the preparation method of the catalyst adopted in the first-stage reaction to the fourth-stage reaction comprises the following steps: preprocessing and loading;
completely soaking activated carbon into absolute ethyl alcohol, performing ultrasonic dispersion, filtering out the activated carbon, putting the filtered activated carbon into deionized water, heating until the deionized water boils, performing heat preservation and reflux for 2-5h, and drying at 95-105 ℃ for 7-10h in a vacuum environment to obtain pretreated activated carbon;
in the pretreatment, the ratio of the weight parts of the activated carbon to the deionized water is 1-8;
the loading method comprises the steps of putting nickel nitrate and cobalt nitrate into deionized water, and adjusting the pH value to 7.5-8.0 by adopting ammonia water to prepare a negative carrier liquid; putting the pretreated activated carbon into a negative carrier liquid with the volume 2-5 times of that of the activated carbon, stirring for 12-16h, filtering out solids, placing in a vacuum environment, drying at 105-115 ℃ until the weight is unchanged, and then carrying out reduction treatment in hydrogen at 350-400 ℃ for 3-5h to prepare a catalyst;
in the load, the concentration of nickel nitrate in the negative carrier liquid is 12-15wt%, and the concentration of cobalt nitrate is 6-10wt%;
the post-treatment method comprises the steps of washing, filtering, concentrating, acidifying and drying the fourth-stage reaction liquid to obtain the topramezone.
2. The process for preparing topramezone according to claim 1, wherein the first raw material solution is prepared by mixing 3- [ 3-bromo-2-methyl-6- (methylsulfonyl) phenyl ] -4, 5-dihydroisoxazole, the first acid scavenger, 1, 4-dioxane, at a weight ratio of 25;
in the preparation of the second raw material liquid, the weight part ratio of the 1-methyl-5-hydroxypyrazole to the second acid-binding agent to the 1, 4-dioxane is 7.7-15.
3. The preparation method of topramezone according to claim 1, wherein in the first-stage reaction, the catalyst is added in an amount of 0.3-0.8wt% based on the total mass of the first raw material liquid and the second raw material liquid;
in the second-stage reaction, the addition amount of the catalyst is 0.3-0.8wt% of the mass of the first-stage reaction liquid;
in the third-stage reaction, the addition amount of the catalyst is 0.3-0.8wt% of the mass of the second-stage reaction liquid;
in the four-stage reaction, the addition amount of the catalyst is 0.3-0.8wt% of the mass of the third-stage reaction liquid.
4. The preparation method of topramezone according to claim 1, wherein the post-treatment is performed by mixing the fourth-stage reaction solution with 0.4-0.8 times of deionized water by volume, stirring uniformly, and filtering to obtain a filtrate; then, under the temperature condition of 105-115 ℃, concentrating the filtrate to 35-45% of the original volume to prepare a concentrated solution; cooling the concentrated solution to 2-6 ℃, dropwise adding dilute sulfuric acid until the pH value is 2.5-3.0, standing until no solid is separated out, filtering out the solid, washing the solid with deionized water, placing in a vacuum environment, and drying at 70-80 ℃ until the weight is unchanged to obtain the topramezone.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104693195A (en) * | 2014-12-27 | 2015-06-10 | 安徽久易农业股份有限公司 | Preparation method of topramezone |
| CN110922367A (en) * | 2019-10-31 | 2020-03-27 | 江苏中旗科技股份有限公司 | Intermediate of topramezone and preparation method of topramezone |
| WO2020152200A1 (en) * | 2019-01-25 | 2020-07-30 | Basf Se | Process for preparation of heteroarylketones |
| CN112125897A (en) * | 2020-09-30 | 2020-12-25 | 江苏七洲绿色化工股份有限公司 | Preparation method of topramezone |
| CN113402511A (en) * | 2021-06-18 | 2021-09-17 | 西安交通大学 | Preparation method of topramezone |
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Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104693195A (en) * | 2014-12-27 | 2015-06-10 | 安徽久易农业股份有限公司 | Preparation method of topramezone |
| WO2020152200A1 (en) * | 2019-01-25 | 2020-07-30 | Basf Se | Process for preparation of heteroarylketones |
| CN110922367A (en) * | 2019-10-31 | 2020-03-27 | 江苏中旗科技股份有限公司 | Intermediate of topramezone and preparation method of topramezone |
| CN112125897A (en) * | 2020-09-30 | 2020-12-25 | 江苏七洲绿色化工股份有限公司 | Preparation method of topramezone |
| CN113402511A (en) * | 2021-06-18 | 2021-09-17 | 西安交通大学 | Preparation method of topramezone |
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