Synthesis method of bromoxynil octanoate active compound

Abstract

The invention belongs to the technical field of pesticide original drug synthesis, and particularly relates to a bromoxynil octanoate original drug synthesis method which comprises the following specific steps: taking p-cyanophenol as a raw material, dissolving the raw material in a mixed solvent, carrying out bromination reaction with bromine and 50% hydrogen peroxide, after the reaction is finished, cooling, crystallizing, carrying out suction filtration, washing with water, and carrying out suction filtration to obtain an intermediate wet material, distilling the mother liquor subjected to suction filtration to recover methanol or ethanol and continuously applying the methanol or ethanol to bromination reaction; and dissolving the intermediate wet material in a solvent, carrying out esterification reaction with 30% caustic soda liquid and capryloyl chloride, layering after the reaction is qualified, washing with water, and desolventizing to obtain the most product bromoxynil octanoate active compound. According to the method, impurities are prevented from entering the next batch, the safety problem caused by hydrogen peroxide residues due to the fact that the impurities participate in the subsequent esterification reaction is solved, the purity of the intermediate and the production safety are improved, the use amount of capryloyl chloride does not need to be additionally increased in the esterification reaction process to compensate the influence of the impurities, and the yield is improved. And the quality of the final product bromoxynil octanoate active compound is guaranteed.

Description

Technical Field

[0001] The present invention belongs to the technical field of synthesis of pesticide technical materials, and particularly relates to a method for synthesizing bromoxynil octanoate technical material. Background Art

[0002] Bromoxynil octanoate technical material is an important pesticide intermediate and a selective herbicide with certain systemic properties. It is mainly used for cereal crops (such as wheat, barley, etc.), corn, sorghum, onions, garlic, mint, grass seed crops, turf, and non-cultivated land to control annual broad-leaved weeds post-emergence, and has wide application value in the agricultural field. Its synthesis process usually involves bromination and esterification reactions of p-cyanophenol. Currently, the preparation process of bromoxynil octanoate requires the use of expensive catalysts and complex recovery processes, which greatly increase the cost and prolong the time of the entire process.

[0003] There are studies on the problems existing in the preparation process of bromoxynil octanoate in the prior art. For example, there are the following two process routes, and each route has its unique technical characteristics and existing problems: Process Route 1: For example, in a method for preparing high-purity bromoxynil octanoate with a patent publication number of CN108569985A published by Deng Guiyuan, Chen Hua, etc. on May 28, 2018, the process route uses p-cyanophenol as the raw material and water as the solvent. After bromination with bromine and hydrogen peroxide, and after sodium carbonate destroys hydrogen peroxide, octanoyl chloride and liquid alkali are used for esterification to obtain bromoxynil octanoate. The reaction route is as follows: ; This process route has the problem that intermediate impurities are not separated at the end of the bromination step. These intermediate impurities contain carboxylic acid groups that will react with sodium carbonate, resulting in insufficient sodium carbonate for destroying hydrogen peroxide, so that hydrogen peroxide remains in the subsequent esterification reaction. The remaining hydrogen peroxide will decompose violently when liquid alkali is added, increasing the danger. At the same time, the introduction of intermediate impurities will also increase the consumption of octanoyl chloride, leading to an increase in the consumption of production raw materials and a decrease in the product content. Moreover, only water is used as the solvent in the bromination of this process route, and the reaction materials are poorly dispersed in water, making it difficult to judge the end point of the reaction.

[0004] Process Route 2: For example, in a synthesis process of halogenated benzonitrile ester series compounds with a patent publication number of CN101328139A published by Zeng Zhongwu, Chen Fan, etc. on August 3, 2008, the process route uses p-cyanophenol as the raw material and ethanol as the solvent. After bromination with bromine and hydrogen peroxide, crystallization is carried out. After taking out the intermediate dry powder, high-temperature esterification is carried out. The reaction route is as follows: ; However, the main raw material of bromoxynil octanoate, p-cyanophenol, is generally synthesized by the p-hydroxybenzoic acid method in industry. Therefore, a small amount of p-hydroxybenzoic acid is contained in p-cyanophenol, and p-hydroxybenzoic acid will react continuously with the system. The reaction route is as follows: ; Although this process route can separate the intermediate, a large amount of toxic dust will be generated during the high-energy-consuming drying process. In addition, the mother liquor is reused without any treatment, resulting in the enrichment of intermediate impurities in the mother liquor and also adhering to the surface of the intermediate during the crystallization process, thus affecting the content of the intermediate. Similarly, the intermediate impurities brought into the esterification process will still lead to an increase in the amount of octanoyl chloride used and a decrease in product quality.

[0005] To sum up, in the existing synthesis process of bromoxynil octanoate, impurities participate in the subsequent reactions, making the synthesis process have potential safety hazards or affecting the content of the intermediate. At the same time, it will also increase the amount of octanoyl chloride used, resulting in a decrease in product quality. Therefore, a new technical solution is needed to solve the above technical problems. Summary of the Invention

[0006] The purpose of the present invention is to provide a method for synthesizing bromoxynil octanoate technical drug to solve the problems mentioned in the above background technology, that is, in the current synthesis process of bromoxynil octanoate, impurities participate in the subsequent reactions, making the synthesis process have potential safety hazards or affecting the content of the intermediate. At the same time, it will also increase the amount of octanoyl chloride used, resulting in a decrease in product quality, etc.

[0007] To achieve the above purpose, the present invention provides the following technical solution: A method for synthesizing bromoxynil octanoate technical drug, including the following specific steps: S1. Using p-cyanophenol as the raw material, dissolve it in a mixed solvent of methanol and water or a mixed solvent of ethanol and water. At 40 - 50 °C, carry out a bromination reaction with bromine and 50% hydrogen peroxide for 4 - 6 hours. After the reaction ends at 60 - 65 °C and is kept warm for 1 - 2 hours, first cool down to 0 - 5 °C for crystallization and keep warm for 2 - 3 hours, then filter by suction. Wash with water and filter by suction to obtain the wet intermediate material. Among them, the mother liquor obtained by filtration is recycled by distillation to recover methanol or ethanol and is continuously reused in the bromination reaction. The weight ratio of p-cyanophenol to the mixed solvent of methanol and water or the mixed solvent of ethanol and water is 1:4 - 6. The molar ratio of p-cyanophenol to bromine and 50% hydrogen peroxide is 1:1.02 - 1.04:1.08 - 1.1. Bromine and 50% hydrogen peroxide are added dropwise to participate in the bromination reaction. The addition amount of bromine is 450 - 750 ml / minute, and the addition amount of 50% hydrogen peroxide is 200 - 350 ml / minute; S2. Dissolve the wet intermediate obtained in S1 in dichloroethane solvent, and carry out an esterification reaction with 30% liquid alkali and octanoyl chloride at 0 - 5°C for 2 - 3 hours. After the reaction is qualified, separate the layers, wash with water, and remove the solvent to obtain the final product, the technical material of bromoxynil octanoate. Among them, the weight ratio of the wet intermediate to the dichloroethane solvent is 1:5 - 7, the molar ratio of the wet intermediate to 30% liquid alkali and octanoyl chloride is 1:1.2 - 1.4:1.05 - 1.08. 30% liquid alkali and octanoyl chloride are added dropwise to participate in the esterification reaction. The addition amount of 30% liquid alkali is 1000 - 1400 ml / minute, and the addition amount of octanoyl chloride is 950 - 1450 ml / minute; Its synthesis route is as follows: 。

[0008] Compared with the prior art, the beneficial effects of the present invention are as follows: 1. The present invention uses methanol - water or ethanol - water as the bromination solvent, which effectively improves the dispersion effect of the reaction materials. Compared with the existing bromination water solvent, it is easier to judge the end point of the reaction. By carrying out the steps of cooling crystallization filtration and water washing filtration after the bromination reaction, impurities in the intermediate are effectively removed, and the purity of the intermediate is significantly improved. Not only can impurities be left only in the mother liquor, but also no additional amount of octanoyl chloride needs to be added during the esterification reaction to compensate for the influence of impurities, providing high - quality raw materials for the subsequent esterification reaction, thus ensuring the quality of the final product, the technical material of bromoxynil octanoate, helping to reduce the generation of by - products, and improving the yield and purity of the product. By distilling and recycling methanol or ethanol in the filtration mother liquor, not only are impurities prevented from entering the next batch, effectively avoiding safety problems caused by the residual hydrogen peroxide due to the participation of impurities in the subsequent esterification reaction, reducing the safety hazard of the violent decomposition of hydrogen peroxide in the esterification reaction, significantly improving the production safety, but also realizing the recycling of resources, reducing resource waste, and at the same time reducing the wastewater discharge during the production process, meeting the environmental protection requirements, and helping to promote the development of green chemistry; 2. By precisely controlling parameters such as the temperature, time, and addition amount of raw materials in the bromination reaction and the esterification reaction, the present invention not only ensures the smooth progress of the reaction and the efficient generation of products, but also guarantees the stability and consistency of the products, improves the production efficiency, helps to enhance the market competitiveness of the products, and at the same time reduces the generation of by - products, improving the utilization rate of raw materials and the yield of products; 3. The present invention directly obtains an intermediate wet material after the bromination reaction. Compared with the prior art, the intermediate can be directly obtained and the purity can reach 99.4%. There is no need for traditional high-energy-consuming drying treatment, which not only simplifies the production process but also reduces production energy consumption. Using the intermediate wet material directly enters the esterification reaction step, effectively avoiding the harm of toxic dust generated during the drying process to the environment and operators, significantly improving production efficiency, ensuring the cleanliness and safety of the production environment, and meeting the environmental protection requirements of modern industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0009] Figure 1 is the process flow chart of the present invention; Figure 2 is the chromatogram and analysis result table of the octanoyl bromobenzonitrile intermediate of the present invention; Figure 3 is the chromatogram and analysis result table of the octanoyl bromobenzonitrile technical drug of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0010] The following examples are used to further illustrate the content of the present invention and do not limit the application of the present invention. Example 1:

[0011] Please refer to Figure 1 , this example provides a method for synthesizing octanoyl bromobenzonitrile technical drug, and the specific steps are as follows: Put 119 kg of p-cyanophenol, 95.2 kg of water, and 380.8 kg of methanol into the bromination kettle, heat up to 40 °C, and simultaneously dropwise add 163.2 kg of bromine and 73.4 kg of 50% hydrogen peroxide, so that the addition amount of bromine is 450 - 750 ml / minute, and the addition amount of 50% hydrogen peroxide is 200 - 350 ml / minute. The dropping temperature is controlled at 40 - 50 °C. After dropping, keep the reaction at this temperature for 4 hours, heat up to 60 °C, keep warm for 1 hour, then cool down to 0 °C, keep warm for crystallization for 2 hours, filter by suction. The intermediate is added with 238 kg of water for washing on the suction filter tank, and the intermediate wet material (i.e., the intermediate damp product) is obtained by suction filtration. The mother liquor of the suction filtration will be recovered by distillation to obtain 322.7 kg of water-containing methanol with 5.6% water; Put the intermediate damp product in the bromination step and 595 kg of dichloroethane into the esterification kettle, cool down to 0 °C, and simultaneously dropwise add 160 kg of 30% liquid alkali and 170.6 kg of octanoyl chloride, so that the addition amount of 30% liquid alkali is 1000 - 1400 ml / minute, and the addition amount of octanoyl chloride is 950 - 1450 ml / minute. The dropping temperature is controlled at 0 - 5 °C. After dropping, keep the reaction at this temperature for 2 hours. After passing the in-process control, separate the upper water layer. After washing three times with 238 kg of water until neutral, distill out dichloroethane to obtain 392.8 g of octanoyl bromobenzonitrile technical drug with a content of 97.5% and a yield of 95.04%. Example 2:

[0012] Please refer to Figure 1 , this embodiment provides a method for synthesizing the technical drug of bromoxynil octanoate, and the specific steps are as follows: Put 119 kg of p-cyanophenol, 322.7 kg of water-containing methanol (with 5.6% water) recovered in Example 1, 124.7 kg of water, and 266.6 kg of methanol into the bromination kettle, heat up to 50 °C, and simultaneously dropwise add 166.4 kg of bromine and 74.8 kg of 50% hydrogen peroxide solution, so that the addition rate of bromine is 450-750 ml / minute, and the addition rate of 50% hydrogen peroxide solution is 200-350 ml / minute. The dropping temperature is controlled at 40-50 °C. After dropping, keep the temperature for reaction for 6 hours, heat up to 65 °C, keep the temperature for 2 hours, then cool down to 5 °C, keep the temperature for crystallization for 3 hours, and carry out suction filtration. The intermediate is washed with 357 kg of water on the suction filtration tank, and the intermediate wet product is obtained by suction filtration (the chromatogram and analysis results table of the intermediate wet product in this embodiment are as Figure 2 shown), and the mother liquor of the suction filtration will be recovered by distillation to obtain 482 kg of water-containing methanol with 6.2% water; Put the intermediate wet product in the bromination step and 833 kg of dichloroethane into the esterification kettle, cool down to 5 °C, and simultaneously dropwise add 186.7 kg of 30% liquid alkali and 175.5 kg of octanoyl chloride, so that the addition rate of 30% liquid alkali is 1000-1400 ml / minute, and the addition rate of octanoyl chloride is 950-1450 ml / minute. The dropping temperature is controlled at 0-5 °C. After dropping, keep the temperature for 3 hours, and the middle control is qualified. Separate the upper water layer, wash it three times with 357 kg of water until neutral, and then distill out dichloroethane to obtain 391.8 g of the technical drug of bromoxynil octanoate with a content of 97.8% and a yield of 95.09% (the chromatogram and analysis results table of the technical drug of bromoxynil octanoate synthesized in this embodiment are as Figure 3 shown). Example 3:

[0013] Please refer to Figure 1 , this embodiment provides a method for synthesizing the technical drug of bromoxynil octanoate, and the specific steps are as follows: Put 119 kg of p-cyanophenol, 50 kg of water, and 450 kg of ethanol into the bromination kettle, heat up to 45 °C, and simultaneously dropwise add 164.1 kg of bromine and 73.9 kg of 50% hydrogen peroxide solution, so that the addition rate of bromine is 450-750 ml / minute, and the addition rate of 50% hydrogen peroxide solution is 200-350 ml / minute. The dropping temperature is controlled at 40-50 °C. After dropping, keep the temperature for reaction for 5 hours, heat up to 62 °C, keep the temperature for 1.5 hours, then cool down to 1 °C, keep the temperature for crystallization for 2 hours, and carry out suction filtration. The intermediate is washed with 260 kg of water on the suction filtration tank, and the intermediate wet product is obtained by suction filtration. The mother liquor of the suction filtration will be recovered by distillation to obtain 383 kg of water-containing ethanol with 6.0% water; In the esterification kettle, put in the wet intermediate product from the bromination step and 650 kg of dichloroethane. Cool down by 1°C, and at the same time, dropwise add 170 kg of 30% liquid caustic soda and 173 kg of octanoyl chloride, with the addition rate of 30% liquid caustic soda being 1000 - 1400 ml / minute and the addition rate of octanoyl chloride being 950 - 1450 ml / minute. Control the dropping temperature at 0 - 5°C. After dropping, keep the temperature at this level for 2.5 hours. After passing the in-process control, separate the upper aqueous layer. Wash it three times with 280 kg of water until neutral, and then distill out dichloroethane to obtain 391.7 g of the crude drug of octanoyl bromobenzonitrile, with a content of 97.9% and a yield of 95.16%. Example 4:

[0014] Please refer to Figure 1 , this example provides a method for synthesizing the crude drug of octanoyl bromobenzonitrile, and the specific steps are as follows: Put 119 kg of p-cyanophenol, 383 kg of water-containing ethanol (with a water content of 6.0%) recovered in Example 3, 47 kg of water, and 270 kg of ethanol into the bromination kettle. Heat up to 46°C, and at the same time, dropwise add 166 kg of bromine and 74.5 kg of 50% hydrogen peroxide, with the addition rate of bromine being 450 - 750 ml / minute and the addition rate of 50% hydrogen peroxide being 200 - 350 ml / minute. Control the dropping temperature at 40 - 50°C. After dropping, keep the temperature at this level for 5.5 hours for the reaction, then heat up to 64°C and keep it for 2 hours, and then cool down to 4°C and keep it for 2.5 hours for crystallization. Filter by suction. Add 350 kg of water to wash the intermediate product on the suction filter tank, and filter by suction to obtain the wet intermediate product. The mother liquor from the suction filtration will be recovered by distillation to obtain 573 kg of water-containing ethanol, with a water content of 6.2%; In the esterification kettle, put in the wet intermediate product from the bromination step and 800 kg of dichloroethane. Cool down by 3°C, and at the same time, dropwise add 185 kg of 30% liquid caustic soda and 175 kg of octanoyl chloride, with the addition rate of 30% liquid caustic soda being 1000 - 1400 ml / minute and the addition rate of octanoyl chloride being 950 - 1450 ml / minute. Control the dropping temperature at 0 - 5°C. After dropping, keep the temperature at this level for 2.5 hours. After passing the in-process control, separate the upper aqueous layer. Wash it three times with 350 kg of water until neutral, and then distill out dichloroethane to obtain 392.9 g of the crude drug of octanoyl bromobenzonitrile, with a content of 97.5% and a yield of 95.06%.

Claims

1. A method for synthesizing bromoxynil octanoyl technical, characterized in that: The specific steps are as follows: S1, using cyanophenol as a raw material, dissolving it in a mixed solvent of methanol and water or a mixed solvent of ethanol and water, and reacting it with bromine and 50% hydrogen peroxide to undergo bromination reaction, cooling and crystallizing after the reaction, and then washing and filtering with water to obtain an intermediate wet material, wherein the mother liquor of the filtration is distilled to recover methanol or ethanol and is further used in the bromination reaction; S2, dissolving the intermediate wet material obtained in S1 in dichloroethane solvent, and reacting with 30% liquid alkali and octanoyl chloride for esterification, and after the reaction is qualified, layering, washing, and desolventizing to obtain the product octanoyl bromoxynil technical drug; Its synthetic route is as follows: 。 2. The method for synthesizing bromoxynil octanoyl technical according to claim 1, characterized in that: In S1, the weight ratio of p-cyanophenol to the mixed solvent of methanol and water or the mixed solvent of ethanol and water is 1:4-6.

3. The method for synthesizing bromoxynil octanoyl technical according to claim 1, characterized in that: In S1, the molar ratio of p-cyanophenol to bromine to 50% hydrogen peroxide is 1:1.02-1.04:1.08-1.

1.

4. The method for synthesizing bromoxynil octanoyl technical according to claim 3, characterized in that: In S1, bromine and 50% hydrogen peroxide are added dropwise to participate in the bromination reaction. The amount of bromine added is 450-750 ml / min, and the amount of 50% hydrogen peroxide added is 200-350 ml / min.

5. The method for synthesizing bromoxynil octanoyl technical according to claim 4, characterized in that: In S1, the temperature during the bromination reaction is controlled at 40-50°C and the insulation time is controlled at 4-6 hours, and the temperature at the end of the bromination reaction is controlled at 60-65°C and the insulation time is controlled at 1-2 hours.

6. The method for synthesizing bromoxynil octanoyl technical according to claim 1, characterized in that: In S1, the temperature during crystallization is controlled at 0 to 5°C and the heat preservation time is controlled at 2 to 3 hours.

7. The method for synthesizing bromoxynil octanoyl technical according to claim 1, characterized in that: In S2, the weight ratio of the intermediate wet material to the dichloroethane solvent is 1:5-7.

8. The method for synthesizing bromoxynil octanoyl technical according to claim 1, characterized in that: In S2, the molar ratio of the intermediate wet material to 30% liquid alkali and octanoyl chloride is 1:1.2~1.4:1.05~1.

08.

9. The method for synthesizing bromoxynil octanoyl technical according to claim 8, characterized in that: In S2, 30% liquid alkali and octanoyl chloride are added dropwise to participate in the esterification reaction. The addition amount of 30% liquid alkali is 1000-1400 ml / min, and the addition amount of octanoyl chloride is 950-1450 ml / min.

10. The method for synthesizing bromoxynil octanoyl technical according to claim 9, characterized in that: In S2, the temperature of the esterification reaction is controlled at 0-5°C and the insulation time is controlled at 2-3 hours.

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