A low consumption 4-bromopyrrole bromine fractional quenching synthesis process

Abstract

The application belongs to the technical field of chemical synthesis, and specifically provides a low-consumption 4-bromopyrrole bromine fractional quenching synthesis process, which comprises the following steps: S1, pyrrole water washing desalting: water is added to pyrrole crude product, then stirring is performed to form a slurry, then centrifugation is performed, and low-salt pyrrole is obtained after drying; S2, hydrogen peroxide and bromine synergistic bromination: low-salt pyrrole is put into a dissolving kettle and methanol is added, then bromine and hydrogen peroxide are synchronously added dropwise, and incubation is performed to ensure sufficient reaction; S3, fractional quenching: any one of sodium thiosulfate, sodium sulfite and sodium bisulfite is put into the solution obtained in S2, and constant stirring and mixing are performed to quench excess hydrogen peroxide; S4, crystallization and drying: the solution obtained in S3 is cooled and incubated for a period of time, then centrifugation is performed to obtain 4-bromopyrrole filter cake, then deionized water is used for leaching, and then vacuum drying is performed to obtain 4-bromopyrrole. The above can significantly reduce the amount of bromine, avoid liquid alkali neutralization and reduce the generation of salt by-product.

Description

Technical Field

[0001] This invention relates to the field of chemical synthesis technology, and in particular to a low-consumption 4-bromopyrrole bromide graded quenching synthesis process. Background Technology

[0002] 4-Bromopyrrole, chemically named 4-bromo-2-(4-chlorophenyl)-5-(trifluoromethyl)-1HH3O-pyrrole-3-carboxynitrile, is an important insecticide intermediate widely used in the synthesis of highly effective insecticides such as bromfenac and flupyrfuranone. Its current industrial preparation methods typically use pyrrole as a starting material, obtained through a bromination reaction.

[0003] In traditional bromination processes, pyrrole is often reacted directly with excess bromine via an electrophilic substitution reaction. To ensure complete pyrrole conversion, the actual molar ratio of pyrrole to bromine in production typically needs to be 1:2.0-2.5, meaning the amount of bromine used is much higher than the theoretical amount. After the reaction, a large amount of unreacted free bromine and hydrogen bromide byproduct remain in the system. Industrially, this is generally neutralized by adding a high-concentration liquid alkali, such as a 30% sodium hydroxide solution.

[0004] The aforementioned traditional process has the following significant drawbacks. In the bromination reaction, only one bromine atom of a bromine molecule participates in aromatic ring substitution, while the other bromine atom generates hydrogen bromide. The utilization rate of bromine atoms is very low. Furthermore, the large amount of bromine added during production to ensure conversion further reduces the actual effective utilization rate of bromine atoms. Simultaneously, due to the excessive bromine input, liquid alkali is required to neutralize the excess bromine and the byproduct hydrogen bromide. This reaction generates large amounts of inorganic salts such as sodium bromide and produces neutralization wastewater with high salt content and high chemical oxygen demand, which is difficult and costly to treat. The crude 4-bromopyrrole obtained after neutralization contains and adsorbs a large amount of inorganic salts. When directly used in subsequent reactions, the salt content interferes with the reaction process and affects the purity of the final product. To reduce the salt content, multiple washings or recrystallizations are often required, leading to product loss and decreased yield.

[0005] In addition, liquid alkali neutralization is an exothermic process, and the pH and temperature of the system are not easy to control precisely, which can easily lead to side reactions caused by local over-alkaliness, increasing the complexity of operation and safety risks. Summary of the Invention

[0006] To address the aforementioned shortcomings, a low-consumption 4-bromopyrrole bromide fractional quenching synthesis process is provided, which can significantly reduce the amount of bromine used, avoid liquid alkali neutralization to reduce the generation of salt-containing byproducts, and effectively control the salt content of the product through simple means.

[0007] To achieve the above objectives, the present invention provides the following technical solution: a low-consumption 4-bromopyrrole bromide stepwise quenching synthesis process, comprising: S1. Pyrrole water washing desalting: Add water to crude pyrrole, stir to form a slurry, then centrifuge, and dry after centrifugation to obtain low-salt pyrrole; S2, synergistic bromination of hydrogen peroxide and bromine: Low-salt pyrrole is added to a dissolving vessel and methanol is added. Then, bromine and hydrogen peroxide are added dropwise simultaneously, and the temperature is maintained to ensure a complete reaction. S3, graded quenching: Add any one of sodium thiosulfate, sodium sulfite and sodium bisulfite to the solution obtained in S2, and stir continuously to quench the excess hydrogen peroxide. S4. Crystallization and drying: The solution obtained in S3 was cooled and kept at that temperature for a period of time, then centrifuged to obtain a 4-bromopyrrole filter cake, which was then rinsed with deionized water and then dried under vacuum to obtain 4-bromopyrrole.

[0008] As a further improvement of the present invention, the mass of water added in S1 is 0.5-1 times that of the crude pyrrole product, the temperature is maintained at 50-60°C during stirring, and the stirring time is 0.8-1.1h.

[0009] As a further improvement of the present invention, the drying temperature after centrifugation in S1 is 75-90°C, and the product is dried to a solid content of over 90%.

[0010] As a further improvement of the present invention, the weight of methanol added in S2 is 4-5 times that of crude pyrrole, the temperature is controlled at 25-35°C, the bromine and hydrogen peroxide are added dropwise for 3-5 hours, and the heat preservation time is 2-4 hours.

[0011] As a further improvement of the present invention, the molar ratio of pyrrole to the added bromine in S2 is 1:1.02-1.05, and the mass of the added hydrogen peroxide is 0.5 times that of the bromine.

[0012] As a further improvement of the present invention, the mass fraction concentration of hydrogen peroxide added in S2 is 27.5%-30%.

[0013] As a further improvement of the present invention, the quenching temperature in S3 is maintained at 48-52°C, and the quenching endpoint is when the solution pH reaches 5-7.

[0014] As a further improvement of the present invention, the cooling and heat preservation temperature in S4 is 20-25℃, and the heat preservation time is 2-2.5h.

[0015] As a further improvement of the present invention, the temperature of the deionized water used for rinsing in S4 is 0-5°C, and the vacuum drying temperature is 95-105°C.

[0016] The beneficial effects of this invention are: 1. Due to the use of in-situ hydrogen peroxide oxidation technology, no inorganic acids are produced during the entire bromination reaction, and the reaction solution remains weakly acidic to near neutral throughout. After the reaction, only one of sodium thiosulfate, sodium sulfite, or sodium bisulfite is added as a quencher to gently reduce the slightly excess bromine to bromide ions. The quenching process is free from drastic exothermic reactions and acid-base fluctuations. After quenching, the pH of the reaction system naturally remains above 6, eliminating the need for adding large amounts of liquid alkali to adjust the pH as in traditional processes. This technology reduces the generation of high-salt, high-COD neutralization wastewater, simplifies the operation steps, eliminates the risk of side reactions caused by localized over-alkaliness, and significantly improves the environmental friendliness and operational safety of the process. Throughout the entire process, the desolvation and crystallization conditions are relatively mild, resulting in high production safety.

[0017] 2. This invention employs a synergistic bromination strategy involving the dual dropwise addition of bromine and hydrogen peroxide. Hydrogen peroxide oxidizes the bromine byproduct of bromination in situ within the reaction system, converting it into reactive bromine. This allows both bromine atoms in the bromine molecule to effectively participate in the aromatic ring substitution reaction. This process reduces the amount of bromine fed in by more than half, significantly lowering raw material costs. Simultaneously, the hydrogen peroxide itself is reduced to water, introducing no byproducts and greatly improving the atom economy of the bromination reaction.

[0018] 3. Before the bromination reaction, the crude pyrrole is pretreated by water pulping. Utilizing the difference in solubility between inorganic salts and organic matter in water, a large amount of inorganic salt impurities entrained and adsorbed in the crude product are effectively washed away. By controlling the pulping temperature and stirring time, and combining this with centrifugal drying to a solids content of over 90%, the salt content of the crude product can be significantly reduced. The low-salt substrate participating in the subsequent bromination reaction reduces the introduction of impurities, allowing the final reaction solution to yield high-purity 4-bromopyrrole after desolvation and hydration crystallization without repeated recrystallization. This improves product yield and reduces wastewater discharge. Detailed Implementation

[0019] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.

[0020] This invention provides a low-consumption, stepwise quenching synthesis process for 4-bromopyrrole bromide, comprising: S1, pyrrole water-eluted salt.

[0021] Add 0.5-1 times the mass of water to crude pyrrole, control the reaction temperature at 50-60℃, stir for 0.8-1.1h to form a slurry, then centrifuge, and dry at 75-90℃ until the solid content is above 90% to obtain low-salt pyrrole.

[0022] S2, hydrogen peroxide and bromine synergistic bromination.

[0023] Add low-salt pyrrole to a dissolving vessel, then add methanol at 4-5 times the weight of the crude pyrrole. Control the temperature at 25-35℃, and then simultaneously add bromine and hydrogen peroxide. The molar ratio of pyrrole to the added bromine is 1:1.02-1.05, and the mass of the added hydrogen peroxide is 0.5 times that of the bromine. The mass fraction concentration of the added hydrogen peroxide is 27.5%-30%, and the addition time is 3-5 hours. Then, keep warm for 2-4 hours.

[0024] S3, graded quenching.

[0025] Maintain the temperature at 48-52℃, then add any one of sodium thiosulfate, sodium sulfite, and sodium bisulfite, and stir continuously to quench excess hydrogen peroxide. Stop when the solution pH reaches 5-7.

[0026] S4. Crystallization and drying.

[0027] The solution obtained from S3 was cooled to 20-25℃ and then kept at that temperature for 2-2.5 hours. After centrifugation, a 4-bromopyrrole filter cake was obtained. The obtained 4-bromopyrrole filter cake was rinsed with deionized water at 0-5℃ and then dried under vacuum at 95-105℃ to obtain 4-bromopyrrole.

[0028] Example 1 S1, pyrrole water-eluted salt.

[0029] Take 1000g of crude pyrrole (salt content 2.3%, i.e., 23g salt per kilogram of crude product), add 500g of deionized water, stir and heat to 55℃, keep warm and slurry for 1.0 hour. Centrifuge to obtain filter cake, and vacuum dry the filter cake at 80℃ to a solid content of 91.2%, obtaining 957g of low-salt pyrrole, with a salt content of 0.32%.

[0030] S2, hydrogen peroxide and bromine synergistic bromination.

[0031] The above-mentioned low-salt pyrrole was added to a dissolving vessel, and 4000g of methanol (4 times the mass of the low-salt pyrrole) was added. The mixture was stirred and dissolved, and the temperature was controlled at 30℃. 160.5g of bromine (1.025mol, pyrrole to bromine molar ratio 1:1.025) and 81.0g of 27.5% hydrogen peroxide solution (0.5 times the mass of bromine) were placed in high-level tanks and added dropwise to the vessel simultaneously. The addition was completed in 4 hours, and the mixture was kept at the same temperature and stirred for another 3 hours.

[0032] S3, graded quenching.

[0033] After the heat preservation is completed, the reaction solution is heated to 50°C, and 6.5g of sodium thiosulfate is slowly added while stirring. Stirring is continued until the pH of the solution is detected to be 6.5, at which point quenching is terminated.

[0034] S4. Crystallization and drying.

[0035] The reaction solution was cooled to 25°C and kept at this temperature for 2 hours to induce crystallization. The crystals were then centrifuged and filtered. The filter cake was rinsed with 50 mL of 3°C deionized water and then vacuum dried at 100°C to constant weight, yielding 148.5 g of white crystalline 4-bromopyrrole with a purity of 99.3% and a salt content of 0.47% (i.e., 4.7 g of salt per kilogram of product). After quenching, the pH of the system was 6.5, and no liquid alkali adjustment was required throughout the process.

[0036] Example 2 S1, pyrrole water-eluted salt.

[0037] Take 1000g of crude pyrrole (salt content 2.1%), add 800g of deionized water, stir and heat to 50℃, keep warm and slurry for 1.1 hours. Centrifuge to obtain filter cake, and vacuum dry the filter cake at 80℃ to a solid content of 93%, to obtain 961g of low-salt pyrrole, with a salt content of 0.25%.

[0038] S2, hydrogen peroxide, and bromine synergistic bromination.

[0039] The above-mentioned low-salt pyrrole was added to a dissolving vessel, and 4500g of methanol (4 times the mass of the low-salt pyrrole) was added. The mixture was stirred and dissolved, and the temperature was controlled at 25℃. 162.8g of bromine (1.04mol, pyrrole to bromine molar ratio 1:1.04) and 81.4g of 30% hydrogen peroxide solution (0.5 times the mass of bromine) were placed in high-level tanks and added dropwise to the vessel simultaneously. The addition was completed in 5 hours, and the mixture was kept at the same temperature and stirred for another 2 hours.

[0040] S3, graded quenching.

[0041] After the heat preservation is completed, the reaction solution is heated to 52°C, and 8.0g of sodium thiosulfate is slowly added while stirring. Stirring is continued until the pH of the solution is detected to be 6.2, at which point quenching is terminated.

[0042] S4. Crystallization and drying.

[0043] The reaction solution was cooled to 20°C and kept at that temperature for 2.5 hours to induce crystallization. The crystals were then centrifuged and filtered. The filter cake was rinsed with 50 mL of 0°C deionized water and then vacuum dried at 105°C to constant weight, yielding 149.2 g of white 4-bromopyrrole crystals with a purity of 99.1% and a salt content of 0.45%. The pH of the system after quenching was 6.2, and no liquid alkali adjustment was required throughout the process.

[0044] Example 3 S1, pyrrole water-eluted salt.

[0045] Take 1000g of crude pyrrole (salt content 2.5%), add 1000g of deionized water, stir and heat to 60℃, keep warm and slurry for 0.8 hours. Centrifuge to obtain filter cake, and vacuum dry the filter cake at 90℃ to a solid content of 90.5%, to obtain 955g of low-salt pyrrole, with a salt content of 0.38%.

[0046] S2, hydrogen peroxide, and bromine synergistic bromination.

[0047] The above-mentioned low-salt pyrrole was added to a dissolving vessel, and 5000g of methanol (5 times the mass of the low-salt pyrrole) was added. The mixture was stirred and dissolved, and the temperature was controlled at 28℃. 164.5g of bromine (1.05mol, pyrrole to bromine molar ratio 1:1.05) and 82.3g of 27.5% hydrogen peroxide solution (0.5 times the mass of bromine) were placed in high-level tanks and added dropwise to the vessel simultaneously. The addition was completed in 3.5 hours, and the mixture was kept at the same temperature and stirred for another 4 hours.

[0048] S3, graded quenching.

[0049] After the heat preservation is completed, the reaction solution is heated to 48°C, and 7.5g of sodium thiosulfate is slowly added while stirring. Stirring is continued until the pH of the solution is detected to be 6.8, at which point quenching is terminated.

[0050] S4. Crystallization and drying.

[0051] The reaction solution was cooled to 22°C and kept at that temperature for 2.2 hours to induce crystallization. The crystals were then centrifuged and filtered. The filter cake was rinsed with 50 mL of 5°C deionized water and then vacuum dried at 98°C to constant weight, yielding 150.5 g of white crystalline 4-bromopyrrole with a purity of 99.4% and a salt content of 0.50%. The pH of the system after quenching was 6.8, and no liquid alkali adjustment was required throughout the process.

[0052] Comparative Example 1 (Traditional Process) 1000g of unwashed wet pyrrole (2.3% salt content) was dissolved directly in 4000g of methanol at a controlled temperature of 30℃. 358g of bromine (2.2mol, pyrrole to bromine molar ratio 1:2.2) was slowly added dropwise over 5 hours, and the mixture was kept at this temperature for 3 hours. After the reaction was complete, a 30% sodium hydroxide solution was slowly added dropwise to adjust the pH to 7-8, neutralizing excess bromine and the byproduct hydrogen bromide, producing a large amount of sodium bromide. The methanol was then recovered by distillation, deionized water was added, and the mixture was cooled to 20℃ to crystallize. The crystals were centrifuged, washed, and dried to obtain 142.3g of 4-bromopyrrole with a purity of 95.6% and a salt content of 2.8% (i.e., 28g of salt per kilogram of product). The wastewater had high salt content and high COD value.

[0053] This invention achieves a green and low-consumption synthesis process by using water pulping pretreatment, synergistic bromination with hydrogen peroxide and bromine, and non-alkali quenching. This reduces the amount of bromine used by more than 50%, completely eliminates liquid alkali, and reduces the salt content of the product from 2.8% to below 0.5%. Furthermore, the pH of the system is maintained above 6 after quenching.

[0054] The above are merely preferred embodiments of the present invention. The scope of protection of the present invention is not limited to the above-described embodiments. All technical solutions falling within the scope of the present invention's concept are within the scope of protection of the present invention. It should be noted that for those skilled in the art, any improvements and modifications made without departing from the principles of the present invention should also be considered within the scope of protection of the present invention.

Claims

1. A low-consumption, stepwise quenching synthesis process for 4-bromopyrrole bromide, characterized in that, include: S1. Pyrrole water washing desalting: Add water to crude pyrrole, stir to form a slurry, then centrifuge, and dry after centrifugation to obtain low-salt pyrrole; S2, synergistic bromination of hydrogen peroxide and bromine: Low-salt pyrrole is added to a dissolving vessel and methanol is added. Then, bromine and hydrogen peroxide are added dropwise simultaneously, and the temperature is maintained to ensure a complete reaction. S3, graded quenching: Add any one of sodium thiosulfate, sodium sulfite and sodium bisulfite to the solution obtained in S2, and stir continuously to quench the excess hydrogen peroxide. S4. Crystallization and drying: The solution obtained in S3 was cooled and kept at that temperature for a period of time, then centrifuged to obtain a 4-bromopyrrole filter cake, which was then rinsed with deionized water and then dried under vacuum to obtain 4-bromopyrrole.

2. The low-consumption 4-bromopyrrole bromide staged quenching synthesis process according to claim 1, characterized in that, The mass of water added in S1 is 0.5-1 times that of the crude pyrrole product. The temperature is maintained at 50-60℃ during stirring, and the stirring time is 0.8-1.1h.

3. The low-consumption 4-bromopyrrole bromide staged quenching synthesis process according to claim 2, characterized in that, The drying temperature after centrifugation in S1 is 75-90℃, and the solid content is dried to over 90%.

4. The low-consumption 4-bromopyrrole bromide staged quenching synthesis process according to claim 1, characterized in that, In step S2, the weight of methanol added is 4-5 times that of the crude pyrrole product, the temperature is controlled at 25-35℃, the bromine and hydrogen peroxide are added dropwise for 3-5 hours, and the heat preservation time is 2-4 hours.

5. The low-consumption 4-bromopyrrole bromide staged quenching synthesis process according to claim 4, characterized in that, The molar ratio of pyrrole to the added bromine in S2 is 1:1.02-1.05, and the mass of the added hydrogen peroxide is 0.5 times that of the bromine.

6. The low-consumption 4-bromopyrrole bromide staged quenching synthesis process according to claim 5, characterized in that, The mass fraction concentration of hydrogen peroxide added in S2 is 27.5%-30%.

7. The low-consumption 4-bromopyrrole bromide staged quenching synthesis process according to claim 1, characterized in that, The quenching temperature in S3 is maintained at 48-52℃, and the quenching endpoint is when the solution pH reaches 5-7.

8. The low-consumption 4-bromopyrrole bromide staged quenching synthesis process according to claim 1, characterized in that, The cooling and heat preservation temperature in S4 is 20-25℃, and the heat preservation time is 2-2.5h.

9. The low-consumption 4-bromopyrrole bromide staged quenching synthesis process according to claim 8, characterized in that, The temperature of the deionized water used for rinsing in S4 is 0-5℃, and the vacuum drying temperature is 95-105℃.