Synthesis method of flonicamid intermediate 4-trifluoromethyl nicotinic acid

Abstract

The invention discloses a synthesis method of flonicamid intermediate 4-trifluoromethyl nicotinic acid, and belongs to the technical field of synthesis of 4-trifluoromethyl nicotinic acid. 2, 6-dichloro-3-cyano-4-trifluoromethylpyridine is subjected to catalytic hydrogenation under catalysis of bimetallic catalyst particles, and 2, 6-dichloro-3-cyano-4-trifluoromethylpyridine is subjected to post-treatment to obtain the flonicamid intermediate 4-trifluoromethyl nicotinic acid. The intermediate product 3-cyano-4-trifluoromethylpyridine is subjected to a cyano hydrolysis reaction in a sodium hydroxide ethanol solution, and the target product 4-trifluoromethyl nicotinic acid is obtained through acidification and purification. According to the preparation method, ferrous sulfate heptahydrate is taken as an iron source, terephthalic acid is taken as an organic ligand, an iron metal organic framework is loaded on the surface of a matrix, then palladium nitrate is taken as a palladium source, bimetallic catalyst particles loaded with zero-valent iron and metal palladium are prepared through heating reduction, and the organic ligand can play a role in supporting a porous structure after carbon formation; according to the method, the capture of the nano zero-valent iron on chlorine is improved, and poisoning of a palladium catalyst is slowed down, so that the service life of the bimetallic catalyst is prolonged, and continuous production of 4-trifluoromethyl nicotinic acid is facilitated.

Description

Technical Field

[0001] The present invention belongs to the technical field of the synthesis of 4-trifluoromethylnicotinic acid, and specifically relates to a method for synthesizing 4-trifluoromethylnicotinic acid, an intermediate of flonicamid. Background Art

[0002] Flonicamid is a novel selective insecticide belonging to the class of pyridine carboxamides. It has a unique mode of action, mainly interfering with the feeding behavior of insects (such as aphids, whiteflies, leafhoppers, thrips, etc.) rather than direct neurotoxicity, and has the characteristics of high efficiency, low toxicity, and environmental friendliness.

[0003] 4-Trifluoromethylnicotinic acid is the core structural unit for synthesizing flonicamid. The trifluoromethyl group and carboxylic acid group on its pyridine ring provide active sites for subsequent amidation reactions. Existing synthesis processes for 4-trifluoromethylnicotinic acid generally include three types: (1) reacting a trifluoromethylpyridine compound with carbon dioxide in the presence of a strong base such as LDA and a catalyst, and then acidifying to prepare 4-trifluoromethylnicotinic acid; (2) reacting trifluoroacetyl chloride or trifluoroacetic anhydride with vinyl ethyl ether, then ammoniating, reacting with methyl 3-methoxyacrylate, and finally cyclizing and hydrolyzing to obtain the target product; (3) using ethyl trifluoroacetoacetate and cyanoacetamide as raw materials, and preparing 4-trifluoromethylnicotinic acid through four steps of cyclization, chlorination, cyano hydrolysis, and catalytic hydrogenolysis.

[0004] The Chinese invention patent with the publication number CN108191749B discloses a method for preparing flonicamid and its intermediate 4-trifluoromethylnicotinic acid. Using cyanoacetamide, ethyl trifluoroacetoacetate, and an organic base as raw materials, first prepare 2,6-dihydroxy-3-cyano-4-trifluoromethylpyridine N-methylmorpholine salt, and then successively chlorinate with phosphorus oxychloride, catalytic hydrogenation, and hydrolysis to obtain 4-trifluoromethylnicotinic acid. This method is simple to operate and has low equipment requirements. However, in the above method, the palladium-carbon catalyst is easily poisoned and inactivated by chloride ions, by-products, etc., and the catalyst life is short. Summary of the Invention

[0005] The purpose of the present invention is to provide a method for synthesizing 4-trifluoromethylnicotinic acid, an intermediate of flonicamid. The present invention prepares a bimetallic catalyst particle loaded with zero-valent iron and metallic palladium using a foam ceramic support particle as the matrix. Nano zero-valent iron has the ability to capture chlorine, which can slow down the poisoning of the palladium catalyst, thereby extending the service life of the bimetallic catalyst and facilitating the continuous production of 4-trifluoromethylnicotinic acid.

[0006] The purpose of the present invention can be achieved by the following technical solutions: Catalytic hydrogenation of 2,6-dichloro-3-cyano-4-trifluoromethylpyridine is carried out under the catalysis of bimetallic catalyst particles. The intermediate 3-cyano-4-trifluoromethylpyridine undergoes a cyano hydrolysis reaction in sodium hydroxide ethanol solution, and the target product 4-trifluoromethylnicotinic acid is obtained through acidification and purification.

[0007] Among them, the specific operation of preparing 3-cyano-4-trifluoromethylpyridine from 2,6-dichloro-3-cyano-4-trifluoromethylpyridine is as follows: Add 2,6-dichloro-3-cyano-4-trifluoromethylpyridine and petroleum ether into the reaction kettle, stir and mix them, then add triethylamine and bimetallic catalyst particles, stir and react for 3-4 h under a hydrogen atmosphere, filter and discharge the material, and carry out vacuum distillation on the reaction solution to obtain 3-cyano-4-trifluoromethylpyridine.

[0008] The dosage ratio of 2,6-dichloro-3-cyano-4-trifluoromethylpyridine, petroleum ether, triethylamine and bimetallic catalyst particles is 10-12 g: 100-120 mL: 10-12 g: 1.5-2 g.

[0009] The specific operation of preparing 4-trifluoromethylnicotinic acid from 3-cyano-4-trifluoromethylpyridine is as follows: Add 3-cyano-4-trifluoromethylpyridine, sodium hydroxide ethanol solution with a mass fraction of 30% and absolute ethanol into the reaction kettle, stir and react for 10-12 h under the conditions of nitrogen protection, 80-85 °C and 200-300 r / min, carry out vacuum distillation to remove the solvent to obtain a concentrated solution, adjust the pH value of the concentrated solution to 0.5-1 with hydrochloric acid, then extract with ethyl acetate and deionized water with a volume ratio of 1: 1-2 for 3-5 times, combine the organic phases, rotate and evaporate to remove ethyl acetate, wash the remaining solid with acetonitrile for 2-3 times, and vacuum dry to constant weight to obtain 4-trifluoromethylnicotinic acid.

[0010] The dosage ratio of 3-cyano-4-trifluoromethylpyridine, sodium hydroxide ethanol solution and absolute ethanol is 10-15 g: 25-35 g: 70-100 mL.

[0011] Furthermore, the bimetallic catalyst particles are prepared through the following steps: Step 1: Shear and mix the prefabricated slurry and the composite carbon fiber powder attached with nano-silica according to a mass ratio of 100: 3-5 to obtain a primary ceramic slurry. Immerse the polyurethane foam pretreated with alkali solution in the primary ceramic slurry, and transfer it to a high-temperature cracking furnace for sintering to obtain a prefabricated foam ceramic.

[0012] Step 2: Shear and mix the prefabricated slurry and PMMA microspheres as the pore-forming agent in a mass ratio of 100:6 - 10 to obtain a secondary ceramic slurry. Immerse the prefabricated foam ceramic in the secondary ceramic slurry, transfer it to a high-temperature pyrolysis furnace for sintering, cut and form it to obtain foam ceramic carrier particles.

[0013] Step 3: Use ferrous sulfate heptahydrate as the iron source and terephthalic acid as the ligand. Generate iron MOF on the foam ceramic carrier particles by the solvothermal method, then perform an impregnation treatment with a palladium nitrate solution as the palladium source, and then calcine in a reducing atmosphere to obtain bimetallic catalyst particles loaded with porous zero-valent iron and palladium.

[0014] Furthermore, the particle size of the foam ceramic carrier particles is 1 - 3 cm.

[0015] Furthermore, the specific preparation method of the prefabricated foam ceramic in Step 1 is as follows: Immerse the polyurethane foam pretreated with alkali solution in the primary ceramic slurry for 15 - 20 s. After taking it out, blow it with hot air at 40 - 60 °C at a flow rate of 0.8 - 1.2 m / s for 25 - 35 s, and then blow it with room temperature air at 15 - 20 °C at a flow rate of 1.5 - 2 m / s for 50 - 60 s to remove the excess primary ceramic slurry and prevent blockage of through holes. Repeat the operations of impregnating the primary ceramic slurry and blowing 3 - 4 times, and then transfer it to a high-temperature pyrolysis furnace. Under argon protection, heat it at a rate of 1 - 1.5 °C / min to 550 - 600 °C and keep it warm for 2 - 3 h, then heat it at a rate of 3 - 5 °C / min to 1750 - 1800 °C and keep it warm for 1.5 - 2 h, and naturally cool it to room temperature to obtain the prefabricated foam ceramic.

[0016] Furthermore, the specific preparation method of the foam ceramic carrier particles in Step 2 is as follows: Immerse the prefabricated foam ceramic in the secondary ceramic slurry for 20 - 30 s. After taking it out, blow it with hot air at 40 - 60 °C at a flow rate of 0.8 - 1.2 m / s for 20 - 30 s, and then blow it with room temperature air at 15 - 20 °C at a flow rate of 1.5 - 2 m / s for 30 - 40 s to remove the excess secondary ceramic slurry and prevent blockage of through holes. Repeat the operations of impregnating the secondary ceramic slurry and blowing 2 - 3 times, and then transfer it to a high-temperature pyrolysis furnace. In an air atmosphere, heat it at a rate of 1.5 - 2 °C / min to 350 - 400 °C and keep it warm for 2 - 3 h, then heat it at a rate of 3 - 5 °C / min to 1600 - 1650 °C and keep it warm for 1 - 1.5 h, and naturally cool it to room temperature, cut and form it to obtain the foam ceramic carrier particles.

[0017] Furthermore, the specific preparation method of the bimetallic catalyst particles in Step 3 is as follows: Dissolve sodium lauryl sulfate in an ethanol solution of 60 - 70 wt%, add it to a reaction kettle, then add foam ceramic carrier particles, ferrous sulfate heptahydrate, and deionized water, stir at 20 - 30 r / min for 1 - 2 h, then add terephthalic acid, stir and react at 140 - 150 °C for 3 - 4 h, filter, wash the particles and transfer them to a palladium nitrate solution of 5 - 10 wt%, adjust the pH value to 7.5 - 8 with ammonia water, impregnate at 45 - 60 °C for 40 - 60 min, stand and age at 20 - 25 °C for 12 h, filter, dry the particles and transfer them to a tubular furnace, calcine at 700 - 900 °C under a reducing atmosphere for 1 - 1.5 h, and cool naturally to obtain bimetallic catalyst particles.

[0018] Furthermore, the dosage ratio of sodium lauryl sulfate, ethanol solution, foam ceramic carrier particles, ferrous sulfate heptahydrate, deionized water, terephthalic acid, and palladium nitrate solution is 15 - 20 g : 100 - 120 mL : 5 g : 20 - 30 g : 400 - 500 mL : 150 - 200 g : 120 - 150 mL.

[0019] Furthermore, the prefabricated slurry in step one is prepared through the following steps: Ball - mill and mix deionized water, zirconia powder, magnesia powder, zirconium carbide precursor powder, ammonium polyacrylate, non - ionic polyacrylamide, polyvinyl alcohol, and sodium carboxymethyl cellulose to obtain a prefabricated slurry.

[0020] Furthermore, the dosage ratio of deionized water, zirconia powder, magnesia powder, zirconium carbide precursor powder, ammonium polyacrylate, non - ionic polyacrylamide, polyvinyl alcohol, and sodium carboxymethyl cellulose is 100 - 120 : 15 - 20 : 8 - 12 : 10 - 15 : 0.3 - 0.5 : 0.15 - 0.2 : 0.1 - 0.15 : 0.1 - 0.15.

[0021] Furthermore, the zirconium carbide precursor powder is prepared through the following steps: Add zirconium tetrachloride, acetylacetone, and methanol to a reaction kettle, stir at 60 - 70 °C and 500 - 600 r / min for 30 - 40 min, add 1,4 - benzenediol, continue to stir for 1 - 2 h, and perform vacuum distillation to obtain zirconium carbide precursor powder.

[0022] The dosage ratio of zirconium tetrachloride, acetylacetone, methanol, and 1,4 - benzenediol is 100 - 120 g : 500 - 600 mL : 200 - 300 mL : 70 - 80 g.

[0023] Furthermore, the specific preparation steps of the composite carbon fiber powder in step one are as follows: The carbon fiber powder is acidified to obtain pretreated carbon fiber powder. The pretreated carbon fiber powder, 25 wt% ammonia water, and 90 wt% ethanol solution are added to a reaction kettle, ultrasonically dispersed for 3 - 5 min, then tetraethyl orthosilicate is added, and stirred at 30 - 35 °C and 200 - 500 r / min for 2 - 2.5 h, filtered by suction, the filter cake is washed and dried to obtain composite carbon fiber powder.

[0024] Furthermore, the dosage ratio of the pretreated carbon fiber powder, ammonia water, ethanol solution, and tetraethyl orthosilicate is 2 g : 18 - 20 mL : 1 mL : 1 mL.

[0025] The beneficial effects of the present invention are as follows: 1. The synthesis method of the flonicamid intermediate 4 - trifluoromethylnicotinic acid of the present invention uses 2,6 - dichloro - 3 - cyano - 4 - trifluoromethylpyridine as the starting material, undergoes catalytic hydrogenation under the catalysis of bimetallic catalyst particles, and the intermediate 3 - cyano - 4 - trifluoromethylpyridine undergoes cyano hydrolysis reaction in sodium hydroxide ethanol solution, and the target product 4 - trifluoromethylnicotinic acid is obtained through acidification and purification.

[0026] The present invention uses foam ceramic carrier particles as the matrix, ferrous sulfate heptahydrate as the iron source, terephthalic acid as the organic ligand, loads iron metal - organic framework on the surface of the matrix, and then uses palladium nitrate as the palladium source, and prepares bimetallic catalyst particles loaded with zero - valent iron and metallic palladium through heating reduction. And after the organic ligand forms carbon, it can play a supporting role, maintain the porous structure of nano - zero - valent iron, improve the chlorine capture ability of nano - zero - valent iron, slow down the poisoning of the palladium catalyst, thereby prolong the service life of the bimetallic catalyst and facilitate the continuous production of 4 - trifluoromethylnicotinic acid.

[0027] 2. The foam ceramic carrier particles of the present invention are prepared by the method of secondary impregnation of ceramic slurry. The primary ceramic slurry contains modified carbon fiber powder, and sintering under argon protection prevents the decomposition of carbon components. Nano - silica is attached to the surface of the modified carbon fiber powder, which helps to improve its bonding force with the pre - formed foam ceramic, improve the strengthening and toughening effects, and thus improve the mass retention rate of the bimetallic catalyst. The secondary ceramic slurry contains pore - forming agents, and sintering in an air atmosphere can increase the surface roughness of the foam ceramic carrier particles, thereby increasing the loading amount of catalytic active substances and further improving the catalytic hydrogenation effect of the bimetallic catalyst. Specific embodiments

[0028] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.

[0029] Example 1: This example provides a method for synthesizing the flonicamid intermediate 4-trifluoromethylnicotinic acid, which includes the following steps: Step S1: Add carbon fiber powder with a length of 0.3 mm and hydrochloric acid with a concentration of 1 mol / L into the reaction kettle according to a mass ratio of 1:8, keep warm at 110 °C for 2.5 h, perform suction filtration, wash the filter cake with deionized water until the last washing liquid is neutral, and dry to constant weight to obtain pretreated carbon fiber powder.

[0030] Add 2 kg of pretreated carbon fiber powder, 18 L of ammonia water with a mass fraction of 25% and 1 L of ethanol solution with a mass fraction of 90% into the reaction kettle, perform ultrasonic dispersion for 3 min, then add 1 L of tetraethyl orthosilicate, stir at 30 °C and 200 r / min for 2 h, perform suction filtration, wash the filter cake with deionized water until the last washing liquid is neutral, and dry to constant weight to obtain composite carbon fiber powder.

[0031] Step S2: Add 10 kg of zirconium tetrachloride, 50 L of acetylacetone and 20 L of methanol into the reaction kettle, stir at 60 °C and 500 r / min for 30 min, add 7 kg of 1,4-benzenediol into the reaction kettle, and continue to stir at 60 °C and 500 r / min for 1 h, then perform vacuum distillation to obtain zirconium carbide precursor powder.

[0032] Step S3: Add 10 kg of deionized water, 1.5 kg of zirconia powder, 0.8 kg of magnesia powder, 1 kg of zirconium carbide precursor powder, 0.03 kg of ammonium polyacrylate as a dispersant, 0.015 kg of non-ionic polyacrylamide as a thickener, 0.01 kg of polyvinyl alcohol as a binder and 0.01 kg of sodium carboxymethylcellulose into a planetary ball mill, use silicon nitride balls as grinding balls, and ball mill at 350 r / min for 2.5 h to obtain a precast slurry.

[0033] Step S4: Immerse the macroporous polyurethane foam in a sodium hydroxide solution with a mass fraction of 20% for 10 h, take it out and dry it to constant weight under vacuum to obtain polyurethane foam pretreated with alkali solution.

[0034] Shear and mix the precast slurry and the composite carbon fiber powder according to a mass ratio of 100:3 to obtain a primary ceramic slurry.

[0035] The polyurethane foam pretreated with lye is impregnated in the primary ceramic slurry for 15 s. After taking it out, hot air at 40 °C is used to blow it for 25 s at a flow rate of 0.8 m / s, and then room-temperature air at 15 °C is used to blow it for 50 s at a flow rate of 1.5 m / s to remove the excess primary ceramic slurry and prevent blockage of the through holes. The operations of impregnating the primary ceramic slurry and blowing are repeated 3 times, and then it is transferred to a high-temperature cracking furnace. Under argon protection, it is heated to 550 °C at a rate of 1 °C / min and held for 2 h, then heated to 1750 °C at a rate of 3 °C / min and held for 1.5 h, and naturally cooled to room temperature to obtain the prefabricated foam ceramic.

[0036] Step S5: The prefabricated slurry and PMMA microspheres used as a pore-forming agent are shear-mixed at a mass ratio of 100:6 to obtain the secondary ceramic slurry.

[0037] The prefabricated foam ceramic is impregnated in the secondary ceramic slurry for 20 s. After taking it out, hot air at 40 °C is used to blow it for 20 s at a flow rate of 0.8 m / s, and then room-temperature air at 15 °C is used to blow it for 30 s at a flow rate of 1.5 m / s to remove the excess secondary ceramic slurry and prevent blockage of the through holes. The operations of impregnating the secondary ceramic slurry and blowing are repeated 2 times, and then it is transferred to a high-temperature cracking furnace. Under an air atmosphere, it is heated to 350 °C at a rate of 1.5 °C / min and held for 2 h, then heated to 1600 °C at a rate of 3 °C / min and held for 1 h, and naturally cooled to room temperature and cut into shape to obtain foam ceramic carrier particles with a particle size of 1 cm.

[0038] Step S6: 15 kg of sodium dodecyl sulfate as a surfactant is dissolved in 100 L of an ethanol solution with a mass fraction of 60% and added to a reaction kettle. Then, 5 kg of foam ceramic carrier particles, 20 kg of ferrous sulfate heptahydrate, and 400 L of deionized water are added. It is stirred for 1 h under the condition of 20 r / min, and then 150 kg of terephthalic acid is added. It is stirred and reacted for 3 h at 140 °C, filtered, and the particles are washed 2 times with deionized water and transferred to 12 L of a palladium nitrate solution with a mass fraction of 5%. The pH value is adjusted to 7.5 with ammonia water, impregnated at 45 °C for 40 min, then left to age at 20 °C for 12 h, filtered again, the particles are vacuum dried to a constant weight and transferred to a tubular furnace, and calcined at 900 °C for 1 h under a reducing atmosphere, where the reducing atmosphere includes hydrogen and argon with a volume ratio of 3:7, and naturally cooled to room temperature to obtain bimetallic catalyst particles loaded with porous zero-valent iron and palladium.

[0039] Step S7: 10 kg of 2,6-dichloro-3-cyano-4-trifluoromethylpyridine and 100 L of petroleum ether are added to a reaction kettle and stirred and mixed. Then, 10 kg of triethylamine and 1.5 kg of bimetallic catalyst particles are added. It is stirred and reacted for 3 h under a hydrogen atmosphere, filtered and discharged, and the reaction solution is distilled under reduced pressure to obtain 3-cyano-4-trifluoromethylpyridine.

[0040] 1 kg of 3-cyano-4-trifluoromethylpyridine, 2.5 kg of a 30% sodium hydroxide ethanol solution, and 7 L of absolute ethanol were added to a reaction kettle. The mixture was stirred and reacted for 10 h under nitrogen protection at 80 °C and 200 r / min. The solvent was removed by vacuum distillation to obtain a concentrated solution. The pH value of the concentrated solution was adjusted to 0.5 with hydrochloric acid, and then extracted 3 times with ethyl acetate and deionized water in a volume ratio of 1:1. The organic phases were combined, and ethyl acetate was removed by rotary evaporation. The remaining solid was washed twice with acetonitrile and dried to a constant weight under vacuum to obtain 4-trifluoromethylnicotinic acid.

[0041] Example 2: This example provides a method for synthesizing 4-trifluoromethylnicotinic acid, an intermediate of flonicamid, which includes the following steps: Step S1: Carbon fiber powder with a length of 0.4 mm and hydrochloric acid with a concentration of 1 mol / L were added to a reaction kettle in a mass ratio of 1:9, and kept warm at 115 °C for 3 h. Then, filtration was carried out. The filter cake was washed with deionized water until the last washing liquid was neutral, and dried to a constant weight to obtain pretreated carbon fiber powder.

[0042] 2 kg of pretreated carbon fiber powder, 19 L of a 25% ammonia water solution, and 1 L of a 90% ethanol solution were added to a reaction kettle, ultrasonically dispersed for 4 min, and then 1 L of tetraethyl orthosilicate was added. The mixture was stirred at 32.5 °C and 350 r / min for 2.25 h. Filtration was carried out. The filter cake was washed with deionized water until the last washing liquid was neutral, and dried to a constant weight to obtain composite carbon fiber powder.

[0043] Step S2: 11 kg of zirconium tetrachloride, 55 L of acetylacetone, and 25 L of methanol were added to a reaction kettle and stirred at 65 °C and 550 r / min for 35 min. 7.5 kg of 1,4-benzenediol was added to the reaction kettle, and stirring was continued at 65 °C and 550 r / min for 1.5 h. Vacuum distillation was carried out to obtain zirconium carbide precursor powder.

[0044] 11 kg of deionized water, 1.75 kg of zirconia powder, 1 kg of magnesia powder, 1.25 kg of zirconium carbide precursor powder, 0.04 kg of ammonium polyacrylate as a dispersant, 0.0175 kg of non-ionic polyacrylamide as a thickener, 0.0125 kg of polyvinyl alcohol as a binder, and 0.0125 kg of sodium carboxymethylcellulose were added to a planetary ball mill. Silicon nitride balls were used as grinding balls, and ball milling was carried out at 375 r / min for 2.75 h to obtain a prefabricated slurry.

[0045] Step S4: Immerse the macroporous polyurethane foam in a sodium hydroxide solution with a mass fraction of 20% for 11 h. After taking it out, vacuum dry it to a constant weight to obtain the polyurethane foam pretreated with the lye.

[0046] Shear-mix the prefabricated slurry and the composite carbon fiber powder according to a mass ratio of 100:4 to obtain the primary ceramic slurry.

[0047] Immerse the polyurethane foam pretreated with the lye in the primary ceramic slurry for 17.5 s. After taking it out, blow it with hot air at 50 °C at a flow rate of 1 m / s for 30 s, and then blow it with room-temperature air at 17.5 °C at a flow rate of 1.75 m / s for 55 s to remove the excess primary ceramic slurry and prevent blockage of the through holes. Repeat the operations of immersing in the primary ceramic slurry and blowing 3.5 times. Then transfer it to a high-temperature cracking furnace. Under argon protection, heat it to 575 °C at a rate of 1.25 °C / min and hold for 2.5 h, and then heat it to 1775 °C at a rate of 4 °C / min and hold for 1.75 h. Naturally cool it to room temperature to obtain the prefabricated foam ceramic.

[0048] Step S5: Shear-mix the prefabricated slurry and PMMA microspheres used as a pore-forming agent according to a mass ratio of 100:8 to obtain the secondary ceramic slurry.

[0049] Immerse the prefabricated foam ceramic in the secondary ceramic slurry for 25 s. After taking it out, blow it with hot air at 50 °C at a flow rate of 1 m / s for 25 s, and then blow it with room-temperature air at 17.5 °C at a flow rate of 1.75 m / s for 35 s to remove the excess secondary ceramic slurry and prevent blockage of the through holes. Repeat the operations of immersing in the secondary ceramic slurry and blowing 2.5 times. Then transfer it to a high-temperature cracking furnace. In an air atmosphere, heat it to 375 °C at a rate of 1.75 °C / min and hold for 2.5 h, and then heat it to 1625 °C at a rate of 4 °C / min and hold for 1.25 h. Naturally cool it to room temperature and cut it into shape to obtain the foam ceramic carrier particles with a particle size of 2 cm.

[0050] Step S6: Dissolve 17.5 kg of sodium dodecyl sulfate as a surfactant in 110 L of an ethanol solution with a mass fraction of 65%, add it to the reaction kettle, then add 5 kg of foam ceramic carrier particles, 25 kg of ferrous sulfate heptahydrate and 450 L of deionized water, stir for 1.5 h under the condition of 25 r / min, then add 175 kg of terephthalic acid, stir and react for 3.5 h under the condition of 145 °C, filter, wash the particles with deionized water 2.5 times and transfer them to 13.5 L of a palladium nitrate solution with a mass fraction of 7.5%, adjust the pH value to 7.75 with ammonia water, impregnate at 52.5 °C for 50 min, then stand and age at 22.5 °C for 12 h, filter again, vacuum dry the particles to constant weight and transfer them to a tubular furnace, roast at 800 °C for 1.25 h under a reducing atmosphere, where the reducing atmosphere includes hydrogen and argon with a volume ratio of 3:7, and cool naturally to room temperature to obtain bimetallic catalyst particles loaded with porous zero-valent iron and palladium.

[0051] Step S7: Add 11 kg of 2,6-dichloro-3-cyano-4-trifluoromethylpyridine and 110 L of petroleum ether to the reaction kettle and stir to mix, then add 11 kg of triethylamine and 1.75 kg of bimetallic catalyst particles, stir and react for 3.5 h under a hydrogen atmosphere, filter and discharge the material, and subject the reaction solution to vacuum distillation to obtain 3-cyano-4-trifluoromethylpyridine.

[0052] Add 1.25 kg of 3-cyano-4-trifluoromethylpyridine, 3 kg of a sodium hydroxide ethanol solution with a mass fraction of 30% and 8.5 L of absolute ethanol to the reaction kettle, stir and react for 11 h under the conditions of nitrogen protection, 82.5 °C and 250 r / min, remove the solvent by vacuum distillation to obtain a concentrated solution, adjust the pH value of the concentrated solution to 0.75 with hydrochloric acid, then extract 4 times with a mixture of ethyl acetate and deionized water with a volume ratio of 1:1.5, combine the organic phases, rotary evaporate to remove ethyl acetate, wash the remaining solid with acetonitrile 2.5 times, and vacuum dry to constant weight to obtain 4-trifluoromethylnicotinic acid.

[0053] Example 3: This example provides a method for synthesizing 4-trifluoromethylnicotinic acid, an intermediate of flonicamid, which includes the following steps: Step S1: Add carbon fiber powder with a length of 0.5 mm and hydrochloric acid with a concentration of 1 mol / L to the reaction kettle according to a mass ratio of 1:10, keep warm at 120 °C for 3.5 h, filter by suction, wash the filter cake with deionized water until the last washing liquid is neutral, and dry to constant weight to obtain pretreated carbon fiber powder.

[0054] Add 2 kg of pretreated carbon fiber powder, 20 L of ammonia water with a mass fraction of 25%, and 1 L of ethanol solution with a mass fraction of 90% into a reaction kettle, ultrasonically disperse for 5 min, then add 1 L of tetraethyl orthosilicate, and stir at 35 °C and 500 r / min for 2.5 h. Filter by suction, wash the filter cake with deionized water until the last washing liquid is neutral, and dry to constant weight to obtain composite carbon fiber powder.

[0055] Step S2: Add 12 kg of zirconium tetrachloride, 60 L of acetylacetone, and 30 L of methanol into a reaction kettle, stir at 70 °C and 600 r / min for 40 min, add 8 kg of 1,4-benzenediol into the reaction kettle, and continue to stir at 70 °C and 600 r / min for 2 h. Distill under reduced pressure to obtain zirconium carbide precursor powder.

[0056] Step S3: Add 12 kg of deionized water, 2 kg of zirconia powder, 1.2 kg of magnesia powder, 1.5 kg of zirconium carbide precursor powder, 0.05 kg of ammonium polyacrylate as a dispersant, 0.02 kg of non-ionic polyacrylamide as a thickener, 0.015 kg of polyvinyl alcohol as a binder, and 0.015 kg of sodium carboxymethylcellulose into a planetary ball mill, use silicon nitride balls as grinding balls, and ball mill at 400 r / min for 3 h to obtain a precast slurry.

[0057] Step S4: Immerse the macroporous polyurethane foam in a sodium hydroxide solution with a mass fraction of 20% for 12 h, take it out and vacuum dry to constant weight to obtain the polyurethane foam pretreated with alkali solution.

[0058] Shear and mix the precast slurry and the composite carbon fiber powder according to a mass ratio of 100:5 to obtain a primary ceramic slurry.

[0059] Immerse the polyurethane foam pretreated with alkali solution in the primary ceramic slurry for 20 s, take it out and blow it with hot air at 60 °C at a flow rate of 1.2 m / s for 35 s, and then blow it with room temperature air at 20 °C at a flow rate of 2 m / s for 60 s to remove the excess primary ceramic slurry and prevent blockage of through holes. Repeat the operations of immersing in the primary ceramic slurry and blowing 4 times, and then transfer it to a high-temperature pyrolysis furnace. Under argon protection, heat it to 600 °C at a rate of 1.5 °C / min and hold for 3 h, then heat it to 1800 °C at a rate of 5 °C / min and hold for 2 h, and naturally cool to room temperature to obtain a precast foam ceramic.

[0060] Step S5: Shear and mix the precast slurry and PMMA microspheres as a pore-forming agent according to a mass ratio of 100:10 to obtain a secondary ceramic slurry.

[0061] The prefabricated foam ceramics were impregnated in the secondary ceramic slurry for 30 s. After taking them out, they were purged with hot air at 60 °C at a flow rate of 1.2 m / s for 30 s, and then purged with room-temperature air at 20 °C at a flow rate of 2 m / s for 40 s to remove the excess secondary ceramic slurry and prevent blockage of the through holes. The operations of impregnating the secondary ceramic slurry and purging were repeated 3 times, and then they were transferred to a high-temperature pyrolysis furnace. Under an air atmosphere, the temperature was raised to 400 °C at a rate of 2 °C / min and held for 3 h, then the temperature was raised to 1650 °C at a rate of 5 °C / min and held for 1.5 h, and then naturally cooled to room temperature and cut into shape to obtain foam ceramic carrier particles with a particle size of 3 cm.

[0062] Step S6: Dissolve 20 kg of sodium dodecyl sulfate as a surfactant in 120 L of an ethanol solution with a mass fraction of 70% and add it to the reaction kettle. Then add 5 kg of foam ceramic carrier particles, 30 kg of ferrous sulfate heptahydrate, and 500 L of deionized water, and stir for 2 h under the condition of 30 r / min. Then add 200 kg of terephthalic acid and stir and react at 150 °C for 4 h. Filter, wash the particles with deionized water 3 times and transfer them to 15 L of a palladium nitrate solution with a mass fraction of 10%. Adjust the pH value to 8 with ammonia water, impregnate at 60 °C for 60 min, then stand and age at 25 °C for 12 h, filter again, vacuum dry the particles to constant weight and transfer them to a tubular furnace, and calcine at 700 °C under a reducing atmosphere for 1.5 h, where the reducing atmosphere includes hydrogen and argon with a volume ratio of 3:7, and naturally cool to room temperature to obtain bimetallic catalyst particles loaded with porous zero-valent iron and palladium.

[0063] Step S7: Add 12 kg of 2,6-dichloro-3-cyano-4-trifluoromethylpyridine and 120 L of petroleum ether to the reaction kettle and stir to mix. Then add 12 kg of triethylamine and 2 kg of bimetallic catalyst particles, and stir and react under a hydrogen atmosphere for 4 h. Filter and discharge the material, and distill the reaction solution under reduced pressure to obtain 3-cyano-4-trifluoromethylpyridine.

[0064] Add 1.5 kg of 3-cyano-4-trifluoromethylpyridine, 3.5 kg of a sodium hydroxide ethanol solution with a mass fraction of 30%, and 10 L of absolute ethanol to the reaction kettle, and stir and react under nitrogen protection, at 85 °C and 300 r / min for 12 h. Distill off the solvent under reduced pressure to obtain a concentrated solution. Adjust the pH value of the concentrated solution to 1 with hydrochloric acid, and then extract 5 times with a mixture of ethyl acetate and deionized water with a volume ratio of 1:2. Combine the organic phases, rotary evaporate to remove ethyl acetate, wash the remaining solid with acetonitrile 3 times, and vacuum dry to constant weight to obtain 4-trifluoromethylnicotinic acid.

[0065] The macroporous polyurethane foam in the example was purchased from Forsman Technology (Beijing) Co., Ltd., with the product number 9519017, a density of 20 - 28 kg / m3, and a porosity of 85%.

[0066] Comparative Example 1: Based on Example 3, in step S4, the composite carbon fiber powder was replaced with the ordinary carbon fiber powder in step S1, and the remaining steps remained unchanged to prepare bimetallic catalyst particles.

[0067] Comparative Example 2: Based on Example 3, without going through step S5 treatment, in step S6, the foam ceramic support particles were directly replaced with prefabricated foam ceramics of the same specifications as in step S4, and the remaining steps remained unchanged to prepare bimetallic catalyst particles.

[0068] Comparative Example 3: Based on Example 3, in step S6, the foam ceramic support particles were replaced with activated carbon particles of the same mass, and the remaining steps remained unchanged to prepare bimetallic catalyst particles.

[0069] Comparative Example 4: Based on Example 3, the steps of step S6 were adjusted as follows: 5 kg of foam ceramic support particles were washed 3 times with deionized water and transferred to a 15 L palladium nitrate solution with a mass fraction of 10%. The pH value was adjusted to 8 with ammonia water, impregnated at 60 °C for 60 min, then left to age at 25 °C for 12 h, filtered again, the particles were dried in vacuo to constant weight and transferred to a tubular furnace, and calcined at 700 °C for 1.5 h under a reducing atmosphere, where the reducing atmosphere included hydrogen and argon with a volume ratio of 3:7, and cooled to room temperature naturally to prepare metal catalyst particles loaded with palladium.

[0070] Control group: Directly use a commercially available palladium-carbon catalyst as the catalyst for catalytic hydrogenation.

[0071] Referring to the method in step S7 of Example 3, the catalyst particles in Examples 1 - 3, Comparative Examples 1 - 4, and the control group were respectively applied for continuous production 10 times. The yield of 3-cyano-4-trifluoromethylpyridine was recorded each time, and the mass retention rate of the final catalyst particles was calculated. Mass retention rate = mass after continuous production / initial mass × 100%.

[0072] Table 1 Statistical table of the yield of continuously producing 3-cyano-4-trifluoromethylpyridine

[0073] Table 2 Results table of the mass retention rate of the final catalyst particles

[0074] As can be seen from Table 1 and Table 2, after continuous production using the bimetallic catalyst particles in Examples 1 - 3, the yield of 3-cyano-4-trifluoromethylpyridine remained stable, and the mass retention rate of the final catalyst particles was relatively high.

[0075] The mass retention rate in Comparative Example 1 decreased, possibly because the binding force between the ordinary carbon fiber powder and the matrix was weak, resulting in the fracture of the foam ceramic carrier particles. In Comparative Example 2, there was no secondary slurry impregnation and sintering, so its specific surface area was small, resulting in a decrease in the loading amount of the final catalytic active substance. Moreover, after continuous production, due to the shedding of metal particles, the mass retention rate further decreased. In Comparative Example 3, activated carbon was used as the carrier, and the catalyst stability was poor. Therefore, after continuous production, the yield of 3-cyano-4-trifluoromethylpyridine and the quality of the catalyst particles both decreased significantly. In Comparative Example 4, there was no zero-valent iron loading, lacking the capture of chloride ions. Therefore, the palladium poisoning was accelerated, leading to a decrease in the yield of 3-cyano-4-trifluoromethylpyridine.

[0076] It should be noted that in this text, terms such as "including", "comprising" or any other variants thereof are intended to cover non-exclusive inclusion, so that a process, method, article or device including a series of elements not only includes those elements, but also includes other elements not explicitly listed, or also includes elements inherent to such process, method, article or device.

[0077] Although the embodiments of the present invention have been shown and described, for those of ordinary skill in the art, it can be understood that various changes, modifications, substitutions and variations can be made to these embodiments without departing from the principles and spirit of the present invention.

Claims

1. A synthetic method of flonicamid intermediate 4-trifluoromethylnicotinic acid, the synthetic method comprising: 2,6-dichloro-3-cyano-4-trifluoromethylpyridine is subjected to catalytic hydrogenation under the catalysis of bimetallic catalyst particles, and the intermediate 3-cyano-4-trifluoromethylpyridine undergoes a cyano hydrolysis reaction in a sodium hydroxide ethanol solution, and after acidification and purification, the target product 4-trifluoromethylnicotinic acid is obtained, characterized in that the bimetallic catalyst particles are prepared by the following steps: Step 1: Shear and mix a prefabricated slurry and composite carbon fiber powder attached with nano-silica in a mass ratio of 100:3-5 to obtain a primary ceramic slurry. Immerse the polyurethane foam pretreated with an alkali solution in the primary ceramic slurry, transfer it to a high-temperature pyrolysis furnace for sintering to obtain a prefabricated foam ceramic; Step 2: Shear and mix the prefabricated slurry and PMMA microspheres in a mass ratio of 100:6-10 to obtain a secondary ceramic slurry. Immerse the prefabricated foam ceramic in the secondary ceramic slurry, transfer it to a high-temperature pyrolysis furnace for sintering, cut and shape it to obtain foam ceramic carrier particles; Step 3: Using ferrous sulfate heptahydrate as the iron source and terephthalic acid as the ligand, generate iron MOF on the foam ceramic carrier particles by a solvothermal method, then perform an impregnation treatment with a palladium nitrate solution, and then calcine it in a reducing atmosphere to obtain bimetallic catalyst particles loaded with porous zero-valent iron and palladium.

2. The synthesis method of a flonicamid intermediate 4-trifluoromethylnicotinic acid according to claim 1, characterized in that, The prefabricated slurry in Step 1 is prepared by the following steps: Mix deionized water, zirconia powder, magnesia powder, zirconium carbide precursor powder, ammonium polyacrylate, non-ionic polyacrylamide, polyvinyl alcohol, and sodium carboxymethyl cellulose by ball milling to obtain a prefabricated slurry.

3. The synthetic method of a flonicamid intermediate 4-trifluoromethylnicotinic acid according to claim 2, characterized in that, The dosage ratio of the deionized water, zirconia powder, magnesia powder, zirconium carbide precursor powder, ammonium polyacrylate, non-ionic polyacrylamide, polyvinyl alcohol, and sodium carboxymethyl cellulose is 100-120:15-20:8-12:10-15:0.3-0.5:0.15-0.2:0.1-0.15:0.1-0.

15.

4. The synthesis method of the flonicamid intermediate 4-trifluoromethylnicotinic acid according to claim 3, characterized in that, The zirconium carbide precursor powder is prepared by the following steps: Add zirconium tetrachloride, acetylacetone, and methanol to a reaction kettle, stir at 60-70 °C and 500-600 r / min for 30-40 min, add 1,4-benzenediol, continue to stir for 1-2 h, and perform vacuum distillation to obtain zirconium carbide precursor powder; The dosage ratio of the zirconium tetrachloride, acetylacetone, methanol, and 1,4-benzenediol is 100-120 g:500-600 mL:200-300 mL:70-80 g.

5. The synthetic method of the flonicamid intermediate 4-trifluoromethylnicotinic acid according to claim 1, characterized in that, The specific preparation steps of the composite carbon fiber powder in Step 1 are as follows: After acidifying the carbon fiber powder to obtain pretreated carbon fiber powder, add the pretreated carbon fiber powder, 25 wt% ammonia water, and 90 wt% ethanol solution to a reaction kettle, ultrasonically disperse for 3-5 min, then add tetraethyl orthosilicate, stir at 30-35 °C and 200-500 r / min for 2-2.5 h, filter by suction, wash the filter cake, and dry it to obtain composite carbon fiber powder; The dosage ratio of the pretreated carbon fiber powder, ammonia water, ethanol solution, and tetraethyl orthosilicate is 2 g:18-20 mL:1 mL:1 mL.

6. The synthesis method of the flonicamid intermediate 4-trifluoromethylnicotinic acid according to claim 1, characterized in that, The specific preparation method of the prefabricated foam ceramic in Step 1 is as follows: Immerse the polyurethane foam pretreated with alkali solution in the primary ceramic slurry for 15 - 20 s, take it out and blow to remove the excess primary ceramic slurry. Repeat the operations of immersing in the primary ceramic slurry and blowing 3 - 4 times. Transfer it to a high-temperature cracking furnace. Under the protection of argon, heat it at a rate of 1 - 1.5 °C / min to 550 - 600 °C and keep it warm for 2 - 3 h, then heat it at a rate of 3 - 5 °C / min to 1750 - 1800 °C and keep it warm for 1.5 - 2 h, and then cool it naturally to obtain the prefabricated foam ceramic.

7. A method for synthesizing the flonicamid intermediate 4-trifluoromethylnicotinic acid according to claim 1, characterized in that, The specific preparation method of the foam ceramic carrier particles in Step 2 is as follows: Immerse the prefabricated foam ceramic in the secondary ceramic slurry for 20 - 30 s, take it out and blow to remove the excess secondary ceramic slurry. Repeat the operations of immersing in the secondary ceramic slurry and blowing 2 - 3 times. Transfer it to a high-temperature cracking furnace. In an air atmosphere, heat it at a rate of 1.5 - 2 °C / min to 350 - 400 °C and keep it warm for 2 - 3 h, then heat it at a rate of 3 - 5 °C / min to 1600 - 1650 °C and keep it warm for 1 - 1.5 h, and then cool it naturally and cut it into shape to obtain the foam ceramic carrier particles.

8. The synthesis method of the flonicamid intermediate 4-trifluoromethylnicotinic acid according to claim 7, characterized in that, The particle size of the foam ceramic carrier particles is 1 - 3 cm.

9. The synthesis method of the flonicamid intermediate 4-trifluoromethylnicotinic acid according to claim 1, wherein, The specific preparation method of the bimetallic catalyst particles in Step 3 is as follows: Dissolve sodium dodecyl sulfate in a 60 - 70 wt% ethanol solution and add it to a reaction kettle. Then add the foam ceramic carrier particles, ferrous sulfate heptahydrate and deionized water, stir at 20 - 30 r / min for 1 - 2 h, then add terephthalic acid, stir and react at 140 - 150 °C for 3 - 4 h, filter, wash the particles and transfer them to a 5 - 10 wt% palladium nitrate solution, adjust the pH value to 7.5 - 8 with ammonia water, immerse at 45 - 60 °C for 40 - 60 min, stand and age at 20 - 25 °C for 12 h, filter, dry the particles and transfer them to a tubular furnace, roast them under a reducing atmosphere at 700 - 900 °C for 1 - 1.5 h, and then cool it naturally to obtain the bimetallic catalyst particles.

10. The synthetic method of the flonicamid intermediate 4-trifluoromethylnicotinic acid according to claim 9, characterized in that, The dosage ratio of sodium dodecyl sulfate, ethanol solution, foam ceramic carrier particles, ferrous sulfate heptahydrate, deionized water, terephthalic acid and palladium nitrate solution is 15 - 20 g: 100 - 120 mL: 5 g: 20 - 30 g: 400 - 500 mL: 150 - 200 g: 120 - 150 mL.

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