Production process of bromo-pyrrole nitrile

Abstract

The invention relates to the field of chemical synthesis, in particular to a production process of bromo-pyrrole nitrile, which comprises the following steps: in a micro-channel reactor, activating p-chlorophenylglycine by using trifluoroacetic acid and phosphorus trichloride, and cyclizing under the catalysis of a bifunctional nano catalyst ZrO2atSBA-15-NH2 to generate a first intermediate; condensing the first intermediate and 2-chloroacrylonitrile to form a second intermediate; then through an electrolytic bromination technology, taking hydrogen bromide as a bromine source, and realizing accurate bromination of alpha-position of a pyrrole ring under the synergistic effect of hydrogen peroxide; and finally cooling, crystallizing and purifying through a methanol program to obtain a final product. Through the design of a mesoporous carrier loaded bifunctional catalyst, reaction site activation and acidic byproduct neutralization are synchronously realized; the electrolysis process replaces traditional liquid bromine bromination, and bromination side reaction is effectively avoided; and the process solvent can be recycled, the catalyst can be reused, and the method has high selectivity, safety and environmental friendliness.

Description

Technical Field

[0001] The present invention relates to the field of chemical synthesis, and particularly to a production process of bromopyruvonitrile. Background Art

[0002] Bromopyruvonitrile (4-bromo-2-(4-chlorophenyl)-5-trifluoromethyl-1H-pyrrole-3-carbonitrile) is a core intermediate for synthesizing the highly efficient insecticide chlorfenapyr. The bromine atom at the α-position of the pyrrole ring in its molecular structure endows the product with significant biological activity. With the increasing resistance of global agricultural pests to pesticides and the growing demand for green pesticides, the efficient synthesis of this compound has become a research hotspot in the field of fine chemicals.

[0003] However, there are still some defects in the current synthesis process of bromopyruvonitrile. The current mainstream method uses p-chlorophenylglycine as the starting material, which is phosphorylated by phosphorus trichloride to generate an acyl chloride intermediate, and then cyclized with acrylonitrile derivatives to construct a pyrroline skeleton. Finally, the product is prepared through a bromination reaction. This process has the following problems: 1. The reaction between phosphorus trichloride and carboxylic acid is highly exothermic, which causes phosphorus trichloride to be easily hydrolyzed to produce HCl. While triggering the decomposition of raw materials, the accumulated HCl will catalyze the hydrolysis of the acyl chloride intermediate, resulting in a sharp drop in the yield; 2. Most of the existing technologies use homogeneous Lewis acid catalysts, which cannot inhibit the self-polymerization and ring-opening side reactions of 2-chloropropionitrile, leading to a large number of side reactions and thus affecting the yield and purity; 3. High-selectivity electrophilic reagents are required for α-bromination of the pyrrole ring. Traditional processes rely on liquid bromine or N-bromosuccinimide. Liquid bromine has strong corrosiveness, volatility, and high toxicity. It is prone to cause competitive bromination during operation, and the treatment cost of bromine-containing waste liquid is high. Although N-bromosuccinimide has good selectivity, it is expensive. Summary of the Invention

[0004] To solve the foregoing technical problems, the present invention provides a production process of bromopyruvonitrile, which solves the problems of low yield and purity caused by multiple side reactions in the synthesis of traditional bromopyruvonitrile through the synergistic effect of catalysts and an electrolytic bromination process. Specifically, it is achieved through the following technical solutions.

[0005] A production process of bromopyruvonitrile according to the present invention specifically includes the following steps: Step 1: In a microchannel reactor, react p-chlorophenylglycine with trifluoroacetic acid and phosphorus trichloride in the presence of a bifunctional nanocatalyst ZrO2@SBA-15-NH2, and obtain a first intermediate through post-treatment; Step 2: In an enamel reaction kettle, react the first intermediate with 2-chloropropionitrile in the presence of a bifunctional nanocatalyst ZrO2@SBA-15-NH2, and obtain a second intermediate through vacuum distillation; Step 3: In the electrolytic cell, the second intermediate is subjected to constant-current electrolytic bromination reaction with HBr solution and aqueous hydrogen peroxide solution, and after post-treatment, the crude product of bromopyrrolecarbonitrile is obtained; Step 4: The crude product of bromopyrrolecarbonitrile is recrystallized in methanol to obtain bromopyrrolecarbonitrile.

[0006] Preferably, the preparation method of the bifunctional nanocatalyst ZrO2@SBA-15-NH2 includes the following steps: S1: Dissolve the template agent P123 in HCl solution, add tetraethyl orthosilicate, and obtain the SBA-15 support after hydrothermal reaction; S2: Introduce 3-aminopropyltriethoxysilane into the SBA-15 support to obtain the SBA-15-NH2 support; S3: Immerse the SBA-15-NH2 support in a zirconium salt solution, and obtain ZrO2@SBA-15-NH2 after drying and calcination.

[0007] Preferably, in step S1, the mass ratio of the template agent P123, HCl solution, and tetraethyl orthosilicate is 1-1.5:30.0-45.2:2-3.1; in step S2, the addition amount of 3-aminopropyltriethoxysilane is 0.2-0.3 times the mass of the template agent P123.

[0008] Preferably, in step 1, the addition amount of the bifunctional nanocatalyst is 10%-15% of the mass of trifluoroacetic acid, and the mass fraction of zirconium ions in the zirconium salt solution is 10%.

[0009] Preferably, step 1 specifically includes: Reaction temperature control: Maintain at 12°C-18°C when dropping trifluoroacetic acid, and raise the temperature to 55°C-65°C after dropping phosphorus trichloride; Post-treatment process: Remove acetonitrile by vacuum distillation, add toluene and deionized water, let it stand for liquid separation, take the organic phase and perform toluene desolvation to obtain the first intermediate, and recover the catalyst in the aqueous phase.

[0010] Preferably, in step 1, the dropping time of trifluoroacetic acid is 30-60 minutes, and the dropping time of phosphorus trichloride is 60-90 minutes; the mass ratio of p-chlorophenylglycine, acetonitrile, trifluoroacetic acid, and phosphorus trichloride is 1:7-10:0.7-0.8:0.85-0.95.

[0011] Preferably, step 2 specifically includes: Dissolve the first intermediate in N,N-dimethylformamide, and drop 2-chloropropionitrile at 5°C-10°C for 30-40 minutes; After adding the catalyst, raise the temperature to 35°C-40°C and react for 2-2.5 hours; The conditions for removing the solvent by vacuum distillation are: pressure -0.12 MPa to -0.1 MPa, temperature 45°C to 50°C.

[0012] Preferably, in step 2, the mass ratio of the first intermediate, N,N-dimethylformamide, and 2-chloropropionitrile is 1:10-12:0.4-0.45.

[0013] Preferably, the conditions for electrolytic bromination in step 3 include: The electrolytic cell temperature is 10°C - 15°C; The anode material is ruthenium-plated titanium, and the cathode material is graphite; The voltage is 3.0V - 5.0V, and the current density is 10 mA / cm 2 - 15 mA / cm 2 ; The concentration of the HBr solution is 30%, and the concentration of the aqueous hydrogen peroxide solution is 30%.

[0014] Preferably, step 4 specifically includes: The amount of methanol used is 7 - 9 times the mass of the crude bromopyrrolecarbonitrile; The dissolution temperature is 60°C - 70°C, the crystallization cooling rate is 1°C / min, and the end temperature is 5°C - 10°C; The drying temperature is 40°C - 50°C.

[0015] After adopting the above technical solutions, the beneficial effects of the present invention are: 1. The bifunctional catalyst has a synergistic effect. By using the self-made ZrO2@SBA-15-NH2 nano-catalyst, the amino sites of the mesoporous support (SBA-15-NH2) adsorb and neutralize HCl, inhibiting the acid-catalyzed side reaction; at the same time, the ZrO2 active component coordinates with the acyl chloride carbonyl group, enhancing the carbon positive charge and accelerating the intramolecular cyclization.

[0016] 2. Electrolytic bromination realizes precise substitution. By adopting the constant current electrolysis and hydrogen peroxide synergistic oxidation bromination process, using HBr as the bromine source, bromide ions are in-situ oxidized to active bromine substances at the ruthenium-plated titanium anode, combined with the enhanced oxidation efficiency of hydrogen peroxide, precisely targeting the α-position bromination of the pyrrole ring.

[0017] 3. The microchannel reactor is used to strengthen the process control. Relying on its high mass transfer and heat transfer efficiency, the precise control of the reaction temperature is realized, and the dropping time of trifluoroacetic acid and phosphorus trichloride is controlled respectively, effectively inhibiting the side reactions caused by the hydrolysis of phosphorus trichloride and local overheating.

[0018] 4. Electrolytic bromination replaces liquid bromine, eliminating the use of high-risk chemicals from the source, and there is no high-toxicity waste discharge in the whole process; the solvent is recovered and reused by vacuum distillation, and the catalyst can be recycled after aqueous phase filtration and drying, effectively reducing costs. Specific Embodiments

[0019] The features and exemplary embodiments of various aspects of the present invention will be described in detail below. In order to make the objectives, technical solutions and advantages of the present invention clearer and more understandable, the present invention will be further described in detail below in conjunction with specific embodiments. It should be understood that the specific embodiments described herein are only configured to explain the present invention and are not configured to limit the present invention. For those skilled in the art, the present invention can be implemented without some of these specific details. The following description of the embodiments is only to provide a better understanding of the present invention by showing examples of the present invention.

[0020] An embodiment of the present invention provides a production process for bromopyronitrile, which specifically includes the following steps.

[0021] Step 1: Add a mixture of p-chlorophenylglycine and acetonitrile to a microchannel reactor, start the circulating cooling system to control the temperature of the microchannel reactor at 12°C to 18°C, then dropwise add trifluoroacetic acid to the microchannel reactor. After the addition is completed, add the bifunctional nanocatalyst ZrO2@SBA-15-NH2, and then dropwise add phosphorus trichloride into the microchannel reactor. After the addition is completed, raise the temperature to 55°C to 65°C and react for 2.5 hours to 3 hours.

[0022] After the reaction is completed, distill off acetonitrile under reduced pressure, add toluene and deionized water, let it stand and separate layers at 30°C to 40°C, and take the organic phase to remove toluene by desolvation to obtain the first intermediate.

[0023] Among them, the mass ratio of added p-chlorophenylglycine, acetonitrile, trifluoroacetic acid, and phosphorus trichloride is 1:7 to 10:0.7 to 0.8:0.85 to 0.95.

[0024] Among them, the dropping processes of trifluoroacetic acid and phosphorus trichloride are both uniform dropping, and the dropping time of trifluoroacetic acid is 30 to 60 minutes, and the dropping time of phosphorus trichloride is 60 to 90 minutes.

[0025] Among them, the bifunctional nanocatalyst is ZrO2@SBA-15-NH2, and its added mass is 10% to 15% of the added mass of trifluoroacetic acid.

[0026] Among them, the preparation method of the bifunctional nanocatalyst ZrO2@SBA-15-NH2 includes the following steps: Step 1: Dissolve the template agent P123 in a 2mol / L HCl solution, heat to 40°C and stir for 24 hours; Step 2: Add tetraethyl orthosilicate to the above solution and hydrothermal react at 100°C for 24 hours; Step 3: Add 3-aminopropyltriethoxysilane to the above solution, stir at 70°C for 5 hours, filter and dry to obtain the SBA-15-NH2 support; Step 4: Immerse the SBA-15-NH2 support in a zirconium salt solution with a zirconium ion mass fraction of 10%, filter it after ultrasonic vibration for 1 hour, dry it in an environment of 120 °C, and obtain the bifunctional nanocatalyst ZrO2@SBA-15-NH2 after calcination at 500 °C for 4 hours.

[0027] Among them, in the above process, the template agent P123 is a non-ionic triblock copolymer with a chemical structure of polyethylene oxide - polypropylene oxide - polyethylene oxide (PEO-PPO-PEO). Its function is that the micelles of the template agent P123 form an ordered template through self-assembly, guiding the inorganic precursor to polymerize around the micelles to generate regular pores, which is beneficial to the construction of the catalyst support.

[0028] Among them, in the preparation process of the above bifunctional nanocatalyst, the mass ratio of the added template agent P123, HCl solution, tetraethyl orthosilicate, and 3-aminopropyltriethoxysilane is: 1 - 1.5:30.0 - 45.2:2 - 3.1, and the addition amount of 3-aminopropyltriethoxysilane is 0.2 - 0.3 times the mass of the template agent P123.

[0029] Among them, the pressure for vacuum distillation removal of acetonitrile is -0.1 MPa to -0.08 MPa, and the temperature is 40 °C to 45 °C. Through the method of vacuum distillation, the solvent acetonitrile can be recovered to realize the recycling of the solvent.

[0030] Among them, during the static stratification process, toluene and deionized water are added in a mass ratio of 4-chlorophenylglycine:toluene:deionized water = 1:5 - 7:4 - 7.

[0031] Among them, the final remaining aqueous phase in the above steps contains the bifunctional nanocatalyst ZrO2@SBA-15-NH2, which can be reused after filtration and drying, and the number of reuse times is less than 4 times.

[0032] In the above reaction steps, during the reaction of 4-chlorophenylglycine, trifluoroacetic acid, and phosphorus trichloride to form the first intermediate, the reaction principle is as follows:

[0033] During the above reaction process, by dropping trifluoroacetic acid, the carboxyl group of 4-chlorophenylglycine is protonated to form a carboxylic acid intermediate with stronger electrophilicity, creating conditions for the subsequent nucleophilic attack of phosphorus trichloride. Phosphorus trichloride reacts with the protonated carboxyl group to generate an acyl chloride intermediate; the precise temperature control effect of the microchannel reactor is adopted in this process, so that the system temperature is in a low-temperature reaction environment, avoiding side reactions caused by subsequent strong exotherm; in addition, low-temperature control can effectively inhibit the hydrolysis of phosphorus trichloride and the accumulation of HCl by-products.

[0034] In the above reaction process, a bifunctional nanocatalyst ZrO2@SBA-15-NH2 was added, and through the modification of the mesoporous support and the design of dual active sites, efficient catalysis was achieved.

[0035] Among them, due to the nano-scale pore diameter and high specific surface area of the SBA-15-NH2 support itself, it has a huge loading space, which can effectively promote the diffusion of reactants. At the same time, the mesoporous channels can limit the spatial orientation of reactants and improve the regioselectivity of cyclization; moreover, the surface amination of the SBA-15-NH2 support, and its basic sites can adsorb the HCl generated in the reaction, inhibit the acid-catalyzed side reaction, and stabilize the intermediate; in addition, as an active component, zirconium ions coordinate with the carbonyl oxygen of acyl chloride, enhancing the positive charge of carbon, thereby accelerating the intramolecular nucleophilic cyclization.

[0036] In the above reaction steps, through the combination of a microchannel reactor and a bifunctional catalyst, the generation of reaction by-products was reduced, the safe progress of the reaction was ensured, and the product yield was improved; at the same time, through efficient mass transfer and heat transfer, the reaction time was effectively shortened and the production efficiency was increased.

[0037] Step 2: Dissolve the first intermediate in N,N-dimethylformamide and then add it to a glass-lined reaction kettle. Adjust the temperature to 5°C - 10°C, and slowly dropwise add 2-chloropropionitrile to the reaction kettle at a constant speed. After the dropwise addition is completed, add the bifunctional nanocatalyst ZrO2@SBA-15-NH2, raise the temperature to 35°C - 40°C, and after reacting for 2 - 2.5 hours, remove N,N-dimethylformamide by vacuum distillation to obtain the second intermediate.

[0038] Among them, N,N-dimethylformamide and 2-chloropropionitrile are added in a ratio of the first intermediate:N,N-dimethylformamide:2-chloropropionitrile = 1:10 - 12:0.4 - 0.45 by mass ratio.

[0039] Among them, the dropwise addition time of 2-chloropropionitrile is 30 - 40 minutes.

[0040] Among them, the pressure for vacuum removal of N,N-dimethylformamide is -0.12 MPa - -0.1 MPa, and the temperature is 45°C - 50°C.

[0041] Among them, the addition amount of the bifunctional nanocatalyst ZrO2@SBA-15-NH2 is the same as that in Step 1.

[0042] In the above reaction steps, in the process of producing the second intermediate from the first intermediate and 2-chloropropionitrile obtained in Step 1, the reaction principle is as follows:

[0043] During the above reaction process, through the intramolecular cyclization of the first intermediate with 2-chloropropionitrile, a second intermediate is formed. 2-chloropropionitrile is added dropwise in a low-temperature environment to avoid self-polymerization of 2-chloropropionitrile and slow down its addition side reaction.

[0044] In addition, adding the ZrO2@SBA-15-NH2 bifunctional nanocatalyst facilitates the activation of the nitrile group or imine group of the pyrroline ring, enhances the carbon positive charge, and simultaneously neutralizes the HCl generated in the reaction to inhibit the acid-catalyzed ring-opening side reaction.

[0045] Step 3: Add the second intermediate, N,N-dimethylformamide, and HBr solution to the electrolytic cell. Control the temperature of the electrolytic cell at 10°C to 15°C, start constant-current electrolysis, and simultaneously add an aqueous hydrogen peroxide solution dropwise at a uniform speed. After the addition is completed, react for 20 to 30 minutes, raise the temperature to 40°C and stir for 1 hour, distill off N,N-dimethylformamide, add deionized water, cool to 10°C and crystallize for 1.5 hours, and then centrifuge and dry to obtain the crude product of bromopyrrole nitrile.

[0046] Among them, the concentration of the HBr solution is 30%, the concentration of the aqueous hydrogen peroxide solution is 30%, and the dropping time of the aqueous hydrogen peroxide solution is 30 minutes.

[0047] Among them, the second intermediate, N,N-dimethylformamide, 30% aqueous HBr solution, 30% aqueous hydrogen peroxide solution, and deionized water are added in a mass ratio of 1:10 to 13:1 to 1.2:1.1 to 1.3:6 to 8.

[0048] Among them, the material of the anode of the electrolytic cell is titanium-plated ruthenium, the cathode material is graphite, and the effective areas of the anode and cathode are 0.5 m 2 .

[0049] Among them, during the cross-flow electrolysis process, the voltage is 3.0 V to 5.0 V, and the current density is 10 mA / cm 2 ~15 mA / cm 2 .

[0050] For the above reaction steps, the reaction principle of preparing bromopyrrole nitrile through the bromination reaction of the second intermediate is as follows:

[0051] During the above reaction process, bromide ions at the anode of the electrolytic cell are oxidized to active bromine substances, and under the simultaneous oxidation of hydrogen peroxide, the concentration of bromine positive ions in the solution is effectively increased. The active bromine substances and bromine positive ions perform selective electrophilic substitution on the second intermediate to achieve bromination at the α-position of the pyrrole ring, thereby obtaining the final product bromopyrrole nitrile.

[0052] Compared with traditional chemical bromination, this electrolytic bromination process uses hydrogen bromide, a cheap bromine source, as a reactant, reducing production costs and avoiding the use of highly toxic and strongly corrosive liquid bromine. There are no large amounts of harmful substances in the reaction process, making it safer and more environmentally friendly. Selective electrophilic substitution of the second intermediate is carried out by active bromine substances and bromonium ions to accurately achieve bromination at the α-position of the pyrrole ring, reducing the generation of polybrominated by-products. Moreover, by changing and controlling the point parameters, the degree of bromination can be accurately controlled to avoid over-bromination.

[0053] Step 4: Put the crude bromopyrrole nitrile into methanol, heat it to 60°C - 70°C and stir until completely dissolved, then slowly cool it to 5°C - 10°C, keep warm for 2 - 4 hours, and then use a centrifuge for solid-liquid separation to obtain a wet product. Transfer the wet product to an environment of 40°C - 50°C and dry it for 2 - 3 hours to obtain the final product.

[0054] Among them, the mass of methanol used is 7 - 9 times the mass of the crude bromopyrrole nitrile.

[0055] Among them, during the cooling process of the above steps, the cooling rate is 1°C / min.

[0056] During the above steps, crystallization is achieved through the dissolution of bromopyrrole nitrile in methanol and slow temperature reduction. By controlling the temperature, the inclusion of impurities in the crystal is reduced, thereby improving the purity of the final product bromopyrrole nitrile. The drying stage is controlled below 50°C to avoid thermal decomposition of the bromide, thereby improving the product yield.

[0057] For the convenience of further understanding of the present invention, several embodiments and comparative examples of the present invention are given below.

[0058] Example 1 Step 1: Add a mixture of 3.5 kg of p-chlorophenylglycine and 19 kg of acetonitrile to a microchannel reactor, start the circulating cooling system to control the temperature of the microchannel reactor at 15°C, and then uniformly drip 2.6 kg of trifluoroacetic acid into the microchannel reactor over 35 minutes. After the dripping is completed, add 0.3 kg of the bifunctional nanocatalyst ZrO2@SBA-15-NH2, and then uniformly drip 3.2 kg of phosphorus trichloride into the microchannel reactor over 60 minutes. After the dripping is completed, heat it to 60°C and react for 2.5 hours.

[0059] After the reaction is completed, reduce the pressure to -0.1 MPa and distill off acetonitrile at a temperature of 40°C. Add 19 kg of toluene and 20 kg of deionized water, let it stand and separate layers at 35°C, filter and dry the aqueous phase to reuse the bifunctional nanocatalyst, and carry out toluene desolvation on the organic phase to obtain the first intermediate.

[0060] Step 2: Dissolve the first intermediate in 44 kg of N,N-dimethylformamide and then add it to a glass-lined reactor. Adjust the temperature to 5 °C, and slowly add 1.9 kg of 2-chloropropionitrile to the reactor at a constant rate over 30 minutes. After the addition is complete, add 0.3 kg of the bifunctional nanocatalyst ZrO2@SBA-15-NH2, and then raise the temperature to 40 °C. After reacting for 2 hours, reduce the pressure to -0.12 MPa, and distill off N,N-dimethylformamide at 45 °C to obtain the second intermediate.

[0061] Step 3: Add the second intermediate, 50 kg of N,N-dimethylformamide, and 4.0 kg of 30% HBr solution to an electrolytic cell. Control the temperature of the electrolytic cell at 10 °C, start constant current electrolysis with a voltage of 3.0 V and a current density of 10 mA / cm 2 . At the same time, slowly add 4.5 kg of 30% aqueous hydrogen peroxide solution at a constant rate over 30 minutes. After the addition is complete, react for 20 minutes, raise the temperature to 40 °C and stir for 1 hour. Distill off N,N-dimethylformamide, add 25 kg of deionized water, cool to 10 °C and crystallize for 1.5 hours, then centrifuge and dry to obtain the crude product of bromopyrrole nitrile.

[0062] Step 4: Put the crude product of bromopyrrole nitrile into 30 kg of methanol, raise the temperature to 65 °C and stir until completely dissolved. Slowly cool to 5 °C at a rate of 1 °C / min, keep the temperature for 2 hours, then separate the solid and liquid by centrifuge to obtain the wet product. Transfer the wet product to a drying environment at 50 °C for 2 hours to obtain the final product.

[0063] Example 2 This example is based on Example 1, and the dropping time of trifluoroacetic acid and phosphorus trichloride in Step 1 is adjusted. Specifically: Step 1: Add a mixture of 3.5 kg of p-chlorophenylglycine and 19 kg of acetonitrile to a microchannel reactor. Start the circulating cooling system to control the temperature of the microchannel reactor at 15 °C. Then slowly add 2.6 kg of trifluoroacetic acid to the microchannel reactor at a constant rate over 50 minutes. After the addition is complete, add 0.3 kg of the bifunctional nanocatalyst ZrO2@SBA-15-NH2. Subsequently, slowly add 3.2 kg of phosphorus trichloride to the microchannel reactor at a constant rate over 80 minutes. After the addition is complete, raise the temperature to 60 °C and react for 2.5 hours.

[0064] After the reaction is complete, reduce the pressure to -0.1 MPa, and distill off acetonitrile at 40 °C. Add 19 kg of toluene and 20 kg of deionized water, and let it stand for phase separation at 35 °C. Filter and dry the aqueous phase to recycle the bifunctional nanocatalyst. Take the organic phase and remove toluene by evaporation to obtain the first intermediate.

[0065] The remaining steps of this embodiment are exactly the same as those of Embodiment 1.

[0066] Embodiment 3 Based on Embodiment 1, this embodiment adjusts the addition amount of the bifunctional nanocatalyst ZrO2@SBA-15-NH2 in Step 1, specifically: Step 1: Add a mixture of 3.5 kg of p-chlorophenylglycine and 19 kg of acetonitrile into the microchannel reactor. Start the circulating cooling system to control the temperature of the microchannel reactor at 15°C. Subsequently, slowly add 2.6 kg of trifluoroacetic acid to the microchannel reactor at a constant rate. The dropping time is 35 minutes. After the dropping is completed, add 0.35 kg of the bifunctional nanocatalyst ZrO2@SBA-15-NH2. Then, slowly add 3.2 kg of phosphorus trichloride to the microchannel reactor at a constant rate. The dropping time is 60 minutes. After the dropping is completed, raise the temperature to 60°C and react for 2.5 hours.

[0067] After the reaction is completed, reduce the pressure to -0.1 MPa and distill off acetonitrile at a temperature of 40°C. Add 19 kg of toluene and 20 kg of deionized water, and let it stand and separate layers at 35°C. Filter and dry the aqueous phase to obtain the reused bifunctional nanocatalyst. Take the organic phase and perform toluene desolvation to obtain the first intermediate.

[0068] The remaining steps of this embodiment are exactly the same as those of Embodiment 1.

[0069] Embodiment 4 Based on Embodiment 1, this embodiment adjusts the dropping time of 2-chloropropionitrile in Step 2, specifically: Step 2: Dissolve the first intermediate in 44 kg of N,N-dimethylformamide and then add it to the glass-lined reaction kettle. Adjust the temperature to 5°C. Slowly add 1.9 kg of 2-chloropropionitrile to the reaction kettle at a constant rate. The dropping time is: 40 minutes. After the dropping is completed, add 0.3 kg of the bifunctional nanocatalyst ZrO2@SBA-15-NH2. Raise the temperature to 40°C. After reacting for 2 hours, reduce the pressure to -0.12 MPa and distill off N,N-dimethylformamide at a temperature of 45°C to obtain the second intermediate.

[0070] The remaining steps of this embodiment are exactly the same as those of Embodiment 1.

[0071] Embodiment 5 Based on Embodiment 1, this embodiment adjusts the voltage and current density parameters of the constant-current electrolysis in Step 3, specifically: Add the second intermediate, 50 kg of N,N-dimethylformamide, and 4.0 kg of 30% HBr solution to the electrolytic cell. Control the temperature of the electrolytic cell at 10°C, start constant current electrolysis, with a voltage of 4.0 V and a current density of 12 mA / cm 2 , and simultaneously add 4.5 kg of 30% aqueous hydrogen peroxide solution dropwise at a constant rate. The dropping time is 30 minutes. After the dropping is completed, react for 20 minutes, raise the temperature to 40°C and stir for 1 hour. Distill off N,N-dimethylformamide, add 25 kg of deionized water, cool to 10°C and crystallize for 1.5 hours, then centrifuge and dry to obtain the crude product of bromopyruvonitrile.

[0072] The remaining steps of this example are exactly the same as those of Example 1.

[0073] Comparative Example 1 This comparative example is based on Example 1 and adjusts the catalyst in Step 1. Specifically: Step 1: Add a mixture of 3.5 kg of p-chlorophenylglycine and 19 kg of acetonitrile to the microchannel reactor. Start the circulating cooling system to control the temperature of the microchannel reactor at 15°C. Subsequently, add 2.6 kg of trifluoroacetic acid dropwise to the microchannel reactor at a constant rate. The dropping time is 35 minutes. After the dropping is completed, add 0.3 kg of AlCl3, and then add 3.2 kg of phosphorus trichloride dropwise to the microchannel reactor at a constant rate. The dropping time is 60 minutes. After the dropping is completed, raise the temperature to 60°C and react for 2.5 hours.

[0074] After the reaction is completed, reduce the pressure to -0.1 MPa and distill off acetonitrile at a temperature of 40°C. Add 19 kg of toluene and 20 kg of deionized water, let it stand and separate layers at 35°C, and take the organic phase to remove toluene by desolvation to obtain the first intermediate.

[0075] The remaining steps of this comparative example are exactly the same as those of Example 1.

[0076] Comparative Example 2 This comparative example is based on Example 1 and adjusts the catalyst in Step 2. Specifically: Step 2: Dissolve the first intermediate in 44 kg of N,N-dimethylformamide and then add it to a glass-lined reaction kettle. Adjust the temperature to 5°C, add 1.9 kg of 2-chloropropionitrile dropwise to the reaction kettle at a constant rate. The dropping time is 30 minutes. After the dropping is completed, add 0.3 kg of AlCl3, raise the temperature to 40°C, react for 2 hours, then reduce the pressure to -0.12 MPa and distill off N,N-dimethylformamide at a temperature of 45°C to obtain the second intermediate.

[0077] The remaining steps of this comparative example are exactly the same as those of Example 1.

[0078] Comparative Example 3 This comparative example is based on Example 1 and adjusts the electrolysis process in Step 3. Specifically: Step 3: Add the second intermediate, 50 kg of N,N-dimethylformamide, and 4.0 kg of 30% HBr solution to the reaction kettle. Control the temperature of the reaction kettle at 10°C, and uniformly add 4.5 kg of 30% hydrogen peroxide aqueous solution dropwise. The dropping time is 30 minutes. After the dropping is completed, react for 20 minutes, then raise the temperature to 40°C and stir for 1 hour. Distill off N,N-dimethylformamide, add 25 kg of deionized water, cool down to 10°C and crystallize for 1.5 hours, and then centrifuge and dry to obtain the crude product of bromopyruvonitrile.

[0079] The remaining steps of this comparative example are exactly the same as those of Example 1.

[0080] For the above examples and comparative examples, weigh the masses of the first intermediate, the second intermediate, the crude product of bromopyruvonitrile, and the final product respectively, calculate their corresponding yields respectively, and measure the purity of the final product by high performance liquid chromatography. The data results are statistically as follows:

[0081] According to the above data, it can be seen that: 1. By comparing Comparative Example 1 and Comparative Example 2 with Example 1, the catalytic effects of the bifunctional nanocatalyst ZrO2@SBA-15-NH2 in Step 1 and Step 2 are verified. The traditional catalyst AlCl3 cannot inhibit the by-product HCl, resulting in acid-catalyzed side reactions such as hydrolysis or over-chlorination. And because AlCl3 lacks an amino carrier to neutralize HCl, it will also cause side reactions such as self-polymerization and ring-opening of 2-chloropropionitrile. Therefore, compared with Example 1, the yield of the first intermediate in Comparative Example 1 decreases by 7.2%, and the yield of the second intermediate in Comparative Example 2 decreases by 7.2%.

[0082] 2. By comparing Comparative Example 3 with Example 1, the role of the electrolytic bromination process in Step 3 is verified. In Comparative Example 3, the electrolytic cell is cancelled and only hydrogen peroxide is used for oxidation. As a result, compared with Example 1, the yield of the crude product of bromopyruvonitrile in Comparative Example 3 decreases by 8.5%, and the purity of the final product decreases by 6.6%. The reason is that the cancellation of the electrolysis process leads to the lack of electrochemically in-situ generated active bromine or bromonium ions in the system, resulting in a decrease in bromination selectivity and an increase in by-products.

[0083] 3. In Example 2, extending the dropping time of the reagent can relieve the local overheating caused by strong exotherm, resulting in a slight increase in the overall yield, but the improvement is limited.

[0084] 4. In Example 3, the amount of the catalyst is increased, so that the yields of each step reach the peak value, and the final yield is the highest value of 87.1% among the examples and comparative examples.

[0085] 5. In Example 4, the electrolysis parameters were adjusted by increasing the electrolysis voltage and current density, which can accelerate the oxidation efficiency of bromide ions to a certain extent and slightly increase the yield of crude bromo-pyrrole nitrile.

[0086] In accordance with the embodiments of the present invention as described above, these embodiments do not describe all the details in detail, nor do they limit the invention to only the specific embodiments. Obviously, many modifications and variations can be made according to the above description. These embodiments are selected and specifically described in this specification in order to better explain the principles and practical applications of the present invention, so that those skilled in the art can make good use of the present invention and its modified use based on the present invention. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims

1. A production process of bromopyruvonitrile, characterized in that, It includes the following steps: Step 1: In a microchannel reactor, react p-chlorophenylglycine with trifluoroacetic acid and phosphorus trichloride in the presence of the bifunctional nanocatalyst ZrO2@SBA-15-NH2, and obtain the first intermediate through post-treatment; Step 2: In an enamel reactor, react the first intermediate with 2-chloropropionitrile in the presence of the bifunctional nanocatalyst ZrO2@SBA-15-NH2, and obtain the second intermediate through vacuum distillation; Step 3: In an electrolytic cell, conduct a constant-current electrolytic bromination reaction on the second intermediate with an HBr solution and an aqueous hydrogen peroxide solution, and obtain the crude product of bromopyrrolecarbonitrile through post-treatment; Step 4: Recrystallize the crude product of bromopyrrolecarbonitrile in methanol to obtain bromopyrrolecarbonitrile.

2. The production process of bromopyruvonitrile according to claim 1, characterized in that, The preparation method of the bifunctional nanocatalyst ZrO2@SBA-15-NH2 includes the following steps: S1: Dissolve the template agent P123 in an HCl solution, add tetraethyl orthosilicate, and obtain the SBA-15 support after hydrothermal reaction; S2: Introduce 3-aminopropyltriethoxysilane into the SBA-15 support to obtain the SBA-15-NH2 support; S3: Immerse the SBA-15-NH2 support in a zirconium salt solution, and obtain ZrO2@SBA-15-NH2 after drying and calcination.

3. The production process of bromopyruvonitrile according to claim 2, characterized in that: In step S1, the mass ratio of the template agent P123, the HCl solution, and tetraethyl orthosilicate is 1-1.5:30.0-45.2:2-3.1; in step S2, the addition amount of 3-aminopropyltriethoxysilane is 0.2-0.3 times the mass of the template agent P123.

4. The production process of bromopyruvonitrile according to claim 3, characterized in that: In step 1, the addition amount of the bifunctional nanocatalyst is 10%-15% of the mass of trifluoroacetic acid, and the mass fraction of zirconium ions in the zirconium salt solution is 10%.

5. The production process of bromopyruvonitrile according to claim 1, characterized in that, Step 1 specifically includes: Reaction temperature control: Maintain at 12°C-18°C when dripping trifluoroacetic acid, and raise the temperature to 55°C-65°C after dripping phosphorus trichloride; Post-treatment process: Remove acetonitrile by vacuum distillation, add toluene and deionized water, let it stand for liquid separation, take the organic phase for toluene desolvation to obtain the first intermediate, and recover the catalyst in the aqueous phase.

6. The production process of bromopyruvonitrile according to claim 5, characterized in that: In step 1, the dripping time of trifluoroacetic acid is 30-60 minutes, and the dripping time of phosphorus trichloride is 60-90 minutes; the mass ratio of p-chlorophenylglycine, acetonitrile, trifluoroacetic acid, and phosphorus trichloride is 1:7-10:0.7-0.8:0.85-0.

95.

7. The production process of bromopyruvonitrile according to claim 1, characterized in that, Step 2 specifically includes: Dissolve the first intermediate in N,N-dimethylformamide, and drip 2-chloropropionitrile at 5°C-10°C for 30-40 minutes; After adding the catalyst, raise the temperature to 35°C-40°C and react for 2-2.5 hours; The conditions for vacuum distillation to remove the solvent are: pressure -0.12MPa--0.1MPa, temperature 45°C-50°C.

8. The production process of bromopyronitrile according to claim 7, characterized in that: In step 2, the mass ratio of the first intermediate, N,N-dimethylformamide, and 2-chloropropionitrile is 1:10-12:0.4-0.

45.

9. The production process of bromopyruvonitrile according to claim 1, characterized in that, The conditions for electrolytic bromination in step 3 include: The temperature of the electrolytic cell is 10°C-15°C; The anode material is titanium-plated ruthenium, and the cathode material is graphite; Voltage 3.0V to 5.0V, current density 10mA / cm 2 to 15mA / cm 2 ; The concentration of the HBr solution is 30%, and the concentration of the aqueous hydrogen peroxide solution is 30%.

10. The production process of bromopyruvonitrile according to claim 1, characterized in that, Step 4 specifically includes: The dosage of methanol is 7-9 times the mass of the crude product of bromopyrrolecarbonitrile; Dissolution temperature: 60°C to 70°C, crystallization cooling rate: 1°C / min, end temperature: 5°C to 10°C; Drying temperature: 40°C to 50°C.

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