A process for the production of bromopyrrol nitrile

Abstract

The present application relates to the field of chemical synthesis, and particularly relates to a production process of bromopyrrole nitrile, which is carried out in a micro-channel reactor, and utilizes trifluoroacetic acid and phosphorus trichloride to activate p-chlorophenylglycine, and then cyclizes the first intermediate under the catalysis of a bifunctional nanometer catalyst ZrO2@SBA-15-NH2; then the first intermediate is condensed with 2-chloropropenyl nitrile to form a second intermediate; then through electrolytic bromination technology, hydrogen bromide is used as a bromine source, and precise bromination of the alpha position of the pyrrole ring is realized under the synergistic effect of hydrogen peroxide; finally, the final product is obtained through methanol programmed cooling crystallization purification. Through the design of the mesoporous carrier loaded bifunctional catalyst, the activation of the reaction site and the neutralization of the acidic by-product are simultaneously realized; the electrolytic process replaces the traditional liquid bromine bromination, effectively avoiding the bromination side reaction; and the solvent of the process can be recycled, the catalyst can be reused, and the process has high selectivity, safety and environmental protection.

Description

Technical Field

[0001] The present invention relates to the field of chemical synthesis, and in particular to a production process of bromopyrrole carbonitrile. Background Art

[0002] Bromopyrrolecarbonitrile (4-bromo-2-(4-chlorophenyl)-5-trifluoromethyl-1H-pyrrole-3-carbonitrile) is a core intermediate in the synthesis of the highly effective insecticide chlorfenapyr. The bromine atom at the α-position of the pyrrole ring in its molecular structure imparts significant biological activity to the product. With increasing pesticide resistance in agricultural pests worldwide and growing demand for eco-friendly pesticides, the efficient synthesis of this compound has become a research hotspot in the fine chemical industry.

[0003] However, the current synthesis process for bromopyrrole carbonitrile still has some defects. The current mainstream method uses p-chlorophenylglycine as the starting material, generates an acyl chloride intermediate through phosphorus trichloride chlorination, and then cyclizes with an acrylonitrile derivative to construct a pyrroline skeleton. The product is finally prepared through bromination. This process has the following problems: 1. The reaction of phosphorus trichloride with carboxylic acid is highly exothermic, causing phosphorus trichloride to hydrolyze to produce HCl. While triggering the decomposition of the raw material, the accumulated HCl catalyzes the hydrolysis of the acyl chloride intermediate, resulting in a sharp drop in yield. 2. The existing technology mostly uses homogeneous Lewis acid catalysts, which cannot inhibit the self-polymerization and ring-opening side reactions of 2-chloroacrylonitrile, resulting in a large number of side reactions, which in turn affect the yield and purity. 3. α-Bromonation of the pyrrole ring requires a highly selective electrophilic reagent. Traditional processes rely on liquid bromine or N-bromosuccinimide. Liquid bromine is highly corrosive, volatile, and highly toxic, which easily causes competitive bromination during operation. The treatment cost of bromine-containing wastewater is high. Although N-bromosuccinimide has good selectivity, it is expensive. Summary of the Invention

[0004] In order to solve the aforementioned technical problems, the present invention provides a production process for bromopyrrole carbonitrile, which solves the problems of low yield and purity caused by many side reactions in the traditional synthesis of bromopyrrole carbonitrile by using catalyst synergistic enhancement and electrolytic bromination process. The production process is specifically achieved through the following technical solutions.

[0005] The present invention provides a production process for bromopyrrole carbonitrile, which specifically comprises the following steps:

[0006] Step 1: In a microchannel reactor, p-chlorophenylglycine is reacted with trifluoroacetic acid and phosphorus trichloride in the presence of a bifunctional nanocatalyst ZrO2@SBA-15-NH2, and the first intermediate is obtained after post-treatment;

[0007] Step 2: In a glass-lined reactor, the first intermediate is reacted with 2-chloroacrylonitrile in the presence of a bifunctional nanocatalyst ZrO2@SBA-15-NH2, and the second intermediate is obtained by vacuum distillation;

[0008] Step 3: In an electrolytic cell, the second intermediate is subjected to a constant current electrolytic bromination reaction with an HBr solution and an aqueous hydrogen peroxide solution, and a crude bromopyrrolecarbonitrile product is obtained through post-treatment;

[0009] Step 4: Recrystallize the crude bromopyrrolecarbonitrile from methanol to obtain bromopyrrolecarbonitrile.

[0010] Preferably, the preparation method of the bifunctional nanocatalyst ZrO2@SBA-15-NH2 comprises the following steps:

[0011] S1: Dissolve the template P123 in HCl solution, add ethyl orthosilicate, and obtain the SBA-15 support after hydrothermal reaction;

[0012] S2: introducing aminopropyltriethoxysilane into the SBA-15 support to obtain the SBA-15-NH2 support;

[0013] S3: The SBA-15-NH2 support is impregnated in a zirconium salt solution, and then dried and calcined to obtain ZrO2@SBA-15-NH2.

[0014] Preferably, in step S1, the mass ratio of template P123, HCl solution, and ethyl orthosilicate is 1-1.5:30.0-45.2:2-3.1; and in step S2, the amount of aminopropyltriethoxysilane added is 0.2-0.3 times the mass of template P123.

[0015] Preferably, the amount of the bifunctional nanocatalyst added in step 1 is 10% to 15% of the mass of trifluoroacetic acid, and the mass proportion of zirconium ions in the zirconium salt solution is 10%.

[0016] Preferably, step 1 specifically includes:

[0017] Reaction temperature control: maintain 12℃~18℃ when adding trifluoroacetic acid, and raise the temperature to 55℃~65℃ after adding phosphorus trichloride;

[0018] Post-treatment process: acetonitrile is removed by vacuum distillation, toluene and deionized water are added and allowed to stand for stratification, the organic phase is taken for toluene desolventizing to obtain the first intermediate, and the catalyst in the aqueous phase is recovered.

[0019] Preferably, in step 1, the time for adding trifluoroacetic acid dropwise is 30 to 60 minutes, and the time for adding phosphorus trichloride dropwise is 60 to 90 minutes; the mass ratio of p-chlorophenylglycine, acetonitrile, trifluoroacetic acid, and phosphorus trichloride is 1:7 to 10:0.7 to 0.8:0.85 to 0.95.

[0020] Preferably, step 2 specifically includes:

[0021] The first intermediate was dissolved in N,N-dimethylformamide, and 2-chloroacrylonitrile was added dropwise at 5°C to 10°C for 30 to 40 minutes;

[0022] After adding the catalyst, heat to 35°C to 40°C and react for 2 to 2.5 hours;

[0023] The conditions for removing the solvent by reduced pressure distillation are: pressure -0.12MPa to -0.1MPa, temperature 45°C to 50°C.

[0024] Preferably, in step 2, the mass ratio of the first intermediate, N,N-dimethylformamide, and 2-chloroacrylonitrile is 1:10-12:0.4-0.45.

[0025] Preferably, the conditions for electrolytic bromination in step 3 include:

[0026] Electrolytic cell temperature 10℃~15℃;

[0027] The anode material is titanium plated with ruthenium, and the cathode material is graphite;

[0028] Voltage 3.0V~5.0V, current density 10mA / cm 2 ~15mA / cm 2 ;

[0029] The concentration of HBr solution is 30%, and the concentration of hydrogen peroxide aqueous solution is 30%.

[0030] Preferably, step 4 specifically includes:

[0031] The amount of methanol used is 7 to 9 times the amount of crude bromopyrrolecarbonitrile;

[0032] The dissolution temperature is 60℃~70℃, the crystallization cooling rate is 1℃ / min, and the endpoint temperature is 5℃~10℃;

[0033] The drying temperature is 40℃~50℃.

[0034] After adopting the above technical solution, the beneficial effects of the present invention are:

[0035] 1. The bifunctional catalysts are synergistically enhanced. A homemade ZrO2@SBA-15-NH2 nanocatalyst is used to adsorb and neutralize HCl through the amino sites of the mesoporous support (SBA-15-NH2), inhibiting acid-catalyzed side reactions. At the same time, the ZrO2 active component coordinates with the carbonyl group of the acyl chloride, enhancing the positive carbon property and accelerating intramolecular cyclization.

[0036] 2. Electrolytic bromination achieves precise substitution. A constant current electrolysis and hydrogen peroxide synergistic oxidative bromination process is used. HBr is used as the bromine source. Bromine ions are in situ oxidized into active bromine species at a titanium ruthenium-plated anode. Combined with the enhanced oxidation efficiency of hydrogen peroxide, the α-position bromination of the pyrrole ring is precisely targeted.

[0037] 3. A microchannel reactor is used to enhance process control. Relying on its high mass and heat transfer efficiency, precise control of the reaction temperature is achieved. The addition time of trifluoroacetic acid and phosphorus trichloride is controlled separately, effectively suppressing side reactions caused by phosphorus trichloride hydrolysis and local overheating.

[0038] 4. Electrolytic bromination replaces liquid bromine, eliminating the use of high-risk chemicals from the source, and no highly toxic waste is discharged throughout the entire process; the solvent is recovered and reused through vacuum distillation, and the catalyst can be recycled after filtration and drying of the aqueous phase, effectively reducing costs. DETAILED DESCRIPTION

[0039] The features and exemplary embodiments of various aspects of the present invention will be described in detail below. In order to make the objects, technical solutions and advantages of the present invention clearer, 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 the need for some of these specific details. The following description of the embodiments is merely to provide a better understanding of the present invention by illustrating examples of the present invention.

[0040] The embodiment of the present invention provides a production process of bromopyrrole carbonitrile, which specifically includes the following steps.

[0041] Step 1:

[0042] A mixture of p-chlorophenylglycine and acetonitrile was added to the microchannel reactor, and the circulating cooling system was started to control the temperature of the microchannel reactor at 12°C to 18°C. Trifluoroacetic acid was then added dropwise to the microchannel reactor. After the addition was complete, the bifunctional nanocatalyst ZrO2@SBA-15-NH2 was added. Phosphorus trichloride was then added dropwise to the microchannel reactor. After the addition was complete, the temperature was raised to 55°C to 65°C and the reaction was carried out for 2.5 hours to 3 hours.

[0043] After the reaction is completed, acetonitrile is removed by distillation under reduced pressure, toluene and deionized water are added, and the mixture is allowed to stand at 30° C. to 40° C. to separate the layers. The organic phase is taken and desolvated with toluene to obtain the first intermediate.

[0044] The mass ratio of the added p-chlorophenylglycine, acetonitrile, trifluoroacetic acid and phosphorus trichloride is 1:7-10:0.7-0.8:0.85-0.95.

[0045] The trifluoroacetic acid and phosphorus trichloride are both added dropwise at a uniform speed, and the addition time of trifluoroacetic acid is 30 to 60 minutes, and the addition time of phosphorus trichloride is 60 to 90 minutes.

[0046] 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.

[0047] The preparation method of the bifunctional nanocatalyst ZrO2@SBA-15-NH2 comprises the following steps:

[0048] Step 1: Dissolve the template P123 in 2 mol / L HCl solution, heat to 40°C and stir for 24 hours;

[0049] Step 2: Add ethyl orthosilicate to the above solution and heat at 100°C for 24 hours;

[0050] Step 3: Add aminopropyltriethoxysilane to the above solution, stir at 70°C for 5 hours, filter and dry to obtain the SBA-15-NH2 support;

[0051] Step 4: Immerse the SBA-15-NH2 carrier in a zirconium salt solution containing 10% zirconium ions by mass, vibrate ultrasonically for 1 hour, filter, and dry at 120°C. Calcinate at 500°C for 4 hours to obtain the bifunctional nanocatalyst ZrO2@SBA-15-NH2.

[0052] 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). The function of the template agent P123 micelles is to form an ordered template through self-assembly, guide the inorganic precursors to polymerize around the micelles, and generate regular channels, which is beneficial to the construction of the catalyst carrier.

[0053] In the preparation process of the above-mentioned bifunctional nanocatalyst, the mass ratio of the added template P123, HCl solution, ethyl orthosilicate, and aminopropyltriethoxysilane is: 1-1.5:30.0-45.2:2-3.1, and the added amount of aminopropyltriethoxysilane is 0.2-0.3 times the mass of the template P123.

[0054] The pressure of acetonitrile removal by vacuum distillation is -0.1 MPa to -0.08 MPa, and the temperature is 40° C. to 45° C. The solvent acetonitrile can be recovered by vacuum distillation, thereby realizing the recycling of the solvent.

[0055] During the static stratification process, toluene and deionized water are added in a mass ratio of p-chlorophenylglycine: toluene: deionized water = 1:5-7:4-7.

[0056] The aqueous phase remaining in the above step contains the bifunctional nanocatalyst ZrO2@SBA-15-NH2, which can be reused after filtration and drying, and the number of reuses is less than 4 times.

[0057] In the above reaction step, in the process of generating the first intermediate by reacting p-chlorophenylglycine, trifluoroacetic acid and phosphorus trichloride, the reaction principle is as follows:

[0058]

[0059] During the reaction, trifluoroacetic acid is added dropwise to protonate the carboxyl group of p-chlorophenylglycine, forming a more electrophilic carboxylic acid intermediate. This creates conditions for the subsequent nucleophilic attack of phosphorus trichloride, which reacts with the protonated carboxyl group to generate an acyl chloride intermediate. The precise temperature control of the microchannel reactor ensures a low-temperature reaction environment, preventing subsequent side reactions caused by strong exothermic reactions. Furthermore, low-temperature control effectively inhibits the hydrolysis of phosphorus trichloride and the accumulation of HCl byproducts.

[0060] During the above reaction process, the bifunctional nanocatalyst ZrO2@SBA-15-NH2 was added, and efficient catalysis was achieved through mesoporous carrier modification and dual active site design.

[0061] Among them, the SBA-15-NH2 carrier has a huge loading space due to its own nanoscale pore size and high specific surface area, 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 regional selectivity of the cyclization. In addition, the surface of the SBA-15-NH2 carrier is amino-treated, and its basic sites can adsorb HCl generated in the reaction, inhibiting acid-catalyzed side reactions and stabilizing intermediates. In addition, ZrO2 is an active component, and the zirconium ion coordinates with the carbonyl oxygen of the acyl chloride, enhancing the positive carbon property, thereby accelerating the intramolecular nucleophilic cyclization.

[0062] The above reaction steps, through the combination of a microchannel reactor and a bifunctional catalyst, reduce the production of reaction by-products, ensure the safe progress of the reaction, and improve the product yield; at the same time, through efficient mass transfer and heat transfer, effectively shorten the reaction time and improve production efficiency.

[0063] Step 2:

[0064] The first intermediate was dissolved in N,N-dimethylformamide and added to a glass-lined reactor. The temperature was adjusted to 5°C to 10°C, and 2-chloroacrylonitrile was added dropwise to the reactor at a uniform rate. After the addition was complete, a bifunctional nanocatalyst ZrO2@SBA-15-NH2 was added. The temperature was raised to 35°C to 40°C, and the reaction was carried out for 2 to 2.5 hours. N,N-dimethylformamide was removed by vacuum distillation to obtain the second intermediate.

[0065] Wherein, N,N-dimethylformamide and 2-chloroacrylonitrile are added in a mass ratio of the first intermediate: N,N-dimethylformamide: 2-chloroacrylonitrile = 1:10-12:0.4-0.45.

[0066] The dropwise addition time of 2-chloroacrylonitrile is 30 to 40 minutes.

[0067] The pressure of the reduced pressure removal of N,N-dimethylformamide is -0.12MPa to -0.1MPa, and the temperature is 45°C to 50°C.

[0068] Among them, the addition amount of the bifunctional nanocatalyst ZrO2@SBA-15-NH2 is the same as that in step 1.

[0069] In the above reaction step, in the process of producing the second intermediate by reacting the first intermediate obtained in step 1 with 2-chloroacrylonitrile, the reaction principle is as follows:

[0070]

[0071] In the above reaction process, the first intermediate undergoes intramolecular cyclization with 2-chloroacrylonitrile to generate the second intermediate. 2-chloroacrylonitrile is added dropwise under low temperature to avoid self-polymerization of 2-chloroacrylonitrile and slow down its addition side reaction.

[0072] In addition, the addition of ZrO2@SBA-15-NH2 bifunctional nanocatalyst facilitates the activation of the nitrile or imine group of the pyrroline ring, enhances the carbon positive charge, and neutralizes the HCl generated by the reaction, inhibiting the acid-catalyzed ring-opening side reaction.

[0073] Step 3:

[0074] The second intermediate, N,N-dimethylformamide and HBr solution were added to the electrolytic cell, the temperature of the electrolytic cell was controlled at 10°C to 15°C, constant current electrolysis was started, and hydrogen peroxide aqueous solution was added dropwise at a uniform rate. After the addition was completed, the reaction lasted for 20 to 30 minutes, the temperature was raised to 40°C and stirred for 1 hour, N,N-dimethylformamide was removed by distillation, deionized water was added, the temperature was lowered to 10°C, crystallized for 1.5 hours, and then centrifuged and dried to obtain a crude bromopyrrolecarbonitrile.

[0075] The concentration of the HBr solution was 30%, the concentration of the hydrogen peroxide aqueous solution was 30%, and the dropwise addition time of the hydrogen peroxide aqueous solution was 30 minutes.

[0076] The second intermediate, N,N-dimethylformamide, 30% HBr aqueous solution, 30% hydrogen peroxide aqueous solution, and deionized water are added in a mass ratio of 1:10-13:1-1.2:1.1-1.3:6-8.

[0077] The anode of the electrolytic cell is made of titanium plated with ruthenium, the cathode is made of graphite, and the effective areas of the anode and cathode are 0.5m 2 .

[0078] During the cross-flow electrolysis process, the voltage is 3.0V to 5.0V and the current density is 10mA / cm 2 ~15mA / cm 2 .

[0079] The reaction principle of the above reaction step, in which the second intermediate undergoes a bromination reaction to prepare bromopyrrolecarbonitrile, is as follows:

[0080]

[0081] During the above reaction process, the bromide ions at the anode of the electrolytic cell are oxidized into active bromine species, and under the simultaneous oxidation action of hydrogen peroxide, the concentration of bromide cations in the solution is effectively increased. The active bromine species and bromide cations selectively electrophilically replace the second intermediate, achieving bromination of the α-position of the pyrrole ring, thereby obtaining the final product, bromopyrrolecarbonitrile.

[0082] Compared with traditional chemical bromination, this electrolytic bromination process uses cheap bromine source hydrogen bromide as a reactant, which reduces production costs and avoids the use of highly toxic and corrosive liquid bromine. The reaction process does not require a large amount of hazardous substances and is safer and more environmentally friendly. The second intermediate is selectively electrophilically substituted by active bromine substances and bromide cations to accurately achieve bromination of the α position of the pyrrole ring and reduce the production of polybrominated by-products. Moreover, the degree of bromination can be precisely controlled by changing and controlling the point parameters to avoid excessive bromination.

[0083] Step 4:

[0084] The crude bromopyrrolecarbonitrile was added into methanol, heated to 60-70°C and stirred until completely dissolved, then slowly cooled to 5-10°C. After keeping warm for 2-4 hours, a centrifuge was used for solid-liquid separation to obtain a wet product, which was then transferred to a 40-50°C environment and dried for 2-3 hours to obtain the final product.

[0085] The quality of the methanol used is 7 to 9 times that of the crude bromopyrrolecarbonitrile.

[0086] Wherein, during the cooling process in the above steps, the cooling rate is 1°C / min.

[0087] During the above steps, crystallization is achieved by dissolving bromopyrrolecarbonitrile in methanol and slowly lowering the temperature. Impurities encapsulated in the crystals are reduced by temperature control, thereby improving the purity of the final product bromopyrrolecarbonitrile. The drying stage is controlled at below 50° C. to avoid thermal decomposition of the bromide, thereby improving the product yield.

[0088] In order to facilitate a further understanding of the present invention, several embodiments and comparative examples of the present invention are given below.

[0089] Example 1

[0090] Step 1:

[0091] A mixture of 3.5 kg of p-chlorophenylglycine and 19 kg of acetonitrile was added to the microchannel reactor, and the circulating cooling system was started to control the temperature of the microchannel reactor at 15°C. Subsequently, 2.6 kg of trifluoroacetic acid was uniformly added dropwise to the microchannel reactor for 35 minutes. After the addition was completed, 0.3 kg of bifunctional nanocatalyst ZrO2@SBA-15-NH2 was added. Subsequently, 3.2 kg of phosphorus trichloride was uniformly added dropwise to the microchannel reactor for 60 minutes. After the addition was completed, the temperature was raised to 60°C and the reaction was carried out for 2.5 hours.

[0092] After the reaction is completed, the pressure is reduced to -0.1 MPa, and the acetonitrile is distilled off at 40°C. 19 kg of toluene and 20 kg of deionized water are added, and the mixture is allowed to stand at 35°C to separate into layers. The aqueous phase is filtered and dried to obtain a bifunctional nanocatalyst for reuse. The organic phase is desolvated with toluene to obtain the first intermediate.

[0093] Step 2:

[0094] The first intermediate was dissolved in 44 kg of N,N-dimethylformamide and added to a glass-lined reactor. The temperature was adjusted to 5°C, and 1.9 kg of 2-chloroacrylonitrile was uniformly added dropwise to the reactor for 30 minutes. After the addition was completed, 0.3 kg of bifunctional nanocatalyst ZrO2@SBA-15-NH2 was added. The temperature was raised to 40°C, and the reaction was carried out for 2 hours. The pressure was reduced to -0.12 MPa and the temperature was 45°C for distillation to remove N,N-dimethylformamide to obtain the second intermediate.

[0095] Step 3:

[0096] The second intermediate, 50 kg N, N-dimethylformamide, and 4.0 kg 30% HBr solution were added to the electrolytic cell. The temperature of the electrolytic cell was controlled at 10 °C. Constant current electrolysis was started with a voltage of 3.0 V and a current density of 10 mA / cm 2 At the same time, 4.5 kg of 30% aqueous hydrogen peroxide solution was added dropwise at a uniform speed for 30 minutes. After the addition was completed, the reaction was continued for 20 minutes, the temperature was raised to 40 ° C and stirred for 1 hour, N, N-dimethylformamide was distilled off, 25 kg of deionized water was added, the temperature was lowered to 10 ° C and crystallized for 1.5 hours, and then centrifuged and dried to obtain a crude bromopyrrolecarbonitrile.

[0097] Step 4:

[0098] The bromopyrrole nitrile crude product was put into 30 kg of methanol, heated to 65 °C and stirred until completely dissolved, slowly cooled to 5 °C at a rate of 1 °C / min, and then kept at 5 °C for 2 hours. The wet product was separated by centrifuge and then transferred to an environment at 50 °C for drying for 2 hours to obtain the final product.

[0099] Example 2

[0100] This example is based on Example 1, and the dropwise addition time of trifluoroacetic acid and phosphorus trichloride in step 1 is adjusted, specifically as follows.

[0101] Step 1:

[0102] A mixture of 3.5 kg of p-chlorophenylglycine and 19 kg of acetonitrile was added to a microchannel reactor, and a circulating cooling system was started to control the temperature of the microchannel reactor at 15 °C. Then, 2.6 kg of trifluoroacetic acid was added to the microchannel reactor at a constant rate, and the dropwise addition time was 50 minutes. After the dropwise addition was completed, 0.3 kg of bifunctional nanocatalyst ZrO2@SBA-15-NH2 was added. Then, 3.2 kg of phosphorus trichloride was added to the microchannel reactor at a constant rate, and the dropwise addition time was 80 minutes. After the dropwise addition was completed, the temperature was increased to 60 °C, and the reaction was carried out for 2.5 hours.

[0103] After the reaction was completed, the acetonitrile was removed by distillation under reduced pressure at a temperature of 40 °C. Then, 19 kg of toluene and 20 kg of deionized water were added, and the mixture was allowed to stand at 35 °C to separate into layers. The water phase was filtered and dried to obtain the bifunctional nanocatalyst for reuse. The organic phase was subjected to toluene desorption to obtain the first intermediate.

[0104] The remaining steps of this example are the same as those of Example 1.

[0105] Example 3

[0106] This example is based on Example 1, and the addition amount of bifunctional nanocatalyst ZrO2@SBA-15-NH2 in step 1 is adjusted, specifically as follows.

[0107] Step 1:

[0108] A mixture of 3.5 kg of p-chlorophenylglycine and 19 kg of acetonitrile was added to a microchannel reactor, and a circulating cooling system was started to control the temperature of the microchannel reactor at 15 °C. Then, 2.6 kg of trifluoroacetic acid was added to the microchannel reactor at a constant rate, and the dropwise addition time was 50 minutes. After the dropwise addition was completed, 0.3 kg of bifunctional nanocatalyst ZrO2@SBA-15-NH2 was added. Then, 3.2 kg of phosphorus trichloride was added to the microchannel reactor at a constant rate, and the dropwise addition time was 80 minutes. After the dropwise addition was completed, the temperature was increased to 60 °C, and the reaction was carried out for 2.5 hours.

[0109] After the reaction is completed, the acetonitrile is removed by distillation under reduced pressure to -0.1 MPa at a temperature of 40 DEG C, 19 kg of toluene and 20 kg of deionized water are added, and the mixture is allowed to stand at 35 DEG C to separate into two layers. The water phase is filtered and dried to obtain a reusable bifunctional nanocatalyst, and the organic phase is subjected to toluene desorption to obtain a first intermediate.

[0110] The remaining steps of this example are identical to those of Example 1.

[0111] Example 4

[0112] This example is based on Example 1, and the dropwise addition time of 2-chloropropenonitrile in Step 2 is adjusted, specifically as follows:

[0113] Step 2:

[0114] The first intermediate is dissolved in 44 kg of N,N-dimethylformamide, and then added to a glass-lined reaction kettle. The temperature is adjusted to 5 DEG C, and 1.9 kg of 2-chloropropenonitrile is added at a constant rate. The dropwise addition time is 40 minutes. After the dropwise addition is completed, 0.3 kg of bifunctional nanocatalyst ZrO2@SBA-15-NH2 is added, and the temperature is raised to 40 DEG C. After 2 hours of reaction, the N,N-dimethylformamide is removed by distillation under reduced pressure to -0.12 MPa at a temperature of 45 DEG C to obtain a second intermediate.

[0115] The remaining steps of this example are identical to those of Example 1.

[0116] Example 5

[0117] This example is based on Example 1, and the voltage and current density parameters of the constant current electrolysis in Step 3 are adjusted, specifically as follows:

[0118] The second intermediate, 50 kg of N,N-dimethylformamide, and 4.0 kg of 30% HBr solution are added to an electrolytic cell, and the temperature of the electrolytic cell is controlled at 10 DEG C. The constant current electrolysis is started, the voltage is 4.0 V, and the current density is 12 mA / cm 2 At the same time, 4.5 kg of 30% hydrogen peroxide aqueous solution is added at a constant rate, and the dropwise addition time is 30 minutes. After the dropwise addition is completed, the reaction is carried out for 20 minutes, the temperature is raised to 40 DEG C, and stirring is carried out for 1 hour. N,N-dimethylformamide is removed by distillation, 25 kg of deionized water is added, the temperature is lowered to 10 DEG C, and crystallization is carried out for 1.5 hours. After centrifugation and drying, a crude bromopyrrolonitrile product is obtained.

[0119] The remaining steps of this example are identical to those of Example 1.

[0120] Comparative Example 1

[0121] This comparative example is based on Example 1, and the catalyst in Step 1 is adjusted, specifically as follows:

[0122] Step 1:

[0123] A mixture of 3.5 kg of p-chlorophenylglycine and 19 kg of acetonitrile was added to the microchannel reactor, the circulating cooling system was started to control the temperature of the microchannel reactor at 15 ° C, and then 2.6 kg of trifluoroacetic acid was added dropwise to the microchannel reactor at a uniform rate, and the addition time was 35 minutes. After the addition was completed, 0.3 kg of AlCl3 was added dropwise to the microchannel reactor, and then 3.2 kg of phosphorus trichloride was added dropwise to the microchannel reactor at a uniform rate, and the addition time was 60 minutes. After the addition was completed, the temperature was raised to 60 ° C and the reaction was reacted for 2.5 hours.

[0124] After the reaction was completed, the pressure was reduced to -0.1 MPa, and the acetonitrile was distilled off at 40°C. 19 kg of toluene and 20 kg of deionized water were added, and the mixture was allowed to stand at 35°C to separate layers. The organic phase was desolvated with toluene to obtain the first intermediate.

[0125] The remaining steps of this comparative example are exactly the same as those in Example 1.

[0126] Comparative Example 2

[0127] This comparative example is based on Example 1, and the catalyst in step 2 is adjusted as follows:

[0128] Step 2:

[0129] The first intermediate was dissolved in 44 kg of N,N-dimethylformamide and added to a glass-lined reactor. The temperature was adjusted to 5°C, and 1.9 kg of 2-chloroacrylonitrile was uniformly added dropwise to the reactor over 30 minutes. After the addition was complete, 0.3 kg of AlCl3 was added. The temperature was raised to 40°C, and the reaction was carried out for 2 hours. The pressure was reduced to -0.12 MPa, and the temperature was 45°C for distillation to remove N,N-dimethylformamide to obtain the second intermediate.

[0130] The remaining steps of this comparative example are exactly the same as those in Example 1.

[0131] Comparative Example 3

[0132] This comparative example is based on Example 1, and the electrolysis process in step 3 is adjusted as follows:

[0133] Step 3:

[0134] The second intermediate, 50 kg of N,N-dimethylformamide and 4.0 kg of 30% HBr solution were added to the reactor. The temperature of the reactor was controlled at 10°C. 4.5 kg of 30% hydrogen peroxide aqueous solution was added dropwise at a uniform rate for 30 minutes. After the addition was completed, the reaction was continued for 20 minutes. The temperature was raised to 40°C and stirred for 1 hour. N,N-dimethylformamide was removed by distillation. 25 kg of deionized water was added. The temperature was lowered to 10°C and crystallized for 1.5 hours. The crude bromopyrrolecarbonitrile was then dried by centrifugation.

[0135] The remaining steps of this comparative example are exactly the same as those in Example 1.

[0136] For the above examples and comparative examples, the masses of the first intermediate, the second intermediate, the crude bromopyrrole carbonitrile, and the final product were respectively weighed, and the corresponding yields were calculated respectively. The purity of the final product was measured by high performance liquid chromatography, and the data results were statistically analyzed as follows:

[0137]

[0138] According to the above data, we can know that:

[0139] 1. By comparing Comparative Example 1 and Comparative Example 2 with Example 1, the catalytic effect of the bifunctional nanocatalyst ZrO2@SBA-15-NH2 in steps 1 and 2 was verified. The traditional catalyst AlCl3 was unable to inhibit the HCl by-product, resulting in acid-catalyzed side reactions such as hydrolysis or over-chlorination. In addition, AlCl3 lacked an amino carrier to neutralize HCl, and also caused 2-chloroacrylonitrile self-polymerization and ring-opening side reactions. Therefore, compared with Example 1, the yield of the first intermediate in Comparative Example 1 was reduced by 7.2%, and the yield of the second intermediate in Comparative Example 2 was reduced by 7.2%.

[0140] 2. By comparing Comparative Example 3 with Example 1, the role of the electrolytic bromination process in step 3 was verified. In Comparative Example 3, the electrolytic cell was eliminated and only hydrogen peroxide was used for oxidation. As a result, the yield of the crude bromopyrrole carbonitrile in Comparative Example 3 was reduced by 8.5% compared with Example 1, and the purity of the final product was reduced by 6.6%. The reason is that the elimination of the electrolysis process resulted in a lack of active bromine or bromide ions generated in situ by the system, resulting in a decrease in bromination selectivity and an increase in by-products.

[0141] 3. In Example 2, extending the addition time of the agent can alleviate the local overheating caused by strong heat release, so that the overall yield is slightly increased, but the improvement is limited.

[0142] 4. In Example 3, the amount of catalyst was increased, so that the yield of each step reached the peak value, and the final yield was 87.1%, the highest value among the examples and comparative examples.

[0143] 5. In Example 4, the electrolysis parameters were adjusted to increase the electrolysis voltage and current density, which can accelerate the oxidation efficiency of bromide ions to a certain extent, so that the yield of crude bromopyrrole carbonitrile is slightly increased.

[0144] While the embodiments of the present invention are described above, these embodiments do not exhaustively describe all details, nor do they limit the present invention to only specific embodiments. Clearly, many modifications and variations can be made based on the above description. This specification selects and specifically describes these embodiments in order to better explain the principles and practical applications of the present invention, thereby enabling those skilled in the art to make good use of the present invention and its modifications and uses. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention shall be included within the scope of protection of the present invention.

Claims

1. A production process for bromopyrrole carbonitrile, characterized in that: The following steps are involved: Step 1: In a microchannel reactor, p-chlorophenylglycine is reacted with trifluoroacetic acid and phosphorus trichloride in the presence of a bifunctional nanocatalyst ZrO2@SBA-15-NH2, and the first intermediate is obtained after post-treatment; Step 2: In a glass-lined reactor, the first intermediate is reacted with 2-chloroacrylonitrile in the presence of a bifunctional nanocatalyst ZrO2@SBA-15-NH2, and the second intermediate is obtained by vacuum distillation; Step 3: In an electrolytic cell, the second intermediate is subjected to a constant current electrolytic bromination reaction with an HBr solution and an aqueous hydrogen peroxide solution, and a crude bromopyrrolecarbonitrile is obtained through post-treatment; Step 4: Recrystallize the crude bromopyrrolecarbonitrile from methanol to obtain bromopyrrolecarbonitrile; The preparation method of the bifunctional nanocatalyst ZrO2@SBA-15-NH2 comprises the following steps: S1: Dissolve the template P123 in HCl solution, add ethyl orthosilicate, and obtain the SBA-15 support after hydrothermal reaction; S2: introducing aminopropyltriethoxysilane into the SBA-15 support to obtain the SBA-15-NH2 support; S3: The SBA-15-NH2 support is impregnated in a zirconium salt solution, and then dried and calcined to obtain ZrO2@SBA-15-NH2.

2. The production process of bromopyrrole carbonitrile according to claim 1, wherein: In step S1, the mass ratio of template P123, HCl solution, and ethyl orthosilicate is 1-1.5:30.0-45.2:2-3.1; and in step S2, the amount of aminopropyltriethoxysilane added is 0.2-0.3 times the mass of template P123.

3. The production process of bromopyrrole carbonitrile according to claim 2, wherein: In step 1, the amount of the bifunctional nanocatalyst added is 10% to 15% of the mass of trifluoroacetic acid, and the mass proportion of zirconium ions in the zirconium salt solution is 10%.

4. The production process of bromopyrrole carbonitrile according to claim 1, wherein Step 1 specifically includes: Reaction temperature control: maintain 12℃~18℃ when adding trifluoroacetic acid, and raise the temperature to 55℃~65℃ after adding phosphorus trichloride; Post-treatment process: acetonitrile is removed by vacuum distillation, toluene and deionized water are added and allowed to stand for stratification, the organic phase is taken for toluene desolventizing to obtain the first intermediate, and the catalyst in the aqueous phase is recovered.

5. The production process of bromopyrrole carbonitrile according to claim 4, wherein: In step 1, the time for adding trifluoroacetic acid dropwise is 30 to 60 minutes, and the time for adding phosphorus trichloride dropwise is 60 to 90 minutes; the mass ratio of p-chlorophenylglycine, acetonitrile, trifluoroacetic acid, and phosphorus trichloride is 1:7 to 10:0.7 to 0.8:0.85 to 0.

95.

6. The production process of bromopyrrole carbonitrile according to claim 1, wherein Step 2 specifically includes: The first intermediate was dissolved in N,N-dimethylformamide, and 2-chloroacrylonitrile was added dropwise at 5°C to 10°C for 30 to 40 minutes; After adding the catalyst, heat to 35°C to 40°C and react for 2 to 2.5 hours; The conditions for removing the solvent by reduced pressure distillation are: pressure -0.12MPa to -0.1MPa, temperature 45°C to 50°C.

7. The production process of bromopyrrole carbonitrile according to claim 6, wherein: In step 2, the mass ratio of the first intermediate, N,N-dimethylformamide, and 2-chloroacrylonitrile is 1:10-12:0.4-0.

45.

8. The production process of bromopyrrole carbonitrile according to claim 1, wherein The conditions for electrolytic bromination in step 3 include: Electrolytic cell temperature 10℃~15℃; The anode material is titanium plated with ruthenium, and the cathode material is graphite; Voltage 3.0V~5.0V, current density 10mA / cm 2 ~15mA / cm 2 ; The concentration of HBr solution is 30%, and the concentration of hydrogen peroxide aqueous solution is 30%.

9. The production process of bromopyrrole carbonitrile according to claim 1, wherein Step 4 specifically includes: The amount of methanol used is 7 to 9 times the amount of crude bromopyrrolecarbonitrile; The dissolution temperature is 60℃~70℃, the crystallization cooling rate is 1℃ / min, and the endpoint temperature is 5℃~10℃; The drying temperature is 40℃~50℃.

Images