Rapid conversion method for continuous production of diazonium salt

Abstract

The invention discloses a rapid conversion method for continuous production of diazonium salt, which comprises the following steps: dissolving an amide raw material in a polar solvent, adding acid to obtain an amide salt solution, and dissolving sodium nitrite in water to obtain a sodium nitrite aqueous solution; constructing a reaction system in the reaction kettle; synchronously dropwise adding the amide salt solution and the sodium nitrite aqueous solution into a reaction system according to a set proportion; enabling the amide salt solution and the sodium nitrite aqueous solution to be subjected to a conversion reaction in the reaction kettle through automatic control while dropwise adding in a certain proportion synchronously, so as to generate diazonium salt; after diazonium salt is generated in the reaction kettle, carrying out instant conversion reaction on the diazonium salt and a reaction system to obtain a rapid conversion reaction mixture; and treating the rapid conversion reaction mixture, and separating to obtain a target product. According to the invention, the safety problem of diazonium salt production, storage, transportation and use is solved, the yield of diazotization and next reaction is greatly improved, the automation degree is high, and the purpose of eliminating the danger of diazonium salt can be achieved.

Description

Technical Field

[0001] This invention relates to the fields of chemical synthesis and safety technology, and in particular to a rapid conversion method for the continuous production of diazonium salts. Background Technology

[0002] Diazotization, a fundamental reaction in fine chemical production, is widely used in the synthesis of intermediates for dyes, pharmaceuticals, and pesticides, resulting in a huge market demand. As the chemical industry moves towards inherent safety, automation, and continuous production, developing more efficient and safer diazotization processes has become a major industry trend. Traditional diazotization reactions typically employ a batch production model. The process usually involves preparing and accumulating diazonium salts at lower temperatures, followed by transferring the diazonium salt solution to the next step for substitution, condensation, cyclization, or deamination reactions.

[0003] However, existing technologies suffer from serious safety defects and technical bottlenecks in production practice. Diazotization is listed as one of the 15 hazardous processes stipulated by the state. Its core problem lies in the extremely poor thermal stability of diazonium salts, which are highly susceptible to violent decomposition or even explosion under conditions of heating, impact, or drying. In traditional processes, the preparation, storage, and transportation of diazonium salts all present significant safety hazards: failure of reactor temperature control, prolonged storage leading to heat accumulation, or friction and temperature rise during transport to elevated tanks can all easily trigger safety accidents. Furthermore, existing preventative measures such as emergency shut-off, accelerated cooling, or backup water systems often rely heavily on power supply, making them difficult to guarantee 100% effectiveness in the event of power outages or equipment failures. This is especially true for smaller units with limited power backup capabilities, where the risk of accidents is even higher.

[0004] Besides safety concerns, existing technologies also have significant shortcomings in terms of reaction efficiency and environmental protection. Taking deamination reactions as an example, traditional processes, due to the instability of diazonium salts and the difficulty in precisely matching reaction rates, easily lead to the polymerization of materials to form tar, or cause severe material overflow due to the instantaneous release of large amounts of nitrogen. This not only results in significant environmental pollution but also often leads to low product yields, only around 70%-75%. In condensation and cyclization reactions, traditional processes involve cumbersome operation steps, including multiple extractions and material transfers, further reducing production efficiency and product yield. Therefore, the market urgently needs an intrinsically safe new diazonium salt conversion technology that can eliminate diazonium salt accumulation from the process principle, enable on-demand use, and significantly improve yield. Summary of the Invention

[0005] The purpose of this invention is to provide a rapid conversion method for the continuous production of diazonium salts, which solves at least one of the above-mentioned technical problems. It is safe, reliable, and easy to operate, solves the safety issues of diazonium salt production, storage, and use, greatly improves the yield of diazotization and subsequent reactions, has a high degree of automation, and can achieve the purpose of eliminating hazards.

[0006] The embodiments of the present invention are implemented as follows:

[0007] A rapid conversion method for continuous production of diazonium salts, comprising:

[0008] S100: Dissolve the ammonium raw material in a polar solvent, add acid to obtain an ammonium salt solution, and dissolve sodium nitrite in water to obtain an aqueous sodium nitrite solution.

[0009] S200: The base system materials and solvents for the conversion reaction with the diazonium salt are added into the reactor. The reactor is then prepared by temperature regulation and stirring to construct the reaction system.

[0010] S300, the ammonium salt solution and the sodium nitrite aqueous solution are simultaneously added dropwise to the reaction system in a set ratio.

[0011] S400, during the synchronous dripping process, through automated control, causes the ammonium salt solution to undergo a conversion reaction with the sodium nitrite aqueous solution in the reaction vessel to generate diazonium salt.

[0012] S500, after the diazonium salt is generated in the reactor, it undergoes an immediate conversion reaction with the reaction system without separate separation, to obtain a rapid conversion reaction mixture.

[0013] S600, the rapid conversion reaction mixture is processed to separate and obtain the target product.

[0014] In a preferred embodiment of the present invention, in the above-described rapid conversion method for continuous production of diazonium salts, in S100, the polar solvent includes at least one of water, ethanol, tetrahydrofuran, and DMF.

[0015] Its technical advantages are: it enables the ammonium raw materials and the ammonium salts formed therefrom to be fully dissolved and the system to be kept uniform, which is beneficial to the rapid mixing and uniform mass transfer of reactants in the reactor during the subsequent synchronous drop addition process.

[0016] In a preferred embodiment of the present invention, in the above-mentioned rapid conversion method for continuous production of diazonium salts, in S200, the substrate material includes at least one of dicyano-based substrates, dicyanate, alkynes, active acrylates, and ketones.

[0017] Its technical advantages are as follows: by pre-constructing a reaction system containing the above-mentioned base materials in the reactor, the diazotization reaction and the subsequent conversion reaction can be completed continuously in the same equipment, reducing intermediate transfer, separation and temporary storage steps, simplifying the process flow, and improving the overall reaction rate and space utilization efficiency.

[0018] In a preferred embodiment of the present invention, in the above-described rapid conversion method for continuous production of diazonium salts, in step S400, the conversion reaction includes at least one of substitution reaction, condensation reaction, cyclization reaction, and deamination reaction.

[0019] Its technical advantage lies in achieving a high degree of coupling between diazonium salt generation and multiple types of chemical transformation reactions within the same process framework.

[0020] In a preferred embodiment of the present invention, in the above-mentioned rapid conversion method for continuous production of diazonium salts, in S400, when the conversion reaction is a deamination reaction, the substrate material is a sodium phosphite solution.

[0021] In S500, the reaction route of the instantaneous conversion reaction is as follows:

[0022] +Phosphorus-containing byproducts, among which... It is aryl or heteroaryl.

[0023] The technical advantages are as follows: it enables the rapid reductive denitrification transformation of the diazonium salt intermediate generated in the reactor, instantly converting the unstable diazonium salt into the corresponding aryl or heteroaryl product, while releasing nitrogen gas and generating controllable phosphorus-containing byproducts, thus effectively avoiding the risks of diazonium salt accumulation and decomposition. The reaction conditions are mild and highly selective, which helps maintain the integrity of other substituents on the aromatic ring, reduces side reactions, and eliminates the need for intermediate separation and transfer steps by completing the diazotization and deamination transformation within the same reaction system, significantly improving process safety, reaction efficiency, and the stability of continuous production.

[0024] In a preferred embodiment of the present invention, in the above-mentioned rapid conversion method for continuous production of diazonium salts, in S400, when the conversion reaction is a condensation reaction and a cyclization reaction, the ammonia raw material is an aromatic amine, and the substrate material is ethyl 2,3-dicyanopropionate.

[0025] In S500, the reaction pathway of the instantaneous conversion reaction includes:

[0026] At 0–5°C, the diazonium salt generated by the conversion reaction undergoes a coupling reaction with ethyl 2,3-dicyanopropionate.

[0027] Add ammonia water to adjust the pH value to 9-10, and keep the reaction at 0-5℃ to complete the cyclization.

[0028] The technical advantages are as follows: Diazonium salts, generated under low-temperature conditions, can immediately couple with highly reactive dicyanate substrates, and subsequently complete cyclization by adjusting the system to weakly alkaline conditions, thus achieving an orderly connection between condensation and cyclization reactions. This reaction route, through low-temperature control and precise pH adjustment, effectively suppresses the decomposition and side reactions of dizonium salts, improves the selectivity and yield of the target heterocyclic product, avoids the separation of dizonium salt intermediates, shortens the reaction process, and significantly improves process safety and repeatability, making it suitable for continuous and large-scale production applications.

[0029] In a preferred embodiment of the present invention, in the above-mentioned rapid conversion method for continuous production of diazonium salt, in S400, when the ammonia feedstock is an aromatic amine, the aromatic amine is 2,6-dichloro-4-trifluoromethylaniline.

[0030] In S500, the target product of the instantaneous conversion reaction is 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole.

[0031] Its technical advantage lies in the fact that by utilizing the strong electron-withdrawing substituents in the aromatic amine molecule to regulate the activity of diazotization and subsequent condensation and cyclization reactions, the diazonium salt can stably and rapidly participate in coupling and cyclization reactions after being generated under low temperature conditions, thereby improving the selectivity and yield of the target pyrazole product.

[0032] In a preferred embodiment of the present invention, in the above-described rapid conversion method for continuous production of diazonium salts, in step S500, when the ammonia feedstock is an aromatic amine, the feedstock in the reactor comprises the following components by weight:

[0033] 35-40 parts of aromatic amines.

[0034] 85-90 parts of 36% concentrated hydrochloric acid.

[0035] 175-180 parts of ethanol.

[0036] 25-26 parts of ethyl 2,3-dicyanopropionate.

[0037] Sodium nitrite 10-12 parts.

[0038] Urea 0.1 to 0.5 parts.

[0039] 50-55 parts of 25% ammonia solution.

[0040] 380-400 parts water.

[0041] The technical advantages lie in achieving a synergistic match between rate and material consumption within the same system. The precise amounts of concentrated hydrochloric acid and sodium nitrite ensure the stable and continuous generation of diazonium salts without excessive accumulation. The solvent system of ethanol and water facilitates the complete dissolution of reactants and provides heat buffering. The small amount of urea introduced effectively consumes residual nitrites in the system to suppress side reactions, while the reasonable control of ammonia usage helps to complete the cyclization reaction rapidly and uniformly. Under the premise of ensuring the safety and controllability of the reaction, the selectivity and yield of the target product are improved, while impurity generation and raw material waste are reduced. It exhibits good stability, repeatability, and feasibility for industrial scale-up.

[0042] In a preferred embodiment of the present invention, in the above-described rapid conversion method for continuous production of diazonium salts, in step S400, the automated control is controlled by a DCS system.

[0043] The DCS system synchronously and interlocks the real-time temperature of the reactor with the dripping flow rate of the ammonium salt solution, and synchronously and interlocks the flow rate of the sodium nitrite aqueous solution with the flow rate of the ammonium salt solution according to a set fixed molar ratio.

[0044] Its technical effect is that it keeps the formation rate of diazonium salts dynamically matched with their subsequent conversion rate, effectively avoiding the accumulation of diazonium salts and exothermic runaway caused by feed imbalance or local overabundance.

[0045] In a preferred embodiment of the present invention, in the above-described rapid conversion method for continuous production of diazonium salts, step S600, which involves processing the rapid conversion reaction mixture to separate and obtain the target product, includes:

[0046] An acid solution was added dropwise to the rapid conversion reaction mixture at 0–5°C to adjust the pH to 7–8. The ethanol solvent was removed by vacuum distillation, the mixture was filtered, the filter cake was washed with water, and dried to obtain the target product solid.

[0047] Its technical advantages are: it effectively neutralizes and terminates the reaction by neutralizing alkaline components and unreacted intermediates in the reaction system, avoiding further side reactions or degradation of the target product; it reduces the heat load and facilitates solvent recovery and utilization, promotes the precipitation of the target product in the system, and, in conjunction with filtration, washing and drying, can efficiently remove inorganic salts and soluble impurities, significantly improving the purity and stability of the target product.

[0048] The beneficial effects of the embodiments of the present invention are:

[0049] The rapid conversion method for continuous production of diazonium salts of the present invention generates and consumes diazonium salts on the spot within a reactor by simultaneously adding amino-containing raw materials and sodium nitrite solution in a predetermined ratio. This avoids the separate accumulation of diazonium salts and intermediate separation steps, fundamentally reducing the retention of unstable diazonium compounds and the associated risks of thermal runaway, explosion, or violent decomposition. The on-the-spot generation and conversion process significantly improves process safety and reduces the operational complexity and management burden caused by intermediate handling and long-term storage.

[0050] The rapid conversion method for continuous production of diazonium salts of this invention incorporates temperature, flow rate, and valve position into a DCS closed-loop interlock control system, enabling real-time monitoring and automatic adjustment. When the reaction temperature or feed flow rate exceeds limits, the pump is automatically stopped, triggering protection procedures such as emergency cooling or reflux dilution. This automation and interlock strategy ensures dynamic matching of the rates between diazotization and subsequent conversions, reducing selectivity losses caused by side reactions and excess reagents. By reducing manual intervention and achieving repeatable feed and temperature programs, it improves production stability and yield, reduces failure rates and safety hazards caused by improper human operation, and facilitates scale-up and large-scale continuous production.

[0051] The rapid conversion method for continuous production of diazonium salts in this invention emphasizes resource utilization and environmental control in both the reaction route and downstream processing. By implementing an integrated purification route after the reaction, including phase separation, stepwise extraction, ammonia washing, and vacuum desolvation, acidic inorganic salts and water-soluble impurities can be efficiently removed, and reusable solvents and valuable mother liquor can be recovered. This improves the purity of the final product while reducing solvent consumption and waste disposal costs. The classified collection and targeted treatment of waste acid, alkaline wastewater, and organic waste liquids helps enterprises meet environmental regulations and reduce their environmental governance burden. Attached Figure Description

[0052] To more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings used in the embodiments will be briefly introduced below. It should be understood that the following drawings only show some embodiments of the present invention and should not be regarded as a limitation on the scope. For those skilled in the art, other related drawings can be obtained based on these drawings without creative effort.

[0053] Figure 1 This is a flowchart of the rapid conversion method for continuous production of diazonium salts according to the present invention;

[0054] Figure 2 This is a schematic diagram of the reaction equation for the rapid conversion method for continuous production of diazonium salts in this invention, where the conversion reaction is a deamination reaction.

[0055] Figure 3This is a schematic diagram of the reaction equations for the instantaneous conversion reaction when the conversion reaction is a condensation reaction and a cyclization reaction in the rapid conversion method for continuous production of diazonium salts of the present invention.

[0056] Figure 4 This is a schematic diagram of the complete steps of the reaction equation for the instantaneous conversion reaction when the conversion reaction is a condensation reaction and a cyclization reaction in the rapid conversion method for continuous production of diazonium salts of the present invention.

[0057] Figure 5 This is a schematic diagram of the process flow for the instantaneous conversion reaction to generate 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole in the rapid conversion method for continuous production of diazonium salts of the present invention. Detailed Implementation

[0058] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. The components of the embodiments of the present invention described and shown in the accompanying drawings can generally be arranged and designed in various different configurations.

[0059] Please refer to Figures 1 to 5 This invention provides a rapid conversion method for the continuous production of diazonium salts, comprising: S100, dissolving an ammonium salt raw material in a polar solvent, adding acid to obtain an ammonium salt solution, and dissolving sodium nitrite in water to obtain an aqueous sodium nitrite solution; S200, adding a base system material and solvent for the conversion reaction with the diazonium salt to a reaction vessel, and preparing the reaction vessel by temperature adjustment and stirring to construct a reaction system; S300, synchronously adding the ammonium salt solution and the aqueous sodium nitrite solution to the reaction system in a set ratio; S400, during the synchronous addition process, through automatic control, causing the ammonium salt solution to undergo a conversion reaction with the aqueous sodium nitrite solution in the reaction vessel to generate diazonium salt; S500, after the diazonium salt is generated in the reaction vessel, it undergoes an immediate conversion reaction with the reaction system without separate separation to obtain a rapid conversion reaction mixture; S600, processing the rapid conversion reaction mixture to separate and obtain the target product.

[0060] In a preferred embodiment of the present invention, in the above-described rapid conversion method for continuous production of diazonium salts, in S100, the polar solvent includes at least one of water, ethanol, tetrahydrofuran, and DMF.

[0061] In a preferred embodiment of the present invention, in the above-mentioned rapid conversion method for continuous production of diazonium salts, in S200, the substrate material includes at least one of dicyano-based substrates, dicyanate, alkynes, active acrylates and ketones, or other organic substrates that undergo substitution, condensation, cyclization and deamination reactions with diazonium salts.

[0062] In a preferred embodiment of the present invention, in the above-described rapid conversion method for continuous production of diazonium salts, in step S400, the conversion reaction includes at least one of substitution reaction, condensation reaction, cyclization reaction, and deamination reaction.

[0063] like Figure 2 As shown, in a preferred embodiment of the present invention, in the above-mentioned rapid conversion method for continuous production of diazonium salts, in S400, when the conversion reaction is a deamination reaction, the substrate material is a sodium phosphite solution; in S500, the reaction route of the instantaneous conversion reaction is as follows: +Phosphorus-containing byproducts, among which... It is aryl or heteroaryl.

[0064] like Figures 3 to 4 As shown, in a preferred embodiment of the present invention, in the above-mentioned rapid conversion method for continuous production of diazonium salt, in S400, when the conversion reaction is a condensation reaction and a cyclization reaction, the ammonia raw material is an aromatic amine, and the substrate material is ethyl 2,3-dicyanopropionate; in S500, the reaction route of the instantaneous conversion reaction includes: at 0-5°C, the diazonium salt generated by the conversion reaction undergoes a coupling reaction with ethyl 2,3-dicyanopropionate; ammonia water is added dropwise to adjust the pH value to 9-10, and the reaction is maintained at 0-5°C to complete the cyclization.

[0065] In a preferred embodiment of the present invention, in the above-mentioned rapid conversion method for continuous production of diazonium salt, in S400, when the ammonia feedstock is an aromatic amine, the aromatic amine is 2,6-dichloro-4-trifluoromethylaniline; in S500, the target product of the instantaneous conversion reaction is 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole.

[0066] like Figure 5 As shown, in a preferred embodiment of the present invention, in the rapid conversion method for continuous production of diazonium salts described above, in step S500, when the ammonia feedstock is an aromatic amine, the feedstock in the reactor comprises the following components by weight: 35-40 parts of 97% aromatic amine; 85-90 parts of 36% concentrated hydrochloric acid; 175-180 parts of ethanol; 25-26 parts of ethyl 2,3-dicyanopropionate; 10-12 parts of sodium nitrite; 0.1-0.5 parts of urea; 50-55 parts of 25% ammonia water; and 380-400 parts of water.

[0067] In a preferred embodiment of the present invention, in the above-mentioned rapid conversion method for continuous production of diazonium salt, in S400, the automated control is controlled by a DCS system; the DCS system synchronously and interlocks the real-time temperature of the reactor with the dripping flow rate of the ammonium salt solution, and synchronously and interlocks the flow rate of the sodium nitrite aqueous solution with the flow rate of the ammonium salt solution according to a set fixed molar ratio.

[0068] Specifically, the DCS system includes two flow measurement units, two electric regulating valves, a reactor temperature sensor, a stirring rate detection unit, a DCS control unit, and an alarm unit. The DCS system implements a closed-loop proportional interlock between the two feed flow rates and the reactor temperature. When the reactor temperature is too high, it automatically reduces at least one feed flow rate or changes the valve position according to a predetermined ratio until the temperature returns to the set range. When any parameter is abnormal, it automatically stops feeding and initiates emergency cooling, nitrogen pressure return, or reflux dilution procedures.

[0069] In a preferred embodiment of the present invention, in the above-mentioned rapid conversion method for continuous production of diazonium salt, in step S600, the step of processing the rapid conversion reaction mixture to separate the target product includes: adding an acid solution dropwise to the rapid conversion reaction mixture at 0-5°C, adjusting the pH value to 7-8, removing the ethanol solvent by vacuum distillation, filtering and rinsing the filter cake with water, and drying to obtain the target product solid with a purity ≥99%.

[0070] The technical solution of the present invention will be clearly and completely described below with reference to the embodiments thereof. Taking the conversion reaction as a condensation reaction and a cyclization reaction, the ammonia raw material as an aromatic amine, and the substrate material as ethyl 2,3-dicyanopropionate as an example, 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole is prepared. In the following embodiments, the content of each component is expressed as a mass ratio, as shown in Table 1.

[0071] Table 1: Distribution ratio of 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole in preparation.

[0072] Component Name Example 1 Example 2 Example 3 Example 4 Example 5 Comparative Example 1 2,6-Dichloro-4-trifluoromethylaniline (97%) 36.7 36.7 36.7 36.7 36.7 36.7 Concentrated hydrochloric acid (36%) 87 80 90 87 85 87 Ethanol (solvent) 178 158 200 170 185 178 Ethyl 2,3-dicyanopropionate 25.9 25.9 25.9 25.9 25.9 25.9 Sodium nitrite 11 11 12 11 11 11 urea 0.3 0.3 0.4 0.3 0.3 0.3 Ammonia (25%) 53 50 55 53 52 53 water 390 390 400 380 390 390

[0073] Each embodiment adopts the following unified process path, and the process parameters are shown in Table 1. Fine-tuning is performed according to the component ratios, and dual-path synchronous proportional dripping and in-situ rapid conversion experiments are conducted. Specific experimental steps include:

[0074] (1) Add aromatic amine and concentrated hydrochloric acid to a 500ml reaction vessel, stir at room temperature for 2 hours to fully form salt, then add some ethanol and stir until the solid is completely dissolved to obtain an aromatic amine hydrochloride ethanol solution;

[0075] (2) Add ethyl 2,3-dicyanopropionate and the remaining ethanol to a 1L reactor and stir to dissolve;

[0076] (3) Under the control of the DCS system, the aromatic amine hydrochloride solution and sodium nitrite aqueous solution, wherein the sodium nitrite is dissolved in 80g of water, are simultaneously added dropwise into a 1L reactor in proportion. The diazonium salt is used as soon as it is generated and directly carried out the coupling reaction.

[0077] (4) After the addition is completed, stir at 0-5℃ for 2 hours, then add urea to eliminate excess nitrite, and continue stirring for 0.5 hours.

[0078] (5) Add ammonia water dropwise at 0-5℃ to adjust the pH of the system to 9-10, and stir for 2 hours to carry out the cyclization reaction;

[0079] (6) Add dilute hydrochloric acid to adjust the pH value to 7-8, remove ethanol by vacuum distillation, and obtain a solid product by washing, filtering and drying.

[0080] The comparative example adopted the following implementation path, with process parameters shown in Table 1. Specific experimental steps included: preparation and accumulation of the diazonium salt in a diazotization reactor, followed by slow dropwise addition of the diazonium salt solution to a reaction vessel containing ethyl 2,3-dicyanopropionate via a high-level tank. In Comparative Example 1, the diazonium salt needed to flow in a transport pipeline, posing a risk of decomposition and explosion due to temperature rise. Furthermore, due to localized overheating during storage, side reactions were highly likely to occur.

[0081] Table 2: Comparison of Performance Test Results

[0082] Test Project Example 1 Example 2 Example 3 Example 4 Example 5 Comparative Example 1 Product yield 96% 94.5% 95.2% 93.8% 94.1% 75% HPLC purity Approximately 100% 99.2% 99.5% 99.0% 99.3% 88% Reaction safety Intrinsic safety Safety Safety Safety Safety Extremely Explosive Diazonium salt accumulation Extremely small amounts (in-situ reaction) trace amount trace amount trace amount trace amount Extremely large, posing a safety hazard Simplicity of process Reduce steps, automate Simple Simple Simple Simple The process is lengthy and requires extraction.

[0083] As shown in the examples and comparative examples, the optimal formulation example 1 (as shown in the examples and comparative examples) Figure 5 (As shown) Under the precise control of the DCS system, the product yield is significantly increased from 75% in the traditional process to 96% through in-situ rapid conversion technology, and the purity reaches nearly 100%. The rapid conversion technology for continuous production of diazonium salts of the present invention eliminates the storage and transportation process of diazonium salts, solving the explosion risk from the source of the process and realizing the inherent safety of the diazotization process.

[0084] Based on the above embodiments and comparative examples, the specific preparation process of the final optimal formulation example 1 is as follows:

[0085] (1) Prepare the raw materials. The specific amount of materials to be added is as follows, by weight:

[0086] 2,6-Dichloro-4-trifluoromethylaniline (97%): 36.7g;

[0087] Concentrated hydrochloric acid (36%): 87g;

[0088] Ethanol (polar solvent): 178g, added in steps, 158g for dissolving aromatic amine salts, 20g for the base system;

[0089] Ethyl 2,3-dicyanopropionate: 25.9g;

[0090] Sodium nitrite: 11g;

[0091] Urea: 0.3g;

[0092] Ammonia (25%): 53g;

[0093] Water: 390g, of which 80g is used to dissolve sodium nitrite, 300g is used for washing, and the remainder is used to prepare dilute acid.

[0094] (2) Add 36.7g of aromatic amine and 87g of 36% concentrated hydrochloric acid to a 500ml reaction vessel and stir for 2 hours at room temperature to fully form salt. Then add 158g of ethanol to the vessel and continue stirring until the white solid is completely dissolved to obtain an aromatic amine hydrochloride ethanol solution. Pour it into the first metering tank. Dissolve 11g of sodium nitrite in 80g of water to prepare a sodium nitrite aqueous solution of a certain concentration and pour it into the second metering tank.

[0095] (3) Add 25.9g of ethyl 2,3-dicyanopropionate and 20g of ethanol to a 1L reactor, turn on the stirring to dissolve them completely, and use the cooling system to adjust and stabilize the internal temperature of the reactor within the range of 0~5℃.

[0096] (4) Turn on the DCS automated control system. Through two feed pumps, flow meters and automatic regulating valves, the aromatic amine salt solution in the first metering tank and the sodium nitrite solution in the second metering tank are simultaneously added to the 1L reactor. The regulating valve is interlocked with the reactor internal temperature. At the same time, the flow meters and regulating valves of the two materials are interlocked according to the set ratio. By adjusting the dripping flow rate of one material, the other material is automatically matched to ensure that the diazonium salt is generated while the next condensation reaction is carried out, thus eliminating the accumulation of diazonium salt.

[0097] (5) Keep the temperature of the vessel at 0-5℃. After the addition is completed, continue to stir the reaction at this temperature for 2 hours. Add 0.3g of urea to the vessel and stir at 0-5℃ for 0.5 hours to eliminate excess nitrite. At 0-5℃, add 25% ammonia water to the system to adjust the pH value to 9-10. After the addition is completed, continue to stir for 2 hours to complete the cyclization reaction.

[0098] (6) Keep the temperature at 0-5℃, add about 17g of 15% dilute hydrochloric acid solution to the kettle, adjust the pH of the system to 7-8 to be neutral, then naturally heat to room temperature and stir for 1 hour, turn on the vacuum distillation device to remove and recover the solvent ethanol in the kettle, filter the remaining material, rinse the obtained filter cake with 300g of water, place the filter cake in the oven to dry, and obtain a yellowish-brown solid product.

[0099] In the final performance test results, the weight of the product 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole was 47.7 g, the HPLC content was approximately 100%, and the total product yield was 96%. Throughout the reaction process, the diazonium salt was used immediately upon production, eliminating storage and transportation risks and achieving intrinsic safety control.

[0100] It should be understood that the specific embodiments described above are merely illustrative or explanatory of the principles of the invention and do not constitute a limitation thereof. Therefore, any modifications, equivalent substitutions, improvements, etc., made without departing from the spirit and scope of the invention should be included within the protection scope of the invention. Furthermore, the appended claims are intended to cover all variations and modifications falling within the scope and boundaries of the appended claims, or equivalent forms of such scope and boundaries.

Claims

1. A rapid conversion method for continuous production of diazonium salts, characterized in that, include: S100, dissolve the ammonium raw material in a polar solvent, add acid to obtain an ammonium salt solution, and dissolve sodium nitrite in water to obtain an aqueous sodium nitrite solution; S200, the base system materials and solvents for the conversion reaction with diazonium salt are added into the reactor, and the reactor is prepared by temperature adjustment and stirring to construct the reaction system; S300, the ammonium salt solution and the sodium nitrite aqueous solution are simultaneously added dropwise to the reaction system in a set ratio; S400, during the synchronous dripping process, through automated control, causes the ammonium salt solution to undergo a conversion reaction with the sodium nitrite aqueous solution in the reaction vessel to generate diazonium salt; S500, after the diazonium salt is generated in the reactor, it undergoes an immediate conversion reaction with the reaction system without separate separation, to obtain a rapid conversion reaction mixture; S600, the rapid conversion reaction mixture is processed to separate and obtain the target product.

2. The rapid conversion method for continuous production of diazonium salts according to claim 1, characterized in that, In S100, the polar solvent includes at least one of water, ethanol, tetrahydrofuran, and DMF.

3. The rapid conversion method for continuous production of diazonium salts according to claim 2, characterized in that, In S200, the substrate material includes at least one of dicyano-based substrates, dicyanate, alkyne, active acrylate, and ketone.

4. The rapid conversion method for continuous production of diazonium salts according to claim 3, characterized in that, In S400, the conversion reaction includes at least one of substitution reaction, condensation reaction, cyclization reaction and deamination reaction.

5. The rapid conversion method for continuous production of diazonium salts according to claim 4, characterized in that, In S400, when the conversion reaction is a deamination reaction, the substrate material is a sodium phosphite solution; In S500, the reaction route of the instantaneous conversion reaction is as follows: +Phosphorus-containing byproducts, among which... It is aryl or heteroaryl.

6. The rapid conversion method for continuous production of diazonium salts according to claim 4, characterized in that, In S400, when the conversion reaction is a condensation reaction and a cyclization reaction, the ammonia raw material is an aromatic amine, and the substrate material is ethyl 2,3-dicyanopropionate. In S500, the reaction pathway of the instantaneous conversion reaction includes: At 0–5°C, the diazonium salt generated in the conversion reaction undergoes a coupling reaction with ethyl 2,3-dicyanopropionate; Add ammonia water to adjust the pH value to 9-10, and keep the reaction at 0-5℃ to complete the cyclization.

7. The rapid conversion method for continuous production of diazonium salts according to claim 6, characterized in that, In S400, when the ammonia raw material is an aromatic amine, the aromatic amine is 2,6-dichloro-4-trifluoromethylaniline; In S500, the target product of the instantaneous conversion reaction is 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole.

8. The rapid conversion method for continuous production of diazonium salts according to claim 6, characterized in that, In S500, when the ammonia raw material is an aromatic amine, the raw material in the reactor comprises the following components by weight: 35-40 parts of aromatic amines; 85-90 parts of 36% concentrated hydrochloric acid; 175-180 parts of ethanol; 25-26 parts of ethyl 2,3-dicyanopropionate; Sodium nitrite 10-12 parts; Urea 0.1–0.5 parts; 50-55 parts of 25% ammonia solution; 380-400 parts water.

9. The rapid conversion method for continuous production of diazonium salts according to claim 1, characterized in that, In S400, the automation control is controlled by a DCS system; The DCS system synchronously and interlocks the real-time temperature of the reactor with the dripping flow rate of the ammonium salt solution, and synchronously and interlocks the flow rate of the sodium nitrite aqueous solution with the flow rate of the ammonium salt solution according to a set fixed molar ratio.

10. The rapid conversion method for continuous production of diazonium salts according to claim 1, characterized in that, In S600, the process of treating the rapid conversion reaction mixture to separate and obtain the target product includes: An acid solution was added dropwise to the rapid conversion reaction mixture at 0–5°C to adjust the pH to 7–8. The ethanol solvent was removed by vacuum distillation, the mixture was filtered, the filter cake was washed with water, and dried to obtain the target product solid.

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