Process for the preparation of pyrazoles

Abstract

The present application relates to the technical fields of compound synthesis, more particularly to a preparation process of pyrazole. The present application aims to improve the preparation efficiency and yield of pyrazole. The preparation process of pyrazole comprises the following steps: mixing glycerol, hydrazine hydrate and a catalyst to form a reaction system, adding a first part of concentrated sulfuric acid dropwise, and generating a first intermediate product; heating the first intermediate product and adding a second part of concentrated sulfuric acid dropwise, so that a cyclization reaction occurs to generate a second intermediate product; the second intermediate product is subjected to an oxidative dehydrogenation reaction at high temperature to generate a crude pyrazole product; and the crude pyrazole product is subjected to neutralization treatment and post-treatment to obtain a final pyrazole product.

Description

Technical Field

[0001] This invention relates to the field of compound synthesis technology, and more specifically, to a process for preparing pyrazole. Background Technology

[0002] Pyrazole (1,2-diazolium) is a key intermediate in the synthesis of pharmaceuticals, pesticides and functional materials. Current industrial production mostly adopts batch process, using a semi-jacketed enamel reactor for liquid phase synthesis. Due to the low heat transfer efficiency, poor temperature control accuracy and long heating time of the enamel reactor, the process has the following shortcomings: (1) The reaction time for a single batch is as long as 40 hours, resulting in low production efficiency. The traditional process uses glycerol, hydrazine hydrate, concentrated sulfuric acid and potassium iodide to be added at one time. The temperature needs to be controlled at about 80°C during the feeding stage. However, the one-time addition of concentrated sulfuric acid is prone to local overheating and violent exothermic reactions. In order to avoid side reactions and the risk of material overflow, the reaction time has to be extended to reduce the rate, which seriously restricts the production capacity. (2) It is difficult to improve the yield of the target product. On the one hand, when the temperature is raised to 100°C, the intermediate product acrolein is partially generated and volatilized and lost, reducing the raw material conversion rate; on the other hand, the local overheating caused by the one-time feeding aggravates the side reactions, increases the by-products, and ultimately affects the yield. (3) Energy consumption is serious. The reaction requires gradual temperature increases to 150°C and a long period of constant temperature. It relies on jacket heat transfer, which results in slow heating and low thermal efficiency, leading to high production costs. Summary of the Invention

[0003] The present invention aims to overcome at least one of the defects of the prior art and provide a pyrazole preparation process, which aims to improve preparation efficiency and yield.

[0004] The technical solution adopted by this invention is to provide a pyrazole preparation process, comprising: Glycerol, hydrazine hydrate, and catalyst are mixed to form a reaction system. The first part of concentrated sulfuric acid is added dropwise, and the reaction produces the first intermediate product. The first intermediate product was heated and a second portion of concentrated sulfuric acid was added dropwise, resulting in a cyclization reaction to generate the second intermediate product. The second intermediate product undergoes an oxidative dehydrogenation reaction at high temperature to generate crude pyrazole product. The crude pyrazole product was neutralized and then post-processed to obtain the final pyrazole product.

[0005] This invention avoids the premature formation and volatilization of the intermediate product acrolein by adding concentrated sulfuric acid in two stages, thereby reducing intermediate product loss and increasing pyrazole yield. It also effectively solves the problem that in the traditional process, adding concentrated sulfuric acid in one stage requires a long cooling time due to temperature control during the initial stage of the reaction, and the heating process consumes a lot of energy.

[0006] Furthermore, the molar ratio of the first part of concentrated sulfuric acid to the second part of concentrated sulfuric acid is 1:1-1.1:0.9.

[0007] Furthermore, during the dropwise addition of the first portion of concentrated sulfuric acid, the reaction temperature is controlled at 40-60℃.

[0008] Furthermore, during the addition of the second portion of concentrated sulfuric acid, the reaction temperature was controlled at 130-135℃.

[0009] Furthermore, the catalyst is any one or a mixture of two of potassium iodide and sodium iodide.

[0010] Furthermore, the molar ratio of the first and second portions of concentrated sulfuric acid to glycerol, hydrazine hydrate, and catalyst is (1.9-2.1):(0.9-1.1):(0.9-1.1):(0.004-0.006).

[0011] Furthermore, the concentration of hydrazine hydrate is 50-80%.

[0012] Furthermore, the concentration of concentrated sulfuric acid is 80-98%.

[0013] Furthermore, the concentration of glycerol is above 95%.

[0014] Further, the heating of the first intermediate product and the dropwise addition of the second portion of concentrated sulfuric acid includes: The first intermediate product is heated and drained until the temperature reaches 110-130℃, then the second part of concentrated sulfuric acid is added dropwise.

[0015] Furthermore, during the oxidative dehydrogenation reaction of the second intermediate, the reaction temperature is controlled at 140-160℃.

[0016] Furthermore, the crude pyrazole product is cooled to below 80°C and then neutralized.

[0017] Furthermore, the post-processing includes extraction, purification, and drying.

[0018] Compared with the prior art, the beneficial effects of the present invention are as follows: By improving the process of adding concentrated sulfuric acid in stages with controlled temperature, the present invention effectively solves the problems of easy loss of the intermediate product acrolein due to the one-time addition of concentrated sulfuric acid in the traditional process, the need to wait for a long cooling time due to temperature control when adding concentrated sulfuric acid in the early stage of the reaction, and the serious energy consumption during the heating process. By adding concentrated sulfuric acid in two stages, the first part of concentrated sulfuric acid is added at 40-60℃ to gently start the reaction, avoiding the premature generation and volatilization of the intermediate product acrolein. The second part of concentrated sulfuric acid is added at 110-130℃, and the temperature of the addition process is controlled at 130-135℃, which reduces the loss of intermediate products, significantly improves the yield of pyrazole, and shortens the reaction time. It also avoids high-temperature preheating throughout the process, thus achieving the purpose of energy saving and efficiency improvement. Attached Figure Description

[0019] Figure 1 The pyrazole preparation process of this invention is as follows. Figure 1 .

[0020] Figure 2 The pyrazole preparation process of this invention is as follows. Figure 2 . Detailed Implementation

[0021] refer to Figure 1 This invention provides a pyrazole preparation process, comprising the following steps: S100. Glycerol, hydrazine hydrate and catalyst are mixed to form a reaction system. The first part of concentrated sulfuric acid is added dropwise, and the reaction produces the first intermediate product. S200. The first intermediate product is heated and concentrated sulfuric acid is added dropwise, resulting in a cyclization reaction to generate the second intermediate product; S300. The second intermediate product undergoes an oxidative dehydrogenation reaction at high temperature to generate crude pyrazole product; S400. The crude pyrazole product was neutralized and then post-treated to obtain the final pyrazole product.

[0022] In a preferred embodiment, the mass concentration of hydrazine hydrate is 50-80%, the mass concentration of concentrated sulfuric acid is 80-98%, and the mass concentration of glycerol is 95% or higher. The catalyst is any one or a mixture of two of potassium iodide and sodium iodide.

[0023] In some specific embodiments, step S100 includes: sequentially adding glycerol, hydrazine hydrate, and a catalyst to a first container equipped with a stirring device, a dripping device, a thermometer, a reflux device, and a heating device; turning on the stirring device to allow the materials to mix thoroughly and uniformly at room temperature to form a homogeneous reaction system; after the mixture stabilizes, turning on the dripping device to uniformly add a first portion of concentrated sulfuric acid; during the dripping process, the temperature is controlled at 40-60°C. Tests of this invention show that by gently initiating the reaction with the first portion of concentrated sulfuric acid at 40-60°C, the premature formation and volatilization of the intermediate product acrolein can be avoided, thereby increasing the retention rate of the intermediate product and thus increasing the yield of the final product pyrazole. Tests show that within this temperature range, a high pyrazole yield can be obtained, and the pyrazole can be guaranteed to have high purity. Lowering or raising the reaction temperature of the initial acidification process leads to a significant decrease in the pyrazole yield. In practice, the initial acidification reaction temperature can be 40℃, 41℃, 42℃, 44℃, 45℃, 47℃, 48℃, 50℃, 41℃, 52℃, 54℃, 55℃, 57℃, 58℃, 60℃, etc.

[0024] In some embodiments, during step S200, when the second portion of concentrated sulfuric acid is added dropwise to initiate the cyclization reaction, the reaction temperature is controlled at 130-135°C. Tests show that within this temperature range, it helps to improve the pyrazole yield and ensures high purity of the pyrazole. Lowering or raising the reaction temperature of the secondary acidification process leads to a decrease in the pyrazole yield. Specifically, the reaction temperature for the secondary acidification can be 130°C, 131°C, 132°C, 133°C, 134°C, 135°C, etc. Tests conducted in this invention show that controlling the reaction temperature of the secondary acidification to 130-135°C can improve the pyrazole yield.

[0025] In some embodiments, step S200 includes: first heating the first intermediate product and draining water during the heating process until a first preset temperature is reached, and then starting to add the second part of concentrated sulfuric acid dropwise. Preferably, the first preset temperature is 110℃-130℃. In specific implementations, the first preset temperature can be 110℃, 112℃, 114℃, 115℃, 117℃, 119℃, 120℃, 122℃, 124℃, 125℃, 127℃, 129℃, 130℃, etc.

[0026] In some embodiments, step S300 includes: heating the second intermediate product to a second preset temperature, and then holding it at that temperature to carry out an oxidative dehydrogenation reaction to generate a crude pyrazole product. Preferably, the second preset temperature is 140-160°C. In specific implementations, the second preset temperature can be 140°C, 142°C, 144°C, 145°C, 147°C, 149°C, 150°C, 152°C, 154°C, 155°C, 157°C, 159°C, 160°C, etc. The preferred time for the oxidative dehydrogenation reaction is 2-3 hours.

[0027] In some embodiments, step S400 includes: cooling the crude pyrazole product to below 80°C, then performing neutralization and post-treatment to obtain the final pyrazole product. Specifically, ammonia is added for neutralization, the pH of the reaction system is adjusted to neutral or weakly alkaline, and then the post-treatment step is performed.

[0028] Better, refer to Figure 2 The pyrazole preparation process of the present invention includes the following steps: T100. Mix glycerol, hydrazine hydrate and catalyst, add the first part of concentrated sulfuric acid dropwise, and react to generate the first intermediate product. The temperature is controlled at 40-60℃ during the dropwise addition process. T200. Heat the first intermediate product to 110-130℃, add the second part of concentrated sulfuric acid dropwise, and a cyclization reaction will occur to generate the second intermediate product. The temperature during the dropwise addition process is controlled at 130-135℃. T300. The second intermediate product is heated to 140-160℃ and subjected to an oxidative dehydrogenation reaction for 2-3 hours at a constant temperature to obtain crude pyrazole product. T400. The crude pyrazole product is cooled to below 80°C, neutralized with ammonia, and then post-treated to obtain the final pyrazole product.

[0029] In some embodiments, the post-processing includes extraction, purification, and drying. Specifically, extraction is performed using organic solvents such as ethyl acetate, dichloromethane, chloroform, diethyl ether, benzene, toluene, and xylene to fully transfer the target product pyrazole into the organic phase, and all organic phases are combined. The organic phase is then transferred to a rotary evaporator and evaporated until crystals precipitate. After crystallization, the water bath temperature is increased to 40°C and rotary evaporation continues to completely remove residual water and solvent, obtaining dry pyrazole crystals, which are the final pyrazole product.

[0030] In some embodiments, the molar ratio of the first part of concentrated sulfuric acid to the second part of concentrated sulfuric acid is 1:1 to 1.1:0.9. In specific implementations, the molar ratio of the first part of concentrated sulfuric acid to the second part of concentrated sulfuric acid can be 1:1, 1.02:0.98, 1.05:0.95, 1.07:0.93, 1.1:0.9, etc.

[0031] In some embodiments, the molar ratio of the first portion of concentrated sulfuric acid and the second portion of concentrated sulfuric acid to glycerol, hydrazine hydrate, and catalyst is (1.9-2.1):(0.9-1.1):(0.9-1.1):(0.004-0.006).

[0032] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0033] Unless otherwise specified, the experimental methods used in the following examples are conventional methods. Unless otherwise specified, the materials, reagents, methods, and instruments used are all conventional materials, reagents, methods, and instruments in the art, and can be obtained commercially by those skilled in the art.

[0034] Example 1 This embodiment provides a pyrazole preparation process, using the following raw materials and reagents: 19g of 99% glycerol, 0.17g of potassium iodide (KI), 13.83g of 80% hydrazine hydrate, 41.50g of 93% concentrated sulfuric acid, and appropriate amounts of ammonia and chloroform. In this embodiment, the molar ratio of the first part of concentrated sulfuric acid to the second part of concentrated sulfuric acid is 1.1:0.9.

[0035] (1) Material premixing and first part of sulfuric acid dropwise addition Add 19g of 99% glycerol, 13.83g of 80% hydrazine hydrate, and 0.17g of potassium iodide sequentially to a four-necked flask equipped with a stirrer, dropping funnel, thermometer, condenser, and oil bath heating device. Turn on the stirrer to allow the materials to mix thoroughly and evenly at room temperature, forming a homogeneous reaction system. After the mixture stabilizes, unscrew the stopcock of the dropping funnel and add 22.83g of concentrated sulfuric acid dropwise at a uniform rate. During the addition, maintain the temperature at 50°C and control the dropping rate to avoid localized overheating of the reaction system, ensuring a stable reaction and the formation of the first intermediate product.

[0036] (2) The heating process and the second part of sulfuric acid addition After the first part of sulfuric acid is added, the oil bath heating device is turned on, and the first intermediate product is slowly and gradually heated to 120°C according to the preset program. During this period, water is drained. When the temperature of the solution in the flask stabilizes at 120°C, the remaining second part of concentrated sulfuric acid, 18.67g, is added dropwise at a uniform rate. The temperature is controlled at 130°C to cause a cyclization reaction and generate the second intermediate product.

[0037] (3) Isothermal reaction stage After the second batch of concentrated sulfuric acid has been completely added, the second intermediate product is heated to 150°C and kept at this temperature for 3 hours to ensure that the reaction proceeds fully and the raw materials are completely converted to produce crude pyrazole.

[0038] (4) Cooling and neutralization treatment After the reaction is complete, stop heating and allow the crude pyrazole product to cool naturally to below 80°C. Then, slowly add ammonia water for neutralization and adjust the pH of the system to neutral or weakly alkaline.

[0039] (5) Product extraction The neutralized reaction solution was extracted three times with chloroform to ensure that pyrazole was fully transferred to the organic phase. All organic phases were then combined. The organic phases were transferred to a rotary evaporator and evaporated until crystals precipitated. After crystals precipitated, the water bath temperature was increased to 40°C and rotary evaporation was continued to completely remove residual water and solvent, obtaining dry pyrazole crystals.

[0040] The final product, pyrazole, was 12.93g, with a yield of 94.96% and a purity of 99.86%.

[0041] Example 2 This embodiment provides a pyrazole preparation process, and the raw materials and reagents used are as follows: 19g of 99% glycerol, 0.17g of potassium iodide (KI), 13.83g of 80% hydrazine hydrate, 41.50g of 93% concentrated sulfuric acid, and appropriate amounts of ammonia and chloroform. In this embodiment, the molar ratio of the first part of concentrated sulfuric acid to the second part of concentrated sulfuric acid is 1:1.

[0042] (1) Material premixing and first part of sulfuric acid dropwise addition Add 19g of 99% glycerol, 13.83g of 80% hydrazine hydrate, and 0.17g of potassium iodide sequentially to a four-necked flask equipped with a stirrer, dropping funnel, thermometer, condenser, and oil bath heating device. Turn on the stirrer to allow the materials to mix thoroughly and evenly at room temperature, forming a homogeneous reaction system. After the mixture stabilizes, unscrew the stopcock of the dropping funnel and add 20.75g of concentrated sulfuric acid dropwise at a uniform rate. During the addition, maintain the temperature at 50°C and control the dropping rate to avoid localized overheating of the reaction system, ensuring a stable reaction and the formation of the first intermediate product.

[0043] (2) The heating process and the second part of sulfuric acid addition After the first part of sulfuric acid is added, the oil bath heating device is turned on, and the first intermediate product is slowly and gradually heated to 120°C according to the preset program. During this period, water is drained. When the temperature of the solution in the flask stabilizes at 120°C, the remaining 20.75g of concentrated sulfuric acid in the second part is added dropwise at a uniform rate. The temperature is controlled at 133°C to cause a cyclization reaction and generate the second intermediate product.

[0044] (3) Isothermal reaction stage After the second batch of concentrated sulfuric acid has been completely added, the second intermediate product is heated to 150°C and kept at this temperature for 3 hours to ensure that the reaction proceeds fully and the raw materials are completely converted to produce crude pyrazole.

[0045] (4) Cooling and neutralization treatment After the reaction is complete, stop heating and allow the crude pyrazole product to cool naturally to below 80°C. Then, slowly add ammonia water for neutralization and adjust the pH of the system to neutral or weakly alkaline.

[0046] (5) Product extraction The neutralized reaction solution was extracted three times with chloroform to ensure that the target product pyrazole was fully transferred to the organic phase. All organic phases were then combined. The organic phase was transferred to a rotary evaporator and evaporated until crystals precipitated. After crystallization, the water bath temperature was increased to 40°C and rotary evaporation was continued to completely remove residual water and solvent, obtaining dry pyrazole crystals.

[0047] The final product, pyrazole, was 12.62g, with a yield of 92.68% and a purity of 99.77%.

[0048] Comparative Example 1 This comparative example provides a pyrazole preparation process. Compared with Example 1, the only difference in this comparative example is that the amounts of the first part of concentrated sulfuric acid and the second part of concentrated sulfuric acid are adjusted to 14.53g and 26.97g, respectively, so that the molar ratio of the first part of concentrated sulfuric acid to the second part of concentrated sulfuric acid is 0.7:1.3. Other raw materials and their amounts, as well as the preparation process and parameters, remain the same.

[0049] The final product, pyrazole, was 10.99g, with a yield of 80.71% and a purity of 99.28%.

[0050] Comparative Example 2 This comparative example provides a pyrazole preparation process. Compared with Example 1, the only difference in this comparative example is that the amounts of the first part of concentrated sulfuric acid and the second part of concentrated sulfuric acid are adjusted to 26.97g and 14.53g, respectively, so that the molar ratio of the first part of concentrated sulfuric acid to the second part of concentrated sulfuric acid is 1.3:0.7. Other raw materials and their amounts, as well as the preparation process and parameters, remain the same.

[0051] The final product, pyrazole, was obtained in the form of 11.76g, with a yield of 86.37% and a purity of 99.59%. Example 3 This embodiment provides a pyrazole preparation process, using the following raw materials and reagents: 19g of 99% glycerol, 0.17g of potassium iodide (KI), 13.83g of 80% hydrazine hydrate, 41.50g of 93% concentrated sulfuric acid, and appropriate amounts of ammonia and chloroform.

[0052] (1) Material premixing and first part of sulfuric acid dropwise addition Add 19g of 99% glycerol, 13.83g of 80% hydrazine hydrate, and 0.17g of potassium iodide sequentially to a four-necked flask equipped with a stirrer, dropping funnel, thermometer, condenser, and oil bath heating device. Turn on the stirrer to allow the materials to mix thoroughly and evenly at room temperature, forming a homogeneous reaction system. After the mixture stabilizes, unscrew the stopcock of the dropping funnel and add 22.83g of concentrated sulfuric acid dropwise at a uniform rate. During the addition, maintain the temperature at 40°C and control the dropping rate to avoid localized overheating of the reaction system, ensuring a stable reaction and the formation of the first intermediate product.

[0053] (2) The heating process and the second part of sulfuric acid addition After the first part of sulfuric acid is added, the oil bath heating device is turned on, and the first intermediate product is slowly heated to 120°C according to the preset program. During this period, water is drained. When the temperature of the solution in the flask stabilizes at 120°C, the second part of concentrated sulfuric acid, 18.67g, is added dropwise at a uniform rate. The temperature is controlled at 135°C, and a cyclization reaction occurs to generate the second intermediate product.

[0054] (3) Isothermal reaction stage After the second batch of concentrated sulfuric acid has been completely added, the second intermediate product is heated to 150°C and kept at this temperature for 3 hours to ensure that the reaction proceeds fully and the raw materials are completely converted to produce crude pyrazole.

[0055] (4) Cooling and neutralization treatment After the reaction is complete, stop heating and allow the crude pyrazole product to cool naturally to below 80°C. Then, slowly add ammonia water for neutralization and adjust the pH of the system to neutral or weakly alkaline to create stable conditions for subsequent extraction operations and prevent the product from decomposing under strongly acidic conditions.

[0056] (5) Product extraction The neutralized reaction solution was extracted three times with chloroform to ensure that the target product pyrazole was fully transferred to the organic phase. All organic phases were then combined. The organic phase was transferred to a rotary evaporator and evaporated until crystals precipitated. After crystallization, the water bath temperature was increased to 40°C and rotary evaporation was continued to completely remove residual water and solvent, obtaining dry pyrazole crystals.

[0057] The final product, pyrazole, was 12.82 g, with a yield of 94.15% and a purity of 99.42%.

[0058] Example 4 This embodiment provides a pyrazole preparation process, using the following raw materials and reagents: 19g of 99% glycerol, 0.17g of potassium iodide (KI), 13.83g of 80% hydrazine hydrate, 41.50g of 93% concentrated sulfuric acid, and appropriate amounts of ammonia and chloroform.

[0059] (1) Material premixing and first part of sulfuric acid dropwise addition Add 19g of 99% glycerol, 13.83g of 80% hydrazine hydrate, and 0.17g of potassium iodide sequentially to a four-necked flask equipped with a stirrer, dropping funnel, thermometer, condenser, and oil bath heating device. Turn on the stirrer to allow the materials to mix thoroughly and evenly at room temperature, forming a homogeneous reaction system. After the mixture stabilizes, unscrew the stopcock of the dropping funnel and add 22.83g of concentrated sulfuric acid dropwise at a uniform rate. During the addition, maintain the temperature at 60℃ and control the dropping rate to avoid localized overheating of the reaction system, ensuring a stable reaction and the formation of the first intermediate product.

[0060] (2) The heating process and the second part of sulfuric acid addition After the first part of sulfuric acid is added, the oil bath heating device is turned on, and the first intermediate product is slowly and gradually heated to 120°C according to the preset program. During this period, water is drained. When the temperature of the solution in the flask stabilizes at 120°C, the remaining second part of concentrated sulfuric acid, 18.67g, is added dropwise at a uniform rate. The temperature is controlled at 130°C to cause a cyclization reaction and generate the second intermediate product.

[0061] (3) Isothermal reaction stage After the second batch of concentrated sulfuric acid has been completely added, the second intermediate product is heated to 150°C and kept at this temperature for 3 hours to ensure that the reaction proceeds fully and the raw materials are completely converted to produce crude pyrazole.

[0062] (4) Cooling and neutralization treatment After the reaction is complete, stop heating and allow the crude pyrazole product to cool naturally to below 80°C. Then, slowly add ammonia water for neutralization and adjust the pH of the system to neutral or weakly alkaline to create stable conditions for subsequent extraction operations and prevent the product from decomposing under strongly acidic conditions.

[0063] (5) Product extraction The neutralized reaction solution was extracted three times with chloroform to ensure that the target product pyrazole was fully transferred to the organic phase. All organic phases were then combined. The organic phase was transferred to a rotary evaporator and evaporated until crystals precipitated. After crystallization, the water bath temperature was increased to 40°C and rotary evaporation was continued to completely remove residual water and solvent, obtaining dry pyrazole crystals.

[0064] The final product, pyrazole, was obtained in the form of 12.68g, with a yield of 93.13% and a purity of 99.15%. Comparative Example 3 This comparative example provides a pyrazole preparation process. Compared with Example 3, the only difference in this comparative example is that the temperature in step (1) during the dropwise addition of the first part of concentrated sulfuric acid is adjusted to 30°C. Other raw materials and their amounts, as well as the preparation process and parameters, remain the same.

[0065] The final product, pyrazole, was 11.64 g, with a yield of 85.49% and a purity of 99.19%.

[0066] Comparative Example 4 This comparative example provides a pyrazole preparation process. Compared with Example 3, the only difference in this comparative example is that the temperature in step (1) during the dropwise addition of the first part of concentrated sulfuric acid is adjusted to 80°C. Other raw materials and their amounts, as well as the preparation process and parameters, remain the same.

[0067] The final product, pyrazole, was 12.08 g, with a yield of 88.72% and a purity of 99.03%.

[0068] Example 5 This embodiment provides a pyrazole preparation process, using the following raw materials and reagents: 19g of 99% glycerol, 0.17g of potassium iodide (KI), 13.83g of 80% hydrazine hydrate, 41.50g of 93% concentrated sulfuric acid, and appropriate amounts of ammonia and chloroform.

[0069] (1) Material premixing and first part of sulfuric acid dropwise addition Add 19g of 99% glycerol, 13.83g of 80% hydrazine hydrate, and 0.17g of potassium iodide sequentially to a four-necked flask equipped with a stirrer, dropping funnel, thermometer, condenser, and oil bath heating device. Turn on the stirrer to allow the materials to mix thoroughly and evenly at room temperature, forming a homogeneous reaction system. After the mixture stabilizes, unscrew the stopcock of the dropping funnel and add 22.83g of concentrated sulfuric acid dropwise at a uniform rate. During the addition, maintain the temperature at 50°C and control the dropping rate to avoid localized overheating of the reaction system, ensuring a stable reaction and the formation of the first intermediate product.

[0070] (2) The heating process and the second part of sulfuric acid addition After the first part of sulfuric acid is added, the oil bath heating device is turned on, and the first intermediate product is slowly and gradually heated to 120°C according to the preset program. During this period, water is drained. When the temperature of the solution in the flask stabilizes at 120°C, the remaining second part of concentrated sulfuric acid, 18.67g, is added dropwise at a uniform rate. The temperature is controlled at 130°C to cause a cyclization reaction and generate the second intermediate product.

[0071] (3) Isothermal reaction stage After the second batch of concentrated sulfuric acid has been completely added, the second intermediate product is heated to 150°C and kept at this temperature for 3 hours to ensure that the reaction proceeds fully and the raw materials are completely converted to produce crude pyrazole.

[0072] (4) Cooling and neutralization treatment After the reaction is complete, stop heating and allow the crude pyrazole product to cool naturally to below 80°C. Then, slowly add ammonia water for neutralization and adjust the pH of the system to neutral or weakly alkaline to create stable conditions for subsequent extraction operations and prevent the product from decomposing under strongly acidic conditions.

[0073] (5) Product extraction The neutralized reaction solution was extracted three times with chloroform to ensure that the target product pyrazole was fully transferred to the organic phase. All organic phases were then combined. The organic phase was transferred to a rotary evaporator and evaporated until crystals precipitated. After crystallization, the water bath temperature was increased to 40°C and rotary evaporation was continued to completely remove residual water and solvent, obtaining dry pyrazole crystals.

[0074] The final product, pyrazole, was 12.89 g, with a yield of 94.67% and a purity of 99.53%.

[0075] Comparative Example 5 This comparative example provides a pyrazole preparation process. Compared with Example 3, the only difference in this comparative example is that the temperature in step (2) during the addition of the second part of concentrated sulfuric acid is adjusted to 120°C. Other raw materials and their amounts, as well as the preparation process and parameters, remain the same.

[0076] The final product, pyrazole, was 12.15g, with a yield of 89.01% and a purity of 99.46%.

[0077] Comparative Example 6 This comparative example provides a pyrazole preparation process. Compared with Example 3, the only difference in this comparative example is that the temperature in step (2) during the addition of the second part of concentrated sulfuric acid is adjusted to 140°C. Other raw materials and their amounts, as well as the preparation process and parameters, remain the same.

[0078] The final product, pyrazole, was 11.99g, with a yield of 88.06% and a purity of 99.76%.

[0079] Comparative Example 7 This comparative example provides a pyrazole preparation process, using the following raw materials and reagents: 19g of 99% glycerol, 0.17g of potassium iodide (KI), 13.83g of 80% hydrazine hydrate, 41.50g of 93% concentrated sulfuric acid, and appropriate amounts of ammonia and chloroform.

[0080] Compared with Example 1, the only difference in this comparative example is that all the sulfuric acid is added dropwise in one step. The specific process is as follows: (1) Material premixing and sulfuric acid addition Add 19g of 99% glycerol, 13.83g of 80% hydrazine hydrate, and 0.17g of potassium iodide sequentially to a four-necked flask equipped with a stirrer, dropping funnel, thermometer, condenser, and oil bath heating device. Turn on the stirrer to allow the materials to mix thoroughly and evenly at room temperature, forming a homogeneous reaction system. After the mixture stabilizes, unscrew the stopcock of the dropping funnel and add all the concentrated sulfuric acid dropwise at a uniform rate. During the dropwise addition, maintain the temperature at 50°C and control the dropping rate to avoid localized overheating of the reaction system, ensuring a stable reaction.

[0081] (2) Isothermal reaction stage The temperature was gradually increased to 150°C and kept at this temperature for 3 hours to ensure that the reaction proceeded fully, the raw materials were completely converted, and the target product pyrazole was generated.

[0082] (4) Cooling and neutralization treatment After the reaction is complete, stop heating and allow the system to cool naturally to below 80°C. Then, slowly add ammonia water for neutralization and adjust the pH of the system to neutral or weakly alkaline to create stable conditions for subsequent extraction operations and prevent the product from decomposing under strongly acidic conditions.

[0083] (5) Product extraction The neutralized reaction solution was extracted three times with chloroform to ensure that the target product pyrazole was fully transferred to the organic phase. All organic phases were then combined. The organic phase was transferred to a rotary evaporator and evaporated until crystals precipitated. After crystallization, the water bath temperature was increased to 40°C and rotary evaporation was continued to completely remove residual water and solvent, obtaining dry pyrazole crystals.

[0084] The final product, pyrazole, was 10.79 g, with a yield of 79.25% and a purity of 99.86%.

[0085] Test case Table 1. Summary of pyrazole yields and reaction periods in Examples 1-5 and Comparative Examples 1-6: The test results show that: Compared to Example 1, the only difference between Comparative Examples 1 and 2 is the molar ratio of the first portion of concentrated sulfuric acid to the second portion of concentrated sulfuric acid. Specifically, Comparative Example 1 lowered the molar ratio of the first portion of concentrated sulfuric acid to the second portion to 0.7:1.3, while Comparative Example 2 increased the molar ratio of the first portion of concentrated sulfuric acid to the second portion to 1.3:0.7. Referring to Table 1, it can be seen that the pyrazole yield of both Comparative Examples 1 and 2 decreased significantly compared to Example 1. Combining the pyrazole yield data of Examples 1-5 in Table 1, it can be seen that when the molar ratio of the first portion of concentrated sulfuric acid to the second portion of concentrated sulfuric acid is set in the range of 1:1-1.1:0.9, the yield of pyrazole is optimal.

[0086] Compared with Example 3, the only difference between Comparative Examples 3 and 4 is the temperature during the addition of the first part of concentrated sulfuric acid in step "(1) Material premixing and first part sulfuric acid dropwise addition". Specifically, Comparative Example 3 lowered the temperature of the first part of concentrated sulfuric acid dropwise addition to 30°C, while Comparative Example 4 raised the temperature of the first part of concentrated sulfuric acid dropwise addition to 80°C. Referring to Table 1, it can be seen that the pyrazole yield of Comparative Examples 3 and 4 decreased compared with Example 3. Combining the pyrazole yield data of Examples 1-5 in Table 1, it can be seen that the present invention controls the temperature during the first part of concentrated sulfuric acid dropwise addition at 40-60°C, which can ensure a high pyrazole yield.

[0087] Compared with Example 3, the only difference between Comparative Examples 5 and 6 is the temperature during the addition of the second part of concentrated sulfuric acid in step "(2) Heating process and second part sulfuric acid addition". Specifically, Comparative Example 5 lowered the temperature of the second part of concentrated sulfuric acid addition process to 120°C, while Comparative Example 6 raised the temperature of the second part of concentrated sulfuric acid addition process to 140°C. Referring to Table 1, it can be seen that the pyrazole yield of Comparative Examples 5 and 6 decreased compared with Example 3. Combining the pyrazole yield data of Examples 1-5 in Table 1, it can be seen that the present invention controls the temperature during the addition of the second part of concentrated sulfuric acid at 130-135°C, which can ensure a high pyrazole yield.

[0088] Compared with Example 1, the only difference in Comparative Example 7 is that the sulfuric acid addition process is changed to a conventional one-step addition. As can be seen from Table 1, the pyrazole yield of Comparative Example 7 is significantly reduced. Combined with the pyrazole yield data of Examples 1-5 in Table 1, it can be seen that the present invention uses a two-stage sulfuric acid addition process, which uses the reaction heat released by the addition of concentrated sulfuric acid to the system to heat the system, eliminating the need for a long heating process and shortening the single reaction cycle from 10 hours to 8 hours. At the same time, the present invention can avoid the premature generation and volatilization of the intermediate product acrolein, and significantly improve the pyrazole yield by reducing the loss of intermediate products, thus achieving energy saving and efficiency improvement.

[0089] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the technical solution of the present invention, and are not intended to limit the specific implementation of the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the claims of the present invention should be included within the protection scope of the claims of the present invention.

Claims

1. A process for preparing pyrazole, characterized in that, include: Glycerol, hydrazine hydrate, and catalyst are mixed to form a reaction system. The first part of concentrated sulfuric acid is added dropwise, and the reaction produces the first intermediate product. The first intermediate product was heated and a second portion of concentrated sulfuric acid was added dropwise, resulting in a cyclization reaction to generate the second intermediate product. The second intermediate product undergoes an oxidative dehydrogenation reaction at high temperature to generate crude pyrazole product. The crude pyrazole product was neutralized and then post-processed to obtain the final pyrazole product.

2. The pyrazole preparation process according to claim 1, characterized in that, The molar ratio of the first part of concentrated sulfuric acid to the second part of concentrated sulfuric acid is 1:1-1.1:0.

9.

3. The pyrazole preparation process according to claim 1, characterized in that, During the addition of the first portion of concentrated sulfuric acid, the reaction temperature is controlled at 40-60℃.

4. The pyrazole preparation process according to claim 1, characterized in that, During the addition of the second batch of concentrated sulfuric acid, the reaction temperature was controlled at 130-135℃.

5. The pyrazole preparation process according to any one of claims 1-4, characterized in that, The catalyst is any one or a mixture of two of potassium iodide and sodium iodide.

6. The pyrazole preparation process according to any one of claims 1-4, characterized in that, The molar ratio of the first and second portions of concentrated sulfuric acid to glycerol, hydrazine hydrate, and catalyst is (1.9-2.1):(0.9-1.1):(0.9-1.1):(0.004-0.006).

7. The pyrazole preparation process according to any one of claims 1-4, characterized in that, The concentration of hydrazine hydrate is 50-80%; and / or, The concentration of concentrated sulfuric acid is 80-98%; and / or, The concentration of glycerol is above 95%.

8. The pyrazole preparation process according to any one of claims 1-4, characterized in that, The heating of the first intermediate product and the dropwise addition of the second portion of concentrated sulfuric acid includes: The first intermediate product is heated and drained until the temperature reaches 110-130℃, then the second part of concentrated sulfuric acid is added dropwise.

9. The pyrazole preparation process according to any one of claims 1-4, characterized in that, During the oxidative dehydrogenation reaction of the second intermediate product, the reaction temperature is controlled at 140-160℃.

10. The pyrazole preparation process according to any one of claims 1-4, characterized in that, The crude pyrazole product is cooled to below 80°C and then neutralized; and / or, The post-processing includes extraction, purification, and drying.

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