Preparation method of pyrazole intermediate

Abstract

The invention discloses a preparation method of a pyrazole intermediate, which comprises the following steps: respectively introducing a glycerol aqueous solution and a concentrated sulfuric acid solution containing a catalyst into a microchannel reactor for reaction to obtain the pyrazole intermediate, and the pyrazole intermediate comprises 3-hydroxypropionaldehyde and acrolein. According to the preparation method of the pyrazole intermediate, based on the efficient heat exchange performance of the microchannel reactor, the reaction time can be obviously shortened, and adverse phenomena such as back-mixing, carbonization and violent heat release in the reaction process can be prevented, so that the yield of the pyrazole intermediate is increased, and the production efficiency of the pyrazole intermediate is greatly improved.

Description

Technical Field

[0001] The present invention relates to the field of compound synthesis, and in particular to a method for preparing a pyrazole intermediate. Background Art

[0002] Glycerol can be used to prepare 3-hydroxypropionaldehyde and acrolein. Among them, 3-hydroxypropionaldehyde can be used to prepare important biological products such as high-efficiency biological sterilants and anti-infection therapeutics; acrolein can be used to prepare important chemical products such as acrylic acid, methacrylic acid and acrylamide.

[0003] In the process of synthesizing pyrazole, it is necessary to first prepare a pyrazole intermediate. In the current conventional synthesis route, the pyrazole intermediate usually includes 3-hydroxypropanal and acrolein. This intermediate can further react with hydrazine sulfate to generate pyrazole, and the two substances can also be separated separately.

[0004] In the traditional production process of preparing pyrazole intermediates from propylene glycol, there are problems such as long reaction time, intense heat release, obvious back-mixing, and severe carbonization. The main reasons for the above problems are: the reaction process is an exothermic reaction, and during the addition of sulfuric acid, the dilution heat is obvious, so the process production requires the slow addition of concentrated sulfuric acid to the propylene glycol in the synthesis kettle under continuous stirring, resulting in a long dropwise addition time; during the reaction, products are continuously generated, but due to the back-mixing caused by the addition of concentrated sulfuric acid under stirring, movement in the opposite direction to the mainstream occurs in the synthesis kettle, which further causes the product to react with the concentrated sulfuric acid, resulting in product decomposition or even carbonization. Summary of the invention

[0005] The present invention is based on the inventor's discovery and understanding of the following facts and problems: in the traditional production process of preparing 3-hydroxypropionaldehyde and acrolein from glycerol, there are problems such as long time consumption, low efficiency, easy back mixing, severe carbonization, low yield, etc.

[0006] The present invention aims to solve one of the technical problems in the related art to at least a certain extent. To this end, the embodiments of the present invention provide a method for preparing a pyrazole intermediate, which can significantly shorten the reaction time based on the efficient heat exchange performance of a microchannel reactor, and can also prevent undesirable phenomena such as back mixing, carbonization and intense heat release during the reaction process, thereby increasing the yield of the pyrazole intermediate, improving the quality of the product, and greatly improving the production efficiency of the pyrazole intermediate.

[0007] The embodiment of the present invention provides a method for preparing a pyrazole intermediate, comprising: introducing a glycerol aqueous solution and a concentrated sulfuric acid solution containing a catalyst into a microchannel reactor respectively for reaction to obtain a pyrazole intermediate, wherein the pyrazole intermediate comprises 3-hydroxypropanal and acrolein.

[0008] The advantages and technical effects brought by the preparation method of the pyrazole intermediate of the embodiment of the present invention are as follows: a glycerol aqueous solution and a concentrated sulfuric acid solution containing a catalyst are respectively introduced into a microchannel reactor for dehydration reaction, and the reaction products are collected to obtain a mixture of 3-hydroxypropanal from which one molecule of water is removed from glycerol and acrolein from which two molecules of water are removed. Unlike large pipes and containers, the channels in the microchannel reactor are much smaller than those in the traditional system, with a microchannel size of about 1 mm. The smaller microchannel increases the effective contact surface area and improves the heat transfer and mass transfer performance. Based on the efficient heat exchange performance of the microchannel reactor, the dehydration reaction of glycerol in the channel can be accelerated at a speed 1000 times faster than the traditional system, which can significantly shorten the reaction time and prevent adverse phenomena such as back mixing, carbonization and intense heat release during the reaction. Specifically, the glycerol aqueous solution and the concentrated sulfuric acid solution containing the catalyst in the microchannel reactor spirally advance in the tube, which can play a certain role in preventing back mixing; the use of a microchannel reactor for the dehydration reaction of glycerol can reduce the reaction time, increase the effective contact area, and can efficiently transfer heat, prevent heat accumulation and intense heat release, and avoid carbonization. Reducing back mixing and reducing carbonization can improve the utilization rate of raw materials, thereby increasing the yield of pyrazole intermediates, and improving the quality of the product, greatly improving the production efficiency of 3-hydroxypropanal and acrolein. Microchannel reactors can also reduce the overall equipment volume, specifically by 10 times or more. Based on this, more microchannels can be connected in series to perform "numerical amplification", which can not only improve reaction efficiency and product quality, but also solve the problem of industrial amplification. The industrial amplification effect is small, thereby reducing the cost of industrial amplification.

[0009] In some embodiments, the reaction temperature is 80-130°C.

[0010] In some embodiments, the flow rate of the glycerol aqueous solution into the microchannel reactor is 20-40 mL / min;

[0011] And / or, the flow rate of the concentrated sulfuric acid solution containing the catalyst into the microchannel reactor is 20-40 mL / min.

[0012] In some embodiments, the mass ratio of the catalyst to glycerol is 0.5-1:10-200;

[0013] And / or, the mass percentage of the catalyst in the concentrated sulfuric acid solution containing the catalyst is 0.5-1%.

[0014] In some embodiments, the concentration of the glycerol aqueous solution is 20-40 wt %;

[0015] And / or, the concentrated sulfuric acid solution containing the catalyst is obtained by mixing the catalyst and the concentrated sulfuric acid solution, and the concentration of the concentrated sulfuric acid solution is 75-98wt%.

[0016] In some embodiments, the catalyst includes at least one of an iodide salt or a sulfate salt.

[0017] In some embodiments, the catalyst includes potassium iodide, potassium sulfate and potassium hydrogen sulfate; the mass ratio of potassium iodide, potassium sulfate and potassium hydrogen sulfate is 0.5-2:0.5-2:0.5-2.

[0018] In some embodiments, after the reaction, the temperature is adjusted to 0-50°C before collecting the reaction product;

[0019] And / or, the reaction product after the reaction is post-treated to obtain a pyrazole intermediate, and the post-treatment includes distillation.

[0020] In some embodiments, the microchannel reactor includes a premixing unit and a process intensification unit, the premixing unit is used to mix the glycerol aqueous solution and the concentrated sulfuric acid solution containing the catalyst, and the process intensification unit is used to react the mixed glycerol aqueous solution and the concentrated sulfuric acid solution containing the catalyst.

[0021] In some embodiments, the microchannel reactor has a microchannel with a diameter of 0.3-1 mm;

[0022] And / or, the microchannel reactor adopts an interdigitated structure;

[0023] And / or, the material of the inner wall of the microchannel reactor includes at least one of pressureless sintered silicon carbide, polytetrafluoroethylene, and perfluoroether rubber. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 It is a schematic diagram of a preparation device for a pyrazole intermediate of the present invention.

[0025] Reference numerals:

[0026] A first infusion pump 1 , a second infusion pump 2 , and a microchannel reactor 3 . DETAILED DESCRIPTION

[0027] Embodiments of the present invention are described in detail below, and examples of the embodiments are shown in the accompanying drawings. The embodiments described below with reference to the accompanying drawings are exemplary and intended to be used to explain the present invention, but should not be understood as limiting the present invention.

[0028] A method for preparing a pyrazole intermediate according to an embodiment of the present invention comprises: introducing a glycerol aqueous solution and a concentrated sulfuric acid solution containing a catalyst into a microchannel reactor 3 respectively for reaction to obtain a pyrazole intermediate, wherein the pyrazole intermediate comprises 3-hydroxypropanal and acrolein.

[0029] The preparation method of the pyrazole intermediate of the embodiment of the present invention is to introduce the glycerol aqueous solution and the concentrated sulfuric acid solution containing the catalyst into the microchannel reactor respectively for dehydration reaction, collect the reaction products, and obtain a mixture of 3-hydroxypropanal from which one molecule of water is removed from glycerol and acrolein from which two molecules of water are removed. Unlike large pipelines and containers, the channels in the microchannel reactor are much smaller than those in the traditional system, and have a microchannel with a size of about 1 mm. The smaller microchannel increases the effective contact surface area, improves the heat transfer and mass transfer performance, and based on the efficient heat exchange performance of the microchannel reactor, the dehydration reaction of glycerol in the channel can be accelerated at a speed 1000 times faster than that of the traditional system to accelerate the process, which can significantly shorten the reaction time, and can also prevent the occurrence of adverse phenomena such as back mixing, carbonization and intense heat release during the reaction process. Specifically, the glycerol aqueous solution and the concentrated sulfuric acid solution containing the catalyst in the microchannel reactor spirally advance in the tube, which can play a certain role in preventing back mixing; the dehydration reaction of glycerol using a microchannel reactor can reduce the reaction time, increase the effective contact area, and can efficiently transfer heat, prevent heat accumulation and intense heat release, and avoid carbonization. Reducing backmixing and carbonization can both improve the utilization rate of raw materials, thereby increasing the yield of pyrazole intermediates and improving the quality of products, greatly improving the production efficiency of 3-hydroxypropanal and acrolein. Microchannel reactors can also reduce the overall equipment volume, specifically reducing the equipment volume by 10 times or more. Based on this, more microchannels can be connected in series to perform "digital amplification", which can improve reaction efficiency and product quality while solving the problem of industrial amplification difficulties, and the industrial amplification effect is small, thereby reducing the cost of industrial amplification.

[0030] In some embodiments, a method for preparing a pyrazole intermediate comprises: regulating the temperature of the microchannel reactor 3 to a preset temperature, and respectively introducing a propylene glycol aqueous solution and a concentrated sulfuric acid solution containing a catalyst into the microchannel reactor 3 for reaction; optionally, it also comprises a first infusion pump 1 and a second infusion pump 2, the propylene glycol aqueous solution is pumped into the microchannel reactor 3 by the first infusion pump 1, and the concentrated sulfuric acid solution containing the catalyst is pumped into the microchannel reactor 3 by the second infusion pump 2, reacting, collecting the reaction products, and obtaining a pyrazole intermediate.

[0031] In some embodiments, the reaction temperature is 80-130°C, specifically, for example, 80°C, 85°C, 90°C, 100°C, 110°C, 120°C, 130°C, optionally, 100-130°C. In the embodiment of the present invention, the reaction temperature is 80-130°C, which is conducive to achieving the best reaction effect. Carbonization can also be avoided by reacting at 100-130°C, because the high temperature can quickly promote the reaction and prevent the contact time from being too long. In addition, 100-130°C is also conducive to increasing the reaction rate, inhibiting the occurrence of side reactions, and improving the yield. Therefore, the temperature is further preferably 100-130°C.

[0032] In some embodiments, the flow rate of the glycerol aqueous solution into the microchannel reactor 3 is 20-40mL / min, specifically, for example, 20mL / min, 25mL / min, 28mL / min, 30mL / min, 33mL / min, 35mL / min, 38mL / min, 40mL / min, optionally, 25-33mL / min. In the embodiment of the present invention, the flow rate of the glycerol aqueous solution is 20-40mL / min, which can improve the utilization rate of raw materials. When the flow rate is too low, carbonization is likely to occur; when the flow rate is too high, the raw material reaction is incomplete.

[0033] In some embodiments, the flow rate of the concentrated sulfuric acid solution containing the catalyst into the microchannel reactor 3 is 20-40mL / min, specifically, for example, 20mL / min, 25mL / min, 28mL / min, 30mL / min, 33mL / min, 35mL / min, 38mL / min, 40mL / min, optionally, 25-38mL / min. In an embodiment of the present invention, the flow rate of the concentrated sulfuric acid containing the catalyst is 20-40mL / min, which can improve the utilization rate of raw materials. When the flow rate is too low, the reaction is insufficient; when the flow rate is too high, carbonization is likely to occur. The flow rate of the glycerol aqueous solution is 20-40 mL / min, the flow rate of the concentrated sulfuric acid solution containing the catalyst is 20-40 mL / min, the liquid holding capacity of the microchannel is 0.1-65 mL (for example, 1 mL, 2 mL, 4 mL, 6 mL, 10 mL, 20 mL, 40 mL, 60 mL, 65 mL), and the residence time is about 3-10 s to fully react and obtain the product, which significantly shortens the reaction time and prevents undesirable phenomena such as carbonization and intense heat release.

[0034] In some embodiments, the mass ratio of the catalyst to glycerol is 0.5-1:10-200, specifically, for example, 0.5-1 (for example, 0.5, 0.6, 0.7, 0.8, 0.9, 1):10-200 (for example, 10, 20, 30, 50, 80, 100, 150, 200). In the embodiment of the present invention, the mass ratio of the catalyst to glycerol is 0.5-1:10-200, which can achieve the best catalytic effect. When the catalyst content is low, the catalytic effect is poor; when the catalyst content is high, it causes waste.

[0035] In some embodiments, the mass percentage of the catalyst in the concentrated sulfuric acid solution containing the catalyst is 0.5-1%, specifically, for example, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%. In the embodiment of the present invention, the catalyst content of 0.5-1% is conducive to the efficient reaction. When the catalyst content in the concentrated sulfuric acid is low, the catalytic effect is not ideal; when the catalyst content is high, it causes a waste of the catalyst.

[0036] In some embodiments, the concentration of the glycerol aqueous solution is 20-40wt%, specifically, for example, 20wt%, 25wt%, 30wt%, 35wt%, 40wt%. In the embodiments of the present invention, when the glycerol concentration is too low, the reaction is not complete; when the glycerol concentration is too high, it will promote side reactions. Directly using glycerol instead of the glycerol aqueous solution may cause side reactions to occur and generate other substances.

[0037] In some embodiments, the concentrated sulfuric acid solution containing the catalyst is obtained by mixing the catalyst and the concentrated sulfuric acid solution, and the concentration of the concentrated sulfuric acid solution is 75-98wt%, specifically, for example, 75wt%, 78wt%, 80wt%, 85wt%, 90wt%, 95wt%, 98wt%, optionally, 75-78wt%. In the embodiment of the present invention, the concentration of the concentrated sulfuric acid solution is 75-98wt%, which can make the raw materials fully react. The present invention can select concentrated sulfuric acid with relatively low concentration, for example, 75-80wt%, because excessively high concentration of sulfuric acid easily causes carbonization of the raw materials, and being lower than 75-80wt% is conducive to suppressing the occurrence of side reactions, but when the concentration of the concentrated sulfuric acid solution is lower than 75wt%, the reaction is not completely carried out.

[0038] In some embodiments, the catalyst includes at least one of iodine salt or sulfate, optionally, the catalyst includes at least one of potassium iodide, potassium sulfate or potassium hydrogen sulfate, the catalyst includes potassium iodide, potassium sulfate and potassium hydrogen sulfate; the mass ratio of potassium iodide, potassium sulfate and potassium hydrogen sulfate is 0.5-2:0.5-2:0.5-2, specifically, for example, 0.5-2 (for example, 0.5, 1, 1.5, 2):0.5-2 (for example, 0.5, 1, 1.5, 2):0.5-2 (for example, 0.5, 1, 1.5, 2). In an embodiment of the present invention, the catalyst may include one of potassium iodide, potassium sulfate or potassium hydrogen sulfate, for example, including potassium iodide, potassium iodide will react with sulfuric acid to generate potassium hydrogen sulfate and / or potassium sulfate. The present invention adopts a microchannel reactor, the material mixing and reaction time is extremely short, the reaction efficiency is high, and the catalyst preferably directly includes potassium iodide, potassium sulfate and potassium hydrogen sulfate, which shortens the time for potassium iodide and sulfuric acid to react to generate potassium sulfate and / or potassium hydrogen sulfate, improves the catalytic efficiency, and further improves the production efficiency and yield of 3-hydroxypropanal and acrolein.

[0039] In some embodiments, after the reaction, the temperature of the reaction product is first adjusted to 0-50°C, that is, cooled to 0-50°C, and then the reaction product is collected, specifically, for example, 10°C, 15°C, 20°C, 25°C, 30°C, 35°C, 40°C, 50°C. In the embodiment of the present invention, after the reaction, the temperature of the reaction product is first adjusted to 0-50°C, so that the gasified product such as acrolein is fully liquefied, which can improve the yield of the obtained pyrazole intermediate and reduce the safety hazards in the process of collecting the product.

[0040] In some embodiments, the reaction product is post-treated to obtain a pyrazole intermediate, and the post-treatment includes distillation. In the embodiments of the present invention, the separation is performed based on the different boiling points of different substances.

[0041] In some embodiments, 3-hydroxypropanal and acrolein in the pyrazole intermediate are determined by gas chromatography.

[0042] In some embodiments, the microchannel reactor 3 includes a premixing unit and a process intensification unit, the premixing unit is used to mix the glycerol aqueous solution and the concentrated sulfuric acid solution containing the catalyst, and the process intensification unit is used to react the mixed glycerol aqueous solution and the concentrated sulfuric acid solution containing the catalyst.

[0043] In the embodiments of the present invention, the microchannel reactor of the present invention can quickly transfer heat, efficiently mix, shorten the reaction time, and prevent undesirable phenomena such as backmixing, carbonization, and violent heat release during the reaction process, thereby increasing the yield of pyrazole intermediates and improving the quality of the product.

[0044] In some embodiments, the microchannel reactor 3 further includes a cooling unit for cooling after the reaction.

[0045] In some embodiments, the microchannel reactor 3 also includes other auxiliary units, specifically, other auxiliary units such as a feeding device, an air intake unit, a material preheating / precooling device, a parameter acquisition device, a back pressure valve, a safety valve, etc., wherein the parameter acquisition device acquires parameters such as temperature and pressure during the reaction process.

[0046] In some embodiments, the microchannel reactor 3 has a microchannel with a diameter of 0.3-1 mm, and optionally, the microchannel is a microchannel of a premixing unit and / or a process intensification unit. In the embodiment of the present invention, the microchannel of 0.3-1 mm can quickly transfer heat and mix quickly. When the microchannel size is too large, the heat transfer effect is poor, which easily leads to carbonization.

[0047] In some embodiments, the microchannel reactor 3 adopts an interdigital structure; optionally, the premixing unit adopts an interdigital structure; optionally, the process intensification unit adopts an interdigital structure. In the embodiments of the present invention, the interdigital structure is beneficial to improving the reaction efficiency and product yield.

[0048] In some embodiments, the microchannel of the microchannel reactor 3 adopts a spiral structure; optionally, the microchannel of the premixing unit adopts a spiral structure; optionally, the microchannel of the process intensification unit adopts a spiral structure; optionally, at least a portion of the microchannel is a spiral structure, and part or all of a microchannel is a spiral structure; optionally, the microchannel reactor 3 includes a plurality of microchannels, at least a portion of the plurality of microchannels is a spiral structure, and part or all of the plurality of microchannels is a spiral structure. In the embodiment of the present invention, the glycerol aqueous solution and the concentrated sulfuric acid solution containing the catalyst spirally advance in the tube, which can prevent back mixing.

[0049] In some embodiments, the material of the inner wall of the microchannel reactor 3 includes at least one of pressureless sintered silicon carbide, quartz, polytetrafluoroethylene, and perfluoroether rubber. In the embodiment of the present invention, the material of the inner wall of the microchannel reactor is conducive to preventing concentrated acid corrosion.

[0050] The present invention is described below with reference to specific embodiments. It should be noted that these embodiments are merely illustrative and do not limit the present invention in any way.

[0051] The microchannel reactor 3 used was purchased from Changzhou Nayang Biotechnology Co., Ltd., model NYA-GM-1X.

[0052] Example 1

[0053] Take 150g 30wt% glycerol solution, 100mL 78% concentrated sulfuric acid, add 1g of potassium iodide, potassium sulfate, potassium hydrogen sulfate mixture to the concentrated sulfuric acid, the mass ratio of the three is 1:1:1, and obtain a concentrated sulfuric acid solution containing a catalyst, the mass ratio of the catalyst to glycerol is 1:45, and use an infusion pump to input the two into the microchannel reactor 3, the flow rate of the glycerol solution is 33mL / min, and the flow rate of the concentrated sulfuric acid solution containing the catalyst is 38mL / min, the microchannel reactor 3 has a microchannel with a diameter of 0.3mm, and the temperature of the microchannel reactor 3 is set to 110°C. After the reaction is completed, adjust the temperature of the reaction product to 30°C, and collect the pyrazole intermediate. The mass percentage of 3-hydroxypropanal and the mass percentage of acrolein in the pyrazole intermediate are shown in Table 1, wherein the yield = pyrazole intermediate yield / (mass percentage of acrolein*theoretical yield of complete conversion of acrolein+mass percentage of 3-hydroxypropanal*theoretical yield of complete conversion of 3-hydroxypropanal)*100%.

[0054] Example 2

[0055] The preparation method is the same as that of Example 1, except that the temperature of the microchannel reactor 3 is set to 80°C.

[0056] Example 3

[0057] The preparation method is the same as that of Example 1, except that the temperature of the microchannel reactor 3 is set to 90°C.

[0058] Example 4

[0059] The preparation method is the same as that of Example 1, except that the temperature of the microchannel reactor 3 is set to 130°C.

[0060] Example 5

[0061] The preparation method is the same as that of Example 1, except that 75% concentrated sulfuric acid is used.

[0062] Example 6

[0063] The preparation method is the same as that of Example 1, except that 90% concentrated sulfuric acid is used.

[0064] Example 7

[0065] The preparation method is the same as that of Example 1, except that 98% concentrated sulfuric acid is used.

[0066] Example 8

[0067] The preparation method is the same as that of Example 1, except that a 20 wt % glycerol solution is used.

[0068] Example 9

[0069] The preparation method is the same as that of Example 1, except that 40 wt % glycerol solution is used.

[0070] Example 10

[0071] The preparation method is the same as that of Example 1, except that the flow rate of the propylene glycol solution is 25 mL / min, and the flow rate of the concentrated sulfuric acid solution containing the catalyst is 25 mL / min.

[0072] Embodiment 11

[0073] The preparation method is the same as that of Example 1, except that the flow rate of the propylene glycol solution is 20 mL / min, and the flow rate of the concentrated sulfuric acid solution containing the catalyst is 40 mL / min.

[0074] Example 12

[0075] The preparation method is the same as that of Example 1, except that the flow rate of the propylene glycol solution input is 40 mL / min, and the flow rate of the concentrated sulfuric acid solution containing the catalyst input is 20 mL / min.

[0076] Comparative Example 1

[0077] The preparation method is the same as that of Example 1, except that the temperature of the microchannel reactor 3 is set to 50°C.

[0078] Comparative Example 2

[0079] The preparation method is the same as that of Example 1, except that the temperature of the microchannel reactor 3 is set to 70°C.

[0080] Comparative Example 3

[0081] The preparation method is the same as that of Example 1, except that the temperature of the microchannel reactor 3 is set to 140°C.

[0082] Comparative Example 4

[0083] The preparation method is the same as that of Example 1, except that the temperature of the microchannel reactor 3 is set to 160°C.

[0084] Comparative Example 5

[0085] The preparation method is the same as that of Example 1, except that 70% concentrated sulfuric acid is used.

[0086] Comparative Example 6

[0087] The preparation method is the same as that of Example 1, except that the flow rate of the propylene glycol solution is 43 mL / min, and the flow rate of the concentrated sulfuric acid solution containing the catalyst is 50 mL / min.

[0088] Comparative Example 7

[0089] The preparation method is the same as that of Example 1, except that the flow rate of the propylene glycol solution is 13 mL / min, and the flow rate of the concentrated sulfuric acid solution containing the catalyst is 15 mL / min.

[0090] Comparative Example 8

[0091] The preparation method is the same as that of Example 1, except that a 10 wt % glycerol solution is used.

[0092] Comparative Example 9

[0093] The preparation method is the same as that of Example 1, except that a 50 wt % glycerol solution is used.

[0094] Comparative Example 10

[0095] The preparation method is the same as that of Example 1, except that no catalyst, a mixture of potassium iodide, potassium sulfate and potassium hydrogen sulfate, is added to the concentrated sulfuric acid, and 78% concentrated sulfuric acid is directly used.

[0096] Comparative Example 11

[0097] The preparation method is the same as that of Example 1, except that the microchannel reactor 3 has a microchannel with a diameter of 1.3 mm.

[0098] Table 1

[0099]

[0100] The difference between Example 1, Example 2-4, and Comparative Example 1-4 is that the setting temperature of the microchannel reactor 3 is different during the reaction, wherein the temperature of the embodiment is set to 80-130°C, and the temperature of the comparative example is set to 50-70°C and 140-160°C. According to Table 1, the temperature of Comparative Example 1 and Comparative Example 2 is too low, lower than 80°C, and the yield is significantly reduced relative to the embodiment, because the temperature is too low and the reaction cannot be fully carried out; the temperature of Comparative Example 3 and Comparative Example 4 is set too high, higher than 130°C, causing the yield to drop to less than 85%, because the temperature is too high to generate other products. Therefore, setting the temperature of the microchannel reactor 3 to 80-130°C can ensure that the pyrazole intermediate has a higher yield, especially in Example 1, the reaction temperature is 110°C, and the yield is as high as 95.3%.

[0101] The difference between Examples 1, 5-7 and Comparative Example 5 is only that the concentration of concentrated sulfuric acid is different, wherein 75%-98% concentrated sulfuric acid is used in the examples, and 70% concentrated sulfuric acid is used in Comparative Example 5. According to Table 1, the concentration of concentrated sulfuric acid in Comparative Example 5 is relatively low, resulting in a decrease in the yield of the pyrazole intermediate to 84.2%. This is because the concentration of concentrated sulfuric acid is too low and the reaction is not complete; further, in particular, when the concentration of concentrated sulfuric acid is 75%-78%, the yield of the pyrazole intermediate can reach more than 90%. Optimally, Example 1 uses 78% concentrated sulfuric acid, and the yield is the highest, reaching 95.3%. This is because the concentration of concentrated sulfuric acid is too high and the raw material is easily carbonized.

[0102] The difference between Example 1, Example 8, Example 9 and Comparative Example 8 and Comparative Example 9 is that the concentration of glycerol solution is different. The glycerol concentration in the embodiment is 20-40wt%, and Comparative Examples 8 and 9 respectively use 10wt% and 50wt% glycerol solutions. According to Table 1, the yields of the pyrazole intermediates in Comparative Examples 8 and 9 are both reduced. This is because when the mass concentration of glycerol is too low, the reaction is not complete. When the mass concentration of glycerol is too high, side reactions will be promoted. Therefore, setting the concentration of glycerol solution to 20-40wt% can make the preparation effect of pyrazole intermediate the best, and the yield can reach more than 90%. In particular, when the glycerol concentration of Example 1 is 30wt%, the yield is the highest, reaching 95.3%.

[0103] The difference between Example 1, Examples 10-12 and Comparative Examples 6-7 is only the flow rate of the glycerol solution and the concentrated sulfuric acid solution containing the catalyst in the microchannel reactor 3. According to Table 1, the embodiment of the present invention sets the flow rate of the glycerol solution and the flow rate of the concentrated sulfuric acid to 20-40 mL / min, which can make the yield of the pyrazole intermediate reach more than 85%, especially when the flow rate of the glycerol solution in Example 1 and Example 10 is set to 25-33 mL / min and the flow rate of the concentrated sulfuric acid solution containing the catalyst is set to 25-38 mL / min. , the yield of the pyrazole intermediate can reach more than 90%; in Comparative Example 6, the flow rates of the glycerol solution and the concentrated sulfuric acid solution containing the catalyst are set to 43mL / min and 50mL / min, both exceeding 40mL / min, and in Comparative Example 7, the flow rates of the glycerol solution and the concentrated sulfuric acid solution containing the catalyst are set to 13mL / min and 15mL / min, both below 20mL / min. In both cases, the yield of the pyrazole intermediate decreases, because too high a flow rate easily causes uneven mixing, resulting in a decrease in yield. Too low a flow rate will lead to the formation of by-products. Therefore, setting the flow rates of the propylene glycol solution and the concentrated sulfuric acid solution containing the catalyst to 20-40 mL / min can obtain better pyrazole intermediate production efficiency. More preferably, setting the flow rate of the propylene glycol solution to 25-33 mL / min and the flow rate of the concentrated sulfuric acid solution containing the catalyst to 25-38 mL / min. In particular, when the flow rate of the propylene glycol solution is set to 33 mL / min and the flow rate of the concentrated sulfuric acid solution containing the catalyst is set to 38 mL / min, Example 1 has the best pyrazole intermediate yield of 95.3%.

[0104] In summary, the present invention adopts microchannel reactor 3 to prepare pyrazole intermediates. A large number of experimental tests show that when the concentration of glycerol solution is set to 20-40wt%, the concentration of concentrated sulfuric acid solution containing catalyst is 75%-98%, the temperature of microchannel reactor 3 is set to 80-130°C, and the flow rates of glycerol solution and concentrated sulfuric acid solution containing catalyst in microchannel reactor 3 are both set to 20-40mL / min, the pyrazole intermediate can obtain a better yield. In particular, the optimal preparation conditions are to use 30wt% glycerol solution, 78wt% concentrated sulfuric acid, the temperature of microchannel reactor 3 is set to 110°C, the flow rate of glycerol solution in microchannel reactor 3 is 33mL / min, and the flow rate of concentrated sulfuric acid solution containing catalyst in microchannel reactor 3 is 38mL / min. Under these conditions, the yield of pyrazole intermediates reaches 95.3%.

[0105] In addition, the terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Therefore, the features defined as "first" and "second" may explicitly or implicitly include at least one of the features. In the description of the present invention, the meaning of "plurality" is at least two, such as two, three, etc., unless otherwise clearly and specifically defined.

[0106] In the present invention, unless otherwise clearly specified and limited, the terms "installed", "connected", "connected", "fixed" and the like should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral one; it can be a mechanical connection, an electrical connection, or communication with each other; it can be a direct connection, or an indirect connection through an intermediate medium, it can be the internal connection of two elements or the interaction relationship between two elements, unless otherwise clearly defined. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0107] In the present invention, the terms "one embodiment", "some embodiments", "examples", "specific examples", or "some examples" etc. mean that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the described specific features, structures, materials or characteristics may be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art may combine and combine the different embodiments or examples described in this specification and the features of the different embodiments or examples, without contradiction.

[0108] Although the above embodiments have been shown and described, it is to be understood that the above embodiments are exemplary and are not to be construed as limitations on the present invention. Changes, modifications, substitutions and variations of the above embodiments by those of ordinary skill in the art are all within the scope of protection of the present invention.

Claims

1. A method for preparing a pyrazole intermediate, characterized in that: include: A glycerol aqueous solution and a concentrated sulfuric acid solution containing a catalyst are respectively introduced into a microchannel reactor for reaction to obtain a pyrazole intermediate, wherein the pyrazole intermediate includes 3-hydroxypropanal and acrolein.

2. The method for preparing a pyrazole intermediate according to claim 1, characterized in that: The reaction temperature is 80-130°C.

3. The method for preparing a pyrazole intermediate according to claim 1, characterized in that: The flow rate of the glycerol aqueous solution into the microchannel reactor is 20-40 mL / min; And / or, the flow rate of the concentrated sulfuric acid solution containing the catalyst into the microchannel reactor is 20-40 mL / min.

4. The method for preparing a pyrazole intermediate according to claim 1, characterized in that: The mass ratio of the catalyst to glycerol is 0.5-1:10-200; And / or, the mass percentage of the catalyst in the concentrated sulfuric acid solution containing the catalyst is 0.5-1%.

5. The method for preparing a pyrazole intermediate according to claim 1, characterized in that: The concentration of the glycerol aqueous solution is 20-40wt%; And / or, the concentrated sulfuric acid solution containing the catalyst is obtained by mixing the catalyst and the concentrated sulfuric acid solution, and the concentration of the concentrated sulfuric acid solution is 75-98wt%.

6. The method for preparing a pyrazole intermediate according to claim 1, characterized in that: The catalyst includes at least one of an iodine salt or a sulfate salt.

7. The method for preparing a pyrazole intermediate according to claim 6, characterized in that: The catalyst comprises potassium iodide, potassium sulfate and potassium hydrogen sulfate; the mass ratio of potassium iodide, potassium sulfate and potassium hydrogen sulfate is 0.5-2:0.5-2:0.5-2.

8. The method for preparing a pyrazole intermediate according to claim 1, characterized in that: After the reaction, the temperature is adjusted to 0-50°C, and then the reaction product is collected; And / or, the reaction product after the reaction is post-treated to obtain a pyrazole intermediate, and the post-treatment includes distillation.

9. The method for preparing a pyrazole intermediate according to claim 1, characterized in that: The microchannel reactor comprises a premixing unit and a process intensification unit. The premixing unit is used for mixing the glycerol aqueous solution and the concentrated sulfuric acid solution containing the catalyst. The process intensification unit is used for reacting the mixed glycerol aqueous solution and the concentrated sulfuric acid solution containing the catalyst.

10. The method for preparing a pyrazole intermediate according to claim 1 or 9, characterized in that: The microchannel reactor has a microchannel with a diameter of 0.3-1 mm; And / or, the microchannel reactor adopts an interdigitated structure; And / or, the material of the inner wall of the microchannel reactor includes at least one of pressureless sintered silicon carbide, polytetrafluoroethylene, and perfluoroether rubber.

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