Preparation method of 1, 3-dimethyl-5-pyrazolone

Abstract

The invention provides a preparation method of 1, 3-dimethyl-5-pyrazolone, and belongs to the field of chemical synthesis. The preparation method of 1, 3-dimethyl-5-pyrazolone provided by the invention comprises the following steps: pumping an acetoacetate solution and a methylhydrazine solution into a microchannel reactor for hydrazinolysis reaction to obtain a mixed solution; and sequentially carrying out reflux, crystallization and drying on the mixed solution to obtain the 1, 3-dimethyl-5-pyrazolone. According to the invention, the concentration and proportion of the raw materials are adjusted, the raw materials are matched with the micro-channel reactor, and the temperature, crystallization and drying parameters of the solution of acetoacetate in hydrazinolysis reaction before being pumped into the micro-channel reactor are adjusted, so that the purity and yield of the product are improved. Results of embodiments show that the purity of the 1, 3-dimethyl-5-pyrazolone prepared by the preparation method provided by the invention is greater than 99%, the yield is greater than 95%, and the 1, 3-dimethyl-5-pyrazolone has high purity and high yield.

Description

Technical Field

[0001] The invention relates to the field of chemical synthesis, and in particular to a method for preparing 1,3-dimethyl-5-pyrazolone. Background Art

[0002] Pyrazolone is an important organic compound, mainly used as an important intermediate in the synthesis of azo dyes (pyrazolone dyes), drugs (aminopyrine, analgin, etc.) and pesticides (fenpyraclostrobin, pyrazolamide, etc.).

[0003] At present, there are usually two routes for preparing 1,3-dimethyl-5-pyrazolone. The first is a synthetic route using methylhydrazine or its salt as raw materials, specifically including (1) reaction of methylhydrazine and ethyl acetoacetate, (2) reaction of methylhydrazine hydrochloride and ethyl acetoacetate, (3) reaction of methylhydrazine and diethylene ketone, (4) reaction of methylhydrazine sulfate and diethylene ketone; the second is a synthetic route for methylation of 3-methyl-5-pyrazolone. The second synthetic route needs to react under pressure, which requires high equipment and is not conducive to industrial production. The first synthetic route is usually an intermittent reaction using a traditional autoclave reactor. On the one hand, the purity of pyrazolone prepared by the autoclave reactor is generally 98-99%, and the product yield is generally 85-90%. The purity and yield need to be further improved; on the other hand, the autoclave reactor also has the problem of large amount of reaction liquid, and it is easy to cause safety problems such as improper operation during the reaction.

[0004] Therefore, providing a safer preparation method that can further improve the purity and yield of 1,3-dimethyl-5-pyrazolone has become a technical problem to be solved in the art. Summary of the invention

[0005] The object of the present invention is to provide a method for preparing 1,3-dimethyl-5-pyrazolone. The method for preparing 1,3-dimethyl-5-pyrazolone provided by the present invention is safer and can further improve the purity and yield of 1,3-dimethyl-5-pyrazolone.

[0006] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0007] The present invention provides a method for preparing 1,3-dimethyl-5-pyrazolone, comprising the following steps:

[0008] (1) pumping a solution of acetoacetate and a solution of methylhydrazine into a microchannel reactor for hydrazinolysis reaction to obtain a mixed solution; the acetoacetate is methyl acetoacetate or ethyl acetoacetate; the concentration of the solution of acetoacetate is 35-55 wt %; the molar ratio of the acetoacetate to methylhydrazine is 1:(1.01-1.05); the temperature of the hydrazinolysis reaction is 25-45° C., the time of the hydrazinolysis reaction is 30-60 s; the temperature of the solution of acetoacetate before being pumped into the microchannel reactor is 15-25° C.;

[0009] (2) The mixed solution obtained in step (1) is refluxed, crystallized and dried in sequence to obtain 1,3-dimethyl-5-pyrazolone; the crystallization temperature is 10 to 20° C.; and the drying temperature is 50 to 80° C.

[0010] Preferably, the concentration of the acetoacetate solution in step (1) is 40-50 wt%.

[0011] Preferably, the solvent in the solution of acetoacetate in step (1) is toluene or xylene.

[0012] Preferably, the molar ratio of acetoacetate to methylhydrazine in step (1) is 1:(1.02-1.04)

[0013] Preferably, the concentration of the methylhydrazine solution in step (1) is 35-45 wt%.

[0014] Preferably, before the acetoacetate solution and the methylhydrazine solution are pumped into the microchannel reactor in step (1), the solvent of the acetoacetate solution is first pumped into the microchannel reactor to fill the microchannels in the microchannel reactor.

[0015] Preferably, the solvent is preheated to the hydrazinolysis reaction temperature before being pumped into the microchannel reactor.

[0016] Preferably, the reflux temperature in step (2) is 80-120°C.

[0017] Preferably, the drying in step (2) is vacuum drying.

[0018] Preferably, the vacuum drying pressure is -0.085 to -0.095 MPa.

[0019] The invention provides a method for preparing 1,3-dimethyl-5-pyrazolone, comprising the following steps: (1) pumping an acetoacetate solution and a methylhydrazine solution into a microchannel reactor for hydrazinolysis reaction to obtain a mixed solution; the acetoacetate is methyl acetoacetate or ethyl acetoacetate; the concentration of the acetoacetate solution is 35-55wt%; the molar ratio of the acetoacetate to the methylhydrazine is 1:(1.01-1.05); the temperature of the hydrazinolysis reaction is 25-45°C, the time of the hydrazinolysis reaction is 30-60s; the temperature of the acetoacetate solution before being pumped into the microchannel reactor is 15-25°C; (2) refluxing, crystallizing and drying the mixed solution obtained in the step (1) in sequence to obtain 1,3-dimethyl-5-pyrazolone; the crystallization temperature is 10-20°C; and the drying temperature is 50-80°C. The present invention can shorten the reaction time and improve the safety of preparation by pumping the reaction raw materials into the microchannel reactor and utilizing the microchannel reactor with a large number of small channels; by adjusting the concentration of the raw materials methyl acetoacetate / ethyl acetoacetate, the ratio of methyl acetoacetate / ethyl acetoacetate to methyl hydrazine and the microchannel reactor, and adjusting the parameters of the hydrazinolysis reaction, the reaction can be made more complete and the generation of side reaction products can be reduced; by adjusting the temperature, crystallization and drying parameters before the acetoacetate solution is pumped into the microchannel reactor, the purity and yield of 1,3-dimethyl-5-pyrazolone are further improved. The results of the embodiments show that the 1,3-dimethyl-5-pyrazolone prepared by the preparation method provided by the present invention has a purity of more than 99% and a yield of more than 95%, and has high purity and high yield. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 The process flow chart of preparing 1,3-dimethyl-5-pyrazolone according to an embodiment of the present invention;

[0021] Figure 2 This is a liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 1 of the present invention;

[0022] Figure 3 This is a liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 2 of the present invention;

[0023] Figure 4 This is a liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 3 of the present invention;

[0024] Figure 5 This is a liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 4 of the present invention;

[0025] Figure 6This is a liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 5 of the present invention;

[0026] Figure 7 This is a liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 6 of the present invention;

[0027] Figure 8 This is a liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 7 of the present invention;

[0028] Fig. 9 This is a liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 8 of the present invention;

[0029] Fig.10 This is a liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 9 of the present invention;

[0030] Fig.11 This is a liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 10 of the present invention;

[0031] Fig.12 This is a liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 11 of the present invention;

[0032] Fig.13 This is a liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 12 of the present invention;

[0033] Fig.14 This is a liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 13 of the present invention;

[0034] Fig.15 This is a liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 1 of the present invention;

[0035] Fig.16 This is a liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 2 of the present invention;

[0036] Fig.17 This is a liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 3 of the present invention;

[0037] Fig.18 This is a liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 4 of the present invention;

[0038] Fig.19 This is a liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 5 of the present invention;

[0039] Fig. 20 This is a liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 6 of the present invention;

[0040] Fig.21 This is a liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 7 of the present invention;

[0041] Fig. 22 This is a liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 8 of the present invention;

[0042] Fig.23 This is a liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 9 of the present invention;

[0043] Fig.24 This is a liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 10 of the present invention;

[0044] Fig.25 This is a liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 11 of the present invention;

[0045] Fig.26 This is a liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 12 of the present invention. DETAILED DESCRIPTION

[0046] The present invention provides a method for preparing 1,3-dimethyl-5-pyrazolone, comprising the following steps:

[0047] (1) pumping an acetoacetate solution and a methylhydrazine solution into a microchannel reactor for hydrazinolysis reaction to obtain a mixed solution;

[0048] (2) The mixed solution obtained in step (1) is refluxed, crystallized and dried in sequence to obtain 1,3-dimethyl-5-pyrazolone.

[0049] The invention pumps an acetoacetate solution and a methylhydrazine solution into a microchannel reactor to carry out a hydrazinolysis reaction to obtain a mixed solution.

[0050] In the present invention, the acetoacetate is methyl acetoacetate or ethyl acetoacetate. The present invention limits the type of acetoacetate to the above range so that the reaction can proceed smoothly.

[0051] As an embodiment of the present invention, the concentration of the solution of acetoacetate can be 35-55wt%, 40-50wt%, or 45wt%. In the present invention, if the content of acetoacetate is too low, the reaction efficiency will be reduced, so that the material will not have enough time to fully react in the microchannel, thereby reducing the product yield; if the content of acetoacetate is too high, although the reaction efficiency can be improved, the by-product generation will increase, resulting in low product purity, and the heat release per unit time is large, and additional energy needs to be consumed for heat exchange, and there is a risk of crystal precipitation blocking the microchannel reactor. The present invention limits the concentration of acetoacetate in the solution of acetoacetate to the above range, which can effectively improve the reaction selectivity, reduce the generation of side reactions, and obtain a relatively high yield.

[0052] In the present invention, the solvent in the solution of acetoacetate is preferably toluene or xylene, more preferably toluene. The present invention limits the type of solvent to the above range that can better dissolve acetoacetate.

[0053] In the present invention, the molar ratio of acetoacetate to methylhydrazine is 1:(1.01-1.05), preferably 1:(1.02-1.04), more preferably 1:(1.02-1.03), and further preferably 1:1.025. In the present invention, when the molar ratio of acetoacetate to methylhydrazine is lower than 1:1.01, the material reaction is incomplete, resulting in a significant decrease in the yield of pyrazolone; when the molar ratio of acetoacetate to methylhydrazine is higher than 1:1.05, although the yield of pyrazolone is improved, the content of by-products is significantly increased, resulting in a low purity of the product. The present invention limits the molar ratio of acetoacetate to methylhydrazine to the above range, so that 1,3-dimethyl-5-pyrazolone can have a higher purity and yield.

[0054] As an embodiment of the present invention, the concentration of the methylhydrazine solution can be 35-45wt%, or 40wt%; the solvent in the methylhydrazine solution can be water. The present invention limits the solvent and concentration of the methylhydrazine solution to the above range to ensure smooth hydrazinolysis reaction.

[0055] As an embodiment of the present invention, the total capacity of the microchannel reactor is 1.5L; three groups of reaction modules are arranged inside the microchannel reactor; the reaction modules are made of 2205 stainless steel; each group of reaction modules is provided with a continuous microchannel with a cross-sectional area of ​​2.2mm×2.2mm; the cross-sectional shape of the microchannel includes circular, elliptical or polygonal.

[0056] As an embodiment of the present invention, a circulating heat exchange pipeline for heating and cooling is provided outside the microchannel reactor to control the reaction temperature.

[0057] As an embodiment of the present invention, the microchannel reactor controls each operating unit through a PLC control system; the operating unit includes a feed pump and a flow controller for the solution of acetoacetate and the solution of methylhydrazine, a temperature sensor and a pressure sensor of the microchannel reactor, and a heating and cooling system of a high and low temperature integrated machine.

[0058] In the present invention, the temperature of the hydrazinolysis reaction is 25 to 45°C, preferably 25 to 40°C, more preferably 25 to 35°C, and further preferably 25 to 30°C; the time of the hydrazinolysis reaction is 30 to 60s, preferably 30 to 50s, more preferably 30 to 45s, and further preferably 30 to 35s. In the present invention, when the reaction temperature is lower than 25°C, the reaction is incomplete, the residual acetoacetate in the product is high, and the yield decreases; when the reaction temperature is higher than 45°C, the content of by-products increases significantly; when the reaction time is less than 30s, the reaction is incomplete, the residual acetoacetate in the product is high, and the yield decreases; when the reaction time is greater than 60s, the content of by-products increases significantly. The present invention limits the temperature and time of the hydrazinolysis reaction to the above range, so that 1,3-dimethyl-5-pyrazolone can have a higher purity and yield.

[0059] In the present invention, taking methyl acetoacetate as a raw material, the chemical reaction equation of the hydrazinolysis reaction is:

[0060]

[0061] In the present invention, the temperature of the acetoacetate solution before being pumped into the microchannel reactor is 15 to 25°C, preferably 20 to 25°C. In the present invention, when the temperature of the acetoacetate solution is too low before being pumped into the microchannel reactor, the reaction efficiency will be affected, and the residual acetoacetate content in the product will increase; if the temperature is too high, it will be unfavorable for the control of the subsequent hydrazinolysis reaction temperature, and the temperature of the entire reaction will be too high to induce side reactions. The present invention limits the temperature of the acetoacetate solution before being pumped into the microchannel to within the above range, so that 1,3-dimethyl-5-pyrazolone can have a higher purity and yield.

[0062] In the present invention, the solvent of the acetoacetate solution is preferably first pumped into the microchannel reactor to fill the microchannels in the microchannel reactor before the acetoacetate solution and the methylhydrazine solution are pumped into the microchannel reactor. The present invention first pumps the solvent into the microchannel reactor to fill the microchannels in the microchannel reactor, which is conducive to smooth feeding and avoids uneven feeding and affecting the reaction.

[0063] As an embodiment of the present invention, the solvent is preheated to the hydrazinolysis reaction temperature in a preheating heat exchanger before being pumped into the microchannel reactor, and then pumped into the microchannel reactor after the temperature is stabilized.

[0064] After obtaining the mixed solution, the present invention sequentially refluxes, crystallizes and dries the mixed solution to obtain 1,3-dimethyl-5-pyrazolone.

[0065] As an embodiment of the present invention, the reflux can be carried out in a distillation kettle; the reflux temperature can be 80-120°C, 90-110°C, or 100°C; the reflux pressure can be normal pressure. In the present invention, the purpose of the reflux is to remove the water and methanol / ethanol generated by the reaction. If the reflux temperature is lower than 80°C, the dehydration is not complete, and a large amount of water and generated alcohol still exist in the system, resulting in a decrease in product yield; if the reflux temperature is higher than 120°C, side reactions occur and the product purity is reduced. The present invention limits the reflux temperature and pressure to the above range so that 1,3-dimethyl-5-pyrazolone has a higher purity and yield.

[0066] As an embodiment of the present invention, the crystallization can be carried out in a crystallization kettle; the crystallization temperature can be 10-20°C, or 15-20°C. In the present invention, if the crystallization temperature is lower than 10°C, the impurity content increases, and the energy consumption increases; if the crystallization temperature is higher than 20°C, some materials will not be precipitated from the solvent, resulting in a reduced yield. The present invention limits the crystallization temperature to the above range so that 1,3-dimethyl-5-pyrazolone has a higher purity and yield.

[0067] The present invention further comprises centrifugation after the crystallization. The present invention has no special limitation on the equipment and operation of the centrifugation, as long as it can achieve solid-liquid separation. In a specific embodiment of the present invention, the centrifugation equipment is preferably a centrifuge.

[0068] In the present invention, the drying is preferably vacuum drying; the drying is preferably carried out in a vacuum dryer.

[0069] As an embodiment of the present invention, the temperature of the vacuum drying can be 50 to 80°C, or 60 to 70°C; the pressure of the vacuum drying can be -0.085 to -0.095MPa. In the present invention, if the temperature is low and the pressure is high, the solvent in the product cannot be completely removed; if the temperature is higher than 80°C, pyrazolone will sublime, and the product yield will be reduced. The present invention limits the drying temperature and pressure to the above range to obtain a product with higher purity and yield.

[0070] The present invention can shorten the reaction time and improve the safety of preparation by pumping the reaction raw materials into the microchannel reactor and utilizing the fact that the microchannel reactor has a large number of small channels; the concentration of the raw material acetoacetate, the ratio of acetoacetate to methylhydrazine and the microchannel reactor are adjusted, and the parameters of the hydrazinolysis reaction are adjusted to make the reaction more complete and reduce the generation of side reaction products; and the temperature, crystallization and drying parameters of the acetoacetate solution before being pumped into the microchannel reactor are adjusted to further improve the purity and yield of 1,3-dimethyl-5-pyrazolone.

[0071] In a specific embodiment of the present invention, the preparation process of 1,3-dimethyl-5-pyrazolone is as follows Figure 1 As shown:

[0072] Toluene is first pumped into a preheating heat exchanger by using pump B for preheating and then pumped into a microchannel reactor. Then, a methylhydrazine solution and a methyl acetoacetate toluene solution with a mass fraction of 40% are simultaneously pumped into the microchannel reactor by using pumps A and B for hydrazinolysis reaction. The hydrazinolysis reaction product is refluxed through a distillation kettle. The refluxed product is sequentially crystallized, centrifuged and dried through a crystallization kettle, a centrifuge and a dryer to obtain 1,3-dimethyl-5-pyrazolone.

[0073] The technical solutions in the present invention will be described clearly and completely below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0074] Example 1

[0075] A method for preparing 1,3-dimethyl-5-pyrazolone:

[0076] (1) Toluene is first pumped into a preheating heat exchanger by pump B to be preheated to a hydrazinolysis reaction temperature, and then pumped into a microchannel reactor after the temperature is stabilized, so that the microchannel is filled with toluene, and then a methylhydrazine solution and a methylacetoacetate solution having a mass fraction of 40% are simultaneously pumped into the microchannel reactor by pumps A and B to perform a hydrazinolysis reaction at 45° C. for 60 seconds to obtain a mixed solution; the concentration of the methylacetoacetate solution is 55 wt %; the molar ratio of the acetoacetate to the methylhydrazine is 1:1.01; the temperature of the acetoacetate solution before being pumped into the microchannel reactor is 25° C.;

[0077] (2) reflux the mixed solution obtained in step (1) in a distillation kettle at normal pressure at a reflux temperature of 80 to 120° C. After the reflux is completed, the material in the distillation kettle is transferred to a crystallization kettle, cooled to 15° C. for crystallization, centrifuged in a centrifuge after crystallization, and then vacuum dried in a vacuum dryer at a controlled temperature of 80° C. and a pressure of -0.085 MPa to -0.095 MPa to obtain 1,3-dimethyl-5-pyrazolone.

[0078] Example 2

[0079] The difference between Example 2 and Example 1 is that the concentration of the solution of methyl acetoacetate in step (1) is 45wt%, and the others are the same as Example 1.

[0080] Example 3

[0081] The difference between Example 3 and Example 1 is that the concentration of the solution of methyl acetoacetate in step (1) is 35wt%, and the others are the same as Example 1.

[0082] Example 4

[0083] The only difference between Example 4 and Example 1 is that the temperature of the hydrazinolysis reaction in step (1) is 35° C., and the rest is the same as Example 1.

[0084] Example 5

[0085] The only difference between Example 5 and Example 1 is that the temperature of the hydrazinolysis reaction in step (1) is 25° C., and the rest is the same as Example 1.

[0086] Example 6

[0087] The only difference between Example 6 and Example 1 is that the time of the hydrazinolysis reaction in step (1) is 45 s, and the rest is the same as Example 1.

[0088] Example 7

[0089] The difference between Example 7 and Example 1 is that the time of the hydrazinolysis reaction in step (1) is 30 s, and the rest is the same as Example 1.

[0090] Example 8

[0091] The difference between Example 8 and Example 1 is that the molar ratio of methyl acetoacetate to methylhydrazine in step (1) is 1:1.025, and the rest is the same as Example 1.

[0092] Example 9

[0093] The difference between Example 9 and Example 1 is that the molar ratio of methyl acetoacetate to methylhydrazine in step (1) is 1:1.05, and the rest is the same as Example 1.

[0094] Example 10

[0095] The only difference between Example 10 and Example 1 is that the temperature of the acetoacetate solution before being pumped into the microchannel reactor in step (1) is 15° C., and the rest is the same as Example 1.

[0096] Embodiment 11

[0097] The only difference between Example 11 and Example 1 is that the crystallization temperature in step (2) is 20° C., and the rest is the same as Example 1.

[0098] Example 12

[0099] The only difference between Example 12 and Example 1 is that the crystallization temperature in step (2) is 10°C, and the rest is the same as Example 1.

[0100] Example 13

[0101] The difference between Example 13 and Example 1 is that the methyl acetoacetate in step (1) is replaced by ethyl acetoacetate, and the rest is the same as Example 1.

[0102] Comparative Example 1

[0103] The difference between Comparative Example 1 and Example 1 is that the concentration of the solution of methyl acetoacetate in step (1) is 60wt%, and the rest is the same as Example 1.

[0104] Comparative Example 2

[0105] The difference between Comparative Example 2 and Example 1 is that the concentration of the solution of methyl acetoacetate in step (1) is 30wt%, and the rest is the same as Example 1.

[0106] Comparative Example 3

[0107] The difference between Comparative Example 3 and Example 1 is that the temperature of the hydrazinolysis reaction in step (1) is 50° C., and the rest is the same as Example 1.

[0108] Comparative Example 4

[0109] The difference between Comparative Example 4 and Example 1 is that the temperature of the hydrazinolysis reaction in step (1) is 20° C., and the rest is the same as Example 1.

[0110] Comparative Example 5

[0111] The difference between Comparative Example 5 and Example 1 is that the time of the hydrazinolysis reaction in step (1) is 65 s, and the rest is the same as Example 1.

[0112] Comparative Example 6

[0113] The difference between Comparative Example 6 and Example 1 is that the time of the hydrazinolysis reaction in step (1) is 25 s, and the rest is the same as Example 1.

[0114] Comparative Example 7

[0115] The difference between Comparative Example 7 and Example 1 is that the molar ratio of methyl acetoacetate to methylhydrazine in step (1) is 1:1, and the rest is the same as Example 1.

[0116] Comparative Example 8

[0117] The difference between Comparative Example 8 and Example 1 is that the molar ratio of methyl acetoacetate to methylhydrazine in step (1) is 1:1.1, and the rest is the same as Example 1.

[0118] Comparative Example 9

[0119] The difference between Comparative Example 9 and Example 1 is that the temperature of the acetoacetate solution before being pumped into the microchannel reactor in step (1) is 10° C., and the rest is the same as Example 1.

[0120] Comparative Example 10

[0121] The only difference between Comparative Example 10 and Example 1 is that the temperature of the acetoacetate solution before being pumped into the microchannel reactor in step (2) is 30° C., and the rest is the same as Example 1.

[0122] Comparative Example 11

[0123] The only difference between Comparative Example 11 and Example 1 is that the crystallization temperature in step (2) is 5°C, and the rest is the same as Example 1.

[0124] Comparative Example 12

[0125] The only difference between Comparative Example 12 and Example 1 is that the crystallization temperature in step (2) is 25° C., and the rest is the same as Example 1.

[0126] The purity of 1,3-dimethyl-5-pyrazolone prepared in Examples 1 to 13 and Comparative Examples 1 to 12 was tested by liquid chromatography;

[0127] The yield calculation formula of 1,3-dimethyl-5-pyrazolone is:

[0128]

[0129] The liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 1 is as follows: Figure 2 As shown, the peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 1 are shown in Table 1.

[0130] Table 1 Peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 1

[0131] name Retention time (minutes) Area (μV × sec) %area 1 5.125 5153651 99.83 2 10.967 3205 0.06 3 21.714 5695 0.11

[0132] The liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 2 is as follows: Figure 3 As shown, the peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 2 are shown in Table 2.

[0133] Table 2 Peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 2

[0134] name Retention time (minutes) Area (μV × sec) %area 1 5.135 5111620 99.87 2 15.086 1971 0.04 3 23.195 4502 0.09

[0135] The liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 3 is as follows: Figure 4 As shown, the peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 2 are shown in Table 3.

[0136] Table 3 Peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 3

[0137] name Retention time (minutes) Area (μV x sec) %area 1 5.074 5472413 99.83 2 8.194 4521 0.08 3 17.956 4749 0.09

[0138] The liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 4 is as follows: Figure 5 As shown, the peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 4 are shown in Table 4.

[0139] Table 4 Peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 4

[0140] name Retention time (minutes) Area (μV x sec) %area 1 5.121 5447083 99.83 2 8.225 2978 0.05 3 12.711 6174 0.11

[0141] The liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 5 is as follows: Figure 6 As shown, the peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 5 are shown in Table 5.

[0142] Table 5 Peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 5

[0143] name Retention time (minutes) Area (μV × sec) %area 1 5.127 5388073 99.96 2 6.379 2333 0.04

[0144] The liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 6 is as follows: Figure 7 The peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 6 are shown in Table 6.

[0145] Table 6 Peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 6

[0146]

[0147]

[0148] The liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 7 is as follows: Figure 8 As shown, the peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 7 are shown in Table 7.

[0149] Table 7 Peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 7

[0150] name Retention time (minutes) Area (μV x sec) %area 1 5.214 5437399 99.96 2 9.580 2225 0.04

[0151] The liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 8 is as follows: Fig. 9 As shown, the peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 8 are shown in Table 8.

[0152] Table 8 Peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 8

[0153] name Retention time (minutes) Area (μV x sec) %area 1 5.179 5413993 99.89 2 9.456 1519 0.03 3 22.760 4308 0.08

[0154] The liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 9 is as follows: Fig.10 As shown, the peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 9 are shown in Table 9.

[0155] Table 9 Peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 9

[0156] name Retention time (minutes) Area (μV x sec) %area 1 5.180 5436217 99.79 2 13.462 3640 0.07 3 16.725 4542 0.08 4 23.662 3350 0.06

[0157] The liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 10 is as follows: Fig.11 As shown, the peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 10 are shown in Table 10.

[0158] Table 10 Peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 10

[0159] name Retention time (minutes) Area (μV × sec) %area 1 5.191 5191853 99.78 2 9.468 11313 0.22

[0160] The liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 11 is as follows: Fig.12 As shown, the peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 11 are shown in Table 11.

[0161] Table 11 Peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 11

[0162] name Retention time (minutes) Area (μV x sec) %area 1 5.183 5309554 99.98 2 6.604 1322 0.02

[0163] The liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 12 is as follows: Fig.13 As shown, the peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 12 are shown in Table 12.

[0164] Table 12 Peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 12

[0165] name Retention time (minutes) Area (μV x sec) %area 1 5.179 5248453 99.80 2 15.004 5458 0.10 3 21.263 5234 0.10

[0166] The liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 13 is as follows: Fig.14 As shown, the peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 13 are shown in Table 13.

[0167] Table 13 Peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Example 13

[0168] name Retention time (minutes) Area (μV x sec) %area 1 5.111 5346984 99.93 2 6.113 479 0.01 3 21.409 3279 0.06

[0169] The liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 1 is as follows: Fig.15 As shown, the peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 1 are shown in Table 14.

[0170] Table 14 Peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 1

[0171] name Retention time (minutes) Area (μV × sec) %area 1 2.830 958 0.011 2 2.976 1200 0.014 3 3.229 8643238 97.688 4 3.487 3288 0.037 5 3.821 865 0.010 6 4.188 3780 0.043 7 4.692 20750 0.235 8 5.372 2997 0.034 9 6.119 1017 0.011 10 6.521 3667 0.041 11 7.507 1573 0.018 12 8.274 25507 0.288 13 11.309 1680 0.019 14 19.457 13129 0.148 15 23.219 33732 0.381 16 24.239 77411 0.875 17 49.857 13015 0.147

[0172] The liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 2 is as follows: Fig.16 As shown, the peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 2 are shown in Table 15.

[0173] Table 15 Peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 2

[0174]

[0175]

[0176] The liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 3 is as follows: Fig.17 As shown, the peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 3 are shown in Table 16.

[0177] Table 16 Peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 3

[0178] name Retention time (minutes) Area (μV x sec) %area 1 2.357 558 0.006 2 2.829 766 0.009 3 2.976 1471 0.017 4 3.228 8596650 97.418 5 3.818 1443 0.016 6 4.181 5718 0.065 7 4.688 20255 0.230 8 5.256 2724 0.031 9 6.126 602 0.007 10 6.513 5140 0.058 11 7.496 1056 0.012 12 8.257 32213 0.365 13 9.855 583 0.007 14 10.947 416 0.005 15 11.288 705 0.008 16 12.621 433 0.005 17 14.339 721 0.008 18 14.798 1359 0.015 19 19.420 7357 0.083 20 23.136 53972 0.612 21 24.187 19018 0.216 22 49.755 71360 0.809

[0179] The liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 4 is as follows: Fig.18 As shown, the peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 4 are shown in Table 17.

[0180] Table 17 Peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 4

[0181]

[0182]

[0183] The liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 5 is as follows: Fig.19 As shown, the peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 5 are shown in Table 18.

[0184] Table 18 Peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 5

[0185] name Retention time (minutes) Area (μV x sec) %area 1 2.360 900 0.010 2 2.856 209 0.002 3 2.988 1603 0.018 4 3.241 8716214 98.998 5 3.505 2866 0.033 6 3.839 1732 0.020 7 4.249 9490 0.108 8 4.758 19576 0.222 9 5.430 1725 0.020 10 6.688 3596 0.041 11 7.622 733 0.008 12 8.522 34778 0.395 13 11.500 722 0.008 14 15.430 341 0.004 15 20.011 5632 0.064 16 24.146 880 0.010 17 24.828 891 0.010 18 51.200 2547 0.029

[0186] The liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 6 is as follows: Fig. 20 As shown, the peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 6 are shown in Table 19.

[0187] Table 19 Peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 6

[0188]

[0189]

[0190] The liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 7 is as follows: Fig.21 As shown, the peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 7 are shown in Table 20.

[0191] Table 20 Peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 7

[0192] name Retention time (minutes) Area (μV x sec) %area 1 2.357 350 0.004 2 2.842 1744 0.020 3 2.983 750 0.008 4 3.238 8448505 95.009 5 3.824 6515 0.073 6 4.207 4117 0.046 7 4.702 10300 0.116 8 5.327 2093 0.024 9 5.732 823 0.009 10 6.577 11539 0.130 11 7.544 940 0.011 12 8.351 26860 0.302 13 9.250 3188 0.036 14 11.367 1001 0.011 15 12.189 184229 2.072 16 12.829 518 0.006 17 14.991 2905 0.033 18 19.615 6209 0.070 19 21.777 9405 0.106 20 23.474 95090 1.069 21 24.409 23843 0.268 22 27.683 8911 0.100 23 41.725 954 0.011 24 50.272 41496 0.467

[0193] The liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 8 is as follows: Fig. 22 As shown, the peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 8 are shown in Table 21.

[0194] Table 21 Peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 8

[0195]

[0196]

[0197] The liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 9 is as follows: Fig.23 As shown, the peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 9 are shown in Table 22.

[0198] Table 22 Peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 9

[0199] name Retention time (minutes) Area (μV x sec) %area 1 2.353 171 0.002 2 2.834 2361 0.027 3 2.981 1361 0.016 4 3.238 8495432 97.379 5 3.551 5150 0.059 6 3.830 1180 0.014 7 4.215 6953 0.080 8 4.721 5604 0.064 9 5.213 1006 0.012 10 5.402 815 0.009 11 6.604 7749 0.089 12 7.555 1118 0.013 13 8.394 36453 0.418 14 10.264 5463 0.063 15 11.397 1115 0.013 16 12.917 662 0.008 17 15.107 4546 0.052 18 16.890 3196 0.037 19 17.595 4225 0.048 20 21.997 2087 0.024 21 24.082 114136 1.308 22 46.980 11915 0.137 23 50.561 11373 0.130

[0200] The liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 10 is as follows: Fig.24 As shown, the peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 10 are shown in Table 23.

[0201] Table 23 Peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 10

[0202] name Retention time (minutes) Area (μV x sec) %area 1 2.844 881 0.01 2 2.986 1226 0.014 3 3.243 8811820 98.758 4 3.53 21515 0.241 5 3.84 1271 0.014 6 4.25 8255 0.093 7 4.761 29889 0.335 8 5.426 1074 0.012 9 6.7 1741 0.02 10 7.612 820 0.009 11 8.534 26683 0.299 12 11.524 858 0.01 13 20.019 12465 0.14 14 24.199 724 0.008 15 24.844 1472 0.016 16 51.221 1923 0.022

[0203] The liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 11 is as follows: Fig.25 As shown, the peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 11 are shown in Table 24.

[0204] Table 24 Peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 11

[0205] name Retention time (minutes) Area (μV × sec) %area 1 2.357 277 0.003 2 2.839 1831 0.021 3 2.985 1137 0.013 4 3.239 8578930 96.655 5 3.530 684 0.008 6 3.827 6470 0.073 7 4.224 7696 0.087 8 4.716 16317 0.184 9 5.349 4343 0.049 10 5.752 833 0.009 11 6.614 5621 0.063 12 7.567 923 0.010 13 8.405 32810 0.370 14 12.283 83287 0.938 15 19.762 7491 0.084 16 23.719 17693 0.199 17 24.564 81517 0.918 18 28.082 3082 0.035 19 50.626 24864 0.280

[0206] The liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 12 is as follows: Fig.26 As shown, the peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 12 are shown in Table 25.

[0207] Table 25 Peak result data in the liquid chromatogram of 1,3-dimethyl-5-pyrazolone prepared in Comparative Example 12

[0208] name Retention time (minutes) Area (μV x sec) %area 1 5.169 5479671 99.82 2 9.660 5219 0.10 3 15.024 4437 0.08

[0209] The purity, impurity content and yield data of 1,3-dimethyl-5-pyrazolone prepared in Examples 1 to 13 and Comparative Examples 1 to 12 are shown in Table 26.

[0210] Table 26 Statistics of purity, impurity content and yield of 1,3-dimethyl-5-pyrazolone prepared in Examples 1 to 13 and Comparative Examples 1 to 12

[0211] Example Pyrazolone content, % Total impurity content, % Pyrazolone yield, % Example 1 99.83 0.17 96.71 Example 2 99.87 0.13 96.75 Example 3 99.83 0.17 96.67 Example 4 99.83 0.16 96.81 Example 5 99.96 0.04 97.37 Example 6 99.90 0.11 97.05 Example 7 99.96 0.04 97.31 Example 8 99.89 0.11 96.85 Example 9 99.79 0.21 96.61 Example 10 99.78 0.22 96.63 Embodiment 11 99.98 0.02 97.55 Example 12 99.80 0.20 96.73 Example 13 99.93 0.07 97.22 Comparative Example 1 97.688 2.312 88.11 Comparative Example 2 99.929 0.071 80.45 Comparative Example 3 97.418 2.582 85.44 Comparative Example 4 98.826 1.174 92.38 Comparative Example 5 98.998 1.002 92.77 Comparative Example 6 98.693 1.307 90.15 Comparative Example 7 95.009 4.991 82.56 Comparative Example 8 99.024 0.976 98.13 Comparative Example 9 97.379 2.621 85.28 Comparative Example 10 98.758 1.242 91.07 Comparative Example 11 96.655 3.345 98.78 Comparative Example 12 99.82 0.18 94.85

[0212] from Figures 2 to 26It can be seen from the data in Tables 1 to 26 that the concentration of the solution of acetoacetate is increased in Comparative Example 1 compared with Example 1, and the impurity content of the obtained 1,3-dimethyl-5-pyrazolone is high, the purity of the product decreases, and the yield also decreases accordingly; the concentration of the solution of acetoacetate is reduced in Comparative Example 2 compared with Example 1, which reduces the reaction efficiency, so that the material does not have time to fully react in the microchannel, thereby reducing the yield of the obtained 1,3-dimethyl-5-pyrazolone; the reaction temperature of hydrazinolysis is increased in Comparative Example 3 compared with Example 1, the reaction by-products increase, the impurities of the product increase, and the purity and yield decrease; the reaction temperature of hydrazinolysis is reduced in Comparative Example 4 compared with Example 1, the reaction is incomplete, the by-products increase, the impurities of the product increase, and the purity and yield decrease; the reaction time of hydrazinolysis is increased in Comparative Example 5 compared with Example 1, the reaction by-products increase, the purity and yield decrease; Comparative Example 6 compared with Example 1 Compared with Example 1, the hydrazinolysis reaction time was reduced, the reaction was incomplete, and the purity and yield decreased; Compared with Example 1, the molar ratio of methyl acetoacetate to methylhydrazine was reduced in Comparative Example 7, and the yield was greatly reduced; Compared with Example 1, the molar ratio of methyl acetoacetate to methylhydrazine was increased in Comparative Example 8, the reaction by-products increased, the impurities of the product increased, and the purity decreased; Compared with Example 1, the temperature of the acetoacetate solution before being pumped into the microchannel reactor was reduced in Comparative Example 9, the reaction efficiency decreased, the reaction was incomplete, and the purity and yield decreased; Compared with Example 1, the temperature of the acetoacetate solution before being pumped into the microchannel reactor was increased in Comparative Example 10, the reaction by-products increased, the purity and yield decreased; Compared with Example 1, the crystallization temperature was reduced in Comparative Example 11, the impurities increased, and the purity decreased; Compared with Example 1, the crystallization temperature was increased in Comparative Example 12, and the yield of the product decreased.

[0213] The invention controls the concentration of the acetoacetate solution to be 35-55wt%, the molar ratio of the acetoacetate to the methylhydrazine to be 1:(1.01-1.05), the hydrazinolysis reaction temperature to be 25-45°C, and the hydrazinolysis reaction time to be 30-60s to prepare 1,3-dimethyl-5-pyrazolone in a microchannel reactor, and then performs reflux at a temperature of 80-120°C, crystallization at a temperature of 10-20°C, and vacuum drying at a temperature of 50-80°C and a pressure of -0.085--0.095MPa to obtain 1,3-dimethyl-5-pyrazolone with a purity greater than 99% and a yield greater than 95%.

[0214] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A method for preparing 1,3-dimethyl-5-pyrazolone, comprising the following steps: (1) pumping a solution of acetoacetate and a solution of methylhydrazine into a microchannel reactor for hydrazinolysis reaction to obtain a mixed solution; the acetoacetate is methyl acetoacetate or ethyl acetoacetate; the concentration of the solution of acetoacetate is 35-55 wt %; the molar ratio of the acetoacetate to methylhydrazine is 1:(1.01-1.05); the temperature of the hydrazinolysis reaction is 25-45° C., the time of the hydrazinolysis reaction is 30-60 s; the temperature of the solution of acetoacetate before being pumped into the microchannel reactor is 15-25° C.; (2) The mixed solution obtained in step (1) is refluxed, crystallized and dried in sequence to obtain 1,3-dimethyl-5-pyrazolone; the crystallization temperature is 10 to 20° C.; and the drying temperature is 50 to 80° C.

2. The preparation method according to claim 1, characterized in that: The concentration of the acetoacetate solution in step (1) is 40-50 wt%.

3. The preparation method according to claim 1, characterized in that: The solvent in the solution of acetoacetate in step (1) is toluene or xylene.

4. The preparation method according to claim 1, characterized in that: In the step (1), the molar ratio of acetoacetate to methylhydrazine is 1:(1.02-1.04).

5. The preparation method according to claim 1, characterized in that: The concentration of the methylhydrazine solution in step (1) is 35-45 wt %.

6. The preparation method according to claim 1, characterized in that: In the step (1), before the acetoacetate solution and the methylhydrazine solution are pumped into the microchannel reactor, the solvent of the acetoacetate solution is first pumped into the microchannel in the microchannel reactor to fill it.

7. The preparation method according to claim 6, characterized in that: The solvent is preheated to the hydrazinolysis reaction temperature before being pumped into the microchannel reactor.

8. The preparation method according to claim 1, characterized in that: The reflux temperature in step (2) is 80-120°C.

9. The preparation method according to claim 1, characterized in that: The drying in step (2) is vacuum drying.

10. The preparation method according to claim 9, characterized in that: The vacuum drying pressure is -0.085 to -0.095 MPa.

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