A kind of synthesis method of azoxystrobin

Abstract

The present invention discloses a method for synthesizing azoxystrobin, which includes: in a water-oil system of an organic solvent and an aqueous solution of trimethylamine, the compound shown in Formula I reacts with 2-cyanophenol to obtain azoxystrobin; wherein, the molar ratio of the compound shown in Formula I to trimethylamine is 1:(0.96-2). The synthesis method of the present invention has higher reaction efficiency, does not generate CO2, avoids the risk of entrainment and overflow of materials, reduces side reactions, reduces solid waste emissions, and is green and environmentally friendly. The present invention does not need to use solid sodium carbonate or potassium carbonate, and the material reaction system is an oil-water reaction system, so the reaction efficiency is greatly improved, and the yield can also be maintained above 95%. It can take into account both efficiency (timeliness) and yield, and is easy to realize continuous reaction, providing technical support for intelligent and unmanned production; and trimethylamine can be recycled, reducing the use of one raw material, and thus does not require cumbersome treatment of mixed salts and their wastewater, and the energy consumption is significantly reduced.

Description

Technical Field

[0001] The invention relates to the field of pesticides, and in particular to a method for synthesizing azoxystrobin. Background Art

[0002] Methyl (E)-2-[2-[6-(2-cyanophenoxy)pyrimidin-4-yloxy]phenyl]-3-methoxyacrylate is a highly effective, broad-spectrum agricultural fungicide with multiple functions such as systemic conduction, prevention, protection and treatment. It has good control effects on powdery mildew, rust, glumemane blight, downy mildew and rice blast of plants. The currently reported synthesis processes are all prepared from methyl (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxyacrylate (compound of formula I) and 2-cyanophenol and solid carbonate in the presence of nearly anhydrous organic solvents and catalysts, or from methyl (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxyacrylate and 2-cyanophenol alkali metal salt. However, the current reaction route still has a series of problems:

[0003] For example, patents WO9208703 and EP0382375 both use (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxy methyl acrylate and o-hydroxybenzonitrile, add potassium carbonate as an acid-binding agent, use cuprous chloride as a catalyst, and DMF as a solvent to react at 120°C. However, this route is difficult to post-process and crystallize (crystallization at room temperature for 3 weeks), and is not suitable for large-scale industrial production. The process route is as follows:

[0004] .

[0005] For another example, patent CN101163682B discloses that in the presence of an acid acceptor (potassium carbonate or sodium carbonate), (E)-2-(2-[6-chloropyrimidin-4-yloxy]phenyl)-3-methoxyacrylate and 2-cyanophenol are reacted in a DMF slurry using DABCO as a catalyst to obtain azoxystrobin. As in step c of Example 1, DMF is removed from the slurry-state reaction liquid under vacuum distillation. The obtained distillation residue has a high solid content and requires a large power for the stirring equipment. 160 mL of toluene and 265 mL of water (a total of 167 g of reaction raw materials) are added to the distillation residue at 60°C, and the two-phase mixture is heated to 70-80°C. The mixture is stirred for 40 minutes and then allowed to settle, and the lower aqueous phase is separated. The amount of solvent and water added during the post-treatment process is very large. The added water is used to dissolve excess acid acceptor (potassium carbonate or sodium carbonate) raw materials and the formed potassium chloride, potassium bicarbonate or sodium chloride, sodium bicarbonate. It can be seen that the post-treatment of the target product is cumbersome and time-consuming. The generated mixed salt also needs to be heated to evaporate water and separated. There are many equipments, it is not easy to be continuous, the energy consumption is large, and the steps are long. It is not easy to realize intelligent and continuous industrial production, and it requires many operators and high costs.

[0006] For another example, patent CN109721548B discloses that in the presence of an acid acceptor (potassium carbonate or sodium carbonate), trimethylamine is used as a catalyst to react 2-cyanophenol or its salt with (E)-2-(2-((6-chloropyrimidin-4-yl)oxy)phenyl)3-methoxyacrylate to obtain azoxystrobin, the amount of trimethylamine used is 0.5-15 mol% of (E)-2-(2-((6-chloropyrimidin-4-yl)oxy)phenyl)3-methoxyacrylate, the acid acceptor is potassium carbonate and / or sodium carbonate, the reaction is carried out at 50-120°C, and usually takes 5-20 hours to complete. In Example 1, after the reaction is completed, 100 g of water is added, and the total amount of raw materials charged in the initial stage of the reaction is 145.5 g. It can be seen that water is added to dissolve excess acid acceptor (potassium carbonate or sodium carbonate) and by-product salts, and the oil phase and the water phase are separated. Although the technical solution for treating the water phase is not described, according to the cognition of those skilled in the art, the treatment method has the same technical problem as that of patent CN101163682B and has not been solved.

[0007] In the above technical scheme, the reaction system materials are usually 2-cyanophenol or its salt and (E)-2-(2-((6-chloropyrimidin-4-yl)oxy)phenyl)3-methoxyacrylate as raw materials, and potassium carbonate and sodium carbonate are used as acid binding agents (or acid acceptors). Although the technical scheme can obtain a relatively high yield of myclobutanil, the reaction process is a solid-liquid mixed system, which is mainly an intermittent reaction. It not only requires a solid feeding device, but also has the problems of long reaction time, low production efficiency and high energy consumption. If continuous operation is carried out, not only the required equipment is complicated, but also the corresponding mass transfer equipment investment cost is higher, which increases the cost and is not suitable for industrial production. Many technicians have also tried to improve its production efficiency for better industrial production, and have tried from multiple aspects such as catalysts and reaction raw materials, but have never found a solution to the above problems, that is, it is difficult to take into account both yield and timeliness at the same time.

[0008] In addition, the above technical solution still has the following problems: high-cost mass transfer equipment is required in production, a large amount of greenhouse gas CO2 will be released during the reaction, and an additional tail gas treatment system needs to be added. In addition, there are risks such as solvent entrainment, foaming, and overflow during the CO2 overflow. In addition, 2-cyanophenol is prone to cyano polymerization at high temperature during the reaction, especially under alkaline conditions, too high temperature and too long time will cause polymerization to varying degrees, and with the increase of temperature and time, the degree of polymerization increases, the by-products increase, and the yield or purity decreases. When the reaction time is too long, the raw material (E)-2-(2-((6-chloropyrimidin-4-yl)oxy)phenyl)3-methoxyacrylate will undergo hydrolysis or alcoholysis. The post-treatment slurry reaction liquid needs to be dissolved by adding a large amount of water before it can be separated normally. There are problems such as chloride, acid carbonate and carbonate solid in the aqueous phase at the same time, and a large amount of hydrochloric acid needs to be added to convert the mixed salt into a single salt to convert it into a single chloride salt, which greatly increases the post-treatment cost, not only increasing the cost, but also increasing carbon emissions and polluting the environment. Summary of the invention

[0009] Purpose of the Invention

[0010] In order to overcome the above-mentioned shortcomings, the purpose of the present invention is to provide a high-efficiency, resource-saving, extremely low solid waste, low capital investment and high degree of automation continuous, low-carbon, high-efficiency synthesis method of myclobutanil. The inventors of the present invention found that by using an aqueous solution of trimethylamine as an acid-binding agent, the material reaction system will become an oil-water reaction system, and the reaction efficiency has been greatly improved; and there is no need to use solid potassium carbonate / sodium carbonate, and the oil-water reaction system equipment is more convenient to use a continuous production device, providing support for the digitalization and intelligent transformation of industrial production, improving competitiveness and achieving higher operational efficiency; and trimethylamine can be recycled, avoiding the cumbersome post-processing mixed salt treatment and other problems; and no additional water is needed to dissolve potassium carbonate / sodium carbonate to achieve liquid separation, reduce the amount of water used, avoid a large amount of mixed salt wastewater treatment, further reduce industrial production energy consumption, and reduce industrial production costs.

[0011] Solution

[0012] To achieve the purpose of the present invention, the technical solution adopted by the present invention is as follows:

[0013] In a first aspect, the present invention provides a method for synthesizing azoxystrobin, comprising: reacting a compound represented by formula I with 2-cyanophenol in a water-oil system of an organic solvent and a trimethylamine aqueous solution to obtain azoxystrobin;

[0014] ;

[0015] Wherein, the molar ratio of the compound represented by formula I to trimethylamine is 1:(0.96~2).

[0016] Furthermore, the molar ratio of the compound represented by formula I to trimethylamine is 1:(1-2), optionally 1:(1.06-1.8), optionally 1:(1.1-1.8).

[0017] Furthermore, the molar ratio of the compound represented by formula I to 2-cyanophenol is 1:(1-5), optionally 1:(1-1.5), optionally 1:(1-1.2).

[0018] Furthermore, the mass fraction of trimethylamine in the trimethylamine aqueous solution is 20% to 40%, optionally 25% to 30%, optionally 30% to 40%.

[0019] Furthermore, there is no need to add additionally or add very small amounts of sodium carbonate or potassium carbonate; (it should be noted that no additional addition means that the present invention does not require the additional addition of sodium carbonate or potassium carbonate as an acid binding agent, but it should be understood that even if a very small amount of sodium carbonate or potassium carbonate is added to the reaction system, it has little effect on the effect of the present invention and can solve the technical problem to be solved by the present invention, which belongs to equivalent replacement).

[0020] Furthermore, the amount of the organic solvent added is at least an amount used to dissolve the compound represented by formula I and 2-cyanophenol or a salt thereof.

[0021] Furthermore, the weight ratio of the compound represented by formula I to the organic solvent is 1:(2-8), optionally 1:(2.3-5.7).

[0022] Furthermore, the organic solvent includes toluene.

[0023] Further, the reaction temperature is 50-170°C, optionally 80-150°C, optionally 80°C to reflux temperature.

[0024] Furthermore, the reaction pressure is 0.5~1.2MPa or 0.55~1.1MPa.

[0025] Furthermore, the reaction time is 5 min to 360 min or 5 min to 60 min or 5 min to 30 min.

[0026] Further, the reaction is carried out in a pipeline continuous reaction equipment, the pipeline temperature is 110~170℃, optionally 110~150℃, optionally 140~170℃, optionally 140~160℃, optionally 140~150℃; the pressure is 0.55~1.1MPa, optionally 0.5~0.7MPa, optionally 0.5~0.6MPa, optionally 0.55~0.6MPa.

[0027] Furthermore, a batch reaction or a continuous reaction is adopted, the reaction temperature is 85-150°C or 85-95°C, and the pressure is normal pressure to 1.1 MPa.

[0028] The reaction system of the present invention can significantly accelerate the reaction speed by increasing the temperature under pressure, and will not produce excessive by-products due to temperature increase or pressure holding.

[0029] Furthermore, the pipeline continuous reaction equipment includes a feed pump, a pressure relief safety valve, a static mixer, a delay pipeline, a back pressure valve, a receiving device and a heat exchanger.

[0030] In the pipeline continuous reaction, the compound represented by formula I, 2-cyanophenol and solvent are used as material A, and trimethylamine aqueous solution is used as material B. The mass ratio of material A to material B is 4~7:1, so that the molar ratio of the compound represented by formula I to trimethylamine in the system is maintained at 1:(1~2), optionally 1:(1.06~1.8), and optionally 1:(1.1~1.8).

[0031] Furthermore, after the reaction is completed, post-treatment is performed to obtain azoxystrobin product; optional post-treatment includes: direct liquid separation of the material after the reaction is completed (direct liquid separation means no need to add additional water), oil phase desolventization, and purification.

[0032] Optionally, purification includes redissolution (redissolution may be performed using methanol), crystallization, filtration, washing and drying.

[0033] Furthermore, the aqueous phase after separation is subjected to trimethylamine recovery and reuse; the optional recovery method includes: adjusting the pH of the aqueous phase to 2-8, adding alkali after concentration, and recovering a solution containing trimethylamine.

[0034] Furthermore, in the recovery and reuse of trimethylamine, the amount of base added is 0.95 to 1.2 times the molar amount of the compound represented by formula I, and optionally 1 to 1.2 times;

[0035] And / or, in the recovery and reuse of trimethylamine, the base is an alkali metal hydroxide, and the alkali metal is optionally sodium or alkali (which may be NaOH or KOH), or other bases.

[0036] Beneficial Effects

[0037] The synthesis method of the present invention is high in efficiency, resource-saving, extremely low in solid waste, low in carbon, and high in benefit, reduces capital investment, can realize continuous reaction, improve reaction efficiency, provide technical support for intelligent and unmanned production, realize intrinsic safety design, and greatly reduce the number of employees required for industrial production. The present invention uses trimethylamine aqueous solution as an acid binding agent, does not need to use solid potassium carbonate or sodium carbonate, does not need to convert 2-cyanophenol into 2-cyanophenol salt, the material reaction system is an oil-water reaction system, and trimethylamine can be recycled, reducing the use of a raw material, and then does not need to deal with cumbersome problems such as mixed salt, and does not need to deal with mixed salt wastewater. The innovative technical solution is designed to have low energy consumption from the source of the reaction; and liquid separation can be achieved without additional water, avoiding waste of water resources; the oil-water reaction system used in the present invention has higher mass transfer and heat transfer efficiency than the solid-liquid slurry reaction system, the reaction time is shortened, and equipment wear is reduced. The present invention does not use potassium carbonate or sodium carbonate, and can avoid the problem of the prior art that a large amount of greenhouse gas CO2 will be generated and the risk of material overflow (a large amount of greenhouse gas CO2 is not conducive to green and low-carbon transformation, and an additional tail gas treatment system needs to be added. In addition, the emission will carry solvents, and the reaction liquid is prone to overflow risks). The use of one raw material can be reduced from the scheme design stage, and low-carbon emissions and inherent safety of the process can be achieved; the synthesis method of the present invention can reduce the problem that cyano polymerization of 2-cyanophenol is prone to occur at high temperatures, the reaction time is greatly shortened, and the hydrolysis or alcoholysis of the compound of formula I can be reduced, thereby improving the yield and purity. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] One or more embodiments are exemplarily described by the pictures in the accompanying drawings, and these exemplary descriptions do not constitute limitations on the embodiments. The special word "exemplary" here means "used as an example, embodiment or illustrative". Any embodiment described as "exemplary" here is not necessarily interpreted as being superior or better than other embodiments.

[0039] Figure 1 The material state changes of Comparative Example 2 and Example 3 of the present invention before and after the reaction. A is the material state of Comparative Example 2 before heating; C is the material state of Comparative Example 2 during heating; E is the material state of Comparative Example 2 during the insulation stage; G is the material state of Comparative Example 2 after the reaction is completed; B is the material state of Example 3 before heating; D is the material state of Example 3 during heating; F is the material state of Example 3 during the insulation stage; H is the material state of Example 3 after the reaction is completed. DETAILED DESCRIPTION

[0040] In order to make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the technical solution in the embodiments of the present invention will be described clearly and completely below. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. 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.

[0041] In addition, in order to better illustrate the present invention, numerous specific details are provided in the specific embodiments below. It should be understood by those skilled in the art that the present invention can be implemented without certain specific details. In some embodiments, raw materials, schemes, methods, means, etc. well known to those skilled in the art are not described in detail, so as to highlight the main purpose of the present invention.

[0042] Unless explicitly stated otherwise, throughout the specification and claims, the term “comprise” or variations such as “include” or “comprising”, etc., will be understood to include the stated elements or components but not to exclude other elements or components.

[0043] In the following examples, (E)-methyl 2-(2-((6-chloropyrimidin-4-yl)oxy)phenyl)-3-methoxyacrylate, 2-cyanophenol, trimethylamine and other reagents are commercially available; unless otherwise specified, the reaction process and results are detected by high performance liquid chromatography (HPLC), and the content is detected by the external standard method.

[0044] The compound represented by formula I of the present invention ((E)-2-(2-((6-chloropyrimidin-4-yl)oxy)phenyl)3-methoxyacrylate) and 2-cyanophenol (compound represented by formula II) are dissolved in an organic solvent and, under the action of a trimethylamine aqueous solution, azoxystrobin (compound represented by formula III) is generated. The reaction scheme is as follows:

[0045] .

[0046] In the following examples, the compound represented by formula I refers to methyl (E)-2-(2-((6-chloropyrimidin-4-yl)oxy)phenyl)3-methoxyacrylate.

[0047] In the following examples, the reference for the detection of by-products is: Chen Haiyan, Tao Wenbo, Ding Kehong. Analysis of side reactions in the synthesis of azoxystrobin by LC-MS [J]. Pesticides, 2016, 55 (10): 725-728. P727 Impurity structures 1 and 4 are .

[0048] Through continuous research, the inventors found that the use of trimethylamine aqueous solution as an acid-binding agent not only changes the material reaction system into an oil-water reaction system, the reaction efficiency is greatly improved, and the yield can be maintained at more than 95%, which can take into account both efficiency (timeliness) and yield, and is easy to achieve continuous reaction, suitable for industrial production; in further research, it was found that other tertiary amines such as triethylamine or NaOH aqueous solution cannot achieve a similar reaction effect as trimethylamine as an acid-binding agent. Specifically, some embodiments are as follows:

[0049] Example 1

[0050] 131g (0.40mol) of the compound shown in formula I and 51.5g (0.424mol) of 2-cyanophenol were added to 301g of toluene to prepare a solution, and 83.4g (30% content, 0.424mol) of trimethylamine aqueous solution were added, and the solution was refluxed at normal pressure for 4.5h. During the insulation process, the color of the liquid gradually became lighter. After the insulation was completed, the temperature was lowered to 30°C and allowed to stand directly to obtain clear oil and water phases. After phase separation, the reddish brown oil phase was washed and then distilled under reduced pressure to remove toluene, and the temperature was lowered to 60-65°C. Methanol was added, and the temperature was raised to reflux to dissolve, and the temperature was lowered to about 0°C. Crystallization was performed for 2h, and suction filtration, washing, and the filter cake was dried to obtain 157.6g of azoxystrobin product, with a content of 98.7% and a yield of 96.4%.

[0051] Example 2

[0052] 131g (0.40mol) of the compound shown in formula I and 55.8g (0.46mol) of 2-cyanophenol were added to 747g of toluene to prepare a solution, and 110.1g (30% content, 0.56mol) of trimethylamine aqueous solution was added. The color of the feed liquid gradually became lighter during the insulation process, and the insulation was completed by reflux at normal pressure for 5h. The color of the feed liquid gradually became lighter during the insulation process. After the insulation was completed, the temperature was lowered to 30°C and allowed to stand directly to obtain clear oil and water phases. After phase separation, the reddish brown oil phase was washed and then distilled under reduced pressure to remove toluene, cooled to 60-65°C, methanol was added, heated and refluxed to dissolve, cooled to about -5°C, crystallized for 2h, filtered, washed, and the filter cake was dried to obtain 159.2g of azoxystrobin product with a content of 98.1% and a yield of 96.8%.

[0053] Example 3

[0054] 131g (0.40mol) of the compound shown in formula I and 55.8g (98% content, 0.46mol) of 2-cyanophenol were added to 400g of toluene to prepare a solution, and 78.7g (30% content, 0.40mol) of trimethylamine aqueous solution were added, and the mixture was refluxed at normal pressure for 6h. During the insulation process, the color of the liquid gradually became lighter. After the insulation was completed, the temperature was lowered to 30°C, and the mixture was allowed to stand directly to obtain clear oil and water phases. After phase separation, the reddish brown oil phase was washed and then distilled under reduced pressure to remove toluene, and the temperature was lowered to 60-65°C. Methanol was added, and the mixture was refluxed at a temperature of 100°C to dissolve. The mixture was cooled to about -5°C, and crystallized for 2h. The mixture was filtered, washed, and the filter cake was dried to obtain 157.7g of azoxystrobin product with a content of 97.9% and a yield of 95.7%.

[0055] Example 4

[0056] In a closed reactor, 131 g (0.40 mol) of the compound shown in formula I, 53.4 g (0.44 mol) of 2-cyanophenol, and 500 g of toluene were added to prepare a solution. After stirring evenly, 102.3 g (30% content, 0.52 mol) of trimethylamine aqueous solution was added, the reactor was closed, the temperature was raised to 150 ° C, the reaction was kept warm for 0.5 h, the system pressure was 0.55 MPa, the reaction was completed, the temperature was lowered to about 30 ° C, and it was directly allowed to stand to obtain clear oil and water phases. The phases were separated, and the oil phase was washed and then distilled under reduced pressure to remove toluene, cooled to 60-65 ° C, methanol was added, the temperature was raised to reflux to dissolve, cooled to about -5 ° C, crystallized for 2 h, filtered, washed, and the filter cake was dried to obtain 158.4 g of azoxystrobin product with a content of 98.2% and a yield of 96.4%.

[0057] Example 5

[0058] In a closed reactor, 131 g (0.40 mol) of the compound shown in formula I, 58.3 g (0.48 mol) of 2-cyanophenol, and 500 g of toluene were added to prepare a solution. After stirring evenly, 118 g (30% content, 0.60 mol) of trimethylamine aqueous solution was added, the reactor was closed, the temperature was raised to 160 ° C, the reaction was kept warm for 0.25 h, the system pressure was 0.77 MPa, the reaction was completed, the temperature was lowered to about 30 ° C, and the mixture was allowed to stand directly to obtain clear oil and water phases. The phases were separated, and the oil phase was washed and distilled under reduced pressure to remove toluene, the temperature was lowered to 60-65 ° C, methanol was added, the temperature was raised to reflux to dissolve, the temperature was lowered to about -5 ° C, crystallized for 2 h, filtered, washed, and the filter cake was dried to obtain 158.2 g of azoxystrobin product with a content of 98.0% and a yield of 96.1%.

[0059] Example 6

[0060] 1310 g (4.00 mol) of the compound represented by formula I and 544 g (4.48 mol) of 2-cyanophenol were added to 5246 g of toluene, stirred to dissolve, and set aside (recorded as material A); 1023 g of trimethylamine aqueous solution (content 30%, 5.20 mol) was weighed and set aside (recorded as material B); material A and material B were connected to a static mixer preheated to 150°C through a metering pump through pipelines, and the outlet of the static mixer was connected to a closed reactor. The pressure relief valve at the outlet of the closed reactor was set to 0.55 MPa, and the outlet of the feed pipeline was set at the bottom of the reactor. The discharge port pipeline is set at the upper part of the liquid surface. The feed mass ratio of material A to material B is 6.94:1. The appropriate feed flow rate is adjusted to control the residence time of the material in the reactor to be 0.5h. After stable operation, the material is continuously taken at the discharge port, cooled, and directly allowed to stand to obtain clarified oil and water phases. After phase separation, the oil phase is washed and then distilled under reduced pressure to remove toluene, cooled to 60~65℃, methanol is added, heated and refluxed to dissolve, cooled to about -5℃, crystallized for 2h, filtered, washed, and the filter cake is dried to obtain 1585.6g of azoxystrobin product with a content of 98.3% and a yield of 96.6%.

[0061] Example 7

[0062] 1310 g (4.00 mol) of the compound represented by formula I and 544 g (4.48 mol) of 2-cyanophenol were added to 5240 g of toluene, stirred to dissolve, and set aside (recorded as material A); 1180 g of trimethylamine aqueous solution (content 30%, 6.00 mol) was weighed and set aside (recorded as material B); material A and material B were connected to a static mixer preheated to 150°C through pipes through a metering pump, and the outlet of the static mixer was connected to a closed reactor. The pressure of the closed reactor outlet pressure relief valve was set to 0.55 MPa, the outlet of the feed pipe was set at the bottom of the reactor, and the outlet of the discharge pipe was set at the upper part of the liquid surface. The feed mass ratio of material A and material B is 6.02:1. The appropriate feed flow rate is adjusted to control the residence time of the material in the reactor to 0.4h. After stable operation, the material is continuously taken at the discharge port, cooled, and directly allowed to stand to obtain clarified oil and water phases. The oil phase is washed and then distilled under reduced pressure to remove toluene. The temperature is lowered to 60-65°C, 550g of methanol is added, the temperature is raised and refluxed to dissolve, the temperature is lowered to about -5°C, crystallized for 3h, filtered, washed, and the filter cake is dried to obtain 1595.4g of myclobutanil product with a content of 98.2% and a yield of 97.1%.

[0063] Example 8

[0064] 1310 g (4.00 mol) of the compound represented by formula I and 544 g (4.48 mol) of 2-cyanophenol were added to 5240 g of toluene, stirred to dissolve, and set aside (recorded as material A); 1416 g of trimethylamine (content 30%, 7.20 mol) was weighed and set aside, recorded as material B; materials A and B were connected to the inlet of the static mixer through pipelines according to the feed mass ratio using metering pumps A and B respectively, and a safety pressure relief valve was connected between metering pump A and the static mixer. The static mixer was preheated to a reaction temperature of 150°C, and the outlet of the static mixer was connected to a delay pipeline, and the temperature of the delay pipeline was controlled at 170°C. The outlet of the delay pipeline was connected to a cooling coil and a back pressure valve, a receiving bottle, and the back pressure valve was set to a pressure of 0.95 MPa, and the length of the delay pipeline was adjusted so that the residence time of the material in the delay pipeline was 12 min. The feed rate ratio of material A to material B was set to 5:1. After the operation was stable, the effluent was collected, cooled, and allowed to stand directly to obtain clarified oil and water phases. The oil phase was washed and then distilled under reduced pressure to remove toluene. Methanol was added and the temperature was raised to reflux for dissolution. The temperature was lowered to about -5°C and crystallized for 3 hours. The product was filtered, washed, and the filter cake was dried to obtain 1583.9 g of azoxystrobin product with a content of 98.0% and a yield of 96.2%.

[0065] Example 9

[0066] 1310g (4.00mol) of the compound represented by formula I and 544g (4.48mol) of 2-cyanophenol were added to 5240g of toluene, stirred to dissolve, and set aside (recorded as material A); 1573g of trimethylamine (content 30%, 8.00mol) was weighed and set aside, recorded as material B; materials A and B were connected to the inlet of the static mixer through pipelines according to the feed mass ratio using metering pumps A and B respectively, and a safety pressure relief valve was connected between metering pump A and the static mixer. The static mixer was preheated to a reaction temperature of 160°C, and the outlet of the static mixer was connected to a delay pipeline, and the temperature of the delay pipeline was controlled at 160°C. The outlet of the delay pipeline was connected to a cooling coil and a back pressure valve, a receiving bottle, and the back pressure valve was set to a pressure of 1.1MPa, and the length of the delay pipeline was adjusted so that the residence time of the material in the delay pipeline was 10min. The feed rate ratio of material A to material B was set to 4.51:1. After stable operation, the effluent was collected, cooled, and allowed to stand directly to obtain clarified oil and water phases. The oil phase was washed and then distilled under reduced pressure to remove toluene. The temperature was lowered to 60-65°C, methanol was added, and the temperature was raised to reflux for dissolution. The temperature was lowered to about -5°C, and crystallization was performed for 1 hour. The product was filtered, washed, and the filter cake was dried to obtain 1573.8 g of azoxystrobin product with a content of 97.5% and a yield of 95.1%.

[0067] Example 10

[0068] The first recovery and application of trimethylamine: hydrochloric acid was added to the aqueous phase obtained in Example 4 to adjust the pH to 2-3, and then 0.2% activated carbon was added, and the temperature was raised to 60°C for adsorption and impurity removal for 0.5h. The filtrate was concentrated to 130°C at normal pressure, and pretreated with 53.4g NaOH solution (content 30%, 0.40mol), and 4.1g trimethylamine aqueous solution (content 30%, 0.021mol) was added and transferred to the reactor. Toluene, 131g (0.40mol) of the compound shown in Formula I, and 51.5g (0.42mol) of 2-cyanophenol were added to the reactor. The reactor was closed and the temperature was raised to 150°C (system pressure 0.55MPa), and the reaction was kept warm for 0.5h. The mixture was cooled to about 30°C and allowed to stand to obtain clear oil and water phases. The phases were separated and the oil phase was washed and then distilled under reduced pressure to remove toluene. The mixture was cooled to 60-65°C and methanol was added. The mixture was heated to reflux and dissolved. The mixture was cooled to about -5°C and crystallized for 2h. The mixture was filtered, washed and dried to obtain 158.1g of myclobutanil product with a content of 98.5% and a yield of 96.5%.

[0069] Embodiment 11

[0070] The aqueous phase obtained in Example 10 was adjusted to pH 2-3 by adding hydrochloric acid, and activated carbon was added in an amount of 0.2% by weight of the aqueous phase. The temperature was raised to about 60° C., and the mixture was stirred for adsorption and impurity removal for 0.5 h. The filtrate was concentrated to 130° C. at normal pressure, and the temperature was lowered to 50° C. to filter and remove salt. A small amount of water was added to wash the salt. The washing liquid was combined with the filtrate, and 53.5 g (30% content, 0.40 mol) of NaOH solution was added for treatment. 4.1 g of trimethylamine aqueous solution (30% content, 0.021 mol) was added and transferred to a reactor. 500 g of toluene, 131 g (0.40 mol) of the compound shown in Formula I, and 51.5 g (0.42 mol) of 2-cyanophenol were added to the reactor. The reactor was closed and the temperature was raised to 150° C. (system pressure 0.55 MPa), and the reaction was kept warm for 0.5 h to terminate. The mixture was cooled to about 30°C and allowed to stand to obtain clear oil and water phases. The phases were separated and the oil phase was washed and then distilled under reduced pressure to remove toluene. The mixture was cooled to 60-65°C and methanol was added. The mixture was heated to reflux and dissolved. The mixture was cooled to about -5°C and crystallized for 2h. The mixture was filtered, washed and dried to obtain 157.8g of myclobutanil product with a content of 98.5% and a yield of 96.3%.

[0071] Example 12

[0072] The aqueous phase obtained in Example 11 was adjusted to pH 2-3 by adding hydrochloric acid, and activated carbon was added in an amount of 0.2% by weight of the aqueous phase. The temperature was raised to about 60°C, and the mixture was stirred for 0.5h for adsorption and impurity removal. The filtrate was concentrated to 130°C at normal pressure, cooled to 50°C, filtered and desalted, and a small amount of water was added to wash the salt. The washing liquid was combined with the filtrate, and 4.1g of trimethylamine aqueous solution (content 30%, 0.021mol) and 50.7g of NaOH solution (content 30%, 0.38mol) were added for treatment, and the mixture was transferred to a reactor. 600g of toluene, 131g (0.40mol) of the compound shown in Formula I, and 51.5g (0.42mol) of 2-cyanophenol were added to the reactor. The reactor was closed and the temperature was raised to 150°C (system pressure 0.55MPa), and the reaction was carried out by heat preservation for 0.5h. The mixture was cooled to about 30°C and allowed to stand to obtain clear oil and water phases. The phases were separated and the oil phase was washed and then distilled under reduced pressure to remove toluene. The mixture was cooled to 60-65°C and methanol was added. The mixture was heated to reflux and dissolved. The mixture was cooled to about -5°C and crystallized for 2h. The mixture was filtered, washed and dried to obtain 158.3g of myclobutanil product with a content of 98.4% and a yield of 96.5%.

[0073] Embodiment 13

[0074] The aqueous phase obtained in Example 12 was adjusted to pH 2-3 by adding hydrochloric acid, and activated carbon was added in an amount of 0.2% by weight of the aqueous phase. The temperature was raised to about 60°C, and the mixture was stirred for 0.5h for adsorption and impurity removal. The filtrate was concentrated to 130°C at normal pressure, and the temperature was lowered to 50°C for filtration and desalination. A small amount of water was added to wash the salt, and the washing liquid was combined with the filtrate, and 56.0g (content 48%, 0.48mol) of KOH solution was added for treatment, and the mixture was transferred into a reactor. Toluene, 131g (0.40mol) of the compound shown in Formula I, and 51.5g (0.42mol) of 2-cyanophenol were added to the reactor. The reactor was closed and the temperature was raised to 150°C (system pressure 0.55MPa), and the reaction was carried out by heat preservation for 0.5h. The mixture was cooled to about 30°C and allowed to stand to obtain clear oil and water phases. The phases were separated and the oil phase was washed and then distilled under reduced pressure to remove toluene. The mixture was cooled to 60-65°C and methanol was added. The mixture was heated to reflux and dissolved. The mixture was cooled to about -5°C and crystallized for 2h. The mixture was filtered, washed and dried to obtain 159.0g of azoxystrobin product with a content of 98.1% and a yield of 96.7%.

[0075] The results of Examples 11 to 13 show that the aqueous phase post-treatment of the present invention is relatively simple, including: adding a small amount of hydrochloric acid (adjusting pH 2 to 3) to fix free trimethylamine (solubility of trimethylamine hydrochloride), decolorizing with activated carbon, desalting under reduced pressure and concentration (no desalting is required for the first application, and a single salt (NaCl in Examples 11 and 12, KCl in Example 13) is removed after the second application. The type of salt is relatively single, and the recovered salt can be used as a recycling resource), and the filtrate is freed of trimethylamine by adding alkali, which can be directly applied without separation.

[0076] Comparative Example 1: Using Liquid Alkali as Acid Binding Agent

[0077] To a 1000ml four-necked bottle, 450g of toluene, 120g (0.370mol, content 99%) of the compound shown in formula I, 49g (0.408mol, content 99%) of 2-cyanophenol, 5.31g (0.0297mol, content 33%) of trimethylamine aqueous solution, and 53.55g (0.428mol, content 32%) of liquid alkali were added, and the temperature was slowly raised to 80°C. The color of the feed liquid deepened during the insulation process. The mixture was kept warm for 10h, the reaction was completed, and the phases were separated to obtain 597.2g of dark red toluene liquid. The external standard azoxystrobin content was 22.73%, and the conversion rate was 90.7%.

[0078] This comparative example 1 shows that when liquid alkali is used as an acid-binding agent, the conversion rate of the product decreases. The inventors speculate that this may be because the alkalinity of the liquid alkali is too strong, resulting in the production of by-products. The presence of a large amount of alkali at high temperature causes the ester group of the compound of formula 1 and azoxystrobin to be hydrolyzed, and the chlorine of the compound of formula 1 is replaced by a hydroxyl group.

[0079] Comparative Example 2: Potassium carbonate as acid binding agent

[0080] To 1000mL, 300g of toluene, 162g (0.500mol, 99%) of the compound shown in Formula I ((E)-2-[2-[6-chloropyrimidin-4-yloxy]phenyl]-3-methoxyacrylate), 66.15g (0.550mol, 99%) of 2-cyanophenol, and 55.8g (0.4mol, 99%) of potassium carbonate were added to the reaction bottle in sequence. The solid content of the material was high and it was difficult to stir. 150g of toluene was added for smooth stirring. 7.15g (0.04mol, concentration 33%) of trimethylamine aqueous solution was added, and the temperature was raised to 80°C under normal pressure. Alkaline gas was discharged from the condenser, the reaction liquid foamed, and the volume expanded. The feed liquid was kept warm for 10h, the reaction was completed, 200g of water was added, and 650.03g of azoxystrobin toluene solution was obtained by layering, with a content of 29.85% and a conversion rate of 96.2%.

[0081] In this comparative example 2, the trimethylamine in the aqueous phase can be recycled and reused, but because the aqueous phase also contains chlorides, acid carbonates and carbonate mixed salts, the post-processing of the aqueous phase is relatively cumbersome, including: nitrogen is required to blow off the trimethylamine and add water (or methanol) for absorption (trimethylamine has a large solubility in water, 20g / 100g (30°C), and a large amount of N2 is required to ensure the recovery rate of trimethylamine). The brine after recovering trimethylamine needs to be treated with acid (usually hydrochloric acid) to treat excess carbonates and bicarbonates, and then decolorized, and the filtrate is concentrated and desalted. In this comparative example 2, the reaction solution needs to be added with water to dissolve the salt until it is clear before separation, and the aqueous phase after separation needs to add a large amount of hydrochloric acid to be treated as chloride, which greatly increases the post-processing cost, and the recovery of trimethylamine also requires more water. That is, this comparative example requires more water resources, resulting in waste of water resources.

[0082] In this comparative example 2, solid potassium carbonate is added, which is complicated to operate and requires a long reaction time (10 hours). Industrial production requires opening a manhole or setting up a solid feeding bin. Theoretically, 1 t of product produces 54.6 kg of CO2 as a by-product. The reaction materials have high requirements on the stirring device, and the system should not be closed, and requires normal pressure reaction.

[0083] Comparative Example 3: Using triethylamine as acid binding agent

[0084] To 500 mL of the reaction bottle, 230 g of toluene, 81 g (0.25 mol, 99%) of the compound shown in Formula I ((E)-2-[2-[6-chloropyrimidin-4-yloxy]phenyl]-3-methoxyacrylate), 33.06 g (0.275 mol, 99%) of 2-cyanophenol, and 20.44 g (0.2 mol, 99%) of triethylamine were added in sequence. The mixture was stirred and heated to 90°C. The liquid was kept warm for 10 h, 100 g of water was added, and 356.78 g of toluene solution of azoxystrobin was obtained by layering. The content of the solution was 6.47%, and the yield was 22.89%.

[0085] In this comparative example 3, triethylamine is used as the acid binding agent. Although it has a similar structure to trimethylamine, it cannot effectively carry out the reaction and the conversion rate is low.

[0086] Comparative Example 4: Using trimethylamine-methanol solution as acid binding agent

[0087] To 500 mL, 230 g of toluene, 81 g (0.25 mol, 99%) of the compound shown in Formula I ((E)-2-[2-[6-chloropyrimidin-4-yloxy]phenyl]-3-methoxyacrylate), 33.06 g (0.275 mol, 99%) of 2-cyanophenol, and 49.2 g (0.275 mol, 33%) of trimethylamine-methanol solution were added to the reaction bottle in sequence, and the mixture was stirred and heated. During the heating process, a large amount of alkaline gas overflowed (the inventors speculated that the solubility of trimethylamine in methanol was 30-47%, which made it easy to volatilize), and the mixture was refluxed for 10 hours, 200 g of water was added, and the mixture was stirred and allowed to stand for phase separation. 335.1 g of oil phase was obtained, with a content of 23.56% and a conversion rate of 78.29%.

[0088] In this comparative example 4, trimethylamine-methanol solution is used as the acid binding agent. Although the reaction system also contains trimethylamine, the reaction conversion efficiency is low.

[0089] Comparative Examples 1 to 4 show that in Comparative Example 2, potassium carbonate is used as an acid-binding agent and trimethylamine is used as a catalyst, and the product yield is relatively high, but it has many problems: Comparative Example 2 (traditional process) is a solid-liquid heterogeneous reaction (see Figure 1 A in the heating or heat preservation process, due to the heterogeneous phase, it is easy to adhere to the wall during stirring (see Figure 1 In actual industrial production, solid materials are also easy to wear the reactor, increasing maintenance costs. After the reaction is completed, a large amount of inorganic salts are deposited at the bottom (see Figure 1 G in the sample), water needs to be added for separation.

[0090] The trimethylamine of the present invention is an acid binding agent, especially an aqueous solution for the synthesis of azoxystrobin, and there is no need to add an additional acid acceptor or convert 2-cyanophenol into 2-cyanophenolate, nor is there a need to use solid potassium carbonate or sodium carbonate. Taking Example 3 as an example, the material reaction system is an oil-water reaction system (see Figure 1 B in the figure), it is easy to stir during the heating and heat preservation process (see Figure 1 D and F in the figure), after the reaction is completed, the clear oil and water phases can be obtained by simply standing (see Figure 1 The H in the solution can be directly separated without adding water, which greatly improves the efficiency and avoids the waste of water resources and post-treatment of a large amount of mixed salt in traditional technologies.

[0091] In addition, the inventors of the present invention have also found that when 2-cyanophenolate is used, trimethylamine will overflow in large quantities, which not only affects the environment but also increases the difficulty of treatment.

[0092] The inventors of the present invention have also studied the stability of 2-cyanophenol and found that it will gradually polymerize at a temperature above 110°C. After 0.5 hours of heat preservation, the clear solution of 2-cyanophenol has become significantly turbid, and the degree of polymerization increases with the increase of temperature and time, and solidifies after cooling. Therefore, improving the reaction efficiency can effectively reduce the generation of 2-cyanophenol polymerization byproducts.

[0093] The reaction temperature of the invention is 50-170°C, the reaction pressure is normal pressure to 1.1Mpa, the reaction time is 5min to 360min, the reaction conditions are mild, the efficiency is high, and the reaction time is short. The invention is based on the method for synthesizing azoxystrobin at normal pressure or slightly positive pressure with trimethylamine as an acid binding agent, and the reaction can be intermittent or continuous.

[0094] In a batch or continuous reaction in a kettle, when the reaction temperature is 150°C, the pressure is 0.55MPa, and the reaction is kept warm for 30 minutes, the reaction endpoint can be reached.

[0095] In a batch reaction, when the reaction temperature is 85-90°C and the pressure is normal pressure, the reaction endpoint is reached after 4-5 hours of heat preservation.

[0096] The reaction time at atmospheric reflux temperature (such as Examples 1-3) is slightly longer, requiring about 4-5 hours, but a higher reaction yield and purity can still be obtained when trimethylamine is used as the acid binding agent and solid sodium carbonate or potassium carbonate is not used.

[0097] The reaction of the present invention can be a kettle-type batch reaction, a kettle-type continuous reaction or a pipeline-type continuous reaction, wherein in the pipeline-type continuous reaction, efficient synthesis can be achieved in a very short time, thereby improving production efficiency.

[0098] When using pipeline continuous reaction, the reaction temperature is 150℃, and the reaction end point is reached after staying for about 10 minutes. The pipeline continuous reaction equipment includes a feed pump, a pressure relief safety valve, a static mixer, a delay pipeline, a back pressure valve, a receiving device, and a heat exchanger.

[0099] The post-treatment schemes of the above-mentioned batch reaction, continuous reaction at normal pressure, and continuous reaction in pipeline are the same. After the reaction is completed, the phases are separated, the pH of the aqueous phase is adjusted to 2-8, and an alkaline substance is added after concentration. The alkaline substance is NaOH or KOH, and the amount of the alkaline substance added is 0.95-1.2 times the molar amount of (E)-2-(2-((6-chloropyrimidin-4-yl)oxy)phenyl)3-methoxyacrylate. After treatment, it is recycled for the next batch; when it is continuously applied, after concentration, NaCl (or KCl) is filtered and separated, and alkali is added to the brine after separation of NaCl (or KCl) and continued to be applied. The oil phase is washed, desolventized, refined, separated, and dried.

[0100] The present invention uses trimethylamine as an acid-binding agent, which can effectively avoid the cyano polymerization of 2-cyanophenol; and by increasing the amount of trimethylamine used, the reaction speed can be significantly accelerated, thereby avoiding the hydrolysis or alcoholysis of the raw material (E)-2-(2-((6-chloropyrimidin-4-yl)oxy)phenyl)3-methoxyacrylate and the occurrence of side reactions of 2-cyanophenol during the heating reaction. The problem of easy foaming and overflowing in the reaction process of the prior art is solved, and the difficulty of post-treatment of the water phase is reduced (the problem of forming chlorides, acid carbonates and carbonate mixed salts after using sodium carbonate in the traditional process requires a large amount of acid to be added after dissolution and separation to neutralize the chlorides, which not only increases the cost, but also increases carbon emissions and pollutes the environment), and the problem of wear of the reactor by solid materials is also avoided. The invention adopts trimethylamine aqueous solution as an acid-binding agent, does not need to add sodium carbonate or potassium carbonate, and does not need to convert 2-cyanophenol into 2-cyanophenol salt. The material reaction system is an oil-water reaction system, which is conducive to molecular or ion diffusion and improves reaction efficiency. The trimethylamine can be recycled, and the problem of cumbersome post-treatment mixed salt treatment is avoided. Liquid separation can be achieved without adding additional water, and waste of water resources is avoided. The high-efficiency reaction time is shortened.

[0101] The present invention does not require a catalyst, and the reaction system is simpler; the acid binding agent used in the present invention can be recycled, avoiding the generation of solid waste and greenhouse gas CO2 by the traditional technology of using sodium carbonate or potassium carbonate, and is cleaner and has lower cost; the present invention does not involve solid materials, is easy to operate, and can be continuous with conventional equipment, thereby improving production efficiency, reducing manpower and equipment investment, and having low cost; the present invention solves the problem of solid-liquid heterogeneous reaction system, realizes efficient mass transfer and heat transfer in the reaction process, and has higher production efficiency and is cleaner; the present invention does not generate gas, fundamentally avoids the risk of overflow, and realizes the inherent safety of the production process.

[0102] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for synthesizing azoxystrobin, characterized in that: It includes: In a water-oil system consisting of an organic solvent and a trimethylamine aqueous solution, the compound represented by formula I reacts with 2-cyanophenol to obtain azoxystrobin; ； Wherein, the molar ratio of the compound represented by formula I to trimethylamine is 1:(1.06-1.8); The molar ratio of the compound represented by formula I to 2-cyanophenol is 1:(1-1.5); The mass fraction of trimethylamine in trimethylamine aqueous solution is 20%~40%; The weight ratio of the compound represented by formula I to the organic solvent is 1:(2.3-5.7); The organic solvent is toluene.

2. The synthesis method according to claim 1, characterized in that The molar ratio of the compound represented by formula I to trimethylamine is 1:(1.1-1.8).

3. The synthesis method according to claim 1, characterized in that The molar ratio of the compound represented by formula I to 2-cyanophenol is 1:(1-1.2).

4. The synthesis method according to claim 1, characterized in that The mass fraction of trimethylamine in trimethylamine aqueous solution is 20%~30%.

5. The synthesis method according to claim 1, characterized in that The mass fraction of trimethylamine in trimethylamine aqueous solution is 25%~30%.

6. The synthesis method according to claim 1, characterized in that The mass fraction of trimethylamine in trimethylamine aqueous solution is 30%~40%.

7. The synthesis method according to claim 1, characterized in that The reaction system does not require the addition of additional sodium carbonate or potassium carbonate.

8. The synthesis method according to claim 1, characterized in that The reaction temperature is 50~170℃.

9. The synthesis method according to claim 1, characterized in that The reaction temperature is 80~150℃.

10. The synthesis method according to claim 1, characterized in that The reaction temperature is 80°C ~ reflux temperature.

11. The synthesis method according to claim 1, characterized in that: The reaction pressure is 0.5~1.2MPa.

12. The synthesis method according to claim 1, characterized in that 0.55~1.1MPa.

13. The synthesis method according to claim 1, characterized in that: The reaction time is 30min~360min.

14. The synthesis method according to claim 1, characterized in that The reaction time is 30min~60min.

15. The synthesis method according to claim 1, characterized in that: The reaction is carried out in a pipeline continuous reaction equipment with a pipeline temperature of 110~170℃ and a pressure of 0.55~1.1MPa.

16. The synthesis method according to claim 15, characterized in that The reaction is carried out in a pipeline continuous reaction equipment with a pipeline temperature of 140~160℃.

17. The synthesis method according to claim 15, characterized in that: The pressure is 0.5~0.7MPa.

18. The synthesis method according to claim 15, characterized in that: The pressure is 0.5~0.6MPa.

19. The synthesis method according to claim 15, characterized in that: The pressure is 0.55~0.6MPa.

20. The synthesis method according to claim 15, characterized in that: The pipeline continuous reaction equipment includes a feed pump, a pressure relief safety valve, a static mixer, a delay pipeline, a back pressure valve, a receiving device and a heat exchanger.

21. The synthesis method according to claim 1, characterized in that A kettle-type intermittent reaction or a kettle-type continuous reaction is adopted, the reaction temperature is 85~150°C, and the pressure is normal pressure~1.1MPa.

22. The synthesis method according to claim 21, characterized in that A batch reaction or a continuous reaction is adopted, and the reaction temperature is 85~95°C.

23. The synthesis method according to any one of claims 1 to 22, characterized in that: After the reaction is completed, the azoxystrobin product is obtained by post-processing; the post-processing includes: direct liquid separation of the material after the reaction is completed, oil phase desolventization, and purification.

24. The synthesis method according to claim 23, characterized in that: Purification includes redissolution, crystallization, filtration, washing and drying.

25. The synthesis method according to claim 23, characterized in that The aqueous phase after separation is used to recover trimethylamine and reuse it; the recovery method includes: adjusting the pH of the aqueous phase to 2-8, adding alkali after concentration, and recovering a solution containing trimethylamine.

26. The synthesis method according to claim 25, characterized in that In the recovery and reuse of trimethylamine, the amount of base added is 0.95 to 1.2 times the molar amount of the compound represented by formula I.

27. The synthesis method according to claim 25, characterized in that In the recovery and reuse of trimethylamine, the amount of base added is 1 to 1.2 times the molar amount of the compound represented by formula I.

28. The synthesis method according to claim 25, characterized in that In the recovery and reuse of trimethylamine, the alkali used is alkali metal hydroxide.

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