Continuous synthesis method of thiophanate-methyl
By using a continuous operation of a microreactor connected in series with a reaction vessel and a self-made catalyst, the problems of violent reaction and low purity in the synthesis of methyl thiophanate were solved, and efficient and stable production of methyl thiophanate was achieved.
Patent Information
- Application Number
- CN202511234507.8
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-09-01
- Publication Date
- 2025-12-05
AI Technical Summary
The existing methyl thiophanate synthesis process has problems such as violent reaction, easy explosion risk, many by-products, low product purity, and harsh operating environment.
The continuous operation of microreactors and reaction vessels in series is adopted, combined with self-made high-efficiency catalysts. The entire process is continuously operated by combining microreactors and series stirred vessels. Composite solvents and programmed cooling crystal growth process are used to reduce reaction temperature and improve product purity.
It significantly improved production efficiency and reaction yield, reduced catalyst usage, improved the operating environment, and enhanced product purity and stability.
Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to the technical field of thiophanate-methyl synthesis, more particularly to a continuous synthesis method of thiophanate-methyl. BACKGROUND
[0002] Thiophanate-methyl, also known as methylthiophanate, is a broad-spectrum systemic fungicide with the chemical name of 1,2-bis-(3-methoxycarbonyl-2-thioureido) benzene. It has the characteristics of high efficiency, strong penetration, long-lasting efficacy, easy transportation and storage, and convenient use. It is widely used in the prevention and treatment of diseases in crops such as vegetables, fruits, cotton, sugar beets, wheat, and rice, and can also be used in textiles, paper, leather, and fruit preservation. It is converted into carbendazim in the plant body, which plays a role by interfering with the formation of the spindle during the mitosis of pathogenic fungi, and has both preventive and therapeutic effects.
[0003] Currently, the traditional synthesis method of thiophanate-methyl mainly uses an intermittent reaction process, which usually uses sodium thiocyanate, methyl chloroformate, and o-phenylenediamine as raw materials to synthesize through thiocyanation and condensation. However, the traditional process requires the addition of o-phenylenediamine in batches at high temperature, which leads to severe heat release and easily causes material overflow, over-temperature, and even explosion. In addition, o-phenylenediamine is easily oxidized and sublimated, which not only reduces the reaction yield, but also worsens the operating environment and threatens personnel health. The intermediate methyl isothiocyanate needs to be synthesized at a relatively high temperature, but high temperature easily induces its decomposition or polymerization, thereby reducing the reaction yield. In the subsequent condensation reaction, by-products such as sodium chloride are easily wrapped in the product, resulting in fluctuation and generally low content of the product. In addition, the catalyst used in the prior art is N,N-dimethyl aniline, which has a pungent and foul odor and a relatively high dosage. Therefore, the present application provides a continuous synthesis method of thiophanate-methyl to solve the above-mentioned technical problems. SUMMARY
[0004] In order to solve the above problems, the present application provides a continuous synthesis method of thiophanate-methyl, which effectively suppresses side reactions, has high product purity and stable quality, significantly improves production efficiency and reaction yield, and realizes full-flow continuous operation by using a micro-reactor and a reaction kettle in series. By using a self-made high-efficiency catalyst, the catalyst dosage is reduced, the reaction conditions are mild, the reaction temperature is effectively reduced, and the process time is shortened. At the same time, the catalyst has no odor, avoiding the problem of pungent odor, and the operating environment is friendly.
[0005] To achieve the above purpose, the present application provides the following technical solutions:
[0006] A continuous synthesis method of thiophanate-methyl, comprising the following steps:
[0007] S1, vacuum drying sodium thiocyanate to moisture content ≤0.15% for standby; at the same time, o-phenylenediamine is dissolved in a composite solvent composed of N-methyl pyrrolidone and ethyl acetate, and stored under nitrogen protection;
[0008] S2, taking the dry sodium thiocyanate obtained in S1 to prepare a 30-34 wt% aqueous solution, and continuously feeding the solution, methyl chloroformate and catalyst into a tubular microreactor respectively, and reacting at 45-50°C for 8-12 min;
[0009] S3, feeding the reaction solution obtained in S2 and the o-phenylenediamine solution obtained in S1 into a series of stirred tanks through a peristaltic pump respectively, and reacting at 280-380 rpm, 45-55°C for 20-30 min, then gradually cooling the slurry to 20-25°C for crystal growth for 1-2 h, centrifuging to obtain a wet product, countercurrently washing with an organic solvent and deionized water, and vacuum drying at 90-105°C for 2-3 h to obtain the product.
[0010] Preferably, in step S1, the sodium thiocyanate is 95-100 parts by weight, the o-phenylenediamine is 8-10 parts by weight, the N-methyl pyrrolidone in the composite solvent is 65-70 parts by weight, and the ethyl acetate is 25-30 parts by weight.
[0011] Preferably, in step S2, the methyl chloroformate is 70-75 parts by weight, and the catalyst is 0.8-1.2 parts by weight.
[0012] Preferably, in the reaction process of step S3, the stirring rate of the series of stirred tanks is 280-380 rpm, the reaction temperature is 45-55°C, and the reaction time is 20-30 min; the crystal growth temperature after gradual cooling is 20-25°C, the crystal growth time is 1-2 h, and the vacuum drying time is 2-3 h.
[0013] Preferably, the preparation step of the catalyst in step S2 is:
[0014] (1) Dissolve N,N-dimethyldodecylamine in anhydrous acetonitrile, and add a solution prepared by dissolving 1,4-dibromobutane in anhydrous acetonitrile dropwise at 70-75°C under nitrogen protection, and control the reaction temperature at 75-80°C and stir at 250-350 rpm for 10-14 h after the dropwise addition is completed. The reaction solution is cooled, crystallized, filtered and dried to obtain an intermediate;
[0015] (2) Mix the intermediate with n-butyl acetate, add 4-dimethylaminopyridine and potassium iodide, and react at 95-105°C and 280-350 rpm for 14-18 h under nitrogen protection. After concentration and recrystallization purification, the catalyst is obtained.
[0016] Preferably, in the step (1), the N,N-dimethyl dodecylamine is 8-12 parts by weight, the anhydrous acetonitrile is 65-75 parts by weight, the 1,4-dibromobutane is 12-15 parts by weight, and the anhydrous acetonitrile used for dissolving the 1,4-dibromobutane is 20-30 parts by weight.
[0017] Preferably, in the step (2), the intermediate is 5-8 parts by weight, the n-butyl acetate is 50-60 parts by weight, the 4-dimethylamino pyridine is 4-7 parts by weight, and the potassium iodide is 0.1-0.3 parts by weight.
[0018] Preferably, in the reaction process of the step (1), the temperature during dropping is 70-75℃, and the dropping time is 1-2h; after the dropping is completed, the reaction temperature is 75-80℃, the stirring rate is 250-350rpm, and the stirring reflux reaction time is 10-14h.
[0019] Preferably, in the reaction process of the step (2), the reaction temperature is 95-105℃, the stirring rate is 280-350rpm, and the reaction time is 14-18h.
[0020] Compared with the prior art, the present application has the following beneficial effects:
[0021] 1. The present application first dries the sodium thiocyanate under vacuum, then prepares an aqueous solution, continuously reacts with methyl chloroformate and a catalyst in a tubular microreactor, then condenses the obtained reaction liquid with o-phenylenediamine dissolved in a composite solvent in a series of stirred tanks, and finally obtains the product after post-treatment. The method realizes continuous operation of the whole process through the combination of the microreactor and the series of stirred tanks, significantly improves the production efficiency and the batch stability of the product; the composite solvent system and the programmed cooling and crystal growing process work together to reduce the wrapping phenomenon of by-products, guarantee the product purity and quality uniformity; in combination with the use of high-efficiency catalyst, the reaction activation energy is further reduced, the catalyst dosage is reduced, the reaction conditions are optimized, the irritating odor problem of traditional catalysts is avoided, and the operating environment is improved.
[0022] 2.The catalyst of the present application is constructed by a step-by-step synthesis strategy to form a quaternary ammonium salt compound with specific spatial structure and electronic properties, which is formed by nucleophilic substitution of N,N-dimethyldodecylamine and 1,4-dibromobutane to form an ammonium bromide intermediate, and then modified by quaternary ammonium with 4-dimethylaminopyridine to form a bifunctional structure containing long-chain alkyl and pyridine groups.The active center of the catalyst can efficiently promote the directional progress of the thiocyanation and condensation reaction, improve the reaction selectivity, significantly reduce the reaction activation energy through synergistic catalytic effect, improve the catalytic efficiency, thereby reducing the amount of catalyst and the reaction temperature;Compared with the catalyst commonly used in the existing process, the self-made catalyst has no irritating odor, which solves the odor pollution problem of the operating environment from the source;At the same time, it has good chemical stability and is not easy to decompose in the reaction system, can maintain stable catalytic activity, ensure the controllability and repeatability of the reaction process, and then shorten the process time and improve the production efficiency. DETAILED DESCRIPTION
[0023] The technical solutions in the embodiments of the present application will be clearly and completely described below in combination with the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, not all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of the present application.
[0024] In the following examples, the experimental methods are conventional methods, and the test materials used are commercially available from conventional biochemical reagent stores, unless otherwise specified. In the quantitative tests in the following examples, three repeated experiments were set, and the data were the average value or average value ± standard deviation of the three repeated experiments.
[0025] Example 1
[0026] The present embodiment provides a continuous synthesis method of thiabendazole, comprising the following steps:
[0027] S1, 95 parts of sodium thiocyanate were vacuum dried to a moisture content of ≤0.15% for standby; at the same time, 8 parts of o-phenylenediamine were dissolved in a composite solvent composed of 65 parts of N-methylpyrrolidone and 25 parts of ethyl acetate, and stored under nitrogen protection;
[0028] S2, the dry sodium thiocyanate obtained in S1 was prepared into a 30wt% aqueous solution, and 70 parts of methyl chloroformate and 0.8 parts of catalyst were continuously introduced into the tubular microreactor by peristaltic pump respectively, and reacted at 45℃ for 12min;
[0029] S3, the reaction solution obtained in S2 and the o-phenylenediamine solution obtained in S1 were respectively introduced into a series of stirred tanks by peristaltic pump, reacted at 280 rpm and 45℃ for 30 min, the slurry was then programmed to cool to 20℃ for crystal growth for 2 h, the wet product was obtained by centrifugation, washed with organic solvent and deionized water countercurrently, and dried at 90℃ under vacuum for 3 h to obtain the product.
[0030] The preparation step of the catalyst in step S2 is:
[0031] (1) 12 parts of N,N-dimethyl dodecylamine were dissolved in 75 parts of anhydrous acetonitrile, and a solution prepared by dissolving 12 parts of 1,4-dibromobutane in 20 parts of anhydrous acetonitrile was added dropwise under nitrogen protection at 70℃, the dropwise addition was completed within 1 h, the reaction temperature was controlled at 75℃, and the reaction was stirred at 250 rpm and refluxed for 14 h. After cooling, crystallization, filtration and drying, the intermediate was obtained.
[0032] (2) 5 parts of the intermediate were mixed with 50 parts of n-butyl acetate, 4 parts of 4-dimethylaminopyridine and 0.1 parts of potassium iodide were added, and the reaction was carried out at 95℃ and 280 rpm for 18 h under nitrogen protection. After concentration and recrystallization purification, the catalyst was obtained.
[0033] Example 2
[0034] The embodiment provides a continuous synthesis method of thiabendazole, comprising the following steps:
[0035] S1, 96 parts of sodium thiocyanate were vacuum dried to a moisture content of ≤0.15% for standby use; at the same time, 9 parts of o-phenylenediamine were dissolved in a composite solvent composed of 66 parts of N-methyl pyrrolidone and 26 parts of ethyl acetate, and stored under nitrogen protection;
[0036] S2, the dried sodium thiocyanate obtained in S1 was prepared into a 32wt% aqueous solution, and 72 parts of methyl chloroformate and 0.9 parts of catalyst were continuously introduced into a tubular microreactor by peristaltic pump, and reacted at 46℃ for 11 min;
[0037] S3, the reaction solution obtained in S2 and the o-phenylenediamine solution obtained in S1 were respectively introduced into a series of stirred tanks by peristaltic pump, reacted at 300 rpm and 48℃ for 27 min, the slurry was then programmed to cool to 24℃ for crystal growth for 1.8 h, the wet product was obtained by centrifugation, washed with organic solvent and deionized water countercurrently, and dried at 95℃ under vacuum for 2.7 h to obtain the product.
[0038] Preferably, the preparation step of the catalyst in step S2 is:
[0039] (1) 9 parts of N,N-dimethyldodecylamine was dissolved in 67 parts of anhydrous acetonitrile, and a solution prepared by dissolving 13 parts of 1,4-dibromobutane in 22 parts of anhydrous acetonitrile was added dropwise at 72°C under nitrogen protection. The dropwise addition was completed within 1.8 hours, and the reaction temperature was controlled at 76°C. The reaction was stirred at 260 rpm for 13.5 hours. After cooling, crystallization, filtration and drying, the intermediate was obtained.
[0040] (2) 6 parts of the intermediate was mixed with 51 parts of n-butyl acetate, 5 parts of 4-dimethylaminopyridine and 0.2 parts of potassium iodide were added, and the reaction was carried out at 96°C under nitrogen protection at 300 rpm for 17 hours. After concentration and recrystallization purification, the catalyst was obtained.
[0041] Example 3
[0042] The present embodiment provides a continuous synthesis method of thiabendazole, comprising the following steps:
[0043] S1, 100 parts of sodium thiocyanate was vacuum dried to a moisture content of ≤0.15% for standby use; at the same time, 10 parts of o-phenylenediamine was dissolved in a composite solvent composed of 70 parts of N-methylpyrrolidone and 30 parts of ethyl acetate, and stored under nitrogen protection;
[0044] S2, the dried sodium thiocyanate obtained in S1 was prepared into a 34wt% aqueous solution, and 75 parts of methyl chloroformate and 1.2 parts of catalyst were continuously introduced into the tubular microreactor by peristaltic pump respectively, and the reaction was carried out at 50°C for 8 minutes;
[0045] S3, the reaction solution obtained in S2 and the o-phenylenediamine solution obtained in S1 were introduced into the series stirred tank by peristaltic pump respectively, and the reaction was carried out at 380 rpm and 55°C for 20 minutes. After the reaction, the slurry was programmed to cool to 20°C for crystal growth for 1 hour, and then centrifuged to obtain the wet product, which was washed with organic solvent and deionized water countercurrently, and then vacuum dried at 105°C for 2 hours to obtain the product.
[0046] Preferably, the preparation step of the catalyst in step S2 is:
[0047] (1) 9 parts of N,N-dimethyldodecylamine was dissolved in 67 parts of anhydrous acetonitrile, and a solution prepared by dissolving 13 parts of 1,4-dibromobutane in 22 parts of anhydrous acetonitrile was added dropwise at 72°C under nitrogen protection. The dropwise addition was completed within 1.8 hours, and the reaction temperature was controlled at 76°C. The reaction was stirred at 260 rpm for 13.5 hours. After cooling, crystallization, filtration and drying, the intermediate was obtained.
[0048] (2) 6 parts of the intermediate was mixed with 51 parts of n-butyl acetate, 5 parts of 4-dimethylaminopyridine and 0.2 parts of potassium iodide were added, and the reaction was carried out at 96°C under nitrogen protection at 300 rpm for 17 hours. After concentration and recrystallization purification, the catalyst was obtained.
[0049] Example 4
[0050] The embodiment provides a continuous synthesis method of thiabendazole, which comprises the following steps:
[0051] S1, 100 parts of sodium thiocyanate are vacuum dried to a moisture content of less than or equal to 0.15% for standby; meanwhile, 10 parts of o-phenylenediamine are dissolved in a composite solvent composed of 70 parts of N-methylpyrrolidone and 25 parts of ethyl acetate, and stored under nitrogen protection;
[0052] S2, the dry sodium thiocyanate obtained in S1 is prepared into a 34wt% aqueous solution, and 75 parts of methyl chloroformate and 1 part of a catalyst are continuously introduced into a tubular microreactor through a peristaltic pump respectively, and reacted at 50℃ for 10 minutes;
[0053] S3, the reaction solution obtained in S2 and the o-phenylenediamine solution obtained in S1 are introduced into a series of stirred tanks through a peristaltic pump respectively, and reacted at 380rpm and 55℃ for 24 minutes, and after the reaction, the slurry is programmed to be cooled to 20℃ for crystal growth for 1.5 hours, centrifuged to obtain a wet product, washed with an organic solvent and deionized water in countercurrent, and vacuum dried at 105℃ for 2 hours to obtain the product.
[0054] Preferably, the preparation step of the catalyst in step S2 is:
[0055] (1) 12 parts of N,N-dimethyl dodecylamine are dissolved in 70 parts of anhydrous acetonitrile, and a solution prepared by dissolving 15 parts of 1,4-dibromobutane in 30 parts of anhydrous acetonitrile is added dropwise under nitrogen protection at 75℃, and the dropwise addition is completed within 1.2 hours, and then the reaction temperature is controlled at 80℃, and the reaction is stirred at 350rpm and refluxed for 10 hours, and then the reaction solution is cooled, crystallized, filtered and dried to obtain an intermediate;
[0056] (2) 8 parts of the intermediate are mixed with 60 parts of n-butyl acetate, and 6 parts of potassium iodide and 0.2 parts of potassium iodide are added, and the reaction is carried out at 105℃ and 350rpm for 14 hours under nitrogen protection, and then the reaction solution is concentrated and recrystallized to obtain the catalyst.
[0057] Comparative Example 1
[0058] A continuous synthesis method of thiabendazole, which is different from Example 4 in that a batch kettle type reaction is used instead of a microreactor-series stirred tank continuous process. Specifically, in step S2, the sodium thiocyanate aqueous solution, methyl chloroformate and catalyst are batch reacted in a single reaction kettle at 50℃; in step S3, the reaction solution and o-phenylenediamine solution are batch charged and reacted in the same reaction kettle, and the rest of the raw material ratio, reaction temperature and post-treatment process are the same as those of Example 4.
[0059] Comparative Example 2
[0060] A continuous synthesis method of thiabendazole, which is different from example 4 in that the addition of catalyst is completely omitted. Specifically, in step S2, the aqueous sodium thiocyanate solution and methyl chloroformate are reacted in the tubular microreactor without adding any catalyst, and the rest of the raw material ratio, reaction conditions and post-treatment process are completely the same as example 4.
[0061] Comparative example 3
[0062] A continuous synthesis method of thiabendazole, which is different from example 4 in that only step (1) of synthesizing intermediates is performed in the preparation of the catalyst. Specifically, only step (1) of synthesizing intermediates is retained in the preparation of the catalyst, and step (2) of quaternization modification of 4-dimethylamino pyridine is omitted, and the intermediate is directly used as a catalyst, and the rest of the raw material ratio, reaction conditions and post-treatment process are completely the same as example 4.
[0063] Comparative example 4
[0064] A continuous synthesis method of thiabendazole, which is different from example 4 in that step (1) is omitted in the preparation of the catalyst, and a commercial quaternary ammonium salt is directly used. Specifically, step (1) is skipped in the preparation of the catalyst, and an equal amount of tetradecyl trimethyl ammonium bromide is directly used as a catalyst, and the rest of the raw material ratio, reaction conditions and post-treatment process are completely the same as example 4.
[0065] Comparative example 5
[0066] A continuous synthesis method of thiabendazole, which is different from example 4 in that the self-made catalyst is omitted and replaced with an equal amount of N,N-dimethylaniline. Specifically, 1 part of N,N-dimethylaniline is used to replace the self-made catalyst in step S2, and the rest of the raw material ratio, reaction conditions and post-treatment process are completely the same as example 4.
[0067] Comparative example 6
[0068] A continuous synthesis method of thiabendazole, which is different from example 4 in that the catalyst is not synthesized in two steps, but is only a physical mixture. Specifically, in step S2, a mixture of N,N-dimethyl dodecylamine and 4-dimethylamino pyridine is directly mixed according to the feeding ratio of steps (1) and (2) of catalyst preparation to form a mixture, and the whole chemical synthesis steps of the catalyst are omitted, and the rest of the raw material ratio, reaction conditions and post-treatment process are completely the same as example 4.
[0069] Performance test
[0070] A continuous synthesis method of thiabendazole is provided for performance testing of examples 1-4 and comparative examples 1-6, and the test results are shown in Table 1.
[0071] Table 1
[0072] Example 1 Example 2 Example 3 Example 4 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Comparative Example 5 Comparative Example 6 Yield % 99.52 99.63 99.73 99.77 92.52 83.31 94.26 90.08 95.65 87.34 Whiteness % 95.38 95.76 96.19 96.27 90.24 84.53 91.86 90.36 89.78 87.61 Purity % 99.74 99.79 99.80 99.85 93.61 90.43 94.84 94.55 95.27 91.19
[0073] From the performance test results, it can be seen that the indicators of Examples 1-4 are maintained at an excellent level, among which the comprehensive performance of Example 4 is the best, with a yield of 99.77%, whiteness of 96.27%, and purity of 99.85%. This is due to the synergistic effect of the microreactor and the series stirred tank in the continuous operation, which improves the mass and heat transfer efficiency, combined with the high selectivity of the self-made bifunctional catalyst and the optimization of the N-methylpyrrolidone and ethyl acetate composite solvent, effectively inhibiting side reactions and reducing impurity generation, while the programmed cooling and crystal growing process further ensures the purity and whiteness stability of the product.
[0074] In contrast, each of the comparative examples has defects in different key links, resulting in a significant decline in performance. Comparative Example 1 uses batch operation, which has poor reaction uniformity, is prone to local overheating and side reactions, resulting in a significant decrease in yield and purity; Comparative Example 2 does not use a catalyst, the reaction driving force is insufficient, the conversion rate is low and the byproduct is increased; Comparative Example 3 and Comparative Example 4 use intermediate catalysts with incomplete structures or ordinary quaternary ammonium salts, respectively, with limited catalytic efficiency; Comparative Example 5 uses N,N-dimethylaniline containing catalytic activity, but its decomposition produces colored impurities, resulting in a decrease in whiteness; Comparative Example 6 uses a physical mixture of catalyst precursors, which fails to form an effective catalytic structure, with poor catalytic performance, ultimately resulting in all indicators being significantly lower than the examples.
[0075] The above is merely an example and description of the present application, and those skilled in the art can make various modifications or supplements to the described specific embodiments or use similar ways to replace, as long as they do not deviate from the invention or exceed the scope defined by the present claims, which shall belong to the protection scope of the present application.
Claims
1. A continuous synthesis method of thiabendazole, characterized by, The method comprises the following steps: S1, vacuum drying sodium thiocyanate to moisture content ≤0.15% for standby; at the same time, dissolving o-phenylenediamine in a composite solvent composed of N-methylpyrrolidone and ethyl acetate, and storing under nitrogen protection; S2, taking the dry sodium thiocyanate obtained in S1 to prepare a 30-34 wt% aqueous solution, and continuously feeding methyl chloroformate and a catalyst into a tubular microreactor through a peristaltic pump for reaction; S3, feeding the reaction solution obtained in S2 and the o-phenylenediamine solution obtained in S1 into a series of stirred tanks through a peristaltic pump for reaction, and after the reaction, the slurry is subjected to programmed temperature reduction and crystal growth, centrifugation to obtain a wet product, countercurrent washing with an organic solvent and deionized water, and vacuum drying to obtain the product.
2. The continuous synthesis of thiabendazole according to claim 1, wherein, In the step S1, by weight, sodium thiocyanate is 95-100 parts, o-phenylenediamine is 8-10 parts, N-methylpyrrolidone in the composite solvent is 65-70 parts, and ethyl acetate is 25-30 parts.
3. The continuous synthesis of thiophalim according to claim 1, wherein, In the step S2, by weight, methyl chloroformate is 70-75 parts, and the catalyst is 0.8-1.2 parts.
4. The continuous synthesis of thiabendazole according to claim 1, wherein, In the reaction process of the step S3, the stirring rate of the series of stirred tanks is 280-380 rpm, the reaction temperature is 45-55℃, and the reaction time is 20-30 min; the crystal growth temperature after programmed temperature reduction is 20-25℃, the crystal growth time is 1-2 h, and the vacuum drying time is 2-3 h.
5. The continuous synthesis of thiabendazole according to claim 1, wherein, The preparation steps of the catalyst in the step S2 are as follows: (1) dissolving N,N-dimethyldodecylamine in anhydrous acetonitrile, and adding a solution prepared by dissolving 1,4-dibromobutane in anhydrous acetonitrile dropwise under nitrogen protection, stirring and refluxing after the dropwise addition is completed, and then cooling, crystallizing, filtering and drying the reaction solution to obtain an intermediate; (2) mixing the intermediate with n-butyl acetate, adding 4-dimethylaminopyridine and potassium iodide, and reacting under nitrogen protection, and then concentrating and recrystallizing and purifying to obtain the catalyst.
6. The continuous synthesis of thiabendazole according to claim 5, wherein, In the step (1), by weight, N,N-dimethyldodecylamine is 8-12 parts, anhydrous acetonitrile is 65-75 parts, 1,4-dibromobutane is 12-15 parts, and anhydrous acetonitrile used for dissolving 1,4-dibromobutane is 20-30 parts.
7. The continuous synthesis of thiophalim according to claim 5, wherein, In the step (2), by weight, the intermediate is 5-8 parts, n-butyl acetate is 50-60 parts, 4-dimethylaminopyridine is 4-7 parts, and potassium iodide is 0.1-0.3 parts.
8. The continuous synthesis of thiophalim according to claim 5, wherein, In the reaction process of the step (1), the temperature during dropwise addition is 70-75℃, and the dropwise addition time is 1-2 h; after the dropwise addition is completed, the reaction temperature is 75-80℃, the stirring rate is 250-350 rpm, and the stirring and refluxing reaction time is 10-14 h.
9. The continuous synthesis of thiabendazole according to claim 5, wherein, In the reaction process of the step (2), the reaction temperature is 95-105℃, the stirring rate is 280-350 rpm, and the reaction time is 14-18 h.