A solvent-free synthesis method of acetamiprid

Abstract

This invention relates to a solvent-free synthesis method of thiamethoxam, comprising the following steps: adding 2-cyanoimino-1,3-thiazolidinyl, 2-chloro-5-chloromethylpyridine, and a solid base to a homogenizer, and reacting under microwave heating conditions while homogenizing to generate thiamethoxam. This invention breaks the limitations of traditional solvent-based chemical reactions, pioneering the use of a homogenizer combined with microwave heating to conduct the reaction in a solvent-free environment. Combined with the purification process of reflux dissolution and cooling recrystallization, this significantly improves the product yield and purity. Furthermore, because no solvent is used, wastewater production is low, thus greatly reducing the production cost of thiamethoxam and alleviating environmental pressure.

Description

Technical Field

[0001] This invention relates to the field of thiamethoxam synthesis technology, and specifically to a solvent-free synthesis method for thiamethoxam. Background Technology

[0002] Thiamethoxam technical grade is a chloronicotinic insecticide developed in the 1990s through a collaboration between Bayer Agrochemicals of Germany and Bayer Agrochemicals of Japan. It possesses broad-spectrum, systemic activity and exhibits excellent control over both piercing-sucking and chewing insects. As a novel biomimetic pesticide, thiamethoxam acts on nicotinic acid acetylcholine receptors and shows no cross-resistance with conventional organophosphates, carbamates, and pyrethroids, making it suitable for resistance management. The pesticide demonstrates excellent control efficacy against significant pests on cotton, vegetables, potatoes, and pome fruits.

[0003] The molecular formula of thiamethoxam is C2 10 H9ClN4S, chemically named [3-(6-chloro-3-pyridinylmethyl)-thiazoline-2-ylidene]cyanamide, commonly known as Thiacloprid, has the following structural formula:

[0004]

[0005] Thiamethoxam has been industrialized for decades, and although there are many documents documenting its synthesis methods, such as Wu Daoxin et al.'s "Research on the Synthetic Process of High-Efficiency and Low-Toxicity Insecticide Thiamethoxam," patents CN201110389533.X, CN00104507.5, CN201711107739.2, CN201811546395.X, WO2017048628, etc., they all have the following problems: First, the solvent consumption is relatively high and the product yield is low, resulting in high production costs and reducing its market competitiveness; second, it generates a lot of wastewater, which is difficult and costly to treat, increasing the hidden costs of its production and also bringing considerable environmental pressure.

[0006] Therefore, developing a solvent-free synthesis method for thiamethoxam with low solvent consumption, low wastewater production and easy treatment, and high product yield and purity is crucial for reducing the production cost of thiamethoxam and alleviating environmental pressure. Summary of the Invention

[0007] The purpose of this invention is to overcome the shortcomings of the prior art and provide a solvent-free synthesis method for thiamethoxam. No solvent needs to be added during the reaction process. After the reaction is completed, only a small amount of alcohol solvent is needed for dissolution and recrystallization. Moreover, the solvent can be recycled, resulting in low processing costs, no pollution, and low environmental pressure.

[0008] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0009] A solvent-free method for synthesizing thiamethoxam includes the following steps:

[0010] 2-cyanoimino-1,3-thiazolidinyl, 2-chloro-5-chloromethylpyridine, and a solid base are added to a homogenizer and reacted under microwave heating to generate thiamethoxam, yielding the reaction product.

[0011] As a further technical solution, the microwave heating power is 60-380W, the microwave heating temperature is 30-60℃, the homogenization speed is 500-4000 rpm, and the reaction time is 2-15h.

[0012] As a further technical solution, the microwave heating power is 100-300W, the microwave heating temperature is 35-55℃, the homogenization speed is 800-3000 rpm, and the reaction time is 2-8h.

[0013] As a further technical solution, the molar ratio of 2-cyanoimino-1,3-thiazolidinyl, 2-chloro-5-chloromethylpyridine and solid alkali is 1.0-1.1 mol: 1.0 mol: 1.0-1.2 mol.

[0014] As a further technical solution, the molar ratio of 2-cyanoimino-1,3-thiazolidinyl, 2-chloro-5-chloromethylpyridine and solid alkali is 1.0-1.05 mol: 1.0 mol: 1.0-1.1 mol.

[0015] As a further technical solution, the solid alkali is one or more of sodium carbonate, potassium carbonate, potassium hydroxide, and sodium hydroxide, with sodium hydroxide being preferred.

[0016] As a further technical solution, after the reaction is completed, post-processing is required. The post-processing includes: adding a recrystallization solvent to the reaction product and refluxing to dissolve thiamethoxam, then centrifuging while hot to obtain thiamethoxam mother liquor, and then sequentially performing cooling recrystallization, water washing to remove salt, filtration, and drying to obtain the thiamethoxam product.

[0017] As a further technical solution, the recrystallization solvent is an alcohol solvent, and the mass concentration of the alcohol solvent is ≥95%.

[0018] As a further technical solution, the alcohol solvent includes one or more of ethanol, methanol, and isopropanol, preferably ethanol with a mass concentration of 95%.

[0019] As a further technical solution, the reflux time is 2-3 hours.

[0020] As a further technical solution, a recrystallization solvent is added to the reaction product at a mass ratio of 94:160-200 to the reaction product and solvent A.

[0021] In this invention, the reaction route for the synthesis of thiamethoxam is as follows:

[0022]

[0023] Compared with the prior art, the beneficial effects achieved by the present invention are as follows:

[0024] 1. This invention utilizes the shear force of high-speed rotation and the impact force generated by forced flow during homogenization to cause high-frequency deformation and fracture of the material. Combined with microwave heating, the material can react smoothly in the absence of solvent, solving a series of problems caused by reacting the material in a solvent, such as increased solvent costs and increased waste liquid.

[0025] 2. After the reaction of this invention is completed, only a small amount of solvent is needed to dissolve the product, and the cooling recrystallization operation can be carried out directly, which further reduces the amount of solvent used. The salt remaining in the crude product in the whole process needs to be removed with a small amount of water, which greatly reduces the amount of wastewater and the cost of wastewater treatment.

[0026] In summary, this invention breaks through the limitations of traditional chemical reactions in solvents. It innovatively uses a homogenizer combined with microwave heating to carry out the reaction in a solvent-free environment. Combined with the purification process of reflux dissolution and cooling recrystallization of this invention, the yield and purity of the product are greatly improved. Furthermore, since no solvent is used, the wastewater production is low, thus greatly reducing the production cost of thiamethoxam and alleviating environmental pressure. Detailed Implementation

[0027] The present invention will be further described in detail below with reference to the embodiments.

[0028] In this invention,

[0029] 2-Cyanoimino-1,3-Thiazolidinyl (purity 95.6%): Produced by the company itself;

[0030] 2-chloro-5-chloromethylpyridine (purity 96%): purchased from Gansu Kesheng Qianyun;

[0031] The solid alkali used was 96% (purity) and purchased from Jinan Feiyue Chemical Co., Ltd.

[0032] Unless otherwise specified, all raw materials used in this invention are commercially available.

[0033] Example 1

[0034] A solvent-free method for synthesizing thiamethoxam includes the following steps:

[0035] Step 1, Homogenization reaction: Add 37.2g (0.28mol) of 2-cyanoimino-1,3-thiazolidinyl ether, 45.4g (0.267mol) of 2-chloro-5-chloromethylpyridine and 12.2g (0.294mol) of solid alkali to a homogenizer. Homogenize and react simultaneously under microwave heating for 5 hours until the normalized content of methylpyridine is less than 1%, then stop the reaction to obtain the thiamethoxam reaction solution. The microwave heating power is 280W, the temperature is 45℃, and the homogenization speed is 3000 rpm.

[0036] Step 2, Post-processing: After the reaction is complete, add 180g of 95% ethanol solvent to the reaction product and reflux at 78℃ for 2h until the thiamethoxam dissolves. Then, centrifuge while hot to obtain the thiamethoxam mother liquor.

[0037] Step 3, Purification: Cool the thiamethoxam mother liquor to 3℃ for recrystallization, then filter. Wash the wet thiamethoxam crystals with 50mL of water to remove salt, filter, and dry to obtain the thiamethoxam product.

[0038] In this embodiment, the yield of thiamethoxam was 93%, and the purity of the obtained thiamethoxam product was 97.8%.

[0039] Example 2

[0040] A solvent-free method for synthesizing thiamethoxam includes the following steps:

[0041] Step 1: Homogenization reaction: Add 36.5g (0.275mol) of 2-cyanoimino-1,3-thiazolidinyl ether, 45.4g (0.267mol) of 2-chloro-5-chloromethylpyridine and 12.2g (0.294mol) of solid base to a homogenizer. Homogenize and react simultaneously under microwave heating for 5 hours until the normalized content of methylpyridine is less than 1%, then stop the reaction to obtain the reaction product. The microwave heating power is 280W, the temperature is 45℃, and the homogenization speed is 3000 rpm.

[0042] Step 2, Post-treatment: After the reaction is complete, add 180g of 95% ethanol solvent to the reaction product and reflux at 78℃ for 2h until the thiamethoxam dissolves. Then centrifuge while hot to obtain the thiamethoxam mother liquor.

[0043] Step 3, Purification: Cool the thiamethoxam mother liquor to 3℃ for recrystallization, then filter. Wash the wet thiamethoxam crystals with 50mL of water to remove salt, filter, and dry to obtain the thiamethoxam product.

[0044] In this embodiment, the yield of thiamethoxam was 91%, and the purity of the obtained thiamethoxam product was 97.6%.

[0045] Example 3

[0046] A solvent-free method for synthesizing thiamethoxam includes the following steps:

[0047] Step 1: Homogenization reaction: Add 35.5g (0.267mol) of 2-cyanoimino-1,3-thiazolidinyl ether, 45.4g (0.267mol) of 2-chloro-5-chloromethylpyridine and 12.2g (0.294mol) of solid base to a homogenizer. Homogenize and react under microwave heating for 5 hours until the normalized content of methylpyridine is less than 1%, then stop the reaction to obtain the reaction product. The microwave heating power is 280W, the temperature is 45℃, and the homogenization speed is 3000 rpm.

[0048] Step 2, Post-treatment: After the reaction is complete, add 180g of 95% ethanol solvent to the reaction product and reflux at 78℃ for 2h until the thiamethoxam dissolves. Then centrifuge while hot to obtain the thiamethoxam mother liquor.

[0049] Step 3, Purification: Cool the thiamethoxam mother liquor to 3℃ for recrystallization, then filter. Wash the wet thiamethoxam crystals with 50mL of water to remove salt, filter, and dry to obtain the thiamethoxam product.

[0050] In this embodiment, the yield of thiamethoxam was 88%, and the purity of the obtained thiamethoxam product was 97.1%.

[0051] Example 4

[0052] A solvent-free method for synthesizing thiamethoxam includes the following steps:

[0053] Step 1, Homogenization reaction: Add 37.2g (0.28mol) of 2-cyanoimino-1,3-thiazolidinyl ether, 45.4g (0.267mol) of 2-chloro-5-chloromethylpyridine and 11.7g (0.28mol) of solid base to a homogenizer. Homogenize and react under microwave heating conditions for 5 hours until the normalized content of methylpyridine is less than 1%, then stop the reaction to obtain the reaction product. The microwave heating power is 280W, the temperature is 45℃, and the homogenization speed is 3000 rpm.

[0054] Step 2, Post-treatment: After the reaction is complete, add 180g of 95% ethanol solvent to the reaction product and reflux at 78℃ for 2h until the thiamethoxam dissolves. Then centrifuge while hot to obtain the thiamethoxam mother liquor.

[0055] Step 3, Purification: Cool the thiamethoxam mother liquor to 3℃ for recrystallization, then filter. Wash the wet thiamethoxam crystals with 50mL of water to remove salt, filter, and dry to obtain the thiamethoxam product.

[0056] In this embodiment, the yield of thiamethoxam was 90%, and the purity of the obtained thiamethoxam product was 97.8%.

[0057] Example 5

[0058] A solvent-free method for synthesizing thiamethoxam includes the following steps:

[0059] Step 1, Homogenization reaction: Add 37.2g (0.28mol) of 2-cyanoimino-1,3-thiazolidinyl ether, 45.4g (0.267mol) of 2-chloro-5-chloromethylpyridine and 11.1g (0.267mol) of solid base to a homogenizer. Homogenize and react under microwave heating for 5 hours until the normalized content of methylpyridine is less than 1%, then stop the reaction to obtain the reaction product. The microwave heating power is 280W, the temperature is 45℃, and the homogenization speed is 3000 rpm.

[0060] Step 2, Post-treatment: After the reaction is complete, add 180g of 95% ethanol solvent to the reaction product and reflux at 78℃ for 2h until the thiamethoxam dissolves. Then centrifuge while hot to obtain the thiamethoxam mother liquor.

[0061] Step 3, Purification: Cool the thiamethoxam mother liquor to 3℃ for recrystallization, then filter. Wash the wet thiamethoxam crystals with 50mL of water to remove salt, filter, and dry to obtain the thiamethoxam product.

[0062] In this embodiment, the yield of thiamethoxam was 86%, and the purity of the obtained thiamethoxam product was 96.3%.

[0063] Example 6

[0064] A solvent-free method for synthesizing thiamethoxam includes the following steps:

[0065] Step 1: Homogenization reaction: Add 37.2 g (0.28 mol) of 2-cyanoimino-1,3-thiazolidinyl ether, 45.4 g (0.267 mol) of 2-chloro-5-chloromethylpyridine and 12.2 g (0.294 mol) of solid base to a homogenizer. Homogenize and react under microwave heating for 5 hours until the normalized content of methylpyridine is less than 1%, then stop the reaction to obtain the reaction product. The microwave heating power is 180 W, the temperature is 45 °C, and the homogenization speed is 3000 rpm.

[0066] Step 2, Post-treatment: After the reaction is complete, add 180g of 95% ethanol solvent to the reaction product and reflux at 78℃ for 2h until the thiamethoxam dissolves. Then centrifuge while hot to obtain the thiamethoxam mother liquor.

[0067] Step 3, Purification: Cool the thiamethoxam mother liquor to 3°C for recrystallization, then filter. Wash the wet thiamethoxam crystals with 50mL of water to remove salt, filter, and dry to obtain the thiamethoxam product.

[0068] In this embodiment, the yield of thiamethoxam was 92%, and the purity of the obtained thiamethoxam product was 97.5%.

[0069] Example 7

[0070] A solvent-free method for synthesizing thiamethoxam includes the following steps:

[0071] Step 1: Homogenization reaction: Add 37.2 g (0.28 mol) of 2-cyanoimino-1,3-thiazolidinyl ether, 45.4 g (0.267 mol) of 2-chloro-5-chloromethylpyridine and 12.2 g (0.294 mol) of solid base to a homogenizer. Homogenize and react simultaneously under microwave heating for 5 hours until the normalized content of methylpyridine is less than 1%, then stop the reaction to obtain the reaction product. The microwave heating power is 100 W, the temperature is 45 °C, and the homogenization speed is 3000 rpm.

[0072] Step 2, Post-treatment: After the reaction is complete, add 180g of 95% ethanol solvent to the reaction product and reflux at 78℃ for 2h until the thiamethoxam dissolves. Then centrifuge while hot to obtain the thiamethoxam mother liquor.

[0073] Step 3, Purification: Cool the thiamethoxam mother liquor to 3°C for recrystallization, then filter. Wash the wet thiamethoxam crystals with 50mL of water to remove salt, filter, and dry to obtain the thiamethoxam product.

[0074] In this embodiment, the yield of thiamethoxam was 92.3%, and the purity of the obtained thiamethoxam product was 97.3%.

[0075] Example 8

[0076] A solvent-free method for synthesizing thiamethoxam includes the following steps:

[0077] Step 1: Homogenization reaction: Add 37.2 g (0.28 mol) of 2-cyanoimino-1,3-thiazolidinyl ether, 45.4 g (0.267 mol) of 2-chloro-5-chloromethylpyridine and 12.2 g (0.294 mol) of solid base to a homogenizer. Homogenize and react simultaneously under microwave heating for 5 hours until the normalized content of methylpyridine is less than 1%, then stop the reaction to obtain the reaction product. The microwave heating power is 100 W, the temperature is 35 °C, and the homogenization speed is 3000 rpm.

[0078] Step 2, Post-treatment: After the reaction is complete, add 180g of 95% ethanol solvent to the reaction product and reflux at 78℃ for 2h until the thiamethoxam dissolves. Then centrifuge while hot to obtain the thiamethoxam mother liquor.

[0079] Step 3, Purification: Cool the thiamethoxam mother liquor to 3°C for recrystallization, then filter. Wash the wet thiamethoxam crystals with 50mL of water to remove salt, filter, and dry to obtain the thiamethoxam product.

[0080] In this embodiment, the yield of thiamethoxam was 90%, and the purity of the obtained thiamethoxam product was 96.5%.

[0081] Example 9

[0082] A solvent-free method for synthesizing thiamethoxam includes the following steps:

[0083] Step 1: Homogenization reaction: Add 37.2 g (0.28 mol) of 2-cyanoimino-1,3-thiazolidinyl ether, 45.4 g (0.267 mol) of 2-chloro-5-chloromethylpyridine and 12.2 g (0.294 mol) of solid base to a homogenizer. Homogenize and react under microwave heating for 5 hours until the normalized content of methylpyridine is less than 1%, then stop the reaction to obtain the reaction product. The microwave heating power is 100 W, the temperature is 55 °C, and the homogenization speed is 3000 rpm.

[0084] Step 2, Post-treatment: After the reaction is complete, add 180g of 95% ethanol solvent to the reaction product and reflux at 78℃ for 2h until the thiamethoxam dissolves. Then centrifuge while hot to obtain the thiamethoxam mother liquor.

[0085] Step 3, Purification: Cool the thiamethoxam mother liquor to 3°C for recrystallization, then filter. Wash the wet thiamethoxam crystals with 50mL of water to remove salt, filter, and dry to obtain the thiamethoxam product.

[0086] In this embodiment, the yield of thiamethoxam was 87%, and the purity of the obtained thiamethoxam product was 96.8%.

[0087] Example 10

[0088] A solvent-free method for synthesizing thiamethoxam includes the following steps:

[0089] Step 1: Homogenization reaction: Add 37.2 g (0.28 mol) of 2-cyanoimino-1,3-thiazolidinyl ether, 45.4 g (0.267 mol) of 2-chloro-5-chloromethylpyridine and 12.2 g (0.294 mol) of solid base to a homogenizer. Homogenize and react under microwave heating for 5 hours until the normalized content of methylpyridine is less than 1%, then stop the reaction to obtain the reaction product. The microwave heating power is 280 W, the temperature is 45 °C, and the homogenization speed is 2000 rpm.

[0090] Step 2, Post-treatment: After the reaction is complete, add 180g of 95% ethanol solvent to the reaction product and reflux at 78℃ for 2h until the thiamethoxam dissolves. Then centrifuge while hot to obtain the thiamethoxam mother liquor.

[0091] Step 3, Purification: Cool the thiamethoxam mother liquor to 3℃ for recrystallization, then filter. Wash the wet thiamethoxam crystals with 50mL of water to remove salt, filter, and dry to obtain the thiamethoxam product.

[0092] In this embodiment, the yield of thiamethoxam was 89%, and the purity of the obtained thiamethoxam product was 97.5%.

[0093] Example 11

[0094] A solvent-free method for synthesizing thiamethoxam includes the following steps:

[0095] Step 1: Homogenization reaction: Add 37.2 g (0.28 mol) of 2-cyanoimino-1,3-thiazolidinyl ether, 45.4 g (0.267 mol) of 2-chloro-5-chloromethylpyridine and 12.2 g (0.294 mol) of solid base to a homogenizer. Homogenize and react under microwave heating for 5 hours until the normalized content of methylpyridine is less than 1%, then stop the reaction to obtain the reaction product. The microwave heating power is 280 W, the temperature is 45 °C, and the homogenization speed is 1500 rpm.

[0096] Step 2, Post-treatment: After the reaction is complete, add 180g of 95% ethanol solvent to the reaction product and reflux at 78℃ for 2h until the thiamethoxam dissolves. Then centrifuge while hot to obtain the thiamethoxam mother liquor.

[0097] Step 3, Purification: Cool the thiamethoxam mother liquor to 3°C for recrystallization, then filter. Wash the wet thiamethoxam crystals with 50mL of water to remove salt, filter, and dry to obtain the thiamethoxam product.

[0098] In this embodiment, the total yield of thiamethoxam was 89%, and the purity of the obtained thiamethoxam product was 97.2%.

[0099] Example 12

[0100] A solvent-free method for synthesizing thiamethoxam includes the following steps:

[0101] Step 1: Homogenization reaction: Add 37.2 g (0.28 mol) of 2-cyanoimino-1,3-thiazolidinyl ether, 45.4 g (0.267 mol) of 2-chloro-5-chloromethylpyridine and 12.2 g (0.294 mol) of solid base to a homogenizer. Homogenize and react under microwave heating for 8 hours until the normalized content of methylpyridine is less than 1%, then stop the reaction to obtain the reaction product. The microwave heating power is 280 W, the temperature is 45 °C, and the homogenization speed is 3000 rpm.

[0102] Step 2, Post-treatment: After the reaction is complete, add 180g of 95% ethanol solvent to the reaction product and reflux at 78℃ for 2h until the thiamethoxam dissolves. Then centrifuge while hot to obtain the thiamethoxam mother liquor.

[0103] Step 3, Purification: Cool the thiamethoxam mother liquor to 3℃ for recrystallization, then filter. Wash the wet thiamethoxam crystals with 50mL of water to remove salt, filter, and dry to obtain the thiamethoxam product.

[0104] In this embodiment, the yield of thiamethoxam was 93.5%, and the purity of the obtained thiamethoxam product was 97.6%.

[0105] Example 13

[0106] A solvent-free method for synthesizing thiamethoxam includes the following steps:

[0107] Step 1: Homogenization reaction: Add 37.2g (0.28mol) of 2-cyanoimino-1,3-thiazolidinyl ether, 45.4g (0.267mol) of 2-chloro-5-chloromethylpyridine and 12.2g (0.294mol) of solid base to a homogenizer. Homogenize and react under microwave heating for 3 hours. At this time, the normalized content of methylpyridine is about 2.6%. Stop the reaction to obtain the reaction product. The microwave heating power is 280W, the temperature is 45℃, and the homogenization speed is 3000 rpm.

[0108] Step 2, Post-processing: After the reaction is complete, add 180g of 95% ethanol solvent to the reaction product, reflux at 78℃ for 2h until the thiamethoxam dissolves, and then centrifuge while hot to obtain the thiamethoxam mother liquor.

[0109] Step 3, Purification: Cool the thiamethoxam mother liquor to 3°C for recrystallization, then filter. Wash the wet thiamethoxam crystals with 50mL of water to remove salt, filter, and dry to obtain the thiamethoxam product.

[0110] In this embodiment, the yield of thiamethoxam was 91.0%, and the purity of the obtained thiamethoxam product was 97.1%.

[0111] Comparative Example 1

[0112] A solvent-free method for synthesizing thiamethoxam includes the following steps:

[0113] Same as in Example 1, except that 100g of 95% ethanol was added to the homogenizer;

[0114] Step 1: Homogenization reaction: Add 37.2g (0.28mol) of 2-cyanoimino-1,3-thiazolidinyl ether, 45.4g (0.267mol) of 2-chloro-5-chloromethylpyridine, 12.2g (0.294mol) of solid base and 100g of 95% ethanol to a homogenizer. Homogenize and react under microwave heating for 5 hours until the normalized content of methylpyridine is less than 1%, then stop the reaction to obtain the reaction product. The microwave heating power is 280W, the temperature is 45℃, and the homogenization speed is 3000 rpm.

[0115] Step 2, Post-processing: After the reaction is complete, add 80g of 95% ethanol solvent to the reaction product, reflux at 78℃ for 2h until the thiamethoxam dissolves, and then centrifuge while hot to obtain the thiamethoxam mother liquor.

[0116] Step 3, Purification: Cool the thiamethoxam mother liquor to 3℃ for recrystallization, then filter. Wash the wet thiamethoxam crystals with 50mL of water to remove salt, filter, and dry to obtain the thiamethoxam product.

[0117] In this comparative example, the yield of thiamethoxam was 79%, and the purity of the obtained thiamethoxam product was 94.2%.

[0118] Due to the addition of ethanol, this comparative example not only exhibited the side reactions described in Examples 1-13, but also added a side reaction between ethanol and 2-chloro-5-chloromethylpyridine. Furthermore, the impurities generated by this side reaction are insoluble in water and cannot be removed during the subsequent recrystallization and washing processes, resulting in a decrease in both yield and product purity.

[0119] Comparative Example 2

[0120] A solvent-free synthesis method for thiamethoxam is the same as in Example 1, except that a traditional round-bottom flask is used instead of a homogenizer, methanol is used as the solvent, and oil bath heating is used instead of microwave heating. The specific operation is as follows:

[0121] Step 1: Add 37.2 g (0.28 mol) of 2-cyanoimino-1,3-thiazolidinane, 45.4 g (0.267 mol) of 2-chloro-5-chloromethylpyridine, 12.2 g (0.294 mol) of solid base and 100 g of methanol to a round-bottom flask. React under oil bath heating for 5 h until the normalized content of methylpyridine is less than 1%, then stop the reaction to obtain the reaction product. The temperature is 45 °C and the rotation speed is 380 rpm.

[0122] Step 2, Post-processing: After the reaction is complete, add 80g of methanol solvent to the reaction product, reflux at 65℃ for 2h until the thiamethoxam dissolves, and then centrifuge while hot to obtain the thiamethoxam mother liquor;

[0123] Step 3, Purification: Cool the thiamethoxam mother liquor to 3℃ for recrystallization, then filter. Wash the wet thiamethoxam crystals with 50mL of water to remove salt, filter, and dry to obtain the thiamethoxam product.

[0124] In this embodiment, the yield of thiamethoxam was 73%, and the purity of the obtained thiamethoxam product was 95.6%.

[0125] In this comparative example, methanol solvent and raw material methylpyridine undergo side reactions; traditional oil bath heating is not as uniform as microwave heating, and local overheating will increase the occurrence of the above-mentioned side reactions; and the mechanical stirring speed of traditional flask is too slow compared with that of a homogenizer, which is not conducive to material mixing. Therefore, compared with microwave heating in Comparative Example 3, the yield and purity of the product are reduced.

[0126] Comparative Example 3

[0127] A solvent-free synthesis method for thiamethoxam is the same as in Example 1, except that a conventional round-bottom flask is used instead of the homogenizer in Example 1, and a conventional mechanical stirring method is used instead of the homogenization speed in Example 1. The specific operation is as follows:

[0128] Step 1: Add 37.2 g (0.28 mol) of 2-cyanoimino-1,3-thiazolidinyl ether, 45.4 g (0.267 mol) of 2-chloro-5-chloromethylpyridine, 12.2 g (0.294 mol) of solid base and 100 g of methanol to a round-bottom flask. React under microwave heating with stirring. The microwave power is 280 W, the temperature is 45 °C, and the stirring speed is 500 rpm. Stop the reaction after 5 hours when the normalized content of the starting material methylpyridine is less than 1%.

[0129] Step 2, Post-processing: After the reaction is complete, add 80g of methanol solvent to the reaction product, reflux at 65℃ for 2h until the thiamethoxam dissolves, and then centrifuge while hot to obtain the thiamethoxam mother liquor;

[0130] Step 3, Purification: Cool the thiamethoxam mother liquor to 3℃ for recrystallization, then filter. Wash the wet thiamethoxam crystals with 50mL of water to remove salt, filter, and dry to obtain the thiamethoxam product.

[0131] In this embodiment, the yield of thiamethoxam was 75%, and the purity of the obtained thiamethoxam product was 97%.

[0132] Comparative Example 4

[0133] Similar to Example 1, except that the microwave heating function of the homogenizer is not activated; instead, an oil bath is used instead of microwave heating.

[0134] Step 1, Homogenization: 37.2 g (0.28 mol) of 2-cyanoimino-1,3-thiazolidinane, 45.4 g (0.267 mol) of 2-chloro-5-chloromethylpyridine, and 12.2 g (0.294 mol) of solid base were added to a homogenizer. The homogenization was carried out simultaneously under oil bath heating conditions at a reaction temperature of 45°C and a homogenization speed of 3000 rpm. After 5 hours of reaction, the reaction process was quality controlled using the area normalization method, and the normalized content of the raw material methylpyridine was approximately 20%.

[0135] Since no solvent is added during the reaction process of this invention, the raw materials are all in solid state. During the homogenization reaction, the materials are in a semi-solid state, resulting in poor thermal conductivity, uneven material temperature, and a significant decrease in reaction rate. Therefore, the reaction is terminated and no further operations are performed.

[0136] In Examples 1-13 and Comparative Example 4 of this invention, the main side reactions are as follows: 1) 2-chloro-5-chloromethylpyridine undergoes a decomposition reaction to generate salt, which can be removed by water washing during post-treatment; 2) Impurities formed by the metamorphism of 2-cyanoimino-1,3-thiazoline are insoluble in water and cannot be removed by cooling recrystallization and water washing during post-treatment, thus remaining in the thiamethoxam product. In Comparative Examples 1-3, in addition to the side reactions present in Examples 1-13, the solvent ethanol / methanol also undergoes a side reaction with methylpyridine to generate impurities that are not easily dissolved in water, thus remaining in the thiamethoxam product.

[0137] The occurrence of these side reactions is closely related to the control of various parameters in the reaction process, such as microwave power, reaction temperature, and stirring speed. Therefore, it is necessary to control these parameters within the range required by this invention so that the yield can be stably controlled at over 86% and the purity of the thiamethoxam product can be stably controlled at over 96%.

[0138] The embodiments described above are merely preferred embodiments of the present invention, and not an exhaustive list of all possible implementations of the present invention. Any obvious modifications made by those skilled in the art without departing from the principles and spirit of the present invention should be considered to be included within the scope of protection of the claims of the present invention.

Claims

1. A process for the solvent-free synthesis of tetraniliprole, characterized in that, Includes the following steps: 2-cyanoimino-1,3-thiazolidinyl, 2-chloro-5-chloromethylpyridine and a solid base are added to a homogenizer and reacted under microwave heating to generate thiamethoxam, yielding the reaction product. The solid alkali is one or more of sodium carbonate, potassium carbonate, potassium hydroxide, and sodium hydroxide. The molar ratio of 2-cyanoimino-1,3-thiazolidinyl, 2-chloro-5-chloromethylpyridine, and solid base is 1.0-1.1 mol: 1.0 mol: 1.0-1.2 mol; The microwave heating power is 60-380W, the microwave heating temperature is 30-60℃, the homogenization speed is 500-4000 rpm, and the reaction time is 2-15h.

2. The process for the solvent-free synthesis of tetramethrin according to claim 1, characterized in that, After the reaction is complete, post-processing is required, which includes: adding a recrystallization solvent to the reaction product and refluxing to dissolve thiamethoxam, then centrifuging while hot to obtain thiamethoxam mother liquor, and then sequentially performing cooling recrystallization, water washing to remove salt, filtration, and drying to obtain the thiamethoxam product.

3. The process for the solvent-free synthesis of tetramethrin according to claim 2, characterized in that, The recrystallization solvent is an alcohol solvent, and the mass concentration of the alcohol solvent is ≥95%.

4. The solvent-free synthesis method of thiamethoxam according to claim 3, characterized in that, The alcohol solvent is selected from one or more of ethanol, methanol, and isopropanol.

5. The solvent-free synthesis method of thiamethoxam according to claim 2, characterized in that, The reflux time is 2-3 hours.

6. The solvent-free synthesis method of thiamethoxam according to claim 2, characterized in that, Add recrystallization solvent to the reaction product at a mass ratio of 94:160-200.

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