A method for synthesizing flonicamid

Abstract

The application discloses a synthetic method of flonicamid, and belongs to the technical field of organic synthesis. 4-trifluoromethyl nicotinic acid and aminoacetonitrile hydrochloride are reacted in the presence of a mixed catalytic system, a dichloromethane and water mixed system is used for refluxing, water is added for crystallization, and then filtering and drying are carried out to obtain white crystal flonicamid product, the purity of which can reach more than 99.0%, and the product is stored in a dry and sealed manner. The method has the advantages of simple operation, less reaction by-products, high product purity and low cost, and has great competitiveness in the market.

Description

Technical Field

[0001] This invention relates to a method for synthesizing flupyradifurone, belonging to the field of organic synthesis technology. Background Technology

[0002] Flupyradifurone, a white crystalline solid with a melting point of 157-158℃, CAS number 158062-67-0, and molecular formula C9H6F3N3O, is a novel low-toxicity pyridine amide insect growth regulator.

[0003] Existing technical methods are divided into direct and indirect methods. The direct method involves first converting 4-trifluoromethylnicotinic acid into an acyl chloride, and then reacting it with aminoacetonitrile hydrochloride. This method has a low yield and is difficult to purify. The indirect method also involves first synthesizing the acyl chloride, then reacting it with methylene aminoacetonitrile, and then obtaining flonicamid through multiple reaction steps. However, both of these methods have low yields, cause significant pollution, involve long and complex processes, and result in low product purity and difficult purification.

[0004] Therefore, in order to save steps, reduce costs, and increase yield, new synthetic methods need to be developed. Summary of the Invention

[0005] To overcome the aforementioned technical deficiencies, this invention provides a method for synthesizing flonicamid. This invention employs a mixed anhydride method, based on the principle that 4-trifluoromethylnicotinic acid reacts with methanesulfonyl chloride to form a carboxylic acid-sulfonic acid anhydride. This species has high reactivity and can be directly reacted with aminoacetonitrile hydrochloride to generate flonicamid.

[0006] To achieve the above objectives, the present invention provides a method for synthesizing flonicamid, which employs the following technical solution and includes the following operations: 4-trifluoromethylnicotinic acid and aminoacetonitrile hydrochloride are reacted under reflux in an organic solvent in the presence of a condensing agent, an acid-binding agent, and a phase transfer catalyst. After the reaction is completed, the mixture is filtered and dried to obtain the flonicamid product.

[0007] Furthermore, in the above technical solution, the condensing agent is methanesulfonyl chloride, and the process is that 4-trifluoromethylnicotinic acid and methanesulfonyl chloride first form a highly active carboxylic acid-sulfonic acid mixed anhydride, and then react with aminoacetonitrile hydrochloride to form flonicamid.

[0008] Furthermore, in the above technical solution, the organic solvent is dichloromethane, chloroform, or 1,2-dichloroethane.

[0009] Furthermore, in the above technical solution, the acid-binding agent is an inorganic base. The inorganic base is preferably sodium bicarbonate or potassium bicarbonate.

[0010] Furthermore, in the above technical solution, before heating, a small amount of water is added to dissolve part of the acid-binding agent, and the water generated by the reaction is absorbed under the action of the phase transfer catalyst to promote the forward reaction.

[0011] Furthermore, in the above technical solution, the reaction operation is as follows: 4-trifluoromethylnicotinic acid and an organic solvent are mixed, then an acid-binding agent and a condensing agent are added, the condensing agent is added dropwise at low temperature, then aminoacetonitrile hydrochloride is added, and finally water is added, and the temperature is raised to reflux reaction.

[0012] Furthermore, in the above technical solution, the molar ratio of 4-trifluoromethylnicotinic acid, aminoacetonitrile hydrochloride, condensing agent, acid-binding agent and phase transfer catalyst is 1:1-1.3:1-1.3:3-3.5:0.1-0.2.

[0013] The typical operation of the technical solution described in this invention is as follows: Sodium bicarbonate and benzyltriethylammonium chloride are added to a mixed solution of 4-trifluoromethylnicotinic acid and dichloromethane. Methylsulfonyl chloride is added dropwise at low temperature. After adding aminoacetonitrile hydrochloride, a small amount of water is added dropwise. The mixture is heated and refluxed for 1 hour. A large amount of water is added dropwise to precipitate crystals. The mixture is then cooled and stirred for 1-2 hours. The wet product is obtained by filtration and dried to obtain the product flonicamid.

[0014] Furthermore, in the above technical solution, the qualified indicators of the flupyradifurone are: white solid powder, purity greater than 99.0%, moisture content less than 0.5%, and stored as a dry and sealed polymerization inhibitor.

[0015] Beneficial effects of the invention

[0016] This invention uses 4-trifluoromethylnicotinic acid and aminoacetonitrile hydrochloride to react under the catalysis of benzyltriethylammonium chloride. Byproducts and other impurities can be dissolved in the mother liquor for removal.

[0017] The route of this invention is simple to operate, produces few reaction byproducts, has high product purity, low cost, and the product has a competitive advantage. Detailed Implementation

[0018] Example 1:

[0019] In a reaction flask, a mixed solution of 50 g (0.261 mol) of 4-trifluoromethylnicotinic acid, 250 mL of dichloromethane, 76.7 g (0.958 mol) of sodium bicarbonate, and 5.9 g (0.025 mol) of benzyltriethylammonium chloride was added dropwise. Then, 38.8 g (0.338 mol) of methanesulfonyl chloride was added dropwise at 0°C, followed by 31.4 g (0.339 mol) of aminoacetonitrile hydrochloride, and then 50 g of water. The mixture was heated to 38-40°C and refluxed. After the reaction was complete (approximately 1.5 hours) as indicated by the control panel, 200 mL of water was added dropwise, and the mixture was cooled to 5°C and stirred for 1 hour. The product, flonicamid, was obtained by filtration and drying, with a purity of 99.2%, a water content of 0.33%, and a yield of 95.2%.

[0020] Precautions

[0021] Although the reaction is a water addition reaction, the moisture content in the reaction system still needs to be controlled before adding aminoacetonitrile hydrochloride. Otherwise, the methanesulfonyl chloride and the generated mixed acid anhydride will be destroyed, affecting the reaction yield.

[0022] When adding methanesulfonyl chloride, the temperature needs to be controlled to not exceed 10℃. The temperature also needs to be controlled when adding water before reflux. Otherwise, if the temperature rises too quickly, it will cause the reaction to start prematurely and reduce the yield.

[0023] During the heating phase, the reaction produces a large amount of carbon dioxide gas, causing the solution to boil violently and the reaction system to expand in volume. It is necessary to increase the stirring speed, activate the venting mechanism, and promptly release the gas to prevent overflow or overpressure. Once reflux begins, the generation of large amounts of gas will cease.

[0024] The reaction time should not be too long, and post-processing filtration is necessary after the reaction is complete. Excessive time will darken the color of the reaction solution, making the product's coloring more pronounced and difficult to wash off. The mother liquor also needs to be separated into aqueous and organic phases for separate treatment.

[0025] During the rinsing of wet products, first use dichloromethane to rinse down the residual material on the vessel wall, and then rinse with water to ensure thorough soaking.

[0026] Example 2:

[0027] In a 500 mL three-necked flask, 20 g (0.104 mol) of 4-trifluoromethylnicotinic acid, 100 mL of dichloromethane, 30.8 g (0.385 mol) of sodium bicarbonate, and 2.3 g (0.01 mol) of benzyltriethylammonium chloride were added and mixed thoroughly. Then, 15.5 g (0.135 mol) of methanesulfonyl chloride was added dropwise at 0 °C, followed by 12.6 g (0.135 mol) of aminoacetonitrile hydrochloride, and then 20 g of water. The mixture was heated to 38-40 °C and refluxed. After the reaction was complete (approximately 1.5 hours) as indicated by the control panel, 80 mL of water was added dropwise, and the mixture was cooled to 5 °C and stirred for 1 hour. The mixture was filtered and dried to obtain 22.5 g of the product flonicamid, with a purity of 99.5%, a water content of 0.18%, and a yield of 93.7%.

[0028] Example 3:

[0029] In a 500 mL three-necked flask, 20 g (0.104 mol) of 4-trifluoromethylnicotinic acid, 100 mL of dichloromethane, 30.8 g (0.385 mol) of sodium bicarbonate, and 1.2 g (0.005 mol) of benzyltriethylammonium chloride were added and mixed thoroughly. Then, 15.5 g (0.135 mol) of methanesulfonyl chloride was added dropwise at 0 °C, followed by 10.7 g (0.114 mol) of aminoacetonitrile hydrochloride, and then 20 g of water. The mixture was heated to 38-40 °C and refluxed. After the reaction was complete (approximately 1.5 hours) as indicated by the control panel, 80 mL of water was added dropwise, and the mixture was cooled to 5 °C and stirred for 1 hour. The mixture was filtered and dried to obtain 22.0 g of the product flonicamid, with a purity of 99.6%, a water content of 0.22%, and a yield of 92.1%.

[0030] Example 4:

[0031] In a 50L jacketed reactor, 2.0 kg (10.4 mol) of 4-trifluoromethylnicotinic acid, 10 L of dichloromethane, 3.08 kg (38.5 mol) of sodium bicarbonate, and 240 g (1.0 mol) of benzyltriethylammonium chloride were added and mixed thoroughly. Then, 1.56 kg (13.6 mol) of methanesulfonyl chloride was added dropwise at 0°C, followed by 10.7 kg (11.5 mol) of aminoacetonitrile hydrochloride, and then 2 kg of water. The mixture was heated to 38-40°C and refluxed. After the reaction was complete (approximately 2.5 hours) as indicated by the control panel, 8 kg of water was added dropwise, and the mixture was cooled to 5°C and stirred for 1.5 hours. The mixture was filtered and dried to obtain 2.225 kg of the product flonicamid, with a purity of 99.4%, a water content of 0.29%, and a yield of 95.7%.

[0032] The above embodiments describe the basic principles, main features, and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The embodiments and descriptions in the specification are merely illustrative of the principles of the present invention. Various changes and modifications can be made to the present invention without departing from its principles, and all such changes and modifications fall within the scope of protection of the present invention.

Claims

1. A method for synthesizing flonicamid, characterized in that, The procedure includes the following steps: In a reaction flask, add 50g of 4-trifluoromethylnicotinic acid, 250mL of dichloromethane, 76.7g of sodium bicarbonate, and a mixed solution of 5.9g of benzyltriethylammonium chloride. Add 38.8g of methanesulfonyl chloride dropwise at 0℃, followed by 31.4g of aminoacetonitrile hydrochloride, and then add 50g of water. Reflux at 38-40℃. After the reaction is complete as indicated by the central control, add 200mL of water, cool to 5℃, stir for 1 hour, filter, and dry to obtain flonicamid.

2. A method for synthesizing flonicamid, characterized in that, The procedure includes the following steps: In a 500 mL three-necked reaction flask, add 20 g of 4-trifluoromethylnicotinic acid, 100 mL of dichloromethane, 30.8 g of sodium bicarbonate, and 2.3 g of benzyltriethylammonium chloride. Mix well and stir. Add 15.5 g of methanesulfonyl chloride dropwise at 0 °C, then add 12.6 g of aminoacetonitrile hydrochloride, followed by 20 g of water. Reflux at 38-40 °C. After the reaction is complete as indicated by the central control, add 80 mL of water dropwise, cool to 5 °C, stir for 1 hour, filter, and dry to obtain flonicamid.

3. A method for synthesizing flonicamid, characterized in that, The procedure includes the following steps: In a 500 mL three-necked reaction flask, add 20 g of 4-trifluoromethylnicotinic acid, 100 mL of dichloromethane, 30.8 g of sodium bicarbonate, and 1.2 g of benzyltriethylammonium chloride. Mix well and stir. Add 15.5 g of methanesulfonyl chloride dropwise at 0 °C, then add 10.7 g of aminoacetonitrile hydrochloride, followed by 20 g of water. Reflux at 38-40 °C. After the reaction is complete as indicated by the central control, add 80 mL of water dropwise, cool to 5 °C, stir for 1 hour, filter, and dry to obtain flonicamid.

4. A method for synthesizing flonicamid, characterized in that, The process includes the following steps: In a 50L jacketed reactor, 2.0 kg of 4-trifluoromethylnicotinic acid, 10 L of dichloromethane, 3.08 kg of sodium bicarbonate, and 240 g of benzyltriethylammonium chloride are added and mixed thoroughly. 1.56 kg of methanesulfonyl chloride is added dropwise at 0°C, followed by 10.7 kg of aminoacetonitrile hydrochloride, and then 2 kg of water. The mixture is heated to 38-40°C and refluxed. After the reaction is complete as indicated by the central control, 8 kg of water is added dropwise, and the mixture is cooled to 5°C and stirred for 1.5 hours. The mixture is then filtered and dried to obtain flonicamid.