Preparation method of flonicamid

Abstract

The invention discloses a preparation method of flonicamid, and belongs to the technical field of pesticide synthesizing.The preparation method comprises the steps that 4-trifluoromethyl nicotinic acid and aminoacetonitrile salt serve as raw materials, alkali metal alkoxide high in cost performance is added, a reaction is conducted in an alcohol solvent to obtain 4-trifluoromethyl nicotinate and free aminoacetonitrile, and the 4-trifluoromethyl nicotinate and the free aminoacetonitrile are subjected to post-treatment to obtain the flonicamid. A sulfonyl chloride compound is added for reaction to obtain an anhydride intermediate product, flonicamid is obtained through efficient condensation of an indirect method, a non-protonic solvent is used as a reaction system solvent, a product is separated out through a low-temperature water phase, high-purity flonicamid is obtained at a time, and the whole preparation method is simple in step, good in reaction selectivity, few in side reaction and suitable for industrial production. The target product flonicamid is high in yield, the byproducts of metal chloride and sulfonate are good in water solubility, the product and the byproducts are convenient to separate, the purity is high, and further decoloration and refining are not needed.

Description

Technical Field

[0001] The invention belongs to the technical field of pesticide synthesis, and particularly relates to a method for preparing flonicamid. Background Art

[0002] Flunicidinamide is a new type of pyridinamide insecticide. In addition to its contact and stomach poisoning effects, it also has good neurotoxic effects, good penetration and rapid antifeedant effects. Moreover, flunicidinamide has no cross-resistance with the widely used pesticides such as imidacloprid, acetamiprid and pymetrozine in production, and its insecticidal effect is very good.

[0003] The synthesis methods of flonicamid are divided into direct method and indirect method. The direct method uses 4-trifluoromethylnicotinic acid as the starting material and directly prepares flonicamid through the reaction of acyl chloride and amine; the indirect method involves multiple steps, including the chlorination of 4-trifluoromethylnicotinic acid, using 4-trifluoromethylnicotinic acid chloride and methyleneaminoacetonitrile as raw materials to prepare the corresponding amide, which is hydrolyzed at room temperature under acidic conditions and then reacted with sodium carbonate aqueous solution at room temperature to obtain the final product flonicamid.

[0004] Although the direct method has a short process, the yield is low, and the product needs to be purified by column chromatography, which is not conducive to industrialization. The indirect method has a long process, and the total yield is slightly higher than the direct method. The product post-processing process is relatively simple, which is conducive to industrialization. The indirect method is more conducive to the production of flonicamid.

[0005] The patent application document with publication number CN115215795A discloses a method for synthesizing flonicamid, using 4-trifluoromethylnicotinic acid or its metal salt as a raw material to generate an intermediate of a structure represented by formula (I) or formula (II) (as shown below), and the intermediate is reacted with an aminoacetonitrile salt to obtain flonicamid.

[0006]

[0007] In the preparation method, the compound represented by the structure of formula (I) or formula (II) is less active than 4-trifluoromethylnicotinyl chloride. When subjected to a substitution reaction with an aminoacetonitrile salt, the reaction has good selectivity, few by-products, and a high yield of the target product. However, the purity of the product flonicamid obtained by recrystallization is only 96%, which cannot meet the requirements of a high-purity product and it is difficult to ensure its high efficiency and stability. Summary of the invention

[0008] The object of the present invention is to provide a method for preparing flonicamid, which can effectively improve the yield and purity of flonicamid.

[0009] The purpose of the present invention can be achieved through the following technical solutions:

[0010] The present invention provides a method for preparing flonicamid, comprising the following steps:

[0011] Step 1: 4-trifluoromethylnicotinic acid and aminoacetonitrile salt are used as raw materials, an alcohol solvent is added and stirred evenly, the temperature is lowered to 5-10° C., an alkali metal alcohol salt is added, and the reaction is stirred at 0-50° C. to generate 4-trifluoromethylnicotinic acid salt, and aminoacetonitrile is released at the same time;

[0012] Step 2: After the salt is freed, the alcohol solvent is concentrated and recovered to obtain a viscous solid residue, which is added to an aprotic solvent and cooled to -10°C to -5°C under continuous stirring. The sulfonyl chloride compound is added and the temperature of the reaction system is controlled at -5 to 0°C. After the addition is completed, the temperature is naturally raised and the temperature is controlled at 5 to 10°C for stirring reaction;

[0013] Step 3: After the reaction is completed, add alkaline aqueous solution, adjust the pH to 9-10, cool to -5-0°C, filter after the product precipitates, wash and dry to obtain an off-white solid.

[0014] The synthetic route of the above preparation method is as follows:

[0015]

[0016] Furthermore, the molar ratio of 4-trifluoromethylnicotinic acid, aminoacetonitrile salt and alkali metal alkoxide is 1:(1-2):(2-3), and the molar amount of alkali metal alkoxide is the sum of the molar amounts of 4-trifluoromethylnicotinic acid and aminoacetonitrile salt. A slight excess of aminoacetonitrile salt compared to 4-trifluoromethylnicotinic acid can promote the conversion of 4-trifluoromethylnicotinic acid to flonicamid in the subsequent reaction.

[0017] Furthermore, the aminoacetonitrile salt is one of aminoacetonitrile hydrochloride and aminoacetonitrile sulfate. Aminoacetonitrile hydrochloride and aminoacetonitrile sulfate have certain solubility in alcohol solvents.

[0018] Furthermore, the alcohol solvent is one of methanol, ethanol and isopropanol.

[0019] Furthermore, the alcohol solvent is methanol.

[0020] Furthermore, the mass ratio of the alcohol solvent to 4-trifluoromethylnicotinic acid is 10 to 20:1.

[0021] Furthermore, the alkali metal alkoxide is one of sodium methoxide, sodium ethoxide, sodium tert-butoxide and potassium tert-butoxide. The alkali metal alkoxide is used to participate in the salt-forming reaction, and its byproduct is alcohol, and no water is produced, which can avoid the negative impact of water on the reaction and improve the yield of the product.

[0022] Furthermore, the alkali metal alkoxide is sodium methoxide, which has a lower cost.

[0023] Furthermore, in step 1, the addition time of the alkali metal alkoxide is 1 to 2 hours.

[0024] Furthermore, in step 1, the temperature of the stirring reaction is 20-30°C.

[0025] Furthermore, in step 1, the stirring time of the stirring reaction is 1 to 2 hours.

[0026] Furthermore, the aprotic solvent is one of dichloromethane, dichloroethane, acetonitrile, acetone, dimethylformamide and tetrahydrofuran.

[0027] Furthermore, the mass ratio of the aprotic solvent to 4-trifluoromethylnicotinic acid is 10 to 20:1.

[0028] Furthermore, the sulfonyl chloride compound is one of methanesulfonyl chloride, phenylmethanesulfonyl chloride and p-toluenesulfonyl chloride. Compared with other acyl chloride reagents, sulfonyl chloride does not need to avoid contact with moisture, which reduces the risks in storage and operation.

[0029] Furthermore, the acyl chloride compound is methanesulfonyl chloride, which has a small molecular weight, a low unit price, and good solubility in aprotic solvents.

[0030] Furthermore, the molar ratio of the sulfonyl chloride compound to 4-trifluoromethylnicotinic acid is 1 to 2:1.

[0031] Furthermore, the alkaline aqueous solution is one of a sodium hydroxide aqueous solution, a potassium hydroxide aqueous solution and a sodium carbonate aqueous solution. The alkaline aqueous solution mainly adjusts the pH and reacts with the acidic substance in the reaction system for neutralization.

[0032] Furthermore, the mass concentration of the alkaline aqueous solution is 1% to 5%.

[0033] Beneficial effects of the present invention:

[0034] (1) From the perspective of cost, environmental protection and operational feasibility, in the method provided by the present invention, the solvent can be recycled and reused, thereby reducing the solvent cost and reducing environmental pollution; the cost-effective alkali metal alkoxide is used instead of the pyridine organic base as the acid-binding agent, the auxiliary material cost is reduced, the environmental hazard of the alkali metal alkoxide is reduced compared with the pyridine organic base, and the wastewater has no odor; the reaction conditions are relatively mild, there is no high temperature or excessively low temperature (below -10°C) temperature requirement, the requirements for equipment and operation are relatively low, the operation is safe, simple and low in cost; the by-products are mainly metal chlorides and sulfonates, and other organic matter residues are small, and the salt after wastewater treatment can be comprehensively utilized.

[0035] (2) In the preparation method of the present invention, 4-trifluoromethylnicotinic acid and aminoacetonitrile salt are used as raw materials, and an alkali metal alcohol salt with high cost performance is added to obtain 4-trifluoromethylnicotinic acid salt and free aminoacetonitrile, and a sulfonyl chloride compound is added to react to obtain an acid anhydride intermediate product, and flonicamid is obtained by an indirect method with high efficiency condensation, and an aprotic solvent is used as the reaction system solvent, and the product is precipitated in a low temperature aqueous phase to obtain high-purity white-like flonicamid at one time. The whole preparation method has simple steps, good reaction selectivity, few side reactions, high yield of the target product flonicamid, and the by-products metal chloride and sulfonate have good water solubility, which is convenient for separation of the product and the by-products, and high purity, without the need for further decolorization and purification. DETAILED DESCRIPTION

[0036] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only 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.

[0037] Example 1

[0038] Step 1: Add 1 kg (5.23 mol) of 4-trifluoromethylnicotinic acid and 0.581 kg (6.28 mol) of aminoacetonitrile hydrochloride to a reaction kettle, then add 15 L of methanol, start stirring, stir evenly and cool to 5° C., add sodium methoxide three times within 1 hour, the total mass of sodium methoxide is 0.622 kg (11.51 mol), and the mass added each time is equal. Stir and react at 25° C. for 2 hours to generate 4-trifluoromethylnicotinic acid salt, and at the same time, free aminoacetonitrile;

[0039] Step 2: After the salt is freed, the temperature is raised to 40°C, and the methanol is recovered by negative pressure concentration until no methanol drips out, and a viscous solid residue is obtained. The temperature is lowered to 10°C, 10 kg of dichloroethane is added thereto, and under continuous stirring, the temperature is lowered to -10°C, and 0.687 kg (6.00 mol) of methanesulfonyl chloride is slowly added dropwise. The temperature is controlled between -5 and 0°C during the addition process. After the addition is completed, the temperature is naturally raised to 5°C for stirring reaction;

[0040] Step three, the reaction process was tracked by TLC and detected by HPLC. The reaction was stopped when the raw material 4-trifluoromethylnicotinic acid was less than 1.0wt%. At this time, the reaction was completed, and 4.8kg of sodium hydroxide aqueous solution (mass concentration was 5%) was added, and the pH was adjusted to 9.0-10.0, and the temperature was cooled to -5 ° C. After the product was precipitated, it was filtered and washed with low temperature (-5 ° C) dichloroethane. After drying, 1.174kg of off-white solid, i.e., flonicamid, was obtained, with a yield of 97% and a purity of 99%.

[0041] Example 2

[0042] The only difference from Example 1 is that the amount of aminoacetonitrile hydrochloride added is adjusted from 0.581 kg (6.28 mol) to 0.968 kg (10.46 mol), and the total mass of sodium methoxide is adjusted from 0.622 kg (11.51 mol) to 0.848 kg (15.69 mol). The specific steps are as follows:

[0043] Step 1: Add 1 kg (5.23 mol) of 4-trifluoromethylnicotinic acid and 0.968 kg (10.46 mol) of aminoacetonitrile hydrochloride to a reaction kettle, then add 15 L of methanol, start stirring, stir evenly and cool to 5° C., add sodium methoxide three times within 1 hour, the total mass of sodium methoxide is 0.848 kg (15.69 mol), the mass added each time is equal, stir and react at 25° C. for 2 hours to generate 4-trifluoromethylnicotinic acid salt, and at the same time, release aminoacetonitrile;

[0044] Step 2: After the salt is freed, the temperature is raised to 40°C, and the methanol is recovered by negative pressure concentration until no methanol drips out, and a viscous solid residue is obtained. The temperature is lowered to 10°C, 10 kg of dichloroethane is added thereto, and under continuous stirring, the temperature is lowered to -10°C, and 0.687 kg (6.00 mol) of methanesulfonyl chloride is slowly added dropwise. The temperature is controlled between -5 and 0°C during the addition process. After the addition is completed, the temperature is naturally raised to 5°C for stirring reaction;

[0045] Step three, the reaction process was tracked by TLC and detected by HPLC. The reaction was stopped when the raw material 4-trifluoromethylnicotinic acid was less than 1.0wt%. At this time, the reaction was completed, and 4.8kg of sodium hydroxide aqueous solution (mass concentration was 5%) was added, and the pH was adjusted to 9.0-10.0, and the temperature was cooled to -5 ° C. After the product was precipitated, it was filtered and washed with low temperature (-5 ° C) dichloroethane. After drying, 1.174kg of off-white solid, i.e., flonicamid, was obtained, with a yield of 96% and a purity of 98%.

[0046] Example 3

[0047] The only difference from Example 1 is that the amount of aminoacetonitrile hydrochloride added is adjusted from 0.58 kg (6.28 mol) to 0.484 kg (5.23 mol), and the total mass of sodium methoxide is adjusted from 0.622 kg (11.51 mol) to 0.565 kg (10.46 mol). The specific steps are as follows:

[0048] Step 1: Add 1 kg (5.23 mol) of 4-trifluoromethylnicotinic acid and 0.484 kg (5.23 mol) of aminoacetonitrile hydrochloride to a reaction kettle, then add 15 L of methanol, start stirring, stir evenly and cool to 5° C., add sodium methoxide three times within 1 hour, the total mass of sodium methoxide is 0.565 kg (10.46 mol), the mass added each time is equal, stir and react at 25° C. for 2 hours to generate 4-trifluoromethylnicotinic acid salt, and at the same time, release aminoacetonitrile;

[0049] Step 2: After the salt is freed, the temperature is raised to 40°C, and the methanol is recovered by negative pressure concentration until no methanol drips out, and a viscous solid residue is obtained. The temperature is lowered to 10°C, 10 kg of dichloroethane is added thereto, and under continuous stirring, the temperature is lowered to -10°C, and 0.687 kg (6.00 mol) of methanesulfonyl chloride is slowly added dropwise. The temperature is controlled between -5 and 0°C during the addition process. After the addition is completed, the temperature is naturally raised to 5°C for stirring reaction;

[0050] Step 3, the reaction process was tracked by TLC and detected by HPLC. The reaction was stopped when the raw material 4-trifluoromethylnicotinic acid was less than 1.0wt%. At this time, the reaction was completed, and 4.8kg of sodium hydroxide aqueous solution (mass concentration was 5%) was added, and the pH was adjusted to 9.0-10.0, and the temperature was cooled to -5 ° C. After the product was precipitated, it was filtered and washed with low temperature (-5 ° C) dichloroethane. After drying, 1.162kg of off-white solid, i.e., flonicamid, was obtained, with a yield of 95% and a purity of 98%.

[0051] Example 4

[0052] The only difference from Example 1 is that the amount of methanesulfonyl chloride added is adjusted from 0.687 kg (6.00 mol) to 1.198 kg (10.46 mol). The amount of sodium hydroxide aqueous solution (mass concentration is 5%) is adjusted from 4.8 kg to 8.368 kg, and the pH is adjusted to 9.0-10.0. The specific steps are as follows:

[0053] Step 1: Add 1 kg (5.23 mol) of 4-trifluoromethylnicotinic acid and 0.581 kg (6.28 mol) of aminoacetonitrile hydrochloride to a reaction kettle, then add 15 L of methanol, start stirring, stir evenly and cool to 5° C., add sodium methoxide three times within 1 hour, the total mass of sodium methoxide is 0.622 kg (11.51 mol), and the mass added each time is equal. Stir and react at 25° C. for 2 hours to generate 4-trifluoromethylnicotinic acid salt, and at the same time, free aminoacetonitrile;

[0054] Step 2: After the salt is freed, the temperature is raised to 40°C, and the methanol is recovered by negative pressure concentration until no methanol drips out, and a viscous solid residue is obtained. The temperature is lowered to 10°C, 10 kg of dichloroethane is added thereto, and the temperature is lowered to -10°C under continuous stirring, and 1.198 kg (10.46 mol) of methanesulfonyl chloride is slowly added dropwise. The temperature is controlled between -5 and 0°C during the addition process. After the addition is completed, the temperature is naturally raised to 5°C for stirring reaction;

[0055] Step three, the reaction process was tracked by TLC and detected by HPLC. The reaction was stopped when the raw material 4-trifluoromethylnicotinic acid was less than 1.0wt%. At this time, the reaction was completed, and 8.368kg of sodium hydroxide aqueous solution (mass concentration was 5%) was added, and the pH was adjusted to 9.0-10.0, cooled to -5 ° C, and the product was filtered after precipitation, washed with low temperature (-5 ° C) dichloroethane, and dried to obtain 1.186kg of off-white solid, i.e., flonicamid, with a yield of 97% and a purity of 98%.

[0056] Example 5

[0057] The only difference from Example 1 is that the amount of methanesulfonyl chloride added is adjusted from 0.687 kg (6.00 mol) to 0.599 kg (5.23 mol). The sodium hydroxide aqueous solution (mass concentration is 5%) is adjusted from 4.8 kg to 4.184 kg, and the pH is adjusted to 9.0-10.0. The specific steps are as follows:

[0058] Step 1: Add 1 kg (5.23 mol) of 4-trifluoromethylnicotinic acid and 0.581 kg (6.28 mol) of aminoacetonitrile hydrochloride to a reaction kettle, then add 15 L of methanol, start stirring, stir evenly and cool to 5° C., add sodium methoxide three times within 1 hour, the total mass of sodium methoxide is 0.622 kg (11.51 mol), and the mass added each time is equal. Stir and react at 25° C. for 2 hours to generate 4-trifluoromethylnicotinic acid salt, and at the same time, free aminoacetonitrile;

[0059] Step 2: After the salt is freed, the temperature is raised to 40°C, and the methanol is recovered by negative pressure concentration until no methanol drips out, and a viscous solid residue is obtained. The temperature is lowered to 10°C, 10 kg of dichloroethane is added thereto, and under continuous stirring, the temperature is lowered to -10°C, and 0.599 kg (5.23 mol) of methanesulfonyl chloride is slowly added dropwise. The temperature is controlled between -5 and 0°C during the addition process. After the addition is completed, the temperature is naturally raised to 5°C for stirring reaction;

[0060] Step three, the reaction process was tracked by TLC and detected by HPLC. The reaction was stopped when the raw material 4-trifluoromethylnicotinic acid was less than 1.0wt%. At this time, the reaction was completed, and 4.184kg of sodium hydroxide aqueous solution (mass concentration was 5%) was added, and the pH was adjusted to 9.0-10.0, cooled to -5 ° C, and the product was precipitated and filtered, washed with low temperature (-5 ° C) dichloroethane, and dried to obtain 1.173kg of off-white solid, i.e., flonicamid, with a yield of 96% and a purity of 98%.

[0061] Example 6

[0062] The only difference from Example 1 is that methanesulfonyl chloride is replaced by phenylmethylsulfonyl chloride. The specific steps are as follows:

[0063] Step 1: Add 1 kg (5.23 mol) of 4-trifluoromethylnicotinic acid and 0.581 kg (6.28 mol) of aminoacetonitrile hydrochloride to a reaction kettle, then add 15 L of methanol, start stirring, stir evenly and cool to 5° C., add sodium methoxide three times within 1 hour, the total mass of sodium methoxide is 0.622 kg (11.51 mol), and the mass added each time is equal. Stir and react at 25° C. for 2 hours to generate 4-trifluoromethylnicotinic acid salt, and at the same time, free aminoacetonitrile;

[0064] Step 2: After the salt is freed, the temperature is raised to 40°C, and the methanol is recovered by negative pressure concentration until no methanol drips out, and a viscous solid residue is obtained. The temperature is lowered to 10°C, 10 kg of ethylene dichloride is added thereto, and the temperature is lowered to -10°C under continuous stirring, and 1.144 kg (6.00 mol) of phenylmethylsulfonyl chloride is added. The temperature is controlled between -5 and 0°C during the addition process. After the addition is completed, the temperature is naturally raised to 5°C for stirring reaction;

[0065] Step three, the reaction process was tracked by TLC and detected by HPLC. The reaction was stopped when the raw material 4-trifluoromethylnicotinic acid was less than 1.0wt%. At this time, the reaction was completed, and 4.8kg of sodium hydroxide aqueous solution (mass concentration was 5%) was added, and the pH was adjusted to 9.0-10.0, and the temperature was cooled to -5 ° C. After the product was precipitated, it was filtered and washed with low temperature (-5 ° C) dichloroethane. After drying, 1.15kg of off-white solid, i.e., flonicamid, was obtained, with a yield of 95% and a purity of 99%.

[0066] Comparative Example 1

[0067] Compared with Example 1, in step 1 of this comparative example, sodium hydroxide is used to replace sodium methoxide, and the specific steps are as follows:

[0068] Step 1: Add 1 kg (5.23 mol) of 4-trifluoromethylnicotinic acid and 0.581 kg (6.28 mol) of aminoacetonitrile hydrochloride to a reaction kettle, then add 15 L of methanol, start stirring, stir evenly and cool to 5° C., add sodium hydroxide three times within 1 hour, the total mass of sodium hydroxide is 0.460 kg (11.51 mol), the mass added each time is equal, stir and react at 25° C. for 2 hours to generate 4-trifluoromethylnicotinic acid salt, and at the same time, free aminoacetonitrile;

[0069] Step 2: After the salt is freed, the temperature is raised to 40°C, and the methanol is recovered by negative pressure concentration until no methanol drips out. The residue is cooled to 10°C, 10 kg of dichloroethane is added thereto, and the temperature is lowered to -10°C under continuous stirring. 0.687 kg (6.00 mol) of methanesulfonyl chloride is slowly added dropwise. The temperature is controlled between -5 and 0°C during the addition process. After the addition is completed, the temperature is naturally raised to 5°C for stirring reaction;

[0070] Step three, the reaction process was tracked by TLC and detected by HPLC. The reaction was stopped when the raw material 4-trifluoromethylnicotinic acid was less than 1.0wt%. At this time, the reaction was completed, and 4.8kg of sodium hydroxide aqueous solution (mass concentration was 5%) was added, and the pH was adjusted to 9.0-10.0, and the temperature was cooled to -5 ° C. After the product was precipitated, it was filtered and washed with low temperature (-5 ° C) dichloroethane. After drying, 0.96kg of off-white solid, i.e., flonicamid, was obtained, with a yield of 71% and a purity of 89%.

[0071] Comparative Example 2

[0072] According to Example 1 of the patent application document with publication number CN113943249A, flonicamid was prepared with a purity of 98% and a yield of 93%.

[0073] It can be seen from the above embodiments and comparative examples that the product prepared by the preparation method provided by the present invention in the embodiments has high purity and high yield, and the preparation process does not need to be equipped with a water separator to remove the generated water compared to Comparative Example 2, and the requirements for the reaction device are simpler. In Comparative Example 1, sodium hydroxide is used instead of sodium methoxide for the reaction. Since sodium hydroxide will produce by-product water during the salt-forming reaction, water will remain in the material when methanol is recovered, resulting in an adverse effect on subsequent reactions, and the yield and purity are significantly lower than those in the embodiments.

[0074] It should be noted that, in this article, relational terms such as first and second, etc. are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Moreover, the terms "include", "comprise" or any other variants thereof are intended to cover non-exclusive inclusion, so that a process, method, article or device including a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements inherent to such process, method, article or device.

[0075] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A method for preparing flonicamid, characterized in that: The following steps are involved: Step 1: 4-trifluoromethylnicotinic acid and aminoacetonitrile salt are used as raw materials, an alcohol solvent is added and stirred evenly, the temperature is lowered to 5-10° C., an alkali metal alcohol salt is added, and the reaction is stirred at 0-50° C. to generate 4-trifluoromethylnicotinic acid salt, and aminoacetonitrile is released at the same time; Step 2: After the salt is freed, the alcohol solvent is concentrated and recovered to obtain a viscous solid residue, which is added to an aprotic solvent and cooled to -10°C to -5°C under continuous stirring. The sulfonyl chloride compound is added and the temperature of the reaction system is controlled at -5 to 0°C. After the addition is completed, the temperature is naturally raised and the temperature is controlled at 5-10°C for stirring reaction; Step 3: After the reaction is completed, add alkaline aqueous solution, adjust the pH to 9-10, cool to -5-0°C, filter out the product after precipitation, wash and dry to obtain an off-white solid.

2. The method for preparing flonicamid according to claim 1, characterized in that: The molar ratio of the 4-trifluoromethylnicotinic acid, aminoacetonitrile salt and alkali metal alcohol salt is 1:(1-2):(2-3), and the molar amount of the alkali metal alcohol salt is the sum of the molar amounts of the 4-trifluoromethylnicotinic acid and aminoacetonitrile salt.

3. The method for preparing flonicamid according to claim 1, characterized in that: The aminoacetonitrile salt is one of aminoacetonitrile hydrochloride and aminoacetonitrile sulfate.

4. The method for preparing flonicamid according to claim 1, characterized in that: The alcohol solvent is one of methanol, ethanol and isopropanol.

5. The method for preparing flonicamid according to claim 1, characterized in that: The mass ratio of the alcohol solvent to 4-trifluoromethylnicotinic acid is 10-20:

1.

6. The method for preparing flonicamid according to claim 1, characterized in that: The alkali metal alkoxide is one of sodium methoxide, sodium ethoxide, sodium tert-butoxide and potassium tert-butoxide.

7. The method for preparing flonicamid according to claim 1, characterized in that: The aprotic solvent is one of dichloromethane, dichloroethane, acetonitrile, acetone, dimethylformamide and tetrahydrofuran.

8. The method for preparing flonicamid according to claim 1, characterized in that: The mass ratio of the aprotic solvent to 4-trifluoromethylnicotinic acid is 10 to 20:

1.

9. The method for preparing flonicamid according to claim 1, characterized in that: The sulfonyl chloride compound is one of methanesulfonyl chloride, phenylmethanesulfonyl chloride and p-toluenesulfonyl chloride.

10. The method for preparing flonicamid according to claim 1, characterized in that: The molar ratio of the sulfonyl chloride compound to 4-trifluoromethylnicotinic acid is 1-2:1.

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