Synthesis method of 2-fluoropyridine-5-formyl chloride

Abstract

The invention discloses a synthesis method of 2-fluoropyridine-5-formyl chloride, which is characterized in that 6-fluoronicotinic acid is used as a raw material, phosgene is used as an acylating chlorination reagent, and the 2-fluoropyridine-5-formyl chloride is prepared through acylating chlorination reaction. According to the synthesis method disclosed by the invention, 6-fluoronicotinic acid is taken as a raw material, phosgene is taken as an acylating chlorination reagent, and the reaction selectivity can be remarkably improved, so that acylating chlorination reaction can be carried out at normal temperature, more 6-fluoronicotinic acid can be converted into 2-fluoropyridine-5-formyl chloride, and meanwhile, generation of byproducts can be effectively inhibited; the 2-fluoropyridine-5-formyl chloride with higher quality can be obtained while the product yield is increased, the method has the advantages of simple process, convenience in operation, low cost, mild reaction conditions, high preparation efficiency, high yield, high purity, environmental friendliness and the like, and the 2-fluoropyridine-5-formyl chloride can be prepared on a large scale; the industrial application of the 2-fluoropyridine-5-formyl chloride can be conveniently realized.

Description

Technical Field

[0001] The invention belongs to the field of organic chemical industry and relates to a method for synthesizing 2-fluoropyridine-5-carbonyl chloride, and specifically relates to a method for preparing 2-fluoropyridine-5-carbonyl chloride at room temperature by using phosgene as an acyl chlorination reagent. Background Art

[0002] 2-Fluoropyridine-5-carbonyl chloride is an important chemical intermediate and has important applications in medicine and pesticides. Its main synthetic route is to use 6-fluoronicotinic acid as a raw material and chlorinate the carboxyl group in 6-fluoronicotinic acid to obtain 2-fluoropyridine-5-carbonyl chloride.

[0003] The currently reported synthesis methods of 2-fluoropyridine-5-carbonyl chloride are mainly divided into two categories according to the different chlorination reagents. One is to use thionyl chloride as the chlorination reagent, and the other is to use oxalyl chloride as the chlorination reagent.

[0004] In the existing preparation method, when oxalyl chloride is used as the chlorination reagent to prepare 2-fluoropyridine-5-carbonyl chloride, the reaction formula is as follows:

[0005]

[0006] In the existing preparation method, when 2-fluoropyridine-5-carbonyl chloride is prepared using thionyl chloride as an acyl chlorination reagent, the reaction formula is as follows:

[0007]

[0008] The inventors of the present application have found in the research process that when using acyl chloride reagents, especially oxalyl chloride, thionyl chloride and other acyl chloride reagents to prepare 2-fluoropyridine-5-carbonyl chloride, a lot of hydrogen chloride gas remains in the reaction system of the acyl chloride reaction, and its presence will cause free Cl in the reaction system to - The F on the pyridine ring can be replaced to obtain the byproduct 6-chloronicotinoyl chloride, and the byproduct content can reach 1.3%-4.0% under reflux conditions. In addition, since the byproduct and the main product have high reactivity in subsequent reactions and are difficult to separate, effectively inhibiting the byproduct and reducing the byproduct content in the product is of great significance to promote the later application of 2-fluoropyridine-5-carbonyl chloride.

[0009] Summary of the invention

[0010] The technical problem to be solved by the present invention is to overcome the deficiencies of the prior art and provide a method for synthesizing 2-fluoropyridine-5-carbonyl chloride with simple process, convenient operation, low cost, mild reaction conditions, high preparation efficiency, high yield, high purity and environmental friendliness.

[0011] In order to solve the above technical problems, the present invention adopts the following technical solutions:

[0012] A method for synthesizing 2-fluoropyridine-5-carbonyl chloride, using 6-fluoronicotinic acid as a raw material and phosgene as an acyl chlorination reagent, to prepare 2-fluoropyridine-5-carbonyl chloride through an acyl chlorination reaction, the reaction formula is as follows:

[0013]

[0014] The above-mentioned synthesis method is further improved and comprises the following steps:

[0015] Step S1, mixing 6-fluoronicotinic acid with a solvent to obtain a mixed solution;

[0016] Step S2, introducing phosgene into the mixed solution obtained in step S1 to carry out acyl chlorination reaction to obtain a reaction product liquid;

[0017] Step S3, removing phosgene and solvent from the reaction product liquid obtained in step S2 to obtain 2-fluoropyridine-5-carbonyl chloride.

[0018] The above synthesis method is further improved, in step S2, the molar ratio of 6-fluoronicotinic acid to phosgene is 1:1.2-5.0.

[0019] The above synthesis method is further improved, in step S2, the introduction rate of phosgene is 120g / h to 200g / h.

[0020] The above-mentioned synthesis method is further improved, in step S2, nitrogen is continuously introduced into the system during the acyl chlorination reaction; the nitrogen introduction rate is 0.1L / min to 0.3L / min.

[0021] The above synthesis method is further improved, in step S2, the acyl chloride reaction is carried out under stirring conditions at a rotation speed of 50r / min to 220r / min.

[0022] The above synthesis method is further improved, in step S2, the temperature of the acyl chlorination reaction is 25°C to 100°C.

[0023] The above synthesis method is further improved, in step S2, the time of the acyl chlorination reaction is 2.5h to 8h.

[0024] The above synthesis method is further improved, in step S1, the mass ratio of 6-fluoronicotinic acid to solvent is 1:1-8; the solvent is at least one of benzene, xylene, dichloromethane, 1,2-dichloroethane, chloroform, chlorobenzene, and dichlorobenzene.

[0025] The above synthesis method is further improved, in step S1, a catalyst is also added to the mixed solution; the mass ratio of the 6-fluoronicotinic acid to the catalyst is 100:0.5-3; and the catalyst is N,N-dimethylformamide.

[0026] Compared with the prior art, the advantages of the present invention are:

[0027] (1) In view of the shortcomings of low yield and low purity in the synthesis method, the present invention creatively proposes a synthesis method of 2-fluoropyridine-5-carbonyl chloride, which uses 6-fluoronicotinic acid as a raw material and phosgene as an acyl chlorination reagent, which can significantly improve the selectivity of the reaction, so that the acyl chlorination reaction can be carried out at room temperature, so that more 6-fluoronicotinic acid can be converted into 2-fluoropyridine-5-carbonyl chloride through the acyl chlorination reaction, and at the same time, the generation of by-products (such as 6-chloronicotinic acid chloride) can be effectively inhibited, and the yield of 2-fluoropyridine-5-carbonyl chloride can be further improved and the content of by-products in the product can be reduced. While improving the product yield, higher quality 2-fluoropyridine-5-carbonyl chloride can also be obtained, wherein the product content is high, calculated as 98.3% to 98.9% by mass (gas chromatography, external standard), and the yield is high, calculated as 97.0% to 99.5% based on 6-fluoronicotinic acid. The synthetic method of 2-fluoropyridine-5-carbonyl chloride provided by the invention has the advantages of simple process, convenient operation, low cost, mild reaction conditions, high preparation efficiency, high yield, high purity, environmental friendliness, etc. 2-fluoropyridine-5-carbonyl chloride can be prepared on a large scale, and the industrial application of 2-fluoropyridine-5-carbonyl chloride is realized conveniently.

[0028] (2) In the present invention, by optimizing the molar ratio of 6-fluoronicotinic acid to phosgene to 1:1.2-5.0, 6-fluoronicotinic acid can be completely converted into 2-fluoropyridine-5-carbonyl chloride to obtain the best yield. In particular, when the amount of phosgene introduced is small, the yield is low, while when the amount of phosgene introduced is too large, the yield does not change significantly, which not only leads to low phosgene utilization, but also makes tail gas recovery difficult.

[0029] (3) In the present invention, during the chlorination reaction, by optimizing the introduction rate of phosgene to 120 g / h to 200 g / h, the contact and reaction of phosgene and 6-fluoronicotinic acid can be promoted, and the yield of 2-fluoropyridine-5-carbonyl chloride can be significantly improved. At the same time, the generation of hydrogen chloride gas can be suppressed, and the hydrogen chloride gas produced in the system can be removed in time, so that the formation of by-products (6-chloronicotinyl chloride) can be further suppressed, the content of by-products in the product can be reduced, and the purity of 2-fluoropyridine-5-carbonyl chloride can be improved. Further, during the chlorination reaction, nitrogen is continuously introduced into the system, and the introduction rate of nitrogen is optimized to 0.1 L / min to 0.3 L / min, which can effectively remove the hydrogen chloride gas produced in the system in time, and at the same time, the content of phosgene taken out can be effectively reduced, while ensuring a high utilization rate of phosgene, the light hydrogen chloride in the system can be effectively removed, and the content of by-products can be significantly reduced while ensuring a high yield of 2-fluoropyridine-5-carbonyl chloride. More importantly, during the chlorination reaction, the reaction system is stirred and the stirring speed is controlled to be 50r / min~220r / min, which can increase the contact between phosgene and 6-fluoronicotinic acid, and then promote the reaction of the two, which is conducive to the generation of 2-fluoropyridine-5-carbonyl chloride, and also helps to promote the overflow of hydrogen chloride gas, and can timely remove the hydrogen chloride gas in the system, and then can avoid the production of by-products, especially, if the speed is too high, it will also increase the escape of phosgene, and then it will also reduce the utilization rate of phosgene. It can be seen that in the present invention, by optimizing the phosgene feeding speed, nitrogen feeding speed, and stirring speed, it can promote the generation of 2-fluoropyridine-5-carbonyl chloride and avoid the generation of by-products under their joint action, and finally ensure that a high-yield, high-purity 2-fluoropyridine-5-carbonyl chloride product is obtained.

[0030] (4) In the present invention, by optimizing the temperature of the chlorination reaction to 25° C. to 100° C., not only the rate of the chlorination reaction is increased, but also the occurrence of side reactions can be suppressed, which is beneficial to reducing the content of by-products and improving the purity of the product, thereby quickly preparing high-quality 2-fluoropyridine-5-carbonyl chloride products, especially when the reaction temperature is 25° C., the by-products are minimal. However, when the temperature is too high, the occurrence of side reactions will be accelerated, and by-products are easily formed, which is not conducive to improving the quality of the product.

[0031] (5) In the present invention, a catalyst is further added to the mixed solution, and the mass ratio of 6-fluoronicotinic acid to the catalyst is 100:0.5-3, and the catalyst is N,N-dimethylformamide, thereby promoting the reaction of 6-fluoronicotinic acid and phosgene, thereby improving the yield of the product and the utilization rate of the raw materials. DETAILED DESCRIPTION

[0032] The present invention is further described below in conjunction with specific preferred embodiments, but the protection scope of the present invention is not limited thereby.

[0033] In the following examples of the present invention, unless otherwise specified, the materials and instruments used are commercially available, the equipment used is conventional equipment, and the data obtained are the average values ​​of more than three repeated experiments.

[0034] Example 1

[0035] A method for synthesizing 2-fluoropyridine-5-carbonyl chloride, using 6-fluoronicotinic acid as a raw material and phosgene as an acyl chlorination reagent, to prepare 2-fluoropyridine-5-carbonyl chloride through an acyl chlorination reaction, the reaction formula is as follows:

[0036]

[0037] In this embodiment, the synthesis method of 2-fluoropyridine-5-carbonyl chloride comprises the following steps:

[0038] Step S1: Add 400.0 g (2.84 mol) of 6-fluoronicotinic acid, 2500 mL of toluene and 2.0 g of N,N-dimethylformamide into a 5000 mL four-necked flask equipped with a thermometer and a condenser, stir mechanically, mix well, and obtain a mixed solution.

[0039] Step S2, at a rotation speed of 150 r / min and a temperature of 25° C., according to the introduction rate of phosgene of 120 g / h and the molar ratio of 6-fluoronicotinic acid to phosgene of 1:1.5, phosgene is introduced into the mixed solution obtained in step S1 to carry out acyl chlorination reaction, the reaction time is 5 hours, the reaction solution becomes clear, and a reaction product solution is obtained.

[0040] Step S3, nitrogen is introduced into the reaction product liquid obtained in step S2 to remove phosgene, and then the solvent is removed by reduced pressure treatment to obtain 2-fluoropyridine-5-carbonyl chloride, wherein the content of the target product is 97.89% and the content of 6-chloronicotinoyl chloride is 1.81%.

[0041] Example 2

[0042] A method for synthesizing 2-fluoropyridine-5-carbonyl chloride, using 6-fluoronicotinic acid as a raw material and phosgene as an acyl chlorination reagent, to prepare 2-fluoropyridine-5-carbonyl chloride through an acyl chlorination reaction, the reaction formula is as follows:

[0043]

[0044] In this embodiment, the synthesis method of 2-fluoropyridine-5-carbonyl chloride comprises the following steps:

[0045] Step S1: Add 400.0 g (2.84 mol) of 6-fluoronicotinic acid, 2500 mL of toluene and 2.0 g of N,N-dimethylformamide into a 5000 mL four-necked flask equipped with a thermometer and a condenser, stir mechanically, mix well, and obtain a mixed solution.

[0046] Step S2, at a rotation speed of 150 r / min and a temperature of 25° C., according to the introduction rate of phosgene of 170 g / h and the molar ratio of 6-fluoronicotinic acid to phosgene of 1:1.5, phosgene is introduced into the mixed solution obtained in step S1 to carry out acyl chlorination reaction, and nitrogen is continuously introduced under the reaction liquid surface at a flow rate of 0.2 L / min. The reaction time is 5 hours, and the reaction liquid becomes clear to obtain a reaction product liquid.

[0047] In step S2, during the chlorination reaction, insulation measures are also taken to ensure that the reaction is carried out under low temperature conditions. At the same time, nitrogen bubbling is continuously introduced under the reaction liquid level during the chlorination reaction to take away hydrogen chloride gas. In the present embodiment, by taking insulation measures, it is possible to ensure that the reaction is carried out under low temperature conditions, the generation of by-products can be effectively avoided, and at the same time, hydrogen chloride gas is taken away by nitrogen, reducing by-products and improving product quality.

[0048] Step S3, nitrogen is introduced into the reaction product liquid obtained in step S2 to remove phosgene, and then the solvent is removed by reduced pressure treatment to obtain 2-fluoropyridine-5-carbonyl chloride.

[0049] In this example, the effects of different molar ratios of 6-fluoronicotinic acid to phosgene on product purity, yield and by-products were also investigated. Other conditions were the same as in Example 2. The results are shown in Table 1.

[0050] Table 1 Comparison of product purity, yield and by-product data under different molar ratios of 6-fluoronicotinic acid to phosgene

[0051] Molar ratio of 6-fluoronicotinic acid to phosgene Product yield (%) Product purity (%) Content of 6-chloronicotinyl chloride (%) 1∶1 70.5 77.5 0.5 1∶1.5 97.5 98.6 0.9 1∶2 97.6 98.8 0.9 1∶3 97.2 98.2 0.9 1∶5 96.8 97.8 0.8

[0052] As shown in Table 1, when the molar ratio of 6-fluoronicotinic acid to phosgene is 1:1.5-5.0, high-yield, high-purity 2-fluoropyridine-5-carbonyl chloride can be prepared, and the content of by-products is very low, which shows that by optimizing the molar ratio of 6-fluoronicotinic acid to phosgene to 1:1.2-5.0 in the present invention, 6-fluoronicotinic acid can be completely converted into 2-fluoropyridine-5-carbonyl chloride to obtain the best yield. In particular, when the amount of phosgene introduced is small, the yield is low, and when the amount of phosgene introduced is too much, the yield will not change significantly, which not only leads to low phosgene utilization, but also causes difficulty in tail gas recovery.

[0053] In this example, the effects of different acyl chloride reaction temperatures on product purity, yield and by-products were also investigated. Other conditions were the same as in Example 2. The results are shown in Table 2.

[0054] Table 2 Comparison of product purity, yield and by-product data under different acyl chloride reaction temperature conditions

[0055] Acylation reaction temperature (℃) Product yield (%) Product purity (%) Content of 6-chloronicotinyl chloride (%) 25 97.5 98.6 0.9 50 97.6 98.1 1.2 90 97.2 97.7 1.5 110 97.0 96.9 2.0

[0056] As shown in Table 2, when the temperature of the chlorination reaction is 25°C to 100°C, high-yield, high-purity 2-fluoropyridine-5-carbonyl chloride can be prepared, and the content of by-products is very low, which shows that the temperature of the chlorination reaction is 25°C to 100°C by optimizing the chlorination reaction in the present invention, not only the rate of the chlorination reaction is increased, but also the occurrence of side reactions can be suppressed, which is conducive to reducing the content of by-products and improving the purity of the product, thus quickly preparing high-quality 2-fluoropyridine-5-carbonyl chloride products, especially, when the reaction temperature is 25°C, the by-products are minimal. However, when the temperature is too high, the occurrence of side reactions can be accelerated, and by-products are easily formed, which is not conducive to improving the quality of the product.

[0057] In this example, the effects of different phosgene introduction rates on product purity, yield and by-products during the acyl chloride reaction were also investigated. Other conditions were the same as in Example 2. The results are shown in Table 3.

[0058] Table 3 Comparison of product purity, yield and by-product data under different phosgene introduction rates during acyl chloride reaction

[0059] Different phosgene introduction speed Product yield (%) Product purity (%) Content of 6-chloronicotinyl chloride (%) 100g / h 96.5 97.0 1.8 120g / h 96.8 97.3 1.5 150g / h 97.3 98.6 1.0 170g / h 97.5 98.6 0.9 200g / h 97.8 98.7 0.9

[0060] As can be seen from Table 3, when the phosgene introduction rate is 120 g / h to 200 g / h, high-yield, high-purity 2-fluoropyridine-5-carbonyl chloride can be prepared, and the content of by-products is very low. This shows that in the present invention, by optimizing the phosgene introduction rate to 120 g / h to 200 g / h, the contact and reaction of phosgene and 6-fluoronicotinic acid can be promoted, and the yield of 2-fluoropyridine-5-carbonyl chloride can be significantly improved. At the same time, the generation of hydrogen chloride gas can also be suppressed, and the hydrogen chloride gas produced in the system can be removed in time, so that the formation of by-products (6-chloronicotinyl chloride) can be further suppressed, the content of by-products in the product can be reduced, and the purity of 2-fluoropyridine-5-carbonyl chloride can be improved.

[0061] In this example, the effects of different nitrogen introduction rates on product purity, yield and by-products during the acyl chloride reaction were also investigated. Other conditions were the same as in Example 2. The results are shown in Table 4.

[0062] Table 4 Comparison of product purity, yield and by-product data under different nitrogen introduction rates during acyl chloride reaction

[0063] Different nitrogen introduction speed Product yield (%) Product purity (%) Content of 6-chloronicotinyl chloride (%) 0.1L / min 97.3 98.0 1.2 0.2L / min 97.5 98.6 0.9 0.25L / min 98.6 99.1 0.6 0.3L / min 99.0 99.1 0.5

[0064] As can be seen from Table 4, when the nitrogen introduction rate is 0.1L / min to 0.3L / min, high-yield, high-purity 2-fluoropyridine-5-carbonyl chloride can be prepared, and the content of by-products is very low, which shows that during the chlorination reaction of the present invention, by continuously introducing nitrogen into the system and optimizing the nitrogen introduction rate to 0.1L / min to 0.3L / min, the hydrogen chloride gas generated in the system can be timely and effectively taken out, and at the same time, the content of phosgene taken out can also be effectively reduced, while ensuring a high utilization rate of phosgene, the light hydrogen chloride in the system can also be effectively removed, and the content of by-products can be significantly reduced while ensuring a high yield of 2-fluoropyridine-5-carbonyl chloride.

[0065] In this example, the effects of different stirring speeds on product purity, yield and by-products during the acyl chloride reaction were also investigated. Other conditions were the same as in Example 2. The results are shown in Table 5.

[0066] Table 5 Comparison of product purity, yield and by-product data at different stirring speeds during acyl chloride reaction

[0067] Different stirring speeds Product yield (%) Product purity (%) Content of 6-chloronicotinyl chloride (%) 50r / min 97.3 97.8 1.2 100r / min 97.4 98.1 1.1 150r / min 97.5 98.6 0.9 180r / min 97.8 98.7 0.9 220r / min 97.5 98.7 0.9

[0068] It can be seen from Table 5 that when the stirring speed is 50 r / min to 220 r / min, high-yield and high-purity 2-fluoropyridine-5-carbonyl chloride can be prepared, and the content of by-products is very low. This shows that in the process of the chlorination reaction of the present invention, stirring the reaction system and controlling the stirring speed to 50 r / min to 220 r / min can increase the contact between phosgene and 6-fluoronicotinic acid, thereby promoting the reaction between the two, which is beneficial to the generation of 2-fluoropyridine-5-carbonyl chloride, and also helps to promote the overflow of hydrogen chloride gas, and can timely remove the hydrogen chloride gas in the system, thereby avoiding the production of by-products. In particular, if the rotation speed is too high, the escape of phosgene will also increase, thereby reducing the utilization rate of phosgene.

[0069] It can be seen from the results in Tables 3 to 5 that in the present invention, by optimizing the phosgene feeding rate, the nitrogen feeding rate, and the stirring rate, the generation of 2-fluoropyridine-5-carbonyl chloride can be promoted under their combined action, and the generation of by-products can be avoided, thereby ultimately ensuring the acquisition of a high-yield, high-purity 2-fluoropyridine-5-carbonyl chloride product.

[0070] It can be seen from the above results that, compared with the conventional method, the synthesis method of 2-fluoropyridine-5-carbonyl chloride of the present invention uses 6-fluoronicotinic acid as a raw material and phosgene as an acyl chlorination reagent, which can significantly improve the selectivity of the reaction, so that the acyl chlorination reaction can be carried out at normal temperature and pressure, and more 6-fluoronicotinic acid can be converted into 2-fluoropyridine-5-carbonyl chloride through the acyl chlorination reaction. At the same time, the generation of by-products (such as 6-chloronicotinic acid chloride) can be effectively inhibited, and the yield of 2-fluoropyridine-5-carbonyl chloride can be further improved and the content of by-products in the product can be reduced. While improving the product yield, higher quality 2-fluoropyridine-5-carbonyl chloride can also be obtained, wherein the product content is high, which is 98.3% to 98.9% (gas chromatography, external standard) in terms of mass content, and the yield is high, which is 97.0% to 99.5% in terms of 6-fluoronicotinic acid. The synthetic method of 2-fluoropyridine-5-carbonyl chloride provided by the invention has the advantages of simple process, convenient operation, low cost, mild reaction conditions, high preparation efficiency, high yield, high purity, environmental friendliness, etc. 2-fluoropyridine-5-carbonyl chloride can be prepared on a large scale, and the industrial application of 2-fluoropyridine-5-carbonyl chloride is realized conveniently.

[0071] The above embodiments are only preferred implementations of the present invention, and the protection scope of the present invention is not limited to the above embodiments. All technical solutions under the concept of the present invention belong to the protection scope of the present invention. It should be pointed out that for ordinary technicians in this technical field, improvements and modifications without departing from the principle of the present invention should also be regarded as the protection scope of the present invention.

Claims

1. A method for synthesizing 2-fluoropyridine-5-carbonyl chloride, characterized in that: 2-Fluoropyridine-5-carbonyl chloride is prepared by acyl chlorination reaction using 6-fluoronicotinic acid as raw material and phosgene as acyl chlorination reagent. The reaction formula is as follows:

2. The synthesis method according to claim 1, characterized in that The following steps are involved: Step S1, mixing 6-fluoronicotinic acid with a solvent to obtain a mixed solution; Step S2, introducing phosgene into the mixed solution obtained in step S1 to carry out acyl chlorination reaction to obtain a reaction product liquid; Step S3, removing phosgene and solvent from the reaction product liquid obtained in step S2 to obtain 2-fluoropyridine-5-carbonyl chloride.

3. The synthesis method according to claim 2, characterized in that In step S2, the molar ratio of 6-fluoronicotinic acid to phosgene is 1:1.2-5.

0.

4. The synthesis method according to claim 3, characterized in that In step S2, the phosgene is introduced at a rate of 120 g / h to 200 g / h.

5. The synthesis method according to claim 4, characterized in that In step S2, nitrogen is continuously introduced into the system during the acyl chlorination reaction; the nitrogen introduction rate is 0.1 L / min to 0.3 L / min.

6. The synthesis method according to claim 5, characterized in that In step S2, the acyl chloride reaction is carried out under stirring conditions at a rotation speed of 50 r / min to 220 r / min.

7. The synthesis method according to any one of claims 2 to 6, characterized in that In step S2, the temperature of the acyl chlorination reaction is 25°C to 100°C.

8. The synthesis method according to claim 7, characterized in that In step S2, the acyl chlorination reaction time is 2.5h to 8h.

9. The synthesis method according to any one of claims 2 to 6, characterized in that In step S1, the mass ratio of 6-fluoronicotinic acid to solvent is 1:1-8; the solvent is at least one of benzene, xylene, dichloromethane, 1,2-dichloroethane, chloroform, chlorobenzene, and dichlorobenzene.

10. The synthesis method according to claim 9, characterized in that In step S1, a catalyst is further added to the mixed solution; the mass ratio of the 6-fluoronicotinic acid to the catalyst is 100:0.5-3; and the catalyst is N,N-dimethylformamide.

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