A kind of preparation method of 4-trifluoromethylnicotinic acid

Abstract

The present invention relates to the technical field of pesticide intermediate synthesis, and in particular to a method for preparing 4-trifluoromethylnicotinic acid, comprising the following steps: S1, 3-cyano-2,6-dichloro-4-trifluoromethylpyridine reacts with alkali solution to obtain 2,6-dichloro-4-trifluoromethylnicotinic acid salt aqueous solution; S2, 2,6-dichloro-4-trifluoromethylnicotinic acid salt aqueous solution is acidified after electrolytic dechlorination under direct current, and the three wastes are greatly reduced while the process simplicity and safety of the present invention are improved, and the electrolytic dechlorination reduction is used instead of the traditional precious metal catalytic hydrogenation dechlorination process, and the raw material cost is greatly reduced. The two-step yield of 4-trifluoromethylnicotinic acid synthesized by the present invention is>97%, which is more than 10% higher than the traditional process, and the raw material cost is significantly reduced.

Description

Technical Field

[0001] The invention relates to the technical field of pesticide intermediate synthesis, and in particular to a method for preparing 4-trifluoromethylnicotinic acid. Background Art

[0002] Flunic acid amide is a pyridine amide insecticide discovered by Ishihara Sangyo Co., Ltd. of Japan. Flunic acid amide has strong neurotoxicity and rapid antifeedant effect. Its mechanism of action is unique, which is different from high-efficiency insecticides such as neonicotinoids and pymetrozine. It has extremely high biological activity and can be used to control aphids and other piercing-sucking mouthparts pests on a wide range of crops. It can also control pests that are resistant to conventional insecticides. As the resistance problem of nicotinoid insecticides and konkuan becomes more serious, the bee venom problem has pushed neonicotinoid insecticides to the forefront of controversy. Many countries and regions around the world have banned or restricted the use of neonicotinoid insecticides. Flunic acid amide is low in toxicity to bees and has no cross-resistance with neonicotinoid insecticides. Due to its good safety for crops, humans, livestock and the environment, it has a good development prospect.

[0003] 4-Trifluoromethylnicotinic acid is one of the important intermediates for the synthesis of flonicamid. In the prior art, there are two main industrial synthesis routes for 4-trifluoromethylnicotinic acid:

[0004] Route 1: Using vinyl ethyl ether and trifluoroacetic acid as starting materials, 4-trifluoromethylnicotinic acid is synthesized through 5 steps of reaction. The chemical reaction equation is as follows:

[0005]

[0006] Route 2: Using ethyl trifluoroacetoacetate and cyanoacetamide as starting materials, 4-trifluoromethylnicotinic acid is synthesized through a four-step reaction.

[0007]

[0008] Because Route 2 has easier access to raw materials than Route 1, has fewer synthesis steps, and has lower production costs, it is currently the preferred route for the industrial synthesis of 4-trifluoromethylnicotinic acid.

[0009] In route 2, 4-trifluoromethylnicotinic acid is synthesized using 3-cyano-2,6-dichloro-4-trifluoromethylpyridine as raw material, and research on its synthesis process has become the focus.

[0010]

[0011] At present, the traditional method for synthesizing 4-trifluoromethylnicotinic acid according to the above route is to dissolve 3-cyano-2,6-dichloro-4-trifluoromethylpyridine in an organic solvent and add activated carbon for refining, filter the activated carbon, add an acid-binding agent to the filtrate, and then use palladium carbon as a catalyst for hydrogenation reduction and dechlorination, then filter the palladium carbon and filtrate for desolventizing, and then evaporate 3-cyano-4-trifluoromethylpyridine for refining, and finally alkaline hydrolysis and acidification to obtain 4-trifluoromethylnicotinic acid, and the operation process is complicated. Since the reduction process uses expensive palladium carbon, palladium carbon is easily poisoned during use, the recovery rate is low, and the production cost is high. At the same time, the reaction process uses organic solvents, activated carbon, acid-binding agents, etc., resulting in more three wastes. According to the journal "Synthesis Process of 4-Trifluoromethylnicotinic Acid" published by Mao Qikun of Nanjing University of Science and Technology, the two-step yield of the traditional process of route 2 is only 83.8%, which is low, but it is the highest process level reported in the literature.

[0012] Therefore, how to develop a method for synthesizing 4-trifluoromethylnicotinic acid with simple process operation, less three wastes, low cost and high yield becomes a problem to be solved urgently. Summary of the invention

[0013] Aiming at the problems of complex synthesis process, more three wastes, high cost and low yield of 4-trifluoromethylnicotinic acid in the prior art, the present invention provides a preparation method of 4-trifluoromethylnicotinic acid, which has the advantages of simple process, less three wastes, low cost and high yield.

[0014] The present invention provides a method for preparing 4-trifluoromethylnicotinic acid, comprising the following steps:

[0015] S1, 3-cyano-2,6-dichloro-4-trifluoromethylpyridine reacts with alkali solution to prepare 2,6-dichloro-4-trifluoromethyl nicotinate aqueous solution;

[0016] S2, 2,6-dichloro-4-trifluoromethylnicotinate aqueous solution is electrolytically dechlorinated under direct current and then acidified to obtain.

[0017] Furthermore, the alkali solution is a sodium hydroxide solution, and the mass concentration of the alkali solution is 5% to 15%.

[0018] Furthermore, the molar ratio of 3-cyano-2,6-dichloro-4-trifluoromethylpyridine to sodium hydroxide is 1:1-3.

[0019] Furthermore, in step S1, the process conditions for the reaction of 3-cyano-2,6-dichloro-4-trifluoromethylpyridine with alkali solution are as follows: the reaction temperature is 90-95° C., and the reaction is completed when the content of 3-cyano-2,6-dichloro-4-trifluoromethylpyridine in the system is ≤0.5%.

[0020] Furthermore, the electrolysis is carried out in an electrolysis device, which includes an electrolytic cell, a DC power supply, a cathode, and an anode.

[0021] Furthermore, a diaphragm is provided in the electrolytic cell.

[0022] Furthermore, the cathode is a Rh / Ni or Pd / Ni composite electrode, and the anode is a Pt or graphite electrode.

[0023] Furthermore, the membrane is a Nafion 117 proton exchange membrane.

[0024] Furthermore, the process conditions of electrolysis are as follows: the electrolysis reaction temperature is 10~50°C and the electrolysis voltage is 5~30V.

[0025] Furthermore, in step S2, the acid used for acidification is hydrochloric acid.

[0026] The synthetic reaction route of the present invention is as follows:

[0027] .

[0028] The invention firstly alkaline hydrolyzes 3-cyano-2,6-dichloro-4-trifluoromethylpyridine into a sodium salt aqueous solution, then directly electrolyzes and reduces the chlorine, and then acidifies to directly obtain 4-trifluoromethylnicotinic acid.

[0029] The electrolysis reaction occurs at the cathode as follows (taking the Rh / Ni composite electrode as the cathode as an example):

[0030] .

[0031] The beneficial effects of the present invention are:

[0032] (1) The present invention applies electrochemical reduction to the synthesis of 4-trifluoromethylnicotinic acid, which greatly simplifies the synthesis steps compared with the traditional process and avoids the operations of raw material refining, catalyst filtration, catalyst recovery, organic solvent desolventizing, intermediate refining, etc. in the traditional process;

[0033] (2) The present invention adopts a three-step "one-pot method" of alkaline hydrolysis, electrolysis and acidification. Water is used as the solvent in the reaction process to replace the organic solvent used in the traditional process. No activated carbon refining is required. While the process safety is improved, the amount of three wastes is greatly reduced;

[0034] (3) The present invention adopts electrolytic dechlorination reduction instead of the traditional noble metal catalytic hydrogenation dechlorination process, which greatly reduces the cost of raw materials;

[0035] (4) The two-step yield of 4-trifluoromethylnicotinic acid synthesized by the present invention is greater than 97%, which is more than 10% higher than that of the traditional process, and the raw material cost is significantly reduced. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, for ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0037] Figure 1 It is a schematic structural diagram of an electrolysis device according to a specific embodiment of the present invention.

[0038] Figure 2 This is the liquid phase spectrum of 4-trifluoromethylnicotinic acid synthesized in Example 2 of the present invention.

[0039] In the figure: 1-DC power supply, 2-cathode, 3-electrolyzer, 4-diaphragm, 5-anode. DETAILED DESCRIPTION

[0040] In order to enable those skilled in the art to better understand the technical solutions in the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings 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 should fall within the scope of protection of the present invention.

[0041] Examples 1-3 Electrolysis was carried out in an electrolysis device, such as Figure 1 The electrolysis device includes an electrolytic cell 3, a DC power supply 1, a cathode 2, and an anode 5. A diaphragm 4 is provided in the electrolytic cell 3, and the diaphragm 4 is a Nafion117 proton exchange membrane.

[0042] Example 1

[0043] A method for preparing 4-trifluoromethylnicotinic acid specifically comprises the following steps:

[0044] (1) Add 241g of 3-cyano-2,6-chloro-4-trifluoromethylpyridine and 1200g of 5% sodium hydroxide solution into a four-necked bottle, react at 90-95°C for 7h, take a sample and HPLC reaction tracking, and the content of 3-cyano-2,6-chloro-4-trifluoromethylpyridine is ≤0.5%, which is qualified. After the reaction is qualified, cool the 2,6-dichloro-4-trifluoromethylnicotinic acid sodium salt aqueous solution to 30-32°C for use;

[0045] (2) Pour the prepared 2,6-dichloro-4-trifluoromethylnicotinic acid sodium salt aqueous solution into an electrolytic cell, wherein the anode of the electrolytic cell is a Pt electrode and the cathode is a Rh / Ni composite electrode, turn on the magnetic stirring, connect the direct current, control the voltage at 10 V, control the electrolysis temperature at 30-32 °C, take samples for HPLC tracking, and the content of 2,6-chloro-4-trifluoromethylnicotinic acid is ≤0.5%, which is qualified.

[0046] (3) After the electrolysis reaction is qualified, the 4-trifluoromethylnicotinic acid sodium salt aqueous solution is transferred to a four-necked bottle, cooled to 0-5°C, and 30% hydrochloric acid is added dropwise for acidification. The pH value is tested to be 2-3. After the acidification is completed, the solution is kept at 0-5°C for 1 hour and then filtered and dried to obtain 184.1 g of 4-trifluoromethylnicotinic acid. The HPLC test showed that the content was 99.3% and the yield was 97.5%.

[0047] According to the above method, different cathode materials were selected, and the cathode materials were Pt, Ni, Rh, Cu, Pd / Ni and Rh / Ni, respectively, and the electrolytic cells all used Pt electrodes as anodes. Electrolysis was performed under the same voltage, electrolysis temperature and other conditions as the above method, and the optimal synthesis effect was obtained. The specific results are shown in Table 1.

[0048] Table 1 Synthesis results of 4-trifluoromethylnicotinic acid under different cathode materials

[0049]

[0050] It can be seen that the cathode material of the present invention uses Pd / Ni or Rh / Ni composite electrode with better synthesis effect.

[0051] Example 2

[0052] A method for preparing 4-trifluoromethylnicotinic acid specifically comprises the following steps:

[0053] (1) Add 241g of 3-cyano-2,6-chloro-4-trifluoromethylpyridine and 800g of 10% sodium hydroxide solution into a four-necked bottle, react at 90-95°C for 6h, take a sample and HPLC reaction tracking, and the content of 3-cyano-2,6-chloro-4-trifluoromethylpyridine is ≤0.5%, which is qualified. After the reaction is qualified, cool the 2,6-dichloro-4-trifluoromethylnicotinic acid sodium salt aqueous solution to 33-35°C for use;

[0054] (2) Pour the prepared 2,6-dichloro-4-trifluoromethylnicotinic acid sodium salt aqueous solution into an electrolytic cell, wherein the anode of the electrolytic cell is a graphite electrode and the cathode is a Rh / Ni composite electrode. Turn on the magnetic stirring, connect the direct current, control the voltage at 15 V, control the electrolysis temperature at 33-35 °C, power on for 4 hours, take samples for HPLC tracking, and the content of 2,6-chloro-4-trifluoromethylnicotinic acid is ≤0.5%, which is qualified.

[0055] (3) After the electrolysis reaction is qualified, the 4-trifluoromethylnicotinic acid sodium salt aqueous solution is transferred to a four-necked bottle, cooled to 0-5°C, and 30% hydrochloric acid is added dropwise for acidification. The pH value is tested to be 2-3. After the acidification is completed, the solution is kept at 0-5°C for 1 hour and then filtered and dried to obtain 186.9 g of 4-trifluoromethylnicotinic acid. The HPLC test showed that the content was 99.4% and the yield was 97.2%. Figure 2 The liquid phase spectrum of synthesized 4-trifluoromethylnicotinic acid is shown.

[0056] Example 3

[0057] A method for preparing 4-trifluoromethylnicotinic acid specifically comprises the following steps:

[0058] (1) Add 241g of 3-cyano-2,6-chloro-4-trifluoromethylpyridine and 800g of 15% sodium hydroxide solution into a four-necked bottle, react at 90-95°C for 5h, take a sample and HPLC reaction tracking, and the content of 3-cyano-2,6-chloro-4-trifluoromethylpyridine is ≤0.5%, which is qualified. After the reaction is qualified, cool the 2,6-dichloro-4-trifluoromethylnicotinic acid sodium salt aqueous solution to 36-40°C for use;

[0059] (2) Pour the prepared 2,6-dichloro-4-trifluoromethylnicotinic acid sodium salt aqueous solution into an electrolytic cell, wherein the anode of the electrolytic cell is a Pt electrode and the cathode is a Rh / Ni composite electrode. Turn on the magnetic stirring, connect the direct current, control the voltage at 30 V, control the electrolysis temperature at 36-40 ° C, power on for 3 hours, take samples for HPLC tracking, and the content of 2,6-chloro-4-trifluoromethylnicotinic acid is ≤0.5%, which is qualified.

[0060] (3) After the electrolysis reaction is qualified, the 4-trifluoromethylnicotinic acid sodium salt aqueous solution is transferred to a four-necked bottle, cooled to 0-5°C, and 30% hydrochloric acid is added dropwise for acidification. The pH value is tested to be 2-3. After the acidification is completed, the solution is kept at 0-5°C for 1 hour and then filtered and dried to obtain 188.2 g of 4-trifluoromethylnicotinic acid. The HPLC test showed that the content was 99.0% and the yield was 97.5%.

[0061] Comparative Example 1

[0062] A method for preparing 4-trifluoromethylnicotinic acid specifically comprises the following steps:

[0063] (1) Add 241g of 3-cyano-2,6-chloro-4-trifluoromethylpyridine and 800g of 15% sodium hydroxide solution into a four-necked bottle and react at 90-95°C for 5h. Sample HPLC reaction tracking: 3-cyano-2,6-chloro-4-trifluoromethylpyridine content ≤ 0.5% is acceptable.

[0064] (2) After the reaction is qualified, cool to 50~55℃, add 5g activated carbon for refining, keep warm at 50~55℃ for 0.5h, filter after the insulation is completed, transfer the filtrate into a four-necked bottle, cool to 10~15℃, add 12.05g 5% palladium carbon, and introduce hydrogen at a slight positive pressure to react. After introducing hydrogen for 5h, sample HPLC tracking 2,6-chloro-4-trifluoromethylnicotinic acid content ≤0.5% qualified. After the reaction is completed, filter the palladium carbon catalyst to obtain 4-trifluoromethylnicotinic acid sodium salt filtrate.

[0065] (3) The filtrate of 4-trifluoromethylnicotinic acid sodium salt was transferred to a four-necked bottle, cooled to 0-5°C, and 365 g of 30% hydrochloric acid was added dropwise to acidify. The pH value was tested to be 2-3. After acidification, the mixture was kept at 0-5°C for 1 hour and then filtered and dried to obtain 164.7 g of 4-trifluoromethylnicotinic acid. The HPLC test showed that the content was 98.8% and the yield was 85.2%.

[0066] From the comparison between the embodiment and comparative example 1, it can be seen that the yield improvement rate of 4-trifluoromethylnicotinic acid prepared by the present invention is greater than 10%.

[0067] Although the present invention has been described in detail with reference to the accompanying drawings and in combination with the preferred embodiments, the present invention is not limited thereto. Without departing from the spirit and essence of the present invention, a person of ordinary skill in the art may make various equivalent modifications or substitutions to the embodiments of the present invention, and these modifications or substitutions shall be within the scope of the present invention. Any person of ordinary skill in the art may easily think of changes or substitutions within the technical scope disclosed by the present invention, and these shall be within the scope of protection of the present invention.

Claims

1. A method for preparing 4-trifluoromethylnicotinic acid, characterized in that: The steps include: S1, 3-cyano-2,6-dichloro-4-trifluoromethylpyridine reacts with alkali solution to prepare 2,6-dichloro-4-trifluoromethyl nicotinate aqueous solution; S2, 2,6-dichloro-4-trifluoromethylnicotinic acid aqueous solution is electrolytically dechlorinated under direct current and then acidified to obtain 4-trifluoromethylnicotinic acid; The electrolysis is carried out in an electrolysis device, which includes an electrolytic cell, a DC power supply, a cathode, and an anode; The cathode is a Rh / Ni or Pd / Ni composite electrode, the anode is a Pt or graphite electrode; a diaphragm is provided in the electrolytic cell; The process conditions of electrolysis are as follows: the electrolysis reaction temperature is 10~50℃ and the electrolysis voltage is 5~30V.

2. The method for preparing 4-trifluoromethylnicotinic acid according to claim 1, characterized in that: The alkali solution is a sodium hydroxide solution, and the mass concentration of the alkali solution is 5%~15%.

3. The method for preparing 4-trifluoromethylnicotinic acid according to claim 2, characterized in that: The feeding molar ratio of 3-cyano-2,6-dichloro-4-trifluoromethylpyridine to sodium hydroxide is 1:1-3.

4. The method for preparing 4-trifluoromethylnicotinic acid according to claim 1, characterized in that: In step S1, the process conditions for the reaction of 3-cyano-2,6-dichloro-4-trifluoromethylpyridine with alkali solution are: the reaction temperature is 90-95° C., and the reaction is completed when the content of 3-cyano-2,6-dichloro-4-trifluoromethylpyridine in the system is ≤0.5%.

5. The method for preparing 4-trifluoromethylnicotinic acid according to claim 1, characterized in that: The diaphragm is Nafion117 proton exchange membrane.

6. The method for preparing 4-trifluoromethylnicotinic acid according to claim 1, characterized in that: In step S2, the acid used for acidification is hydrochloric acid.

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