Synthesis method of 2, 3, 5-trichloropyridine

Abstract

The invention discloses a synthesis method of 2, 3, 5-trichloropyridine, which comprises the following steps: by taking 2, 3, 5, 6-tetrachloropyridine as an initial raw material, triethylamine as an acid-binding agent and isopropanol as a solvent, carrying out nucleophilic substitution reaction to generate an intermediate 2, 3, 5-trichloro-6-hydrazinopyridine; according to the method, 2, 3, 5-trichloropyridine is synthesized through an oxidation reaction by taking water as a solvent and taking ammonium persulfate or sodium persulfate as an oxidizing agent for oxidizing and removing hydrazine groups. The yield of 2, 3, 5-trichloropyridine at normal pressure and low temperature is about 95%, the purity of 2, 3, 5-trichloropyridine at normal pressure and low temperature is more than 99.5%, a traditional high-risk oxidizing agent is replaced, the oxidation process is milder, oxidation can be completed at low temperature in a short time, the reaction process is simple, the yield and the purity are high, and industrialization is easy; the preparation process is green and environment-friendly, and the problems of consumption of a large amount of hydrogen peroxide and sodium hypochlorite aqueous solution and large wastewater generation amount are effectively avoided.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of organic synthesis and chemical engineering, and particularly relates to a synthesis method of 2,3,5-trichloropyridine. BACKGROUND

[0002] 2,3,5-trichloropyridine is an important fine chemical intermediate, which can be used to synthesize 3,5-dichloro-2-ethoxy ether pyridine, oxydeem, oxabetrinil and other pesticide products. In the existing synthesis process of 2,3,5-trichloropyridine, it is mainly divided into one-step method and two-step method, but there are certain defects in general. For example, by one-step synthesis method, in the Chinese patent with publication number CN110551062A, Pd / C is used to hydrogenate 2,3,5,6-tetrachloropyridine to prepare 2,3,5-trichloropyridine, but the process involves high temperature and high pressure and hydrogenation, which needs to be equipped with a high-pressure reaction kettle for production, and the equipment requirement is high; in the Chinese patent with publication number CN111909080A, zinc powder is used to reduce 2,3,4,5-tetrachloropyridine to prepare 2,3,5-trichloropyridine, but there are defects such as high cost of zinc powder, heavy pollution and low efficiency; in the Chinese patent with publication number CN107815702A, 2,3,5,6-tetrachloropyridine is used as a starting material, and 2,3,5-trichloropyridine is synthesized by electrolytic reaction in a weak alkaline solution, but the yield is only 60%, and the selectivity of 2,3,5-trichloropyridine is only about 80%.

[0003] And by two-step synthesis method, in the Chinese patent with publication number CN108912043A, in the first step, hydrazine hydrate and 2,3,5,6-tetrachloropyridine are subjected to nucleophilic substitution reaction to prepare intermediate 2,3,5-trichloro-6-hydrazinylpyridine, there are problems of long reaction time and incomplete reaction of raw materials, and in the second step, a large amount of low-content sodium hypochlorite aqueous solution needs to be added in the process of removing hydrazine group by oxidation reaction, which causes large amount of wastewater, high cost and difficulty in wastewater treatment; in the Chinese patent with publication number CN108358835A, two-step reaction continuous feeding method is adopted, but the reaction conditions of the process are complex, especially the second step uses two immiscible solvents, and a phase transfer catalyst needs to be added to promote the normal progress of the reaction, which has large process control difficulty, complex and difficult post-treatment, high energy consumption and large environmental pollution. Therefore, it is urgent to develop a new synthesis process of 2,3,5-trichloropyridine with simple reaction conditions and process control, and green environmental protection. SUMMARY

[0004] In order to solve the defects in the prior art, the application provides a synthesis method of 2,3,5-trichloropyridine.

[0005] In order to solve the above technical problems, the application provides the following technical scheme:

[0006] This invention provides a method for synthesizing 2,3,5-trichloropyridine, the synthetic route of which is shown below:

[0007] ;

[0008] Specifically, the following steps are included:

[0009] S1. Using 2,3,5,6-tetrachloropyridine as the starting material, triethylamine as the acid-binding agent, and isopropanol as the solvent, a nucleophilic substitution reaction is carried out to generate the intermediate 2,3,5-trichloro-6-hydrazinopyridine hydrate.

[0010] S2. Using water as a solvent, ammonium persulfate or sodium persulfate as the oxidant for hydrazine oxidation removal, and adding a pH adjuster, 2,3,5-trichloropyridine is synthesized through an oxidation reaction.

[0011] Preferably, in step S1, the amount of triethylamine added is 0.5 to 2 equivalents, and the amount of isopropanol added is 3 to 6 volumes.

[0012] Preferably, in step S1, the reaction temperature is 75~83 ℃ and the reaction time is 1~2 h.

[0013] Preferably, in step S2, the molar ratio of the oxidant to the intermediate 2,3,5-trichloro-6-hydrazinopyridine hydrate is 1:1 to 1:2.

[0014] Preferably, in step S2, the oxidation reaction is carried out at a temperature of 20-40 °C for 30-60 min.

[0015] Preferably, in step S2, sodium citrate, sodium phosphate, sodium lactate, and sodium acetate are used as pH adjusters in the oxidation reaction.

[0016] Preferably, in step S2, the amounts of sodium citrate, sodium phosphate, sodium lactate, and sodium acetate are 1 to 3 equivalents.

[0017] Compared with the prior art, the present invention has the following beneficial effects:

[0018] The present invention uses isopropanol as a solvent to significantly improve the solubility of the raw material 2,3,5,6-tetrachloropyridine, making the reaction system more homogeneous and significantly increasing the reaction rate.

[0019] This invention uses triethylamine as an acid-binding agent, which has better compatibility with solvents. Compared with solid inorganic substances as acid-binding agents, it is easier to form hydrochloride with HCl generated in the first step of the reaction, promoting the reaction to proceed in the forward direction and improving the conversion rate of raw materials and the purity of intermediate products.

[0020] This invention uses ammonium persulfate or sodium persulfate as an oxidant, which significantly reduces the amount of oxidant added in traditional processes. The oxidation process is gentler and can be completed at low temperature and in a short time to obtain high-purity 2,3,5-trichloropyridine. Simultaneously, compared to using hydrogen peroxide or sodium hypochlorite aqueous solution as an oxidant, it can effectively reduce wastewater generation by 60%.

[0021] The second step of this invention uses water as a solvent, eliminating the need for dual solvents and phase transfer catalysts, thus reducing the difficulty of post-processing.

[0022] The reaction process of this invention is simple, with high yield and purity, and is easy to industrialize; the preparation process is green and environmentally friendly, and effectively avoids the problems of large consumption of hydrogen peroxide and sodium hypochlorite aqueous solution and large amount of wastewater generation. Attached Figure Description

[0023] Figure 1 This is an HPLC chromatogram of 2,3,5-trichloropyridine synthesized in Example 2 of this invention. Detailed Implementation

[0024] The preferred embodiments of the present invention will be described below with reference to the accompanying drawings. It should be understood that the preferred embodiments described herein are for illustration and explanation only and are not intended to limit the present invention.

[0025] Example 1

[0026] Step 1: Preparation of 2,3,5-trichloro-6-hydrazinopyridine hydrate.

[0027] 20 g of 2,3,5,6-tetrachloropyridine, 100 mL of isopropanol, and 11.2 g of triethylamine were added to a 250 mL reaction flask. The mixture was refluxed at 75 °C for 2 hours. After filtration, washing with water, and drying, 19.2 g of 2,3,5-trichloro-6-hydrazinopyridine hydrate with a purity of 99.8% and a yield of 98% was obtained.

[0028] Step 2: Preparation of 2,3,5-trichloropyridine.

[0029] 19.2 g of the product from the first step was added to 100 mL of deionized water and 7.4 g of sodium acetate, followed by the addition of 10.7 g of sodium persulfate. The mixture was heated to 40 °C and reacted for 30 minutes. After the reaction was complete, 60 mL x 2 dichloromethane was added, and the phases were separated to obtain an organic layer. The organic layers were combined and washed once with 50 mL of deionized water. Distillation yielded 16 g of the product 2,3,5-trichloropyridine, with a yield of 95.1% and a purity of 99.5%.

[0030] Example 2

[0031] Step 1: Preparation of 2,3,5-trichloro-6-hydrazinopyridine hydrate according to the method in Example 1.

[0032] Step 2: Preparation of 2,3,5-trichloropyridine.

[0033] 19.2 g of the product from the first step was added to 100 mL of deionized water and 7.4 g of sodium acetate, followed by the addition of 10.3 g of ammonium persulfate. The mixture was heated to 35 °C and reacted for 60 minutes. After the reaction was complete, 60 mL x 2 dichloromethane was added, and the phases were separated to obtain an organic layer. The combined organic layers were washed once with 50 mL of deionized water, and distilled to obtain 16.2 g of the product 2,3,5-trichloropyridine, with a yield of 96.3% and a purity of 99.6%. The HPLC chromatogram of the synthesized 2,3,5-trichloropyridine is shown below. Figure 1 As shown.

[0034] Example 3

[0035] Step 1: Preparation of 2,3,5-trichloro-6-hydrazinopyridine hydrate.

[0036] 20 g of 2,3,5,6-tetrachloropyridine, 150 mL of isopropanol, and 11.2 g of triethylamine were added to a 250 mL reaction flask. The mixture was refluxed at 75 °C for 2 hours. After filtration, washing with water, and drying, 18.6 g of 2,3,5-trichloro-6-hydrazinopyridine hydrate with a purity of 99.9% and a yield of 95% was obtained.

[0037] Step 2: Preparation of 2,3,5-trichloropyridine.

[0038] 18.6 g of the product from the first step was added to 100 mL of deionized water and 7.2 g of sodium acetate, followed by the addition of 10 g of sodium persulfate. The mixture was heated to 45 °C and reacted for 30 minutes. After the reaction was complete, 60 mL x 2 dichloromethane was added, and the phases were separated to obtain an organic layer. The organic layers were combined and washed once with 50 mL of deionized water. Distillation yielded 15.7 g of the product 2,3,5-trichloropyridine, with a yield of 93.6% and a purity of 99.8%.

[0039] Example 4

[0040] Step 1: Preparation of 2,3,5-trichloro-6-hydrazinopyridine hydrate.

[0041] 20 g of 2,3,5,6-tetrachloropyridine, 100 mL of isopropanol, and 13.1 g of triethylamine were added to a 250 mL reaction flask. The mixture was refluxed at 75 °C for 2 hours. After filtration, washing with water, and drying, 18.2 g of 2,3,5-trichloro-6-hydrazinopyridine hydrate with a purity of 99.4% and a yield of 93% was obtained.

[0042] Step 2: Preparation of 2,3,5-trichloropyridine.

[0043] 18.2 g of the product from the first step was added to 100 mL of deionized water and 7.2 g of sodium acetate, followed by 9.8 g of sodium persulfate. The mixture was heated to 45 °C and reacted for 60 minutes. After the reaction was complete, 60 mL x 2 dichloromethane was added, and the phases were separated to obtain an organic layer. The organic layers were combined and washed once with 50 mL of deionized water. Distillation yielded 15.4 g of the product 2,3,5-trichloropyridine, with a yield of 91.8% and a purity of 99.4%.

[0044] Finally, it should be noted that the above descriptions are merely preferred embodiments of the present invention and are not intended to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for synthesizing 2,3,5-trichloropyridine, characterized in that, The synthetic route is shown below: ； Specifically, the following steps are included: S1. Using 2,3,5,6-tetrachloropyridine as the starting material, triethylamine as the acid-binding agent, and isopropanol as the solvent, a nucleophilic substitution reaction is carried out to generate the intermediate 2,3,5-trichloro-6-hydrazinopyridine hydrate. S2. Using water as a solvent, ammonium persulfate or sodium persulfate as the oxidant for hydrazine oxidation removal, and adding a pH adjuster, 2,3,5-trichloropyridine is synthesized through an oxidation reaction.

2. The method for synthesizing 2,3,5-trichloropyridine according to claim 1, characterized in that, In step S1, the amount of triethylamine added is 0.5 to 2 equivalents, and the amount of isopropanol added is 3 to 6 volumes.

3. The method for synthesizing 2,3,5-trichloropyridine according to claim 1, characterized in that, In step S1, the reaction temperature is 75~83 ℃ and the reaction time is 1~2 h.

4. The method for synthesizing 2,3,5-trichloropyridine according to claim 1, characterized in that, In step S2, the molar ratio of the oxidant to the intermediate 2,3,5-trichloro-6-hydrazinopyridine hydrate is 1:1 to 1:

2.

5. The method for synthesizing 2,3,5-trichloropyridine according to claim 1, characterized in that, In step S2, the oxidation reaction is carried out at a temperature of 20-40 °C for 30-60 min.

6. The method for synthesizing 2,3,5-trichloropyridine according to claim 1, characterized in that, In step S2, sodium citrate, sodium phosphate, sodium lactate, and sodium acetate are used as pH adjusters in the oxidation reaction.

7. The method for synthesizing 2,3,5-trichloropyridine according to claim 1, characterized in that, In step S2, the amounts of sodium citrate, sodium phosphate, sodium lactate, and sodium acetate are 1 to 3 equivalents.

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