Preparation method of 2, 3, 5-trichloropyridine

Abstract

The invention relates to the technical field of synthesis of chlorine-containing pyridine intermediates, and discloses a preparation method of 2, 3, 5-trichloropyridine, which comprises the following steps: S1, adding raw materials 2, 3, 4, 5-tetrachloropyridine, an acid-binding agent, a metal catalyst and a solvent into a high-pressure reaction kettle; s2, replacing the reaction kettle with nitrogen and hydrogen in sequence, and removing impurity gas in the kettle; s3, introducing hydrogen into the reaction kettle, then raising the reaction temperature to 90-150 DEG C, and starting the reaction; s4, after the reaction is completed, cooling a reaction system to room temperature, and filtering reaction liquid to recover the metal catalyst; and separating out the solvent from the filtered filtrate to obtain a 2, 3, 5-trichloropyridine crude product, and rectifying to obtain the high-purity 2, 3, 5-trichloropyridine. According to the method, the bottleneck of poor selectivity of the traditional process is broken through, 4-bit directional dechlorination of 2, 3, 4, 5-tetrachloropyridine is realized through the synergistic effect of the metal catalyst and the acid-binding agent, byproducts are extremely few, and the raw material conversion rate is greater than or equal to 80%.

Description

Technical Field

[0001] This invention relates to the field of chloropyridine intermediate synthesis technology, specifically to a method for preparing 2,3,5-trichloropyridine. Background Technology

[0002] 2,3,5-Trichloropyridine is a pale yellow solid and an important intermediate in the synthesis of chlorinated pyridines, widely used in the synthesis of pesticides (such as insecticides and herbicides), pharmaceuticals, and fine chemicals. For example, 2,3,5-trichloropyridine reacts with alkali metal hydroxides to prepare 3,5-dichloro-2-pyridinephenol, an important raw material for the synthesis of acaricides and herbicides such as oxadiazon. 2,3,5-Trichloropyridine can also be further fluorinated to synthesize 2,3-difluoro-5-chloropyridine, the basic raw material for the synthesis of the herbicide clodinafop-propargyl. The core of the synthesis of 2,3,5-trichloropyridine lies in the "selective introduction of chlorine atoms" and the "control of the substitution positions of the pyridine ring." Currently, the mainstream synthetic routes include chloropyridine derivatization chlorination, cyclization synthesis, and aminopyridine conversion. Among them, the 2,5-dichloropyridine chlorination method has become the mainstream process due to its low raw material cost and high yield. This method uses 2,5-dichloropyridine as raw material and introduces a chlorine atom at the 3-position through selective chlorination. The key depends on the catalyst and temperature control to improve the chlorination selectivity at the 3-position.

[0003] However, existing technologies have significant drawbacks: on the one hand, the chlorination process for 2,5-dichloropyridine exhibits poor selectivity and easily generates chlorinated byproducts at the 4- or 6-position, leading to increased difficulty in product purification and waste of raw materials; on the other hand, traditional catalytic hydrogenation methods (such as palladium catalytic hydrogenation) have extremely low selectivity, with the vast majority of the product being converted to 3,4,5-trichloropyridine, while rhodium catalytic hydrogenation suffers from both low conversion rate and low selectivity, with most raw materials failing to react. Furthermore, some processes may generate waste salts, resulting in insufficient environmental friendliness and failing to meet the current fine chemical industry's demand for efficient, low-by-product, and environmentally friendly production. Summary of the Invention

[0004] The present invention aims to provide a method for preparing 2,3,5-trichloropyridine, in order to solve the problems of high reaction temperature and numerous by-products in the synthesis of 2,3,5-trichloropyridine in the prior art.

[0005] To achieve the above objectives, the present invention adopts the following technical solution: a method for preparing 2,3,5-trichloropyridine, using 2,3,4,5-tetrachloropyridine as raw material, selectively hydrogenating it under the action of a metal catalyst and an acid-binding agent, wherein the metal catalyst is an elemental metal such as nickel, ruthenium, zinc, iron, platinum, or gold, or a metal supported on a support, and the metal catalyst is one metal or a mixture of several metals. Preferably, as an improvement, the method for preparing 2,3,5-trichloropyridine includes the following steps: S1. Add the raw material 2,3,4,5-tetrachloropyridine, acid-binding agent, metal catalyst and solvent to the high-pressure reactor; S2. The reactor is purged with nitrogen and then hydrogen gas in succession to remove impurity gases from the reactor. S3. Introduce hydrogen gas into the reactor, then raise the reaction temperature to 90~150℃ to start the reaction; S4. After the reaction is complete, the reaction system is cooled to room temperature, and the reaction solution is filtered to recover the metal catalyst. The solvent is separated from the filtrate to obtain crude 2,3,5-trichloropyridine, which is then distilled to obtain high-purity 2,3,5-trichloropyridine.

[0006] Preferably, as an improvement, in step one, the acid-binding agent is at least one of monomethylamine, dimethylamine, triethylamine, n-propylamine, alcoholic ammonia, and ammonia water.

[0007] Preferably, as an improvement, in step one, the solvent is methanol, and the methanol is purified by reflux and distillation before use.

[0008] Preferably, as an improvement, in step three, when hydrogen is introduced, the initial pressure is maintained >0.1 MPa.

[0009] Preferably, as an improvement, in step three, the reaction is started and the reaction progress is monitored in real time by gas chromatography until the raw material conversion rate is ≥80%.

[0010] Preferably, as an improvement, in step four, the recovered metal catalyst is washed with the reaction solvent and then reused.

[0011] Preferably, as an improvement, in step four, the solvent is separated by vacuum distillation.

[0012] The principle and advantages of this scheme are as follows: In practical applications, addressing the problems of high reaction temperature, numerous byproducts, and low selectivity associated with the commonly used chlorination method for 2,5-dichloropyridine in existing technologies, this scheme uses 2,3,4,5-tetrachloropyridine as a raw material. Under the synergistic effect of a metal catalyst and an acid-binding agent, using hydrogen as the hydrogen source and methanol as the solvent, a catalytic hydrogenation reaction is employed to achieve selective dechlorination at the 4-position of 2,3,4,5-tetrachloropyridine, ultimately producing 2,3,5-trichloropyridine. The core of this reaction is utilizing the synergistic effect of the catalyst and the acid-binding agent to precisely control the position selectivity of the hydrodechlorination, avoiding the removal of chlorine atoms at other positions. The reaction equation is as follows:

[0013] During the technical solution development phase, optimizing the types and ratios of metal catalysts and acid-binding agents was crucial to solving the major challenge of low reaction selectivity. Compared to traditional methods that directly generate the target product through metal reduction, this technical solution reduces the cost of metal usage, requiring only a catalytic amount of metal to successfully obtain the target product. In the condition screening process, the inventors used triethylamine and amine alcohols as the main acid-binding agents to screen commonly used hydrogenation catalysts, ultimately determining that elemental metals such as nickel, ruthenium, zinc, iron, platinum, and gold, or metals supported on a support, could synthesize the target product with high selectivity. During the condition screening, it was found that when amine alcohols were used as acid-binding agents, ammonia readily reacted with the raw materials to generate byproducts, leading to reduced reaction selectivity. After a series of explorations and screenings, it was finally discovered that using iron powder as a catalyst and triethylamine as an acid-binding agent achieved optimal selectivity and conversion rate for the reaction.

[0014] The beneficial effects of this technical solution are as follows: 1. This technical solution breaks through the bottleneck of poor selectivity in traditional processes. By using metal catalysts (metal elements such as nickel, ruthenium, zinc, iron, platinum, gold, etc. or metals supported on a support, the catalyst can be a single metal or a mixture of several metals) and acid-binding agents, the 4-position directional dechlorination of 2,3,4,5-tetrachloropyridine is achieved with very few byproducts and a raw material conversion rate of ≥80%.

[0015] 2. The reaction process of this technical solution does not generate waste salt, thus reducing environmental pollution; the recovered metal catalyst can be recycled after solvent washing, reducing catalyst procurement costs; the solvent can be recovered through vacuum distillation, further reducing raw material waste and meeting the requirements of green chemical production.

[0016] 3. Compared with some traditional processes involving high temperature, high pressure and strong corrosion, this solution controls the reaction temperature at 90~150℃ and requires only >0.1MPa, which reduces the difficulty of operation, significantly reduces the danger of the reaction process, and makes it easier to achieve industrial mass production. Attached Figure Description

[0017] Figure 1 This is a gas chromatogram of the product of metal catalyst group 1 in the embodiments of the present invention. Detailed Implementation

[0018] The following detailed description provides further details on specific embodiments, but the embodiments of the present invention are not limited thereto. Unless otherwise specified, the technical means used in the following embodiments are conventional means well known to those skilled in the art; the experimental methods used are all conventional methods; and the materials and reagents used are all commercially available.

[0019] Overview of the plan: A method for preparing 2,3,5-trichloropyridine, comprising the following steps: S1. Add 2,3,4,5-tetrachloropyridine (50.0 g), acid-binding agent (2~6 equiv.), metal catalyst (1.0~5.0 g), and solvent (400.0 g, methanol) obtained by reflux and distillation purification to a high-pressure reactor. The acid-binding agent is at least one of monomethylamine, dimethylamine, triethylamine, n-propylamine, alcoholic ammonia, and ammonia water; the metal catalyst is an elemental metal such as nickel, ruthenium, zinc, iron, platinum, or gold, or a metal supported on a support. The catalyst can be a single metal or a mixture of several metals.

[0020] S2. The reactor was purged three times with nitrogen and then three times with hydrogen to remove air and other impurities from the reactor.

[0021] S3. Introduce hydrogen into the reactor and maintain the initial pressure > 0.1 MPa. Then raise the reaction temperature to 90~150℃, start the reaction, and monitor the reaction progress in real time by gas chromatography until the raw material conversion rate is ≥ 80%.

[0022] S4. After the reaction is complete, the reaction system is cooled to room temperature, and the reaction solution is filtered to recover the metal catalyst (which can be reused after washing with the reaction solvent); the filtrate is subjected to vacuum distillation to separate the solvent; crude 2,3,5-trichloropyridine is obtained, and finally, high-purity target product is obtained by distillation, with the structural formula as shown in formula (I).

[0023] Formula (I) Experimental Example 1 This experiment investigated the effects of different catalyst types and acid-binding agents on the synthesis of 2,3,5-trichloropyridine under fixed conditions: reaction temperature (150℃), reaction time (8.0 h), hydrogen atmosphere, and acid-binding agent equivalent (2 equiv). The specific experimental design and results are detailed in Table 1. The conversion rate is the ratio of the amount of raw material reduced in gas chromatography to the initial amount of raw material; the selectivity is the ratio of the amount of target product detected in the gas chromatography results to the amount of raw material converted.

[0024] Table 1

[0025] The above results indicate that traditional noble metal catalysts (Rh / C, Pd / C) exhibit inherent defects such as low conversion rate (maximum only 10.1%) and poor selectivity (maximum only 24.1%). In contrast, the iron powder catalyst in this technical solution achieves a conversion rate of 93.2% and a selectivity of 84.1% under optimized conditions. This represents a significant leap in conversion rate and selectivity, demonstrating that the synergistic system of the metal catalyst (iron), acid-binding agent (TEA), and solvent (MeOH) fundamentally overcomes the limitations of traditional noble metal catalysis, showcasing the creativity in catalyst selection. Furthermore, through optimization of reaction temperature, catalyst dosage, and acid-binding agent equivalent, the optimal treatment conditions were determined for catalyst group 1 (2% iron powder, MeOH, TEA (2.0 equiv), 150 ℃), resulting in a conversion rate as high as 93.2%, a selectivity as high as 84.1%, and a purity as high as 95%, as shown in the gas chromatogram. Figure 1 As shown.

[0026] The above descriptions are merely embodiments of the present invention, and common knowledge such as specific technical solutions and / or characteristics are not described in detail here. It should be noted that those skilled in the art can make various modifications and improvements without departing from the technical solutions of the present invention, and these should also be considered within the scope of protection of the present invention. These modifications and improvements will not affect the effectiveness of the implementation of the present invention or the practicality of the patent. The scope of protection claimed in this application should be determined by the content of its claims, and the specific embodiments described in the specification can be used to interpret the content of the claims.

Claims

1. A process for the preparation of 2, 3, 5-trichloropyridine, characterized in that: The selective hydrogenation of 2, 3, 4, 5-tetrachloropyridine is carried out in the presence of a metal catalyst and an acid binding agent, wherein the metal catalyst is a metal element of nickel, ruthenium, zinc, iron, platinum or gold, or a metal supported on a carrier, and the metal catalyst is a single metal or a mixture of several metals.

2. A process for the preparation of 2, 3, 5-trichloropyridine according to claim 1, characterized in that, The method comprises the following steps: S1, adding raw material 2, 3, 4, 5-tetrachloropyridine, an acid binding agent, a metal catalyst and a solvent into a high-pressure reaction kettle; S2, replacing the reaction kettle with nitrogen and hydrogen in sequence to remove impurity gases in the kettle; S3, filling hydrogen into the reaction kettle, and then increasing the reaction temperature to 90-150℃ to start the reaction; S4, after the reaction is completed, cooling the reaction system to room temperature, filtering the reaction liquid to recover the metal catalyst, separating the solvent from the filtered liquid, obtaining crude 2, 3, 5-trichloropyridine and rectifying the crude 2, 3, 5-trichloropyridine to obtain high-purity 2, 3, 5-trichloropyridine.

3. A process for the preparation of 2, 3, 5-trichloropyridine according to claim 2, characterized in that: In step one, the acid binding agent is at least one of monomethylamine, dimethylamine, triethylamine, n-propylamine, alcohol amine and aqueous ammonia.

4. A process for the preparation of 2, 3, 5-trichloropyridine according to claim 3, characterized in that: In step one, the solvent is methanol, and the methanol is purified by reflux and distillation before use.

5. A process for the preparation of 2, 3, 5-trichloropyridine according to claim 4, characterized in that: In step three, when hydrogen is filled, the initial pressure is kept greater than 0.1 MPa.

6. A process for the preparation of 2, 3, 5-trichloropyridine according to claim 5, characterized in that: In step three, the reaction is started and the reaction progress is detected in real time by gas chromatography until the conversion rate of the raw material is greater than or equal to 80%.

7. A process for the preparation of 2, 3, 5-trichloropyridine according to claim 6, characterized in that: In step four, the recovered metal catalyst is washed with a reaction solvent and reused.

8. A process for the preparation of 2, 3, 5-trichloropyridine according to claim 7, characterized in that: In step four, the solvent is separated by vacuum distillation.

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