Preparation method of 2-chloro-6-trichloromethylpyridine
By using 6-hydroxypyridine-2-carboxylic acid and a composite solid-phase catalyst, the problems of low yield and poor selectivity in the synthesis of 2-chloro-6-trichloromethylpyridine were solved, achieving an efficient preparation process and catalyst recyclability.
Patent Information
- Application Number
- CN202511650644.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-11-12
- Publication Date
- 2026-01-02
AI Technical Summary
Existing methods for synthesizing 2-chloro-6-trichloromethylpyridine suffer from problems such as complex reaction conditions, numerous byproducts, low yield, and poor selectivity.
Using 6-hydroxypyridine-2-carboxylic acid as raw material, the active groups are exposed by acidification and hydrolysis, and then reacted with phosphorus pentachloride using a composite solid-phase catalyst to form chlorine and acyl chloride. Subsequently, phenylphosphoryl dichloride in the composite solid-phase catalyst is used as a secondary chlorinating agent to prepare 2-chloro-6-trichloromethylpyridine.
It improved the yield and selectivity of 2-chloro-6-trichloromethylpyridine, reduced the formation of byproducts, and simplified the catalyst recovery process.
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Figure CN121248486A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of organic synthesis technology, specifically to a method for preparing 2-chloro-6-trichloromethylpyridine. Background Technology
[0002] 2-Chloro-6-trichloromethylpyridine is an important organic synthetic intermediate widely used in the synthesis of pesticides, pharmaceuticals, and other chemical products. It is also used as a pesticide and nitrogen fertilizer synergist. Currently, there are two main synthetic methods for 2-chloro-6-trichloromethylpyridine: one involves the gas-phase chlorination of 2-methylpyridine with chlorine at high temperature; the other involves a catalytic reaction of pyridine-2-carboxylic acid with chlorine. However, these methods are prone to competitive chlorination and over-chlorination at multiple sites on the pyridine ring, resulting in numerous byproducts that are difficult to separate, complex operational control conditions, and low yields of the target product. Therefore, a method for preparing 2-chloro-6-trichloromethylpyridine with simple reaction conditions, fewer byproducts, and high yield and selectivity is needed. Summary of the Invention
[0003] The purpose of this invention is to provide a method for preparing 2-chloro-6-trichloromethylpyridine. This method uses 6-hydroxypyridine-2-carboxylic acid as a raw material, exposes active groups through acidification and hydrolysis, and then uses a composite solid-phase catalyst as a catalytic chlorination agent. The activated 6-hydroxypyridine-2-carboxylic acid reacts with phosphorus pentachloride, where its hydroxyl and carboxyl groups are first chlorinated to chlorine and acyl chloride, respectively. The acyl chloride is further chlorinated to form trichloromethyl, thereby obtaining 2-chloro-6-trichloromethylpyridine. The introduction of a highly selective composite solid-phase catalyst solves the problems of poor yield and low selectivity in the existing 2-chloro-6-trichloromethylpyridine preparation process, and the catalyst used is easy to recover.
[0004] A method for preparing 2-chloro-6-trichloromethylpyridine, comprising the following steps: Step S1: Mix 6-hydroxypyridine-2-carboxylic acid and sodium hydroxide solution, stir at a stirring rate of 250-300 rpm and a temperature of 90-95℃ for 35-40 min, cool to room temperature, stir and add hydrochloric acid solution to adjust the pH to 3-3.5, stir for 3-5 min, cool to 0-2℃, continue stirring for 50-60 min, filter, wash with ice water, dry to obtain intermediate; Step S2: Mix the intermediate and the composite solid catalyst, stir at 250-300 rpm at room temperature, add phosphorus pentachloride, stir for 2-3 min, heat to 80-90℃, react for 1.5-2 h, then heat to 160-165℃ and continue the reaction for 10-12 h, and collect the distillate. After the reaction is complete, cool to room temperature, filter, recover the catalyst from the filter cake, add deionized water at 2-5℃ to the filtrate, adjust the pH to 8 with sodium carbonate solution, extract with ethyl acetate, dry, and recrystallize with anhydrous ethanol to obtain 2-chloro-6-trichloromethylpyridine.
[0005] Furthermore, in step S1, the ratio of 6-hydroxypyridine-2-carboxylic acid to sodium hydroxide solution is 13.9-14g:35-40mL, the mass fraction of sodium hydroxide solution is 15%, and the mass fraction of hydrochloric acid solution is 37%.
[0006] Furthermore, in step S2, the ratio of intermediate, composite solid catalyst and phosphorus pentachloride is 13.5-13.8g: 5.2-5.4g: 45.5-46g, the collected fraction is phosphorus oxychloride as a byproduct, the catalyst recovery process is washing and drying with ethyl acetate, and the sodium carbonate solution has a mass fraction of 8%.
[0007] Furthermore, in the reaction process for preparing 2-chloro-6-trichloromethylpyridine, an intermediate is first obtained by acidifying and hydrolyzing to expose the active groups of 6-hydroxypyridine-2-carboxylic acid. The hydroxyl and carboxyl groups in the intermediate react with phosphorus pentachloride to form chlorine and acyl chloride groups, forming a primary chlorination intermediate and the byproduct phosphorus oxychloride. The added phosphorus pentachloride reacts with phenylphosphoryl dichloride present in the composite solid-phase catalyst to form tetrachlorophenylphosphine and the byproduct phosphorus oxychloride. Tetrachlorophenylphosphine acts as a chlorinating agent for secondary chlorination, reacting with the primary chlorination intermediate to obtain the secondary chlorination product, namely 2-chloro-6-trichloromethylpyridine. A schematic diagram of the chemical reaction is attached to the instruction manual. Figure 2 .
[0008] The composite solid-phase catalyst was prepared by the following steps: Step A1: N-methylimidazolium, 3-chloropropylamine hydrochloride and acetonitrile were mixed and reacted for 24 h under nitrogen protection, stirring at 120-150 rpm and temperature of 72-75℃. After cooling to room temperature, the mixture was washed with diethyl ether, filtered, and dried to obtain 1-aminopropyl-3-methylimidazolium chloride. The 1-aminopropyl-3-methylimidazolium chloride ionic liquid, sodium fluoroborate and acetone were mixed and reacted for 24 h under nitrogen protection, stirring at 120-150 rpm and temperature of 58-60℃. After filtration, vacuum distillation was performed to precipitate dichloromethane. The precipitate was filtered, rotary evaporated, and dried under vacuum to obtain 1-aminopropyl-3-methylimidazolium tetrafluoroborate ionic liquid. Furthermore, in step A1: the ratio of N-methylimidazolium, 3-chloropropylamine hydrochloride, and acetonitrile is 9-9.1g: 13-13.2g: 45-50mL, and the ratio of 1-aminopropyl-3-methylimidazolium chloride ionic liquid, sodium fluoroborate, and acetone is 12.4-12.8g: 10.8-11g: 35-40min.
[0009] Step A2: Mix 1-aminopropyl-3-methylimidazolium tetrafluoroborate and aluminum chloride, and react under nitrogen protection at a temperature of 78-80℃ for 5-6 hours to obtain a metal-based 1-aminopropyl-3-methylimidazolium tetrafluoroborate ionic liquid. Furthermore, in step A2, the ratio of 1-aminopropyl-3-methylimidazolium tetrafluoroborate to aluminum chloride is 21-22g: 13.2-13.3g.
[0010] Step A3: Mix SBA-15 molecular sieve, 3-chloropropyltrimethoxysilane and toluene, and react for 24 h under nitrogen protection, stirring at 120-150 rpm and temperature of 105-110℃. Then, perform Soxhlet extraction with dichloromethane for 12 h, filter, and vacuum dry to obtain silane-modified molecular sieve. Mix silane-modified molecular sieve, metal-based 1-aminopropyl-3-methylimidazolium tetrafluoroborate ionic liquid and anhydrous ethanol, and react for 12 h under temperature of 88-90℃. Then, perform Soxhlet extraction with dichloromethane for 12 h, filter, and vacuum dry to obtain immobilized molecular sieve. Furthermore, in step A3: the ratio of SBA-15 molecular sieve, 3-chloropropyltrimethoxysilane and toluene is 5.8-6g: 4.5-5g: 50-55mL, and the ratio of silane-modified molecular sieve, metal-based 1-aminopropyl-3-methylimidazolium tetrafluoroborate ionic liquid and anhydrous ethanol is 7.2-7.8g: 2.32-2.35g: 40-45mL.
[0011] Step A4: Mix phenylphosphoryl dichloride and dichloromethane at a stirring rate of 120-150 rpm and at room temperature for 15-20 min, then add the supported molecular sieve, ultrasonically disperse for 5-8 min, continue stirring for 2-3 h, filter, rotary evaporate, and vacuum dry to obtain the composite solid catalyst. Furthermore, in step A4, the ratio of phenylphosphodichloro, dichloromethane, and immobilized molecular sieve is 1.4-1.45g: 15-20mL: 5.1-5.2g.
[0012] Furthermore, in the preparation process of the composite solid-phase catalyst, SBA-15 molecular sieve is used as a support. It is first modified with 3-chloropropyltrimethoxysilane to introduce chloropropyl groups, thus obtaining a silane-modified molecular sieve. Through the reaction of N-methylimidazolium with 3-chloropropylamine hydrochloride, an imidazolium structure is formed, yielding 1-aminopropyl-3-methylimidazolium chloride. Tetrafluoroborate anions are then introduced through ion exchange to obtain 1-aminopropyl-3-methylimidazolium tetrafluoroborate. Aluminum chloride is then added to react and form a stable aluminochlorochloroate ion, which reacts with 1-aminopropyl- 3-Methylimidazolium forms ionic bonds to prepare a metal-based 1-aminopropyl-3-methylimidazolium tetrafluoroborate ionic liquid. The ionic liquid is then loaded onto a molecular sieve via the reaction of the amino group in the metal-based 1-aminopropyl-3-methylimidazolium tetrafluoroborate ionic liquid with the chloropropyl group in a silane-modified molecular sieve, thus preparing a supported molecular sieve for the ionic liquid. Finally, phenylphosphoryl dichloride is anchored onto the molecular sieve support via coordination with the metal ions in the metal-based 1-aminopropyl-3-methylimidazolium tetrafluoroborate ionic liquid, thus preparing a composite solid-phase catalyst.
[0013] The beneficial effects of this invention are as follows: This invention discloses a method for preparing 2-chloro-6-trichloromethylpyridine, which uses 6-hydroxypyridine-2-carboxylic acid as raw material. The active groups are exposed by acidification and hydrolysis. Then, a composite solid-phase catalyst is used as a catalytic chlorination agent. The activated 6-hydroxypyridine-2-carboxylic acid reacts with phosphorus pentachloride. Its hydroxyl and carboxyl groups are first chlorinated to chlorine and acyl chloride, respectively. The acyl chloride is further chlorinated to form trichloromethyl. During the reaction, the collected distillate byproduct is phosphorus oxychloride, which is purified to obtain 2-chloro-6-trichloromethylpyridine. The introduction of a highly selective composite solid-phase catalyst solves the problems of poor yield and low selectivity in the existing preparation process of 2-chloro-6-trichloromethylpyridine. At the same time, the catalyst used is easy to recover.
[0014] In the reaction process for the preparation of 2-chloro-6-trichloromethylpyridine, a composite solid-phase catalyst is used as the chlorination catalyst. The composite solid-phase catalyst itself uses SBA-15 molecular sieve as the matrix, and is covalently supported on an ionic liquid after silane modification. Chloroaluminate ions are introduced through ionic bonding of the ionic liquid, and then phenylphosphoryl dichloride is introduced through coordination. The phenylphosphoryl dichloride introduced in the resulting composite solid-phase catalyst serves as the raw material for tetrachlorophenylphosphine, the secondary chlorinating agent in the preparation reaction of 2-chloro-6-trichloromethylpyridine. This tetrachlorophenylphosphine reacts with pentachlorophenylphosphine... After the phosphorus reaction forms tetrachlorophenylphosphine, it can react with the primary chlorination intermediate in the molecular sieve channel. Due to the synergistic effect of the metal-based catalyst introduced into the molecular sieve, the positive charge of the phosphorus atom is significantly enhanced, thus forming a super-activated phosphorus center that can more effectively react with the acyl chloride intermediate, thereby converting the acyl chloride structure into a trichloromethyl structure, reducing the generation of by-products, and improving the selectivity of the reaction. After the secondary chlorination is completed, the newly generated phenylphosphine dichloride can be fixed on the molecular sieve again due to coordination, thus allowing the composite solid-phase catalyst to be reused. Attached Figure Description
[0015] Figure 1 This is a process flow diagram of the present invention; Figure 2 This is a schematic diagram of the reaction process for preparing 2-chloro-6-trichloromethylpyridine according to the present invention. Detailed Implementation
[0016] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.
[0017] Example 1: Reference Figure 1 A method for preparing 2-chloro-6-trichloromethylpyridine, comprising the following steps: Step S1: Mix 6-hydroxypyridine-2-carboxylic acid and sodium hydroxide solution, stir at 250 rpm and 90°C for 35 min, cool to room temperature, stir and add hydrochloric acid solution to adjust the pH to 3, stir for 3 min, cool to 0°C, continue stirring for 50 min, filter, wash with ice water, dry to obtain intermediate. Step S2: Mix the intermediate and the composite solid catalyst, stir at 250 rpm at room temperature, add phosphorus pentachloride, stir for 2-3 min, heat to 90℃, react for 1.5 h, then heat to 165℃ and continue the reaction for 10 h, and collect the distillate. After the reaction is complete, cool to room temperature, filter, recover the catalyst from the filter cake, add deionized water at 2℃ to the filtrate, adjust the pH to 8 with sodium carbonate solution, extract with ethyl acetate, dry, and recrystallize with anhydrous ethanol to obtain 2-chloro-6-trichloromethylpyridine.
[0018] Furthermore, in step S1, the ratio of 6-hydroxypyridine-2-carboxylic acid to sodium hydroxide solution is 13.9 g: 35 mL, the mass fraction of sodium hydroxide solution is 15%, and the mass fraction of hydrochloric acid solution is 37%.
[0019] Furthermore, in step S2, the ratio of intermediate, composite solid catalyst and phosphorus pentachloride is 13.5g:5.2g:45.5g, the collected fraction is phosphorus oxychloride as a byproduct, the catalyst recovery process is washing and drying with ethyl acetate, and the sodium carbonate solution has a mass fraction of 8%.
[0020] The composite solid-phase catalyst was prepared by the following steps: Step A1: N-methylimidazolium, 3-chloropropylamine hydrochloride and acetonitrile were mixed and reacted for 24 h under nitrogen protection, stirring at 150 rpm and temperature of 72 °C. After cooling to room temperature, the mixture was washed with ether, filtered, and dried to obtain 1-aminopropyl-3-methylimidazolium chloride. The 1-aminopropyl-3-methylimidazolium chloride ionic liquid, sodium fluoroborate and acetone were mixed and reacted for 24 h under nitrogen protection, stirring at 150 rpm and temperature of 58 °C. After filtration, vacuum distillation was performed to precipitate dichloromethane. The precipitate was filtered, rotary evaporated, and dried under vacuum to obtain 1-aminopropyl-3-methylimidazolium tetrafluoroborate ionic liquid. Furthermore, in step A1, the ratio of N-methylimidazolium, 3-chloropropylamine hydrochloride, and acetonitrile is 9g:13.2g:45mL, and the ratio of 1-aminopropyl-3-methylimidazolium chloride ionic liquid, sodium fluoroborate, and acetone is 12.8g:10.8g:40min.
[0021] Step A2: Mix 1-aminopropyl-3-methylimidazolium tetrafluoroborate and aluminum chloride, and react for 5 h under nitrogen protection and at 80 °C to obtain a metal-based 1-aminopropyl-3-methylimidazolium tetrafluoroborate ionic liquid. Furthermore, in step A2, the ratio of 1-aminopropyl-3-methylimidazolium tetrafluoroborate to aluminum chloride is 22g:13.2g.
[0022] Step A3: SBA-15 molecular sieve, 3-chloropropyltrimethoxysilane and toluene were mixed and reacted for 24 h under nitrogen protection, stirring at 120 rpm and temperature of 105 °C. After Soxhlet extraction with dichloromethane for 12 h, the mixture was filtered and vacuum dried to obtain silane-modified molecular sieve. Silane-modified molecular sieve, metal-based 1-aminopropyl-3-methylimidazolium tetrafluoroborate ionic liquid and anhydrous ethanol were mixed and reacted for 12 h at temperature of 88 °C. After Soxhlet extraction with dichloromethane for 12 h, the mixture was filtered and vacuum dried to obtain immobilized molecular sieve. Furthermore, in step A3, the ratio of SBA-15 molecular sieve, 3-chloropropyltrimethoxysilane, and toluene is 5.8g:4.5g:50mL, and the ratio of silane-modified molecular sieve, metal-based 1-aminopropyl-3-methylimidazolium tetrafluoroborate ionic liquid, and anhydrous ethanol is 7.2g:2.32g:40mL.
[0023] Step A4: Mix phenylphosphoryl dichloride and dichloromethane, stir at 120 rpm at room temperature for 15 min, then add the supported molecular sieve, ultrasonically disperse for 5 min, continue stirring for 2 h, filter, rotary evaporate, and vacuum dry to obtain the composite solid catalyst. Furthermore, in step A4, the ratio of phenylphosphodichloro, dichloromethane, and immobilized molecular sieve is 1.4g:15mL:5.1g.
[0024] Example 2: Reference Figure 1 A method for preparing 2-chloro-6-trichloromethylpyridine, comprising the following steps: Step S1: Mix 6-hydroxypyridine-2-carboxylic acid and sodium hydroxide solution, stir at 250 rpm and 95°C for 35 min, cool to room temperature, stir and add hydrochloric acid solution to adjust the pH to 3.5, stir for 3 min, cool to 2°C, continue stirring for 50 min, filter, wash with ice water, dry to obtain intermediate; Step S2: Mix the intermediate and the composite solid catalyst, stir at 250 rpm at room temperature, add phosphorus pentachloride, stir for 2 min, heat to 80℃, react for 1.5 h, then heat to 160℃ and continue the reaction for 10 h, and collect the distillate. After the reaction is complete, cool to room temperature, filter, recover the catalyst from the filter cake, add deionized water at 2℃ to the filtrate, adjust the pH to 8 with sodium carbonate solution, extract with ethyl acetate, dry, and recrystallize with anhydrous ethanol to obtain 2-chloro-6-trichloromethylpyridine.
[0025] Furthermore, in step S1, the ratio of 6-hydroxypyridine-2-carboxylic acid to sodium hydroxide solution is 13.9 g: 35 mL, the mass fraction of sodium hydroxide solution is 15%, and the mass fraction of hydrochloric acid solution is 37%.
[0026] Furthermore, in step S2, the ratio of intermediate, composite solid catalyst and phosphorus pentachloride is 13.5g:5.2g:45.5g, the collected fraction is phosphorus oxychloride as a byproduct, the catalyst recovery process is washing and drying with ethyl acetate, and the sodium carbonate solution has a mass fraction of 8%.
[0027] The composite solid-phase catalyst was prepared by the following steps: Step A1: N-methylimidazolium, 3-chloropropylamine hydrochloride and acetonitrile were mixed and reacted for 24 h under nitrogen protection, stirring at 120 rpm and temperature of 72 °C. After cooling to room temperature, the mixture was washed with diethyl ether, filtered, and dried to obtain 1-aminopropyl-3-methylimidazolium chloride. The 1-aminopropyl-3-methylimidazolium chloride ionic liquid, sodium fluoroborate and acetone were mixed and reacted for 24 h under nitrogen protection, stirring at 120 rpm and temperature of 58 °C. After filtration, vacuum distillation was performed to precipitate dichloromethane. The precipitate was filtered, rotary evaporated, and dried under vacuum to obtain 1-aminopropyl-3-methylimidazolium tetrafluoroborate ionic liquid. Furthermore, in step A1, the ratio of N-methylimidazolium, 3-chloropropylamine hydrochloride, and acetonitrile is 9g:13g:45mL, and the ratio of 1-aminopropyl-3-methylimidazolium chloride ionic liquid, sodium fluoroborate, and acetone is 12.4g:10.8g:35min.
[0028] Step A2: Mix 1-aminopropyl-3-methylimidazolium tetrafluoroborate and aluminum chloride, and react for 5 h under nitrogen protection and at 78 °C to obtain a metal-based 1-aminopropyl-3-methylimidazolium tetrafluoroborate ionic liquid. Furthermore, in step A2, the ratio of 1-aminopropyl-3-methylimidazolium tetrafluoroborate to aluminum chloride is 21g:13.2g.
[0029] Step A3: SBA-15 molecular sieve, 3-chloropropyltrimethoxysilane and toluene were mixed and reacted for 24 h under nitrogen protection, stirring at 150 rpm and temperature of 110 °C. After Soxhlet extraction with dichloromethane for 12 h, the mixture was filtered and vacuum dried to obtain silane-modified molecular sieve. Silane-modified molecular sieve, metal-based 1-aminopropyl-3-methylimidazolium tetrafluoroborate ionic liquid and anhydrous ethanol were mixed and reacted for 12 h at temperature of 88 °C. After Soxhlet extraction with dichloromethane for 12 h, the mixture was filtered and vacuum dried to obtain immobilized molecular sieve. Furthermore, in step A3: the ratio of SBA-15 molecular sieve, 3-chloropropyltrimethoxysilane and toluene is 5.8g:4.5g:55mL, and the ratio of silane-modified molecular sieve, metal-based 1-aminopropyl-3-methylimidazolium tetrafluoroborate ionic liquid and anhydrous ethanol is 7.2g:2.32g:45mL.
[0030] Step A4: Mix phenylphosphoryl dichloride and dichloromethane, stir at 120 rpm at room temperature for 20 min, then add immobilized molecular sieve, ultrasonically disperse for 5 min, continue stirring for 2 h, filter, rotary evaporate, and vacuum dry to obtain composite solid catalyst; Furthermore, in step A4, the ratio of phenylphosphodichloro, dichloromethane, and immobilized molecular sieve is 1.45g:15mL:5.1g.
[0031] Example 3: Reference Figure 1 A method for preparing 2-chloro-6-trichloromethylpyridine, comprising the following steps: Step S1: Mix 6-hydroxypyridine-2-carboxylic acid and sodium hydroxide solution, stir at 300 rpm and 95°C for 40 min, cool to room temperature, stir and add hydrochloric acid solution to adjust the pH to 3.5, stir for 5 min, cool to 2°C, continue stirring for 60 min, filter, wash with ice water, dry to obtain intermediate; Step S2: Mix the intermediate and the composite solid catalyst, stir at 300 rpm at room temperature, add phosphorus pentachloride, stir for 3 min, heat to 90℃, react for 2 h, then heat to 165℃ and continue the reaction for 12 h, and collect the distillate. After the reaction is complete, cool to room temperature, filter, recover the catalyst from the filter cake, add deionized water at 5℃ to the filtrate, adjust the pH to 8 with sodium carbonate solution, extract with ethyl acetate, dry, and recrystallize with anhydrous ethanol to obtain 2-chloro-6-trichloromethylpyridine.
[0032] Furthermore, in step S1, the ratio of 6-hydroxypyridine-2-carboxylic acid to sodium hydroxide solution is 14g:40mL, the mass fraction of sodium hydroxide solution is 15%, and the mass fraction of hydrochloric acid solution is 37%.
[0033] Furthermore, in step S2, the ratio of intermediate, composite solid catalyst and phosphorus pentachloride is 13.8g:5.4g:46g, the collected fraction is phosphorus oxychloride as a byproduct, the catalyst recovery process is washing and drying with ethyl acetate, and the sodium carbonate solution has a mass fraction of 8%.
[0034] The composite solid-phase catalyst was prepared by the following steps: Step A1: N-methylimidazolium, 3-chloropropylamine hydrochloride and acetonitrile were mixed and reacted for 24 h under nitrogen protection, stirring at 150 rpm and temperature of 75 °C. After cooling to room temperature, the mixture was washed with diethyl ether, filtered, and dried to obtain 1-aminopropyl-3-methylimidazolium chloride. The 1-aminopropyl-3-methylimidazolium chloride ionic liquid, sodium fluoroborate and acetone were mixed and reacted for 24 h under nitrogen protection, stirring at 150 rpm and temperature of 60 °C. After filtration, vacuum distillation was performed to precipitate dichloromethane. The precipitate was filtered, rotary evaporated, and dried under vacuum to obtain 1-aminopropyl-3-methylimidazolium tetrafluoroborate ionic liquid. Furthermore, in step A1, the ratio of N-methylimidazolium, 3-chloropropylamine hydrochloride, and acetonitrile is 9.1g:13.2g:50mL, and the ratio of 1-aminopropyl-3-methylimidazolium chloride ionic liquid, sodium fluoroborate, and acetone is 12.8g:11g:40min.
[0035] Step A2: Mix 1-aminopropyl-3-methylimidazolium tetrafluoroborate and aluminum chloride, and react for 6 h under nitrogen protection and at 80 °C to obtain a metal-based 1-aminopropyl-3-methylimidazolium tetrafluoroborate ionic liquid. Furthermore, in step A2, the ratio of 1-aminopropyl-3-methylimidazolium tetrafluoroborate to aluminum chloride is 22g:13.3g.
[0036] Step A3: SBA-15 molecular sieve, 3-chloropropyltrimethoxysilane and toluene were mixed and reacted for 24 h under nitrogen protection, stirring at 150 rpm and temperature of 110 °C. After Soxhlet extraction with dichloromethane for 12 h, the mixture was filtered and vacuum dried to obtain silane-modified molecular sieve. Silane-modified molecular sieve, metal-based 1-aminopropyl-3-methylimidazolium tetrafluoroborate ionic liquid and anhydrous ethanol were mixed and reacted for 12 h at temperature of 90 °C. After Soxhlet extraction with dichloromethane for 12 h, the mixture was filtered and vacuum dried to obtain immobilized molecular sieve. Furthermore, in step A3, the ratio of SBA-15 molecular sieve, 3-chloropropyltrimethoxysilane, and toluene is 6g:5g:55mL, and the ratio of silane-modified molecular sieve, metal-based 1-aminopropyl-3-methylimidazolium tetrafluoroborate ionic liquid, and anhydrous ethanol is 7.8g:2.35g:45mL.
[0037] Step A4: Mix phenylphosphoryl dichloride and dichloromethane, stir at 150 rpm at room temperature for 20 min, then add the supported molecular sieve, ultrasonically disperse for 8 min, continue stirring for 3 h, filter, rotary evaporate, and vacuum dry to obtain the composite solid catalyst. Furthermore, in step A4, the ratio of phenylphosphodichloro, dichloromethane, and immobilized molecular sieve is 1.45g:20mL:5.2g.
[0038] Comparative Example 1: Compared with Example 3, this comparative example replaces the supported molecular sieve in the preparation process of the composite solid catalyst in Example 3 with SBA-15 molecular sieve, and adds thionyl chloride in step S2. The other steps are the same, and the weight ratio of phenylphosphine dichloride to SBA-15 molecular sieve is 1:5.
[0039] Comparative Example 2: Compared with Example 3, this comparative example replaces the supported molecular sieve in the preparation process of the composite solid catalyst in Example 3 with the SBA-15 molecular sieve in Example 3. At the same time, phenylphosphodichloride is added in step S2, and the other steps are the same. The weight ratio of phenylphosphodichloride to SBA-15 molecular sieve is 1:5.
[0040] Comparative Example 3: Compared with Example 3, this comparative example replaces the composite solid catalyst in the preparation process of 2-chloro-6-trichloromethylpyridine in Example 3 with the supported molecular sieve in Example 3. At the same time, phenylphosphoryl dichloride is added in step S2, and the other steps are the same. The weight ratio of phenylphosphoryl dichloride to SBA-15 molecular sieve is 1:5.
[0041] Based on the process flows of Examples 1, 2, 3, Comparative Examples 1, 2, and 3, the reaction yield of 2-chloro-6-trichloromethylpyridine was calculated, and its purity was determined. The test results are shown in Table 1 below: Table 1 Test Results Testing items Example 1 Example 2 Example 3 Comparative Example 1 Comparative Example 2 Comparative Example 3 Yield (%) 95.31 96.28 96.77 34.13 84.45 95.15 purity(%) 97.20 98.43 98.94 43.36 91.90 92.20 According to the process flow of Example 3, Comparative Example 2, and Comparative Example 3, the process flow was repeated 5 times without changing the composite solid catalyst. The reaction yield and product purity of 2-chloro-6-trichloromethylpyridine were then determined, and the test results are shown in Table 2 below: Table 2. Catalyst reuse test results Testing items Example 3 Comparative Example 2 Comparative Example 3 Yield (%) after catalyst reuse 94.48 65.25 93.73 Purity (%) of the catalyst after reuse 98.31 78.37 93.13 As shown in the table, comparing Examples 1, 2, and 3 with Comparative Examples 1, 2, and 3, the data from Examples 1-3 indicate that the 2-chloro-6-trichloromethylpyridine preparation method used in this invention has a high reaction yield and high product purity, suggesting that the process used in this invention produces fewer byproducts and the prepared composite solid-phase catalyst has strong selectivity. Comparative Example 1 uses molecular sieves and thionyl chloride as catalysts, resulting in extremely low product yield and purity, significantly inferior to the composite solid-phase catalyst used in this invention. Comparative Example 2, compared to Example 3, uses SBA-15 molecular sieves and phenylphosphine dichloride to form a catalytic system. While it maintains some catalytic activity during the initial reaction, resulting in a good reaction yield, this method is less efficient. The product purity was also high. However, during the catalyst reuse process, due to the lack of molecular sieve modification, the phenylphosphine dichloride catalyst could not be immobilized on the molecular sieve support, resulting in reduced catalytic activity in subsequent reactions. Additionally, the lack of introduced metal-based ions also contributed to the decrease in reaction yield and product purity. Comparative Example 3, compared to Example 3, used a composite of immobilized molecular sieve and phenylphosphine dichloride to form a catalytic system. In the first reaction, it exhibited a similar reaction yield to Examples 1-3. However, because the phenylphosphine dichloride catalyst did not completely penetrate the molecular sieve, it could not achieve high-selectivity catalysis, leading to a significant decrease in product purity. During catalyst reuse, the new catalyst generated by the reaction itself coordinates with and is immobilized on the immobilized molecular sieve, which actually resulted in a certain increase in product purity after catalyst reuse.
[0042] In the description of this specification, the references to terms such as "an embodiment," "example," "specific example," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of the present invention. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples.
[0043] The above content is merely an example and illustration of the concept of the present invention. Those skilled in the art can make various modifications or additions to the specific embodiments described or use similar methods to replace them, as long as they do not deviate from the concept of the invention, they should all fall within the protection scope of the present invention.
Claims
1. A method for preparing 2-chloro-6-trichloromethylpyridine, characterized in that: The process includes the following steps: Step S1: Mix 6-hydroxypyridine-2-carboxylic acid and sodium hydroxide solution, stir at a stirring rate of 250-300 rpm and a temperature of 90-95℃ for 35-40 min, cool to room temperature, stir and add hydrochloric acid solution to adjust the pH to 3-3.5, stir for 3-5 min, cool to 0-2℃, continue stirring for 50-60 min, filter, wash with ice water, dry, and obtain the intermediate; Step S2: Mix the intermediate and the composite solid catalyst, stir at 250-300 rpm at room temperature, add phosphorus pentachloride, stir for 2-3 min, heat to 80-90℃, react for 1.5-2 h, then heat to 160-165℃ and continue the reaction for 10-12 h, and collect the distillate. After the reaction is complete, cool to room temperature, filter, recover the catalyst from the filter cake, add deionized water at 2-5℃ to the filtrate, adjust the pH to 8 with sodium carbonate solution, extract with ethyl acetate, dry, and recrystallize with anhydrous ethanol to obtain 2-chloro-6-trichloromethylpyridine.
2. The method for preparing 2-chloro-6-trichloromethylpyridine according to claim 1, characterized in that: In step S1, the ratio of 6-hydroxypyridine-2-carboxylic acid to sodium hydroxide solution is 13.9-14g:35-40mL, the mass fraction of sodium hydroxide solution is 15%, and the mass fraction of hydrochloric acid solution is 37%.
3. The method for preparing 2-chloro-6-trichloromethylpyridine according to claim 1, characterized in that: In step S2, the ratio of intermediate, composite solid catalyst and phosphorus pentachloride is 13.5-13.8g: 5.2-5.4g: 45.5-46g. The collected fraction is phosphorus oxychloride as a byproduct. The catalyst recovery process involves washing and drying with ethyl acetate, and the sodium carbonate solution has a mass fraction of 8%.
4. The method for preparing 2-chloro-6-trichloromethylpyridine according to claim 1, characterized in that: The composite solid-phase catalyst was prepared by the following steps: Step A1: N-methylimidazolium, 3-chloropropylamine hydrochloride and acetonitrile were mixed and reacted for 24 h under nitrogen protection, stirring at 120-150 rpm and temperature of 72-75℃. After cooling to room temperature, the mixture was washed with diethyl ether, filtered, and dried to obtain 1-aminopropyl-3-methylimidazolium chloride. The 1-aminopropyl-3-methylimidazolium chloride ionic liquid, sodium fluoroborate and acetone were mixed and reacted for 24 h under nitrogen protection, stirring at 120-150 rpm and temperature of 58-60℃. After filtration, vacuum distillation was performed to precipitate dichloromethane. The precipitate was filtered, rotary evaporated, and dried under vacuum to obtain 1-aminopropyl-3-methylimidazolium tetrafluoroborate ionic liquid. Step A2: Mix 1-aminopropyl-3-methylimidazolium tetrafluoroborate and aluminum chloride, and react under nitrogen protection at a temperature of 78-80℃ for 5-6 hours to obtain a metal-based 1-aminopropyl-3-methylimidazolium tetrafluoroborate ionic liquid. Step A3: Mix SBA-15 molecular sieve, 3-chloropropyltrimethoxysilane and toluene, and react for 24 h under nitrogen protection, stirring at 120-150 rpm and temperature of 105-110℃. Then, perform Soxhlet extraction with dichloromethane for 12 h, filter, and vacuum dry to obtain silane-modified molecular sieve. Mix silane-modified molecular sieve, metal-based 1-aminopropyl-3-methylimidazolium tetrafluoroborate ionic liquid and anhydrous ethanol, and react for 12 h under temperature of 88-90℃. Then, perform Soxhlet extraction with dichloromethane for 12 h, filter, and vacuum dry to obtain immobilized molecular sieve. Step A4: Mix phenylphosphine dichloride and dichloromethane at a stirring rate of 120-150 rpm and at room temperature for 15-20 min. Then add the supported molecular sieve, ultrasonically disperse for 5-8 min, and continue stirring for 2-3 h. Filter, rotary evaporate, and vacuum dry to obtain the composite solid catalyst.
5. The method for preparing 2-chloro-6-trichloromethylpyridine according to claim 4, characterized in that: In step A1: the ratio of N-methylimidazolium, 3-chloropropylamine hydrochloride, and acetonitrile is 9-9.1g:13-13.2g:45-50mL; the ratio of 1-aminopropyl-3-methylimidazolium chloride ionic liquid, sodium fluoroborate, and acetone is 12.4-12.8g:10.8-11g:35-40min.
6. The method for preparing 2-chloro-6-trichloromethylpyridine according to claim 4, characterized in that: In step A2, the ratio of 1-aminopropyl-3-methylimidazolium tetrafluoroborate to aluminum chloride is 21-22g: 13.2-13.3g.
7. The method for preparing 2-chloro-6-trichloromethylpyridine according to claim 4, characterized in that: In step A3: the ratio of SBA-15 molecular sieve, 3-chloropropyltrimethoxysilane and toluene is 5.8-6g: 4.5-5g: 50-55mL; the ratio of silane-modified molecular sieve, metal-based 1-aminopropyl-3-methylimidazolium tetrafluoroborate ionic liquid and anhydrous ethanol is 7.2-7.8g: 2.32-2.35g: 40-45mL.
8. The method for preparing 2-chloro-6-trichloromethylpyridine according to claim 4, characterized in that: In step A4, the ratio of phenylphosphodichloro, dichloromethane, and immobilized molecular sieve is 1.4-1.45g: 15-20mL: 5.1-5.2g.