High-purity 4-chloro-3, 5-dimethylphenol and ionic liquid oxidation and chlorination preparation method thereof

Abstract

The invention relates to an ionic liquid oxidation and chlorination preparation method of high-purity 4-chloro-3, 5-dimethylphenol, which comprises the following steps: firstly, mixing a phenolic compound, a transition metal salt catalyst, an ionic liquid and hydrochloric acid at the temperature of 60-95 DEG C, stirring in an oxygen atmosphere, and continuously introducing oxygen to realize reaction; the ionic liquid is a mixture of choline chloride / urea or choline chloride / glycerol; and then, continuously dropwise adding hydrochloric acid into the reaction mixture, and continuously reacting after dropwise adding until high-purity 4-chloro-3, 5-dimethylphenol is generated. According to the preparation method disclosed by the invention, the ionic liquid is adopted, so that environmental pollution can be avoided, the complexity of post-treatment is reduced, and meanwhile, the production cost is greatly reduced by recycling the catalyst and the solvent; compared with the prior art, the chlorination method provided by the invention is green, economical and efficient, high-purity preparation of 4-chloro-3, 5-dimethylphenol can be realized, and the method has a good industrial application prospect.

Description

Technical Field

[0001] The present invention relates to the technical field of chemical synthesis, and in particular, to a method for preparing high-purity 4-chloro-3,5-dimethylphenol by oxidative chlorination with an ionic liquid. Background Art

[0002] 4-Chloro-3,5-dimethylphenol (PCMX) is a broad-spectrum bactericidal disinfectant, which is widely used in the anti-mildew and sterilization treatments in daily life and industrial fields. In addition to being a traditional disinfectant and anti-mildew agent, PCMX and its lead compounds containing the PCMX structural fragment also exhibit activities such as anti-tumor, anti-inflammatory, antibacterial, and antiviral activities, and have become one of the potential drugs for treating related diseases. Currently, the industrial synthesis of PCMX mainly involves using 3,5-dimethylphenol as a raw material and obtaining it through a chlorination reaction. However, in this traditional chlorination reaction process, by-products such as 2-chloro-3,5-dimethylphenol and 2,4-dichloro-3,5-dimethylphenol will be generated. These by-products not only affect the purity of the product but also increase the complexity of the post-treatment.

[0003] In the prior art, the synthesis methods of PCMX mainly include the chlorine method, the sulfonyl chloride method, the oxychlorination reaction method, and other chlorinating reagent methods, etc. The oxychlorination reaction method has become a more promising synthesis method in industrial production due to its high para-selectivity, high atomic efficiency, no waste gas emission, and the catalyst can be recycled multiple times. This method usually uses copper chloride as a catalyst, chloride ions (such as hydrochloric acid or chloride inorganic salts) as a chlorine source, and oxygen as an oxidant. Compared with chlorine, sulfonyl chloride, and hypochlorite, the use of hydrochloric acid or chloride inorganic salts is more convenient and safe to operate, and at the same time, the cost is lower. The oxychlorination reaction method provides a continuous phenol chlorination process, in which phenol contacts with copper chloride in an aqueous medium containing hydrochloric acid, and an oxygen-containing gas is introduced into the reactor. Subsequently, the chlorinated phenol is separated from the reaction product, and the unchanged reactants are recycled back to the reactor. In this process, hydrochloric acid and air or oxygen are consumed, and phenol undergoes a chlorination reaction to mainly produce p-chlorophenol. According to the reaction mechanism of phenolic compounds, the reaction step of cupric oxychloride (II) with cupric chloride (II) is a key step in the oxychlorination process. This process can be divided into two main steps. The usual operating procedure includes: First, chlorinate an organic substrate (such as a phenolic compound) with cupric chloride (II) (Step 1); then, use atmospheric oxygen to oxidize the generated cuprous chloride (I) to cupric oxychloride (II) (Step 2); finally, restore cupric chloride (II) by reacting cupric oxychloride (II) with hydrogen chloride to complete the copper cycle (Step 3). The reaction formulas are as follows: 2CuCl2 +C8H9OH=C8H9ClO+2CuCl +HCl (1); 2CuCl + 1 / 2O2 = Cu2OCl2 (2); Cu2OCl2 + 2HCl = 2CuCl2 + H2O (3).

[0004] Although the oxidative chlorination method has obvious advantages in the chlorination reaction of phenolic compounds, there are still relatively few relevant studies and patents at present. Although the existing oxychlorination reaction method has potential, there are also some problems that need to be solved urgently: First of all, traditional oxidative chlorination reactions are usually carried out in organic solvents or aqueous media. The use of organic solvents is not only environmentally unfriendly but also may increase production costs. On the other hand, although some patents (such as CN111440051A, CN101624333A, CN103351282A and British patent GB1240829) use the oxidative chlorination method to react in organic solvents or aqueous media to synthesize 4-chloro-3,5-dimethylphenol (PCMX), the aqueous reaction system is often limited by proton transfer, making it difficult to effectively control the reaction progress and improve the reaction selectivity. In addition, the application of the "green solvent" ionic liquid in such reactions has not been widely studied, and the aqueous reaction system is often difficult to achieve high selectivity and high efficiency in complex reactions.

[0005] With the promotion of the concept of green chemistry, the environmental impact of traditional organic solvents and some conventional catalysts has gradually become a major issue in research and industrial production. Especially some highly toxic and difficult-to-degrade catalysts, such as alkylimidazole ionic liquids, Chinese patent application with publication number CN114805033A discloses a method for synthesizing chlorophenol compounds. Using a Lewis acid-based alkylimidazole ionic liquid as a catalyst, the phenolic compound is subjected to oxidative chlorination reaction with hydrochloric acid and an oxidant to obtain chlorophenol compounds. Its high cost and strong toxicity (such as the LC50 value as low as 1 - 580 mg / L) limit its wide application in the field of green chemistry. There is still room for improvement in the operation safety, economy and environmental friendliness of the existing oxidative chlorination methods.

[0006] The patent with the publication number CN114805033A proposes a method for oxidative chlorination reaction based on copper chloride catalysis for synthesizing 4-chloro-3,5-dimethylphenol. This method uses copper chloride as a catalyst, oxygen as an oxidant, and hydrochloric acid as a chlorine source, and promotes the reaction by continuously introducing oxygen. The reaction is usually carried out in an organic solvent or an aqueous medium. Although this method has certain advantages in catalyst recovery and oxygen-promoted reaction, there are still multiple problems. First, the traditional solvent system may cause environmental pollution, and the proton transfer in the aqueous medium is insufficient, which limits the reaction selectivity. Second, the catalyst recovery effect is not ideal, and there are certain by-products generated, which affects the product purity and post-treatment efficiency. In addition, this method relies on a relatively high catalyst dosage and does not optimize the catalyst usage efficiency.

[0007] Therefore, how to develop a safer, more economical and environmentally friendly catalytic system during the selective chlorination of phenolic compounds, and be able to achieve efficient and selective reactions under mild conditions has become a technical problem to be solved urgently. The current methods not only have environmental pollution problems, but also are difficult to effectively control the generation of by-products and improve the product selectivity. Therefore, developing a selective oxidative chlorination method for phenolic compounds with safety, economy, excellent catalytic activity and environmental friendliness has important industrial application value and green chemistry significance. Summary of the Invention

[0008] The technical problem to be solved by the present invention is to provide an ionic liquid oxidative chlorination preparation method for high-purity 4-chloro-3,5-dimethylphenol to solve the problems of difficult catalyst recovery, poor reaction selectivity, low product purity, environmental pollution and complex post-treatment existing in the prior art.

[0009] To overcome the above defects of the prior art, the present invention provides an ionic liquid oxidative chlorination preparation method for high-purity 4-chloro-3,5-dimethylphenol, which includes the following steps: S1: Mix a phenolic compound, a transition metal salt catalyst, an ionic liquid and initial hydrochloric acid, stir in an oxygen atmosphere at 60 - 95 °C to obtain a mixture, and continuously introduce oxygen into the mixture. The ionic liquid is liquid choline chloride / urea or choline chloride / glycerol eutectic solvent; S2: Continuously dropwise add hydrochloric acid to the mixture in step S1, continuously react after the addition is completed, and control the reaction temperature at 60 - 95 °C to obtain high-purity 4-chloro-3,5-dimethylphenol.

[0010] Compared with the prior art, the method for preparing high-purity 4-chloro-3,5-dimethylphenol by ionic liquid oxidation chlorination of the present application has the following advantages: The preparation method of the present invention is based on the principle of oxidation chlorination reaction. Using transition metal salts (including copper chloride, etc.) as catalysts and oxygen as the oxidant, acting together with the chlorine source provided by hydrochloric acid, a highly selective chlorination reaction is carried out in the solvent environment of ionic liquid to synthesize 4-chloro-3,5-dimethylphenol. The continuous introduction of oxygen not only promotes the recycling of the copper oxide catalyst but also accelerates the progress of the chlorination reaction.

[0011] Compared with the prior art, the present invention has significant advantages in the amount of catalyst used. A relatively small amount of catalyst is adopted, reducing the consumption of the catalyst and lowering the cost. In addition, the catalyst of the present invention can be effectively recovered and reused after the reaction, realizing the efficient recycling of the catalyst, avoiding the waste of the catalyst, and improving the use efficiency of the catalyst. This advantage makes the present invention more economical and environmentally friendly in the production process, avoiding the problem of difficult recovery of the catalyst in the traditional method and eliminating the need for frequent catalyst replacement.

[0012] In terms of the purity of the reaction product, the present invention adopts practical separation and purification methods, avoiding the problems of residual moisture and polymers in the product in the original technology. In the prior art, when using chromatographic detection, the presence of polymers often leads to the presence of moisture in the product, resulting in a low actual yield. The method of the present invention ensures the preparation of high-purity 4-chloro-3,5-dimethylphenol by optimizing the process flow and solvent environment, so that the product is obtained in a more pure form.

[0013] The preparation method of the present invention realizes an efficient reaction under mild conditions by reasonably controlling the amount of oxygen introduced (4 times the theoretical oxygen demand) and the reaction temperature (60 - 95 °C). It not only improves the purity of the product but also effectively reduces the generation of by-products. In addition, the recycling of ionic liquids and the reuse of catalysts not only greatly reduce the production cost but also reduce the generation of waste, which conforms to the concept of green chemistry. The system of the present invention has significant advantages of low cost, environmental friendliness, and high safety. The ionic liquids (choline chloride / urea or choline chloride / glycerol solvent) of the present invention have excellent solubility and low melting point characteristics, can effectively dissolve reactants and catalysts during the reaction process, and provide a good reaction environment for transition metal salts such as copper chloride, thereby improving the reaction selectivity and reaction rate. At the same time, the ionic liquid can dissolve the catalyst and reactants during the reaction process, improve proton transport, significantly improve the reaction efficiency, and does not require high-pressure operation, greatly reducing the requirements for production conditions. The synergistic effect between the catalyst and the ionic liquid, while the ionic liquid dissolves the catalyst and reactants, improves the proton transport in the reaction system, making the reaction more efficient and the reaction conditions milder and safer. Through this synergistic effect, the present invention not only improves the reaction selectivity and yield but also makes the reaction conditions milder and safer, with good industrial application prospects.

[0014] In summary, the present invention uses ionic liquids (choline chloride / urea or choline chloride / glycerol solvent) as reaction solvents, solves the environmental pollution problems caused by the use of organic solvents in the prior art, and improves the reaction selectivity and yield; uses transition metal salt catalysts such as copper chloride, combined with the action of ionic liquids, not only improves the reaction efficiency but also enables the catalyst to be recycled multiple times, reducing the production cost; through mild reaction conditions and excessive oxygen introduction, the high efficiency and selectivity of the reaction are ensured, while avoiding the use of high-pressure equipment, reducing the operation difficulty and equipment cost; the present invention significantly improves the overall efficiency of the reaction through the synergistic effect of the catalyst and the ionic liquid, solves the problems of difficult catalyst recovery, poor reaction selectivity, and by-product generation in the existing methods.

[0015] As a preferred solution, in the step S1, the phenolic compound is m-xylenol.

[0016] Compared with the prior art, by adopting the above technical solution and using m-xylenol as the phenolic compound, the selectivity and yield of the reaction can be improved. Due to the good steric hindrance effect of the molecular structure of m-xylenol, it has a higher para-selectivity in the chlorination reaction, which can reduce the formation of by-products, especially the ortho-chlorinated products. This structural characteristic can better guide the selectivity of the reaction in the oxidative chlorination reaction, ensure the high purity of 4-chloro-3,5-dimethylphenol as the main product, significantly improve the yield of the product, and the use of m-xylenol as the raw material avoids the multiple chlorination or by-product formation that may occur in the traditional method, thereby improving the purity of the final product.

[0017] As a preferred solution, in the step S1, the transition metal salt catalyst is one of copper chloride, copper acetate, basic copper carbonate, copper nitrate hexahydrate, and anhydrous copper sulfate.

[0018] Compared with the prior art, the use of the above transition metal salt catalyst can effectively promote the oxidative chlorination reaction. The above catalyst has good catalytic activity under mild reaction conditions and can efficiently convert phenolic compounds into chlorinated products in an oxygen atmosphere; compared with traditional catalysts, the catalyst within the above range of the present invention has a lower catalyst consumption, and its reaction mechanism is relatively clear, which can effectively avoid the formation of by-products; and the recyclability of the catalyst of the present invention makes it have good economy in industrial production, reduces the reaction cost, and can maintain a high catalytic activity in multiple reactions, further improving the raw material utilization rate and product yield, ultimately realizing an efficient chlorination reaction, and improving the selectivity and yield of the reaction while reducing the environmental burden.

[0019] As a preferred solution, in the step S1, the feeding ratio of the phenolic compound, the transition metal salt catalyst, the ionic liquid, and hydrochloric acid is: 1:(0.25 - 1.0):(0.5 - 2.0):0.5.

[0020] Compared with the prior art, adopting the above-mentioned feeding ratio can effectively optimize the selectivity of the reaction and the purity of the product. The feeding ratio of the transition metal salt catalyst (0.25 - 1.0) relative to the phenolic compound ensures the efficient progress of the catalytic reaction without generating excessive by-products. The feeding ratio of the ionic liquid (0.5 - 2.0) ensures that the solvent plays a good dissolving role during the reaction and avoids the decrease in reaction efficiency or unnecessary waste of resources caused by excessive solvent. The appropriate addition of hydrochloric acid (0.5 times the molar amount of the phenolic compound) ensures an adequate supply of the chlorine source, further promotes the chlorination reaction, and at the same time avoids the influence of excessive hydrochloric acid on the product purity. And it synergistically acts with the re-addition of hydrochloric acid in step S2. By optimizing the above-mentioned feeding ratio, the present invention can significantly improve the yield and purity of 4-chloro-3,5-dimethylphenol, while ensuring the efficient progress of the reaction under mild conditions, reducing the generation of by-products, and improving the atom utilization rate.

[0021] As a preferred solution, in step S1, the pressure of the introduced oxygen is 0.5 - 1 bar, and the amount of oxygen introduced is in excess, and the introduced amount is 4 times the theoretical oxygen demand.

[0022] Compared with the prior art, adopting the above-mentioned oxygen pressure and the scheme of introducing excessive oxygen can effectively increase the reaction rate and ensure the efficient progress of the oxidative chlorination reaction. Under the condition that the oxygen pressure is 0.5 - 1 bar, the oxygen supply during the reaction process can be stably maintained, avoiding the situation of insufficient or excessive oxygen in the reaction, and thus ensuring the stability and efficiency during the reaction process. The amount of oxygen introduced is 4 times the theoretical oxygen demand, which can ensure the full conversion of cupric oxide to cupric oxychloride in the reaction and the full circulation of cupric chloride, promoting the progress of the whole reaction. By ensuring an adequate supply of oxygen, the reaction stagnation or efficiency reduction caused by insufficient oxygen is avoided, the selectivity of the reaction is improved, and the generation of unnecessary by-products during the reaction process is reduced.

[0023] As a preferred solution, in step S2, the total molar amount of the added hydrochloric acid is 50 - 150% of the phenolic compound, and the time for adding the hydrochloric acid is 3 - 5 hours.

[0024] Compared with the prior art, adopting the above-mentioned scheme where the total molar amount of hydrochloric acid added is 50 - 150% of the phenolic compound can effectively control the reaction rate and reaction selectivity of the chlorination reaction. The optimization of the dropping amount and dropping time of hydrochloric acid ensures sufficient but not excessive supply of the chlorine source during the reaction process, thereby avoiding the generation of side reactions or by-products caused by excessive hydrochloric acid. And in cooperation with the hydrochloric acid in step S1, it effectively promotes the formation of 4-chloro-3,5-dimethylphenol and improves the selectivity of the target product. By dropping hydrochloric acid within the time range of 3 - 5 hours, the concentration of hydrochloric acid during the reaction process can be ensured to remain stable, which is beneficial to the efficient action of the catalyst and further improves the controllability and repeatability of the reaction.

[0025] As a preferred scheme, in the step S2, the duration of the continuous reaction is 1 - 24 h.

[0026] Compared with the prior art, adopting the above-mentioned scheme where the duration of the continuous reaction is 1 - 24 hours can ensure that the reaction proceeds completely and achieves high selectivity.

[0027] As a preferred scheme, after the step S2, it further includes step S3: After the reaction is completed, separate high-purity 4-chloro-3,5-dimethylphenol and recover the catalyst and ionic liquid.

[0028] As a preferred scheme, separating high-purity 4-chloro-3,5-dimethylphenol and recovering the catalyst and ionic liquid includes: (1) Cool the reaction solution to 0 - 30 °C for low-temperature crystallization, and filter to obtain the crude product; (2) After washing the crude product with water, recrystallize it with tetrachloroethylene to obtain high-purity 4-chloro-3,5-dimethylphenol; (3) Extract the filtrate and washing solution obtained after the treatment in step (2) with toluene, concentrate and recover the catalyst and ionic liquid, and recycle them for subsequent reactions.

[0029] Compared with the prior art, adopting the separation and recovery scheme of the above step S3 can significantly improve the purity of the product, effectively recover the catalyst and ionic liquid, reduce production costs and environmental pollution. By combining low-temperature crystallization and recrystallization with tetrachloroethylene, not only the purity of 4-chloro-3,5-dimethylphenol is improved, but also impurities can be effectively removed to obtain a high-purity final product. The above operations not only optimize the extraction and purification effects of the product, but also further ensure the efficient recovery of the catalyst and ionic liquid, avoid waste of resources, and improve the overall economy and sustainability. By extracting and recovering the solvent and catalyst with toluene, the recovery efficiency of the system is improved, and it can be recycled in multiple reaction cycles, thereby reducing the environmental impact and production costs during the production process.

[0030] The present invention also provides high-purity 4-chloro-3,5-dimethylphenol prepared by the above preparation method, and the purity of the 4-chloro-3,5-dimethylphenol > 99%.

[0031] Compared with the prior art, the high-purity 4-chloro-3,5-dimethylphenol prepared by the method for preparing an ionic liquid by oxidative chlorination in this application has the following advantages: Conventional preparation methods usually use organic solvents, generating a large amount of waste and being difficult to recycle. In contrast, the preparation method of the present invention uses an ionic liquid (choline chloride / glycerol or choline chloride / urea) as the reaction solvent, which has good environmental friendliness and biodegradability, significantly reducing environmental pollution problems. The synergistic effect of the ionic liquid and the catalyst improves the selectivity and efficiency of the reaction, effectively reducing the generation of by-products and increasing the yield and purity of the target product. The preparation method of the present invention avoids the generation of by-products and impurities at high temperatures through mild reaction conditions (60-95 °C), ensuring the high purity (>99%) of the final product. It not only achieves remarkable results in improving product purity but also effectively solves technical problems such as environmental pollution, resource waste, and difficult catalyst recovery in traditional methods, and has high industrial application value. Detailed implementation modes

[0032] First of all, those skilled in the art should understand that these implementation modes are only used to explain the technical principles of the embodiments of this application and are not intended to limit the protection scope of the embodiments of this application. Those skilled in the art can make adjustments according to needs to adapt to specific application scenarios.

[0033] The present invention provides a method for preparing high-purity 4-chloro-3,5-dimethylphenol by oxidative chlorination of an ionic liquid, comprising the following steps: S1: Mix a phenolic compound, a transition metal salt catalyst, an ionic liquid, and initial hydrochloric acid, stir in an oxygen atmosphere at 60-95 °C to obtain a mixture, and continuously introduce oxygen into the mixture. The ionic liquid is a liquid choline chloride / urea or choline chloride / glycerol eutectic solvent; S2: Continuously add hydrochloric acid dropwise to the mixture in step S1. After the addition is completed, continue the reaction and control the reaction temperature at 60-95 °C to obtain high-purity 4-chloro-3,5-dimethylphenol.

[0034] As a preferred scheme, in step S1, the phenolic compound is m-xylenol.

[0035] As a preferred scheme, in step S1, the transition metal salt catalyst is one of copper chloride, copper acetate, basic copper carbonate, copper nitrate hexahydrate, and anhydrous copper sulfate.

[0036] As a preferred embodiment, in the step S1, the feeding ratio of the phenolic compound, transition metal salt catalyst, ionic liquid, and hydrochloric acid is: 1:(0.25 - 1.0):(0.5 - 2.0):0.5.

[0037] As a preferred embodiment, in the step S1, the pressure of the introduced oxygen is 0.5 - 1 bar, and the introduced amount of oxygen is in excess, and the introduced amount is 4 times the theoretical oxygen demand.

[0038] As a preferred embodiment, in the step S2, the total molar amount of the added hydrochloric acid is 50 - 150% of the phenolic compound, and the time for adding the hydrochloric acid is 3 - 5 hours.

[0039] As a preferred embodiment, in the step S2, the time for the continuous reaction is 1 - 24 h.

[0040] As a preferred embodiment, after the step S2, it further includes the step S3: after the reaction is completed, separate high-purity 4-chloro-3,5-dimethylphenol and recover the catalyst and ionic liquid.

[0041] As a preferred embodiment, separating the high-purity 4-chloro-3,5-dimethylphenol and recovering the catalyst and ionic liquid includes: (1) Cooling the reaction solution to 0 - 30 °C for low-temperature crystallization, and filtering to obtain a crude product; (2) After washing the crude product with water, recrystallize it with tetrachloroethylene to obtain high-purity 4-chloro-3,5-dimethylphenol; (3) Extract the filtrate and washing solution obtained in the step (2) with toluene, concentrate and recover the catalyst and ionic liquid, and recycle them for subsequent reactions.

[0042] The present invention aims to solve the problems mentioned in the above background art, and provides a novel ionic liquid eutectic solvent. Using this as a solvent, a method for the selective oxidative chlorination of 4-chloro-3,5-dimethylphenol (PCMX) compounds has mild catalytic system conditions, a safe process, no generation of toxic gases, and good economy; high activity and good product selectivity; convenient catalyst recovery and recyclability; in the present invention: Ionic liquids are a class of salts with a melting point below 100 °C and in a liquid state at room temperature. A typical ionic liquid consists of a large and asymmetric organic cation and an organic or inorganic anion. Ionic liquids are considered potential "green solvents" in processes such as synthesis, analysis, and separation due to their unique properties such as almost no vapor pressure, low melting point, non-flammability, good thermal stability, electrochemical stability, wide electrochemical window, good conductivity, and adjustable physical properties; Deep eutectic solvents are a new type of ionic liquid. Deep eutectic solvents are composed of amine salts (R1R2R3R4N+ ∙X-) and complexing agents, where the complexing agents can be substances such as urea, glycerol, and ethylene glycol, and X represents a halide ion; deep eutectic solvents have similar physical and chemical properties to traditional ionic liquids and have the characteristics of simple synthesis, environmental friendliness, and biodegradability. Deep eutectic solvents have been widely used in the fields of electrochemistry, catalysis, organic synthesis, dissolution and extraction, and materials chemistry; Choline chloride / urea and choline chloride / glycerol are two typical deep eutectic solvents. The synthesis processes of choline chloride / urea and choline chloride / glycerol are simple and can be prepared by mixing choline chloride with urea and glycerol at 80 °C respectively. In addition, choline chloride / urea and choline chloride / glycerol are inexpensive and can be applied on a large scale industrially.

[0043] In this invention, a new type of ionic liquid, deep eutectic solvents of choline chloride / urea and choline chloride / glycerol, is used as the solvent, copper chloride is used as the catalyst, and hydrochloric acid is used as the chlorine source. An appropriate excess of hydrochloric acid can provide a rich chlorine source. Not only does this invention provide a higher para-chlorophenol ratio than previously encountered, but the operating properties of the ortho-chlorine reaction are lower than those of the prior art processes, and expensive high-pressure equipment is not used; in addition, under the conditions of this invention, when the temperature is below 95 °C, by carrying out the chlorination reaction, the coupling and polymerization reactions that are often encountered in the chlorination reaction can be inhibited. In an aqueous phase or ionic liquid reaction medium, with a new type of ionic liquid as the solvent and oxygen as the oxidant, a green synthesis method for preparing halogenated phenol compounds by the oxidative halogenation reaction of phenolic compounds and halogenated salts (or hydrohalic acids) is achieved. The prepared halogenated phenol compounds have good selectivity, high yield, mild reaction conditions, do not require the use of volatile organic solvents, and the new type of ionic liquid and catalyst used can be recycled.

[0044] This invention also provides high-purity 4-chloro-3,5-dimethylphenol prepared by the above preparation method, and the purity of the 4-chloro-3,5-dimethylphenol > 99%.

[0045] The following provides examples combined with specific data and experimental results to further expand the above technical solutions of this invention: Example 1

[0046] This example provides a method for preparing high-purity 4-chloro-3,5-dimethylphenol and its oxidative chlorination using ionic liquids. The high-purity 4-chloro-3,5-dimethylphenol is prepared by this preparation method, and the preparation method includes the following steps: S1: Raw material mixing and initial reaction Add m - xylenol (3,5 - dimethylphenol, 488.6 g, 4 mol), copper(II) chloride dihydrate (CuCl₂·2H₂O, 682 g, 4 mol), choline chloride / glycerol ionic liquid (1295.3 g, 4 mol), and initial concentrated hydrochloric acid (203 g, 2 mol, 37% by mass) into a 5000 mL four - necked flask, and stir to mix. Under the conditions of 85 °C and an oxygen pressure of 1 bar, continuously introduce excessive oxygen (4 times the theoretical oxygen demand) to form a homogeneous reaction system.

[0047] S2: Dropwise addition of hydrochloric acid in stages and reaction Dropwise add the remaining concentrated hydrochloric acid (406 g, 4 mol) evenly within 4 hours while maintaining the reaction temperature at 85 °C. After the addition is complete, continue the reaction for 7 hours.

[0048] S3: Product separation and solvent recovery (1) Crystallization at low temperature: Cool the reaction solution to 25 °C to precipitate a brown crude product, and filter to obtain the crude product; (2) Purification by recrystallization: After washing the crude product with water, dissolve it in tetrachloroethylene for recrystallization to obtain 424.2 g of white crystals with a purity of 99.3% and a yield of 86.2%; (3) Recovery of solvent and catalyst: Extract the filtrate and washing solution with toluene, concentrate to a volume of 1150 mL, and recover the choline chloride / glycerol ionic liquid and CuCl₂ catalyst, which can be directly used for the next batch of reactions.

[0049] Example 2 (Catalyst recycling) Example 2 is based on Example 1 and continues with the recycling reaction. The separated catalyst CuCl₂ and choline chloride / glycerol eutectic ionic liquid are reused repeatedly, and it specifically includes the following steps: S1: Raw material mixing and initial reaction Add the recycled CuCl₂ catalyst (from Example 1), choline chloride / glycerol ionic liquid (1150 mL, containing 4 mol of solvent), m - xylenol (488.6 g, 4 mol), and initial concentrated hydrochloric acid (203 g, 2 mol) into a 5000 mL four - necked flask, and stir to mix. Under the conditions of 85 °C and an oxygen pressure of 1 bar, introduce excessive oxygen (4 times the theoretical oxygen demand).

[0050] S2: Dropwise addition of hydrochloric acid in stages and reaction Dropwise add the remaining concentrated hydrochloric acid (406 g, 4 mol) evenly within 4 hours while maintaining the reaction temperature at 85 °C. After the addition is complete, continue the reaction for 9 hours.

[0051] S3: Product separation and secondary recovery (1)Low-temperature crystallization: After the reaction solution was cooled to 25 °C, it was filtered by suction to obtain the crude product; (2)Purification by recrystallization: The crude product was recrystallized with tetrachloroethylene to obtain 398.0 g of white crystals, with a purity of 99.2% and a yield of 80.8%; (3)Secondary recovery: The filtrate was recovered for the solvent and catalyst according to the steps of Example 1 and continued to be recycled.

[0052] Example 3-7 Examples 3-7 were similar to Example 2. Based on the previous example, the recycling reaction was continued. The catalyst CuCl2 and choline chloride / glycerol eutectic ionic liquid separated in the previous example were used and recycled repeatedly. Table 1 shows the results of the liquid-phase oxidative chlorination reaction of m-xylenol and copper chloride using CuCl2 / choline chloride / glycerol eutectic ionic liquid as the solvent: Table 1. Reaction results of the recycling of CuCl2 / choline chloride / glycerol eutectic ionic liquid Example Number of repeated cycles of use Conversion rate Selectivity (PCMX) Yield (PCMX) 2 1 94.2 91.5 86.2 3 2 90.7 89.1 80.8 4 3 93.3 90.3 84.2 5 4 93.1 89.5 83.3 6 5 95.1 88.7 84.4 7 6 91.6 90.6 83.0 According to the results in Table 1, it can be seen that with the recycling of the catalyst and ionic liquid, the conversion rate, selectivity, and yield of the reaction remained stable in multiple cycles and were always maintained at a relatively high level. For example, in the first cycle (Example 2), the conversion rate was 94.2%, the selectivity was 91.5%, and the yield was 86.2%; even in the sixth cycle (Example 7), the conversion rate and yield still remained at 91.6% and 83.0% respectively. These results indicate that the catalyst CuCl2 and choline chloride / glycerol ionic liquid have good recycling stability, can continuously and effectively catalyze the reaction in multiple reaction cycles, and the reaction selectivity and yield remain at a relatively high level. Therefore, the preparation method provided by the present invention has good industrial application prospects, can improve production efficiency while reducing resource waste, and has significant economic and sustainability.

[0053] Through the above embodiments, it is further proved that the present invention provides a method for preparing high-purity 4-chloro-3,5-dimethylphenol by oxidative chlorination using ionic liquid choline chloride / glycerol or choline chloride / urea as the reaction solvent. This not only has the physical and chemical properties of traditional ionic liquids, such as low melting point, good thermal stability and electrochemical stability, but also has the characteristics of environmental friendliness and biodegradability of ionic liquids, making this method have broad application potential in the field of green chemistry. Compared with the traditional organic solvent or water medium reaction system, the use of ionic liquids avoids environmental pollution, reduces the complexity of post-treatment, and effectively improves the selectivity and yield of the reaction; by using transition metal salts (including copper chloride) as catalysts in the present invention and combining the role of ionic liquids, the high efficiency of the catalyst and the excellent solubility of ionic liquids are exerted, and the two cooperate with each other, significantly improving the reaction efficiency and chlorine selectivity. Copper chloride can not only efficiently catalyze the chlorination reaction of phenol, but also promote the oxidation process of oxygen, thereby enhancing the overall atomic efficiency of the reaction and avoiding the generation of by-products; the technical solution of the present invention also has advantages in reaction conditions. By carrying out the reaction under mild conditions (60-95 °C) and continuously introducing oxygen within the range of oxygen pressure controlled at 0.5-1 bar, the stability and high efficiency of the reaction are ensured, unnecessary energy consumption is reduced, and the use of high-pressure reaction equipment is avoided, reducing the operation difficulty and equipment cost.

[0054] The preparation method of the present invention not only improves the yield and purity of 4-chloro-3,5-dimethylphenol (>99%), but also significantly reduces the production cost, promoting the large-scale and low-cost production of this chemical. These technological innovations provide strong support for industrial production and also provide new ideas for the synthesis of future environmentally friendly chemicals.

[0055] In the description of the present application, the description with reference to terms such as "one embodiment", "some embodiments", "in this embodiment", "specific examples", or "some examples" means that the specific features, mechanisms, materials or characteristics described in connection with the embodiment or example are included in at least one embodiment or example of the present application. In this specification, the schematic descriptions of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, mechanisms, materials or characteristics described can be combined in a suitable manner in any one or more embodiments or examples. In addition, without contradiction, those skilled in the art can combine and combine the different embodiments or examples described in this specification and the features of different embodiments or examples.

[0056] As described above, it is only the specific implementation manner of the present application, but the protection scope of the present application is not limited thereto. Any changes or substitutions that can be easily thought of by those skilled in the art within the technical scope disclosed in the present application should be covered by the protection scope of the present application. Therefore, the protection scope of the present application shall be subject to the protection scope of the claims.

Claims

1. A method for preparing high-purity 4-chloro-3,5-dimethylphenol by ionic liquid oxidation and chlorination, characterized in that, It includes the following steps: S1: Mix a phenolic compound, a transition metal salt catalyst, an ionic liquid and initial hydrochloric acid, stir in an oxygen atmosphere at 60 - 95 °C to obtain a mixture, and continuously introduce oxygen into the mixture. The ionic liquid is liquid choline chloride / urea or choline chloride / glycerol eutectic solvent; S2: Continuously dropwise add hydrochloric acid to the mixture obtained in step S1, continuously react after the addition is completed, and control the reaction temperature at 60 - 95 °C to obtain high-purity 4-chloro-3,5-dimethylphenol.

2. The method for preparing high-purity 4-chloro-3,5-dimethylphenol by ionic liquid oxidation chlorination according to claim 1, characterized in that, In step S1, the phenolic compound is m-xylenol.

3. The method for preparing high-purity 4-chloro-3,5-dimethylphenol by ionic liquid oxidation chlorination according to claim 1, characterized in that, In step S1, the transition metal salt catalyst is one of copper chloride, copper acetate, basic copper carbonate, copper nitrate hexahydrate, and anhydrous copper sulfate.

4. The method for preparing high-purity 4-chloro-3,5-dimethylphenol by ionic liquid oxidation chlorination according to claim 1, characterized in that, In step S1, the feeding ratio of the phenolic compound, the transition metal salt catalyst, the ionic liquid, and hydrochloric acid is: 1:(0.25 - 1.0):(0.5 - 2.0):0.

5.

5. The method for preparing high-purity 4-chloro-3,5-dimethylphenol by ionic liquid oxidation chlorination according to claim 1, wherein, In step S1, the pressure of introducing oxygen is 0.5 - 1 bar, and the amount of oxygen introduced is in excess, and its introduction amount is 4 times the theoretical oxygen demand.

6. The method for preparing high-purity 4-chloro-3,5-dimethylphenol by ionic liquid oxidation chlorination according to claim 1, characterized in that, In step S2, the total molar amount of the dropwise added hydrochloric acid is 50 - 150% of the phenolic compound, and the time for dropwise adding hydrochloric acid is 3 - 5 hours.

7. The method for preparing high-purity 4-chloro-3,5-dimethylphenol by ionic liquid oxidation chlorination according to claim 1, characterized in that, In step S2, the time for continuous reaction is 1 - 24 h.

8. The method for preparing high-purity 4-chloro-3,5-dimethylphenol by ionic liquid oxidation chlorination according to claim 1, characterized in that, After step S2 is completed, it further includes step S3: After the reaction is completed, separate high-purity 4-chloro-3,5-dimethylphenol and recover the catalyst and the ionic liquid.

9. The method for preparing high-purity 4-chloro-3,5-dimethylphenol by ionic liquid oxidation chlorination according to claim 8, characterized in that, The separation of high-purity 4-chloro-3,5-dimethylphenol and the recovery of the catalyst and the ionic liquid include: (1) Cool the reaction solution to 0 - 30 °C for low-temperature crystallization, and filter to obtain a crude product; (2) Wash the crude product with water and then recrystallize with tetrachloroethylene to obtain high-purity 4-chloro-3,5-dimethylphenol; (3) Extract the filtrate and washing solution obtained after the treatment in step (2) with toluene, concentrate and recover the catalyst and the ionic liquid, and recycle them for subsequent reactions.

10. A high-purity 4-chloro-3,5-dimethylphenol prepared by the preparation method of any one of claims 1-9, characterized in that, The purity of the 4-chloro-3,5-dimethylphenol > 99%.