A method for coupling cross-phase chlorine transfer and in-situ chlorination
By coupling transphase chlorine transfer with in-situ chlorination, the safety hazards and low utilization rate of traditional chlorination methods have been solved, achieving a high-efficiency and low-cost chlorination reaction. The products are suitable for the synthesis of pesticide and pharmaceutical intermediates.
Patent Information
- Application Number
- CN202610721346.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2026-05-25
- Publication Date
- 2026-08-25
AI Technical Summary
Traditional chemical chlorination methods pose safety risks in chlorine storage and transportation, have low chlorine atom utilization rates, and involve complex processes. Directly using chlorine for chlorination reactions results in high process costs, a heavy environmental burden, and large chlorine consumption.
A two-electrode system was used to couple cross-phase chlorine transfer and in-situ chlorination between the aqueous and organic phases. Chlorine was adsorbed by ethyl acetate, and the chlorination of p-chloroacetanilide was achieved in the organic phase by electrocatalysis, thus avoiding the independent preparation, storage, transportation and transfer of chlorine.
It improves the utilization rate of chlorine atoms, reduces safety hazards, simplifies the process, reduces costs, and improves the selectivity and efficiency of the chlorination reaction. The conversion rate of the product 2,4-dichloroacetanilide reaches 82.6%, making it suitable for the synthesis of pesticide and pharmaceutical intermediates.
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Figure CN122629503A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of electrocatalysis, and specifically relates to a method for coupling transphase chlorine transfer and in-situ chlorination. Background Technology
[0002] In traditional organic chlorination reactions, conventional chemical chlorination methods rely on chlorine as the chlorinating agent, which presents problems such as safety hazards in chlorine storage and transportation, poor atom economy, and difficulty in selective control. In recent years, significant progress has been made in the research of electrocatalytic chlorine generation reactions, and coupling traditional processes with electrocatalytic experiments is an inevitable trend for achieving green and sustainable industry. For example, Jeon et al. (Industrial & Engineering Chemistry Research, 2024, 63(13), 5742-5751) directly used commercial chlorine to synthesize target materials through chlorination reactions. However, due to the loss of most of the chlorine, the process cost is high and the environmental burden is heavy. Not only is it necessary to treat toxic tail gas, but the large amount of chlorine consumed also increases production costs. Li et al. (AIChE Journal, 2021, 67(10), e17341) also directly used chlorine for chlorination reactions, but there were safety hazards in chlorine storage and transportation, and the chlorine atom utilization rate was low, which seriously restricted the economic efficiency of the process. Summary of the Invention
[0003] The purpose of this invention is to address the shortcomings of existing technologies, such as safety hazards in chlorine storage and transportation, low chlorine atom utilization, and cumbersome processes, by providing a method for coupling cross-phase chlorine transfer and in-situ chlorination. This method employs a two-electrode system under a constant current of 3-50 mA, adding a low-density organic phase above the aqueous phase to achieve cross-phase chlorine transfer and chlorination of reactants. Ethyl acetate in the organic phase is used to adsorb chlorine to prevent over-chlorination, thus achieving the chlorination reaction of p-chloroacetanilide. This invention improves the direct utilization rate of chlorine atoms and significantly reduces the safety hazards in chlorine storage and transportation, providing a feasible method for coupling traditional processes with electrocatalytic experiments.
[0004] The objective of this invention is achieved through the following solution: A method for coupling transphase chlorine transfer and in-situ chlorination, comprising the following steps: In a two-electrode system, the working electrode is inserted into the aqueous phase of the anode chamber and the counter electrode is inserted into the electrolyte of the cathode chamber. The reaction is carried out under a constant current of 3 mA-50 mA for 1-4 h, and the entire reaction system is allowed to stand for 6-14 h to obtain the target chlorination product. In the anode chamber, the lower part is the anolyte and the upper part is the organic phase; the volume ratio of the two is 1-3:1; and the working electrode is completely immersed in the lower aqueous phase and does not contact the upper organic phase. The anolyte is a hydrochloric acid solution containing 230-360 g / L of chloride salt; the concentration of hydrochloric acid is 0.1-9 g / L. The working electrode is a coated titanium electrode, a sub-titanium oxide electrode, or a carbon rod; the counter electrode is a platinum sheet. The chloride salt is potassium chloride or sodium chloride.
[0005] The cathode electrolyte is a sulfuric acid solution; the concentration of sulfuric acid is 40-50 g / L. The organic phase consists of dichloromethane, ethyl acetate, and p-chloroacetanilide, wherein the volume ratio of dichloromethane to ethyl acetate is 8-12:4-6; 0.15-0.25 g of p-chloroacetanilide is added to every 12-18 mL of the dichloromethane and ethyl acetate mixture. The working electrode mentioned in step (1) is a commercially available conventional electrode and undergoes electrode pretreatment.
[0006] The substrate was p-chloroacetanilide, and the chlorinated product was 2,4-dichloroacetanilide.
[0007] The preferred pretreatment methods for the electrodes are oxalic acid etching, sandblasting, dilute acid cleaning, micro-arc oxidation, and electrochemical oxidation.
[0008] The room temperature mentioned in this invention refers to 25±1 ℃.
[0009] The essential features of this invention are: In current technology, commercial chlorine gas is often used directly to achieve the chlorination reaction of organic matter. However, the cost of transporting, storing and purifying chlorine gas is too high, and the utilization rate of chlorine atoms in the chlorination reaction is low. Alternatively, hydrochloric acid can be used directly as the chlorine source, but the solubility between the aqueous phase and the oil phase is too low, and the chlorination effect of organic matter is not ideal. In addition, hydrochloric acid is a strong acid and has certain dangers. This invention reduces the overall density of the organic phase by adding ethyl acetate to the oil phase, allowing it to float on the aqueous phase. Simultaneously, chlorine radicals or chlorine gas generated in the aqueous phase are transferred to the organic phase. Since chlorine gas escapes from the aqueous phase and floats to the surface, this arrangement allows for efficient extraction of chlorine gas from the aqueous phase by the organic phase. Secondly, the lone pair electrons of the carbonyl oxygen in the ethyl acetate molecule act as a Lewis base, forming a weak coordination complex with highly reactive chloride ions or polarized chlorine molecules. This reduces the activity of the electrophilic reagent, making the chlorination reaction rate more gradual and controllable. It avoids over-chlorination, ring-opening degradation, and polychlorination side reactions caused by excessively high instantaneous concentrations of highly reactive chlorine species, thus significantly improving the selectivity of monochlorinated products.
[0010] The mechanism is that during electrocatalytic oxidation, chloride ions at the working electrode are oxidized to generate chlorine free radicals or chlorine gas. Cl - - e- → Cl· Cl· + Cl· → Cl2 At the counter electrode, hydrogen ions undergo electrolysis to produce hydrogen gas: 2H + + 2e - → H2 The chlorination reaction of p-chloroacetanilide occurs in the organic phase: C8H8ClNO + Cl2 → C8H7Cl2NO + HCl Compared with the prior art, the present invention has the following advantages and beneficial effects: 1. This invention is simple and easy to implement. The electrocatalytic reaction only requires simple equipment (H-type electrolytic cell) and operating technology (two-electrode kit), so the cost is relatively low and the operation is relatively easy. 2. This invention has high controllability. By adjusting parameters such as electrocatalytic reaction time, current magnitude, and solution composition, the reaction process of the organic phase can be precisely controlled, and the utilization rate of chlorine atoms is greatly improved. 3. The present invention has excellent scalability and strong versatility. Different organic phase reactants can be replaced in the reaction system to achieve the chlorination reaction. 4. This invention is time-efficient, energy-saving, and eliminates the problems of chlorine purification, transfer, and storage. In this invention, the chlorine generated in the aqueous phase directly enters the organic phase for chlorination, with a chlorine purity close to 100%. Furthermore, the HCl product of the chlorination reaction is redissolved in the aqueous phase and further electrolyzed, thereby achieving the recycling of the entire system. This greatly improves the atomic utilization rate of the entire system, providing higher efficiency and economy for future commercial applications. Scale-up experiments have proven its effectiveness, and a complete experiment was conducted in a 1 L volume reaction tank. 5. This invention utilizes electrocatalytic cross-phase chlorine transfer coupled with in-situ chlorination technology to directly utilize the active chlorine species generated by electrolysis under a constant current of 3-50 mA, completely avoiding the independent preparation, storage, transportation, and transfer of chlorine gas, thus eliminating safety hazards at the source. At the same time, this method seamlessly connects the generation and consumption of chlorine atoms, which can increase the direct utilization rate of chlorine atoms by about 30%, overcoming the shortcomings of traditional processes such as low atom utilization and cumbersome processes. 6. When p-chloroacetanilide is used as a substrate, the product 2,4-dichloroacetanilide achieves a conversion rate of 82.6% within 12 hours of standing reaction. It is mainly used as an intermediate in pesticides and pharmaceuticals, and is used to synthesize acetochlor, ciprofloxacin, etc. Some isomers have antibacterial activity, making it an important chemical raw material. Attached Figure Description
[0011] Figure 1This is an experimental assembly diagram, including a cathode chamber, an anode chamber, and two electrodes placed within them.
[0012] Figure 2 The anode chamber has a two-phase distribution, with the lower layer being the aqueous phase and the upper layer being the organic phase.
[0013] Figure 3 The results are the test results of sodium chloride solutions under different acid concentrations in Examples 1-4.
[0014] Figure 4 The results are the test results of potassium chloride solution under different acid concentrations in Examples 5-8. Detailed Implementation
[0015] The present invention will be further described in detail below with reference to the embodiments and accompanying drawings, but the implementation of the present invention is not limited thereto.
[0016] The mechanism of this invention is shown in the following equation: chloride ions lose electrons at the anode to generate chlorine free radicals, the chlorine free radicals combine to generate chlorine gas, and the chlorine gas is transferred to the organic phase to participate in the chlorination reaction of p-chloroacetanilide.
[0017] Cl - - e - → Cl· Cl· + Cl· → Cl2 Unless otherwise specified, all reagents used in the examples are commercially available; the mass fraction of concentrated sulfuric acid is 98%; and the mass fraction of concentrated hydrochloric acid is 37%-38%.
[0018] Example 1: Transphase chlorine transfer and in-situ chlorination coupling 1. Pre-treat and clean the DSA electrode; (Depending on the actual stains on the substrate surface, you can choose to use detergent, alcohol, or gasoline or other organic solvents for ultrasonic cleaning to remove dirt, followed by rinsing with water; if the electrode material is corroded, an additional rust removal step is required, that is, use acidic solutions such as dilute nitric acid, dilute sulfuric acid, dilute hydrochloric acid, phosphoric acid, or oxalic acid to rinse or ultrasonically treat the substrate to remove rust, and finally rinse with deionized water.) II. Preparation of the anolyte, catholyte, and organic phase solution. Add 0.75 mL of sulfuric acid (98% by mass) to 30 mL of water to prepare the catholyte. Add 5.4 g of sodium chloride and 0.03 mL of hydrochloric acid (commercially available concentrated hydrochloric acid, 37-38% by mass, 12 mol / L) to 15 mL of water to prepare the anolyte (density approximately 1.36 g / mL). Add 5 mL of ethyl acetate and 0.17 g of p-chloroacetanilide to 10 mL of dichloromethane to prepare the organic phase solution (density approximately 1.19 g / mL).
[0019] 3. Assemble the H-type reaction cell and place a proton exchange membrane (DuPont Nafion 117) in the middle. Add the cathode electrolyte to the cathode chamber and the anolyte to the anode chamber sequentially. Then, slowly pour the organic phase over the anolyte. Use the DSA electrode as the working electrode and a platinum sheet as the counter electrode.
[0020] 4. Place the working electrode and counter electrode, treated in step one, into the aqueous phase of the anode chamber and the electrolyte of the cathode chamber, respectively, ensuring that the electrodes are completely immersed in the aqueous phase and do not come into contact with the organic phase. The organic phase should be positioned above the anolyte (e.g., Figure 2 As shown in the figure, the reaction was carried out at 25 °C and 5 mA for 2 h, and then allowed to stand for 10 h to allow the organic phase to fully capture and consume the active chlorine species that continuously escaped from the aqueous phase, ensuring the complete reaction and finally obtaining 2,4-dichloroacetanilide.
[0021] 5. Take the organic phase solution for product determination.
[0022] In Example 1, the conversion rate of p-chloroacetanilide was 78.2% as determined by gas chromatography (GC). Figure 3 As shown in the first bar chart.
[0023] Example 2: The other steps are the same as in Example 1, except that the amount of hydrochloric acid in the anolyte is changed from 0.03 mL to 0.06 mL.
[0024] In Example 2, the conversion rate of p-chloroacetanilide was 76.0%, which was not significantly different from that in Example 1 within the experimental error range.
[0025] Example 3: The other steps are the same as in Example 1, except that the amount of hydrochloric acid in the anolyte is changed from 0.03 mL to 0.12 mL.
[0026] In Example 3, the conversion rate of p-chloroacetanilide was 76.2%, which was not significantly different from that in Example 1 within the experimental error range.
[0027] Example 4: The other steps are the same as in Example 1, except that the amount of hydrochloric acid in the anolyte is changed from 0.03 mL to 0.24 mL.
[0028] In Example 4, the conversion rate of p-chloroacetanilide was 76.0%, which was not significantly different from that in Example 1 within the experimental error range. These results indicate that within the currently investigated range of hydrochloric acid dosage, variations in its concentration did not have a clear impact on the conversion rate. It is speculated that there exists a minimum effective concentration of hydrochloric acid in the reaction system; once the actual dosage exceeds this threshold, further increases in hydrochloric acid have limited effect on improving the reaction conversion rate.
[0029] Example 5: The other steps are the same as in Example 1, except that 5.4 g of sodium chloride in the anolyte is replaced with 5.3 g of potassium chloride.
[0030] In Example 5, the conversion rate of p-chloroacetanilide was 78.6%, slightly higher than that in Example 1. Although the molar concentration of chloride ions decreased, the conversion rate increased, suggesting that the type of cation may have a slight influence on the reaction by affecting ionic strength, solution conductivity, or the release / transfer efficiency of chloride.
[0031] Example 6: The other steps are the same as in Example 1, except that 5.4 g of sodium chloride in the anolyte is replaced with 5.3 g of potassium chloride, and the amount of hydrochloric acid is changed from 0.03 mL to 0.06 mL.
[0032] In Example 6, the conversion rate of p-chloroacetanilide was 82.6%, indicating that potassium ions may be more conducive to the generation and cross-phase transfer of chlorine in the anodic region in this electrochemical system, thereby improving the conversion rate.
[0033] Example 7: The other steps are the same as in Example 1, except that 5.4 g of sodium chloride in the anolyte is replaced with 5.3 g of potassium chloride, and the hydrochloric acid is changed from 0.03 mL to 0.12 mL.
[0034] In Example 7, the conversion rate of p-chloroacetanilide was 75.9%. Combining the results of Examples 3 and 6, it is evident that further increasing the amount of hydrochloric acid in the potassium chloride system inhibits the reaction. It is speculated that excessive hydrochloric acid may have negative effects; an excessively low interfacial pH may affect the stable existence of chlorine species and the efficiency of cross-phase transfer, hindering the effective transfer of chlorine to the organic phase. Furthermore, a strongly acidic environment may also adversely affect the electrode materials or reactants, thereby inhibiting the overall improvement of the reaction conversion rate.
[0035] Example 8: The other steps are the same as in Example 1, except that 5.4 g of sodium chloride in the anolyte is replaced with 5.3 g of potassium chloride, and the hydrochloric acid is changed from 0.03 mL to 0.24 mL.
[0036] In Example 8, the conversion rate of p-chloroacetanilide was 76.1%, which is basically consistent with 75.9% in Example 7, further confirming the inhibitory effect of excess hydrochloric acid.
[0037] In this invention, the addition of a second organic solvent, ethyl acetate, to the organic phase achieves a dual effect: firstly, ethyl acetate reduces the overall density of the organic phase, allowing it to float on the aqueous phase; secondly, in the electrophilic chlorination mechanism, the lone pair of electrons on the carbonyl oxygen in the ethyl acetate molecule acts as a Lewis base, forming a weak coordination complex with the highly reactive chloride cation, thereby effectively reducing the activity of the electrophilic reagent. This coordination effect makes the chlorination reaction rate more gradual and controllable, avoiding the degradation caused by Cl... + Excessive reactivity leads to overchlorination, ring-opening degradation, and polychlorination side reactions, which significantly improve the selectivity of monochlorinated products.
[0038] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.
[0039] Matters not covered in this invention are common knowledge.
Claims
1. A method for coupling transphase chlorine transfer and in-situ chlorination, characterized in that, The method includes the following steps: In a two-electrode system, the working electrode is inserted into the aqueous phase of the anode chamber and the counter electrode is inserted into the electrolyte of the cathode chamber. The reaction is carried out under a constant current of 3 mA-50 mA for 1-4 h, and the entire reaction system is allowed to stand for 6-14 h to obtain the chlorination product. In the anode chamber, the lower part is the anolyte and the upper part is the organic phase; the volume ratio of the two is 1-3:
1. The anolyte is a hydrochloric acid solution containing 230-360 g / L of chloride salt; the concentration of hydrochloric acid is 0.1-9 g / L. The working electrode is a coated titanium anode, sub-titanium oxide, or a carbon rod; the counter electrode is a platinum sheet. The cathode electrolyte is a sulfuric acid solution; the concentration of sulfuric acid is 40-50 g / L. The organic phase consists of dichloromethane, ethyl acetate, and p-chloroacetanilide, wherein the volume ratio of dichloromethane to ethyl acetate is 8-12:4-6; 0.15-0.25 g of p-chloroacetanilide is added to every 12-18 mL of the mixture of dichloromethane and ethyl acetate.
2. The method for coupling transphase chlorine transfer and in-situ chlorination as described in claim 1, characterized in that, The concentration of sulfuric acid is 40-50 g / L.
3. The method for coupling transphase chlorine transfer and in-situ chlorination as described in claim 1, characterized in that, The working electrode described in the steps undergoes electrode pretreatment.
4. The method for coupling transphase chlorine transfer and in-situ chlorination as described in claim 1, characterized in that, The chloride salt is potassium chloride or sodium chloride.
5. The method for coupling transphase chlorine transfer and in-situ chlorination as described in claim 3, characterized in that, The electrode pretreatment method is one or more of the following: oxalic acid etching, sandblasting, dilute acid cleaning, micro-arc oxidation, and electrochemical oxidation.