A method for preparing 2-chloro-benzoic acid by electrochemical debromination in a continuous flow microreactor
By employing electrochemical reduction technology in a continuous flow microreactor, the problems of low conversion and yield in the preparation of 2-chlorobenzoic acid have been solved, achieving efficient and safe preparation of 2-chlorobenzoic acid, which is suitable for industrial applications.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- FUJIAN LISHAN HEGUANG ENGINEERING TECHNOLOGY RESEARCH CO LTD
- Filing Date
- 2026-05-09
- Publication Date
- 2026-07-10
AI Technical Summary
The existing technologies for the preparation of 2-chlorobenzoic acid have low conversion rates and product yields. Traditional methods suffer from poor atom economy, generate large amounts of wastewater containing heavy metals or high salt content, pose significant safety hazards, and have low mass and heat transfer efficiency, long reaction times, and high energy consumption, making them difficult to scale up.
By employing a continuous flow microreactor combined with electrochemical reduction technology, selective debromination reaction is carried out in a microchannel electrochemical reactor using a polar aprotic solvent and supporting electrolyte. The cathode material is carbon cloth or modified carbon cloth. By controlling the current density, temperature, and material residence time, efficient preparation of 2-chlorobenzoic acid is achieved.
It significantly improves the conversion rate and selectivity of 2-chlorobenzoic acid, shortens the reaction time, increases the space-time yield, simplifies the post-processing procedures, ensures stable product quality, and is suitable for industrial production.
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Abstract
Description
Technical Field
[0001] This invention belongs to the field of organic electrochemical synthesis and microchemical technology, specifically relating to a method for preparing 2-chlorobenzoic acid by electrochemical reduction debromination in a continuous flow microreactor. Background Technology
[0002] 2-Chlorobenzoic acid is an important fine chemical intermediate widely used in the synthesis of pharmaceuticals, pesticides, and dyes. Traditional synthesis methods often employ strong oxidants such as potassium permanganate to oxidize the corresponding chlorotoluene, or utilize methods like the Sandmeier reaction. These methods generally suffer from poor atom economy, generate large amounts of wastewater containing heavy metals or high salinity, and pose significant safety hazards. In recent years, electrochemical reduction dehalogenation has gained attention due to its advantages, including mild conditions, no need for external reducing agents, and the use of electrons as a clean reducing agent. However, traditional batch electrolytic cells (breeding electrolysis) suffer from the following bottlenecks: low mass and heat transfer efficiency, leading to uneven local concentration and current density distribution, easily triggering side reactions; long reaction times, high energy consumption, and difficulty in scale-up, resulting in a significant "scale-up effect" from milligram-level laboratory to industrial production.
[0003] Continuous flow chemistry technology is widely recognized as an ideal solution for highly exothermic, high-pressure, and hazardous reagent-related catalytic hydrogenation processes due to its excellent mass and heat transfer efficiency, precise reaction parameter control, intrinsic safety, and ease of scale-up. In particular, combining microchemical technology with fixed-bed reactors can construct efficient and continuous synthesis platforms: microstructures enhance mixing and heat exchange, while fixed beds enable bed-type catalyst packing and online fixation. This method avoids the auxiliary time consumption of batch operations, eliminates the need for additional catalyst separation, significantly shortens the reaction cycle, simplifies post-processing, and improves space-time yield, while simultaneously achieving process safety and low carbon emissions, demonstrating significant industrial application potential. Summary of the Invention
[0004] This invention provides a method for preparing 2-chlorobenzoic acid by electrochemical reduction debromination in a continuous flow microreactor, in order to solve the problems of low conversion rate and product yield in the preparation of 2-chlorobenzoic acid in the prior art.
[0005] This invention provides the following technical solution: a method for preparing 2-chlorobenzoic acid by electrochemical reduction debromination in a continuous flow microreactor, comprising the following steps: S1. Dissolve 3-bromo-2-chlorobenzoic acid, supporting electrolyte, and proton source in a polar aprotic solvent to form a homogeneous solution; S2. The cathode reaction liquid is continuously fed into the cathode channel of the microchannel electrochemical reactor, and anolyte is fed into the anode channel of the reactor at the same time. A DC power supply is turned on to carry out a continuous electrochemical reduction reaction. Under the set current density, reaction temperature and material residence time conditions, 3-bromo-2-chlorobenzoic acid undergoes a selective debromination reaction and is converted into 2-chlorobenzoic acid reaction effluent. S3. The effluent from the 2-chlorobenzoic acid reaction is subjected to gas-liquid separation, neutralization, extraction, drying, concentration and recrystallization in sequence to obtain high-purity 2-chlorobenzoic acid.
[0006] Furthermore, the microchannel electrochemical reactor consists of an anode plate and a cathode plate with microchannel structures; The hydraulic diameter of the microchannel is 218–286 μm.
[0007] Furthermore, the set current density is 10–25 mA / cm², the reaction temperature is 35–50°C, and the material residence time is 2–10 min.
[0008] Furthermore, the molar ratio of 3-bromo-2-chlorobenzoic acid to the supporting electrolyte is 5:1; The polar aprotic solvent is at least one of N,N-dimethylformamide and acetonitrile.
[0009] Furthermore, the volume ratio of the proton source to the solvent is 1~4:6~9; The proton source is water.
[0010] Furthermore, the supporting electrolyte is at least one of tetrabutylammonium tetrafluoroborate and tetraethylammonium tetrafluoroborate; The molar concentration of the supporting electrolyte in the cathode reaction solution is 0.02 mol / L.
[0011] Furthermore, the cathode material is carbon cloth, which is any one of plain weave carbon cloth, electrodeposited silver nanoparticle modified carbon cloth, or electrodeposited palladium nanoparticle modified carbon cloth.
[0012] Furthermore, the total effective volume of the microchannel electrochemical reactor is 17.6–280 mL.
[0013] Compared with the prior art, the present invention has the following technical effects: This invention combines a microchannel reactor with an electrochemical reduction debromination reaction. The extremely short molecular diffusion distance and large specific surface area of the microreactor enhance the mass transfer process, allowing for rapid replenishment of 3-bromo-2-chlorobenzoic acid molecules on the cathode surface. This enables the use of higher current densities, reducing the reaction time of traditional batch reactions, which can take hours or even longer, to less than 10 minutes, significantly improving the space-time yield.
[0014] The continuous flow microreactor provides uniform and controllable temperature, potential, and reactant concentration, effectively overcoming the localized overreduction or coupling side reactions caused by concentration polarization in traditional batch electrolysis. The method of this invention achieves a conversion rate of over 98% for 3-bromo-2-chlorobenzoic acid, a selectivity for 2-chlorobenzoic acid approaching 100%, and a final product yield consistently above 90%.
[0015] Microreactors have a small liquid holding volume (milliliters), resulting in inherently high safety for treating hazardous bromine-containing systems. The scale-up method is a simple "quantity scaling up" (increasing the number of microreactor channels in parallel) rather than the traditional "size scaling up," eliminating the scale-up effect and making the transition from laboratory research to industrial production extremely quick and reliable.
[0016] Using electrons as a cleaning reducing agent, there is no need to add expensive or dangerous chemical reducing agents. In continuous operation mode, the operation is stable and the product quality varies very little between batches, making it suitable for industrial continuous production. Attached Figure Description
[0017] Figure 1 This is a flowchart of the technology of the present invention.
[0018] Figure 2 This is a schematic diagram of the synthesis steps of 2-chloro-benzoic acid in this invention. Detailed Implementation
[0019] The present invention will be further illustrated below with reference to embodiments. These embodiments are for illustrative purposes only and are not intended to limit the invention in any way. It should be understood that the described embodiments are merely some, not all, of the embodiments described in this application. All other embodiments obtained by those skilled in the art based on the embodiments in this application without inventive effort are within the scope of protection of this application.
[0020] Example 1 Figure 1 This is a flowchart of the technology of the present invention. Figure 2 This is a schematic diagram of the synthesis steps of 2-chlorobenzoic acid in this invention; like Figure 1 and Figure 2 As shown, in this embodiment, the catholy solution is prepared by dissolving 0.1 mol of 3-bromo-2-chlorobenzoic acid and 0.02 mol of tetrabutylammonium tetrafluoroborate in 1 L of a mixed solvent of N,N-dimethylformamide (DMF) and water in a volume ratio of 9:1; the anolyte is a 0.02 mol / L aqueous solution of tetrabutylammonium tetrafluoroborate.
[0021] A microchannel electrochemical reactor was used, with a cathode made of silver nanoparticle-modified carbon cloth and an anode made of platinum sheet. The microchannel was 500 μm wide and 200 μm deep, with a reaction volume of 110 mL. Both the catholyte and anolyte were continuously fed at a flow rate of 10 mL / min, with a constant current density of 15 mA / cm², a reaction temperature of 40 °C, and a material residence time of 5.5 min. Samples were taken for analysis after 1 hour of stable operation.
[0022] The conversion rate of 3-bromo-2-chlorobenzoic acid was 98.5%, and the chromatographic yield of 2-chlorobenzoic acid was 94.2%. After post-treatment, white crystals with a melting point of 142-144℃ and an HPLC purity of 99.1% were obtained.
[0023] Example 2 The overall materials, solvents, electrodes, and reactor conditions are the same as in Example 1; The feed flow rates of both catholyte and anolyte were adjusted to 6 mL / min, the material residence time was 9.17 min, the current density was adjusted to 10 mA / cm², and the other conditions remained unchanged.
[0024] The conversion rate of the raw materials was measured to be 99.2%, and the chromatographic yield of 2-chlorobenzoic acid was 95.1%.
[0025] Example 3 Preparation of the cathode reaction solution: Dissolve 0.1 mol of 3-bromo-2-chlorobenzoic acid and 0.02 mol of tetraethyltetrafluoroborate in 1 L of a mixed solvent of acetonitrile and water in a volume ratio of 8:2; the anolyte is a 0.02 mol / L aqueous solution of tetraethyltetrafluoroborate.
[0026] The microchannel dimensions are 440 μm wide and 180 μm deep, with a total reaction volume of 17.6 mL. The cathode is plain-weave carbon cloth without metal loading, and the anode is a platinum sheet. The flow rates of both liquids are 8.8 mL / min, the current density is 12.8 mA / cm², the reaction temperature is 45 °C, the residence time is 2 min, and samples are taken after 45 min of stable operation.
[0027] The raw material conversion rate was 98.16%, and the chromatographic yield of 2-chlorobenzoic acid was 91.8%.
[0028] Example 4 The basic formulation, electrodes, and reactor structure were the same as in Example 3. The current density was fixed at 12 mA / cm², the reaction temperature at 35°C, and the residence time at 6 min. The two-phase feed flow rate was 1.0 mL / min. Only the ratio of acetonitrile to water was adjusted, with an acetonitrile:water volume ratio of 8:2. The raw material conversion rate was 98.1%, and the product yield was 92.3%.
[0029] Example 5 The basic formulation, electrodes, and reactor structure were the same as in Example 3. The current density was fixed at 12 mA / cm², the reaction temperature at 35°C, and the residence time at 6 min. The two-phase feed flow rate was 1.0 mL / min. Only the ratio of acetonitrile to water was adjusted, with an acetonitrile:water volume ratio of 7:3. The raw material conversion rate was 98.9%, and the product yield was 93.5%.
[0030] Example 6 The basic formulation, electrodes, and reactor structure were the same as in Example 3. The current density was fixed at 12 mA / cm², the reaction temperature at 35°C, and the residence time at 6 min. The two-phase feed flow rate was 1.0 mL / min. Only the ratio of acetonitrile to water was adjusted, with an acetonitrile:water volume ratio of 6:4. The raw material conversion rate was 97.5%, and the product yield was 90.2%.
[0031] Example 7 The solvent, electrolyte, and basic process were the same as in Example 1. The microchannel electrochemical reactor dimensions were identical, with a fixed flow rate of 22 mL / min, current density of 15 mA / cm², temperature of 40°C, and residence time of 5 min. Only the cathode material was changed: this example used a pure unmodified carbon cloth cathode, achieving a feed conversion rate of 96.8% and a product yield of 89.5%. Example 8 The solvent, electrolyte, and basic process are the same as in Example 1. The microchannel electrochemical reactor is the same size, with a fixed flow rate of 22 mL / min, current density of 15 mA / cm², temperature of 40 °C, and residence time of 5 min. Only the cathode material is changed: In this example, an electrodeposited nano-silver modified carbon cloth cathode is used with a silver loading of 0.5 mg / cm², a raw material conversion rate of 99.1%, and a product yield of 94.8%.
[0032] Example 9 The solvent, electrolyte, and basic process are the same as in Example 1. The microchannel electrochemical reactor is the same size, with a fixed flow rate of 22 mL / min, current density of 15 mA / cm², temperature of 40 °C, and residence time of 5 min. Only the cathode material is changed: In this example, an electrodeposited nano-palladium modified carbon cloth cathode is used with a palladium loading of 0.3 mg / cm², a raw material conversion rate of 99.5%, and a product yield of 93.2%.
[0033] Example 10 In this embodiment, an electrodeposited nano-silver modified carbon cloth cathode was used, and the electrode configuration and other conditions were the same as in Example 1. Only the feed flow rate, current density and reaction temperature were adjusted. In this embodiment, the flow rate was 6 mL / min, the residence time was 8.3 min, the current density was 10 mA / cm², and the temperature was 35 °C. The raw material conversion rate was 99.3% and the product yield was 95.2%.
[0034] Example 11 In this embodiment, an electrodeposited nano-silver modified carbon cloth cathode was used, and the electrode configuration and other conditions were the same as in Example 1. Only the feed flow rate, current density and reaction temperature were adjusted. In this embodiment, the flow rate was 12 mL / min, the residence time was 4.2 min, the current density was 20 mA / cm², and the temperature was 45 °C. The raw material conversion rate was 98.7% and the product yield was 93.8%.
[0035] Example 12 In this embodiment, an electrodeposited nano-silver modified carbon cloth cathode was used, and the electrode configuration and other conditions were the same as in Example 1. Only the feed flow rate, current density and reaction temperature were adjusted. In this embodiment, the flow rate was 15 mL / min, the residence time was 3.3 min, the current density was 25 mA / cm², and the temperature was 50 °C. The raw material conversion rate was 97.2% and the product yield was 89.5%.
[0036] Example 13 (Enlarged Example) The reactor used was a stacked reactor containing eight parallel micro-reaction units, each with an effective volume of 280 mL and a total reaction volume of 2240 mL. The cathode of each unit was made of nano-silver modified carbon cloth, and the anode was a platinum sheet.
[0037] A 60L catholyte was prepared using the same formulation as in Example 1. The total feed flow rate was 1120mL / min, the single-unit distribution flow rate was 140mL / min, and each unit was independently controlled by constant flow. The current density was 15mA / cm², the reaction temperature was 40℃, and the process was continuously and stably run for 4 hours. Samples were taken every 30 minutes, for a total of 8 samples. Analytical method: HPLC external standard method. The average conversion rate of this example was 98.9%±0.3%, and the average chromatographic yield was 94.5%±0.5%.
[0038] The products were post-processed and combined to obtain white crystalline 2-chlorobenzoic acid with a separation yield of 94.9% and an HPLC purity of 99.2%.
[0039] Comparative Example 1 (Traditional Intermittent Electrolysis) Intermittent electrolysis was carried out in a 100mL diaphragm-free beaker reactor. A carbon rod was used as the cathode and a platinum sheet was used as the anode. The electrolyte composition was the same as in Example 1. The reactor was magnetically stirred, with a constant current of 50mA, corresponding to a current density of about 5mA / cm², a reaction temperature of 40℃, and a reaction time of 6-7h.
[0040] The raw material conversion rate was 96.2%, and 8% dechlorination byproducts and a small amount of coupling byproducts were detected in the product. The 2-chlorobenzoic acid separation yield was only 84.5%.
[0041] Of course, the above description is not intended to limit the present invention, and the present invention is not limited to the examples given above. Any changes, modifications, additions or substitutions made by those skilled in the art within the scope of the present invention should also fall within the protection scope of the present invention.
Claims
1. A method for preparing 2-chlorobenzoic acid by electrochemical reduction debromination in a continuous flow microreactor, characterized in that, Includes the following steps: S1. Dissolve 3-bromo-2-chlorobenzoic acid, supporting electrolyte, and proton source in a polar aprotic solvent to form a homogeneous solution; S2. The cathode reaction liquid is continuously fed into the cathode channel of the microchannel electrochemical reactor, and anolyte is fed into the anode channel of the reactor at the same time. A DC power supply is turned on to carry out a continuous electrochemical reduction reaction. Under the set current density, reaction temperature and material residence time conditions, 3-bromo-2-chlorobenzoic acid undergoes a selective debromination reaction and is converted into 2-chlorobenzoic acid reaction effluent. S3. The effluent from the 2-chlorobenzoic acid reaction is subjected to gas-liquid separation, neutralization, extraction, drying, concentration and recrystallization in sequence to obtain high-purity 2-chlorobenzoic acid.
2. The method for preparing 2-chlorobenzoic acid by electrochemical reduction debromination in a continuous flow microreactor according to claim 1, characterized in that, The microchannel electrochemical reactor consists of an anode plate and a cathode plate with microchannel structures. The hydraulic diameter of the microchannel is 218–286 μm.
3. The method for preparing 2-chlorobenzoic acid by electrochemical reduction debromination in a continuous flow microreactor according to claim 1, characterized in that, The set current density is 10-25 mA / cm², the reaction temperature is 35-50°C, and the material residence time is 2-10 min.
4. The method for preparing 2-chlorobenzoic acid by electrochemical reduction debromination in a continuous flow microreactor according to claim 1, characterized in that, The molar ratio of 3-bromo-2-chlorobenzoic acid to the supporting electrolyte is 5:1; The polar aprotic solvent is at least one of N,N-dimethylformamide and acetonitrile.
5. The method for preparing 2-chlorobenzoic acid by electrochemical reduction debromination in a continuous flow microreactor according to claim 1, characterized in that, The volume ratio of the proton source to the solvent is 1~4:6~9; The proton source is water.
6. The method for preparing 2-chlorobenzoic acid by electrochemical reduction debromination in a continuous flow microreactor according to claim 1, characterized in that, The supporting electrolyte is at least one of tetrabutylammonium tetrafluoroborate and tetraethylammonium tetrafluoroborate; The molar concentration of the supporting electrolyte in the cathode reaction solution is 0.02 mol / L.
7. The method for preparing 2-chlorobenzoic acid by electrochemical reduction debromination in a continuous flow microreactor according to claim 1, characterized in that, The cathode material is carbon cloth; The cathode material is carbon cloth, which can be any one of plain weave carbon cloth, electrodeposited silver nanoparticle modified carbon cloth, or electrodeposited palladium nanoparticle modified carbon cloth.
8. The method for preparing 2-chlorobenzoic acid by electrochemical reduction debromination in a continuous flow microreactor according to claim 1, characterized in that, The total effective volume of the microchannel electrochemical reactor is 17.6–280 mL.