A separation method of HPLC grade ethyl acetate azeotrope system based on multi-stage collaborative process

Abstract

The application provides a kind of HPLC grade ethyl acetate azeotrope separation method based on multi-stage collaborative process, belongs to the technical field of acyclic compound purification;The method comprises the following steps: raw material pretreatment, low pressure rectification, high pressure azeotrope purification;The method for high pressure azeotrope purification is that the operating absolute pressure of high pressure rectification column is controlled at 200-250kPa, the overhead temperature is 85-95℃, the column bottom temperature is 110-120℃, the organic phase from the layering device is preheated to 80-85℃ by preheater, and then continuously fed from the middle part of high pressure rectification column;At the same time, the compounded auxiliary solution is continuously injected into the column from the lower part of high pressure column rectification section, a side line liquid phase outlet is set above the compounded auxiliary solution feeding port, and ethyl acetate product is continuously taken out;The separation method makes the purity of final product reach 99.96%-99.98%, the water content in product is <0.01%, the ethanol content is ≤0.03%, the evaporation residue is ≤3ppm;The ultraviolet absorption characteristics meet the quality requirements of HPLC grade solvent.

Description

Technical Field

[0001] This invention belongs to the field of acyclic compound purification technology, specifically relating to an HPLC-grade ethyl acetate azeotropic system separation method based on a multi-stage synergistic process. Background Technology

[0002] Ethyl acetate is a widely used bulk organic solvent, with substantial demand in coatings, pharmaceutical synthesis, and chromatographic analysis. HPLC-grade ethyl acetate, as a high-end solvent in chromatographic analysis and electronics manufacturing, has stringent requirements regarding purity, moisture content, evaporation residue, and UV transmittance. In industrial production, crude ethyl acetate obtained through esterification or addition methods typically contains impurities such as water, ethanol, and acetic acid. Furthermore, ethyl acetate readily forms a ternary azeotropic system with water and ethanol, making deep separation difficult with conventional distillation. Therefore, efficient and low-energy-consumption azeotropic purification processes have always been a key focus of industry research.

[0003] Currently, industrial purification of ethyl acetate azeotropic systems primarily employs azeotropic distillation or extractive distillation processes. For example, Chinese patent CN110885283A discloses a thermally integrated extractive distillation process for separating ethyl acetate-ethanol, using dimethyl sulfoxide as the extractant to break the azeotrope. While this achieves a certain separation effect, it requires a large amount of extractant, necessitates a separate solvent recovery tower, and results in high equipment investment and energy consumption. Furthermore, the extractant is prone to remain in the product, making it difficult to meet the cleanliness requirements of HPLC-grade solvents. Other enhanced processes, such as salt distillation, also suffer from difficulties in salt recovery and severe equipment corrosion, limiting their industrial application.

[0004] Pressure swing distillation utilizes the thermodynamic property that the composition of an azeotrope changes with operating pressure. By employing a dual-tower configuration—a low-pressure tower and a high-pressure tower connected in series—the azeotropic equilibrium is broken. The low-pressure tower performs initial deimpurification of the feedstock, while the high-pressure tower alters the azeotropic composition by increasing the pressure, thereby increasing the ethanol and water content in the azeotrope. Leveraging this pressure-sensitive characteristic, high-purity ethyl acetate can be obtained from the high-pressure tower bottoms by operating the low-pressure and high-pressure towers in series. Pressure swing distillation requires no large amount of external separation medium throughout the process, resulting in a high product purity, and is gradually being adopted in the field of ethyl acetate refining.

[0005] Chinese patent CN109534998B discloses an energy-saving process for separating ethyl acetate and ethanol by pressure swing distillation with side-stream sampling. This process utilizes side-stream sampling for pressure swing distillation to separate ethyl acetate and ethanol. By using high- and low-pressure dual towers in conjunction with side-stream sampling to optimize material distribution, the system energy consumption of the continuous production process is reduced. The high-pressure distillation tower operates at an absolute pressure of 6.0 atm to 8.0 atm.

[0006] Liu Qiao and Gao Ruichang (2016) published a research paper entitled "Simulation of Separation of Ethyl Acetate and Methanol by Fully Integrated Thermal Swing Distillation" in *Modern Chemical Industry*. This study also used Aspen Plus software and the NRTL model to simulate the fully integrated thermal swing distillation of the ethyl acetate-methanol system. Using the mass fractions of ethyl acetate and methanol as constraint functions and the reboiler heat load as the objective function, parameters such as the reflux ratio were comprehensively optimized. The results showed that when the reflux ratio of the high-pressure column was 4 and the reflux ratio of the atmospheric column was as high as 5.7, the mass fraction of ethyl acetate at the bottom of the high-pressure column was 99.5%. This study reveals that although fully integrated thermal swing distillation can reduce some energy consumption through heat recovery, its separation capability still highly depends on an extremely high reflux ratio: a reflux ratio of 4 in the high-pressure column and a reflux ratio of 5.7 in the atmospheric column mean a large amount of circulating material within the column and a significantly increased reboiler heating load and column top condensation load, resulting in persistently high separation energy consumption.

[0007] Yang J, Zhou ML, Wang YJ, et al. (2017) published a research paper entitled "Simulation of Pressure-swing Distillation for Separation of Ethyl Acetate-Ethanol-Water" in the IOP Conference Series: Materials Science and Engineering. Their results indicate that obtaining 0.9990 ethyl acetate requires a relatively high operating pressure of 500 kPa.

[0008] The above studies indicate that to obtain high-purity ethyl acetate products through pressure swing distillation, high operating pressures (typically ≥500 kPa) or high reflux ratios are often required. High operating pressures directly increase the pressure resistance requirements of the equipment and raise safety management costs. High reflux ratios mean a significant increase in the amount of circulating material within the column, leading to a substantial increase in the reboiler heating load and the overhead condensation load, resulting in persistently high separation energy consumption. Meanwhile, ethanol, as a co-solvent in the ethyl acetate-ethanol-water ternary azeotropic system, tends to accumulate continuously in the dual-column circulation. The residual ethanol content in the products from the above studies was generally high, making it difficult to stably reduce to the HPLC-grade solvent requirements.

[0009] In summary, existing pressure swing distillation technology still struggles to achieve deep removal of both water and ethanol simultaneously under mild operating conditions when separating the ethyl acetate-ethanol-water ternary azeotropic system, thus failing to obtain ethyl acetate products that meet all HPLC-grade requirements. How to overcome the separation limitations of conventional pressure swing distillation while simultaneously achieving efficient removal of water and ethanol and significantly reducing separation energy consumption without requiring excessively high operating pressures and high reflux ratios remains a pressing technical challenge in this field. Summary of the Invention

[0010] To address the problems existing in the prior art, this invention provides a multi-stage synergistic process-based HPLC-grade ethyl acetate azeotropic system separation method. Under conventional medium-pressure conditions of 200-250 kPa, the method achieves deep separation of the ethyl acetate azeotropic system at low reflux ratios through the synergistic effect of compounded additives and side-stream interception in the rectification section. This method stably produces high-purity products that meet HPLC-grade standards, while reducing separation energy consumption and equipment investment, and eliminating additive residue pollution.

[0011] To solve the above technical problems, the technical solution adopted by the present invention is as follows: A method for separating ethyl acetate azeotropic systems based on a multi-stage synergistic process, comprising the following steps: raw material pretreatment, low-pressure distillation, and high-pressure azeotropic purification; 1. Raw material pretreatment Add sodium carbonate solution to industrial grade crude ethyl acetate, stir and wash at 35-45℃ for 18-22 min, let stand and separate into layers, remove the lower alkaline aqueous phase, then wash once with deionized water to remove the aqueous phase, and obtain pretreated crude ester. The industrial-grade crude ethyl acetate contains 0.4-0.6 wt% acetic acid, 2.5-3.5 wt% ethanol, and 3.5-4.5 wt% water, respectively. The concentration of the sodium carbonate solution is 4-6%; The mass ratio of the sodium carbonate solution to industrial-grade crude ethyl acetate is 8-12:100.

[0012] Rinse once with deionized water to remove residual salt; This step effectively removes corrosive acidic impurities, protects subsequent distillation equipment, and reduces side reactions that may be caused by the presence of acidic substances.

[0013] 2. Low-pressure distillation The pretreated crude ester is fed into the middle of a low-pressure distillation column. The absolute pressure at the top of the column is controlled at 28-32 kPa, the temperature at the top of the column is controlled at 34-36℃, and the temperature at the bottom of the column is controlled at 73-78℃. The ethyl acetate-water-ethanol ternary azeotrope collected at the top of the column is condensed and then subjected to liquid-liquid phase separation to separate the organic phase and the aqueous phase. The middle part of the low-pressure distillation column is located at the 18th-22nd theoretical plate counting downwards from the top of the column; The theoretical number of plates inside the tower is 35-40; The reflux ratio should be controlled between 1.7 and 2.3.

[0014] The residual liquid containing high-boiling-point byproducts is collected from the bottom of the low-pressure tower and continuously discharged from the system.

[0015] This step utilizes negative pressure to lower the azeotropic temperature, allowing most of the water and ethanol to be removed from the top of the column as an azeotrope under mild conditions. This achieves the initial dehydration and removal of light components from the crude ester, while avoiding side reactions such as hydrolysis or thermal decomposition of ethyl acetate at high temperatures.

[0016] 3. High-pressure azeotropic purification The absolute operating pressure of the high-pressure distillation column is controlled at 200-250 kPa, the top temperature is 85-95℃, and the bottom temperature is 105-115℃. The organic phase from the separator is preheated to 80-85℃ by a preheater and then continuously fed into the middle of the high-pressure distillation column. At the same time, the compound additive solution is continuously injected into the column from the lower part of the rectification section. A side stream liquid phase outlet is set above the inlet of the compound additive solution to continuously collect the ethyl acetate product. Aqua-boiling steam rich in water is collected from the top of the column. After condensation, the azeotropic steam undergoes liquid-liquid phase separation. A portion of the upper ester-rich phase is returned to the top of the high-pressure distillation column as reflux, with the reflux ratio controlled at 1.4-1.7. The remaining portion is recycled back to the feed inlet of the low-pressure column, forming a closed-loop cycle for pressure swing distillation; The lower layer, rich in water, is sent to the wastewater treatment unit for processing.

[0017] The material in the bottom of the high-pressure distillation column is continuously collected, and the collected liquid is recovered by vacuum distillation. The bottom material of the high-pressure distillation column mainly contains enriched additives and small amounts of ethyl acetate, water, and ethanol; The theoretical number of plates inside the tower is 45-55; The middle part of the high-pressure distillation column is the 27th-33rd theoretical plate counting down from the top of the column; The compound additive solution is a solution obtained by dissolving the compound additive in the organic phase of a separator with 10-15 times its mass. The compounding agent is obtained by compounding 3,4,5-trihydroxybenzoic acid and (2S)-2-hydroxysuccinic acid in a mass ratio of 3:0.8-1.2. (2S)-2-hydroxysuccinic acid is commonly referred to as L-malic acid; The amount of the compound additive is 0.3%-0.4% of the mass of the reflux liquid at the top of the high-pressure distillation column; The lower part of the rectification section of the high-pressure distillation column is located at the 7th to 9th theoretical plates counting upwards from the bottom of the column. The area above the inlet of the compound additive solution is the 4th-5th theoretical plate counting upwards from the theoretical plate of the compound additive solution feed tower. The yield of the ethyl acetate product is controlled at 18%-22% of the total liquid volume descending in the tower.

[0018] As the pressure increases, the azeotropic composition changes (the solubility of water in the azeotrope decreases), the water-rich phase is collected from the top of the column, and a high-purity ethyl acetate semi-finished product is obtained from the bottom of the column, with a purity of over 99.9%.

[0019] The injected additive flows downward with the liquid phase and comes into countercurrent contact with the rising gas phase in the rectification section. The three phenolic hydroxyl groups of 3,4,5-trihydroxybenzoic acid synergistically interact with the carboxyl and hydroxyl groups of (2S)-2-hydroxysuccinic acid to form an association system with water and ethanol molecules through hydrogen bonds. This changes the activity coefficients of water and ethanol in the liquid phase, increases the relative volatility of ethyl acetate relative to water and ethanol, and thus makes it easier to separate ethyl acetate from the azeotropic system.

[0020] Compared with the prior art, the beneficial effects of the present invention are as follows: This invention addresses the problems of low separation limit, high reflux ratio, and difficulty in deep ethanol removal in conventional pressure swing distillation separation of ethyl acetate azeotropic systems. Through a coupled configuration of directional association of two auxiliary agents and side-stream interception in the rectification section, it achieves simultaneous improvements in separation efficiency, product quality, and operating costs. Specific beneficial effects are as follows: 1. This invention uses a complex system of 3,4,5-trihydroxybenzoic acid and (2S)-2-hydroxysuccinic acid as an azeotropic destructive agent. The 3,4,5-trihydroxybenzoic acid molecule contains three phenolic hydroxyl groups, and the (2S)-2-hydroxysuccinic acid molecule contains two carboxyl groups and one hydroxyl group, forming a complementary relationship in spatial structure. When the complex agent flows downward with the liquid phase, the phenolic hydroxyl groups and carboxyl groups form associations with water and ethanol molecules through hydrogen bonding, significantly reducing the activity coefficients of water and ethanol in the liquid phase.

[0021] When the activity coefficients of water and ethanol in the liquid phase decrease, their fugacity decreases, and the corresponding partial pressures of water and ethanol in the equilibrium gas phase decrease simultaneously. At operating pressures of 200-250 kPa, this effect is further amplified, resulting in a significant shift in the azeotropic composition. The relative volatility of ethyl acetate relative to water and ethanol increases substantially, making ethyl acetate easier to separate from the azeotropic system and extract as a high-purity product from the side stream.

[0022] From the perspective of distillation principles, the core function of the additive is to alter the activity coefficients of water and ethanol in the descending liquid phase, ensuring that the water and alcohol content of the rising gas phase is significantly lower than it would be without the additive before entering the upper rectification section. This rising gas phase then undergoes final purification in the rectification section, achieving excellent separation results.

[0023] Compared with conventional pressure swing distillation without additives (Comparative Example 2), the reflux ratio of the high-pressure distillation column decreased from 3.0 to 1.6, and the product purity increased from 99.55% to 99.98%.

[0024] 2. This invention features a liquid-phase side-stream outlet above the additive inlet. This location is designed based on the concentration gradient distribution within the distillation column and the physicochemical properties of the additives: 3,4,5-trihydroxybenzoic acid has a boiling point of 501.1℃, and (2S)-2-hydroxysuccinic acid has a boiling point of 306.4℃. Both are high-boiling-point substances that hardly volatilize upwards under distillation conditions, mainly flowing downwards with the liquid phase, thus preventing the additives from entering the product. Simultaneously, the closer to the bottom of the high-pressure distillation column, the higher the purity of ethyl acetate in the liquid phase. No additive residues are detected in the side-stream product, resulting in improved purity. Furthermore, the additives enriched in the bottom of the column can be recovered and recycled through simple vacuum distillation, without significantly increasing operating costs.

[0025] 3. With the combined effect of enhanced separation by compound additives and improved efficiency of side-stream distillation, a high-pressure distillation column reflux ratio of only 1.4-1.7 is sufficient to achieve efficient separation. Three examples demonstrate that under this low reflux ratio condition, the purity of the ethyl acetate product from the side-stream is ≥99.96%, water content <0.01%, and ethanol content ≤0.03%, with comprehensive indicators meeting HPLC-grade standards. Low reflux ratio operation directly reduces the reboiler heating load and the column top condensation load, enabling the separation process to be completed with lower energy consumption. Furthermore, the operating pressure of 200-250 kPa falls within the range of conventional medium-pressure distillation, requiring moderate material and wall thickness for equipment. The initial investment in the column and related auxiliary equipment is low, resulting in a low threshold for industrial implementation and excellent operational economics.

[0026] 4. This invention employs a multi-stage synergistic process involving alkaline washing pretreatment for deacidification, low-pressure distillation for preliminary dehydration and light component removal, high-pressure compounding of additives to enhance extraction distillation, and side-stream sampling. This process achieves a final product purity of 99.96%-99.98%, with water content ≤0.01%, ethanol content ≤0.03%, and evaporation residue ≤3ppm. The UV absorption curve is smooth, meeting all HPLC-grade wavelength requirements, specifically: 255nm ≤1.00AU, 260nm ≤0.30AU, 263nm ≤0.10AU, 265nm ≤0.05AU, and 300-400nm ≤0.01AU. Attached Figure Description

[0027] Figure 1 The above are the overall gas chromatogram and peak / quantitative results table of the ethyl acetate product obtained in Example 2 of this invention; Figure 2 for Figure 1 A magnified view of a portion of the image; Figure 3 This is the ultraviolet absorption spectrum of the ethyl acetate product obtained in Example 2 of the present invention. Detailed Implementation

[0028] Example 1 A method for separating ethyl acetate azeotropic systems using HPLC based on a multi-stage synergistic process includes the following steps: Step 1: Raw material pretreatment Industrial grade crude ethyl acetate (composition: 0.4 wt% acetic acid, 2.5 wt% ethanol, 3.5 wt% water, the remainder being ethyl acetate) was taken and added to a 6% sodium carbonate solution at a mass ratio of 8:100. The mixture was stirred and washed at 35°C for 22 min. After standing and separating into layers, the lower alkaline aqueous phase was removed. The mixture was then washed once with deionized water to remove the aqueous phase, thus obtaining the pretreated crude ester.

[0029] Step 2: Low-pressure distillation The pretreated crude ester is fed into the middle section of a low-pressure distillation column (at the 18th theoretical plate from the top), which has 35 theoretical plates. The absolute pressure at the top of the column is controlled at 28 kPa, the top temperature at 34°C, the bottom temperature at 73°C, and the reflux ratio at 1.7. The ethyl acetate-water-ethanol ternary azeotrope collected at the top of the column is condensed and then subjected to liquid-liquid phase separation to separate the organic and aqueous phases. The residual liquid containing high-boiling-point byproducts is collected from the bottom of the column and continuously discharged from the system.

[0030] Step 3: High-pressure azeotropic purification The organic phase from the separator is preheated to 80°C in a preheater and then continuously fed from the middle of the high-pressure distillation column (the 27th theoretical plate from the top). The high-pressure distillation column operates at an absolute pressure of 200 kPa, a top temperature of 85°C, a bottom temperature of 110°C, and has 45 theoretical plates.

[0031] 3,4,5-Trihydroxybenzoic acid and (2S)-2-hydroxysuccinic acid were compounded at a mass ratio of 3:0.8, dissolved in 10 times their mass of organic phase, and continuously injected into the column from the 7th theoretical plate (lower part of the rectification section) upwards from the bottom. The amount of additive was 0.3% of the mass of the reflux liquid at the top of the high-pressure distillation column. A side-stream liquid phase outlet was set at the 4th theoretical plate above the additive inlet, and the output was controlled at 18% of the total liquid volume descending in the column. The reflux ratio at the top of the column was controlled at 1.4. After the water-rich azeotropic vapor at the top of the column was condensed and separated, part of the upper ester-rich phase was refluxed, and the rest was recycled back to the feed inlet of the low-pressure column. The lower water-rich phase was sent to wastewater treatment. The material at the bottom of the column was continuously collected and the additive was recovered and reused through vacuum distillation.

[0032] After the above processing, the ethyl acetate liquid product obtained from the side stream of the high-pressure distillation column has a purity of 99.97% as determined by gas chromatography, with an ethanol content of 0.02%; the moisture content is <0.01% as determined by Karl Fischer moisture analyzer; the evaporation residue is 2 ppm; the finished product has a smooth ultraviolet absorption curve, meeting the requirements of HPLC grade in all wavelength ranges, specifically: 255nm≤1.00AU, 260nm≤0.30AU, 263nm≤0.10AU, 265nm≤0.05AU, 300-400nm≤0.01AU.

[0033] Example 2 Step 1. Raw material pretreatment Industrial grade crude ethyl acetate (composition: 0.5 wt% acetic acid, 3.0 wt% ethanol, 4.0 wt% water, the remainder being ethyl acetate) was taken and added to a 5% sodium carbonate solution at a mass ratio of 10:100 to the crude ester. The mixture was stirred and washed at 40°C for 20 min. After standing and separating into layers, the lower alkaline aqueous phase was removed. The mixture was then washed once with deionized water to remove the aqueous phase, thus obtaining the pretreated crude ester.

[0034] Step 2. Low-pressure distillation The pretreated crude ester is fed into the middle section of a low-pressure distillation column (the 20th theoretical plate from the top), which has 38 theoretical plates. The absolute pressure at the top of the column is controlled at 30 kPa, the top temperature at 35°C, the bottom temperature at 76°C, and the reflux ratio at 2.0. The ethyl acetate-water-ethanol ternary azeotrope collected at the top of the column is condensed and then subjected to liquid-liquid phase separation to separate the organic and aqueous phases. The residual liquid containing high-boiling-point byproducts is collected from the bottom of the column and continuously discharged from the system.

[0035] Step 3. High-pressure azeotropic purification The organic phase from the separator is preheated to 83°C in a preheater and then continuously fed into the middle of the high-pressure distillation column (the 30th theoretical plate from the top). The high-pressure distillation column operates at an absolute pressure of 225 kPa, a top temperature of 90°C, a bottom temperature of 115°C, and has 50 theoretical plates.

[0036] 3,4,5-Trihydroxybenzoic acid and (2S)-2-hydroxysuccinic acid were compounded at a mass ratio of 3:1.0, dissolved in 12 times their mass of organic phase, and continuously injected into the column from the 8th theoretical plate (lower part of the rectification section) upwards from the bottom. The amount of additive was 0.35% of the mass of the reflux liquid at the top of the high-pressure distillation column. A side stream liquid phase outlet was set at the 4th theoretical plate above the additive inlet, and the amount collected was controlled at 20% of the total liquid volume descending in the column. The reflux ratio at the top of the column was controlled at 1.6. After the water-rich azeotropic vapor at the top of the column was condensed and separated, part of the upper ester-rich phase was refluxed, and the rest was recycled back to the feed inlet of the low-pressure column. The lower water-rich phase was sent to wastewater treatment. The material at the bottom of the column was continuously collected and the additive was recovered and reused through vacuum distillation.

[0037] After the above process, the purity of the ethyl acetate liquid product obtained from the side stream of the high-pressure distillation column was 99.98% as determined by gas chromatography, with an ethanol content of 0.02%; the evaporation residue was 2 ppm; and the water content was <0.01%. The ultraviolet absorption characteristics of this product fully meet the quality requirements of HPLC-grade solvents.

[0038] The gas chromatogram of the ethyl acetate prepared in this embodiment is shown in the figure. Figure 1 In the figure, retention time 1.5592 corresponds to the peak of ethyl acetate, and retention time 1.2592 corresponds to the peak of ethanol. Figure 2 This is a partially enlarged view of the overall gas chromatogram of the ethyl acetate product obtained in this embodiment; Figure 3 The image shows the UV absorption curve of the ethyl acetate product obtained in this embodiment. The product has a smooth UV absorption curve that meets the requirements of all wavelengths for HPLC grade, specifically: 255nm≤1.00AU, 260nm≤0.30AU, 263nm≤0.10AU, 265nm≤0.05AU, and 300-400nm≤0.01AU.

[0039] Example 3 Step 1. Raw material pretreatment Industrial grade crude ethyl acetate (composition: 0.6 wt% acetic acid, 3.5 wt% ethanol, 4.5 wt% water, the remainder being ethyl acetate) was taken and added to a 4% sodium carbonate solution at a mass ratio of 12:100 to the crude ester. The mixture was stirred and washed at 45°C for 18 min. After standing and separating into layers, the lower alkaline aqueous phase was removed. The mixture was then washed once with deionized water to remove the aqueous phase, thus obtaining the pretreated crude ester.

[0040] Step 2. Low-pressure distillation The pretreated crude ester is fed into the middle section of a low-pressure distillation column (the 22nd theoretical plate from the top), which has 40 theoretical plates. The absolute pressure at the top of the column is controlled at 32 kPa, the top temperature at 36°C, the bottom temperature at 78°C, and the reflux ratio at 2.3. The ethyl acetate-water-ethanol ternary azeotrope collected at the top of the column is condensed and then subjected to liquid-liquid phase separation to separate the organic and aqueous phases. The residual liquid containing high-boiling-point byproducts is collected from the bottom of the column and continuously discharged from the system.

[0041] Step 3. High-pressure azeotropic purification The organic phase from the separator is preheated to 85°C in a preheater and then continuously fed into the middle of the high-pressure distillation column (the 33rd theoretical plate from the top). The high-pressure distillation column operates at an absolute pressure of 250 kPa, a top temperature of 95°C, a bottom temperature of 120°C, and has 55 theoretical plates.

[0042] 3,4,5-Trihydroxybenzoic acid and (2S)-2-hydroxysuccinic acid were compounded at a mass ratio of 3:1.2, dissolved in 15 times their mass of organic phase, and continuously injected into the column from the 9th theoretical plate (lower part of the rectification section) upwards from the bottom. The amount of additive was 0.4% of the mass of the reflux liquid at the top of the high-pressure distillation column. A side-stream liquid phase outlet was set at the 5th theoretical plate above the additive inlet, and the output was controlled at 22% of the total liquid volume descending in the column. The reflux ratio at the top of the column was controlled at 1.7. After the water-rich azeotropic vapor at the top of the column was condensed and separated, part of the upper ester-rich phase was refluxed, and the rest was recycled back to the feed inlet of the low-pressure column. The lower water-rich phase was sent to wastewater treatment. The bottom material was continuously collected and the additive was recovered and reused through vacuum distillation.

[0043] After the above process, the ethyl acetate liquid product obtained from the side stream of the high-pressure distillation column has a purity of 99.96% as determined by gas chromatography, with an ethanol content of 0.03%, a water content of <0.01%, and an evaporation residue of 3 ppm. The finished product has a smooth ultraviolet absorption curve, meeting the requirements of HPLC grade in all wavelength ranges, specifically: 255nm≤1.00AU, 260nm≤0.30AU, 263nm≤0.10AU, 265nm≤0.05AU, and 300-400nm≤0.01AU.

[0044] Comparative Example 1 Based on Example 2, the difference is that in step 3, the addition of compounding additives is omitted, a side-stream outlet is not set, and the product is drawn from the bottom of the high-pressure distillation column; the remaining steps are the same.

[0045] When the reflux ratio of the high-pressure distillation column is 1.6, the purity of the ethyl acetate product is 98.72%, the ethanol content is 0.65%, the evaporation residue is 13 ppm, and the water content is 0.42%. The ultraviolet absorption of this product is significantly high across the entire wavelength range, specifically: 1.85 AU at 255 nm, 0.62 AU at 260 nm, 0.32 AU at 263 nm, 0.18 AU at 265 nm, and 0.08 AU at 300-400 nm, all of which do not meet the ultraviolet absorption requirements of HPLC-grade solvents.

[0046] Comparative Example 2 Based on Comparative Example 1, the difference is that in step 3, the reflux ratio of the high-pressure distillation column is increased to 3; the rest of the steps are the same.

[0047] When the reflux ratio of the high-pressure distillation column was 3, the purity of the ethyl acetate product reached 99.55%, with an ethanol content of 0.30%; the evaporation residue was 11 ppm; and the water content was 0.11%. The UV absorption of this product decreased compared to Comparative Example 1, but still exceeded the limits in all areas, specifically: 1.23 AU at 255 nm, 0.48 AU at 260 nm, 0.17 AU at 263 nm, 0.09 AU at 265 nm, and 0.05 AU at 300-400 nm, failing to meet the UV quality standards for HPLC-grade solvents.

[0048] Comparative Example 3 Based on Example 2, the difference is that in step 3, an equal mass of 3,4,5-trihydroxybenzoic acid is used instead of the compounding agent, while the other steps are the same.

[0049] After the above processing, the purity of the ethyl acetate liquid product obtained from the side stream of the high-pressure distillation column was 99.74% as determined by gas chromatography, with an ethanol content of 0.17%, a water content of 0.06%, and an evaporation residue of 4 ppm. The short-wavelength ultraviolet absorption of this product basically met the standards, but the mid- and long-wavelength ranges exceeded the limits, specifically: 0.82 AU at 255 nm, 0.36 AU at 260 nm, 0.13 AU at 263 nm, 0.07 AU at 265 nm, and 0.02 AU at 300-400 nm. This does not fully meet the requirements of HPLC-grade solvents across all wavelengths.

[0050] In summary: Comparative Example 1 omitted the addition of compounding agents and did not include a side-stream outlet, with the product collected from the bottom of the high-pressure distillation column, based on Example 2. When the reflux ratio was controlled at 1.6, the product purity was only 98.72%, with a water content as high as 0.42%, an ethanol content of 0.65%, and an evaporation residue of 13 ppm. Simultaneously, the full-spectrum UV absorption far exceeded the HPLC grade limit. Compared to Example 2 (purity 99.98%, ethanol content 0.02%, water content <0.01%, evaporation residue 2 ppm), all indicators showed orders of magnitude difference. This indicates that, without the addition of additives, relying solely on the azeotropic composition difference of pressure swing distillation at low reflux ratios is insufficient for efficient removal of water and ethanol; furthermore, the bottom-stream collection method resulted in residues from the feedstock entering the product, leading to severely excessive evaporation residue. This comparative example demonstrates that the introduction of compounding agents and the establishment of a side-stream outlet are indispensable key technical measures.

[0051] Comparative Example 2 increased the reflux ratio of the high-pressure distillation column to 3.0, based on Comparative Example 1. At this point, the product purity increased to 99.55%, water content decreased to 0.11%, ethanol content decreased to 0.30%, and evaporation residue decreased to 11 ppm; however, the full-band UV absorption still exceeded the standard limit. This indicates that a high reflux ratio is required to improve product purity without the addition of additives, but this also means a significant increase in heat load and condensation load, resulting in a significant rise in energy consumption.

[0052] Comparative Example 3, based on Example 2, used an equal mass of 3,4,5-trihydroxybenzoic acid as a single auxiliary agent instead of the compound auxiliary agent (a mixture of 3,4,5-trihydroxybenzoic acid and (2S)-2-hydroxysuccinic acid), with all other conditions remaining identical. The results showed that the product purity was 99.74%, water content was 0.06%, ethanol content was 0.17%, and evaporation residue was 4 ppm. However, the control of mid-to-long wavelength ultraviolet impurities was poor, with absorbance exceeding the standard at 263 nm and above, failing to fully meet the requirements for HPLC-grade full-band ultraviolet light. Compared to Example 2 (purity 99.98%, ethanol content 0.02%, water content <0.01%, evaporation residue 2 ppm), the product purity decreased, while the ethanol content increased. This indicates that while 3,4,5-trihydroxybenzoic acid (3,4,5-trihydroxybenzoic acid) is reasonably effective at removing water through association, its ability to associate with ethanol is significantly insufficient. The addition of (2S)-2-hydroxysuccinic acid (2S) compensates for this deficiency. Its carboxyl and hydroxyl groups associate with ethanol molecules through specific hydrogen bonds, forming a synergistic complement to the strong hydrogen bonding of 3,4,5-trihydroxybenzoic acid with water molecules. This comparative example demonstrates that the combined formulation of 3,4,5-trihydroxybenzoic acid and (2S)-2-hydroxysuccinic acid can simultaneously and efficiently remove both water and ethanol.

Claims

1. A method for separating ethyl acetate azeotropic systems using HPLC based on a multi-stage synergistic process, characterized in that: The separation method includes the following steps: raw material pretreatment, low-pressure distillation, and high-pressure azeotropic purification. The method for pretreatment of the raw materials is as follows: sodium carbonate solution is added to industrial grade crude ethyl acetate, and the mixture is stirred and washed at 35-45℃ for 18-22 min. After standing and separating into layers, the lower alkaline aqueous phase is removed, and then the mixture is washed once with deionized water to remove the aqueous phase, thereby obtaining the pretreated crude ester. The industrial-grade crude ethyl acetate contains 0.4-0.6 wt% acetic acid, 2.5-3.5 wt% ethanol, and 3.5-4.5 wt% water, respectively. The low-pressure distillation method involves feeding the pretreated crude ester into the middle of a low-pressure distillation column, controlling the absolute pressure at the top of the column at 28-32 kPa, the temperature at the top of the column at 34-36°C, and the temperature at the bottom of the column at 73-78°C. The ethyl acetate-water-ethanol ternary azeotrope collected at the top of the column is condensed and then subjected to liquid-liquid phase separation to separate the organic phase and the aqueous phase. The high-pressure azeotropic purification method involves controlling the absolute operating pressure of the high-pressure distillation column at 200-250 kPa, the top temperature at 85-95°C, and the bottom temperature at 110-120°C. The organic phase from the separator is preheated to 80-85°C by a preheater and then continuously fed into the middle of the high-pressure distillation column. Simultaneously, a compound additive solution is continuously injected into the column from the lower part of the rectification section. A side-stream liquid phase outlet is set above the inlet of the compound additive solution to continuously collect the ethyl acetate product. Azeotropic vapor rich in water is collected from the top of the column. After condensation, the azeotropic vapor undergoes liquid-liquid phase separation. A portion of the upper ester-rich phase is returned to the top of the high-pressure distillation column as reflux, with the reflux ratio controlled at 1.4-1.

7. The remainder is recycled back to the feed inlet of the low-pressure column. The material in the bottom of the high-pressure distillation column is continuously collected, and the collected liquid is recovered by vacuum distillation. The compound additive solution is a solution obtained by dissolving the compound additive in the organic phase of a separator with 10-15 times its mass. The compounding agent is obtained by compounding 3,4,5-trihydroxybenzoic acid and (2S)-2-hydroxysuccinic acid in a mass ratio of 3:0.8-1.

2.

2. The HPLC-grade ethyl acetate azeotropic system separation method based on a multi-stage synergistic process according to claim 1, characterized in that: In the high-pressure azeotropic purification step, the theoretical number of plates in the column is 45-55. The middle part of the high-pressure distillation column is the 27th-33rd theoretical plate counting down from the top of the column; The lower part of the rectification section of the high-pressure distillation column is located at the 7th to 9th theoretical plates counting upwards from the bottom of the column. The inlet of the compound additive solution is located at the 4th-5th theoretical plate counting upwards from the theoretical plate of the compound additive solution feed tower.

3. The HPLC-grade ethyl acetate azeotropic system separation method based on a multi-stage synergistic process according to claim 1, characterized in that: In the high-pressure azeotropic purification step, the amount of the compound additive is 0.3%-0.4% of the mass of the reflux liquid at the top of the high-pressure distillation column.

4. The HPLC-grade ethyl acetate azeotropic system separation method based on a multi-stage synergistic process according to claim 1, characterized in that: In the high-pressure azeotropic purification step, the amount of ethyl acetate product extracted is controlled at 18%-22% of the total liquid volume descending in the tower.

5. The HPLC-grade ethyl acetate azeotropic system separation method based on a multi-stage synergistic process according to claim 1, characterized in that: In the raw material pretreatment step The concentration of the sodium carbonate solution is 4-6%; The mass ratio of the sodium carbonate solution to industrial-grade crude ethyl acetate is 8-12:

100.

6. The HPLC-grade ethyl acetate azeotropic system separation method based on a multi-stage synergistic process according to claim 1, characterized in that: In the low-pressure distillation step, the middle part of the low-pressure distillation column is the 18th-22nd theoretical plate counting downwards from the top of the column; the number of theoretical plates in the column is 35-40.

7. The HPLC-grade ethyl acetate azeotropic system separation method based on a multi-stage synergistic process according to claim 1, characterized in that: In the low-pressure distillation step, the reflux ratio is controlled between 1.7 and 2.3.

Images