Green preparation method of high-purity medicinal glacial acetic acid

Abstract

The invention discloses a green preparation method of high-purity medicinal glacial acetic acid. Belongs to the technical field of fine chemical engineering. According to the method, bio-based ethanol is used as a raw material and is subjected to a catalytic oxidation reaction with oxygen in a reactive distillation tower under the action of a self-designed multifunctional composite ionic liquid catalyst. After the reaction, a crude acetic acid solution is sequentially subjected to specific molecular sieve adsorption and multi-stage low-temperature gradient crystallization purification. The core of the invention lies in catalyst design: ultrahigh selectivity (gt; 99.8%) and ultra-long catalytic stability from ethanol to acetic acid are realized under mild conditions by utilizing the template effect of acetate anions and the synergistic effect of palladium-ruthenium bimetallic nanoclusters. According to the integrated process, halogen and heavy metal pollution is avoided from the source, the product purity is larger than or equal to 99.99%, the content of key impurities (formic acid and propionic acid) is reduced by 1-2 orders of magnitude compared with a traditional process, energy consumption is remarkably reduced, and the integrated process is an efficient and green medicinal glacial acetic acid preparation path.

Description

Technical Field

[0001] This invention relates to the field of fine chemical preparation technology, and more specifically to a green method for preparing high-purity pharmaceutical-grade glacial acetic acid. Background Technology

[0002] Glacial acetic acid is a crucial basic organic chemical raw material, and its high-purity product (pharmaceutical grade) is widely in demand in the pharmaceutical, food, and high-end electronic chemical industries. While the current mainstream methanol carbonylation methods (such as the Cativa process) are large-scale, they rely on highly toxic iodomethane co-catalysts and expensive iridium-based catalysts, resulting in high reaction pressures (3.0-10.0 MPa). Furthermore, they inevitably introduce iodine and heavy metal impurities into the product. Subsequent purification processes to meet pharmaceutical standards are complex, energy-intensive, and involve significant waste treatment challenges, contradicting the development direction of green chemistry.

[0003] Ethanol oxidation is a potential green route using biomass as a raw material, aligning with the carbon neutrality strategy. However, this route has long faced core challenges: First, catalyst selectivity control is difficult. Ethanol oxidation is a typical tandem reaction (ethanol-acetaldehyde-acetic acid-over-oxidation products (CO2, formic acid, etc.)). Traditional heterogeneous catalysts (such as supported Au and Pd catalysts) often lead to over-oxidation in the gas phase due to high reaction temperatures (>250℃), making it difficult to stably maintain an acetic acid selectivity exceeding 90%. Second, catalyst stability is poor. Noble metal nanoparticles are prone to leaching, migration, aggregation, and sintering in the liquid reaction medium, resulting in a rapid decline in activity. Third, product separation is energy-intensive. The reaction products are a mixture of acetic acid, water, a small amount of unreacted ethanol, and various trace byproducts. Separating and purifying them to pharmaceutical grade requires multiple energy-intensive distillation steps, which is not economically viable.

[0004] Ionic liquids, as novel reaction media and catalysts, have attracted attention due to their high designability, extremely low vapor pressure, and good stabilizing effect on metal species. Existing technologies have reported the use of ionic liquids as solvents or simple catalysts for alcohol oxidation. Some studies have attempted to disperse metal nanoparticles in ionic liquids, but their designs are often relatively simple, treating the ionic liquid merely as an inert support or stabilizer, without deeply considering the intrinsic relationship between the ionic liquid's structure and the target reaction. Therefore, breakthroughs in catalytic performance (especially selectivity and stability) are limited, and there is still a significant gap between these advancements and the requirements for industrial applications.

[0005] Therefore, developing a novel, green method for preparing high-purity pharmaceutical-grade glacial acetic acid is a technical problem that urgently needs to be solved by those skilled in the art. Summary of the Invention

[0006] In view of this, the present invention develops a green preparation method for high-purity pharmaceutical-grade glacial acetic acid.

[0007] To solve the above-mentioned technical problems, this application adopts the following technical solution:

[0008] The primary objective of this application is to provide a green method for preparing high-purity pharmaceutical-grade glacial acetic acid, comprising the following steps:

[0009] S1. Catalytic oxidation reaction: Using bio-based ethanol as raw material, an oxidation reaction is carried out with oxygen-containing gas in the reaction section of a reactive distillation column in the presence of a multifunctional composite ionic liquid catalyst; the reaction temperature is 95-115℃, the reaction pressure is 0.1-0.4 MPa, and the oxygen partial pressure is 0.1-0.6 MPa.

[0010] S2. Separation of reaction products: Unreacted ethanol, byproduct acetaldehyde, and water are distilled off from the top of the reactive distillation column. After condensation, part of the product is refluxed and part is returned to the feed system. Crude product liquid rich in acetic acid is continuously collected from the bottom of the column.

[0011] S3. Crude Product Refining: The crude acetic acid liquid collected from the bottom of the column is subjected to adsorption pretreatment and multi-stage low-temperature gradient crystallization to obtain high-purity acetic acid crystals. The adsorption pretreatment aims to selectively capture long-chain carboxylic acid impurities with slightly larger molecular sizes (such as propionic acid and butyric acid). These impurities have boiling points close to acetic acid and are the main interferences in subsequent crystallization purification. Adsorption pretreatment can be regarded as a "pre-purification" of the crude product, laying the foundation for obtaining extremely high-purity crystals in subsequent crystallization.

[0012] S4. Post-processing: After melting the acetic acid crystals, filter them through a membrane to obtain high-purity pharmaceutical-grade glacial acetic acid;

[0013] The multifunctional composite ionic liquid catalyst described in step S1 consists of a functionalized ionic liquid and highly dispersed palladium-ruthenium bimetallic nanoclusters therein, and its structural formula is represented as: [BMIM + [CH3COO] - ] / Pd-Ru NCs, where:

[0014] BMIM + [CH3COO] - [It is 1-butyl-3-methylimidazolium acetate, CAS number 284049-75-8;]

[0015] Pd-Ru NCs represent active metal components of palladium and ruthenium existing in the form of nanoclusters, wherein the molar ratio of palladium to ruthenium is 1:0.1-1:1;

[0016] The bimetallic nanoclusters are stabilized by coordination with the acetate anion of the ionic liquid, and the total mass of the metal accounts for 0.1% to 5.0% of the total mass of the catalyst.

[0017] As a preferred technical solution, in the reactive distillation column described in step S1, the multifunctional composite ionic liquid catalyst is filled in the reaction section in the middle of the column. The upper part of the reaction section is the rectification section, and the lower part is the stripping section. The upper rectification section continuously distills off the light components (unreacted ethanol, acetaldehyde, and water) and partially refluxes them, controlling the composition of the reaction zone. The lower stripping section promptly removes the generated heavy component products (acetic acid and water) from the reaction zone. This process breaks the thermodynamic equilibrium limitations of traditional batch reactions, making the ethanol conversion rate close to 100%, and further suppresses the occurrence of cascade side reactions from a kinetic perspective by utilizing the strategy of immediate product removal, pushing selectivity to the extreme.

[0018] As a preferred technical solution, the palladium-ruthenium bimetallic nanoclusters have an average particle size of 1.0-3.0 nm and a standard deviation of particle size distribution of less than 0.5 nm.

[0019] The structural formula is [BMIM] + [CH3COO] - The multifunctional composite ionic liquid catalyst of Pd-Ru NCs is not a simple physical mixture of ionic liquid and metal nanoparticles, but an organic-inorganic composite catalytic system with specific interactions and functions:

[0020] Selection of functionalized ionic liquid matrix: This invention abandons the commonly used [BF4] matrix. - [PF6] - Inert anions, but deliberately selected acetate ([CH3COO) - [CH3COO] is used as the anion of the ionic liquid. This choice is based on the profound ideas of "biomimetic catalysis" and "template effect". The target product is acetic acid, and the catalyst itself is the acetate anion. This "product analogue" environment can produce the following key effects: (a) Promote product desorption: Acetic acid molecules generated at the reaction site react with the surrounding [CH3COO] - The anions have similar structures and polarities, which can effectively lower the energy barrier for acetic acid to desorb from the active site, preventing it from further excessive oxidation and decomposition into CO2 or formic acid. This is the structural basis for achieving ultra-high selectivity. (b) Stable reaction intermediate: [CH3COO - It may stabilize key intermediates in the ethanol oxidation process (such as acetaldehyde) through hydrogen bonding or weak coordination, guiding its directional conversion to acetic acid. (c) As a ligand to stabilize metal nanoclusters: [CH3COO - The oxygen atoms in the bimetallic nanoclusters can coordinate to Pd and Ru metal atoms, becoming one of the surface ligands of the bimetallic nanoclusters. This not only prevents the excessive growth and aggregation of the nanoclusters, but also regulates their surface electronic state, optimizing their adsorption and activation capabilities for reactants (ethanol, O2).

[0021] Design of Active Centers: This invention employs palladium-ruthenium (Pd-Ru) bimetallic nanoclusters (NCs) as active centers. Compared to single-metal Pd (which is prone to over-oxidation) or single-metal Ru (which has lower activity), the atomic-level mixing of Pd and Ru to form nanoclusters produces unique electronic synergistic and geometric effects. Theoretical calculations and experiments show that the introduction of Ru can moderately weaken the adsorption strength of Pd for intermediate products, avoiding deep oxidation caused by strong adsorption. Simultaneously, the Pd-Ru interface sites exhibit stronger dissociation activation ability for O2. This invention limits the average particle size of the bimetallic nanoclusters to 1.0-3.0 nm and controls their high dispersion to expose the maximum number of active and interface sites.

[0022] As a preferred technical solution, the multifunctional composite ionic liquid catalyst is prepared by the following method:

[0023] a. Under an inert atmosphere, the selected acetate-based ionic liquid [BMIM] + [CH3COO] - Heat to 60-90℃ and stir continuously;

[0024] b. Dissolve a soluble metal salt of palladium and a soluble metal salt of ruthenium together in deionized water to prepare a mixed metal salt solution; wherein the metal salt is selected from chlorides, nitrates or acetates;

[0025] c. Slowly add the mixed metal salt solution prepared in step b to the ionic liquid in step a, and stir at a constant temperature for 1-4 hours to allow the metal ions to fully coordinate with the ionic liquid;

[0026] d. Slowly add an aqueous solution of reducing agent dropwise to the mixture obtained in step c, and carry out an in-situ reduction reaction for 0.5-2 hours with stirring;

[0027] e. After the reaction is complete, allow the mixture to stand and separate into layers. Separate and discard the upper aqueous phase. Wash the lower ionic liquid phase with deionized water and dry it under vacuum to obtain the multifunctional composite ionic liquid catalyst.

[0028] As a preferred technical solution, the reducing agent in step d is sodium borohydride or hydrazine hydrate, and its amount is 1.5-3.0 times the stoichiometric amount required for the theoretical reduction of metal ions.

[0029] As a preferred technical solution, in step S3, the adsorption pretreatment involves passing crude acetic acid liquid through an adsorption tower filled with aluminosilicate molecular sieves. The molecular sieves have a pore size of 0.45-0.5 nm and are used to selectively adsorb propionic acid and butyric acid impurities.

[0030] As a preferred technical solution, in step S3, the multi-stage low-temperature gradient crystallization includes at least: a first stage of crystallization at 8-15℃ to remove most of the water; a second stage of crystallization at -3 to 3℃ to obtain acetic acid hydrate crystals; and a third stage of crystallization at -18 to -8℃ to obtain high-purity acetic acid crystals.

[0031] As a preferred technical solution, the green preparation method further includes an energy integration step: recovering the reaction heat in step S1 and the crystal melting heat in step S4 through a heat pump system, which is used to preheat the raw materials and / or provide some cooling for the crystallization device in step S3.

[0032] Another object of this application is to provide: a high-purity pharmaceutical-grade glacial acetic acid product prepared by the above-described green preparation method, wherein the product has a purity ≥99.99%, moisture ≤0.015%, formic acid content ≤5 ppm, propionic acid content ≤10 ppm, heavy metal content (Pb) ≤0.1 ppm, non-volatile matter ≤0.001%, and no iodides detected.

[0033] As can be seen from the above technical solution, compared with the prior art, the present invention has the following beneficial effects:

[0034] 1. A disruptive breakthrough in catalyst performance (the core manifestation of non-obviousness)

[0035] Based on conventional understanding, those skilled in the art would typically choose inert or acidic anionic liquids to support noble metals for oxidation catalysis. This invention takes the opposite approach, selecting the acetate anion, which has the same structure as the target product, and constructing a Pd-Ru bimetallic system based on it. This design concept is not obvious. The resulting synergistic effect brings about a qualitative leap in performance:

[0036] Exceptionally high selectivity: Under mild conditions of 95-115℃ and below 0.5 MPa, the selectivity for the oxidation of ethanol to acetic acid is consistently greater than 99.8%, with a yield greater than 98.5%. This data far exceeds the best reported performance in its class (typically 90-95% selectivity and 85-90% yield). Comparative experiments (see below) demonstrate that replacing the anion with [BF4]... - Alternatively, using single-metal Pd significantly reduces selectivity to below 95%, accompanied by noticeable formic acid and CO2 generation. This strongly demonstrates that the specific combination of "acetate anion + Pd-Ru bimetal" produces a synergistic catalytic effect of "1+1>>2," which cannot be easily derived or anticipated by those skilled in the art from existing technologies.

[0037] Exceptional stability: After more than 500 cycles of continuous or intermittent operation, the catalyst exhibits less than 3% activity decay. Transmission electron microscopy (TEM) observation shows almost no increase in the Pd-Ru nanocluster size, and metal leaching is less than 1 ppm. This stability stems from [CH3COO] - The strong coordination and anchoring effect of nanoclusters and the good compatibility with ionic liquid matrices solve the global problem of difficult recovery of homogeneous catalytic metals and easy deactivation of heterogeneous catalysis.

[0038] 2. Comprehensive optimization of process flow and final product

[0039] Green from the source, simplified process: Starting with bio-based ethanol, the entire process uses no halogens or toxic heavy metal additives, eliminating iodide and heavy metal pollution at the source. Utilizing high-performance catalysts and reactive distillation as the core, the generation of byproducts is minimized from the reaction source, significantly simplifying subsequent purification processes and overcoming the drawbacks of traditional "pollute first, then treat" methods.

[0040] The product achieves ultimate purity: thanks to high selectivity at the source and efficient adsorption-crystallization coupling purification, the product purity easily reaches over 99.99%. The content of key trace impurities such as formic acid (<5 ppm) and propionic acid (<10 ppm) is reduced by 1-2 orders of magnitude compared to products purified by the traditional methanol carbonylation method. The product fully meets and exceeds all requirements of the Chinese Pharmacopoeia, the European Pharmacopoeia (EP), and the United States Pharmacopoeia (USP).

[0041] Significant improvements in energy consumption and economic efficiency: Mild reaction conditions, enhanced reactive distillation processes, and integrated heat pump energy reduce the overall energy consumption per unit product. The long catalyst life and easy recovery methods also significantly reduce operating costs.

[0042] In summary, this invention is not a simple patchwork or parameter optimization of existing technologies, but rather proposes a novel catalyst design philosophy. Based on this philosophy, a green manufacturing system with a rigorous internal logic and synergistic effects among its components is constructed. Its overall technical solution possesses outstanding substantive features and significant advancements. Detailed Implementation

[0043] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0044] Example 1

[0045] Preparation of multifunctional composite ionic liquid catalysts ([BMIM][CH3COO] / Pd-Ru NCs)

[0046] In a nitrogen-filled glove box, add 50.0 g of 1-butyl-3-methylimidazolium acetate ([BMIM][CH3COO], purity >99%) to a 100 mL three-necked flask equipped with a magnetic stirrer and a condenser. Remove the flask and heat it to 80°C in an oil bath under nitrogen protection while stirring.

[0047] Accurately weigh 0.177 g PdCl2 (1.0 mmol Pd) and 0.052 g RuCl3·3H2O (0.2 mmol Ru), and dissolve them together in 10 mL of deionized water to prepare a mixed metal salt solution. Using a constant-pressure dropping funnel, slowly add this solution dropwise to the aforementioned ionic liquid at 80°C over 30 minutes. After the addition is complete, maintain the temperature at 80°C and continue vigorous stirring for 2 hours. The solution color turns dark brown, indicating that the metal ions and the ionic liquid are fully coordinated.

[0048] Prepare 20 mL (10 mmol) of a 0.5 M NaBH4 aqueous solution. Under ice-water bath cooling and vigorous stirring, slowly add the NaBH4 solution dropwise to the reaction mixture over 15 minutes. A large number of bubbles will be observed to form instantaneously, and the mixture will gradually turn dark black. After the addition is complete, remove the ice bath and continue stirring at 80°C for 1 hour to complete the reduction.

[0049] The reaction mixture was transferred to a separatory funnel and allowed to stand overnight until complete separation of the phases. The upper colorless or pale yellow aqueous phase was carefully separated and discarded. The lower black ionic liquid phase (i.e., the catalyst) was washed three times with 30 mL of deionized water at 60 °C (stirring for 10 minutes each time followed by separation) to remove residual inorganic salts. Finally, the resulting black viscous liquid was vacuum dried at 70 °C and -0.095 MPa for 24 hours to obtain approximately 50.2 g of [BMIM][CH3COO] / Pd-Ru NCs catalyst (Pd:Ru molar ratio = 5:1, total metal loading approximately 0.45 wt%).

[0050] Measurements showed that the Pd-Ru bimetallic nanoclusters were highly uniformly dispersed in the matrix, with an average particle size of 2.2 nm and a narrow particle size distribution (standard deviation 0.4 nm). No obvious aggregates were observed.

[0051] To demonstrate the necessity of the specific structure of this invention (acetate anion and Pd-Ru bimetal), the following comparative catalysts were prepared:

[0052] Comparative Example 1: [BMIM][BF4] / Pd-Ru NCs: Except for replacing the ionic liquid with an equal mass of 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM][BF4]), the metal species, loading, and preparation steps were exactly the same as in Example 1.

[0053] Comparative Example 2: [BMIM][CH3COO] / Pd NCs: Except for not adding RuCl3, only using 0.212 g PdCl2 (1.2 mmol Pd) to keep the total number of metal moles approximately the same as in Example 1, the other steps were the same as in Example 1.

[0054] Comparative Example 3: [BMIM][CH3COO] / Ru NCs: Except for not adding PdCl2, only using 0.313 g RuCl3·3H2O (1.2 mmol Ru), the other steps are the same as in Example 1.

[0055] Example 2

[0056] Catalyst performance evaluation (batch reactor)

[0057] In a 300 mL jacketed high-pressure reactor, 100 g of deionized water and 5.0 g of the catalyst prepared in Example 1 were added sequentially. After sealing, the reactor was purged three times with nitrogen, followed by three times with oxygen. Oxygen was then introduced to bring the initial pressure to 0.8 MPa (at room temperature). 40 g of anhydrous ethanol was injected via a feed pump. Stirring was started (1000 rpm), and the reactor temperature was raised to 105 °C using an oil bath, at which point the pressure was approximately 1.2 MPa. The reaction was carried out under these conditions for 4 hours.

[0058] After the reaction was completed, the mixture was rapidly cooled to room temperature in an ice-water bath, and the pressure was released. The reaction solution naturally separated into two phases: the upper layer was mainly aqueous (containing the product acetic acid), and the lower layer was the catalyst phase. The two phases were carefully separated. The composition of the upper aqueous phase product was analyzed by gas chromatography (GC, HP-INNOWax column, FID detector), and the ethanol conversion, acetic acid selectivity, and yield were calculated. The results are shown in Table 1.

[0059] The catalysts prepared in Comparative Examples 1, 2, and 3 were used respectively, and their performance was evaluated and cycled (5 cycles) were performed under the same reaction conditions as in Example 2. The results are shown in Table 1.

[0060] Table 1. Comparison of the performance of different catalysts in the oxidation of ethanol to acetic acid (reaction conditions: 105℃, 4h)

[0061] catalyst system Ethanol conversion rate (%) Acetic acid selectivity (%) Acetic acid yield (%) Major byproducts (selectivity %) Example 1 Catalyst 99.7 99.82 99.52 Acetaldehyde (0.10), formic acid (0.05) Comparative Example 1 Catalyst 98.5 94.3 92.9 Acetaldehyde (3.1%), Formic acid (1.8%), CO2 (0.5%) Comparative Example 2 Catalyst 99.2 96.5 95.7 Acetaldehyde (2.1), Formic acid (1.2) Comparative Example 3 Catalyst 45.6 88.4 40.3 Acetaldehyde (9.5%), unreacted ethanol

[0062] Results Analysis: Table 1 clearly demonstrates the non-obviousness and synergistic effect of the catalyst design in this invention. Only by transferring the anion from [CH3COO...] - Replace with lazy [BF4] - (Comparative Example 1) The selectivity of acetic acid dropped sharply from 99.82% to 94.3%, while the over-oxidation products such as formic acid increased significantly. While maintaining [CH3COO] - Under the premise of […], the performance of using single-metal Pd (Comparative Example 2) or single-metal Ru (Comparative Example 3) is far inferior to that of the bimetallic system. This strongly demonstrates that "acetate anion" and "Pd-Ru bimetallic nanoclusters" are two indispensable and mutually reinforcing core elements of this invention, and their combination produces unexpectedly high selective catalytic performance.

[0063] Example 3

[0064] Integrated process for preparing high-purity pharmaceutical-grade glacial acetic acid (continuous small-scale laboratory tests)

[0065] The reactive distillation column is made of glass, with an inner diameter of 30 mm and a packing height of 1.2 m. The reaction section is filled with structured packing, and the catalyst is either coated on the packing surface in liquid film form or exists directly as a liquid phase in the reaction section. The feed is a 95 wt% bio-based ethanol aqueous solution, with a feed rate of 20 mL / h. Oxygen is introduced from the bottom of the reaction section at a flow rate of 50 mL / min. The bottom temperature is controlled at 118℃, the reaction section temperature at 105℃, the top temperature at 80-85℃, and the system pressure is maintained at approximately 0.2 MPa (gauge pressure). After condensation, part of the distillate from the top is refluxed (reflux ratio R=2), and part is collected and returned to the feed tank. A crude acetic acid solution is continuously collected from the bottom (flow rate approximately 18 mL / h, GC analysis shows an acetic acid concentration of approximately 82%).

[0066] Crude acetic acid solution was pretreated by passing it at a flow rate of 1 BV / h through an adsorption column (Φ15×150 mm) packed with 20 mL of SAPO-34 molecular sieve with a pore size of 0.48 nm. When the propionic acid concentration in the feed solution at the adsorption column outlet reached 10% of the inlet concentration, the column was switched to a standby adsorption column for adsorption. The saturated adsorption column could be regenerated by countercurrent desorption with hot acetic acid at 80-90°C.

[0067] The pretreated acid solution is fed into a three-stage temperature-programmed crystallizer (100 mL glass jacketed reactors connected in series). Stage 1: Cooling to 10°C at 0.3°C / min, crystallizing at this temperature for 30 minutes, then centrifuging to remove ice crystals; Stage 2: The mother liquor is transferred to the next reactor, cooled to 0°C at 0.2°C / min, crystallized for 60 minutes, and centrifuged to obtain acetic acid monohydrate crystals (partially used as seed crystals for the third stage); Stage 3: The remaining mother liquor is transferred to the final reactor, cooled to -12°C at 0.1°C / min, crystallized for 120 minutes, and centrifuged to obtain high-purity acetic acid crystals.

[0068] The crystals were melted to room temperature (20-25℃) and then passed through a 0.22 μm polytetrafluoroethylene (PTFE) flat sheet membrane filter to obtain the final product. Samples were taken and analyzed hourly for 120 hours (5 days) of continuous operation, and the product indicators remained stable. Representative samples were sent to a third-party testing institution for full-item testing according to the methods in the 2020 edition of the Chinese Pharmacopoeia. The results are shown in Table 2.

[0069] Comparative Example 4: Samples from Traditional Processes

[0070] Commercially available pharmaceutical-grade glacial acetic acid produced via methanol carbonylation and verified to meet the standards of the Chinese Pharmacopoeia was selected as a control sample. This sample represents the typical purity level achievable by current mainstream industrial processes.

[0071] Table 2: Comparison of Key Product Quality Indicators

[0072] Testing items Chinese Pharmacopoeia Standard Comparative Example 4 (Commercially Available) Example 3 Product (This Invention) Detection methods purity(%) ≥99.5 99.85 99.996 GC Moisture (%) ≤0.20 0.048 0.008 Karl Fischer Formic acid (ppm) Through the experiment 38 <2 Ion chromatography Propionic acid (ppm) Through the experiment 122 <5 GC-MS Heavy metals (as Pb, ppm) ≤0.5 0.25 <0.05 Atomic absorption Non-volatile matter (%) ≤0.01 0.0027 <0.0005 Gravimetric method Iodides (ppm) Through the experiment <1 (limit of detection) Not detected Ion chromatography

[0073] Results Analysis: Table 2 shows that the glacial acetic acid prepared using the integrated process of this invention is significantly superior to the product prepared by the traditional carbonylation method in all key indicators, especially in the reduction of organic impurities such as formic acid and propionic acid, which have a significant impact on drug safety, by orders of magnitude. This fully demonstrates that the green process based on the high-performance catalyst of this invention can directly produce ultra-high-quality pharmaceutical raw materials.

[0074] Example 4

[0075] Long-term stability testing of catalysts (pilot-scale simulation)

[0076] 500 g of the catalyst from Example 1 was charged into a 1-liter continuous stirred tank reactor (CSTR). An aqueous ethanol solution (ethanol space velocity 0.5 h⁻¹) was continuously circulated at 105°C and 1.0 MPa oxygen pressure. The reaction mixture rapidly separated into phases in a settling tank; the upper product phase was collected, and the lower catalyst phase was continuously recycled back to the reactor. Samples were taken every 168 hours (one week) for analysis of product composition and catalyst metal content (ICP-OES). This simulation experiment was conducted for over 6000 hours (approximately 250 days, corresponding to a theoretical catalyst contact count >500).

[0077] Table 3 Long-cycle reaction performance data

[0078] Cumulative running time (hours) Ethanol conversion rate (%) Acetic acid selectivity (%) Acetic acid yield (%) Notes (e.g., temporary system adjustments) 0 (Initial) 99.7 99.82 99.52 Reaction start-up, performance baseline 672 (Week 4) 99.6 99.80 99.40 Stable performance 1344 (Week 8) 99.6 99.78 99.38 Continuous operation 2016 (Week 12) 99.6 99.77 99.37 No performance degradation 2688 (Week 16) 99.5 99.76 99.26 The conversion rate fluctuated slightly, which is within the normal range. 3360 (Week 20) 99.5 99.75 99.25 Selectively maintain a high level 4032 (Week 24) 99.5 99.75 99.25 Entering a long-term stable plateau period 4704 (Week 28) 99.5 99.74 99.24 The performance remains stable 5376 (Week 32) 99.5 99.73 99.23 Nearly 500 theoretical cycles 6048 (Week 36) 99.5 99.72 99.22 The test is complete; the performance degradation is negligible.

[0079] Table 4. Structural characterization and metal retention data of the catalyst before and after the reaction.

[0080] Analysis Project Fresh catalyst (before reaction) Deactivated / aged catalyst (after 6048 hours of operation) Changes and Analysis Average particle size (TEM) of bimetallic nanoclusters 2.2 nm 2.8 nm The particle size only increased by 27%, and no obvious sintering agglomeration was observed, proving the strong coordination stabilization of [CH3COO - ]. Metal retention ratio (ICP-OES) Pd: 100% (Baseline) Ru: 100% (Baseline) Pd: >99.7% Ru: >99.6% The total metal leaching loss is less than 0.5%, which is negligible, and the problem of homogeneous catalytic metal loss is solved. Surface electronic states (XPS) Pd 3d5 / 2 binding energy: 335.8 eV (positive shift of 0.4 eV from metallic Pd) Pd 3d5 / 2 binding energy: 335.9 eV The fact that the binding energy remains essentially unchanged proves that the electronic structure of the bimetallic nanoclusters is stable, which is the intrinsic reason for the stable catalytic performance.

[0081] The results showed that the ethanol conversion rate remained above 99.5% throughout the entire operation, and the acetic acid selectivity remained stable between 99.7% and 99.8%. After the operation, TEM analysis of catalyst samples revealed that the average particle size of the bimetallic nanoclusters only increased to 2.8 nm, with no significant agglomeration observed. The retention rates of Pd and Ru in the catalyst exceeded 99.5%, and the leaching loss was negligible. This demonstrates that the catalyst of this invention possesses the ultra-long service life and extreme stability necessary for industrial applications.

[0082] Example 5

[0083] Industrial Application Examples

[0084] Based on the above experimental data, an industrial plant with an annual production capacity of 50,000 tons of high-purity pharmaceutical-grade glacial acetic acid was designed. The core reactor is a large reactive distillation column, with a catalyst loading of approximately 30 tons per cycle. The overall energy consumption (steam and electricity) is expected to be about 35% lower than that of a traditional methanol carbonylation-refining plant of the same scale. Due to the extremely long catalyst lifespan, the annual cost of replenishing precious metals is extremely low. The entire process generates no iodine-containing wastewater or spent catalyst, demonstrating significant environmental advantages.

[0085] The various embodiments in this specification are described in a progressive manner, with each embodiment focusing on the differences from other embodiments. The same or similar parts between the various embodiments can be referred to each other.

[0086] The above description of the disclosed embodiments enables those skilled in the art to make or use the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention. Therefore, the invention is not to be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A green process for the preparation of high purity pharmaceutical grade glacial acetic acid characterized in that, Comprising the following steps: S1. Catalytic oxidation reaction: bio-based ethanol as raw material, with oxygen-containing gas in the presence of multifunctional composite ionic liquid catalyst, in the reaction section of the reaction rectifying column to carry out oxidation reaction; the reaction temperature is 95-115℃, the reaction pressure is 0.1-0.4 MPa, and the oxygen partial pressure is 0.1-0.6 MPa; S2. Reaction product separation: the unreacted ethanol, byproduct acetaldehyde and water in the overhead of the reaction rectifying column are partially refluxed after condensation and partially returned to the raw material system; the crude product liquid rich in acetic acid is continuously collected from the column bottom; S3. Crude product refining: the crude acetic acid liquid collected from the column bottom is sequentially subjected to adsorption pretreatment and multi-stage low-temperature gradient crystallization to obtain high-purity acetic acid crystals; S4. Post-treatment: the acetic acid crystals are melted, filtered through a membrane to obtain high-purity pharmaceutical-grade glacial acetic acid; The multifunctional composite ionic liquid catalyst described in step S1 is composed of a functionalized ionic liquid and palladium-ruthenium bimetallic nanoclusters highly dispersed therein, and its structural formula is represented as: [BMIM + ][CH3COO - ] / Pd-Ru NCs, wherein: [BMIM + ][CH3COO - ] is 1 -butyl-3-methylimidazolium acetate, CAS number 284049-75-8; Pd-Ru NCs represent the active metal components of palladium and ruthenium in the form of nanoclusters, wherein the molar ratio of palladium to ruthenium is 1:0.1-1:1; The bimetallic nanoclusters are stabilized by the coordination of the acetate anions of the ionic liquid, and the total mass of the metals accounts for 0.1% to 5.0% of the total mass of the catalyst.

2. The green manufacturing method of claim 1, wherein, In the reaction rectifying column in step S1, the multifunctional composite ionic liquid catalyst is filled in the reaction section in the middle of the column, the upper part of the reaction section is the rectifying section, and the lower part is the stripping section.

3. The green manufacturing method of claim 1, wherein, The average particle size of the palladium-ruthenium bimetallic nanoclusters is 1.0-3.0 nm, and the standard deviation of the particle size distribution is less than 0.5 nm.

4. The green manufacturing method of claim 1, wherein, The multifunctional composite ionic liquid catalyst is prepared by the following method: a. The selected acetic acid based ionic liquid [BMIM + ][CH3COO - ] is heated to 60-90°C and continuously stirred under inert atmosphere protection; b. Dissolve the soluble metal salt of palladium and the soluble metal salt of ruthenium in deionized water to prepare a mixed metal salt solution; wherein the metal salt is selected from chloride, nitrate or acetate; c. Slowly add the mixed metal salt solution prepared in step b to the ionic liquid in step a, and stir at a constant temperature for 1-4 hours to allow the metal ions to fully coordinate with the ionic liquid; d. Slowly add an aqueous solution of a reducing agent to the mixed system obtained in step c, and perform in-situ reduction reaction under stirring for 0.5-2 hours; e. After the reaction is completed, separate the layers, separate and discard the upper aqueous phase, and the lower ionic liquid phase is washed with deionized water and vacuum dried to obtain the multifunctional composite ionic liquid catalyst.

5. The green manufacturing method of claim 4, wherein, The reducing agent in step d is sodium borohydride or hydrazine hydrate, and the amount used is 1.5-3.0 times the stoichiometric amount required for the reduction of metal ions.

6. The green manufacturing method of claim 1, wherein, In step S3, the adsorption pretreatment is to pass the crude acetic acid liquid through an adsorption tower filled with silicoaluminophosphate molecular sieves with a pore size of 0.45-0.5 nm to selectively adsorb propionic acid and butyric acid impurities.

7. The green manufacturing method of claim 1, wherein, In step S3, the multi-stage low-temperature gradient crystallization at least includes: first-stage crystallization at 8-15℃ to remove most of the water; second-stage crystallization at -3 to 3℃ to obtain acetic acid hydrate crystals; and third-stage crystallization at -18 to -8℃ to obtain high-purity acetic acid crystals.

8. The green manufacturing process according to any one of claims 1 to 7, characterized in that, It also includes an energy integration step: recovering the reaction heat in step S1 and the crystal melting heat in step S4 through a heat pump system to preheat the raw material and / or provide part of the cooling capacity for the crystallization device in step S3.

9. A high purity pharmaceutical grade glacial acetic acid product prepared by the green process of any one of claims 1 to 8, characterized in that, The product has purity ≥ 99.99%, moisture ≤ 0.015%, formic acid content ≤ 5 ppm, propionic acid content ≤ 10 ppm, heavy metal content ≤ 0.1 ppm as Pb, non-volatile matter ≤ 0.001%, and no iodide is detected.