A continuous esterification synthesis method of a photocurable monomer

Abstract

The application discloses a continuous esterification synthesis method of a photocuring monomer, and comprises the following steps: in a reactor, a substrate mixture containing a carboxylic acid component and an alcohol component is subjected to an esterification reaction under the catalysis of a lipase; in the esterification reaction process, an ultrasonic wave treatment is applied to a reaction system composed of the substrate mixture and the lipase; meanwhile, water generated in the reaction is removed on line through a membrane separation unit, so that the continuous synthesis of the photocuring monomer is realized. Through in-situ coupling of ultrasonic wave reinforced mass transfer, enzyme catalysis reaction and membrane separation dehydration, the application realizes the synergistic promotion of the reaction rate, the conversion rate and the selectivity under mild conditions, significantly shortens the reaction time, improves the product yield and purity, and eliminates the pollution of acidic waste water from the source.

Description

Technical Field

[0001] This invention relates to the field of organic compound synthesis technology, and in particular to a continuous esterification synthesis method for photocurable monomers. Background Technology

[0002] Multifunctional (meth)acrylates, due to the presence of two or more acrylate functional groups in their molecular structure, can form a highly cross-linked network structure under photoinitiation conditions. This endows cured coatings with excellent hardness, abrasion resistance, and chemical corrosion resistance, making them indispensable core substrates in fields such as photocurable coatings, inks, 3D printing photosensitive resins, and fiber optic coatings. Typical multifunctional (meth)acrylates include, but are not limited to, dipentaerythritol hexaacrylate (DPHA) and pentaerythritol triacrylate (PETA).

[0003] Currently, the industrial production of multifunctional (meth)acrylates mainly employs the traditional acid-catalyzed esterification process. This process uses strong protic acids such as concentrated sulfuric acid and p-toluenesulfonic acid as catalysts, and at high temperatures (typically above 120°C), polyols (such as dipentaerythritol, pentaerythritol, and trimethylolpropane) react with excess (meth)acrylate. Since esterification is a reversible equilibrium reaction, this process requires organic solvents such as toluene and cyclohexane as azeotropic dehydrating agents to continuously remove the water generated in the reaction, thereby shifting the reaction equilibrium towards the product side.

[0004] Although this traditional process technology is mature and the substrate cost is relatively low, its inherent drawbacks are becoming increasingly apparent: First, the strong acid catalyst severely corrodes the reaction equipment, requiring the use of reaction vessels made of special corrosion-resistant materials, resulting in high equipment investment and maintenance costs. After the reaction, the product needs to undergo complex post-treatment processes such as alkali neutralization and multiple water washings to remove residual acid catalyst. This process generates a large amount of highly acidic wastewater, leading to high environmental remediation costs.

[0005] Secondly, high-temperature reaction conditions easily trigger thermal polymerization, oxidation, and coking side reactions of the unsaturated double bonds in (meth)acrylic acid, resulting in a dark final product (APHA color typically exceeds 200) and the presence of dimers and polymeric impurities, affecting product purity and subsequent application performance. For high-end applications (such as optical coatings and electronic packaging materials), the product's color and purity often fail to meet requirements.

[0006] Finally, the post-processing involves multiple steps such as neutralization, washing, solvent removal, and drying. The process is lengthy, solvent recovery consumes a lot of energy, the overall product yield is limited, and the production cost is high.

[0007] To overcome the drawbacks of traditional strong acid catalysis processes, researchers have recently attempted to introduce bio-enzyme catalysis into the esterification reaction field, aiming to utilize the high selectivity, mild conditions, and environmental friendliness of enzyme-catalyzed reactions to solve the pollution and side reaction problems of traditional processes. For example, Chinese patent CN120485298B, entitled "A Method for Preparing a Pentaerythritol Tetramercaptocarboxylic Acid Ester Composition," addresses the technical bottlenecks of traditional processes, such as strong catalyst corrosivity, numerous side reactions, and cumbersome post-processing, by proposing an enzyme-photocatalytic synergistic catalysis solution. The disclosed technical solution includes the following steps: First, thiourea undergoes an addition reaction with acrylic acid under photocatalysis to generate mercaptopropionic acid in situ; second, photo-enzyme catalyzes the esterification reaction of mercaptopropionic acid with pentaerythritol to obtain colorless, transparent, high-purity pentaerythritol tetramercaptocarboxylic acid ester. This method employs a one-pot process, utilizing enzyme-photocatalysis to accelerate free radical esterification reactions, replacing strong acids and significantly improving reaction efficiency, economy, and safety. Low-temperature stepwise control precisely regulates the degree of substitution, shortens reaction time, and reduces high-temperature side reactions. The introduction of green post-processing simplifies purification steps while recovering and reusing lipases and organic solvents, reducing production costs.

[0008] However, the technical solution of Chinese patent CN120485298B still has the following technical defects in practical applications: First, mass transfer efficiency is limited. For the synthesis of multifunctional (meth)acrylates, the reaction substrates are typically polyols (such as pentaerythritol and dipentaerythritol). The system formed by these substrates and the reaction medium has high viscosity and exhibits a multiphase heterogeneous state. In the conventional stirred reactor used in this scheme, there is a lack of effective mass transfer enhancement methods. The diffusion efficiency of substrate molecules to the surface of immobilized enzyme particles and active sites is extremely low, resulting in insufficient catalytic activity of the enzyme, slow reaction rate, and long reaction time.

[0009] Secondly, there is the limitation of reaction equilibrium. Esterification is a reversible equilibrium reaction. If the water generated during the reaction is not removed in time, the equilibrium point will shift to the left, limiting the final conversion rate of the substrate. This scheme uses a one-pot reaction and does not have a device or unit for in-situ removal of reaction water. The accumulation of water in the reaction system makes it difficult to further improve the conversion rate, and unreacted hydroxyl groups often remain in the product, affecting the purity and functionality of the product.

[0010] Third, the process is discontinuous. This scheme adopts a batch one-pot operation, with the reaction and post-processing carried out in separate steps, failing to achieve continuous operation. This not only leads to low production efficiency and requires frequent catalyst recovery and reactor cleaning, increasing non-production time and operational complexity, but also makes process scale-up face more uncertainties, making it difficult to meet the efficiency and stability requirements of industrial-scale production. Summary of the Invention

[0011] To address the aforementioned technical problems, the present invention aims to provide a continuous esterification synthesis method for photocurable monomers. This invention achieves a synergistic improvement in reaction rate, conversion rate, and selectivity under mild conditions through in-situ coupling of ultrasound-enhanced mass transfer, enzyme-catalyzed reaction, and membrane separation dehydration. This significantly shortens reaction time, improves product yield and purity, and eliminates acidic wastewater pollution at its source.

[0012] To achieve the above-mentioned technical objectives and effects, the present invention is implemented through the following technical solution: A continuous esterification synthesis method for a photocurable monomer includes the following steps: In a reactor, a substrate mixture containing carboxylic acid and alcohol components is subjected to esterification under the catalysis of lipase. During the esterification process, the reaction system consisting of the substrate mixture and lipase is subjected to ultrasonic treatment. Simultaneously, water generated in the reaction is removed online through a membrane separation unit, thereby achieving continuous synthesis of photocurable monomers.

[0013] Furthermore, the ultrasonic treatment includes ultrasonic premixing of the substrate mixture before the reaction and continuous or pulsed ultrasonic irradiation of the reaction system during the reaction.

[0014] Preferably, the lipase is an immobilized lipase or a phospholipase.

[0015] Preferably, the membrane separation unit is a pervaporation membrane assembly, used to selectively separate and remove the water generated in the reaction from the resulting mixture.

[0016] Furthermore, the temperature of the esterification reaction is controlled at 50-70℃.

[0017] Furthermore, the discharge side of the membrane separation unit is maintained under vacuum, with a vacuum level of 0.01-0.2 atmospheres; the frequency of the ultrasonic waves is 20kHz to 1MHz.

[0018] Furthermore, the esterification reaction is a reaction between a polyhydroxy compound and an unsaturated carboxylic acid or its active ester.

[0019] Preferably, the carboxylic acid component is acrylic acid, the alcohol component is dipentaerythritol, and the photocurable monomer is dipentaerythritol hexaacrylate.

[0020] Furthermore, the reaction system also includes an organic solvent.

[0021] Furthermore, the lipase and reaction solvent can be recycled and reused.

[0022] The beneficial effects of this invention are as follows: This invention achieves significant synergistic effects by in-situ coupling ultrasonic treatment, lipase catalysis, and online membrane separation for dehydration. Specifically, the invention utilizes the cavitation effect and microjets of ultrasound to effectively overcome the mass transfer barriers in high-viscosity multiphase reaction systems, significantly enhancing the diffusion efficiency of substrates to the enzyme's active site. This allows the intrinsic rate of the enzyme-catalyzed reaction to be fully realized, while maintaining the enzyme's highly active conformation. While achieving ultrasound-assisted enzyme catalysis, the invention also perturbs the reaction system, improving catalytic efficiency and accelerating the reaction process through the micro-perturbation effect of ultrasound, thereby significantly shortening the reaction cycle. Furthermore, the rapidly occurring reaction continuously generates water, providing a stable driving force for the efficient dehydration of the pervaporation membrane. Meanwhile, the online in-situ removal of byproduct water through membrane separation breaks the reversible equilibrium of the esterification reaction at its source, continuously propelling the reaction towards complete esterification, forming a positive closed loop of "enhanced mass transfer promoting the reaction, accelerated reaction facilitating dehydration, and efficient dehydration driving the equilibrium." Therefore, the esterification reaction of this invention can proceed smoothly under mild conditions, effectively avoiding side reactions such as thermal polymerization and oxidation of double bonds caused by high temperatures, thus ensuring the high purity of the product. Simultaneously, this invention eliminates the use of strong acid catalysts, removing pollution at the source of cumbersome post-treatment processes such as neutralization and washing, as well as the generation of highly hydrochloric acid wastewater. The catalyst and solvent can also be recycled and reused, achieving a green and low-carbon process throughout.

[0023] In summary, this invention has achieved breakthrough improvements in four aspects: reaction rate, conversion rate, product selectivity, and environmental friendliness, and has successfully realized the efficient, continuous, and green synthesis of high-quality photocurable monomers. Attached Figure Description

[0024] Figure 1 This is a schematic diagram of the apparatus used in the continuous esterification synthesis method of the photocurable monomer of the present invention. Detailed Implementation

[0025] The technical solutions of the present invention will be clearly and completely described below with reference to specific embodiments. 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 skilled in the art without creative effort are within the scope of protection of the present invention.

[0026] This invention provides a continuous esterification synthesis method for photocurable monomers. The method includes the following steps: in a reactor, an esterification reaction is carried out on a substrate mixture containing a carboxylic acid component and an alcohol component under the catalysis of a lipase; during the esterification reaction, the reaction system consisting of the substrate mixture and the lipase is subjected to ultrasonic treatment; simultaneously, water generated in the reaction is removed online through a membrane separation unit, thereby achieving continuous synthesis of photocurable monomers.

[0027] The ultrasonic treatment comprises two stages: ultrasonic premixing of the substrate mixture before the reaction, and continuous or pulsed ultrasonic irradiation of the reaction system during the reaction. Ultrasonic premixing allows high-viscosity alcohol components (polyhydroxy compounds, such as dipentaerythritol) to form highly dispersed homogeneous or microemulsions with carboxylic acid components in organic solvents, eliminating interfacial mass transfer resistance. During the reaction, ultrasonic irradiation generates cavitation effects and microjets that continuously scour the surface of the immobilized enzyme particles, significantly enhancing the mass transfer efficiency from the substrate to the enzyme's active site. Simultaneously, the gentle physical perturbation may help maintain the enzyme's highly active conformation, thereby fully realizing its catalytic potential.

[0028] The lipase is preferably an immobilized lipase or a phospholipase. The immobilized enzyme form facilitates the continuous use and recovery of the catalyst, simplifies post-processing, and reduces production costs.

[0029] The membrane separation unit is preferably a pervaporation membrane module. This membrane module can selectively separate and remove water generated in the reaction mixture. Due to the use of membrane separation technology, the water removal process is carried out simultaneously with the reaction process, eliminating the need for additional entrainers or high-temperature operations as required by traditional azeotropic dehydration, and avoiding reaction equilibrium limitations caused by water accumulation.

[0030] In the method of this invention, the esterification reaction temperature is controlled at 50-70°C. This mild temperature range ensures that the lipase has high catalytic activity while effectively avoiding the side reactions of acrylic acid double bond thermal polymerization, oxidation, and coking that are prone to occur in traditional high-temperature processes (>120°C), thereby ensuring that the product has low color and high purity.

[0031] During the esterification reaction, a vacuum is maintained on the discharge side of the membrane separation unit, preferably at 0.01-0.2 atmospheres. This vacuum condition provides the driving force for the pervaporation process, causing the water permeating the membrane to rapidly vaporize and be removed, thus maintaining the membrane's continuous dehydration capacity. The frequency of the ultrasound is preferably between 20 kHz and 1 MHz, a frequency range that can generate an effective cavitation effect while avoiding the adverse effects that excessively high frequencies may have on enzyme activity.

[0032] The reaction system also includes an organic solvent. A suitable organic solvent helps reduce the system viscosity, improve mass transfer, and provide a suitable microenvironment for the enzyme-catalyzed reaction. Exemplary organic solvents include, but are not limited to, tert-butanol, methyl tert-butyl ether, toluene, cyclohexane, or mixtures thereof.

[0033] Both the lipase and the reaction solvent used in the method of this invention can be recovered and reused. The immobilized enzyme can be separated from the reaction system through simple solid-liquid separation (such as filtration) and used directly in the next batch of reaction; the reaction solvent can be recovered and reused through methods such as distillation. This feature significantly reduces raw material consumption and production costs.

[0034] The method of this invention is applicable to various types of esterification reactions. Preferably, the esterification reaction is a reaction between a polyhydroxy compound and an unsaturated carboxylic acid or its reactive ester. The polyhydroxy compound includes, but is not limited to, diols, triols, and polyols with higher functionality, such as ethylene glycol, glycerol, trimethylolpropane, pentaerythritol, dipentaerythritol, etc. The unsaturated carboxylic acid includes, but is not limited to, acrylic acid, methacrylic acid, and their reactive ester forms.

[0035] In a particularly preferred embodiment, the carboxylic acid component is acrylic acid, the alcohol component is dipentaerythritol, and the photocurable monomer is dipentaerythritol hexaacrylate (DPHA). DPHA is an important monomer in the field of photocurable materials. Its synthesis is challenging because the six hydroxyl groups of dipentaerythritol need to be completely esterified, and the reaction system has extremely high viscosity. The method of this invention is particularly suitable for solving this technical problem.

[0036] This invention couples ultrasonic physical field enhancement, bio-enzyme catalysis, and membrane separation process engineering in situ to form a positive cycle of "enhanced mass transfer - accelerated reaction - efficient dehydration - driving equilibrium", which can achieve an efficient, continuous, and green esterification process under mild conditions.

[0037] The apparatus used in the continuous esterification synthesis method of the present invention is as follows: Figure 1 As shown, the device includes a reactor 1 with an inlet 101, an outlet 102, and a vacuum interface 103. The vacuum interface 103 is used to connect a vacuum pump or a vacuum generator to achieve vacuum treatment. The reactor contains a stirring paddle 3, a pervaporation membrane 2, and an ultrasonic system for performing ultrasonic treatment. The ultrasonic system includes an ultrasonic generator, an ultrasonic transducer, and an ultrasonic amplitude transformer 4. The ultrasonic generator converts AC power into high-frequency electrical energy to provide driving energy for the entire system. The ultrasonic transducer converts the high-frequency electrical energy output by the ultrasonic generator into high-frequency mechanical vibration. The ultrasonic amplitude transformer 4 is connected to the ultrasonic transducer and its main function is to amplify the small amplitude generated by the ultrasonic transducer (which can be amplified to the desired value).

[0038] The esterification reaction in the following examples uses dipentaerythritol as the alcohol group: Step (1), ultrasonic premixing: Dipentaerythritol, acrylic acid and organic solvent (such as toluene, cyclohexane, toluene-cyclohexane mixed solvent) are added to the reactor in a mass ratio of (1~2):(1~3):(5~12) to form a highly dispersed homogeneous or microemulsion reaction solution under ultrasonic action, and preheated to 30~45℃. Step (2), esterification reaction: Add lipase to the homogeneous or microemulsion from step (1). The lipase can be immobilized lipase or phospholipase. After mixing thoroughly, heat to 50-70℃. The mass ratio of enzyme to reaction solution is (1-5):(25-50). Step (3): The ultrasonic system operates continuously, and its microjets significantly enhance the mass transfer of substrates (pentaerythritol, acrylic acid) to the surface of enzyme particles and maintain the high-activity conformation of the enzyme; the operating frequency is 20kHz to 1MHz. Step 4: The water generated in the reaction is selectively removed from the reaction system online by the pervaporation membrane. The outlet of the pervaporation membrane is maintained at a vacuum of 0.01-0.2 atmospheres using a small vacuum pump / vacuum generator, and is connected to a condenser for condensation and drainage.

[0039] Example 1 Step (1), ultrasonic premixing: Dipentaerythritol, acrylic acid and organic solvent (toluene-cyclohexane mixed solvent) are added to the reactor at a mass ratio of 1000g:1000g:5000g, and a highly dispersed reaction liquid is formed under ultrasonic action and preheated to 30°C; Step (2), esterification reaction: Add lipase to the reaction solution described in step (1). The lipase can be immobilized lipase or phospholipase. After mixing evenly, heat to 50°C. The mass ratio of enzyme to reaction solution is 280g:7000g. Step (3): The ultrasonic system continues to work, and its microjets significantly enhance the mass transfer of substrate to the surface of enzyme particles and may maintain the high-activity conformation of the enzyme; the working frequency is 20kHz. Step (4): The water generated in the reaction is selectively removed from the reaction system online by the pervaporation membrane. The outlet of the pervaporation membrane is maintained at a vacuum of 0.01 atmospheres using a small vacuum pump / vacuum generator, and is connected to a condenser for condensation and drainage.

[0040] Example 2 Step (1), ultrasonic premixing: Dipentaerythritol, acrylic acid and organic solvent (toluenecyclohexane mixed solvent) are added to the reactor at a mass ratio of 1000g:1000g:12000g. Under ultrasonic action, a highly dispersed reaction liquid is formed and preheated to 45°C.

[0041] Step (2), esterification reaction: Add lipase to the reaction solution described in step (1). The lipase can be immobilized lipase or phospholipase. After mixing evenly, heat to 70°C. The mass ratio of enzyme to reaction solution is 280g:140000g. Step (3): The ultrasonic system continues to work, and its microjets significantly enhance the mass transfer of substrate to the surface of enzyme particles and may maintain the high-activity conformation of the enzyme; the working frequency is 20kHz. Step (4): The water generated in the reaction is selectively removed from the reaction system online by the pervaporation membrane. The outlet of the pervaporation membrane is maintained at a vacuum of 0.02 atmospheres using a small vacuum pump / vacuum generator, and is connected to a condenser for condensation and drainage.

[0042] Example 3 Step (1), ultrasonic premixing: Dipentaerythritol, acrylic acid and organic solvent (toluenecyclohexane mixed solvent) are added to the reactor at a mass ratio of 1000g:1000g:8000g. Under ultrasonic action, a highly dispersed reaction liquid is formed and preheated to 40°C.

[0043] Step (2), esterification reaction: Add lipase to the reaction solution described in step (1). The lipase can be immobilized lipase or phospholipase. After mixing evenly, heat to 60°C. The mass ratio of enzyme to reaction solution is 120g:10000g. Step (3): The ultrasonic system works continuously, and its microjets significantly enhance the mass transfer of substrate to the surface of enzyme particles and may maintain the high-activity conformation of the enzyme; the working frequency is 500 kHz. Step (4): The water generated in the reaction is selectively removed from the reaction system online by the pervaporation membrane. The outlet of the pervaporation membrane is maintained at a vacuum of 0.01 atmospheres using a small vacuum pump / vacuum generator, and is connected to a condenser for condensation and drainage.

[0044] Comparative Example 1 Step (1): Dipentaerythritol, acrylic acid and organic solvent (toluene-cyclohexane mixed solvent) are added to the reactor at a mass ratio of 1000g:1000g:5000g and preheated to 45°C; Step (2), esterification reaction: Add lipase to the reaction solution described in step (1). The lipase can be immobilized lipase or phospholipase. After mixing evenly, heat to 70°C. The mass ratio of enzyme to reaction solution is 140g:7000g. Step (3): The water generated in the reaction is selectively removed from the reaction system online by the pervaporation membrane. The outlet of the pervaporation membrane is maintained at a vacuum of 0.01 atmospheres using a small vacuum pump / vacuum generator, and is connected to a condenser for condensation and drainage.

[0045] Comparative Example 2 Step (1), ultrasonic premixing: Dipentaerythritol, acrylic acid and organic solvent (toluenecyclohexane mixed solvent) are added to the reactor at a mass ratio of 1000g:1000g:8000g, and a highly dispersed reaction liquid is formed under ultrasonic action and preheated to 40℃; Step (2), esterification reaction: Add lipase to the reaction solution described in step (1). The lipase can be immobilized lipase or phospholipase. After mixing evenly, heat to 60°C. The mass ratio of enzyme to reaction solution is 120g:10000g. Step (3): The ultrasonic system works continuously, and its microjets significantly enhance the mass transfer of substrate to the surface of enzyme particles and may maintain the high-activity conformation of the enzyme; the working frequency is 500 kHz; the water generated in the reaction is discharged by the water separator.

[0046] The reaction time, product yield, and product purity of the above-described embodiments and comparative examples are shown in Table 1.

[0047] Table 1 As shown in Table 1, compared with Comparative Example 1 and Comparative Example 2, the continuous esterification synthesis method of the present invention has the advantages of short reaction time, high product yield and high product purity.

[0048] It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above, and that the invention can be implemented in other specific forms without departing from the spirit or essential characteristics of the invention. Therefore, the embodiments should be considered in all respects as exemplary and non-limiting, and the scope of the invention is defined by the appended claims rather than the foregoing description. Thus, it is intended that all variations falling within the meaning and scope of equivalents of the claims be included within the present invention.

[0049] Furthermore, it should be understood that although this specification describes embodiments, not every embodiment contains only one independent technical solution. This narrative style is merely for clarity. Those skilled in the art should consider the specification as a whole, and the technical solutions in each embodiment can also be appropriately combined to form other embodiments that can be understood by those skilled in the art.

Claims

1. A continuous esterification synthesis method for a photocurable monomer, characterized in that, Includes the following steps: In a reactor, a substrate mixture containing carboxylic acid and alcohol components is subjected to esterification under the catalysis of lipase. During the esterification reaction, the reaction system consisting of the substrate mixture and lipase is subjected to ultrasonic treatment; simultaneously, the water generated in the reaction is removed online through a membrane separation unit, thereby achieving continuous synthesis of photocurable monomers.

2. The continuous esterification synthesis method for photocurable monomers according to claim 1, characterized in that, The ultrasonic treatment includes ultrasonic premixing of the substrate mixture before the reaction and continuous or pulsed ultrasonic irradiation of the reaction system during the reaction.

3. The continuous esterification synthesis method for photocurable monomers according to claim 1, characterized in that, The lipase is an immobilized lipase.

4. The continuous esterification synthesis method for photocurable monomers according to claim 1, characterized in that, The membrane separation unit is a pervaporation membrane assembly used to selectively separate and remove the water generated in the reaction from the resulting mixture.

5. The continuous esterification synthesis method for photocurable monomers according to claim 1, characterized in that, The temperature of the esterification reaction is controlled at 50-70℃.

6. The continuous esterification synthesis method for photocurable monomers according to claim 1, characterized in that, The discharge side of the membrane separation unit is kept under vacuum, with a vacuum level of 0.01-0.2 atmospheres; the frequency of the ultrasonic waves is 20kHz to 1MHz.

7. The continuous esterification synthesis method of photocurable monomers according to any one of claims 1, characterized in that, The esterification reaction is a reaction between a polyhydroxy compound and an unsaturated carboxylic acid or its active ester.

8. The continuous esterification synthesis method for photocurable monomers according to claim 1, characterized in that, The carboxylic acid component is acrylic acid, the alcohol component is dipentaerythritol, and the photocurable monomer is dipentaerythritol hexaacrylate.

9. The continuous esterification synthesis method for photocurable monomers according to claim 1, characterized in that, The reaction system also includes organic solvents.

10. The continuous esterification synthesis method of the photocurable monomer according to claim 9, characterized in that, The lipase and reaction solvent can be recycled and reused.

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