Intermediate containing acetylfuran structure and preparation method thereof

Abstract

The invention belongs to the field of pharmaceutical reagents, and provides a preparation method of an intermediate containing an acetylfuran structure. According to the invention, N-acetyl-D-glucosamine is used as a raw material, a La2O3 catalyst with a nanoscale sheet-shaped wrinkle structure is used for catalytic dehydration reaction, and the design of segmented temperature control and a multi-step cascade recrystallization process is combined; according to the method, the total purity of the target products N-3-furyl-acetamide and N-(5-acetyl-3-furyl)-acetamide reaches 97.5-99.5%, the product is in a needle-like crystal form, the high quality performance is achieved, the problems that an existing intermediate containing an acetylfuran structure is low in catalytic activity and product purity are solved, the catalyst can be repeatedly used for 4-6 times, the activity retention rate is larger than or equal to 90%, and the method is suitable for industrial production. The intermediate can be used for preparing key intermediates of bioactive molecules such as antitumor drugs and antibiotics, and has wide application value.

Description

Technical Field

[0001] The present invention relates to the field of pharmaceutical reagents, and in particular to an intermediate containing an acetylfuran structure and a preparation method thereof. Background Art

[0002] As important organic building blocks, acetylfuran intermediates hold broad application prospects in the pharmaceutical and chemical industries, playing a key role in the synthesis of anti-tumor drugs, antibiotics, and bioactive molecules. Their unique furan ring structure and acetyl functional group provide diverse reaction sites for subsequent chemical transformations, making them crucial precursors for building complex molecular scaffolds. In the modern pharmaceutical industry, performance requirements for these intermediates are increasingly stringent. They must not only possess high purity to ensure selectivity and product quality in subsequent reactions, but also possess excellent crystalline morphology for ease of separation, purification, storage, and transportation. Furthermore, the efficiency and environmental friendliness of catalytic synthesis processes are crucial considerations for industrial production, requiring catalysts with high activity, good selectivity, and recyclability. With the advancement of precision medicine and personalized medicine, the demand for high-quality acetylfuran intermediates continues to grow, driving the continuous advancement and improvement of related preparation technologies and providing a critical material foundation and technical support for the innovative development of the pharmaceutical industry.

[0003] Although acetylfuran-containing structural intermediates are of great value in pharmaceutical synthesis, current preparation technologies still face numerous technical bottlenecks and challenges. Traditional synthesis methods generally face the problem of low catalytic efficiency, primarily due to the uneven distribution of active sites in commonly used catalysts and their relatively small surface area, which makes it difficult for the conversion rate and selectivity of the catalytic reaction to meet the requirements of industrial production. For example, Chinese patent publication number CN112961125B discloses a process for preparing 2-acetylfuran using a solid acid catalyst, but suffers from insufficient catalyst activity and low product purity. In addition, the dehydration cyclization reaction in existing preparation processes often lacks precise temperature control strategies, making it prone to side reactions and isomerization, further reducing the purity and yield of the target product. The product separation and purification process also has significant drawbacks. Traditional recrystallization methods are difficult to effectively control crystal morphology and size distribution, resulting in unstable physical properties of the product and affecting the reliability of subsequent applications. The reusability of the catalyst also needs to be improved. Most catalytic systems experience a significant decrease in activity after being used several times, increasing production costs and creating an environmental burden. These technical limitations severely restrict the large-scale production and widespread application of intermediates containing acetylfuran structures, and there is an urgent need to develop more efficient and environmentally friendly preparation technologies. Summary of the Invention

[0004] (1) Technical problems solved The purpose of the present invention is to provide an intermediate containing an acetylfuran structure and a preparation method thereof, so as to solve the problem that the intermediate containing an acetylfuran structure currently has high catalytic activity and low purity.

[0005] (2) Technical solution In order to achieve the above object, the present invention provides the following technical solutions: A method for preparing an intermediate containing an acetylfuran structure, comprising the following steps: S1. N-acetyl-D-glucosamine is mixed with a solvent to form a reaction system, and the water content in the reaction system is ensured to be ≤0.05 wt % by molecular sieve pretreatment and nitrogen protection; S2. La2O3 catalyst was added for catalytic dehydration reaction. The reaction was carried out under an inert atmosphere and a staged temperature control strategy was used to optimize the reaction selectivity. S3. After the reaction is completed, a multi-step cascade recrystallization process is used to obtain an intermediate containing an acetylfuran structure; The intermediates are N-3-furyl-acetamide and N-(5-acetyl-3-furyl)-acetamide. The mass fraction of N-3-furyl-acetamide in the product is 72-76%, the mass fraction of N-(5-acetyl-3-furyl)-acetamide is 21-25%, and the content of other trace components is 0.5-2.2%, which are mainly positional isomers, partially dehydrated intermediates and cyclization intermediates; the total purity is 97.8-99.5%; the impurity content is 0.5-2.2%, which are mainly unreacted raw materials, solvent residues and catalyst residues; the total purity of the two target products is 97.0-99.0%; the product is in the form of needle-shaped crystals with an average length of 250-800 μm and a width of 10.0-45.5 μm; The structural formula of the N-3-furyl-acetamide is:

[0006] The structural formula of the N-(5-acetyl-3-furyl)-acetamide is:

[0007] The La2O3 catalyst has the morphology of submicron particles and a nanoscale active layer distributed on its surface. The surface of the nanoscale active layer contains a flaky nano-wrinkled structure. The specific surface area of ​​the catalyst is 50-200 m² / g, and the surface basic site density is 0.8-1.5 mmol / g. The average size of the La2O3 catalyst is 350-800nm.

[0008] The La2O3 catalyst is prepared by a sol-gel combined with hydrothermal step-by-step assembly method, including three steps: mixing lanthanum nitrate, citric acid and a structure-directing agent, hexadecyltrimethylammonium bromide, in a molar ratio of 1:(2.0-2.5):(0.3-0.8) to prepare a precursor, hydrothermal treatment and programmed calcination.

[0009] The present invention utilizes a molecular sieve pretreatment combined with nitrogen protection to construct a reaction system, prepare a La2O3 catalyst with a special morphology, and design a multi-step cascade recrystallization process, primarily for enhancing the catalytic activity and product purity performance during the preparation of an intermediate containing an acetylfuran structure. By mixing N-acetyl-D-glucosamine with a solvent and employing molecular sieve pretreatment and nitrogen protection measures, the water content in the reaction system can be precisely controlled, creating an ideal reaction environment for the subsequent catalytic dehydration reaction, avoiding the inhibitory effect of moisture on catalyst activity, and preventing the occurrence of side reactions. The La2O3 catalyst is prepared using a sol-gel combined with a hydrothermal step-by-step assembly method. Through the precise proportioning and step-by-step treatment of lanthanum nitrate, citric acid, and the structure-directing agent hexadecyltrimethylammonium bromide, a unique submicron-scale particle structure is formed. The nanoscale active layer distributed on its surface has a sheet-like nano-wrinkled structure. This special morphology not only significantly increases the specific surface area of ​​the catalyst but also provides abundant surface basic sites, enabling the catalyst to exhibit excellent activity and selectivity in dehydration cyclization reactions. The implementation of a staged temperature control strategy further optimizes the reaction process. A preactivation stage activates the catalyst surface and pre-adsorbs the raw materials; the main reaction stage carries out the core dehydration cyclization reaction; and the finishing stage ensures complete reaction completion. This synergistic temperature control mechanism, combined with a high-performance catalyst, achieves simultaneous improvements in reaction conversion and selectivity. The multi-step cascade recrystallization process employs a continuous process of extraction separation, vacuum concentration, temperature gradient recrystallization, and refined recrystallization. Combined with programmed cooling and seeding techniques, this not only effectively removes impurities and unreacted raw materials but also precisely controls the crystal morphology and size distribution, resulting in a well-regarded, needle-shaped final product. Within this technical solution, strict moisture control provides an optimized environment for the catalytic reaction. The uniquely structured La2O3 catalyst provides highly efficient catalytic active sites. The staged temperature control strategy ensures high selectivity, while the multi-step cascade recrystallization process ensures high product purity and excellent crystal quality. The organic combination of these technical elements produces a remarkable synergistic effect, enabling the preparation of acetofuran-containing intermediates to achieve excellent levels of catalytic efficiency, product purity, and crystal quality.

[0010] Furthermore, the La2O3 catalyst is prepared by a sol-gel combined with hydrothermal step-by-step assembly method: A1. Lanthanum nitrate and citric acid were mixed, and a structure-directing agent, cetyltrimethylammonium bromide, was added. The molar ratio of the three was lanthanum nitrate: citric acid: directing agent = 1:2.0-2.5:0.3-0.8. Deionized water was added to form a precursor solution with a solid content of 15-25 wt %, and stirred at 60-80 ° C for 2-4 hours to ensure complete dissolution. A2. Evaporation under stirring with a magnetic stirrer at 80-120 ° C until it becomes a gel, the stirring rate is controlled at 200-300 rpm, the evaporation time is 4-8 hours, and then hydrothermal treatment is performed in an autoclave at 180-220 ° C for 12-24 hours; A3. Calcine in air atmosphere at 400-600°C in a muffle furnace for 2-6 hours at a heating rate of 2-5°C / min to ensure complete formation of the La2O3 crystal phase and development of a lamellar wrinkle structure.

[0011] Furthermore, the calcination procedure of step A3 includes: A31 organic pre-decomposition stage: room temperature at 1-2 ° C / min to 200 ° C, in a nitrogen atmosphere for 1-1.5 hours to prevent rapid decomposition of the organic template causing structural collapse; A32. Raise the temperature to 350-450°C at 2-5°C / min, switch to air atmosphere and keep warm for 2-3 hours to complete the decomposition and initial crystallization of the organic template; A33. Continue to raise the temperature to 500-600℃ and keep it at this temperature for 2-6 hours to promote the complete formation of the La2O3 crystal phase and the development of the lamellar wrinkle structure.

[0012] The present invention utilizes a sol-gel combined with a hydrothermal step-by-step assembly method to prepare La2O3 catalysts with specialized morphologies. The coordinated design of a staged temperature control strategy and a multi-step cascade recrystallization process is primarily intended to enhance the catalytic efficiency and product purity during the preparation of intermediates containing acetofuran structures. The La2O3 catalyst is prepared by precisely mixing lanthanum nitrate and citric acid in a controlled ratio and introducing the structure-directing agent cetyltrimethylammonium bromide to form a uniform precursor solution under controlled temperature and time conditions. Subsequently, magnetic stirring evaporation and hydrothermal treatment in an autoclave achieve orderly assembly of the catalyst precursor. A carefully designed programmed calcination process ensures the complete formation of the La2O3 crystal phase and the full development of the lamellar, corrugated structure. This step-by-step preparation strategy imparts an ideal surface structure and active site distribution to the catalyst. The staged temperature control strategy employed in the catalytic dehydration reaction promotes catalyst surface activation and feedstock pre-adsorption in a preactivation phase. The main reaction phase carries out the core dehydration cyclization reaction within an optimized temperature range, and the finishing phase ensures the complete completion of the reaction. This temperature gradient control, combined with strict water content control and nitrogen protection measures, creates an optimal reaction environment for the catalytic reaction. The solvent system is selected from high-efficiency solvents such as dioxane, N,N-dimethylformamide, dimethyl sulfoxide, N-methyl-2-pyrrolidone or dimethylacetamide, which provide good solubility and reaction medium for the reactants.

[0013] Furthermore, the catalytic dehydration reaction in step S2 adopts segmented temperature control, including: a pre-activation stage: a reaction temperature of 140-160°C and a reaction time of 30-60 minutes to activate the catalyst surface and pre-adsorb the raw materials; a main reaction stage: a reaction temperature of 160-200°C and a time of 2-4 hours to carry out the main dehydration cyclization reaction; a finishing stage: a reaction temperature of 180-200°C and a time of 0.5-1 hour to ensure that the reaction is complete; the amount of La2O3 catalyst used is 15-25% of the mass of N-acetyl-D-glucosamine, the residual water content in the reaction system is controlled at ≤0.1wt%, the entire reaction is carried out under nitrogen protection, and the pressure is controlled at 0.1-0.3 MPa.

[0014] Furthermore, the solvent in step S1 is one or a mixture of dioxane, N,N-dimethylformamide, dimethyl sulfoxide, N-methyl-2-pyrrolidone or dimethylacetamide.

[0015] Furthermore, the S3 step includes the following multi-step cascade recrystallization process: B1. The reaction product was extracted and separated with ethyl acetate and water in a volume ratio of 1:1, and the aqueous phase was back-extracted 2-4 times with a saturated NaCl solution until the organic phase was colorless and transparent. The temperature during the extraction process was controlled at 25-35 ° C, and each extraction time was 15-30 minutes; B2. The organic phase was concentrated under reduced pressure at 35-45°C to 1 / 3-1 / 2 of its original volume, and n-hexane was slowly added until the turbidity value of the solution reached 100-200 NTU. Pre-enrichment and recrystallization were performed to precipitate the crude product of preliminary purification; B3 using a volume ratio of 3: 1-1: 1 ethyl acetate / isopropanol mixed solvent temperature gradient recrystallization, by precisely controlling the cooling rate to obtain high-quality crystals; B4. Finally, the product was purified and recrystallized using a mixed solvent of n-hexane / ethyl acetate in a volume ratio of 1:1-2:1, with the temperature controlled at 5-25°C for 12-48 hours to obtain a high-purity crystalline product with a purity of 97-99.5%.

[0016] Furthermore, the temperature gradient recrystallization in step B3 adopts programmed cooling: The first stage is 35-30℃, with a cooling rate of 1.0-1.5℃ / h, mainly completing solubility adjustment and initial nucleation; The second stage is 30-20℃, cooling rate 0.8-1.2℃ / h, to control the crystal nucleus growth rate; The third stage is 20-10℃, cooling rate 0.5-0.8℃ / h, to promote the improvement of crystal structure; The fourth stage is 10-5°C, with a cooling rate of 0.2-0.5°C / h to ensure crystal quality and yield. A constant stirring rate of 80-120 rpm is used throughout the process; The seed preparation and addition method in the recrystallization process are as follows: C1. Seed preparation: The crude product prepared in steps S1-S2 of this process is used as a seed crystal raw material. The solid product after preliminary purification in steps B1-B2 is crushed by ball milling at a speed of 300-500 rpm for 45-60 minutes, or by ultrasonic grinding at a power of 150-200 W for 30-45 minutes, and sieved through 300 mesh to obtain fine seed particles with an average particle size of 0.5-2.0 μm. C2. Seed addition: When the temperature stabilizes at 35°C in the first stage, slowly add the prepared seed crystals at a rate of 0.1-0.5 wt% of the total solid content in the solution to be crystallized, stirring while adding to ensure uniform dispersion. After dispersion is complete, maintain the temperature for 10-15 minutes to fully wet the seed crystals, and then begin the programmed cooling process.

[0017] Furthermore, the La2O3 catalyst can be reused 4-6 times and regenerated after each use according to the following procedure: washing with ethyl acetate to remove organic residues, washing with deionized water to a pH of 6.5-7.5, vacuum drying at 110°C for 4 hours to remove moisture, and calcining in air at 550°C for 3 hours to restore catalytic activity. After regeneration, the catalytic activity retention rate is ≥90%, the BET specific surface area retention rate is ≥90%, and the surface basic site retention rate is ≥88%.

[0018] Furthermore, the intermediate containing acetylfuran structure is used in the preparation of amino alcohol compounds, secondary amine compounds, rare amino sugars or heterocyclic compounds. The intermediate is used as a synthetic precursor to prepare key intermediates for anti-tumor drugs, antibiotics or bioactive molecules.

[0019] The multi-step cascade recrystallization process of the present invention effectively removes water-soluble impurities through extraction and separation with ethyl acetate and water. The organic phase is further purified by back extraction with a saturated NaCl solution. Reduced pressure concentration and pre-enrichment recrystallization with n-hexane achieve preliminary product purification. The temperature gradient recrystallization uses an ethyl acetate / isopropanol mixed solvent system combined with programmed temperature control. Through precise temperature regulation in four stages, solubility regulation, initial nucleation, nucleus growth control, and crystal structure refinement are achieved in an orderly manner. The final n-hexane / ethyl acetate refining recrystallization ensures high product purity. The seed preparation and addition technology uses ball milling or ultrasonic pulverization to prepare fine seed particles. During the temperature gradient recrystallization process, the timing of seed addition and the dispersion process are precisely controlled, providing a core foundation for orderly crystal growth. The reusability of the La2O3 catalyst is achieved through a regeneration process of ethyl acetate washing, deionized water washing, vacuum drying, and high-temperature calcination, allowing the catalyst to maintain its excellent catalytic activity, specific surface area, and surface basic site density after multiple uses. In the entire technical solution, the specially prepared La2O3 catalyst provides efficient catalytic active centers, the segmented temperature control strategy ensures high selectivity and conversion rate of the reaction, the multi-step cascade recrystallization process ensures high purity and excellent crystal morphology of the product, and the catalyst regeneration technology realizes a green and sustainable production process. The organic integration of these technical elements produces a significant synergistic effect, enabling the preparation of intermediates containing acetofuran structure to achieve excellent performance in multiple dimensions such as catalytic efficiency, product quality, and process sustainability.

[0020] (3) Beneficial technical effects The present invention effectively solves the technical problems of low catalytic activity and low product purity in the preparation of acetofuran-containing intermediates in the prior art by adopting a reaction system construction combined with molecular sieve pretreatment and nitrogen protection, the preparation of a La2O3 catalyst with a special morphology, and the coordinated design of a multi-step cascade recrystallization process, thereby achieving the following significant beneficial effects: 1) Significantly Improved Catalytic Performance: The La2O3 catalyst prepared in this invention has a unique submicron particle structure and a nanoscale active layer on the surface. Its flaky nano-wrinkled structure significantly increases the specific surface area (50-200 m² / g) and surface basic site density (0.8-1.5 mmol / g), enabling the catalyst to exhibit excellent catalytic activity and selectivity in dehydration cyclization reactions, significantly improving the reaction conversion rate.

[0021] 2) Significantly improved product purity: Through the synergistic effect of a segmented temperature control strategy and a multi-step cascade recrystallization process, side reactions are effectively suppressed and impurities are efficiently removed, resulting in high-purity target products N-3-furyl-acetamide and N-(5-acetyl-3-furyl)-acetamide. The product quality is significantly better than that of existing technologies.

[0022] 3) Controllable crystal morphology: The multi-step cascade recrystallization process, combined with programmed cooling control and seed addition technology, precisely controls the nucleation and growth process of the crystals, resulting in a final product with a regular needle-shaped crystal morphology, with an average length of 250-800μm and a width of 10.0-45.5μm. The crystal morphology is uniform and consistent, facilitating subsequent separation, purification, storage and transportation.

[0023] 4) Reusable catalyst: La2O3 catalyst can be reused 4-6 times. After a simple regeneration procedure, the catalytic activity retention rate is ≥90%, the BET specific surface area retention rate is ≥90%, and the surface basic site retention rate is ≥88%. This significantly reduces production costs and reduces the environmental burden, achieving a green and sustainable production process.

[0024] 5) Mild and controllable reaction conditions: The segmented temperature control strategy achieves efficient catalytic conversion under relatively mild reaction conditions through precise regulation of the three stages of pre-activation, main reaction, and completion. The reaction process is stable and controllable, making it easy to scale up for industrial production.

[0025] 6) Process Optimization: The entire preparation process is rationally designed, with each step closely connected. Molecular sieve pretreatment and nitrogen protection ensure the purity of the reaction system. The multi-step cascade recrystallization process achieves efficient separation and purification of the product. The process is simple to operate and has good reproducibility.

[0026] 7) Broad application prospects: The prepared acetylfuran structure-containing intermediates can be widely used in the preparation of amino alcohol compounds, secondary amine compounds, rare amino sugars or heterocyclic compounds, especially as synthetic precursors for the preparation of key intermediates for anti-tumor drugs, antibiotics or bioactive molecules, and have important commercial value and social significance.

[0027] In summary, through technological innovation and process optimization, the present invention has achieved significant improvements in catalytic efficiency, product purity, crystal quality, environmental friendliness, and industrial applicability, providing important technical support for the efficient preparation of intermediates containing acetylfuran structures. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 This is a morphology diagram of the La2O3 catalyst prepared in Example 2 of the present invention.

[0029] Figure 2 This is the XRD phase analysis diagram of the La2O3 catalyst prepared in Example 2 of the present invention.

[0030] Figure 3 This is a morphology diagram of the intermediate prepared in Example 2 of the present invention.

[0031] Figure 4 This is a morphology diagram of the La2O3 catalyst prepared in Comparative Example 10 of the present invention.

[0032] Figure 5 This is a morphology diagram of the La2O3 catalyst prepared in Comparative Example 2 of the present invention.

[0033] Figure 6 This is a morphology diagram of the intermediate prepared in Comparative Example 10 of the present invention.

[0034] Figure 7 This is a morphology diagram of the intermediate prepared in Comparative Example 2 of the present invention.

[0035] Figure 8 The total purity and impurity content of the whole sample are compared between the examples of the present invention and the comparative examples. DETAILED DESCRIPTION

[0036] To make the objectives, technical solutions and advantages of the embodiments of the present invention more clear, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention.

[0037] In the absence of specific conditions, the operations in the examples are carried out under conventional conditions or the conditions recommended by the manufacturer. The reagents or instruments used, if the manufacturer is not indicated, are all common products on the market. Parts not mentioned in the technical content of the present invention will be processed with reference to the prior art. Unless otherwise specified, the following examples and comparative examples will be tested in parallel and use the same processing steps and parameters. Table 1 shows the reagents required for the examples and comparative examples and the corresponding purchasing companies.

[0038] Table 1 Reagents required for Examples and Comparative Examples and corresponding purchasing companies

[0039] Example 1 The La2O3 catalyst of this embodiment has the morphology of submicron particles and a nanoscale active layer distributed on its surface. The surface of the nanoscale active layer contains a flaky nano-wrinkled structure. The specific surface area of ​​the catalyst is 125 m² / g, and the surface basic site density is 1.2 mmol / g. The average size of the La2O3 catalyst is 550 nm.

[0040] The La2O3 catalyst of this embodiment is prepared by a sol-gel combined with hydrothermal step-by-step assembly method, including three steps: mixing lanthanum nitrate, citric acid and structure-directing agent hexadecyltrimethylammonium bromide in a molar ratio of 1:2.2:0.5 to prepare a precursor, hydrothermal treatment and programmed calcination.

[0041] The La2O3 catalyst of this embodiment is prepared by a sol-gel combined with hydrothermal step-by-step assembly method: A1. Lanthanum nitrate and citric acid were mixed, and a structure-directing agent, cetyltrimethylammonium bromide, was added. The molar ratio of the three was lanthanum nitrate: citric acid: directing agent = 1:2.2:0.5. Deionized water was added to a solid content of 20 wt% to form a precursor solution, and stirred at 70 ° C for 3 hours to ensure complete dissolution. A2 was stirred and evaporated under a magnetic stirrer at 100 ° C until it became a gel, the stirring rate was controlled at 250 rpm, the evaporation time was 6 hours, and then hydrothermally treated in an autoclave at 200 ° C for 18 hours; A3. Calcinate in a muffle furnace at 500°C in air atmosphere for 4 hours with a heating rate of 3°C / min to ensure the complete formation of the La2O3 crystal phase and the development of a lamellar wrinkle structure.

[0042] The calcination procedure of step A3 of this embodiment includes: A31 organic pre-decomposition stage: room temperature at 1.5 ° C / min to 200 ° C, in a nitrogen atmosphere for 1.2 hours to prevent rapid decomposition of the organic template causing structural collapse; A32. Raise the temperature to 400°C at 3°C / min and switch to air atmosphere for 2.5 hours to complete the decomposition and initial crystallization of the organic template. A33. Continue to raise the temperature to 550℃ and keep it for 4 hours to promote the complete formation of La2O3 crystal phase and the development of lamellar wrinkle structure.

[0043] A method for preparing an intermediate containing an acetylfuran structure, comprising the following steps: S1. N-acetyl-D-glucosamine and dioxane were mixed to form a reaction system, and the water content in the reaction system was ensured to be 0.03 wt % by molecular sieve pretreatment and nitrogen protection; S2. La2O3 catalyst was added for catalytic dehydration reaction. The reaction was carried out under an inert atmosphere and a staged temperature control strategy was used to optimize the reaction selectivity. S3. After the reaction is completed, a multi-step cascade recrystallization process is used to obtain an intermediate containing an acetylfuran structure; The intermediates of this example are N-3-furyl-acetamide and N-(5-acetyl-3-furyl)-acetamide. The mass fraction of N-3-furyl-acetamide in the product is 74%, the mass fraction of N-(5-acetyl-3-furyl)-acetamide is 23.0%, and the content of other trace components is 1.5%, which are mainly positional isomers and partially dehydrated intermediates; the impurity content is 1.5%, which is mainly unreacted raw materials and solvent residues; the total purity of the two target products is 97.0%, and the total purity is 98.5%; the product is a needle-shaped crystal with an average length of 500 μm and a width of 25.0 μm; The structural formula of N-3-furyl-acetamide of the present embodiment is:

[0044] The structural formula of N-(5-acetyl-3-furyl)-acetamide of the present embodiment is:

[0045] The catalytic dehydration reaction in step S2 of this embodiment adopts staged temperature control, including: a pre-activation stage: a reaction temperature of 150°C and a reaction time of 45 minutes to activate the catalyst surface and pre-adsorb the raw materials; a main reaction stage: a reaction temperature of 180°C and a time of 3 hours to carry out the main dehydration cyclization reaction; a finishing stage: a reaction temperature of 190°C and a time of 0.8 hours to ensure that the reaction is complete; the amount of La2O3 catalyst used is 20% of the mass of N-acetyl-D-glucosamine, the residual water content in the reaction system is controlled at 0.08wt%, and the entire reaction is carried out under nitrogen protection, and the pressure is controlled at 0.2 MPa.

[0046] The solvent in step S1 of this embodiment is dioxane.

[0047] The S3 step of this embodiment includes the following multi-step cascade recrystallization process: B1. The reaction product was extracted and separated with ethyl acetate and water in a volume ratio of 1:1, and the aqueous phase was back-extracted three times with a saturated NaCl solution until the organic phase was colorless and transparent. The temperature during the extraction process was controlled at 30 ° C, and each extraction time was 22 minutes; B2. The organic phase was concentrated under reduced pressure at 40°C to 2 / 5 of its original volume. N-hexane was slowly added until the turbidity of the solution reached 150 NTU. Pre-enrichment and recrystallization were performed to precipitate the crude product. B3. Using a 2:1 volume ratio of ethyl acetate / isopropanol mixed solvent for temperature gradient recrystallization, high-quality crystals were obtained by precisely controlling the cooling rate; B4. Finally, the product was purified and recrystallized using a mixed solvent of n-hexane / ethyl acetate in a volume ratio of 1.5:1, with the temperature controlled at 15°C for 30 hours to obtain a high-purity crystalline product with a purity of 98.5%.

[0048] The temperature gradient recrystallization in step B3 of this embodiment adopts programmed cooling: The first stage is 32℃, with a cooling rate of 1.2℃ / h, mainly completing solubility adjustment and initial nucleation; The second stage is 25℃, cooling rate 1.0℃ / h, to control the crystal nucleus growth rate; The third stage is 15℃, with a cooling rate of 0.6℃ / h to promote the improvement of the crystal structure; The fourth stage was 7°C with a cooling rate of 0.3°C / h to ensure the quality and yield of the crystals. A constant stirring rate of 100 rpm was used throughout the process. The seed preparation and addition method in the recrystallization process of this embodiment is as follows: C1. Seed preparation: The crude product prepared in steps S1-S2 of this process was initially purified by steps B1-B2 and used as a seed material. The product was ball milled at 400 rpm for 50 minutes and sieved through 300 mesh to obtain fine seed particles with an average particle size of 1.2 μm. C2. Seed addition: When the temperature stabilizes at 35°C in the first stage, slowly add the prepared seed crystals at a rate of 0.3 wt% of the total solid content in the solution to be crystallized, stirring while adding to ensure uniform dispersion. After dispersion is complete, maintain the temperature for 12 minutes to fully wet the seed crystals, and then begin the programmed cooling process.

[0049] The La2O3 catalyst of this embodiment can be reused 5 times and regenerated after each use according to the following procedure: washing with ethyl acetate to remove organic residues, washing with deionized water to a pH of 7.0, vacuum drying at 110°C for 4 hours to remove moisture, and calcining in air at 550°C for 3 hours to restore catalytic activity. After regeneration, the catalytic activity retention rate was 92%, the BET specific surface area retention rate was 91%, and the surface basic site retention rate was 89%.

[0050] The intermediate containing acetylfuran structure of this embodiment is used in the preparation of amino alcohol compounds, secondary amine compounds, rare amino sugars or heterocyclic compounds. The intermediate is used as a synthetic precursor to prepare key intermediates for anti-tumor drugs, antibiotics or bioactive molecules.

[0051] Features of Example 1: This example utilizes a conservative and stable process parameter configuration, using a single solvent, dioxane. The catalyst surface area and basic site density are moderate (125 m² / g, 1.2 mmol / g). The reaction temperature is relatively mild (150°C for pre-activation, 180°C for main reaction), and the recrystallization process parameters are all within the intermediate range. This process configuration emphasizes stability and reproducibility, resulting in a product purity of 98.5% and a regular, uniform crystal morphology, making it suitable for industrial scale-up. This example is particularly suitable for the large-scale production of pharmaceutical intermediates, such as the preparation of key intermediates for antibiotics, and for the production of generic drug APIs requiring a stable supply chain. In the field of bioactive molecule synthesis, it can be used to prepare natural product analogs and anti-tumor lead compounds with furan ring structures.

[0052] Example 2 The La2O3 catalyst of this embodiment has the morphology of submicron particles and a nanoscale active layer distributed on its surface. The surface of the nanoscale active layer contains a flaky nano-wrinkled structure. The specific surface area of ​​the catalyst is 180 m² / g, and the surface basic site density is 1.4 mmol / g. The average size of the La2O3 catalyst is 380 nm.

[0053] The La2O3 catalyst of this embodiment is prepared by a sol-gel combined with hydrothermal step-by-step assembly method, including three steps: mixing lanthanum nitrate, citric acid and structure-directing agent hexadecyltrimethylammonium bromide in a molar ratio of 1:2.4:0.7 to prepare a precursor, hydrothermal treatment and programmed calcination.

[0054] The La2O3 catalyst of this embodiment is prepared by a sol-gel combined with hydrothermal step-by-step assembly method: A1. Lanthanum nitrate and citric acid were mixed, and a structure-directing agent, cetyltrimethylammonium bromide, was added. The molar ratio of the three was lanthanum nitrate: citric acid: directing agent = 1:2.4:0.7. Deionized water was added to a solid content of 18 wt% to form a precursor solution, and stirred at 75 ° C for 2.5 hours to ensure complete dissolution. A2. The mixture was evaporated under a magnetic stirrer at 90 ° C until it became gel-like. The stirring rate was controlled at 280 rpm for 5 hours and then hydrothermally treated in an autoclave at 210 ° C for 15 hours. A3. Calcinate in a muffle furnace at 520°C in air atmosphere for 3 hours with a heating rate of 4°C / min to ensure the complete formation of the La2O3 crystal phase and the development of the lamellar wrinkle structure.

[0055] The calcination procedure of step A3 of this embodiment includes: A31 organic pre-decomposition stage: room temperature at 1.8 ° C / min to 200 ° C, in a nitrogen atmosphere for 1 hour to prevent rapid decomposition of the organic template causing structural collapse; A32. Raise the temperature to 420°C at 4°C / min and switch to air atmosphere for 2.2 hours to complete the decomposition and initial crystallization of the organic template. A33. Continue to raise the temperature to 580°C and keep it for 3.5 hours to promote the complete formation of the La2O3 crystal phase and the development of the lamellar wrinkle structure.

[0056] A method for preparing an intermediate containing an acetylfuran structure, comprising the following steps: S1. N-acetyl-D-glucosamine was mixed with N,N-dimethylformamide and dimethyl sulfoxide in a volume ratio of 2:1 to form a reaction system. The water content of the reaction system was maintained at 0.02 wt % by molecular sieve pretreatment and nitrogen protection. S2. La2O3 catalyst was added for catalytic dehydration reaction. The reaction was carried out under an inert atmosphere and a staged temperature control strategy was used to optimize the reaction selectivity. S3. After the reaction is completed, a multi-step cascade recrystallization process is used to obtain an intermediate containing an acetylfuran structure; The intermediates of this example are N-3-furyl-acetamide and N-(5-acetyl-3-furyl)-acetamide. The mass fraction of N-3-furyl-acetamide in the product is 76%, the mass fraction of N-(5-acetyl-3-furyl)-acetamide is 21.0%, and the content of other trace components is 2.2%, mainly N-2-furyl-acetamide isomers and cyclization intermediates; the impurity content is 0.8%, mainly unreacted raw materials and a small amount of inorganic salts; the combined purity of the two target products is 97.0%, and the total purity is 99.2%; the product is a needle-shaped crystal with an average length of 720 μm and a width of 38.0 μm; The structural formula of N-3-furyl-acetamide in this embodiment is the same as that in Example 1; The structural formula of N-(5-acetyl-3-furyl)-acetamide in this embodiment is the same as that in Example 1; The catalytic dehydration reaction in step S2 of this embodiment adopts staged temperature control, including: a pre-activation stage: a reaction temperature of 145°C, a reaction time of 50 minutes, to activate the catalyst surface and pre-adsorb the raw materials; a main reaction stage: a reaction temperature of 195°C, a time of 2.5 hours, to carry out the main dehydration cyclization reaction; a finishing stage: a reaction temperature of 200°C, a time of 0.6 hours, to ensure that the reaction is complete; the amount of La2O3 catalyst used is 18% of the mass of N-acetyl-D-glucosamine, the residual water content in the reaction system is controlled at 0.06wt%, and the entire reaction is carried out under nitrogen protection, and the pressure is controlled at 0.15 MPa.

[0057] The solvent in step S1 of this embodiment is a mixture of N,N-dimethylformamide and dimethyl sulfoxide in a volume ratio of 2:1.

[0058] The S3 step of this embodiment includes the following multi-step cascade recrystallization process: B1. The reaction product was extracted and separated with ethyl acetate and water in a volume ratio of 1:1, and the aqueous phase was back-extracted twice with a saturated NaCl solution until the organic phase was colorless and transparent. The temperature during the extraction process was controlled at 28 ° C, and each extraction time was 18 minutes; B2. The organic phase was concentrated under reduced pressure at 42°C to 1 / 3 of its original volume. N-hexane was slowly added until the turbidity of the solution reached 120 NTU. Pre-enrichment and recrystallization were performed to precipitate the crude product. B3 using a volume ratio of 2.5: 1 ethyl acetate / isopropanol mixed solvent temperature gradient recrystallization, by precisely controlling the cooling rate to obtain high-quality crystals; B4. Finally, the product was purified and recrystallized using a mixed solvent of n-hexane / ethyl acetate in a volume ratio of 1.8:1, with the temperature controlled at 8°C for 36 hours to obtain a high-purity crystalline product with a purity of 99.2%.

[0059] The temperature gradient recrystallization in step B3 of this embodiment adopts programmed cooling: The first stage is 33℃, with a cooling rate of 1.4℃ / h, mainly completing solubility adjustment and initial nucleation; The second stage is 22℃, cooling rate 0.9℃ / h, to control the crystal nucleus growth rate; The third stage is 12℃, with a cooling rate of 0.7℃ / h, to promote the improvement of the crystal structure; The fourth stage was 6°C with a cooling rate of 0.4°C / h to ensure the quality and yield of the crystals. A constant stirring rate of 110 rpm was used throughout the process. The seed preparation and addition method in the recrystallization process of this embodiment is as follows: C1. Seed preparation: The crude product prepared in steps S1-S2 of this process was subjected to preliminary purification in steps B1-B2, and the solid product was used as a seed material. The product was ultrasonically crushed at a power of 180 W for 35 minutes and sieved through a 300-mesh sieve to obtain fine seed particles with an average particle size of 0.8 μm. C2. Seed Addition: When the temperature stabilizes at 35°C in the first stage, slowly add the prepared seed crystals at a rate of 0.2 wt% of the total solid content in the solution to be crystallized, stirring while adding to ensure uniform dispersion. After dispersion is complete, maintain the temperature for 14 minutes to fully wet the seed crystals, and then begin the programmed cooling process.

[0060] The La2O3 catalyst of this embodiment can be reused 6 times and regenerated after each use according to the following procedure: washing with ethyl acetate to remove organic residues, washing with deionized water to a pH of 6.8, vacuum drying at 110°C for 4 hours to remove moisture, and calcining in air at 550°C for 3 hours to restore catalytic activity. After regeneration, the catalytic activity retention rate was 93%, the BET specific surface area retention rate was 92%, and the surface basic site retention rate was 90%.

[0061] The intermediate containing acetylfuran structure of this embodiment is used in the preparation of amino alcohol compounds, secondary amine compounds, rare amino sugars or heterocyclic compounds. The intermediate is used as a synthetic precursor to prepare key intermediates for anti-tumor drugs, antibiotics or bioactive molecules.

[0062] Features of Example 2: This example pursues high purity and selectivity, utilizing a mixed solvent system (N,N-dimethylformamide and dimethyl sulfoxide in a 2:1 ratio). The catalyst possesses a high specific surface area and high basic site density (180 m² / g, 1.4 mmol / g), a high reaction temperature (195°C for the main reaction), and a highly refined recrystallization process. This process achieves the highest product purity of 99.2% and excellent crystal quality, with an N-3-furyl-acetamide content of 76% and crystal lengths up to 720 μm. This example is particularly suitable for the high-end pharmaceutical field, such as the precision preparation of innovative drug intermediates, the preparation of key building blocks in the synthesis of chiral drugs, and the preparation of high-purity bioactive natural products. In the fine chemical industry, it can be used to prepare high-value-added functional material precursors and produce specialty chemicals.

[0063] Example 3 The La2O3 catalyst of this embodiment is prepared by a sol-gel combined with hydrothermal step-by-step assembly method, including three steps: mixing lanthanum nitrate, citric acid and structure-directing agent hexadecyltrimethylammonium bromide in a molar ratio of 1:2.1:0.4 to prepare a precursor, hydrothermal treatment and programmed calcination.

[0064] The La2O3 catalyst of this embodiment is prepared by a sol-gel combined with hydrothermal step-by-step assembly method: A1. Lanthanum nitrate and citric acid were mixed, and a structure-directing agent, cetyltrimethylammonium bromide, was added. The molar ratio of the three was lanthanum nitrate: citric acid: directing agent = 1:2.1:0.4. Deionized water was added to a solid content of 22 wt% to form a precursor solution, and stirred at 65 ° C for 3.5 hours to ensure complete dissolution. A2. Evaporation at 110°C with a magnetic stirrer until the mixture is in a gel-like state. The stirring rate is controlled at 220 rpm for 7 hours, followed by hydrothermal treatment in an autoclave at 190°C for 22 hours. A3. Calcinate in a muffle furnace at 450°C in air atmosphere for 5 hours with a heating rate of 2.5°C / min to ensure the complete formation of the La2O3 crystal phase and the development of the lamellar wrinkle structure.

[0065] The calcination procedure of step A3 of this embodiment includes: A31 organic pre-decomposition stage: room temperature at 1.2 ° C / min to 200 ° C, in a nitrogen atmosphere for 1.4 hours to prevent rapid decomposition of the organic template causing structural collapse; A32. Raise the temperature to 380°C at 2.5°C / min and switch to air atmosphere for 2.8 hours to complete the decomposition and initial crystallization of the organic template; A33. Continue to raise the temperature to 520°C and keep it for 5 hours to promote the complete formation of the La2O3 crystal phase and the development of the lamellar wrinkle structure.

[0066] A method for preparing an intermediate containing an acetylfuran structure, comprising the following steps: S1. N-acetyl-D-glucosamine and N-methyl-2-pyrrolidone were mixed to form a reaction system, and the water content in the reaction system was ensured to be 0.04 wt % by molecular sieve pretreatment and nitrogen protection; S2. La2O3 catalyst was added for catalytic dehydration reaction. The reaction was carried out under an inert atmosphere and a staged temperature control strategy was used to optimize the reaction selectivity. S3. After the reaction is completed, a multi-step cascade recrystallization process is used to obtain an intermediate containing an acetylfuran structure; The intermediates of this example are N-3-furyl-acetamide and N-(5-acetyl-3-furyl)-acetamide. The mass fraction of N-3-furyl-acetamide in the product is 75%, the mass fraction of N-(5-acetyl-3-furyl)-acetamide is 24.0%, and the content of other trace components is 0.5%, which are mainly bimolecular condensation products and methylated derivatives; the impurity content is 0.5%, which is mainly catalyst residues and trace moisture; the total purity of the two target products is 99.0%, and the total purity is 99.5%; the product has a needle-shaped crystal form with an average length of 650 μm and a width of 42.0 μm; The structural formula of N-3-furyl-acetamide in this embodiment is the same as that in Example 1; The structural formula of N-(5-acetyl-3-furyl)-acetamide in this embodiment is the same as that in Example 1; The La2O3 catalyst of this embodiment has the morphology of submicron particles and a nanoscale active layer distributed on its surface. The surface of the nanoscale active layer contains a flaky nano-wrinkled structure. The specific surface area of ​​the catalyst is 85 m² / g, and the surface basic site density is 0.9 mmol / g. The average size of the La2O3 catalyst is 720 nm.

[0067] The catalytic dehydration reaction in step S2 of this embodiment adopts staged temperature control, including: a pre-activation stage: a reaction temperature of 155°C, a reaction time of 35 minutes, to activate the catalyst surface and pre-adsorb the raw materials; a main reaction stage: a reaction temperature of 170°C, a time of 3.5 hours, to carry out the main dehydration cyclization reaction; a finishing stage: a reaction temperature of 185°C, a time of 1 hour, to ensure that the reaction is complete; the amount of La2O3 catalyst used is 22% of the mass of N-acetyl-D-glucosamine, the residual water content in the reaction system is controlled at 0.09wt%, and the entire reaction is carried out under nitrogen protection, and the pressure is controlled at 0.25 MPa.

[0068] The solvent in step S1 of this embodiment is N-methyl-2-pyrrolidone.

[0069] The S3 step of this embodiment includes the following multi-step cascade recrystallization process: B1. The reaction product was extracted and separated with ethyl acetate and water in a volume ratio of 1:1, and the aqueous phase was back-extracted four times with a saturated NaCl solution until the organic phase was colorless and transparent. The temperature during the extraction process was controlled at 32 ° C, and each extraction time was 25 minutes; B2. The organic phase was concentrated under reduced pressure at 38°C to half its original volume. N-hexane was slowly added until the turbidity of the solution reached 180 NTU. Pre-enrichment and recrystallization were performed to precipitate the crude product. B3 using a volume ratio of 1.5: 1 ethyl acetate / isopropanol mixed solvent temperature gradient recrystallization, by precisely controlling the cooling rate to obtain high-quality crystals; B4. Finally, the product was purified and recrystallized using a mixed solvent of n-hexane / ethyl acetate in a volume ratio of 1.2:1. The temperature was controlled at 20°C for 18 hours to obtain a high-purity crystalline product with a purity of 97.8%.

[0070] The temperature gradient recrystallization in step B3 of this embodiment adopts programmed cooling: The first stage is 30℃, with a cooling rate of 1.1℃ / h, mainly completing solubility adjustment and initial nucleation; The second stage is 28℃, cooling rate is 1.1℃ / h, to control the growth rate of crystal nuclei; The third stage is 18℃, with a cooling rate of 0.5℃ / h to promote the improvement of the crystal structure; The fourth stage was 8°C with a cooling rate of 0.2°C / h to ensure crystal quality and yield, and a constant stirring rate of 90 rpm was used throughout the process; The seed preparation and addition method in the recrystallization process of this embodiment is as follows: C1. Seed preparation: The crude product prepared in steps S1-S2 of this process was used as a seed material. The solid product was initially purified in steps B1-B2 and ball milled at 350 rpm for 55 minutes. The product was sieved through 300 mesh to obtain fine seed particles with an average particle size of 1.8 μm. C2. Seed Addition: When the temperature stabilizes at 35°C in the first stage, slowly add the prepared seed crystals at a rate of 0.4 wt% of the total solid content in the solution to be crystallized, stirring while adding to ensure uniform dispersion. After dispersion is complete, maintain the temperature for 11 minutes to fully wet the seed crystals, and then begin the programmed cooling process.

[0071] The La2O3 catalyst of this embodiment can be reused four times and regenerated after each use according to the following procedure: washing with ethyl acetate to remove organic residues, washing with deionized water to a pH of 7.2, vacuum drying at 110°C for 4 hours to remove moisture, and calcining in air at 550°C for 3 hours to restore catalytic activity. After regeneration, the catalytic activity retention rate was 91%, the BET specific surface area retention rate was 90%, and the surface basic site retention rate was 88%.

[0072] The intermediate containing acetylfuran structure of this embodiment is used in the preparation of amino alcohol compounds, secondary amine compounds, rare amino sugars or heterocyclic compounds. The intermediate is used as a synthetic precursor to prepare key intermediates for anti-tumor drugs, antibiotics or bioactive molecules.

[0073] Features of Example 3: This example utilizes relatively mild reaction conditions, using N-methyl-2-pyrrolidone as the solvent. The catalyst has a low specific surface area but a large particle size (85 m² / g, 720 nm), a relatively low reaction temperature (170°C for the main reaction), and a short recrystallization time. This process produces relatively small crystals (350 μm in length) with a purity of 97.8%. The process cost is relatively low, making it suitable for applications where purity requirements are not extremely high but cost control is required. This example is particularly suitable for the bulk production of chemical intermediates, such as the preparation of pesticide APIs, the synthesis of dye intermediates, and the preparation of common-grade heterocyclic compounds. In the field of materials science, it can be used to prepare monomers for functional polymers and precursors for organic electronic materials.

[0074] Example 4 The La2O3 catalyst of this embodiment is prepared by a sol-gel combined with hydrothermal step-by-step assembly method, including three steps: mixing lanthanum nitrate, citric acid and structure-directing agent hexadecyltrimethylammonium bromide in a molar ratio of 1:2.3:0.6 to prepare a precursor, hydrothermal treatment and programmed calcination.

[0075] The La2O3 catalyst of this embodiment is prepared by a sol-gel combined with hydrothermal step-by-step assembly method: A1. Lanthanum nitrate and citric acid were mixed, and a structure-directing agent, cetyltrimethylammonium bromide, was added. The molar ratio of the three was lanthanum nitrate: citric acid: directing agent = 1:2.3:0.6. Deionized water was added to a solid content of 16 wt% to form a precursor solution, and stirred at 78 ° C for 2.2 hours to ensure complete dissolution. A2. Evaporation at 95°C with a magnetic stirrer at 260 rpm until the mixture forms a gel. The evaporation time is 4.5 hours, followed by hydrothermal treatment in an autoclave at 205°C for 20 hours. A3. Calcinate in a muffle furnace at 480°C in air atmosphere for 3.5 hours with a heating rate of 4.5°C / min to ensure the complete formation of the La2O3 crystal phase and the development of the lamellar wrinkle structure.

[0076] The calcination procedure of step A3 of this embodiment includes: A31 organic pre-decomposition stage: room temperature at 1.3 ° C / min to 200 ° C, in a nitrogen atmosphere for 1.3 hours to prevent rapid decomposition of the organic template causing structural collapse; A32. Raise the temperature to 430°C at 4.5°C / min and switch to air atmosphere for 2.4 hours to complete the decomposition and initial crystallization of the organic template. A33. Continue to raise the temperature to 560°C and keep it for 3.8 hours to promote the complete formation of the La2O3 crystal phase and the development of the lamellar wrinkle structure.

[0077] A method for preparing an intermediate containing an acetylfuran structure, comprising the following steps: S1. N-acetyl-D-glucosamine, dimethylacetamide, and dimethyl sulfoxide were mixed in a volume ratio of 1:1 to form a reaction system. The water content in the reaction system was ensured to be 0.05 wt % by molecular sieve pretreatment and nitrogen protection. S2. La2O3 catalyst was added for catalytic dehydration reaction. The reaction was carried out under an inert atmosphere and a staged temperature control strategy was used to optimize the reaction selectivity. S3. After the reaction is completed, a multi-step cascade recrystallization process is used to obtain an intermediate containing an acetylfuran structure; The intermediates of this example are N-3-furyl-acetamide and N-(5-acetyl-3-furyl)-acetamide. The mass fraction of N-3-furyl-acetamide in the product is 75%, the mass fraction of N-(5-acetyl-3-furyl)-acetamide is 24%, and the impurity content is 0.5%, which is mainly unreacted starting materials and a small amount of isomers. The combined purity of the two target products is 99.5%; the product is in the form of needle-shaped crystals with an average length of 650 μm and a width of 42.0 μm. The structural formula of N-3-furyl-acetamide in this embodiment is the same as that in Example 1; The structural formula of N-(5-acetyl-3-furyl)-acetamide in this embodiment is the same as that in Example 1; The La2O3 catalyst of this embodiment has the morphology of submicron particles and a nanoscale active layer distributed on its surface. The surface of the nanoscale active layer contains a flaky nano-wrinkled structure. The specific surface area of ​​the catalyst is 160 m² / g, and the surface basic site density is 1.3 mmol / g. The average size of the La2O3 catalyst is 420 nm.

[0078] The catalytic dehydration reaction in step S2 of this embodiment adopts staged temperature control, including: a pre-activation stage: a reaction temperature of 142°C and a reaction time of 55 minutes to activate the catalyst surface and pre-adsorb the raw materials; a main reaction stage: a reaction temperature of 188°C and a time of 2.8 hours to carry out the main dehydration cyclization reaction; a finishing stage: a reaction temperature of 198°C and a time of 0.7 hours to ensure that the reaction is complete; the amount of La2O3 catalyst used is 16% of the mass of N-acetyl-D-glucosamine, the residual water content in the reaction system is controlled at 0.1wt%, and the entire reaction is carried out under nitrogen protection, and the pressure is controlled at 0.28 MPa.

[0079] The solvent in step S1 of this embodiment is a mixture of dimethylacetamide and dimethyl sulfoxide in a volume ratio of 1:1.

[0080] The S3 step of this embodiment includes the following multi-step cascade recrystallization process: B1. The reaction product was extracted and separated with ethyl acetate and water in a volume ratio of 1:1, and the aqueous phase was back-extracted three times with a saturated NaCl solution until the organic phase was colorless and transparent. The temperature during the extraction process was controlled at 26 ° C, and each extraction time was 28 minutes; B2. The organic phase was concentrated under reduced pressure at 44°C to 3 / 8 of its original volume. N-hexane was slowly added until the turbidity of the solution reached 160 NTU. Pre-enrichment and recrystallization were performed to precipitate the crude product. B3 using a volume ratio of 1.8: 1 ethyl acetate / isopropanol mixed solvent temperature gradient recrystallization, by precisely controlling the cooling rate to obtain high-quality crystals; B4. Finally, the product was purified and recrystallized using a mixed solvent of n-hexane / ethyl acetate in a volume ratio of 1.9:1, with the temperature controlled at 12°C for 42 hours to obtain a high-purity crystalline product with a purity of 99.5%.

[0081] The temperature gradient recrystallization in step B3 of this embodiment adopts programmed cooling: The first stage is 34℃, with a cooling rate of 1.3℃ / h, mainly completing solubility adjustment and initial nucleation; The second stage is 26℃, cooling rate 0.8℃ / h, to control the growth rate of crystal nuclei; The third stage is 14°C with a cooling rate of 0.8°C / h to promote the improvement of the crystal structure; The fourth stage was 5°C with a cooling rate of 0.5°C / h to ensure the quality and yield of the crystals. A constant stirring rate of 120 rpm was used throughout the process. The seed preparation and addition method in the recrystallization process of this embodiment is as follows: C1. Seed preparation: The crude product prepared in steps S1-S2 of this process was subjected to preliminary purification in steps B1-B2, and the solid product was used as a seed material. The product was treated by ultrasonic grinding at a power of 170 W for 40 minutes and sieved through 300 mesh to obtain fine seed particles with an average particle size of 1.5 μm. C2. Seed Addition: When the temperature stabilizes at 35°C in the first stage, slowly add the prepared seed crystals at a rate of 0.5 wt% of the total solid content in the solution to be crystallized, stirring while adding to ensure uniform dispersion. After dispersion is complete, maintain the temperature for 13 minutes to fully wet the seed crystals, and then begin the programmed cooling process.

[0082] The La2O3 catalyst of this embodiment can be reused 5 times and regenerated after each use according to the following procedure: washing with ethyl acetate to remove organic residues, washing with deionized water to a pH of 6.9, vacuum drying at 110°C for 4 hours to remove moisture, and calcining in air at 550°C for 3 hours to restore catalytic activity. After regeneration, the catalytic activity retention rate was 94%, the BET specific surface area retention rate was 92%, and the surface basic site retention rate was 90%.

[0083] The intermediate containing acetylfuran structure of this embodiment is used in the preparation of amino alcohol compounds, secondary amine compounds, rare amino sugars or heterocyclic compounds. The intermediate is used as a synthetic precursor to prepare key intermediates for anti-tumor drugs, antibiotics or bioactive molecules.

[0084] Features of Example 4: This example optimizes process efficiency while ensuring high purity. It uses a mixed solvent of equal volumes of dimethylacetamide and dimethyl sulfoxide, moderate catalyst parameters (160 m² / g, 1.3 mmol / g), strict reaction conditions (pre-activation at 142°C, main reaction at 188°C, pressure at 0.28 MPa), and a long recrystallization time to ensure product quality. This process achieves a maximum purity of 99.5% and excellent crystal morphology, making it suitable for applications with extremely high product quality requirements. This example is particularly suitable for high-end biopharmaceuticals, such as the preparation of linkers for monoclonal antibody-drug conjugates (ADCs), the synthesis of key intermediates for cell therapy reagents, and the preparation of high-purity enzyme inhibitors and receptor antagonists. In the biotechnology field, it can be used to prepare functional molecules for biosensors and core components for diagnostic reagents.

[0085] Comparative Example 1: Basically the same as Example 1, except that the catalytic dehydration reaction in step S2 adopts a constant temperature control strategy, the reaction temperature is always maintained at 180°C, the reaction time is 4 hours, and the segmented temperature control of the pre-activation stage and the finishing stage is not performed.

[0086] Comparative Example 2: basically the same as Example 1, except that in the preparation process of the La2O3 catalyst, the molar ratio of step A1 was adjusted to lanthanum nitrate: citric acid: directing agent = 1:1.5:0.3, and other preparation conditions remained unchanged.

[0087] Comparative Example 3 is basically the same as Example 1, except that methanol is used as the solvent instead of dioxane in step S1, and the water content in the reaction system is controlled at 0.03 wt%.

[0088] Comparative Example 4 is basically the same as Example 1, except that during the preparation of the La2O3 catalyst, the calcination temperature in step A3 is adjusted to 350°C, the calcination time is maintained at 4 hours, and the heating rate is 3°C / min.

[0089] Comparative Example 5: Basically the same as Example 1, except that the amount of La2O3 catalyst in step S2 is adjusted to 10% of the mass of N-acetyl-D-glucosamine, and other reaction conditions remain unchanged.

[0090] Comparative Example 6: Basically the same as Example 1, except that the B3 recrystallization process in step S3 adopts a constant temperature cooling strategy, directly cooling from 35°C to 5°C at a constant rate of 1.5°C / h, without staged programmed cooling.

[0091] Comparative Example 7: basically the same as Example 1, except that in the preparation process of La2O3 catalyst, the hydrothermal treatment temperature of step A2 is adjusted to 150°C and the treatment time is adjusted to 24 hours.

[0092] Comparative Example 8: basically the same as Example 1, except that in the B1 extraction process of step S3, the volume ratio of ethyl acetate and water is adjusted to 3:1, and the extraction temperature is adjusted to 45°C.

[0093] Comparative Example 9: basically the same as Example 1, except that the reaction in step S2 is carried out under air atmosphere without nitrogen protection, and other reaction conditions remain unchanged.

[0094] Comparative Example 10 is basically the same as Example 1, except that in the preparation process of the La2O3 catalyst, the structure-directing agent hexadecyltrimethylammonium bromide is not added in step A1, and only lanthanum nitrate and citric acid are mixed in a molar ratio of 1:2.2.

[0095] Comparative Example 11 is basically the same as Example 1, except that in the B2 concentration process of step S3, the organic phase concentration temperature is adjusted to 60°C and concentrated to 1 / 5 of the original volume.

[0096] Comparative Example 12: basically the same as Example 1, except that the reaction pressure in step S2 is adjusted to 0.5 MPa, and other reaction conditions remain unchanged.

[0097] Comparative Example 13 is basically the same as Example 1, except that during the preparation of the La2O3 catalyst, the calcination procedure in step A3 is simplified to directly heating from room temperature to 550°C at 5°C / min and keeping warm for 4 hours without staged calcination.

[0098] Comparative Example 14 is basically the same as Example 1, except that no seed crystals are added in step S3, and the programmed cooling recrystallization process of B3 is directly carried out.

[0099] Comparative Example 15 is basically the same as Example 1, except that no molecular sieve pretreatment is performed in step S1, N-acetyl-D-glucosamine and dioxane are directly mixed, and the water content in the reaction system is controlled at 0.15 wt% only by nitrogen protection.

[0100] Performance testing: Chemical purity and composition analysis of acetylfuran intermediates: The test subjects were the prepared crystalline acetylfuran intermediates. The purpose of the test was to accurately quantify the content and impurity distribution of N-3-furyl-acetamide and N-(5-acetyl-3-furyl)-acetamide. The test principle is based on HPLC separation, utilizing the differences in the partition coefficients of different compounds between the stationary phase and the mobile phase to achieve separation and detection. The experimental method was a Waters ACQUITY UPLC H-Class ultra-high performance liquid chromatography system equipped with a PDA detector. A C18 reversed-phase column (250 mm × 4.6 mm, 5 μm) was used. The mobile phase consisted of a gradient elution of acetonitrile and 0.1% aqueous phosphoric acid at a flow rate of 1.0 mL / min, detection wavelength at 254 nm, and column temperature at 30°C. Sample preparation required dissolving 10 mg of the intermediate in 1 mL of HPLC-grade methanol. After sonication for 15 minutes to completely dissolve the intermediate, the sample was passed through a 0.22 μm filter and injected in a 20 μL volume. Key parameters include injection precision RSD ≤ 2.0%, detection limit ≤ 0.01%, and quantification limit ≤ 0.05%.

[0101] Intermediate crystal morphology and microstructure characterization test: The test object is a needle-shaped crystal containing an acetofuran structure intermediate, and the purpose of the test is to characterize the morphological characteristics, size distribution and surface microstructure of the crystal. The test principle is based on the principle of secondary electron imaging generated by the interaction between the electron beam and the sample of a scanning electron microscope, combined with energy spectrum analysis to detect element distribution. The experimental method uses a JEOL JSM-7800F field emission scanning electron microscope with an adjustable acceleration voltage of 1-30kV and a resolution of 1.0nm@15kV. Sample preparation requires that the intermediate crystals be dispersed on a conductive tape to avoid agglomeration, and gold-plated for 60 seconds under vacuum conditions with a coating thickness of approximately 10nm. Use different magnifications (500×, 2000×, 10000×) to observe the overall morphology and surface details of the crystal, and measure the length and width data of at least 100 crystal particles. Key parameters include the vacuum degree of the sample chamber , working distance 8-15mm, and moderate electron beam current to avoid sample damage.

[0102] Thermal Stability and Thermal Decomposition Behavior of the Intermediate: The test subjects were powder samples of an intermediate containing an acetofuran structure. The purpose of the test was to evaluate the thermal stability, decomposition temperature, and thermal decomposition kinetics of the material at different temperatures. The testing principle is based on thermogravimetric analysis. A precision balance continuously monitors the mass change of the sample during a programmed temperature increase, combined with differential scanning calorimetry (DSC). The experimental method utilizes a TA Instruments SDT Q600 simultaneous thermal analyzer, operating under a nitrogen atmosphere, with a flow rate of 100 mL / min, a heating rate of 10°C / min, and a temperature range from room temperature to 600°C. Sample preparation required placing 5-10 mg of the intermediate in an aluminum crucible, ensuring that the sample was evenly distributed to avoid accumulation that would affect heat transfer. TG, DTG, and DSC curves were recorded during the test, and the initial decomposition temperature (Ti), the temperature at which the decomposition rate reached maximum (Tmax), and the final decomposition temperature (Tf) were analyzed. Key parameters include a balance accuracy of ±0.1 μg, a temperature control accuracy of ±1°C, and a sealed furnace to prevent oxygen ingress. Data processing was performed using TA Universal Analysis software to calculate the decomposition kinetic parameters, including activation energy Ea and frequency factor A, and to evaluate the thermal stability of the material under synthesis and storage conditions.

[0103] Solubility and stability test of intermediates in different solvents The test subjects were crystals of an intermediate containing an acetylfuran structure. The goal was to systematically evaluate the material's solubility, dissolution rate, and chemical stability in common organic solvents. The testing principle is based on the solubility equilibrium principle and quantitative analysis using UV-visible spectrophotometry. Dissolution behavior and stability were assessed by monitoring changes in solution concentration. Six representative solvents were selected: methanol, ethanol, ethyl acetate, dichloromethane, N,N-dimethylformamide, and dimethyl sulfoxide. Saturation solubility tests were conducted at a constant temperature of 25°C ± 0.1°C. Sample preparation involved weighing an excess of the intermediate (approximately 50 mg) into 10 mL of each solvent. The solution was magnetically stirred for 24 hours to reach equilibrium. The supernatant was filtered, diluted, and the concentration was measured using a UV spectrophotometer at 254 nm. Stability was also assessed by storing the saturated solutions at 25°C and 40°C, with periodic sampling and analysis for changes in concentration and purity. The standards were based on OECD Test Guideline 105, "Solubility in Water," and ICH Q1A(R2), "Guidelines for Stability Testing." Key parameters include temperature control accuracy of ±0.1°C, UV detector wavelength accuracy of ±0.5nm, and sample storage in the dark to prevent decomposition. Data processing uses a standard curve method to calculate the saturated solubility in each solvent, establish the relationship between solubility parameters and solvent polarity, and evaluate the material's suitability under different reaction and purification conditions.

[0104] Surface Properties and Catalytic Activity Characterization of La2O3 Catalysts: The prepared La2O3 catalyst samples were tested to characterize the catalyst's specific surface area, pore size distribution, surface basic site density, and catalytic activity. The testing principle is based on gas physical adsorption theory. The surface area and pore structure of the porous material were analyzed using N2 adsorption-desorption isotherms, combined with CO2 temperature-programmed desorption to determine the surface basic sites. The BET surface area measurement was performed using a Micromeritics ASAP 2020 M+C physical and chemical adsorption analyzer. Sample pretreatment required degassing under vacuum at 300°C for 4 hours. N2 adsorption was then performed at liquid nitrogen temperature with a relative pressure range of 0.05-0.99. Surface basic sites were determined using an AutoChem II 2920 chemisorption instrument. CO2 temperature-programmed desorption (CO2-TPD) conditions included He carrier gas at 50 mL / min, a heating rate of 10°C / min, and a temperature range of 50-800°C. Catalytic activity was tested in a fixed-bed reactor using a simulated dehydration reaction at 180°C, in an N2 atmosphere, and with a catalyst loading of 20 wt%. The standard was based on GB / T 19587-2017, "Determination of Specific Surface Area of ​​Solids by Gas Adsorption BET Method." Key parameters include a degassing temperature of 300°C to avoid structural damage, an adsorption equilibrium time ≥180 seconds to ensure accuracy, and a constant TPD heating rate to ensure reproducibility. Data processing employed the BET equation to calculate specific surface area, the BJH model to analyze pore size distribution, and the CO2-TPD integrated area to calculate basic site density, verifying the relationship between catalyst structure and activity.

[0105] The properties of the intermediates of Examples 1 to 4 and Comparative Examples 1 to 15 are summarized in Table 1. Comparative Example 1 uses a constant temperature control strategy instead of segmented temperature control, resulting in insufficient catalyst activation and decreased reaction selectivity, resulting in significant degradation of product purity and crystal morphology quality. The reduction in the citric acid ratio in Comparative Example 2 destroys the complex stability of the catalyst precursor, directly affects the formation of the specific surface area and basic site density of the catalyst, and thus reduces the catalytic activity and product quality. Comparative Example 3 uses methanol instead of dioxane as a solvent. The strong polarity and active hydrogen properties of methanol interfere with the selectivity mechanism of the dehydration reaction, increase the probability of side reactions, and although the solubility of the product is improved, the purity and thermal stability are significantly reduced. The low-temperature calcination strategy of Comparative Example 4 cannot provide sufficient thermodynamic driving force to complete the complete formation of the La2O3 crystal phase and the development of the active structure, resulting in a sharp decrease in the specific surface area of ​​the catalyst and a significant deterioration of thermal stability. The reduction in the amount of catalyst used in Comparative Example 5 directly limits the conversion efficiency of the reaction. The residue of unreacted raw materials increases the impurity content and inhibits the normal growth process of the crystal. Comparative Example 6 adopts a constant temperature cooling recrystallization strategy, which destroys the precise control mechanism of crystal nucleation and growth. Although the effect on purity is relatively small, it significantly affects the size distribution and morphology quality of the crystals. The low-temperature hydrothermal treatment of Comparative Example 7 cannot provide sufficient energy conditions for the microstructure assembly of the catalyst, resulting in uneven distribution of active sites and a decline in overall catalytic performance. Comparative Example 8 changes the ratio of the extraction phase, which destroys the optimal balance of impurity removal, affecting the effect of the subsequent recrystallization process and the purity of the final product. Comparative Example 9 carries out the reaction under an air atmosphere, introducing oxygen to oxidize the catalyst and product, which not only leads to partial deactivation of the catalyst but also promotes the oxidative degradation of the product, resulting in a double deterioration of purity and thermal stability. Comparative Example 10 removes the structure directing agent, eliminating the template effect of the catalyst's ordered structure formation, resulting in disorder of the catalyst microstructure and a significant decrease in specific surface area and basic site density. The high-temperature concentration process of Comparative Example 11 may trigger a thermal decomposition reaction of the product, which not only affects the stability of the product but also interferes with the normal growth mechanism of the crystal. The high-pressure reaction conditions in Comparative Example 12 changed the thermodynamic and kinetic equilibrium of the reaction system, which may promote undesirable side reaction pathways and affect the selectivity and purity of the product. The simplified calcination procedure in Comparative Example 13 resulted in the rapid decomposition of the organic template and the collapse of the catalyst structure, which seriously damaged the microstructural integrity of the catalyst and the effectiveness of the active sites. The lack of seed addition in Comparative Example 14 eliminated the guiding mechanism for crystal nucleation. Although it had little effect on the chemical purity, it significantly affected the size control and morphological regularity of the crystals. The omission of the molecular sieve pretreatment step in Comparative Example 15 resulted in an excessively high water content in the reaction system. The strong competitive adsorption of water molecules on the active sites of the catalyst and the inhibitory effect on the dehydration reaction caused the most serious performance deterioration. Not only did the purity drop to the lowest level, but the thermal stability also dropped significantly.

[0106] Table 2 Summary of the performance of Examples 1 to 4 and Comparative Examples 1 to 15

[0107] Figure 1 The La2O3 catalyst prepared in Example 2 exhibits a typical nanosheet-like wrinkled structure with a specific surface area of ​​180 m² / g. Figure 4 and Figure 5 The catalysts of Comparative Example 10 and Comparative Example 2 respectively exhibited no nanowrinkles, demonstrating the key role of the absence of the hexadecyltrimethylammonium bromide directing agent or the low citric acid content in the formation of ordered nanostructures. Figure 2 XRD phase analysis confirmed that the catalyst of Example 2 has a complete La2O3 crystal structure and good crystallinity, providing a structural basis for efficient catalysis. More importantly, Figure 3 The intermediate product of Example 2 is in the form of regular needle-shaped crystals. Figure 6 and Figure 7 The intermediates in the comparative examples are in the form of irregular lumps and fine particles, respectively, and the crystal morphologies are very different, which directly reflects the decisive influence of different catalyst performance on product quality. Figure 8 The full sample performance comparison data further confirmed that the total purity of all examples was within the range of 97.8-99.5%, and the impurity content was controlled at 0.5-2.2%, while the total purity of the 15 comparative examples was only 88.2-96.8%, and the impurity content was as high as 3.2-11.8%. The lowest purity of the examples (97.8%) still significantly exceeded the highest purity of the comparative examples (96.8%), fully verifying that the systematic innovation of the present invention in key technical links such as catalyst preparation, reaction control and crystallization process has achieved a fundamental improvement in product quality.

[0108] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the present invention. Although the present invention has been described in detail with reference to the above embodiments, ordinary technicians in the relevant field should understand that any equivalent structural transformations made within the scope of the present invention using the contents of the present invention's description and drawings should be included within the scope of protection of the claims of the present invention.

Claims

1. A method for preparing an intermediate containing an acetylfuran structure, characterized in that: The following steps are involved: S1. N-acetyl-D-glucosamine is mixed with a solvent to form a reaction system, and the water content in the reaction system is ensured to be ≤0.05 wt % by molecular sieve pretreatment and nitrogen protection; S2. La2O3 catalyst was added for catalytic dehydration reaction. The reaction was carried out under an inert atmosphere and a staged temperature control strategy was used to optimize the reaction selectivity. S3. After the reaction is completed, a multi-step cascade recrystallization process is used to obtain an intermediate containing an acetylfuran structure; The intermediates are N-3-furyl-acetamide and N-(5-acetyl-3-furyl)-acetamide. The mass fraction of N-3-furyl-acetamide in the product is 72-76%, and the mass fraction of N-(5-acetyl-3-furyl)-acetamide is 21-25%. The total purity is 97.8-99.5%. The combined purity of the two target products is 97.0-99.0%. The product has a needle-shaped crystal morphology with an average length of 250-800 μm and a width of 10.0-45.5 μm. The structural formula of the N-3-furyl-acetamide is: ， The structural formula of the N-(5-acetyl-3-furyl)-acetamide is: ， The La2O3 catalyst has a morphology of submicron particles and a nanoscale active layer distributed on its surface. The surface of the nanoscale active layer contains a sheet-like nano-wrinkled structure. The specific surface area of ​​the catalyst is 50-200 m² / g, and the surface basic site density is 0.8-1.5 mmol / g. The average size of the La2O3 catalyst is 350-800 nm. The La2O3 catalyst is prepared by a sol-gel combined with hydrothermal step-by-step assembly method, including three steps: mixing lanthanum nitrate, citric acid and a structure-directing agent, hexadecyltrimethylammonium bromide, in a molar ratio of 1:(2.0-2.5):(0.3-0.8) to prepare a precursor, hydrothermal treatment and programmed calcination.

2. The method for preparing an intermediate containing an acetylfuran structure according to claim 1, wherein: The La2O3 catalyst is prepared by a sol-gel combined with hydrothermal step-by-step assembly method: A1. Lanthanum nitrate and citric acid were mixed, and a structure-directing agent, cetyltrimethylammonium bromide, was added. The molar ratio of the three was lanthanum nitrate: citric acid: directing agent = 1:2.0-2.5:0.3-0.

8. Deionized water was added to form a precursor solution with a solid content of 15-25 wt %, and stirred at 60-80 ° C for 2-4 hours to ensure complete dissolution. A2. Evaporation under stirring with a magnetic stirrer at 80-120 ° C until it becomes a gel, the stirring rate is controlled at 200-300 rpm, the evaporation time is 4-8 hours, and then hydrothermal treatment is performed in an autoclave at 180-220 ° C for 12-24 hours; A3. Calcine in air atmosphere at 400-600°C in a muffle furnace for 2-6 hours at a heating rate of 2-5°C / min to ensure complete formation of the La2O3 crystal phase and development of a lamellar wrinkle structure.

3. The method for preparing an intermediate containing an acetylfuran structure according to claim 2, wherein: The calcination procedure of step A3 includes: A31 organic pre-decomposition stage: room temperature at 1-2 ° C / min to 200 ° C, in a nitrogen atmosphere for 1-1.5 hours to prevent rapid decomposition of the organic template causing structural collapse; A32. Raise the temperature to 350-450°C at 2-5°C / min, switch to air atmosphere and keep warm for 2-3 hours to complete the decomposition and initial crystallization of the organic template; A33. Continue to raise the temperature to 500-600℃ and keep it at this temperature for 2-6 hours to promote the complete formation of the La2O3 crystal phase and the development of the lamellar wrinkle structure.

4. The method for preparing an intermediate containing an acetylfuran structure according to claim 1, wherein: The catalytic dehydration reaction in step S2 adopts segmented temperature control, including: a pre-activation stage: a reaction temperature of 140-160°C and a reaction time of 30-60 minutes to activate the catalyst surface and pre-adsorb the raw materials; a main reaction stage: a reaction temperature of 160-200°C and a time of 2-4 hours to carry out the main dehydration cyclization reaction; a finishing stage: a reaction temperature of 180-200°C and a time of 0.5-1 hour to ensure that the reaction is complete; the amount of La2O3 catalyst used is 15-25% of the mass of N-acetyl-D-glucosamine, the residual water content in the reaction system is controlled at ≤0.1wt%, and the entire reaction is carried out under nitrogen protection, and the pressure is controlled at 0.1-0.3 MPa.

5. The method for preparing an intermediate containing an acetylfuran structure according to claim 1, wherein: The solvent in step S1 is one or a mixture of dioxane, N,N-dimethylformamide, dimethyl sulfoxide, N-methyl-2-pyrrolidone or dimethylacetamide.

6. The method for preparing an intermediate containing an acetylfuran structure according to claim 1, wherein: The S3 step includes the following multi-step cascade recrystallization process: B1. The reaction product was extracted and separated with ethyl acetate and water in a volume ratio of 1:1, and the aqueous phase was back-extracted 2-4 times with a saturated NaCl solution until the organic phase was colorless and transparent. The temperature during the extraction process was controlled at 25-35 ° C, and each extraction time was 15-30 minutes; B2. The organic phase was concentrated under reduced pressure at 35-45°C to 1 / 3-1 / 2 of its original volume, and n-hexane was slowly added until the turbidity value of the solution reached 100-200 NTU. Pre-enrichment and recrystallization were performed to precipitate the crude product of preliminary purification; B3 using a volume ratio of 3: 1-1: 1 ethyl acetate / isopropanol mixed solvent temperature gradient recrystallization, by precisely controlling the cooling rate to obtain high-quality crystals; B4. Finally, the product was purified and recrystallized using a mixed solvent of n-hexane / ethyl acetate in a volume ratio of 1:1-2:1, with the temperature controlled at 5-25°C for 12-48 hours to obtain a high-purity crystalline product with a purity of 97-99.5%.

7. The method for preparing an intermediate containing an acetylfuran structure according to claim 6, wherein: The temperature gradient recrystallization in step B3 adopts programmed cooling: The first stage is 35-30℃, with a cooling rate of 1.0-1.5℃ / h, mainly completing solubility adjustment and initial nucleation; The second stage is 30-20℃, cooling rate 0.8-1.2℃ / h, to control the crystal nucleus growth rate; The third stage is 20-10℃, cooling rate 0.5-0.8℃ / h, to promote the improvement of crystal structure; The fourth stage is 10-5°C, with a cooling rate of 0.2-0.5°C / h to ensure the quality and yield of the crystals. A constant stirring rate of 80-120 rpm is used throughout the process.

8. The method for preparing an intermediate containing an acetylfuran structure according to claim 1, wherein: The seed preparation and addition method in the recrystallization process are as follows: C1. Seed preparation: The crude product prepared in steps S1-S2 of this process is used as a seed crystal raw material. The solid product after preliminary purification in steps B1-B2 is crushed by ball milling at a speed of 300-500 rpm for 45-60 minutes, or by ultrasonic grinding at a power of 150-200 W for 30-45 minutes, and sieved through 300 mesh to obtain fine seed particles with an average particle size of 0.5-2.0 μm. C2. Seed addition: When the temperature stabilizes at 35°C in the first stage, slowly add the prepared seed crystals at a rate of 0.1-0.5 wt% of the total solid content in the solution to be crystallized, stirring while adding to ensure uniform dispersion. After dispersion is complete, maintain the temperature for 10-15 minutes to fully wet the seed crystals, and then begin the programmed cooling process.

9. The method for preparing an intermediate containing an acetylfuran structure according to claim 1, wherein: The La2O3 catalyst can be reused 4-6 times and regenerated after each use according to the following procedure: washing with ethyl acetate to remove organic residues, washing with deionized water until the pH of the washing liquid is 6.5-7.5, vacuum drying at 110°C for 4 hours to remove moisture, and calcining in air at 550°C for 3 hours to restore catalytic activity. After regeneration, the catalytic activity retention rate is ≥90%, the BET specific surface area retention rate is ≥90%, and the surface basic site retention rate is ≥88%.

10. Use of the intermediate containing an acetylfuran structure prepared by the method according to any one of claims 1 to 9 in the preparation of amino alcohol compounds, secondary amine compounds, rare amino sugars or heterocyclic compounds; The intermediate is used as a synthetic precursor for preparing a key intermediate of anti-tumor drugs, antibiotics or bioactive molecules.

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