Production process of N-acetylglucosamine

Abstract

The invention discloses a production process of N-acetylglucosamine, and belongs to the technical field of N-acetylglucosamine production. Methanol is used as a solvent, glucosamine hydrochloride and acetic anhydride are used as raw materials, sodium hydroxide is added as a catalyst, other toxic chemical substances are not introduced, and meanwhile, the product yield is increased. In addition, in the product purification treatment process, a specific fixing agent is added, the specific fixing agent is a magnetic nanoparticle immobilized phenylboronic acid derivative, and the phenylboronic acid derivative can recognize and combine D-glucosamine with cis-dihydroxyl and cannot react with N-acetylglucosamine; the D-glucosamine in the N-acetylglucosamine can be effectively and selectively removed; and after the magnetic nanoparticles are immobilized, the selective adsorption reaction can be amplified, the separation and removal are facilitated, and the operation steps are simplified.

Description

Technical Field

[0001] The present invention belongs to the technical field of N-acetylglucosamine production, and particularly relates to a production process of N-acetylglucosamine. Background Art

[0002] N-acetylglucosamine is a monosaccharide in organisms, widely existing in bacteria, plants and animals, and is one of the components of microbial cell walls. At the same time, N-acetylglucosamine is a component of macromolecules in organisms such as glycosaminoglycans, glycoproteins, proteoglycans and other connective tissues. Glycoproteins containing N-acetylglucosamine are found in the mucosa of the digestive tract. Glycosylation can promote the combination with pathogens, participate in the synthesis of macromolecules in organisms, and can also be used as a basic material for tissue repair.

[0003] N-acetylglucosamine molecules with various functional group substitutions can act as components of cell surface decoration or directly participate in cell interactions. These functions enable the development of some drugs containing N-acetylglucosamine. These drugs have certain applications in diseases such as arthritis and tumors. In addition, N-acetylglucosamine also has good application effects in the fields of health products, cosmetics, etc.

[0004] Currently, there are mainly three methods for producing N-acetylglucosamine: chemical method, bioenzyme method and microorganism method. Each of the three methods has its own advantages and disadvantages. Currently, the chemical method is mainly used in the market. By hydrolyzing chitin with hot concentrated hydrochloric acid, D-glucosamine hydrochloride can be obtained. Using D-glucosamine hydrochloride and acetic anhydride as raw materials, N-acetylglucosamine can be prepared with triethylamine as a catalyst through acetylation with acetic anhydride. However, there is a certain danger in the chemical process. And generally, in order to improve the yield of the product, an excessive amount of glucosamine hydrochloride raw material is added. The excessive glucosamine hydrochloride is difficult to separate and purify in the subsequent treatment process, and the unreacted glucosamine hydrochloride will affect the purity and yield of the product. Summary of the Invention

[0005] The purpose of the present invention is to provide a production process of N-acetylglucosamine to solve the problems of low yield and difficult separation of excessive raw materials in the preparation of N-acetylglucosamine by the chemical method.

[0006] The purpose of the present invention can be achieved by the following technical solutions: The present invention provides a production process of N-acetylglucosamine, including the following process steps: S1. After mixing and dissolving methanol and sodium hydroxide, adjust the temperature to 10 - 20°C, add glucosamine hydrochloride, and stir to dissolve to obtain a pre-reaction solution; S2. Control the temperature of the pre-reaction solution at 20 - 30 °C, dropwise add acetic anhydride, stir and react for 3 - 5 h, and perform suction filtration to obtain the solid crude product; S3. Add the solid crude product to purified water for dissolution, add a specific fixing agent, stir and mix at room temperature for 3 - 4 h, then perform centrifugal separation. Electrodialysis is carried out on the obtained crude product aqueous solution through bag filtration to obtain electrodialyzed fresh water; S4. Add activated carbon to the electrodialyzed fresh water, stir and decolorize at room temperature, and filter to obtain the filtrate; S5. Concentrate the filtrate under reduced pressure for crystallization, and finally obtain N-acetylglucosamine through suction filtration, rinsing, centrifugation and drying; The specific fixing agent is a magnetic nanoparticle-supported phenylboronic acid derivative.

[0007] Preferably, the temperature for concentration under reduced pressure for crystallization is 60 - 65 °C.

[0008] Preferably, the mass ratio of glucosamine hydrochloride to acetic anhydride is 1:(0.6 - 0.65).

[0009] Preferably, the addition amount of the specific fixing agent is 0.6 - 1.5% of the mass of glucosamine hydrochloride.

[0010] Preferably, the addition amount of sodium hydroxide is 19 - 21% of the mass of glucosamine hydrochloride.

[0011] Preferably, the addition amount of activated carbon is 0.3 - 0.5% of the mass of glucosamine hydrochloride.

[0012] By adopting the above technical solution, the present invention uses methanol as the reaction solvent. Compared with other solvents, the polarity of the methanol reaction system is greater, which is beneficial to the synthesis of the target compound, namely N-acetylglucosamine, and effectively improves the reaction yield; and sodium hydroxide is added during the reaction. On the one hand, it can effectively neutralize the hydrogen chloride released during the dissolution of glucosamine hydrochloride, provide a good and stable pH value environment, help improve the selectivity and efficiency of the reaction, and reduce unnecessary side reactions; on the other hand, the addition of sodium hydroxide can help promote the reaction, improve the synthesis of the reaction product without the need to add an additional catalyst, and can also promote the dehydration reaction, reduce the water content in the system, thereby effectively preventing the hydrolysis of acetic anhydride and improving the yield of N-acetylglucosamine.

[0013] Meanwhile, the obtained crude solid is dissolved in purified water, and then a specific fixing agent is added. The main purpose is to adsorb and remove the unreacted glucosamine raw material during the preparation process. The unreacted glucosamine hydrochloride has similar physical and chemical properties to the target product N-acetylglucosamine, making separation and purification difficult, resulting in reduced purity and yield of the product. Moreover, excessive glucosamine will increase side reactions, which is not conducive to improving the product yield and purity, nor to the progress of vacuum concentration and crystallization.

[0014] The specific fixing agent added in the present invention is a magnetic nanoparticle-supported phenylboronic acid derivative. Among them, the phenylboronic acid derivative can recognize and bind saccharide substances containing cis-dihydroxy structures. During the reaction process, glucosamine hydrochloride will hydrolyze to obtain free D-glucosamine. In the synthesis process, it is the reaction between free D-glucosamine and acetic anhydride to obtain N-acetylglucosamine. However, excessive D-glucosamine will affect the subsequent impurity removal and crystallization. The phenylboronic acid derivative can recognize and bind this kind of free D-glucosamine with cis-dihydroxy and free amino groups, and can capture amino groups by forming a stable complex through covalent bonds. However, for N-acetylglucosamine, it does not contain cis-dihydroxy and the amino group has been acetylated, and it will not produce a similar reaction with the phenylboronic acid derivative. Therefore, the specific fixing agent of the present invention has high selectivity for free D-glucosamine and can effectively separate and remove D-glucosamine without affecting the product yield.

[0015] Meanwhile, the present invention designs to support the phenylboronic acid derivative on magnetic nanoparticles, which can not only improve the selective adsorption ability for D-glucosamine, but also facilitate removal from the reaction solution after the adsorption reaction, and can utilize the magnetic properties for easy separation and treatment, simplify the operation steps, and reduce non-specific binding.

[0016] Preferably, the raw materials of the specific fixing agent include magnetic iron oxide nanoparticles and 3-aminophenylboronic acid with a mass ratio of 1:(0.1 - 0.2).

[0017] Preferably, the particle size of the magnetic iron oxide nanoparticles is 100 - 200 nm.

[0018] Preferably, the specific fixing agent is prepared according to the following method: Disperse the magnetic iron oxide nanoparticles in deionized water, adjust the reaction pH value to 7 - 8, add a crosslinking agent under ice bath conditions, stir and react for 30 - 60 min, and then add 3-aminophenylboronic acid at room temperature and stir and react for 2 - 3 h to obtain.

[0019] Preferably, the crosslinking agent is a bifunctional NHS ester crosslinking agent; the addition amount of the crosslinking agent is 2 - 6% of the mass of the magnetic iron oxide nanoparticles.

[0020] More preferably, the bifunctional NHS ester crosslinking agent includes any one of disuccinimidyl suberate and disuccinimidyl sebacate.

[0021] By adopting the above technical solution, the present invention uses magnetic iron oxide nanoparticles as the solid support carrier of phenylboronic acid derivatives. The surface of the magnetic iron oxide nanoparticles contains amino groups, which can react and connect with 3-aminophenylboronic acid under the action of a crosslinking agent, thereby realizing the solid support of the phenylboronic acid derivatives.

[0022] By immobilizing 3-aminophenylboronic acid on the magnetic nanoparticles, the selective adsorption effect of the phenylboronic acid derivatives on free D-glucosamine can be significantly amplified, and the stability of the reaction can also be improved, facilitating subsequent separation and treatment.

[0023] Specifically, on the one hand, the magnetic nanoparticles have a large specific surface area, which can provide a large number of surface sites for 3-aminophenylboronic acid. The obtained magnetic nanoparticles with a high density of 3-aminophenylboronic acid can capture more target molecules in a short time, improving the binding efficiency, and also providing more potential binding sites for subsequent D-glucosamine; on the other hand, the magnetic nanoparticles are small in size and can diffuse rapidly in the solution, reducing the mass transfer resistance and accelerating the binding speed. Moreover, the magnetic nanoparticles can be easily separated and recovered by an external magnetic field, without introducing impurity molecules into the original reaction solution, and also improving the subsequent separation and recovery efficiency, thereby simplifying the operation process and also improving the yield and purity of the reaction.

[0024] Preferably, the magnetic iron oxide is coated and modified with polyethyleneimine; the mass ratio of the magnetic iron oxide to polyethyleneimine is 1:(4-5).

[0025] Preferably, the coating and modification treatment includes the following steps: Disperse the magnetic iron oxide nanoparticles in water, add polyethyleneimine, stir to dissolve, raise the temperature to 55-65 °C, stir and react for 20-24 h, and finally obtain the product through centrifugation, washing, drying and grinding.

[0026] By adopting the above technical solution, since the activity of the amino groups on the surface of the magnetic iron oxide is not high, the binding force with 3-aminophenylboronic acid is not strong. Furthermore, after the combination of 3-aminophenylboronic acid and free D-glucosamine, the problem of easy shedding of the phenylboronic acid derivatives still occurs, resulting in the combination or complex of the two still entering the reaction solution containing N-acetylglucosamine, and it is not easy to separate. To solve this problem, the present invention conducts a coating and modification treatment on the magnetic iron oxide nanoparticles.

[0027] Specifically, polyethyleneimine is used to coat and modify magnetic iron oxide nanoparticles. Polyethyleneimine is a polymer rich in amino groups, which can provide a large number of positive charge centers, making the surface of the coated and modified magnetic iron oxide nanoparticles expose more active free amino groups. These amino groups can be used as connection points to covalently bind 3-aminophenylboronic acid, improving the binding force of phenylboronic acid derivatives on the carrier, and can also adjust the surface charge properties of the material, better improving the selectivity of the specific fixative; a densely distributed phenylboronic acid derivative layer is formed on the surface of the magnetic nanoparticles, which can increase the specific binding sites with free D-glucosamine, so the binding efficiency and quantity are greatly increased, effectively improving the removal efficiency.

[0028] Moreover, polyethyleneimine has a certain flexibility and tunability, which can improve the effective utilization rate of 3-aminophenylboronic acid molecules, enhance the binding force with the target molecule, namely D-glucosamine, and ensure a more stable binding; and after being modified by polyethyleneimine, the magnetic nanoparticles can show better dispersibility and stability, are not easy to agglomerate, and are more conducive to reducing the mass transfer resistance, approaching and capturing more D-glucosamine molecules, thereby improving the yield and purity of the product.

[0029] Advantages of the present invention:

[0030] 1. After the synthesis of N-acetylglucosamine, the present invention is subjected to adsorption treatment with a specific fixative. The specific fixative is magnetic nanoparticles immobilized with phenylboronic acid derivatives, which can remove the unreacted D-glucosamine in the preparation process. The phenylboronic acid derivatives can recognize and bind D-glucosamine with cis-dihydroxy groups, and will not react with N-acetylglucosamine, effectively selectively removing D-glucosamine in N-acetylglucosamine; and after being immobilized on the magnetic nanoparticles, the selective adsorption reaction can be amplified, which is also beneficial for separation and removal, simplifying the operation steps.

[0031] 2. The magnetic nanoparticle raw material used in the specific fixative of the present invention has also been coated and modified with polyethyleneimine, which can improve the binding force with phenylboronic acid derivatives, increase the stability of the material, and can also improve the binding efficiency between phenylboronic acid derivatives and D-glucosamine. After being modified, the dispersibility and stability of the magnetic nanoparticles are also improved, which is more conducive to reducing the mass transfer resistance, and then more effectively removing free D-glucosamine, improving the yield and purity of N-acetylglucosamine. Specific embodiments

[0032] Next, in combination with the embodiments of the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts belong to the scope of protection of the present invention.

[0033] Preparation Example: Preparation Example 1, a specific fixative, is prepared according to the following method: Take 10 g of magnetic iron oxide nanoparticles (average particle size of 120 nm) and disperse them in deionized water. Adjust the reaction pH value to 7.5. Add 0.4 g of disuccinimidyl suberate under ice bath conditions and stir for 40 min. Then add 1.5 g of 3-aminophenylboronic acid at room temperature and stir for 2 h to obtain the product.

[0034] Preparation Example 2, a specific fixative, is different from Preparation Example 1 only in that the addition amount of 3-aminophenylboronic acid is 1 g.

[0035] Preparation Example 3, a specific fixative, is different from Preparation Example 1 only in that the addition amount of 3-aminophenylboronic acid is 2 g.

[0036] Preparation Example 4, a specific fixative, is different from Preparation Example 1 only in that the addition amount of 3-aminophenylboronic acid is 0.5 g.

[0037] Preparation Example 5, a specific fixative, is different from Preparation Example 1 only in that the addition amount of 3-aminophenylboronic acid is 3 g.

[0038] Preparation Example 6, a specific fixative, is prepared according to the following method: Take 10 g of magnetic iron oxide nanoparticles (average particle size of 120 nm) and disperse them in water. Add 40 g of polyethyleneimine and stir to dissolve. Raise the temperature to 60 °C and stir for 24 h. Finally, obtain the product through centrifugation, washing, drying, and grinding.

[0039] Take 10 g of the magnetic iron oxide nanoparticles coated with polyethyleneimine obtained above and disperse them in deionized water. Adjust the reaction pH value to 7.5. Add 0.4 g of disuccinimidyl suberate under ice bath conditions and stir for 40 min. Then add 1.5 g of 3-aminophenylboronic acid at room temperature and stir for 2 h to obtain the product.

[0040] Preparation Example 7, a specific fixative, is different from Preparation Example 6 only in that the addition amount of polyethyleneimine is 50 g.

[0041] Example: Example 1. A kind of N-acetylglucosamine is prepared according to the following technological steps: S1. Add 0.9 kg of sodium hydroxide to 13.5 kg of methanol. After mixing and dissolving, adjust the temperature to 15 °C, and add 4.5 kg of glucosamine hydrochloride. Stir and dissolve to obtain a pre-reaction solution. S2. Control the temperature of the pre-reaction solution at 25 °C, dropwise add 2.8 kg of acetic anhydride, stir and react for 4 h, and perform suction filtration to obtain a solid crude product. S3. Add the solid crude product to 15 kg of purified water for dissolution, add 0.045 kg of the specific fixing agent prepared in Preparation Example 1, stir and mix at room temperature for 3 h, then perform centrifugal separation. The obtained crude product aqueous solution is subjected to electrodialysis through bag filtration to obtain electrodialyzed fresh water. S4. Add 0.018 kg of activated carbon to the electrodialyzed fresh water, stir and decolorize at room temperature, and filter to obtain a filtrate. S5. Concentrate and crystallize the filtrate under reduced pressure at 65 °C, and finally obtain N-acetylglucosamine through suction filtration, rinsing, centrifugation and drying.

[0042] Example 2. A kind of N-acetylglucosamine, the difference from Example 1 is only that the addition amount of sodium hydroxide is 0.855 kg; the addition amount of acetic anhydride is 2.7 kg.

[0043] Example 3. A kind of N-acetylglucosamine, the difference from Example 1 is only that the addition amount of sodium hydroxide is 0.945 kg; the addition amount of acetic anhydride is 2.9 kg.

[0044] Example 4. A kind of N-acetylglucosamine, the difference from Example 1 is only that the addition amount of the specific fixing agent prepared in Preparation Example 1 is 0.027 kg.

[0045] Example 5. A kind of N-acetylglucosamine, the difference from Example 1 is only that the addition amount of the specific fixing agent prepared in Preparation Example 1 is 0.067 kg.

[0046] Example 6. A kind of N-acetylglucosamine, the difference from Example 1 is only that the specific fixing agent prepared in Preparation Example 1 is replaced with the same amount of the specific fixing agent prepared in Preparation Example 2.

[0047] Example 7. A kind of N-acetylglucosamine, the difference from Example 1 is only that the specific fixing agent prepared in Preparation Example 1 is replaced with the same amount of the specific fixing agent prepared in Preparation Example 3.

[0048] Example 8. A kind of N-acetylglucosamine, the difference from Example 1 is only that the specific fixing agent prepared in Preparation Example 1 is replaced with the same amount of the specific fixing agent prepared in Preparation Example 4.

[0049] Example 9. A N-acetylglucosamine, which is different from Example 1 only in that the specific fixative prepared in Preparation Example 5 is used to replace the specific fixative prepared in Preparation Example 1 in an equal amount.

[0050] Example 10. A N-acetylglucosamine, which is different from Example 1 only in that the specific fixative prepared in Preparation Example 6 is used to replace the specific fixative prepared in Preparation Example 1 in an equal amount.

[0051] Example 11. A N-acetylglucosamine, which is different from Example 1 only in that the specific fixative prepared in Preparation Example 7 is used to replace the specific fixative prepared in Preparation Example 1 in an equal amount.

[0052] Comparative Examples: Comparative Example 1. A N-acetylglucosamine, which is different from Example 1 only in that the addition amount of the specific fixative prepared in Preparation Example 1 is 0.01 kg.

[0053] Comparative Example 2. A N-acetylglucosamine, which is different from Example 1 only in that the addition amount of the specific fixative prepared in Preparation Example 1 is 0.09 kg.

[0054] Comparative Example 3. A N-acetylglucosamine, which is different from Example 1 only in that the specific fixative prepared in Preparation Example 1 is not added.

[0055] Comparative Example 4. A N-acetylglucosamine, which is different from Example 1 only in that 3-aminophenylboronic acid is used to replace the specific fixative prepared in Preparation Example 1 in an equal amount.

[0056] Performance Detection Test: Calculate the yields of the N-acetylglucosamine products in each example and comparative example; use HPLC (High Performance Liquid Chromatography) method to test the purities of the N-acetylglucosamine products obtained in the examples and comparative examples. The above test results are shown in Table 1: .

[0057] According to Table 1, in combination with Example 1, Example 8, and Example 9, it can be seen that the product yields and purities of Example 8 and Example 9 have both decreased. The reason is that the only difference between Example 8 and Example 9 compared to Example 1 is the adjustment of the content of 3-aminophenylboronic acid immobilized on the specific fixative. Specifically, in Example 8, the content of 3-aminophenylboronic acid is reduced, resulting in a decrease in the number of effective adsorption groups on the obtained specific fixative, which in turn affects the binding effect between the specific fixative and the residual free glucosamine in the system, leading to a decrease in the purity of the obtained product; in Example 9, the content of 3-aminophenylboronic acid is increased, and the number of active groups on the surface of the magnetic nanoparticles is limited. The binding of a large amount of phenylboronic acid derivatives to the magnetic nanoparticles will lead to a decrease in the binding force, and it will also affect the pore structure of the magnetic nanoparticles, resulting in an increase in the mass transfer resistance, which is instead not conducive to the adsorption and binding of free glucosamine.

[0058] In combination with Example 1 and Example 10, it can be seen that the product yields and purities of Example 10 are both increased compared to Example 1. The reason is that for the specific fixative in Example 10, the magnetic nanoparticles are coated with polyethyleneimine, which can better amplify the recognition and adsorption effect of phenylboronic acid derivatives on free glucosamine, and can also improve the binding force between 3-aminophenylboronic acid and the magnetic nanoparticles, thereby ensuring that during the purification process, the phenylboronic acid derivatives will not fall off and other problems occur, and can also adjust the charge properties on the surface of the specific fixative, better improving the selectivity of the specific fixative, and also increasing the specific binding sites with free D-glucosamine, greatly increasing the binding efficiency and quantity, and effectively improving the removal efficiency.

[0059] In combination with Example 1, Comparative Example 1 to Comparative Example 3, it can be seen that the product yields and purities of Comparative Example 1 to Comparative Example 3 are significantly decreased compared to Example 1. The reason is that the only difference between Comparative Example 1 to Comparative Example 3 compared to Example 1 is the adjustment of the addition amount of the specific fixative. Among them, in Comparative Example 1, the addition amount of the specific fixative is reduced. Correspondingly, it will lead to a decrease in the removal effect of free D-glucosamine in the system and a decrease in the binding and adsorption probability between the specific fixative, resulting in an increase in the influence of glucosamine on the product, and both the product yield and purity are decreased. In Comparative Example 3, no specific fixative is added, then the residual free glucosamine in the system will directly affect the crystallization process of N-acetylglucosamine, affecting both the yield and the product purity. In Comparative Example 2, the addition amount of the specific fixative is increased. Excessive addition will cause the nanoscale specific fixative to easily aggregate due to the mutual attraction between its own groups, which will instead increase the mass transfer resistance and adsorption effect of the specific fixative.

[0060] Combined with Example 1 and Comparative Example 4, it can be seen that the difference between Comparative Example 4 and Example 1 lies only in that the phenylboronic acid derivative is not immobilized on the magnetic nanoparticles. On the one hand, it will reduce the amplification effect of the magnetic nanoparticles on the recognition and adsorption of free glucosamine by the phenylboronic acid derivative, and the selective adsorption ability of the specific immobilizer will also decrease, resulting in a decrease in efficiency. On the other hand, without being immobilized on the magnetic nanoparticles, the phenylboronic acid derivative and the product after binding with free glucosamine are not easily separated and removed from the system, which is instead not conducive to the improvement of product purity.

[0061] It should be noted that in this article, relational terms such as first and second are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any actual relationship or order between these entities or operations. Moreover, the term "comprising", "including" or any other variant thereof is intended to cover non-exclusive inclusion, so that a process, method, article or device including a series of elements not only includes those elements, but also includes other elements not expressly listed, or further includes elements inherent to such process, method, article or device.

[0062] Although the embodiments of the present invention have been shown and described, for those of ordinary skill in the art, it can be understood that various changes, modifications, substitutions and variations can be made to these embodiments without departing from the principles and spirit of the present invention. The scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A production process of N-acetylglucosamine, characterized in that, It includes the following technological steps: S1. After mixing and dissolving methanol and sodium hydroxide, adjust the temperature to 10 - 20 °C, add glucosamine hydrochloride, and stir to dissolve to obtain a pre-reaction solution; S2. Control the temperature of the pre-reaction solution at 20 - 30 °C, dropwise add acetic anhydride, stir and react for 3 - 5 h, and perform suction filtration to obtain a solid crude product; S3. Add the solid crude product to purified water to dissolve, add a specific immobilizer, stir and mix at room temperature for 3 - 4 h, then perform centrifugal separation, and subject the obtained crude product aqueous solution to electrodialysis through bag filtration to obtain electrodialyzed fresh water; S4. Add activated carbon to the electrodialyzed fresh water, stir and decolorize at room temperature, and filter to obtain a filtrate; S5. Concentrate the filtrate under reduced pressure for crystallization, and finally obtain N-acetylglucosamine through suction filtration, rinsing, centrifugation and drying; The specific immobilizer is a magnetic nanoparticle-supported phenylboronic acid derivative.

2. The production process of N-acetylglucosamine according to claim 1, characterized in that, The raw materials of the specific immobilizer include magnetic iron oxide nanoparticles and 3-aminophenylboronic acid with a mass ratio of 1:(0.1 - 0.2).

3. The production process of N-acetylglucosamine according to claim 1, characterized in that, The specific immobilizer is prepared according to the following method: Disperse magnetic iron oxide nanoparticles in deionized water, adjust the reaction pH value to 7 - 8, add a crosslinking agent under ice bath conditions, stir and react for 30 - 60 min, then add 3-aminophenylboronic acid at room temperature, and stir and react for 2 - 3 h to obtain it.

4. The production process of N-acetylglucosamine according to claim 3, characterized in that, The crosslinking agent is a bifunctional NHS ester crosslinking agent; the addition amount of the crosslinking agent is 2 - 6% of the mass of the magnetic iron oxide nanoparticles.

5. The production process of N-acetylglucosamine according to claim 2, characterized in that, The magnetic iron oxide is subjected to a coating modification treatment with polyethyleneimine; the mass ratio of the magnetic iron oxide to polyethyleneimine is 1:(4 - 5).

6. The production process of N-acetylglucosamine according to claim 5, characterized in that, The coating modification treatment includes the following steps: Disperse magnetic iron oxide nanoparticles in water, add polyethyleneimine, stir to dissolve, raise the temperature to 55 - 65 °C, stir and react for 20 - 24 h, and finally obtain it through centrifugation, washing, drying and grinding.

7. The production process of N-acetylglucosamine according to claim 1, characterized in that, The mass ratio of glucosamine hydrochloride to acetic anhydride is 1:(0.6 - 0.65).

8. The production process of N-acetylglucosamine according to claim 1, characterized in that, The addition amount of the specific immobilizer is 0.6 - 1.5% of the mass of glucosamine hydrochloride.

9. The production process of N-acetylglucosamine according to claim 1, characterized in that, The addition amount of sodium hydroxide is 19 - 21% of the mass of glucosamine hydrochloride.

10. The production process of N-acetylglucosamine according to claim 1, characterized in that, The addition amount of activated carbon is 0.3 - 0.5% of the mass of glucosamine hydrochloride.