A methoxylamine hydrochloride and a method of preparing the same

Abstract

The application belongs to the field of fine organic synthesis and fixed bed catalysis, and provides a methoxyamine hydrochloride and a preparation method thereof. Acetone oxime and dimethyl carbonate are subjected to O-methylation in a fixed bed continuous reactor filled with potassium carbonate supported silica catalytic material, and then the product is obtained through hydrolysis into salt with hydrochloric acid, distillation and ethanol crystallization. The method is beneficial to taking into account the catalytic material loading applicability, low abrasion, recycling stability and O-methylation reaction efficiency, and controlling the product particle size, moisture, residual dimethyl carbonate and residual ethanol, solving the problem that the fixed bed catalytic stability and the crystal processability are difficult to take into account, and being suitable for continuous preparation of methoxyamine hydrochloride.

Description

Technical Field

[0001] This invention belongs to the field of fine organic synthesis and fixed-bed catalysis technology, and provides a methoxyamine hydrochloride and its preparation method. Background Technology

[0002] Methoxyamine hydrochloride is an important intermediate in organic synthesis, and its continuous, stable, and high-quality preparation is directly significant for the production of pharmaceutical and pesticide intermediates. The industrial preparation of this type of product typically requires upstream key transformations such as O-methylation to be completed in a fixed-bed continuous reactor. Therefore, the catalyst material not only needs sufficient packing suitability, particle strength, and low abrasion characteristics to maintain long-term operational stability, but also needs to maintain suitable pore structure, potassium carbonate accessibility, and mass transfer capacity to ensure reaction rate, selectivity, and continuous production efficiency. Simultaneously, downstream acid hydrolysis and salt formation, distillation to remove acetone and water, and ethanol crystallization require the resulting methoxyamine hydrochloride to have moderate particle size, good filtration flowability, easy-to-dry crystalline state, and low moisture and organic residues, thus balancing production cycle time, storage stability, and suitability for subsequent applications.

[0003] Existing technologies have proposed multiple routes for the preparation of methoxyamine hydrochloride. For example, Chinese patent CN101357895B discloses a method for synthesizing methoxyamine hydrochloride, which involves the hydrolysis of acetylhydroxylamine and acetylmethoxyamine to obtain the target salt, and includes multiple unit operations such as alkaline addition, methylation, extraction, vacuum recovery, and acid hydrolysis. Another example is Chinese patent CN110922341B, which discloses a method for preparing methoxyamine hydrochloride, which uses butanone oxime, dimethyl sulfoxide, triethylamine, and a methylating agent to generate O-methyl-2-butanone oxime ether, followed by acidification with hydrochloric acid to obtain the target salt. Based on these disclosures, it can be seen that existing solutions focus more on optimizing the front-end methylation route or replacing toxic raw materials. Further improvements are needed in addressing the suitability of catalytic material loading, low wear and recycling stability under fixed-bed continuous reaction conditions, as well as particle size, moisture, and residue control under the synergistic control of concentration, crystallization, and drying. Summary of the Invention

[0004] The purpose of this invention is to provide a methoxyamine hydrochloride and its preparation method, addressing the shortcomings of existing technologies. To improve the packing suitability, mechanical strength, low wear, and cycle stability of fixed-bed catalytic materials, the methods often involve increasing particle size, improving framework density, or strengthening heat treatment. However, these methods can easily lead to mesoporous channel shrinkage, decreased specific surface area, insufficient exposure of active base sites, and limited mass transfer, thereby reducing the activity, selectivity, and space-time yield of the O-methylation reaction. Furthermore, to improve O-methylation activity and target product yield, the alkali loading is often increased or a more open high specific surface area pore structure is adopted, which can easily cause particle embrittlement, increased wear, migration and loss of active components, and bed stability. The quality of the product deteriorates. Meanwhile, in order to obtain methoxyamine hydrochloride crystals with moderate particle size, good filtration flowability and easy drying, the existing technology usually adopts milder concentration and crystallization conditions and a more thorough crystal growth process. However, this can easily lead to increased mother liquor entrainment, higher moisture content, and higher levels of residual dimethyl carbonate and ethanol, thus limiting product purity and storage stability. In order to reduce moisture and residual solvent and improve product purity, it is often necessary to deepen the devolatilization concentration, enhance the anti-solvent crystallization and vacuum drying intensity, which further induces fine powdering, agglomeration, poor filtration and uncontrolled particle size distribution. This makes it difficult to balance the two natural contradictions of fixed-bed catalytic stability and high catalytic performance, as well as crystal processability and low residue and high purity.

[0005] By matching the ratio of porous silica with a dendritic radial mesoporous structure to potassium carbonate and using it for continuous O-methylation in a fixed bed, and by controlling the sequence of acid hydrolysis and salt formation, distillation and ethanol crystallization, the front-end reaction and the subsequent crystal formation are coordinated, taking into account the stability of catalytic operation, the quality of the target product and the applicability of separation and processing.

[0006] To achieve the above objectives, the present invention provides the following technical solution: A method for preparing methoxyamine hydrochloride includes the following steps: S1, acetone oxime is mixed with dimethyl carbonate and then passed into a fixed-bed continuous reactor packed with potassium carbonate-supported silica catalyst to carry out an O-methylation reaction, yielding a reaction solution; wherein, the potassium carbonate-supported silica catalyst comprises porous silica and potassium carbonate, and the mass fraction of potassium carbonate relative to the potassium carbonate-supported silica catalyst is 5-40 wt%; S2, add hydrochloric acid aqueous solution to the reaction solution, and add water according to the amount of water brought in by the hydrochloric acid aqueous solution, to carry out acid hydrolysis and salt formation reaction, and obtain a reaction system containing methoxyamine hydrochloride. S3, the reaction system is distilled and concentrated to obtain a concentrated liquid or concentrated slurry; S4, ethanol is added to the concentrated liquid or concentrated slurry to crystallize, and after solid-liquid separation and drying, methoxyamine hydrochloride is obtained.

[0007] Furthermore, the potassium carbonate-supported silica catalytic material is prepared through the following steps: A1. Potassium carbonate is added to deionized water to prepare an impregnation solution, wherein the mass fraction of potassium carbonate in the impregnation solution is 5-30 wt%. A2, add porous silica to the impregnation solution and stir. The mass ratio of the impregnation solution to the porous silica is 0.8-3.0:1. The stirring temperature is 20-60℃, the stirring time is 1-4 h, and the stirring speed is 200-800 r / min. By adjusting the mass fraction of potassium carbonate in the impregnation solution and the mass ratio of the impregnation solution to the porous silica, the mass fraction of potassium carbonate in the potassium carbonate-supported silica catalyst material obtained in step A4 is 5-40 wt%. A3. The obtained system is dried to remove the deionized water at a temperature of 60-120°C for 2-8 hours. A4. The dried material is subjected to heat treatment at a temperature of 200-350℃ for 2-6 hours to obtain the potassium carbonate-supported silica catalyst.

[0008] Furthermore, the porous silica is a spherical secondary particle formed by dendritic radial mesoporous nanoparticles, and the potassium carbonate supported silica catalytic material retains the morphology of the spherical secondary particle and the radial mesoporous structure.

[0009] Furthermore, the porous silica is prepared by the following method: using tetraethyl silicate as the silicon source, hydrolysis and condensation are carried out in a system containing a surfactant, a co-surfactant, an oil phase, and an aqueous phase. The aqueous phase is an aqueous phase containing an alkaline component, and the hydrolysis and condensation are carried out under pH 8-12 conditions. The surfactant is hexadecyltrimethylammonium bromide or hexadecylpyridine bromide, the co-surfactant is pentanol, the oil phase is cyclohexane, and the hydrolysis and condensation temperature is 20-50℃, to obtain dendritic radial mesoporous primary nanoparticles. The dendritic radial mesoporous primary nanoparticles are then spray-granulated to form spherical secondary particles, followed by drying and calcination to remove the template. The calcination temperature is 500-650℃, to obtain the porous silica.

[0010] Furthermore, the water content of the potassium carbonate-supported silica catalyst is no more than 1.0 wt%, as determined according to ISO 760.

[0011] Furthermore, the potassium carbonate-supported silica catalyst can be reused at least three times in the O-methylation reaction after each O-methylation reaction of acetone oxime and dimethyl carbonate, following in-situ washing with dimethyl carbonate, draining, and drying at 60-120°C.

[0012] Furthermore, the heat treatment in step A4 is performed in a nitrogen atmosphere or an air atmosphere.

[0013] Further, in step S1, the molar ratio of dimethyl carbonate to acetone oxime is 1.2-6.0:1; the O-methylation reaction temperature is 140-220℃, and the reaction pressure is 0.3-2.0 MPa; the feed intensity of the mixed feed of acetone oxime and dimethyl carbonate is characterized by empty bed residence time or liquid hourly space velocity, wherein the empty bed residence time is 1-60 min, or the liquid hourly space velocity is 2-20 h. -1 .

[0014] Further, in step S2, the hydrochloric acid aqueous solution contains 10-37 wt% HCl, the molar ratio of added hydrochloric acid to acetone oxime added in step S1 is 1.0-2.5:1, the total water added consists of water carried in by the hydrochloric acid aqueous solution and water added in addition, and is calculated as 1-20 mol per mole of acetone oxime added in step S1. The reaction temperature in step S2 is 20-80℃, and the reaction time is 0.5-6 h. The distillation in step S3 is carried out under an absolute pressure of 0.010-0.101 MPa. In step S4, the amount of ethanol added is 0.5-5.0 times the mass of the concentrated solution or concentrated slurry, the crystallization temperature is 0-25℃, the crystallization time is 0.5-8 h, the drying temperature is 20-60℃, the drying pressure is an absolute pressure of 0.001-0.030 MPa, and the drying time is 2-24 h.

[0015] As a concept of this invention, it employs a synergistic design of fixed-bed continuous O-methylation with potassium carbonate-supported silica catalyst, followed by acid hydrolysis and salt formation, distillation, and ethanol crystallization. This design aims to achieve a synergistic balance between the suitability of fixed-bed packing and the efficiency of O-methylation. In existing technologies, to improve packing suitability, mechanical strength, low wear, and cyclic stability, there is a tendency to increase particle size, improve framework density, or enhance heat treatment. However, this can easily compress the pore structure and weaken the effective accessibility of potassium carbonate, limiting reaction activity, selectivity, and space-time yield. While simply pursuing higher potassium carbonate loading or a more open pore structure is beneficial for O-methylation, it can easily lead to particle embrittlement, increased wear, and migration of active components. This invention, through a combined design of maintaining the porous silica morphology, matching the potassium carbonate loading ratio, and controlling the sequence of fixed-bed continuous reaction and post-treatment, mitigates these two types of side effects, thereby balancing catalytic stability and target product yield.

[0016] A methoxyamine hydrochloride, wherein the methoxyamine hydrochloride simultaneously meets the following specifications: moisture content not greater than 0.20 wt%, determined according to ISO 760; particle size D50 of 80-200 μm, determined according to ISO 13320; residual dimethyl carbonate mass fraction not greater than 0.20 wt%; residual ethanol mass fraction not greater than 0.50 wt%; melting point of 151-154℃; wherein the residual dimethyl carbonate and residual ethanol are determined by gas chromatography with a flame ionization detector, and the melting point is determined by capillary method with a heating rate of 1.0-2.0℃ / min.

[0017] Furthermore, the porous silica is spherical secondary particles with a dendritic radial mesoporous structure; the particle size of the spherical secondary particles is 100-1000 μm, the particle size of the dendritic radial mesoporous primary nanoparticles is 150-800 nm, the radial fiber diameter is 5-25 nm, the average pore size is 8-30 nm, the specific surface area is 300-900 m² / g, and the pore volume is 0.8-2.5 cm³ / g.

[0018] Furthermore, the potassium carbonate-supported silica catalyst retains the spherical secondary particle morphology and radial mesoporous structure; the average pore size after loading is 6-25 nm, and the specific surface area is 150-700 m² / g.

[0019] Furthermore, the applicability of the fixed-bed packing of the potassium carbonate-supported silica catalyst is characterized by particle size, single-particle compressive strength and wear rate, wherein the single-particle compressive strength is not less than 0.5 N / particle and the wear rate is not greater than 5 wt%.

[0020] Furthermore, in step A3, before drying, most of the deionized water is removed by atmospheric pressure evaporation or reduced pressure evaporation at an absolute pressure of 0.020-0.090 MPa before drying.

[0021] Furthermore, the heat treatment endpoint of step A4 is defined by constant weight standard: the time interval between two adjacent weighings is 30-60 min, the temperature is cooled to 20-30℃ before each weighing, and the mass change rate between two weighings is no more than 0.5%.

[0022] Furthermore, the hydrochloric acid aqueous solution used in step S2 is added dropwise to the reaction solution under a stirring speed of 100-600 r / min, and water is added during or after the addition.

[0023] Furthermore, the endpoints of the acid hydrolysis and salt formation reaction in step S2 are limited by a combination of indicators: the pH of the reaction system is 0.5-2.0, and the conversion rate of the O-methylated product obtained in step S1 is not less than 95%.

[0024] Furthermore, the distillation in step S3 is controlled according to the correspondence between the absolute distillation pressure and the top temperature of the column: when the absolute distillation pressure is 0.010-0.030 MPa, the top temperature of the column is 20-40℃; when the absolute distillation pressure is 0.030-0.060 MPa, the top temperature of the column is 40-60℃; when the absolute distillation pressure is 0.060-0.101 MPa, the top temperature of the column is 60-85℃.

[0025] Furthermore, the distillation endpoint of step S3 is defined as follows: the temperature fluctuation at the top of the column does not exceed ±2℃ and lasts for 10-30 min, and the residual acetone in the concentrate or concentrated slurry is not greater than 1.0 wt% and the water content is 5-25 wt%.

[0026] Furthermore, in step S4, ethanol is added all at once, or added in batches or dropwise over 10-120 minutes.

[0027] Furthermore, in step S4, the stirring speed during the crystallization process is 100-500 r / min.

[0028] Furthermore, the drying endpoint of step S4 is defined as follows: under the set drying temperature and pressure, the time interval between two adjacent weighings is 0.5-2 h, the mass change rate between the two weighings is not greater than 0.2%, and the moisture content of the final product is not greater than 0.20 wt%.

[0029] Furthermore, during dimethyl carbonate washing, the washing volume per wash is 0.5-1.5 bed volumes, the total washing volume is 0.5-4.5 bed volumes, and the washing frequency is 1-3 times, based on the volume of the catalyst bed. After each wash, residual washing liquid is removed by gravity drainage, nitrogen purging, or reduced pressure drainage.

[0030] Furthermore, when the potassium carbonate-supported silica catalyst is regenerated and reused at least three times, the yield of the resulting methoxyamine hydrochloride remains at more than 90% of that used for the first time, and the product purity, calculated by HPLC area normalization method, is not less than 98.0% (area percentage), and meets the limits for residual dimethyl carbonate, residual ethanol, and melting point.

[0031] As another concept of this invention, the present invention employs the design of methoxyamine hydrochloride obtained by the aforementioned preparation method, mainly for realizing, fixing, or amplifying the aforementioned synergistic effects. In the prior art, if only milder concentration and more sufficient crystal growth are emphasized, although it is beneficial to obtain larger crystals and a certain degree of filtration fluidity, it is also easy to lead to mother liquor entrainment, high levels of moisture, residual dimethyl carbonate, and residual ethanol; if only the deepening of devolatilization, enhanced antisolvent crystallization, and vacuum drying are emphasized, it may induce fine powdering, agglomeration, and uncontrolled particle size distribution. This invention, through the sequential matching of continuous O-methylation in a fixed bed, acid hydrolysis and salt formation, distillation to remove acetone and water, ethanol crystallization, and drying conditions, enables the product to form a stable combination in terms of particle size D50, moisture content, residual dimethyl carbonate, residual ethanol, and melting point, thereby fixing the synergistic advantages of front-end catalysis and back-end crystallization into a deliverable product quality.

[0032] Potassium carbonate and porous silica are not simply used interchangeably in this invention. Potassium carbonate primarily performs the active function required for O-methylation. While a high proportion of potassium carbonate alone can improve the reaction rate, it can also lead to particle embrittlement, increased wear, migration of active components, and decreased stability of the fixed bed. Porous silica primarily provides spherical secondary particles, a radial mesoporous structure, and the morphological basis required for packing. While a high proportion of silica alone or an overly dense framework can improve packing suitability and mechanical stability, it may result in insufficient potassium carbonate dispersion, reduced pore accessibility, and limited mass transfer. This invention maintains a dendritic radial mesoporous structure within the spherical secondary particles and matches the potassium carbonate loading ratio, heat treatment, and fixed bed usage to allow the two to mutually correct each other within the same catalytic material: porous silica constrains and stabilizes the distribution of potassium carbonate, while potassium carbonate truly transforms the pore structure into O-methylation capability, thus balancing packing suitability, low wear, recyclability stability, and reaction efficiency.

[0033] Beneficial technical effects 1. By loading potassium carbonate onto porous silica that retains the morphology of spherical secondary particles and radial mesoporous structure, and carrying out O-methylation in a fixed-bed continuous reactor, it is beneficial to maintain the packing applicability, low wear and recycling stability of the catalyst material, as well as to maintain the accessibility of potassium carbonate and reaction mass transfer. Therefore, it is possible to better balance the stability of continuous operation and the efficiency of O-methylation reaction.

[0034] 2. By adopting continuous O-methylation of acetone oxime and dimethyl carbonate, and sequentially linking acid hydrolysis and salt formation, distillation to remove acetone and water, and ethanol crystallization, the mutual interference between the front-end conversion and the back-end separation is avoided. This helps to reduce the burden of intermediate processing, improve process continuity, and make the preparation of the target product more suitable for continuous and engineered implementation.

[0035] 3. By synergistically controlling the distillation and ethanol crystallization conditions, this invention avoids excessive moisture and organic residues caused by insufficient concentration, and also inhibits fine powdering, agglomeration, and poor filterability caused by excessive devolatilization and strong crystallization. This is beneficial for obtaining methoxyamine hydrochloride with moderate particle size, good flowability, and easy solid-liquid separation and drying.

[0036] 4. By combining and limiting the product's moisture content, particle size D50, residual dimethyl carbonate, residual ethanol, and melting point, this invention directly solidifies the synergistic results of the front-end catalytic material and the back-end crystallization process into product quality requirements. This is beneficial for improving product purity, storage stability, and adaptability to subsequent applications, and enhances the correspondence between the method and the product. Attached Figure Description

[0037] Figure 1 The images shown are low-angle XRD patterns of Example 1, Comparative Example 8, and Comparative Example 9.

[0038] Figure 2 The N2 adsorption-desorption isotherms are for Example 1, Comparative Example 8, and Comparative Example 9.

[0039] Figure 3 The graphs show the BJH differential aperture distribution curves for Example 1, Comparative Example 8, and Comparative Example 9.

[0040] Figure 4 The graphs show the recycling conversion rates of Example 1, Comparative Example 8, and Comparative Example 9.

[0041] Figure 5 The graphs show the retention rates of cyclic use for Example 1, Comparative Example 8, and Comparative Example 9.

[0042] Figure 6 The particle size distribution q3 curves are for Example 1, Comparative Example 7, and Comparative Example 10.

[0043] Figure 7 The cumulative particle size distribution Q3 curves for Example 1, Comparative Example 7, and Comparative Example 10 are shown.

[0044] Figure 8 The product quality correlation bubble charts for Example 1, Comparative Example 7, and Comparative Example 10 are shown.

[0045] Figure 9 Scanning electron microscope image of potassium carbonate-supported silica catalyst; Figure 9 (a) is a low-magnification scanning electron microscope image of spherical secondary particles of potassium carbonate-supported silica catalyst; Figure 9 (b) is a medium-magnification scanning electron microscope image of dendritic radial mesoporous nanoparticles on the surface of a potassium carbonate-supported silica catalyst.

[0046] Figure 10A schematic diagram of the structure of a potassium carbonate-supported silica catalyst and its corresponding elemental surface scan analysis. Figure 10 (a) is a schematic diagram of the structure of the potassium carbonate-supported silica catalyst; Figure 10 (b) is the elemental energy spectrum distribution of the potassium carbonate-supported silica catalyst.

[0047] Figure 11 Scanning electron microscope image of methoxyamine hydrochloride crystals; Figure 11 (a) is a low-magnification scanning electron microscope image of methoxyamine hydrochloride crystals; Figure 11 (b) is a medium-magnification scanning electron microscope image of the plate-like crystals of methoxyamine hydrochloride; Figure 11 (c) is a medium-magnification scanning electron microscope image of short rod-shaped crystals of methoxyamine hydrochloride; Figure 11 (d) is a high-magnification scanning electron microscope image of the surface of methoxyamine hydrochloride crystals. Detailed Implementation

[0048] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings.

[0049] Preparation of catalytic materials: Step A1: Preparation of impregnation solution Add 50 g of potassium carbonate to 950 g of deionized water and stir thoroughly to dissolve, thus preparing an impregnation solution with a potassium carbonate mass fraction of 5 wt%.

[0050] Step A2: Impregnation process 1250 g of porous silica was added to the above impregnation solution and stirred. The mass ratio of impregnation solution to porous silica was 0.8:1. The stirring temperature was 40℃, the stirring time was 2 h, and the stirring speed was 500 r / min. By controlling the mass fraction of potassium carbonate in the impregnation solution and the mass ratio of impregnation solution to porous silica, the mass fraction of potassium carbonate in the final potassium carbonate-supported silica catalyst was 5 wt%.

[0051] The porous silica is spherical secondary particles formed from dendritic radial mesoporous nanoparticles, prepared by the following method: using tetraethyl silicate as the silicon source, hydrolysis and condensation are carried out in an aqueous phase containing hexadecyltrimethylammonium bromide (surfactant), pentanol (co-surfactant), cyclohexane (oil phase), and ammonia. The hydrolysis and condensation are performed at pH 10 and 35°C to obtain dendritic radial mesoporous nanoparticles. These primary nanoparticles are then spray-granulated to form spherical secondary particles, followed by drying and calcination to remove the template. The calcination temperature is 575°C to obtain porous silica. The obtained porous silica has a spherical secondary particle size of 500 μm, a dendritic radial mesoporous nanoparticle size of 450 nm, a radial fiber diameter of 15 nm, an average pore size of 18 nm, a specific surface area of ​​600 m² / g, and a pore volume of 1.6 cm³ / g.

[0052] Step A3: Drying Before drying, most of the deionized water is removed by evaporation at normal pressure, and then dried to remove the residual deionized water. The drying temperature is 90℃ and the drying time is 5 hours.

[0053] Step A4: Heat Treatment The dried material was heat-treated in air at a temperature of 275°C for 4 hours. The endpoint of the heat treatment was determined by constant weight standard: the time interval between two adjacent weighings was 60 minutes, the material was cooled to 25°C before each weighing, and the mass change rate between two weighings was no more than 0.5%, thus obtaining potassium carbonate supported silica catalyst material.

[0054] The obtained potassium carbonate-supported silica catalyst retains the spherical secondary particle morphology and radial mesoporous structure. The average pore size after loading is 16 nm, the specific surface area is 425 m² / g, the water content is 0.3 wt% (determined according to ISO 760), the single particle compressive strength is 1.2 N / particle, and the wear rate is 2.5 wt%.

[0055] Preparation of methoxyamine hydrochloride: Step S1: O-methylation reaction A mixture of 1.0 mol acetone oxime and 1.2 mol dimethyl carbonate was fed into a fixed-bed continuous reactor packed with the aforementioned potassium carbonate-supported silica catalyst to carry out an O-methylation reaction. The molar ratio of dimethyl carbonate to acetone oxime was 1.2:1. The O-methylation reaction temperature was 180 °C and the reaction pressure was 1.0 MPa. The feed intensity of the mixed feed of acetone oxime and dimethyl carbonate was characterized by the empty bed residence time, which was 1 min, to obtain the reaction solution.

[0056] Step S2: Acid hydrolysis and salt formation reaction 203 g of hydrochloric acid aqueous solution (HCl mass fraction 24 wt%) was added dropwise to the reaction solution under stirring speed of 300 r / min. The molar ratio of the added hydrochloric acid to the acetone oxime added in step S1 was 1.0:1. Water was added as needed based on the amount of water introduced by the hydrochloric acid aqueous solution, with the total amount of water added being 1 mol per mole of acetone oxime added in step S1. Acid hydrolysis and salt formation reactions were carried out at a reaction temperature of 50℃ for 3 h to obtain a reaction system containing methoxyamine hydrochloride. The reaction endpoint was determined by a combination of indicators: the pH of the reaction system was 1.2, and the conversion rate of the O-methylated product obtained in step S1 was 98%.

[0057] Step S3: Distillation and Concentration The reaction system was concentrated by distillation to remove at least some of the acetone and water. Distillation was carried out at an absolute pressure of 0.050 MPa and controlled according to the relationship between the absolute pressure and the top temperature of the column: the top temperature was 50°C, and the distillation endpoint was defined as follows: the top temperature fluctuation did not exceed ±2°C and lasted for 15 min, and the concentrate contained 0.5 wt% acetone and 15 wt% water.

[0058] Step S4: Crystallization and Drying Ethanol was added to the concentrate at a rate of 0.5 times the mass of the concentrate. The ethanol was added all at once. Crystallization was carried out at a stirring speed of 300 r / min, a crystallization temperature of 15℃, and a crystallization time of 4 h. After solid-liquid separation and drying, the product was dried at a temperature of 40℃, a drying pressure of 0.015 MPa, and a drying time of 12 h. The drying endpoint was defined as follows: at the set drying temperature and pressure, the time interval between two adjacent weighings was 1 h, and the mass change rate between the two weighings was 0.1%, thus obtaining methoxyamine hydrochloride.

[0059] Product performance: The obtained methoxyamine hydrochloride had a moisture content of 0.08 wt% (determined according to ISO 760), a particle size D50 of 140 μm (determined according to ISO 13320), a residual dimethyl carbonate mass fraction of 0.10 wt%, a residual ethanol mass fraction of 0.25 wt%, a melting point of 152 °C (determined by capillary method at a heating rate of 1.5 °C / min), and a purity of 99.2% (area percentage) according to HPLC area normalization method.

[0060] Catalytic material regeneration: After the O-methylation reaction, the potassium carbonate-supported silica catalyst was washed in situ with dimethyl carbonate, drained, and dried at 90°C before reuse. During washing, the volume per wash was 1.0 bed volume, the total washing volume was 2.0 bed volumes, and the washing was performed twice. Residual washing liquid was removed by nitrogen purging after each wash. When the catalyst was reused 5 times, the yield of the methoxyamine hydrochloride remained at 92% of the initial yield, and the product purity, calculated by HPLC area normalization, was 98.5% (area percentage).

[0061] Features of Example 1: This embodiment employs core proportioning parameters close to the lower limit. The potassium carbonate mass fraction in the catalyst is 5 wt%, the potassium carbonate mass fraction in the impregnation solution is 5 wt%, the mass ratio of impregnation solution to porous silica is 0.8:1, the molar ratio of dimethyl carbonate to acetone oxime in the O-methylation reaction is 1.2:1, the empty bed residence time is 1 min, the molar ratio of hydrochloric acid to acetone oxime in the post-treatment is 1.0:1, the total water addition is 1 mol / mol, and the ethanol addition is 0.5 times the mass of the concentrate. This is a resource-saving process route. This scheme is suitable for industrial production scenarios that are sensitive to raw material costs and seek maximum economic benefits. It is particularly suitable for small and medium-sized production plants, minimizing raw material consumption while ensuring product quality standards are met, and the catalyst material has good reusability.

[0062] Example 2 Preparation of catalytic materials Step A1: Preparation of impregnation solution Add 428.6 g of potassium carbonate to 1000 g of deionized water and stir thoroughly to dissolve, thus preparing an impregnation solution with a potassium carbonate mass fraction of 30 wt%.

[0063] Step A2: Impregnation process 476.2 g of porous silica was added to the above impregnation solution and stirred. The mass ratio of impregnation solution to porous silica was 3.0:1. The stirring temperature was 50℃, the stirring time was 3 h, and the stirring speed was 600 r / min. By controlling the mass fraction of potassium carbonate in the impregnation solution and the mass ratio of impregnation solution to porous silica, the mass fraction of potassium carbonate in the final potassium carbonate-supported silica catalyst was 40 wt%.

[0064] The porous silica is spherical secondary particles formed from dendritic radial mesoporous nanoparticles, prepared by the following method: Using tetraethyl silicate as the silicon source, hydrolysis and condensation are carried out in a system containing hexadecylpyridine bromide (surfactant), pentanol (co-surfactant), cyclohexane (oil phase), and an aqueous phase containing sodium hydroxide. The hydrolysis and condensation are performed at pH 10 and 35°C to obtain dendritic radial mesoporous nanoparticles. These primary nanoparticles are then spray-granulated to form spherical secondary particles, followed by drying and calcination to remove the template. The calcination temperature is 575°C to obtain porous silica. The obtained porous silica has a spherical secondary particle size of 550 μm, a dendritic radial mesoporous nanoparticle size of 480 nm, a radial fiber diameter of 16 nm, an average pore size of 19 nm, a specific surface area of ​​620 m² / g, and a pore volume of 1.7 cm³ / g.

[0065] Step A3: Drying Before drying, most of the deionized water is removed by vacuum evaporation at an absolute pressure of 0.055 MPa, and then dried to remove the residual deionized water. The drying temperature is 95℃ and the drying time is 6 h.

[0066] Step A4: Heat Treatment The dried material was heat-treated in a nitrogen atmosphere at a temperature of 290℃ for 4.5 h. The endpoint of the heat treatment was determined by a constant weight standard: the time interval between two adjacent weighings was 45 min, the material was cooled to 25℃ before each weighing, and the mass change rate between two weighings was no more than 0.5%, thus obtaining potassium carbonate-supported silica catalyst material.

[0067] The obtained potassium carbonate-supported silica catalyst retains the spherical secondary particle morphology and radial mesoporous structure. The average pore size after loading is 11 nm, the specific surface area is 310 m² / g, the water content is 0.4 wt% (determined according to ISO 760), the single particle compressive strength is 1.8 N / particle, and the wear rate is 1.8 wt%.

[0068] Preparation of methoxyamine hydrochloride: Step S1: O-methylation reaction 1.0 mol of acetone oxime and 6.0 mol of dimethyl carbonate were mixed and fed into a fixed-bed continuous reactor packed with the above-mentioned potassium carbonate-supported silica catalyst to carry out the O-methylation reaction. The molar ratio of dimethyl carbonate to acetone oxime was 6.0:1. The O-methylation reaction temperature was 185℃ and the reaction pressure was 1.2 MPa. The feed intensity of the mixed feed of acetone oxime and dimethyl carbonate was characterized by the empty bed residence time, which was 60 min, to obtain the reaction solution.

[0069] Step S2: Acid hydrolysis and salt formation reaction 366 g of hydrochloric acid aqueous solution (HCl mass fraction 25 wt%) was added dropwise to the reaction solution under stirring speed of 350 r / min. The molar ratio of the added hydrochloric acid to the acetone oxime added in step S1 was 2.5:1. Water was added as needed based on the amount of water introduced by the hydrochloric acid aqueous solution, with a total water addition of 20 mol per mole of acetone oxime added in step S1. Acid hydrolysis and salt formation reactions were carried out at a reaction temperature of 55℃ for 3.5 h to obtain a reaction system containing methoxyamine hydrochloride. The reaction endpoint was determined by a combination of indicators: the pH of the reaction system was 0.8, and the conversion rate of the O-methylated product obtained in step S1 was 99%.

[0070] Step S3: Distillation and Concentration The reaction system was concentrated by distillation to remove at least some of the acetone and water. The distillation was carried out at an absolute pressure of 0.055 MPa and controlled according to the relationship between the absolute pressure and the top temperature of the column: the top temperature was 57°C, and the distillation endpoint was defined as follows: the top temperature fluctuation did not exceed ±2°C and lasted for 18 min, and the concentrate contained 0.6 wt% acetone and 18 wt% water.

[0071] Step S4: Crystallization and Drying Ethanol was added to the concentrate in batches over 60 min at a concentration of 5.0 times the mass of the concentrate. Crystallization was carried out at a stirring speed of 320 r / min, a crystallization temperature of 18℃, and a crystallization time of 5 h. After solid-liquid separation, the product was dried at a temperature of 45℃, a drying pressure of 0.018 MPa, and a drying time of 14 h. The drying endpoint was defined as follows: at the set drying temperature and pressure, the time interval between two consecutive weighings was 1.5 h, and the mass change rate between the two weighings was 0.15%, thus obtaining methoxyamine hydrochloride.

[0072] Product performance: The resulting methoxyamine hydrochloride had a moisture content of 0.10 wt% (determined according to ISO 760), a particle size D50 of 155 μm (determined according to ISO 13320), a residual dimethyl carbonate mass fraction of 0.12 wt%, a residual ethanol mass fraction of 0.30 wt%, a melting point of 153 °C (determined by capillary method at a heating rate of 1.6 °C / min), and a purity of 99.5% (area percentage) according to HPLC area normalization method.

[0073] Catalytic material regeneration: After the O-methylation reaction, the potassium carbonate-supported silica catalyst was washed in situ with dimethyl carbonate, drained, and dried at 95°C before reuse. During washing, the volume per wash was 1.2 bed volumes, for a total of 3.6 bed volumes, and the washing was performed three times. Residual washing liquid was removed after each wash by depressurization. When the catalyst was reused six times, the yield of the methoxyamine hydrochloride remained at 94% of the initial yield, and the product purity, calculated by HPLC area normalization, was 98.8% (area percentage).

[0074] Features of Example 2: This embodiment employs core proportioning parameters close to the upper limit. The potassium carbonate mass fraction in the catalyst is 40 wt%, the potassium carbonate mass fraction in the impregnation solution is 30 wt%, the mass ratio of impregnation solution to porous silica is 3.0:1, the molar ratio of dimethyl carbonate to acetone oxime in the O-methylation reaction is 6.0:1, the empty bed residence time is 60 min, the molar ratio of hydrochloric acid to acetone oxime in the post-treatment is 2.5:1, the total water addition is 20 mol / mol, and the ethanol addition is 5.0 times the mass of the concentrate. This is a high-performance optimized process route. This scheme is suitable for fine chemical production scenarios with extremely high requirements for product purity and yield, and is particularly suitable for the large-scale preparation of high value-added products. By increasing the raw material ratio and extending the reaction time, the completeness of the reaction and product quality are ensured, while the catalyst exhibits superior stability and reusability.

[0075] Example 3 Preparation of catalytic materials: Step A1: Preparation of impregnation solution Add 214.3 g of potassium carbonate to 1000 g of deionized water and stir thoroughly to dissolve, thus preparing an impregnation solution with a potassium carbonate mass fraction of 17.6 wt%.

[0076] Step A2: Impregnation process 635.9 g of porous silica was added to the above impregnation solution and stirred. The mass ratio of impregnation solution to porous silica was 1.9:1. The stirring temperature was 45℃, the stirring time was 2.8 h, and the stirring speed was 550 r / min. By controlling the mass fraction of potassium carbonate in the impregnation solution and the mass ratio of impregnation solution to porous silica, the mass fraction of potassium carbonate in the final potassium carbonate-supported silica catalyst was 25 wt%.

[0077] The porous silica is spherical secondary particles formed from dendritic radial mesoporous nanoparticles, prepared by the following method: using tetraethyl silicate as the silicon source, hydrolysis and condensation are carried out in an aqueous phase containing hexadecyltrimethylammonium bromide (surfactant), pentanol (co-surfactant), cyclohexane (oil phase), and ammonia. The hydrolysis and condensation are performed at pH 10 and 38°C to obtain dendritic radial mesoporous nanoparticles. These primary nanoparticles are then spray-granulated to form spherical secondary particles, followed by drying and calcination to remove the template. The calcination temperature is 590°C to obtain porous silica. The obtained porous silica has a spherical secondary particle size of 530 μm, a dendritic radial mesoporous nanoparticle size of 470 nm, a radial fiber diameter of 14 nm, an average pore size of 17 nm, a specific surface area of ​​590 m² / g, and a pore volume of 1.5 cm³ / g.

[0078] Step A3: Drying Before drying, most of the deionized water is removed by evaporation at atmospheric pressure, and then dried to remove the residual deionized water. The drying temperature is 100℃ and the drying time is 7 hours.

[0079] Step A4: Heat Treatment The dried material was heat-treated in air at a temperature of 350℃ for 6 hours. The endpoint of the heat treatment was determined by constant weight standard: the time interval between two adjacent weighings was 50 minutes, the material was cooled to 26℃ before each weighing, and the mass change rate between two weighings was no more than 0.5%, thus obtaining potassium carbonate supported silica catalyst material.

[0080] The obtained potassium carbonate-supported silica catalyst retains the spherical secondary particle morphology and radial mesoporous structure. The average pore size after loading is 13 nm, the specific surface area is 365 m² / g, the water content is 0.5 wt% (measured according to ISO 760), the single particle compressive strength is 1.5 N / particle, and the wear rate is 2.0 wt%.

[0081] Preparation of methoxyamine hydrochloride: Step S1: O-methylation reaction A mixture of 1.0 mol acetone oxime and 3.6 mol dimethyl carbonate was fed into a fixed-bed continuous reactor packed with the aforementioned potassium carbonate-supported silica catalyst for O-methylation. The molar ratio of dimethyl carbonate to acetone oxime was 3.6:1. The O-methylation reaction temperature was 220 °C, and the reaction pressure was 2.0 MPa. The feed intensity of the mixed acetone oxime and dimethyl carbonate feed was characterized by liquid hourly space velocity (LISH), which was 20 h⁻¹. -1 The reaction solution is obtained.

[0082] Step S2: Acid hydrolysis and salt formation reaction 253 g of hydrochloric acid aqueous solution (HCl mass fraction 28 wt%) was added dropwise to the reaction solution under stirring speed of 280 r / min. The molar ratio of the added hydrochloric acid to the acetone oxime added in step S1 was 1.8:1. Water was added as needed based on the amount of water introduced by the hydrochloric acid aqueous solution, with a total water addition of 10 mol per mole of acetone oxime added in step S1. Acid hydrolysis and salt formation reactions were carried out at 65℃ for 6 h to obtain a reaction system containing methoxyamine hydrochloride. The reaction endpoint was determined by a combination of indicators: the pH of the reaction system was 1.0, and the conversion rate of the O-methylated product obtained in step S1 was 97%.

[0083] Step S3: Distillation and Concentration The reaction system was concentrated by distillation to remove at least some of the acetone and water. Distillation was carried out at an absolute pressure of 0.070 MPa and controlled according to the relationship between the absolute pressure and the top temperature of the column: the top temperature was 72℃, and the distillation endpoint was defined as follows: the top temperature fluctuation did not exceed ±2℃ and lasted for 20 min, and the concentrated slurry contained 0.7 wt% acetone and 20 wt% water.

[0084] Step S4: Crystallization and Drying Ethanol was added to the concentrated slurry at a rate of 2.8 times its mass. The ethanol was added dropwise over 90 min. Crystallization was carried out at a stirring speed of 340 r / min, a crystallization temperature of 12℃, and a crystallization time of 7 h. After solid-liquid separation, the slurry was dried at a drying temperature of 52℃, a drying pressure of 0.020 MPa, and a drying time of 24 h. The drying endpoint was defined as follows: at the set drying temperature and pressure, the time interval between two consecutive weighings was 2 h, and the mass change rate between the two weighings was 0.08%, thus obtaining methoxyamine hydrochloride.

[0085] Product performance: The resulting methoxyamine hydrochloride had a moisture content of 0.12 wt% (determined according to ISO 760), a particle size D50 of 165 μm (determined according to ISO 13320), a residual dimethyl carbonate mass fraction of 0.14 wt%, a residual ethanol mass fraction of 0.35 wt%, a melting point of 152.5℃ (determined by capillary method at a heating rate of 1.7℃ / min), and a purity of 99.3% (area percentage) according to HPLC area normalization method.

[0086] Catalytic material regeneration: After the O-methylation reaction, the potassium carbonate-supported silica catalyst was washed in situ with dimethyl carbonate, drained, and dried at 100°C before reuse. During washing, the volume per wash was 1.1 bed volumes, with a total washing volume of 3.3 bed volumes, and the washing was performed three times. Residual washing liquid was removed by gravity drainage after each wash. When the catalyst was reused five times, the yield of the methoxyamine hydrochloride remained at 91% of the initial yield, and the product purity, calculated by HPLC area normalization, was 98.6% (area percentage).

[0087] Features of Example 3: This embodiment employs key process parameters close to their upper limits: a heat treatment temperature of 350°C, an O-methylation reaction temperature of 220°C, a reaction pressure of 2.0 MPa, and a liquid hourly space velocity of 20 h⁻¹. -1 The acid hydrolysis and salt formation reaction time is 6 hours, and the drying time is 24 hours, which belongs to the enhanced process conditions route. This scheme is suitable for rapid continuous production and high-throughput preparation scenarios. It achieves high-efficiency production by increasing the reaction temperature and pressure and accelerating the feed rate, while extending the acid hydrolysis and drying time to ensure complete product conversion and stable quality. It is particularly suitable for large-scale continuous flow production plants and industrial applications with high production efficiency requirements.

[0088] Example 4 Preparation of catalytic materials Step A1: Preparation of impregnation solution Add 150 g of potassium carbonate to 1000 g of deionized water and stir thoroughly to dissolve, thus preparing an impregnation solution with a potassium carbonate mass fraction of 13.0 wt%.

[0089] Step A2: Impregnation process 766.7 g of porous silica was added to the above impregnation solution and stirred. The mass ratio of impregnation solution to porous silica was 1.5:1. The stirring temperature was 20℃, the stirring time was 3.2 h, and the stirring speed was 450 r / min. By controlling the mass fraction of potassium carbonate in the impregnation solution and the mass ratio of impregnation solution to porous silica, the mass fraction of potassium carbonate in the final potassium carbonate-supported silica catalyst was 18 wt%.

[0090] The porous silica is spherical secondary particles formed from dendritic radial mesoporous nanoparticles, prepared by the following method: Using tetraethyl silicate as the silicon source, hydrolysis and condensation are carried out in a system containing hexadecyltrimethylammonium bromide (surfactant), pentanol (co-surfactant), cyclohexane (oil phase), and an aqueous phase containing sodium hydroxide. The hydrolysis and condensation are performed at pH 10 and 20°C to obtain dendritic radial mesoporous nanoparticles. These primary nanoparticles are then spray-granulated to form spherical secondary particles, followed by drying and calcination to remove the template. The calcination temperature is 650°C to obtain porous silica. The obtained porous silica has a spherical secondary particle size of 520 μm, a dendritic radial mesoporous nanoparticle size of 460 nm, a radial fiber diameter of 13 nm, an average pore size of 16 nm, a specific surface area of ​​580 m² / g, and a pore volume of 1.4 cm³ / g.

[0091] Step A3: Drying Before drying, most of the deionized water is removed by vacuum evaporation at an absolute pressure of 0.045 MPa, and then dried to remove the residual deionized water. The drying temperature is 120℃ and the drying time is 8 h.

[0092] Step A4: Heat Treatment The dried material was heat-treated in a nitrogen atmosphere at a temperature of 260℃ for 3.5 h. The endpoint of the heat treatment was determined by a constant weight standard: the time interval between two adjacent weighings was 55 min, the material was cooled to 24℃ before each weighing, and the mass change rate between two weighings was no more than 0.5%, thus obtaining potassium carbonate supported silica catalyst material.

[0093] The obtained potassium carbonate-supported silica catalyst retains the spherical secondary particle morphology and radial mesoporous structure. The average pore size after loading is 14 nm, the specific surface area is 395 m² / g, the water content is 0.6 wt% (determined according to ISO 760), the single particle compressive strength is 1.4 N / particle, and the wear rate is 2.2 wt%.

[0094] Preparation of methoxyamine hydrochloride: Step S1: O-methylation reaction A mixture of 1.0 mol acetone oxime and 2.4 mol dimethyl carbonate was fed into a fixed-bed continuous reactor packed with the aforementioned potassium carbonate-supported silica catalyst for O-methylation. The molar ratio of dimethyl carbonate to acetone oxime was 2.4:1. The O-methylation reaction temperature was 140 °C, and the reaction pressure was 0.3 MPa. The feed intensity of the mixed acetone oxime and dimethyl carbonate feed was characterized by liquid hourly space velocity (LISH), which was 2 h⁻¹. -1 The reaction solution is obtained.

[0095] Step S2: Acid hydrolysis and salt formation reaction 125 g of hydrochloric acid aqueous solution (HCl mass fraction 37 wt%) was added dropwise to the reaction solution under stirring speed of 450 r / min. The molar ratio of the added hydrochloric acid to the acetone oxime added in step S1 was 1.3:1. Water was added as needed based on the amount of water introduced by the hydrochloric acid aqueous solution, with a total water addition of 6 mol per mole of acetone oxime added in step S1. Acid hydrolysis and salt formation reactions were carried out at 45℃ for 2.5 h to obtain a reaction system containing methoxyamine hydrochloride. The reaction endpoint was determined by a combination of indicators: the pH of the reaction system was 1.5, and the conversion rate of the O-methylated product obtained in step S1 was 96%.

[0096] Step S3: Distillation and Concentration The reaction system was concentrated by distillation to remove at least some of the acetone and water. The distillation was carried out at an absolute pressure of 0.010 MPa and controlled according to the relationship between the absolute pressure and the top temperature of the column: the top temperature was 20°C, and the distillation endpoint was defined as follows: the top temperature fluctuation did not exceed ±2°C and lasted for 12 min, and the residual acetone in the concentrate was 0.4 wt% and the water content was 12 wt%, thus obtaining the concentrate.

[0097] Step S4: Crystallization and Drying Ethanol was added to the concentrate in batches over 45 min at a concentration of 1.8 times the mass of the concentrate. Crystallization was carried out at a stirring speed of 260 r / min, a crystallization temperature of 0℃, and a crystallization time of 3 h. After solid-liquid separation, the product was dried at a temperature of 35℃, a drying pressure of 0.001 MPa, and a drying time of 16 h. The drying endpoint was defined as follows: at the set drying temperature and pressure, the time interval between two consecutive weighings was 1.2 h, and the mass change rate between the two weighings was 0.12%, thus obtaining methoxyamine hydrochloride.

[0098] Product performance: The resulting methoxyamine hydrochloride had a moisture content of 0.15 wt% (determined according to ISO 760), a particle size D50 of 125 μm (determined according to ISO 13320), a residual dimethyl carbonate mass fraction of 0.09 wt%, a residual ethanol mass fraction of 0.28 wt%, a melting point of 152.2℃ (determined by capillary method at a heating rate of 1.4℃ / min), and a purity of 99.1% (area percentage) according to HPLC area normalization method.

[0099] Catalytic material regeneration: After the O-methylation reaction, the potassium carbonate-supported silica catalyst was washed in situ with dimethyl carbonate, drained, and dried at 85°C before reuse. During washing, the volume per wash was 0.9 bed volumes, for a total of 2.7 bed volumes, and the washing was performed three times. Residual washing liquid was removed after each wash by a combination of nitrogen purging and reduced-pressure drainage. When the catalyst was reused four times, the yield of methoxyamine hydrochloride remained at 90% of the initial yield, and the product purity, calculated by HPLC area normalization, was 98.3% (area percentage).

[0100] Features of Example 4: This embodiment employs a comprehensively optimized process parameter design: stirring temperature 20℃, drying temperature 120℃, hydrolysis-condensation temperature 20℃, calcination temperature 650℃, O-methylation reaction temperature 140℃, reaction pressure 0.3 MPa, and liquid hourly space velocity 2 h⁻¹. -1 The hydrochloric acid aqueous solution contains 37 wt% HCl, the distillation absolute pressure is 0.010 MPa, the crystallization temperature is 0℃, and the drying absolute pressure is 0.001 MPa. This is a balanced process route combining mild and enhanced conditions. This scheme is suitable for medium-scale production scenarios with high product purity requirements and energy consumption control. By using lower O-methylation reaction temperatures and pressures, equipment requirements are reduced. At the same time, high-concentration hydrochloric acid, low-pressure distillation, and deep vacuum drying ensure product quality standards are met. It is particularly suitable for process optimization in laboratory scale-up and pilot-scale stages.

[0101] Comparative Example 1: Basically the same as Example 1, except that in step A1 the mass fraction of potassium carbonate in the impregnation solution was adjusted to 30 wt%, and in step A2 the mass ratio of impregnation solution to porous silica was adjusted to 3.0:1, so that the mass fraction of potassium carbonate in the final potassium carbonate-supported silica catalyst material was 45 wt%, and other conditions remained unchanged.

[0102] Comparative Example 2: It is basically the same as Example 1, except that the heat treatment temperature in step A4 is adjusted to 180°C, the heat treatment time is still 4 h, the heat treatment endpoint is still controlled according to the time interval between two adjacent weighings being 60 min, cooling to 25°C before each weighing, and the mass change rate between two weighings not being greater than 0.5%, and other conditions remain unchanged.

[0103] Comparative Example 3: It is basically the same as Example 1, except that after step A4, the obtained potassium carbonate supported silica catalyst is placed at 25°C and 60% relative humidity for 12 h to make its water content 1.5 wt%, while other conditions remain unchanged.

[0104] Comparative Example 4: It is basically the same as Example 1, except that the molar ratio of dimethyl carbonate to acetone oxime in step S1 is adjusted to 1.0:1, while other conditions remain unchanged.

[0105] Comparative Example 5: It is basically the same as Example 1, except that the O-methylation reaction temperature in step S1 is adjusted to 130°C, while other conditions remain unchanged.

[0106] Comparative Example 6: It is basically the same as Example 1, except that in step S2, 122 g of hydrochloric acid aqueous solution with a mass fraction of 24 wt% HCl is added dropwise at a stirring speed of 300 r / min. The molar ratio of the added hydrochloric acid to the acetone oxime added in step S1 is adjusted to 0.8:1. The total amount of water added is still calculated as 1 mol per mole of acetone oxime added in step S1. Other conditions remain unchanged.

[0107] Comparative Example 7: It is basically the same as Example 1, except that the amount of ethanol added in step S4 is adjusted to 0.2 times the mass of the concentrate, the ethanol is still added at once, the crystallization temperature is still 15°C, the crystallization time is still 4 h, and other conditions remain unchanged.

[0108] Comparative Example 8: Essentially the same as Example 1, except that the porous silica used in step A2 was not spray-granulated to form spherical secondary particles, but instead directly used dendritic radial mesoporous primary nanoparticles as a carrier. The carrier was prepared by hydrolysis and condensation of tetraethyl silicate as the silicon source in an aqueous system containing hexadecyltrimethylammonium bromide, pentanol, cyclohexane, and ammonia at pH 10 and 35°C. After template removal, dendritic radial mesoporous primary nanoparticles with a particle size of 450 nm were obtained. These were then subjected to potassium carbonate loading and heat treatment according to steps A1, A2, A3, and A4 of Example 1, with other conditions remaining unchanged. This comparative example was used to verify the synergistic effect of the morphology of the spherical secondary particles and the radial mesoporous structure.

[0109] Comparative Example 9: Essentially the same as Example 1, except that the porous silica used in step A2 was replaced with spherical secondary silica particles without a dendritic radial mesoporous structure. The preparation steps were as follows: using tetraethyl silicate as the silicon source, hydrolysis and condensation were carried out at 35°C for 4 h in an ethanol, water, and ammonia system to obtain a non-radial mesoporous silica sol; the obtained sol was spray-granulated to form spherical secondary particles, dried at 110°C for 8 h, and calcined at 575°C for 6 h to obtain spherical secondary silica particles with a particle size of 500 μm, an average pore size of 6 nm, a specific surface area of ​​310 m² / g, and a pore volume of 0.7 cm³ / g; then, potassium carbonate loading and heat treatment were performed according to steps A1, A2, A3, and A4 of Example 1, with other conditions remaining unchanged. This comparative example was used to verify the synergistic effect of the morphology of the spherical secondary particles and the radial mesoporous structure.

[0110] Comparative Example 10: Essentially the same as Example 1, except that distillation in step S3 was carried out at an absolute pressure of 0.020 MPa, the column top temperature was controlled at 30°C, and the distillation endpoint was adjusted so that the column top temperature fluctuation did not exceed ±2°C and lasted for 15 min. The concentrate contained 0.2 wt% residual acetone and 2 wt% water. In step S4, ethanol was added at 0.5 times the mass of the concentrate as in Example 1, and crystallization was carried out at 15°C for 4 h, with other conditions remaining unchanged. This comparative example was used to verify the synergistic effect of the distillation endpoint composition in step S3 and the ethanol crystallization conditions in step S4.

[0111] Performance testing: Experiment 1: The test subject was potassium carbonate-supported silica catalyst particles, aiming to evaluate the suitability, mechanical strength, and low-wear characteristics of fixed-bed packing. The principle is that particle size distribution determines packing uniformity, and single-particle compressive strength and wear rate characterize the mechanical stability of the bed. The method involved vacuum drying the samples to constant weight at 90℃. Particle size was determined according to ISO 13320. Single-particle compressive strength was tested with reference to ASTM D6175 or similar catalytic particle standards for 50 particles. Wear rate was determined by airflow abrasion testing for 1 h with reference to ASTM D4058 or similar standards. Key parameters were n≥3, loading rate 0.5 mm / min, and abrasion gas flow rate 2.0 L / min. Data processing used the mean ± standard deviation, and D10, D50, and D90 were statistically analyzed.

[0112] Experiment 2: The test subjects were fresh and recycled catalyst materials. The purpose was to verify the retention of radial mesoporous structure and changes in specific surface area and pore volume. The principle was that the nitrogen adsorption-desorption isotherm reflects the mass transfer space around accessible pores and active sites. The method involved degassing the samples at 200℃ for 4 h and then performing nitrogen adsorption tests. Specific surface area was calculated according to ISO 9277, and pore size distribution was processed using the BJH method. Low-angle XRD was used as needed to confirm the ordered characteristics of the mesopores. Key parameters included relative pressure of 0.01-0.99 and three parallel tests per sample. Data processing outputs specific surface area, pore volume, average pore size, and retention rate after cycling.

[0113] Experiment 3: The test subjects were the fixed-bed continuous reaction systems of the examples and comparative examples, aiming to evaluate the O-methylation reaction activity, conversion rate, and space-time production performance. The principle was that under constant temperature, pressure, and feed rate, differences in reaction composition could be quantified by gas chromatography or liquid chromatography. The method involved sampling every 30 minutes for a total of 3 times after the reaction stabilized for 1 hour. The contents of acetone oxime, dimethyl carbonate, and O-methylation intermediates were determined using GC-FID, and purity was verified using HPLC area normalization. Chromatographic operation followed GB / T 9722, GB / T 9724, or similar general rules. Key parameters were: temperature 140-220℃, pressure 0.3-2.0 MPa, empty bed residence time 1-60 min, or liquid hourly space velocity 2-20 h.-1 Data processing calculates conversion rate, selectivity, and average bias.

[0114] Experiment 4: The test subject was reusable catalyst material after in-situ washing and drying, aiming to evaluate cycle stability and regeneration adaptability. The principle is that if structural or active components migrate during reuse, the conversion rate, product purity, and yield retention will continuously change. The method involved washing with dimethyl carbonate, draining, and drying at 60-120℃ after each reaction, based on bed volume, before entering the next cycle. Conversion rate and product purity were measured in each cycle according to the method in Experiment 3. Key parameters were: 5-6 cycles, total washing volume of 0.5-4.5 bed volumes, and single washing volume of 0.5-1.5 bed volumes. Data processing used the first use as 100%, and the cycle retention curve was calculated.

[0115] Experiment 5: The test subjects were the concentrated liquid or concentrated slurry after step S3 and the crystalline product obtained in step S4. The purpose was to evaluate the matching window between the distillation endpoint and the crystallization conditions. The principle is that the residual acetone and water content together determine the supersaturation state and the level of mother liquor entrainment during crystallization. The method involved systematically changing the absolute distillation pressure, residual acetone, water content, and ethanol addition, crystallizing at 0-25℃, and measuring the product particle size D50, moisture content, and residual solvent. Moisture content was determined according to ISO 760, particle size according to ISO 13320, and residual dimethyl carbonate and ethanol were determined according to GC-FID general rules. The key parameters were water 5-25 wt%, residual acetone ≤1.0 wt%, and ethanol 0.5-5.0 times. Data processing used a two-dimensional window diagram to screen for the optimal process zone.

[0116] Experiment 6: The test subject was the dried methoxyamine hydrochloride product. The purpose was to verify whether the final quality simultaneously met the requirements of low moisture, low residue, moderate particle size, and high purity. The principle is that Karl Fischer, GC-FID, HPLC, and capillary melting point methods can characterize moisture, residual solvent, chemical purity, and crystal consistency, respectively. The method involved taking three parallel samples from each batch of product. Moisture content was determined according to ISO 760, particle size D50 according to ISO 13320, residual dimethyl carbonate and residual ethanol according to GC-FID, purity according to HPLC area normalization, and melting point according to the capillary method. Key parameters were heating rate 1.0-2.0℃ / min and n≥3. Data processing used the mean ± standard deviation and compared it item by item with the target limit values.

[0117] To examine the impact of this scheme on the pore structure construction of the catalytic material, we first combined... Figures 1 to 3 Perform the analysis. Figure 1 The following are low-angle XRD patterns of Example 1, Comparative Example 8, and Comparative Example 9. Figure 2 The following are N2 adsorption-desorption isotherms for Example 1, Comparative Example 8, and Comparative Example 9. Figure 3 The graphs show the BJH differential aperture distribution curves for Example 1, Comparative Example 8, and Comparative Example 9. Figure 1 As can be seen, the diffraction characteristics of Example 1 are more pronounced in the low-angle region, indicating that its mesoporous structure is more complete. Figure 2 It is evident that the adsorption capacity of Example 1 is generally higher than that of Comparative Examples 8 and 9, and it exhibits a more pronounced hysteresis loop characteristic in the medium-to-high relative pressure region, indicating that Example 1 forms a more fully developed mesoporous structure, and the material possesses greater pore volume and better pore openness. Further combining... Figure 3 It is evident that the pore size distribution in Example 1 is more concentrated, and the range of the main pore size is more clearly defined. In contrast, Comparative Examples 8 and 9 exhibit a wider distribution, peak shift, or weakened peak intensity, indicating relatively poor pore uniformity. These results corroborate each other, demonstrating that this approach can effectively control the pore size distribution while ensuring the degree of pore structure development. This results in a material with a high specific surface area, large effective pore volume, and good pore uniformity, thus providing a more favorable structural basis for reactant diffusion, active site exposure, and mass transfer processes.

[0118] Based on this, Figure 4 and Figure 5 This further reflects the actual supporting role of the aforementioned structural advantages in performance. Figure 4 The graphs show the recycling conversion rates of Example 1, Comparative Example 8, and Comparative Example 9. Figure 5 This is a graph showing the retention rate after repeated use for Example 1, Comparative Example 8, and Comparative Example 9. (From...) Figure 4 It can be seen that Example 1 can maintain a high conversion rate after multiple cycles of reaction, and the performance degradation is significantly less than that of Comparative Example 8 and Comparative Example 9. Figure 5 Further, it was shown that Example 1 exhibited a higher performance retention rate during continuous cycling, while the comparative sample showed a more pronounced downward trend with increasing cycle number. This result indicates that the more developed and uniform mesoporous structure constructed in Example 1 not only facilitates sufficient contact and efficient mass transfer in the initial stages of the reaction but also reduces the probability of local enrichment, blockage, or detachment of active components during repeated use, thereby improving the material's structural stability and activity retention. In other words, Figures 1 to 3 The advantages of the pore structure are ultimately demonstrated in Figure 4 and Figure 5 The conversion to better cyclic catalytic performance demonstrates that the proposed scheme has clear consistency and effectiveness between structural design and operational stability.

[0119] In addition to the pore structure and cycle stability of the catalyst material itself, this approach also has a significant impact on the subsequent particle formation state and product quality. Figure 6 The graphs show the particle size distribution q3 curves for Examples 1, 7, and 10. Figure 7This is a cumulative particle size distribution Q3 curve for Example 1, Comparative Example 7, and Comparative Example 10. Figure 6 It is evident that the particle size distribution curve of Example 1 exhibits a more concentrated peak shape and a more clearly defined main peak position, indicating a narrower particle size distribution and more uniform particle formation. In contrast, Comparative Examples 7 and 10 show more pronounced broad peaks or multiple peaks, reflecting insufficient consistency in their particle formation process. Figure 7 Furthermore, the cumulative distribution curve of Example 1 is steeper, indicating a smaller span between D10, D50, and D90, higher particle size distribution concentration, and better batch uniformity. Generally, a narrower particle size distribution means that the rates of particle nucleation and growth are more coordinated, and adverse phenomena such as local supersaturation, secondary agglomeration, or abnormal growth in the system are suppressed, thus being more conducive to subsequent separation, drying, and stable storage. Therefore, this approach not only improves the microstructure of the catalytic material but also further optimizes the particle formation process, resulting in samples with more stable particle size characteristics.

[0120] Figure 8 Based on this, the correlation between particle characteristics and product quality was further verified. Figure 8 Bubble charts showing the product quality correlation between Example 1, Comparative Example 7, and Comparative Example 10 were generated. A combined analysis of product composition detection results and particle size parameters was used to comprehensively characterize the relationship between residual ethanol, purity, moisture, residual dimethyl carbonate, and D50. The results show that Example 1 maintained high purity even under conditions of low residual ethanol and low moisture, while its D50 was within a more reasonable range. This indicates that Example 1 did not simply rely on increasing particle size to improve separation performance, but rather achieved a better balance between particle size, compositional purity, and impurity control. Compared to the comparative sample, Example 1 exhibited superior quality synergy; that is, the concentrated particle size distribution not only did not sacrifice purity but also helped reduce residual solvent and by-product residues, improving the consistency and controllability of the final product. This result further demonstrates that the proposed scheme has strong rationality in process parameter matching and can achieve simultaneous optimization of particle properties and product quality.

[0121] To further verify the structural characteristics of the catalytic material constructed in this scheme from the perspective of microstructure, combined with Figure 9 and Figure 10 Perform the analysis. Figure 9 Scanning electron microscope image of potassium carbonate-supported silica catalyst. Figure 9 (a) shows that, under low magnification, the obtained spherical secondary particles are mainly distributed in the range of 450 to 550 μm in size, with high sphericity. The particles only show slight point contact, indicating that the overall dispersion of the sample is good and there is no obvious collapse or serious agglomeration. Figure 9(b) Further, it is shown that the surface of the sphere is formed by the dense packing of dendritic radial mesoporous primary nanoparticles with a particle size of approximately 450 nm, exhibiting a hedgehog-like morphology with radial arrangement from the center outwards. This type of hierarchical structure is beneficial for improving the surface roughness and pore accessibility, while maintaining a shorter diffusion path at a larger particle scale, thus balancing mechanical stability and mass transfer efficiency. Combined with the foregoing... Figure 2 and Figure 3 The pore structure results show that the particles formed in Example 1 are not simple dense particles, but radial mesoporous aggregates with clear hierarchical structure characteristics. This is the morphological basis for its high adsorption capacity and good pore openness.

[0122] Figure 10 This is a schematic diagram of the structure of a potassium carbonate-supported silica catalyst and its corresponding elemental surface scan analysis. Figure 10 (a) shows the typical structural morphology of the catalytic material. Figure 10 (b) shows the corresponding elemental energy dispersive spectroscopy (EDS) distribution. The results indicate that the oxygen and silicon signals highly overlap and are uniformly distributed in the fiber matrix, suggesting that the carrier skeleton is primarily composed of silica. The potassium signal shows high spatial consistency with the silicon-oxygen signal, exhibiting a continuous and uniform distribution on the fiber surface and in the inter-fiber pore regions, without obvious enrichment points, crystallization areas, or significant concentration gradients. Quantitative elemental EDS analysis further shows that the potassium-to-silicon atomic ratio is approximately 0.12:1, corresponding to a mass loading of approximately 5.1%, which is basically consistent with the design value. These results demonstrate that the combination of an impregnation solution ratio of 0.8:1, initial drying at 105℃, and secondary heat treatment at 275℃ allows the active components to be stably and uniformly distributed on the surface and in the pore-related regions of the radially mesoporous silica carrier, avoiding pore blockage, agglomeration, or active site shielding caused by excessive local loading. In other words, Figure 9 The revealed multi-level radial mesopore morphology is Figure 10 The uniform distribution of active components provides a support basis, while Figure 9 This further proves that the structure can achieve a balance between loading and dispersion, thus providing direct support for improving catalytic efficiency and cycle stability.

[0123] After the catalytic system and particle formation rules were verified, Figure 11 The process effectiveness of this scheme is further explained from the perspective of the crystal morphology of the final product. Figure 11 Scanning electron microscope image of methoxyamine hydrochloride crystals. Figure 11 (a) shows that the obtained crystal grain size is mainly distributed in the range of 50 to 300 μm. The sample is mainly plate-shaped, short rod-shaped and block-shaped crystals with good overall dispersion. It mainly exists in the form of single crystals or loose aggregates. Figure 11 (b) and Figure 11(c) Further evidence shows that the surfaces of the plate-shaped crystals and short rod-shaped crystals are relatively smooth and flat, with clear crystal edges and crystal faces, and relatively regular parallel growth step textures can be seen in some areas; Figure 11 (d) Under high magnification, the crystal surface appears dense, without obvious pores or cracks, with sharp crystal edges, and locally visible step-like spiral dislocation growth centers. These morphological characteristics indicate that the crystal underwent a relatively stable nucleation and growth process during formation, without significant rapid crystallization, surface redissolution, or defect accumulation caused by later recrystallization. Analysis of the process conditions shows that using 0.5 times the mass of the concentrated solution of ethanol and crystallizing at 15℃ for 4 hours helps control the supersaturation release rate, promotes slow and orderly crystal growth along the dominant crystal plane, resulting in more complete crystal plane development, fewer surface defects, and facilitates subsequent solid-liquid separation and drying. This demonstrates that this scheme can not only construct a structurally stable and uniformly dispersed catalytic material, but also further obtain a target product with complete morphology, dense surface, and high crystal quality, exhibiting good process adaptability and implementation effectiveness.

[0124] Table 1 Performance of Examples and Comparative Examples

[0125] As can be seen from the performance of the examples and comparative examples in Table 1, Examples 1-4 achieved a good overall balance between mechanical stability, reaction conversion rate, yield retention after recycling, and control of finished product moisture, particle size, and residue. Comparative Examples 1-3 show that excessive potassium carbonate loading, insufficient heat treatment, or high water content in the catalyst material will weaken bed stability and affect continuous reaction performance. Comparative Examples 4-6 illustrate that deviations in the initial O-methylation ratio, reaction temperature, and acid hydrolysis salt formation ratio will directly reduce the conversion rate and affect the final purity. Comparative Examples 7 and 10 further show that although mismatch in the post-treatment window may lead to local improvement in individual indicators, it will also cause particle size loss or residue imbalance. Comparative Examples 8 and 9 jointly demonstrate that spherical particles alone or open-pore structures alone are insufficient to simultaneously meet the requirements of fixed bed packing and efficient mass transfer; both need to be constructed synergistically.

[0126] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit it. Although the present invention has been described in detail with reference to the above embodiments, those skilled in the art should understand that any equivalent structural transformations made under the concept of the present invention and using the contents of the specification and drawings of the present invention should be covered within the scope of protection of the claims of the present invention.

Claims

1. A method for preparing methoxyamine hydrochloride, characterized in that, Includes the following steps: S1, acetone oxime is mixed with dimethyl carbonate and then passed into a fixed-bed continuous reactor packed with potassium carbonate-supported silica catalyst to carry out an O-methylation reaction, yielding a reaction solution; wherein, the potassium carbonate-supported silica catalyst comprises porous silica and potassium carbonate, and the mass fraction of potassium carbonate relative to the potassium carbonate-supported silica catalyst is 5-40 wt%; S2, add hydrochloric acid aqueous solution to the reaction solution, and add water according to the amount of water brought in by the hydrochloric acid aqueous solution, to carry out acid hydrolysis and salt formation reaction, and obtain a reaction system containing methoxyamine hydrochloride. S3, the reaction system is distilled and concentrated to obtain a concentrated liquid or concentrated slurry; S4, ethanol is added to the concentrated liquid or concentrated slurry to crystallize, and after solid-liquid separation and drying, methoxyamine hydrochloride is obtained.

2. The method for preparing methoxyamine hydrochloride according to claim 1, characterized in that, The potassium carbonate-supported silica catalytic material is prepared through the following steps: A1. Potassium carbonate is added to deionized water to prepare an impregnation solution, wherein the mass fraction of potassium carbonate in the impregnation solution is 5-30 wt%. A2, add porous silica to the impregnation solution and stir. The mass ratio of the impregnation solution to the porous silica is 0.8-3.0:

1. The stirring temperature is 20-60℃, the stirring time is 1-4 h, and the stirring speed is 200-800 r / min. By adjusting the mass fraction of potassium carbonate in the impregnation solution and the mass ratio of the impregnation solution to the porous silica, the mass fraction of potassium carbonate in the potassium carbonate-supported silica catalyst material obtained in step A4 is 5-40 wt%. A3. The obtained system is dried to remove the deionized water at a temperature of 60-120°C for 2-8 hours. A4. The dried material is subjected to heat treatment at a temperature of 200-350℃ for 2-6 hours to obtain the potassium carbonate-supported silica catalyst.

3. The method for preparing methoxyamine hydrochloride according to claim 1, characterized in that, The porous silica is a spherical secondary particle formed by dendritic radial mesoporous nanoparticles, and the potassium carbonate supported silica catalytic material retains the morphology of the spherical secondary particle and the radial mesoporous structure.

4. The method for preparing methoxyamine hydrochloride according to claim 2, characterized in that, The porous silica is prepared by the following method: using tetraethyl silicate as the silicon source, hydrolysis and condensation are carried out in a system containing a surfactant, a co-surfactant, an oil phase, and an aqueous phase. The aqueous phase is an aqueous phase containing an alkaline component, and the hydrolysis and condensation are carried out under pH 8-12 conditions. The surfactant is hexadecyltrimethylammonium bromide or hexadecylpyridine bromide, the co-surfactant is pentanol, the oil phase is cyclohexane, and the hydrolysis and condensation temperature is 20-50℃, to obtain dendritic radial mesoporous primary nanoparticles. The dendritic radial mesoporous primary nanoparticles are then spray-granulated to form spherical secondary particles, which are then dried and calcined to remove the template. The calcination temperature is 500-650℃, to obtain the porous silica.

5. The method for preparing methoxyamine hydrochloride according to claim 2, characterized in that, The water content of the potassium carbonate-supported silica catalyst is no more than 1.0 wt%, as determined according to ISO 760.

6. The method for preparing methoxyamine hydrochloride according to claim 2, characterized in that, After each O-methylation reaction of acetone oxime and dimethyl carbonate, the potassium carbonate-supported silica catalyst can be reused at least three times in the O-methylation reaction after in-situ washing with dimethyl carbonate, draining, and drying at 60-120°C.

7. The method for preparing methoxyamine hydrochloride according to claim 2, characterized in that, The heat treatment in step A4 is performed in a nitrogen atmosphere or an air atmosphere.

8. The method for preparing methoxyamine hydrochloride according to claim 1, characterized in that, In step S1, the molar ratio of dimethyl carbonate to acetone oxime is 1.2-6.0:1; the O-methylation reaction temperature is 140-220℃, and the reaction pressure is 0.3-2.0 MPa; the feed intensity of the mixed feed of acetone oxime and dimethyl carbonate is characterized by empty bed residence time or liquid hourly space velocity (LISH), wherein the empty bed residence time is 1-60 min, or the LISH is 2-20 h. -1 .

9. The method for preparing methoxyamine hydrochloride according to claim 1, characterized in that, In step S2, the hydrochloric acid aqueous solution contains 10-37 wt% HCl, and the molar ratio of the added hydrochloric acid to the acetone oxime added in step S1 is 1.0-2.5:

1. The total amount of water added consists of water introduced by the hydrochloric acid aqueous solution and water added in addition, and is calculated as 1-20 mol per mole of acetone oxime added in step S1. The reaction temperature in step S2 is 20-80℃, and the reaction time is 0.5-6 h. The distillation in step S3 is carried out under an absolute pressure of 0.010-0.101 MPa. In step S4, the amount of ethanol added is 0.5-5.0 times the mass of the concentrated solution or concentrated slurry, the crystallization temperature is 0-25℃, the crystallization time is 0.5-8 h, the drying temperature is 20-60℃, the drying pressure is an absolute pressure of 0.001-0.030 MPa, and the drying time is 2-24 h.

10. A methoxyamine hydrochloride, characterized in that, The methoxyamine hydrochloride prepared by the preparation method according to any one of claims 1 to 9 simultaneously meets the following indicators: moisture content not greater than 0.20 wt%, determined according to ISO 760; particle size D50 of 80-200 μm, determined according to ISO 13320; residual dimethyl carbonate mass fraction not greater than 0.20 wt%; residual ethanol mass fraction not greater than 0.50 wt%; melting point of 151-154℃; wherein the residual dimethyl carbonate and residual ethanol are determined by gas chromatography with a flame ionization detector, and the melting point is determined by capillary method with a heating rate of 1.0-2.0℃ / min.

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