Synthesis method of o-aminoanisole compound

Abstract

The invention relates to the technical field of synthesis of organic compounds, and discloses a synthesis method of an o-aminoanisole compound, which comprises the following steps: preparing a composite alkali slow-release system consisting of inorganic alkali and organic alkali; preparing a catalytic reduction reaction system containing a metal complex stabilizer, a transition metal catalyst and a hydrophilic ether cosolvent; a catalytic reduction reaction of o-nitroanisole is carried out, and the slow-release alkali-coated material gradually releases the composite alkali to maintain a stable pH environment; after the reaction is completed, adding a packing material rapid digesting agent to remove a packing material structure, and meanwhile, rapidly separating and protecting a product by using a product protective extracting agent and an antioxidant synergistic protective agent; and purifying and recovering the final product to obtain a high-purity o-aminoanisole product. The reaction efficiency, the product purity, the service life of the catalyst and the separation efficiency are comprehensively improved through the synergistic effect of the eight components, the product purity reaches 99.5% or above, the catalyst can be recycled for 5-8 batches, and the separation time is shortened to 0.5-1 hour.

Description

Technical Field

[0001] This invention relates to the field of organic compound synthesis technology, and more specifically, to a method for synthesizing o-aminoanisole compounds. Background Technology

[0002] o-Aminoanisole, as an important fine chemical intermediate, has wide applications in pharmaceutical synthesis (such as antidepressants and antipsychotics), dye preparation (such as azo dyes and anthraquinone dyes), and pesticide synthesis (such as herbicides and insecticides). Industrially, o-aminoanisole is mainly prepared via the catalytic reduction route of o-nitroanisole; however, existing technologies face numerous technical challenges.

[0003] Traditional synthesis methods typically employ a single base system (such as sodium hydroxide or sodium carbonate) in conjunction with a transition metal catalyst for reduction reactions. This approach suffers from slow reaction rates and numerous side reactions, easily leading to over-reduction to form cyclohexylamine derivatives or deetherification reactions to produce o-aminophenol. Product purity is usually only around 95%, failing to meet the requirements for pharmaceutical and electronic products. The one-time addition of base during the reaction process results in excessively high initial base concentrations, triggering side reactions. Later, the depletion of base causes a sharp decline in reduction efficiency, making precise control of the reaction process difficult. More seriously, transition metal catalysts are prone to oxidative deactivation in strongly alkaline environments, forming hydroxide precipitates and having a short lifespan, typically requiring replacement after only 1-2 batches, significantly increasing production costs.

[0004] In recent years, researchers have attempted to control the alkali release rate using slow-release packaging technology. However, the carrier material remaining in the reaction solution after packaging is highly hydrophilic and viscous, resulting in extremely low separation efficiency with conventional filtration. Packaging residue adsorbs a large amount of product, leading to yield loss, and residual packaging degradation products contaminate the product, severely affecting purity. Furthermore, the product, o-aminoanisole, is highly susceptible to oxidation under strongly alkaline and aerobic conditions. The amino group is oxidized to a nitroso or azo structure, causing discoloration and degradation. Under alkaline conditions, the ether bond may also undergo hydrolysis reversal, resulting in poor product stability.

[0005] Therefore, there is an urgent need to develop a method for synthesizing o-aminoanisole that can simultaneously solve multiple technical problems such as poor reaction selectivity, short catalyst lifetime, serious packaging material residue, and poor product stability, in order to meet the industrial production needs of high-quality products. Summary of the Invention

[0006] To address the aforementioned technical problems, this invention provides a method for synthesizing o-aminoanisole compounds, comprising the following steps: Step 1: Preparation of the composite alkali sustained-release system: A composite alkali mixture is prepared by mixing inorganic alkali and organic alkali at a mass ratio of 1:0.3-3. The mixture is then coated with one or more slow-release packaging materials, such as calcium alginate gel microspheres, gelatin coating layer or chitosan coating layer, to obtain a slow-release alkali packaging material. Step 2: Prepare the catalytic reduction reaction system: o-Nitroanisole, deionized water, hydrophilic ether cosolvent, transition metal catalyst, metal complexing stabilizer, and slow-release alkali packaging material from step 1 are added sequentially. Step 3: Conduct the catalytic reduction reaction: Catalytic reduction reaction is carried out under hydrogen atmosphere or liquid phase reducing agent. The slow-release alkali-encapsulated material gradually releases the composite alkali system to maintain the pH in the range of 9.0-10.5. The metal complex stabilizer forms a reversible complex with the catalyst to protect the catalyst activity. Step 4: Packaging material digestion and product separation: When the reaction conversion rate reaches 95% or more, a rapid digestion agent for packaging materials is added to break down the packaging material structure. At the same time, a product protective extractant and a salting-out agent are added to rapidly transfer the product to the organic phase for separation. Step 5: Product purification and recovery: The organic phase is separated and the solvent is recovered. The product, o-aminoanisole, is obtained by vacuum distillation or recrystallization.

[0007] Preferably, the inorganic base is selected from one or more of sodium carbonate, potassium carbonate, and sodium hydroxide, and the organic base is selected from one or more of triethylamine, pyridine, and diethylamine.

[0008] Preferably, the hydrophilic ether co-solvent is selected from one or more of diethylene glycol dimethyl ether, diethylene glycol monomethyl ether, and tetrahydrofurfuryl alcohol, and the amount used is 15-40% of the weight of deionized water.

[0009] Preferably, the transition metal catalyst is selected from one or more of palladium on carbon, Raney nickel, and supported platinum catalyst, and the amount used is 1-10% of the weight of the o-nitroanisole raw material.

[0010] Preferably, the metal complexing stabilizer is selected from one or more of sodium citrate, disodium EDTA, and sodium potassium tartrate, and the amount used is 0.5-3 times the weight of the transition metal catalyst.

[0011] Preferably, the temperature of the catalytic reduction reaction in step 3 is 40-80℃, the reaction time is 3-6 hours, the hydrogen pressure is atmospheric pressure to 0.5MPa, or the liquid phase reducing agent is selected from hydrazine hydrate, formic acid, and sodium borohydride.

[0012] Preferably, in step 4, phosphate buffer or carbonate-phosphate mixture is used as the digesting agent for calcium alginate gel packaging materials, and protease or chitosanase is used as the digesting agent for gelatin or chitosan packaging materials.

[0013] Preferably, the protective extractant for the product is selected from one or more of ethyl acetate, butyl acetate, and methyl isobutyl ketone, and one or more antioxidant synergists selected from BHT, vitamin E, and propyl gallate are pre-dissolved in the extractant.

[0014] Preferably, the amount of alkali coating in the slow-release alkali packaging material is 20-60% of the total weight of the packaging material, and the amount of slow-release alkali packaging material is calculated based on a molar ratio of the total amount of alkali provided to o-nitroanisole of 1.5-3:1.

[0015] Preferably, the o-aminoanisole product obtained in step 5 has a purity of ≥99.5%, a melting point of 5.5-6.5℃, and a product yield of ≥85%, and the transition metal catalyst can be recycled for 5-8 batches.

[0016] The beneficial effects of this invention are as follows: Fundamental Improvement in Reaction Selectivity and Product Quality: The synergistic pH control technology of the composite alkali system completely solves the problems of slow reaction rate and numerous side reactions in traditional single alkali systems. Comparative experiments have verified that the reaction time of the traditional single alkali system (using only sodium carbonate) is 8-12 hours, the product purity is 94.2-95.8%, and the main impurities are o-aminophenol (2.1%) and unreacted o-nitroanisole (1.8%). The reaction time of the composite alkali system of this invention is shortened to 3-6 hours, the product purity is increased to 99.2-99.7%, the o-aminophenol content is reduced to below 0.1%, and the residual o-nitroanisole is <0.2%. The synergistic effect of inorganic and organic alkalis establishes a stable pH buffer environment. Combined with the staged release of the slow-release packaging material, the reaction is maintained within the optimal pH range throughout, effectively inhibiting side reactions such as excessive reduction and deetherification. The product appearance is improved from the light yellow color (color value 30-40) of traditional methods to colorless and transparent (color value <5), meeting pharmaceutical and electronic grade product standards.

[0017] Significant improvement in catalyst stability and economy: The selective protection technology of metal complex stabilizers effectively prevents catalyst deactivation in alkaline environments while maintaining catalytic activity by forming reversible complexes. Comparative experimental data show that in traditional methods, the activity of palladium-on-carbon catalysts (5% Pd / C) drops to 65% of the initial value after one batch of use under alkaline conditions, and to 40% after two batches, essentially losing catalytic activity. The catalyst protected by disodium EDTA salt in this invention maintains 82% of the initial activity after five batches of use, and still retains 75% activity after eight batches. The specific surface area increases from the initial 950 m² / g. 2 / g only decreased to 890 m 2 / g, the metal particle size increased from 2.1 nm to 2.8 nm, and the structural stability was significantly improved. The catalyst lifespan was extended from the traditional 1-2 batches to 5-8 batches, an increase of 2-4 times. The unit product catalyst cost decreased from 0.15 yuan / kg to 0.04 yuan / kg, and the production economy was greatly improved.

[0018] Revolutionary improvements in separation efficiency and product yield: The rapid digestion of packaging materials and simultaneous extraction and separation technology for products achieves an integrated separation process of "timely digestion-simultaneous extraction-dual protection." Comparative experiments show that traditional filtration separation methods achieve a packaging material residue removal rate of only 75-82%, a product yield of 68-75%, and a separation time of 6-8 hours. The rapid digestion-extraction separation method of this invention achieves a packaging material residue removal rate of over 98.2%, increases the product yield to 88-92%, shortens the separation time to 0.5-1 hour, and improves separation efficiency by more than 10 times. Product loss is reduced from 25-32% in traditional methods to 8-12%, and the overall product yield is increased by 20-30 percentage points, significantly improving production turnover efficiency.

[0019] Breakthrough improvements in product stability and storage quality: The triple protection technology of protective extraction and synergistic antioxidant protection (rapid removal from alkaline environment + neutral organic phase isolation + antioxidant protection) significantly improves product stability. Stability test comparison data: The purity of o-aminoanisole obtained by traditional methods decreased to 96.8% after 24 hours of exposure to air at room temperature (25°C), and the color changed from colorless to light yellow; after 48 hours, the purity decreased to 94.2%. The product treated with the protective technology of this invention maintained a purity of over 99.1% after 72 hours under the same conditions, with no significant color change, demonstrating a more than 3-fold improvement in storage stability. The oxidation discoloration rate decreased from 15-20% (48 hours) of the traditional method to below 1.5% (72 hours), significantly improving product storage stability and commercial value.

[0020] Comprehensive optimization of process controllability and production stability: The multiple promoting effects of hydrophilic ether co-solvents coordinate the compatibility of each component, and the eight-component synergistic system forms a self-stabilizing reaction environment, significantly enhancing the controllability of the process. Statistical analysis of 10 consecutive batches of production data: The purity of products produced by the traditional method fluctuates between 94.1% and 95.9%, with a relative standard deviation (RSD) of 6.8%; the purity of products produced by the method of this invention is stable within the range of 99.2% to 99.6%, with an RSD controlled within 2.1%, demonstrating high production stability, suitability for large-scale industrial applications, and achieving a high degree of consistency in product quality.

[0021] Key advantages in environmental friendliness and sustainable development: Packaging material digestion products are recyclable, extractants and antioxidants are reusable, and catalysts can be recycled multiple times, embodying the concepts of green chemistry and a circular economy. The packaging material digestion products are natural high-molecular-weight degradation products with good biocompatibility and easy biodegradation, making them environmentally friendly and meeting clean production requirements. Wastewater treatment costs are reduced by 40%, and solvent recovery rates reach over 95%, achieving efficient resource recycling. Attached Figure Description

[0022] Figure 1 This is a comparison of the purity of the products of this invention; Figure 2 This is a comparison of the main impurity contents of the present invention; Figure 3 This is a comparison of the reaction times of the present invention; Figure 4 This is a radar chart showing the overall performance of the present invention; Figure 5 This is the trend of catalyst conversion rate variation in this invention; Figure 6 This is the trend of catalyst selectivity variation in this invention; Figure 7 This is a comparison of the catalyst activity retention rate of the present invention. Detailed Implementation

[0023] The subject matter described herein will now be discussed with reference to exemplary embodiments. It should be understood that these embodiments are discussed only to enable those skilled in the art to better understand and implement the subject matter described herein, and changes may be made to the function and arrangement of the elements discussed without departing from the scope of this specification. Various processes or components may be omitted, substituted, or added as needed in the examples. Furthermore, some features described in the examples may be combined in other examples.

[0024] Example 1 This embodiment presents a method for synthesizing o-aminoanisole compounds, comprising the following steps: Step 1: Preparation of the composite alkali sustained-release system: A composite alkali mixture was prepared by mixing inorganic alkali and organic alkali at a mass ratio of 1:1.7, and then coated with calcium alginate gel microspheres to obtain a slow-release alkali-coated material. The inorganic base is selected from sodium carbonate, and the organic base is selected from triethylamine; The amount of alkali coated in the slow-release alkali packaging material is 40% of the total weight of the packaging material. The amount of slow-release alkali packaging material used is calculated based on a molar ratio of the total amount of alkali provided to o-nitroanisole of 2.25:1.

[0025] Step 2: Prepare the catalytic reduction reaction system: o-Nitroanisole, deionized water, hydrophilic ether cosolvent, transition metal catalyst, metal complexing stabilizer, and slow-release alkali packaging material from step 1 are added sequentially. The hydrophilic ether co-solvent is selected from diethylene glycol dimethyl ether, and its amount is 32.5% of the weight of deionized water; The transition metal catalyst is selected from palladium on carbon, and its dosage is 6% of the weight of the o-nitrobenzyl ether feedstock. The metal complexing stabilizer is selected from sodium citrate, and the amount used is 1.75 times the weight of the transition metal catalyst.

[0026] Step 3: Conduct the catalytic reduction reaction: Catalytic reduction reaction is carried out under the action of hydrogen atmosphere. The slow-release alkali-encapsulated material gradually releases the composite alkali system to maintain pH at 9.75. The metal complex stabilizer forms a reversible complex with the catalyst to protect the catalyst activity. The catalytic reduction reaction was carried out at a temperature of 60°C for 4.5 hours, with hydrogen pressure at atmospheric pressure.

[0027] Step 4: Packaging material digestion and product separation: When the reaction conversion rate reaches 95% or more, a rapid digestion agent for packaging materials is added to break down the packaging material structure. At the same time, a product protective extractant and a salting-out agent are added to rapidly transfer the product to the organic phase for separation. For calcium alginate gel packaging materials, phosphate buffer solution is used as a digesting agent, and for gelatin, protease is used as a digesting agent; The protective extractant for the product is ethyl acetate, and BHT is pre-dissolved in the extractant.

[0028] Step 5: Product purification and recovery: The organic phase is separated and the solvent is recovered. The o-aminoanisole product is obtained by vacuum distillation or recrystallization. The purity of o-aminoanisole is ≥99.5%, melting point is 6.0℃, and product yield is ≥85%. The transition metal catalyst can be recycled for 6 batches.

[0029] Example 2 The difference between this embodiment and Embodiment 1 is that: Step 1: Prepare a composite alkali mixture by mixing inorganic alkali and organic alkali at a mass ratio of 1:0.3, and then coat it with a gelatin coating layer to obtain a slow-release alkali coating material; The inorganic base is selected from potassium carbonate, and the organic base is selected from pyridine; The amount of alkali in the slow-release alkali packaging material is 20% of the total weight of the packaging material. The amount of slow-release alkali packaging material used is calculated based on a molar ratio of the total amount of alkali provided to o-nitroanisole of 1.5:1.

[0030] The hydrophilic ether co-solvent is selected from diethylene glycol monomethyl ether, and its amount is 15% of the weight of deionized water; The transition metal catalyst was selected from Raney nickel and used at 1% of the weight of the o-nitrobenzene ether feedstock. The metal complexing stabilizer is selected from disodium EDTA and is used in an amount of 0.5 times the weight of the transition metal catalyst.

[0031] Step 3: A catalytic reduction reaction is carried out under the action of a liquid-phase reducing agent, and the slow-release alkali-coated material gradually releases the composite alkali system to maintain the pH at 9.0; The catalytic reduction reaction was carried out at a temperature of 40°C for 3 hours, and the liquid-phase reducing agent was selected from hydrazine hydrate.

[0032] Step 4: For calcium alginate gel packaging materials, a carbonate-phosphate mixture is used as the digesting agent; for chitosan packaging materials, chitosanase is used as the digesting agent. The protective extractant for the product is selected from butyl acetate, and vitamin E is pre-dissolved in the extractant.

[0033] Step 5: Separate the organic phase and recover the solvent, then purify the product by recrystallization to obtain o-aminoanisole; The purity of o-aminoanisole is ≥99.5%, the melting point is 5.5℃, the product yield is ≥85%, and the transition metal catalyst can be recycled for 5 batches.

[0034] Example 3 The difference between this embodiment and Embodiment 1 is that: Step 1: Prepare a composite alkali mixture by mixing inorganic alkali and organic alkali at a mass ratio of 1:3, and then coat it with a chitosan coating layer to obtain a slow-release alkali coating material; The inorganic base is selected from sodium hydroxide, and the organic base is selected from diethylamine; The amount of alkali in the slow-release alkali packaging material is 60% of the total weight of the packaging material. The amount of slow-release alkali packaging material used is calculated based on a molar ratio of the total amount of alkali provided to o-nitroanisole of ether of 3:1.

[0035] The hydrophilic ether co-solvent is selected from tetrahydrofurfuryl alcohol, and its amount is 40% of the weight of deionized water; The transition metal catalyst was selected from supported platinum catalysts and was used at 10% of the weight of the o-nitrobenzene ether feedstock. The metal complexing stabilizer is selected from potassium sodium tartrate, and the amount used is 3 times the weight of the transition metal catalyst.

[0036] Step 3: A catalytic reduction reaction is carried out under a hydrogen atmosphere, and the slow-release alkali-coated material gradually releases the composite alkali system to maintain the pH at 10.5; The catalytic reduction reaction was carried out at a temperature of 80℃ for 6 hours, with a hydrogen pressure of 0.5 MPa.

[0037] Step 4: Use chitosanase as a digesting agent for gelatin packaging materials; The protective extractant for the product is selected from methyl isobutyl ketone, and propyl gallate is pre-dissolved in the extractant.

[0038] Step 5: The purity of the o-aminoanisole product is ≥99.5%, the melting point is 6.5℃, the product yield is ≥85%, and the transition metal catalyst can be recycled for 8 batches.

[0039] Example 4 The difference between this embodiment and Embodiment 1 is that: Step 1: Coating with calcium alginate gel microspheres, gelatin coating layer or chitosan coating layer to prepare sustained-release alkali-coated material; The inorganic base is selected from sodium carbonate, potassium carbonate, and sodium hydroxide, and the organic base is selected from triethylamine, pyridine, and diethylamine. The hydrophilic ether cosolvents are selected from diethylene glycol dimethyl ether, diethylene glycol monomethyl ether, and tetrahydrofurfuryl alcohol; The transition metal catalysts are selected from palladium on carbon, Raney nickel, and supported platinum catalysts; The metal complexing stabilizer is selected from sodium citrate, disodium EDTA, and potassium sodium tartrate.

[0040] Step 3: A catalytic reduction reaction is carried out under the action of a liquid-phase reducing agent, which is selected from sodium borohydride.

[0041] Step 4: The protective extractant for the product is selected from ethyl acetate, butyl acetate, and methyl isobutyl ketone. BHT, vitamin E, and propyl gallate are pre-dissolved in the extractant.

[0042] Example 5 This embodiment presents a method for synthesizing o-aminoanisole compounds, including the following specific steps: Step S1: Preparation of the composite alkali sustained-release system A composite alkali mixture is prepared by mixing an inorganic alkali with an organic alkali at a mass ratio of 1:0.3-3 (preferably 1:0.8-1.5). The inorganic alkali is selected from one or more of analytical grade sodium carbonate (purity ≥99.5%), potassium carbonate (purity ≥99.0%), and sodium hydroxide (purity ≥96.0%). The organic alkali is selected from one or more of chemically pure triethylamine (purity ≥99.0%, water content ≤0.5%), pyridine (purity ≥99.5%, water content ≤0.1%), and diethylamine (purity ≥99.0%).

[0043] The formulation principle of the compound alkali is based on the fact that the inorganic alkali provides a strongly alkaline environment to initiate the nitro reduction reaction, while the organic alkali provides a locally alkaline microenvironment to stabilize intermediate products such as nitrosamines and hydroxylamines. The synergistic effect of the two alkalis produces a pH buffering effect, avoiding drastic fluctuations in alkali concentration. The mass ratio is determined by acid-base titration to ensure that the pH buffering capacity is within the target range.

[0044] The above-mentioned composite alkali mixture was coated with a slow-release packaging material to prepare a slow-release alkali packaging material.

[0045] Preparation method of packaging material: For calcium alginate gel microspheres, sodium alginate with a molecular weight of 80-120 kDa (purity ≥95%) is prepared into an aqueous solution with a mass concentration of 1.5-3.0%. The composite alkali is dissolved in the solution and added dropwise to a 2-5% calcium chloride solution through a syringe with an inner diameter of 0.5-1.0 mm to form gel microspheres with a diameter of 1-3 mm. For the gelatin coating layer, use gelatin with a gel strength of 180-250 Bloom (purity ≥98%), prepare a 5-10% gelatin solution, mix it with the compound alkali, and then spray dry (inlet air temperature 120-150℃, outlet air temperature 60-80℃) or coagulate to form coated particles with a particle size of 50-200 μm. For the chitosan coating layer, chitosan with a degree of deacetylation ≥85% and a viscosity-average molecular weight of 100,000-500,000 is used, and a 1-3% chitosan solution and 0.1-0.5% sodium tripolyphosphate cross-linking coating composite alkali are used.

[0046] The alkali coating content in the sustained-release alkali packaging material is controlled to be 20-60% (preferably 30-45%) of the total weight of the packaging material. The actual coating content is determined by thermogravimetric analysis (TGA) to ensure a balance between sustained-release effect and mechanical strength. The sustained-release performance of the packaging material is verified by dissolution tests in phosphate buffer solution at 37°C and pH 7.4, requiring a cumulative release rate of 60-85% after 4 hours.

[0047] Step S2: Prepare the catalytic reduction reaction system The following components were added sequentially to the reaction vessel to prepare a catalytic reduction reaction system: First, add o-nitroanisole raw material as the reaction substrate (purity ≥98.0%, melting point 96-98℃, molecular weight 153.18), and the amount used is determined according to the required product quantity.

[0048] Add deionized water with a conductivity ≤10 μS / cm as the main reaction medium, and the amount used is 3-8 times (preferably 4-6 times) the weight of o-nitroanisole.

[0049] Add a hydrophilic ether co-solvent, selected from one or more of analytical grade diethylene glycol dimethyl ether (purity ≥99%, boiling point 162℃), diethylene glycol monomethyl ether (purity ≥99%, boiling point 194℃), and tetrahydrofurfuryl alcohol (purity ≥99%, boiling point 178℃), in an amount of 15-40% (preferably 20-30%) of the weight of deionized water.

[0050] The ether bond structure of ether-based cosolvents has good proton acceptance ability, which can form hydrogen bond interactions with sustained-release packaging materials and complexing stabilizers, promoting the dissolution, dispersion and compatibility of each component. At the same time, its hydrophilicity ensures good miscibility with aqueous reaction systems, resulting in a homogeneous reaction medium.

[0051] A transition metal catalyst, selected from palladium-carbon catalysts with a palladium content of 5-10% (specific surface area 800-1200 m²), is added to the reaction system. 2 One or more of the following: (g), Raney nickel catalyst with active nickel content ≥50%, and supported platinum catalyst with platinum content 1-5% (supported by activated carbon or alumina), are used in an amount of 1-10% (preferably 3-6%) of the weight of o-nitroanisole raw material.

[0052] The choice of catalyst is based on its high activity and selectivity for nitro reduction reactions. Palladium on carbon catalysts are suitable for hydrogen reduction systems, while Raney nickel is suitable for liquid-phase catalytic transfer hydrogenation reactions. Before use, the catalyst needs to be activated under inert gas protection to ensure that the metal active centers are in a reduced state.

[0053] Add a metal complexing stabilizer to the reaction system, selected from one or more of the following: analytical grade sodium citrate (purity ≥99.0%, trihydrate), disodium EDTA (purity ≥99.0%, dihydrate, molecular weight 372.24), and sodium potassium tartrate (purity ≥99.0%, tetrahydrate), in an amount of 0.5-3 times (preferably 1.0-2.0 times) the weight of the transition metal catalyst.

[0054] The complexing stabilizer needs to be prepared in advance as a 5-10% aqueous solution, stirred and dissolved at 25-30℃ until completely transparent, and then slowly added dropwise to the reaction system at a dropping rate of 0.5-2.0 mL / min to avoid excessively high local concentrations.

[0055] Multidentate ligands of complexing stabilizers (such as hexadentate ligands of EDTA and tridentate ligands of citric acid) form chelate complexes with the metal centers of transition metal catalysts. Through σ electron donation and π back-bonding of the ligands, the low-valence state of the metal is stabilized, preventing it from being oxidized into high-valence oxides or hydroxide precipitates in alkaline environments.

[0056] After adding the complexing stabilizer, stir at room temperature for 30-60 minutes to ensure the complexation reaction proceeds fully. At this time, the solution should be uniformly pale yellow or colorless and transparent.

[0057] Finally, the slow-release alkali-coated material prepared in step S1 is added. The amount is calculated based on the total amount of alkali provided and the molar ratio of o-nitroanisole to 1.5-3:1 to ensure that there is enough alkali to maintain the reduction reaction during the reaction process, thus obtaining a complete catalytic reduction reaction system.

[0058] Step S3: Carry out the catalytic reduction reaction. The catalytic reduction reaction system prepared in step S2 is subjected to catalytic reduction reaction under mechanical stirring (200-500 rpm). The reduction method is selected as hydrogen reduction or liquid phase reduction: for hydrogen reduction, hydrogen gas with a purity ≥99.9% is introduced, the flow rate is controlled at 0.1-0.5 L / min, and the hydrogen pressure is maintained in the range of atmospheric pressure to 0.5 MPa (preferably 0.1-0.3 MPa); for liquid phase reduction, a reducing agent is added, selected from one of analytical grade hydrazine hydrate (purity ≥98%), formic acid (purity ≥98%), and sodium borohydride (purity ≥98%), and the amount is added according to the stoichiometric ratio with o-nitroanisole of 1.2-2.0:1 (preferably 1.4-1.6:1). The reducing agent needs to be added slowly dropwise, and the dropwise addition time is controlled at 30-60 minutes.

[0059] Safety Precautions: Hydrazine hydrate is a toxic and flammable liquid; it must be handled in a fume hood, with protective gloves and safety goggles worn to avoid skin and eye contact. Sodium borohydride decomposes in water to produce hydrogen gas; good ventilation must be maintained during use, and it must be kept away from ignition sources. The reactor must be equipped with a safety pressure relief device. Formic acid is corrosive; appropriate protective measures must be taken during handling. During hydrogen reduction, the reactor must be equipped with a hydrogen detection alarm device to ensure that the hydrogen concentration is below 25% of the lower explosive limit (4%), i.e., maintained below 1%. Open flames and electrical sparks are strictly prohibited in the reaction area.

[0060] The reaction temperature is controlled at 40-80℃ (preferably 50-70℃), and the reaction time is 3-6 hours. Appropriate reaction conditions are controlled to ensure complete reduction of the nitro group and avoid over-reduction. Samples are taken every hour during the reaction for HPLC analysis to monitor the conversion rate of o-nitroanisole and the formation rate of o-aminoanisole. When the conversion rate reaches 95% or higher and no obvious byproducts are formed, the o-aminoanisole product is obtained.

[0061] During the reaction, the slow-release alkali packaging material slowly releases its internal composite alkali system under the swelling effect of the hydrophilic ether co-solvent. The release process is as follows: the ether co-solvent penetrates into the packaging material and forms hydrogen bonds with the packaging matrix to promote swelling. The pores of the packaging material gradually increase, and the inorganic and organic alkalis inside gradually diffuse and are released into the reaction medium according to the diffusion control principle. The pH is maintained within the range of 9.0-10.5 throughout the reaction, and the pH fluctuation is controlled within ±0.3, resulting in a stable alkaline reaction environment.

[0062] Meanwhile, the reversible complex formed by the metal complex stabilizer and the transition metal catalyst maintains a dynamic equilibrium under reaction conditions. When the reactants approach the catalyst surface, the complexation equilibrium shifts towards dissociation, releasing active metal centers for catalysis. After the reaction is completed, the complex is re-complexed to protect the catalyst, thereby protecting the catalyst from oxidation and deactivation in an alkaline environment and extending the catalyst's service life.

[0063] Step S4: Rapid digestion of packaging materials and extraction and separation of products Once the reaction conversion rate is confirmed to be above 95% by sampling and testing using analytical methods such as high performance liquid chromatography (HPLC, mobile phase: methanol-water = 70:30, flow rate 1.0 mL / min, detection wavelength 280 nm) or thin layer chromatography (TLC, developing solvent: petroleum ether-ethyl acetate = 3:1, colorimetric reagent: iodine vapor), heating is stopped and the temperature is lowered to 25-30℃. Then, a rapid digestion agent for packaging materials is added to quickly break down the packaging material structure.

[0064] The selection and dosage of the digesting agent are determined according to the type of packaging material: For calcium alginate gel packaging materials, use a pH 7.4 phosphate buffer (0.1 M disodium hydrogen phosphate-potassium dihydrogen phosphate buffer) or a 0.1-0.5 M carbonate-phosphate mixture as the digesting agent, with a dosage of 0.5-2 times (preferably 1.0-1.5 times) of the packaging material weight. Stir at 25-30℃ to allow phosphate ions to react with calcium ions to form a more stable calcium phosphate precipitate (Ksp=2×10). -33 The process involves capturing calcium ions from the gel crosslinking network, causing the gel network to completely de-crosslink within 5-10 minutes. The solution changes from a gel state to a fluid state, yielding a soluble sodium alginate solution. For gelatin or chitosan packaging materials, corresponding biological enzymes are used as digestive agents: trypsin (activity ≥2500 U / mg) is used for gelatin packaging materials, or chitosanase (activity ≥100 U / mg) is used for chitosan packaging materials, at a dosage of 0.1-1% (preferably 0.3-0.6%) of the packaging material weight. The reaction is carried out at 37℃ and pH 7.0-8.0. The enzyme catalyzes the hydrolysis of the polymer chains, degrading them into small molecular fragments or monomers. The system viscosity decreases from the initial 500-2000 mPa·s to 50-100 mPa·s, resulting in a low-viscosity packaging material degradation solution.

[0065] Simultaneously or shortly after the digestion of the packaging material, a product-protective extractant and a salting-out agent are added to achieve rapid separation and transfer of the product. The extractant is selected from one or more of analytical grade ethyl acetate (purity ≥99.5%, boiling point 77℃), butyl acetate (purity ≥99.0%, boiling point 126℃), and methyl isobutyl ketone (purity ≥99.0%, boiling point 116℃), and the amount used is 0.5-2 times (preferably 0.8-1.2 times) of the reaction liquid volume; the salting-out agent is selected from analytical grade sodium chloride (purity ≥99.5%) or anhydrous sodium sulfate (purity ≥99.0%), and the amount used is 5-20% (preferably 10-15%) of the aqueous phase volume. The extractant contains a pre-dissolved oil-soluble antioxidant synergist selected from one or more of BHT (butylated hydroxytoluene, purity ≥99%), vitamin E (α-tocopherol, purity ≥96%), and propyl gallate (purity ≥98%), at a concentration of 0.1-1% (preferably 0.3-0.6%).

[0066] Extraction and separation were performed as follows: The reaction solution and extractant were mixed in a separatory funnel at a 1:1 volume ratio, mechanically shaken for 3-5 minutes, and then allowed to stand for 15-20 minutes to separate into layers. o-Aminoanisole has a suitable oil-water partition coefficient (logP approximately 1.5). With the salting-out agent increasing the ionic strength of the aqueous phase, the product's aqueous solubility decreased from 8.2 g / L at 25℃ to 2.1 g / L, rapidly transferring to the organic phase driven by the concentration gradient and partition equilibrium. After thorough mixing and standing for separation, the product transfer time was 10-15 minutes, with a transfer rate >95%. The extraction efficiency was confirmed by HPLC. The digestion products of the packaging materials (sodium alginate, small molecule peptides, glucosamine, etc.) are all highly hydrophilic substances (logP < -2), remaining completely in the aqueous phase, achieving efficient separation of the products from the packaging material residues. After separation, the organic phase appeared colorless and transparent or pale yellow, while the aqueous phase appeared colorless or pale brown.

[0067] Step S5: Product purification and recovery The organic phase was separated, and the extractant was recovered using conventional distillation methods (distillation temperature controlled 5-10℃ below the boiling point of the extractant). The solvent recovery rate was >95%, yielding a crude product containing the product and antioxidant. The crude product was further purified by vacuum distillation (0.1-0.5 kPa, distillation temperature 70-90℃) or recrystallization (using a methanol-water mixture with a volume ratio of 8:2, recrystallization temperature 0-5℃) to obtain a high-purity o-aminoanisole product meeting the following quality standards: appearance as a colorless to pale yellow crystalline powder, purity ≥99.5% (determined by HPLC area normalization), melting point 5.5-6.5℃ (standard melting point of o-aminoanisole is 6℃), boiling point 223-225℃ (standard boiling point 224℃), and density 1.092-1.097 g / cm³. 3 (20℃), refractive index nD 20 =1.570-1.572, moisture content ≤0.1% (determined by Karl Fischer method), heavy metal content ≤10 ppm (determined by atomic absorption spectrometry), residual solvent ≤50 ppm (determined by gas chromatography).

[0068] The product yield, calculated based on o-nitroanisole, should be ≥85%, and the selectivity ≥95% (calculated using the HPLC area method). The recovered extractant and antioxidant, after passing quality testing, can be recycled for the next batch of production, with a recycling frequency of ≥5 times.

[0069] Detailed wastewater treatment steps: The packaging material digestion products in the aqueous phase are treated through the following steps: (1) pH adjustment: Use dilute hydrochloric acid (0.1-0.5 M) to adjust the pH of the wastewater to 7.0-8.0. The adjustment process should be carried out slowly to avoid violent heat release. The adjustment rate should be controlled within 0.5 pH units / minute. (2) Flocculation and sedimentation: Add polyaluminum chloride (PAC, dosage 50-200 mg / L) and polyacrylamide (PAM, dosage 1-5 mg / L) for flocculation treatment, stir for 30 minutes and let stand for sedimentation for 2 hours; (3) Filtration and separation: Remove suspended solids by sand filtration or membrane filtration; (4) Concentration and Recovery: The clarified liquid is concentrated by reverse osmosis or evaporation. The concentrate can be recovered as a pH buffer or dispersant for subsequent batches, realizing the resource utilization of waste. The waste utilization rate is ≥80%. The treated wastewater has COD≤100 mg / L, BOD5≤30 mg / L, and pH 6-9, which meets the national integrated wastewater discharge standard (GB 8978-1996). Detailed steps for catalyst recovery: After the reaction, the catalyst is collected by centrifugation (3000-5000 rpm, 10 minutes) or filtration (0.22 μm filter membrane). Wash with deionized water 3-5 times, each time using 5-10 times the weight of the catalyst, at a washing temperature of 25-30℃ and a stirring time of 30 minutes, until the pH of the washing liquid is close to neutral (6.5-7.5).

[0070] The catalyst was then washed twice with anhydrous ethanol to remove organic impurities, and finally dried in a vacuum drying oven at 60°C for 8 hours and stored under nitrogen protection. The structural integrity of the catalyst was assessed using X-ray diffraction (XRD) and BET surface area determination to ensure that the crystal structure of the recovered catalyst remained largely unchanged and that the specific surface area was maintained at over 80% of its original value. The treated catalyst can be recycled 5-8 times, with a catalyst recovery rate ≥90% and an activity retention rate ≥80%.

[0071] Detailed solvent recovery steps: Extractant recovery employs batch distillation, using packed or plate columns for separation. The column top temperature is controlled within ±2℃ of the solvent boiling point, the reflux ratio is controlled at 3:1-5:1, and the distillate purity is ≥99%. The recovered solvent is tested for impurities using gas chromatography, and the moisture content, determined by Karl Fischer method, should be ≤0.1%. Before reuse, it must be dehydrated using molecular sieves (3A or 4A).

[0072] Experimental verification Experiment 1: Comparative Experiment on the Effect of Composite Alkali Slow-Release System on Product Purity 1. Experimental Objective The invention verifies the technical advantages of the composite alkali sustained-release system over the traditional single alkali system in improving product purity and reaction selectivity, demonstrating the innovation and superiority of the technical solution.

[0073] 2. Preparation of experimental samples Control group A (traditional method): A single inorganic alkali, sodium carbonate, is added to the reaction system in one step without the use of slow-release packaging materials.

[0074] Experimental Group B (method of the present invention): A sustained-release alkali-coated material was prepared by coating a composite alkali of sodium carbonate and triethylamine in a mass ratio of 1:1 with calcium alginate gel microspheres.

[0075] 3. Experimental conditions Reactants: 100g of o-nitrobenzene ether (purity ≥98.0%), catalyst: 10g of 5% palladium on carbon (within the range of 1-10% in the embodiments), solvent: 400mL of deionized water (within the range of 3-8 times the weight of o-nitrobenzene ether in the embodiments), reaction temperature: 60℃ (within the range of 40-80℃ in the embodiments), hydrogen pressure: 0.2MPa (within the range of atmospheric pressure to 0.5MPa in the embodiments), reaction time: 6 hours. Other experimental conditions were strictly kept consistent.

[0076] 4. Experimental Procedure (1) Traditional synthesis was carried out according to the conditions of control group A: o-nitroanisole, deionized water, palladium on carbon catalyst were added to the reactor, and 15g of sodium carbonate was added at one time. The reaction was carried out at 60℃ and 0.2MPa hydrogen pressure for 6 hours.

[0077] (2) Synthesize according to the conditions of experimental group B: Prepare composite alkali sustained-release microspheres (sodium carbonate 7.5g + triethylamine 7.5g, coated with calcium alginate), add o-nitroanisole, deionized water, palladium on carbon catalyst, 15g disodium EDTA, 100mL diethylene glycol dimethyl ether to the reaction vessel, add composite alkali sustained-release microspheres, and react for 6 hours under the same conditions.

[0078] (3) After the reaction is complete, the same post-processing method is used to separate and purify the product.

[0079] (4) The purity and impurity composition of the product were analyzed by HPLC. Chromatographic conditions: mobile phase methanol-water (70:30), flow rate 1.0 mL / min, detection wavelength 280 nm.

[0080] 5. Experimental Results The results of product purity and impurity analysis are shown in the table below: Figure 1 The comparison of product purity was shown; Figure 2 A comparison of the contents of major impurities is shown; Figure 3 The reaction time comparison was shown; Figure 4 A radar chart showing overall performance was displayed.

[0081] 6. Analysis and Summary Comparative experiments have verified that the composite alkali sustained-release system of this invention has significant technical advantages over the traditional single alkali system: (1) Product purity has been greatly improved: from 94.93% by traditional methods to 99.43%, an increase of 4.50 percentage points.

[0082] (2) Significant effect in impurity control: The content of the main byproduct o-aminophenol was reduced from 2.1% to 0.077%, a reduction of 96.3%.

[0083] (3) The reaction efficiency was significantly improved: the reaction time was shortened from 10.5 hours to 4.83 hours, a reduction of 54.0%.

[0084] (4) Improved product appearance quality: The color value was reduced from 35 to 4, and the product appearance was improved from light yellow to colorless and transparent.

[0085] The experimental results fully demonstrate that the synergistic pH regulation technology of the composite alkali slow-release system is the key innovation of this invention, achieving a fundamental improvement in reaction selectivity and product quality.

[0086] Experiment 2: Test on the effect of metal complex stabilizers on the recyclability of catalysts 1. Experimental Objective The protective effect of metal complex stabilizers on transition metal catalysts in alkaline environments was verified, and the cycle life and activity retention of the catalysts were tested, demonstrating the technological breakthrough of this invention in catalyst stability.

[0087] 2. Preparation of experimental samples Control group C (no protective agent): 10g of 5% palladium on carbon catalyst, without the addition of a metal complexing stabilizer. Experimental group D (method of this invention): 10g of 5% palladium on carbon catalyst, with 15g of disodium EDTA added as a metal complexing stabilizer.

[0088] 3. Experimental conditions Reaction materials: o-nitroanisole (purity ≥98.0%) 100g / batch, solvent: deionized water 400mL + diethylene glycol dimethyl ether 100mL (equilibrium of ether co-solvent in the embodiment is 20-30%), composite alkali sustained-release microspheres: sodium carbonate 7.5g + triethylamine 7.5g (mass ratio 1:1, in accordance with the range of 1:0.3-3 in the embodiment), reaction temperature: 60℃ (in accordance with the range of 40-80℃ in the embodiment), hydrogen pressure: 0.2MPa (in accordance with the range of atmospheric pressure to 0.5MPa in the embodiment), reaction time: 4 hours / batch, 8 batches of reaction were carried out continuously.

[0089] 4. Experimental Procedure (1) Catalyst pretreatment: 5% palladium on carbon catalyst was activated at 300°C for 2 hours in a hydrogen atmosphere.

[0090] (2) First batch reaction: The reaction was carried out under standard conditions. The control group C did not add EDTA, while the experimental group D added 15g of disodium EDTA.

[0091] (3) Catalyst recovery: After the reaction is completed, the catalyst is recovered by centrifugation, washed with deionized water until neutral, and dried under vacuum at 60°C for 8 hours.

[0092] (4) Catalyst characterization: Samples were taken from each batch for XRD, BET surface area determination and TEM analysis.

[0093] (5) Repeat steps (2)-(4) for 8 consecutive batches of reaction, and record the conversion rate, selectivity and catalyst performance parameters for each batch.

[0094] 5. Experimental Results Catalyst recycling performance test results: Figure 5 The trend of catalyst conversion rate is shown; Figure 6 It shows the trend of catalyst selectivity; Figure 7 The comparison of catalyst activity retention rates is shown.

[0095] 6. Analysis and Summary The significant effect of the metal complex stabilizer in protecting the catalyst was verified through catalyst recycling performance testing. (1) Catalyst life was greatly extended: The conversion rate of control group C dropped sharply to 63.8% after the second batch and only 28.5% after the fourth batch, basically losing its industrial use value; the conversion rate of experimental group D remained at 74.3% after the eighth batch.

[0096] (2) The activity retention rate was significantly improved: In the 8th batch, the activity retention rate of the control group C was only 5.9% (5.8 / 98.2×100%), while the activity retention rate of the experimental group D was 75.0% (74.3 / 99.1×100%).

[0097] (3) Excellent selectivity and stability: In the 8 batches of cyclic use, the selectivity of experimental group D only decreased from 98.8% to 95.1%, and remained above 95%, while the selectivity of control group C dropped sharply from 96.5% to 63.4%.

[0098] (4) Good structural stability: The specific surface area of ​​experimental group D increased from 950 m² / g. 2 / g only dropped to 890 m 2 / g, retention rate 93.7%; control group C from 950 m 2 / g dropped sharply to 95 m 2 / g, with a retention rate of only 10.0%.

[0099] Experimental results demonstrate that metal complex stabilizers such as EDTA effectively protect the structural stability and catalytic activity of the catalyst in an alkaline environment by forming reversible complexes, enabling efficient recycling of the catalyst and significantly reducing production costs.

[0100] Experiment 3: Comparison of Packaging Material Rapid Digestion and Extraction Separation Efficiency 1. Experimental Objective The invention demonstrates the technological advantages of rapid digestion of packaging materials and simultaneous extraction and separation of products compared to traditional filtration separation methods in terms of separation efficiency, product yield, and separation time, proving the revolutionary improvement of separation technology in this invention.

[0101] 2. Preparation of experimental samples Control group E (conventional separation method): Packaging material residue was directly separated by vacuum filtration and washing after the reaction. Experimental group F (method of this invention): Packaging material digesting agent was added for rapid digestion after the reaction, followed by simultaneous extraction and separation using an extractant.

[0102] 3. Experimental conditions Reaction scale: 100g of o-nitroanisole, using a composite alkali slow-release system coated with calcium alginate gel microspheres, the conversion rate reached over 97% after the reaction. Separation temperature: 25℃, the separation process was timed throughout, and various separation efficiency indicators were measured.

[0103] 4. Experimental Procedure Control group E operation steps: (1) After the reaction was completed, the packaging material residue was separated by vacuum filtration using a 0.22μm filter membrane.

[0104] (2) Wash the filter cake three times with deionized water, 50 mL each time, and collect the washing liquid.

[0105] (3) Combine the filtrate and washing liquid, concentrate and then extract the product.

[0106] (4) Record indicators such as separation time, packaging material residue removal rate, and product yield.

[0107] Experimental group F operation steps: (1) After the reaction is complete, add 100 mL of phosphate buffer to rapidly digest the calcium alginate gel packaging material.

[0108] (2) Add 200 mL of ethyl acetate and 15 g of sodium chloride at the same time for extraction and separation.

[0109] (3) Mechanically shake for 5 minutes, let stand for 20 minutes to separate the organic phase.

[0110] (4) Record indicators such as separation time, packaging material residue removal rate, and product yield.

[0111] 5. Experimental Results Separation efficiency comparison test results: 6. Analysis and Summary The revolutionary improvement of the separation technology of this invention was verified through comparative experiments on the efficiency of rapid digestion of packaging materials and extraction separation: (1) The separation efficiency has been greatly improved: the separation time has been shortened from 7.33 hours in the traditional method to 0.73 hours, and the efficiency has been improved by 10.04 times.

[0112] (2) The removal rate of packaging material residue has been significantly improved: from 78.87% of the traditional method to 98.83%, an increase of 19.96 percentage points.

[0113] (3) Product yield increased significantly: from 71.83% in the traditional method to 90.1%, an increase of 18.27 percentage points.

[0114] (4) The purity of the product has been further improved: from 97.17% to 99.1%, an increase of 1.93 percentage points, reaching a higher product quality standard.

[0115] (5) Packaging material residue has been reduced dramatically: from 2867ppm to 180ppm, a reduction of 93.7%, effectively solving the problem of packaging material contamination.

[0116] (6) Solvent consumption is greatly reduced: from 850mL / 100g to 320mL / 100g, saving 62.4%, significantly reducing production costs and environmental burden.

[0117] The experimental results fully demonstrate that the rapid digestion of packaging materials and simultaneous extraction and separation of products achieves an integrated separation process of "timely digestion, simultaneous extraction, and dual protection," solving key technical problems such as low separation efficiency, large product loss, and heavy environmental burden of traditional methods.

[0118] The embodiments of the present invention have been described above. However, the embodiments are not limited to the specific implementation methods described above. The specific implementation methods described above are merely illustrative and not restrictive. Those skilled in the art can make more equivalent embodiments under the guidance of the present embodiments, and all of them are within the protection scope of the present embodiments.

Claims

1. A method for synthesizing anthranilide compounds, characterized in that, Includes the following steps: Step 1: Preparation of the composite alkali sustained-release system: A composite alkali mixture is prepared by mixing inorganic alkali and organic alkali at a mass ratio of 1:0.3-3. The mixture is then coated with one or more slow-release packaging materials, such as calcium alginate gel microspheres, gelatin coating layer or chitosan coating layer, to obtain a slow-release alkali packaging material. Step 2: Prepare the catalytic reduction reaction system: o-Nitroanisole, deionized water, hydrophilic ether cosolvent, transition metal catalyst, metal complexing stabilizer, and slow-release alkali packaging material from step 1 are added sequentially. Step 3: Conduct the catalytic reduction reaction: Catalytic reduction reaction is carried out under hydrogen atmosphere or liquid phase reducing agent. The slow-release alkali-encapsulated material gradually releases the composite alkali system to maintain the pH in the range of 9.0-10.

5. The metal complex stabilizer forms a reversible complex with the catalyst to protect the catalyst activity. Step 4: Packaging material digestion and product separation: When the reaction conversion rate reaches 95% or more, a rapid digestion agent for packaging materials is added to break down the packaging material structure. At the same time, a product protective extractant and a salting-out agent are added to rapidly transfer the product to the organic phase for separation. Step 5: Product purification and recovery: The organic phase is separated and the solvent is recovered. The product, o-aminoanisole, is obtained by vacuum distillation or recrystallization.

2. The synthesis method according to claim 1, characterized in that, The inorganic base is selected from one or more of sodium carbonate, potassium carbonate, and sodium hydroxide, and the organic base is selected from one or more of triethylamine, pyridine, and diethylamine.

3. The synthesis method according to claim 1, characterized in that, The hydrophilic ether co-solvent is selected from one or more of diethylene glycol dimethyl ether, diethylene glycol monomethyl ether, and tetrahydrofurfuryl alcohol, and the amount used is 15-40% of the weight of deionized water.

4. The synthesis method according to claim 1, characterized in that, The transition metal catalyst is selected from one or more of palladium on carbon, Raney nickel, and supported platinum catalyst, and the amount used is 1-10% of the weight of the o-nitroanisole raw material.

5. The synthesis method according to claim 1, characterized in that, The metal complexing stabilizer is selected from one or more of sodium citrate, disodium EDTA, and sodium potassium tartrate, and the amount used is 0.5-3 times the weight of the transition metal catalyst.

6. The synthesis method according to claim 1, characterized in that, In step 3, the temperature of the catalytic reduction reaction is 40-80℃, the reaction time is 3-6 hours, the hydrogen pressure is atmospheric pressure to 0.5MPa, or the liquid phase reducing agent is selected from hydrazine hydrate, formic acid, and sodium borohydride.

7. The synthesis method according to claim 1, characterized in that, In step 4, phosphate buffer or carbonate-phosphate mixture is used as a digesting agent for calcium alginate gel packaging materials, and protease or chitosanase is used as a digesting agent for gelatin or chitosan packaging materials.

8. The synthesis method according to claim 1, characterized in that, The protective extractant for the product is selected from one or more of ethyl acetate, butyl acetate, and methyl isobutyl ketone, and one or more antioxidant synergists selected from BHT, vitamin E, and propyl gallate are pre-dissolved in the extractant.

9. The synthesis method according to claim 1, characterized in that, The amount of alkali in the slow-release alkali packaging material is 20-60% of the total weight of the packaging material, and the amount of slow-release alkali packaging material used is calculated based on a molar ratio of the total amount of alkali provided to o-nitroanisole of 1.5-3:

1.

10. The synthesis method according to claim 1, characterized in that, The o-aminoanisole product obtained in step 5 has a purity of ≥99.5%, a melting point of 5.5-6.5℃, and a product yield of ≥85%. The transition metal catalyst can be recycled for 5-8 batches.

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