Phenolamine medical intermediate based on biomass pyrolysis scale and preparation method thereof

Abstract

The invention provides a large-scale phenol amine medical intermediate based on biomass pyrolysis and a preparation method thereof, and belongs to the technical field of high-value conversion and utilization of biomass resources, and the preparation method comprises the following steps: preparing an ammonium tungstate-biomass compound, adding a demethylation catalyst or a demethoxylation catalyst into the ammonium tungstate-biomass compound, introducing argon gas, and carrying out high-value conversion and utilization on the ammonium tungstate-biomass compound to obtain the high-value conversion and utilization of the high-value conversion and utilization of the high-value conversion and utilization of the high-value conversion and utilization of the biomass resources. Then carrying out a microwave pyrolysis reaction to obtain a pyrolysis gas product and a pyrolysis solid product, condensing the pyrolysis gas product to obtain a condensation product, heating the condensation product, and carrying out reduced pressure distillation to obtain the phenol amine medical intermediate; the preparation method can solve the problems that raw materials depend on fossil resources, the resource utilization efficiency is low in the synthesis process, a large amount of solvents are needed in the preparation process, the process is tedious, the production cost is high, and large-scale preparation of products is difficult in the traditional preparation process of the phenol amine medical intermediates; a new method is provided for large-scale preparation of phenol amine medical intermediates from biomass resources, and the economic value and application potential of the biomass resources are improved.

Description

Technical Field

[0001] The present invention relates to the technical field of high-value conversion and utilization of biomass resources, and in particular to a phenolamine pharmaceutical intermediate based on large-scale pyrolysis of biomass and a preparation method thereof. Background Art

[0002] As the world pays more and more attention to sustainable development and environmental protection, finding renewable resources to replace traditional fossil resources has become a research hotspot in the energy and chemical industry. Biomass, as a widely available and renewable resource, has the advantages of abundant sources, environmental protection, high calorific value, low pollution, economy and carbon neutrality. It includes various forms such as crop straw, forestry waste, and herbaceous plants, with huge annual output. However, the current utilization efficiency of biomass is still low, and a large amount of biomass resources are idle or even irrationally handled, resulting in resource waste and environmental problems.

[0003] Phenolamine compounds have a wide range of application values ​​in industry and pharmaceutical preparation. Phenolamine compounds are important chemical raw materials and can be used to produce a variety of products such as phenolic resins, antioxidants, coatings, and fragrances. They also play an indispensable role in the fields of medicine, pesticides, dyes, rubber additives, etc. At present, phenolamine pharmaceutical intermediates are mainly prepared by traditional chemical synthesis methods. Most of these methods rely on non-renewable fossil resources, which are not only costly, but also may produce a large amount of pollutants during the production process. In addition, with the continuous improvement of environmental protection requirements, it is urgent to develop green and sustainable methods for preparing phenolamine pharmaceutical intermediates.

[0004] At present, there are some studies and reports on the preparation of phenolic compounds or amine compounds by pyrolysis of biomass. For example, in "A method for preparing phenolic substances by catalytic pyrolysis of biomass by nitrogen-doped carbon" (CN108129270A), the biomass is crushed and dried, and then rapidly pyrolyzed in an ammonia atmosphere to obtain a nitrogen-doped carbon catalyst with developed porosity and rich in active nitrogen-containing functional groups. A large amount of high-value-added phenolic substances can be obtained by catalytic pyrolysis of biomass by nitrogen-doped carbon catalyst; in "A method for preparing phenolic compounds by catalytic pyrolysis of lignin by double perovskite" (CN117582990A), a MOFs precursor is first prepared, and then calcined to obtain a MOFs-based double perovskite. Then, the double perovskite and lignin are evenly mixed, pressed into tablets and crushed into particles with a particle size of 0.3~1 mm. The particles are filled in a fixed bed reactor and heated at 500~700 °C. ℃, in an inert atmosphere, the lignin is catalytically pyrolyzed, and the reaction product is condensed and separated to obtain a liquid product containing phenolic compounds; in "A method for preparing bio-based amine compounds by converting marine biomass" (CN117551056A), it is introduced that the oxygen element of chitin is removed by a loaded ruthenium catalyst and a phosphoric acid co-catalyst, while the amino group in chitin is retained, and chitin is converted into biogenic amines. Through the optimization of the catalyst, the amino group is retained by the co-catalyst, thereby improving the conversion rate of chitin and achieving the selective production of amines. Most of the published patents involve the preparation of phenolic compounds or amine compounds, while there are few reports on the preparation of phenolic amine compounds, especially pharmaceutical intermediates.

[0005] The research on the preparation of phenolamine pharmaceutical intermediates by biomass pyrolysis currently faces many challenges, such as limited scale, low product selectivity and complex process flow. It is difficult to directly transform laboratory-scale research into industrial applications, and low product selectivity leads to high costs in the subsequent separation process. The existing process has not been able to effectively optimize and integrate the biomass pyrolysis process with the generation mechanism of phenolamine compounds, which limits the ability to produce phenolamine compounds on a large scale, efficiently and at low cost. Therefore, it is urgent to develop a new biomass pyrolysis method to prepare phenolamine compounds on a large scale, break through the limitations of existing technologies, achieve efficient utilization of biomass resources and sustainable production of phenolamine compounds, and promote the high-value transformation of biomass resources. Summary of the invention

[0006] The purpose of the present invention is to provide a phenolamine pharmaceutical intermediate based on large-scale pyrolysis of biomass and a preparation method thereof, so as to overcome the problems existing in the prior art. The present invention can solve the problems that in the preparation process of traditional phenolamine pharmaceutical intermediates, raw materials rely on fossil resources, resource utilization efficiency is low in the synthesis process, a large amount of solvent is required in the preparation process and the process is complicated, the production cost is high, and the large-scale preparation of products is difficult. The present invention aims to provide a new method for the large-scale preparation of phenolamine pharmaceutical intermediates from biomass resources, and further enhance the economic value and application potential of biomass resources.

[0007] In order to achieve the above object, the technical solution adopted by the present invention is as follows: A method for preparing phenolamine pharmaceutical intermediates based on large-scale biomass pyrolysis, comprising the following steps: Step 1, adding biomass into sodium hydroxide solution, adding ammonium tungstate substance after stirring at room temperature, performing ultrasonic treatment, then washing, and then vacuum drying to obtain ammonium tungstate-biomass composite; Step 2: adding a demethylation catalyst or a demethoxylation catalyst to the ammonium tungstate-biomass composite, introducing argon gas, and then performing a microwave pyrolysis reaction to obtain a pyrolysis gas product and a pyrolysis solid product, condensing the pyrolysis gas product to obtain a condensed product, and cooling the pyrolysis solid product to obtain a sodium tungstate-catalyst-pyrolysis carbon mixture; Step 3, heating the condensed product obtained in step 2 and performing reduced pressure distillation to obtain a phenolamine pharmaceutical intermediate; Step 4: Mix the sodium tungstate-catalyst-pyrolytic carbon mixture obtained in step 2 with deionized water, perform ultrasonic treatment and centrifuge to obtain a sodium tungstate solution and a catalyst-pyrolytic carbon solid mixture, dry the catalyst-pyrolytic carbon solid mixture, and then calcine it in an oxygen atmosphere to obtain the demethylation catalyst or demethoxylation catalyst in step 2; treat the sodium tungstate solution with acid, then perform ammoniation treatment, and then evaporate to obtain the ammonium tungstate substance in step 1; Furthermore, the mass ratio of the biomass, the sodium hydroxide solution and the ammonium tungstate substance in the step 1 is 1: (0.2-0.5): (1.5-2); the stirring speed is 500-800 rpm, and the time is 10-30 min; the power of the ultrasonic treatment is 120-180 W, and the time is 20-30 min; the number of washings is 5-10 times; the temperature of the vacuum drying is 45-55 ° C, and the time is 8-12h; the biomass is a coniferous wood, a broadleaf wood or a grass raw material containing lignin; the ammonium tungstate substance is ammonium tungstate, ammonium paratungstate or ammonium metatungstate; Furthermore, the step 2 is specifically as follows: A demethylation catalyst is added to the ammonium tungstate-biomass composite, 600 mL / min of argon is continuously introduced per kilogram of the ammonium tungstate-biomass composite, and then a microwave pyrolysis reaction is performed to obtain a pyrolysis gas product and a pyrolysis solid product, the pyrolysis gas product is condensed to obtain a catecholamine bio-oil, and the pyrolysis solid product is cooled to obtain a sodium tungstate-catalyst-pyrolysis carbon mixture; The demethylation catalyst is a modified molecular sieve with a Brönsted acid center; the time for passing argon is 1-1.5 h; the power of the microwave is 800-1500 W; the pyrolysis reaction is specifically: heating to 350-550 °C at a heating rate of 80-150 °C / min and keeping the temperature for 30 min for pyrolysis; the condensation temperature is -25 °C; the cooling is specifically cooling to below 100 °C; Furthermore, the preparation method of the modified molecular sieve with Brönsted acid center is as follows: calcining the silicon-aluminum molecular sieve at 550°C for 2 h to remove impurities, then immersing it in a 1-3 mol / L nitric acid solution, stirring it at 40-80°C for 4-6 h, so that part of the aluminum atoms in the molecular sieve are combined with protons to form a silicon-aluminum bridge hydroxyl structure, thereby introducing a Brönsted acid center, washing it to neutrality by centrifugation, and then centrifuging and washing it to neutrality, and then vacuum drying it at 80°C for 8 h to obtain a modified molecular sieve with Brönsted acid center; Furthermore, the step 2 is specifically as follows: A demethoxy catalyst is added to the ammonium tungstate-biomass composite, argon is continuously introduced at a rate of 600 mL / min per kg of the ammonium tungstate-biomass composite, and then a microwave pyrolysis reaction is performed to obtain a pyrolysis gas product and a pyrolysis solid product, the pyrolysis gas product is condensed to obtain a phenolamine bio-oil, and the pyrolysis solid product is cooled to obtain a sodium tungstate-catalyst-pyrolysis carbon mixture; The demethoxylation catalyst is a modified molecular sieve with Lewis acid centers; the time for introducing argon is 1 to 1.5 hours; the power of the microwave is 2000 to 4000 W; the pyrolysis reaction is specifically: heating to 600 to 800 °C at a heating rate of 300 to 450 °C / min and keeping the temperature for 5 minutes for pyrolysis; the condensation temperature is -25 °C; the cooling is specifically cooling to below 100 °C; Furthermore, the preparation method of the modified molecular sieve with Lewis acid center is as follows: calcining the silicon-aluminum molecular sieve at 550°C for 2 h to remove impurities, then immersing it in a 0.5-1 mol / L dilute hydrochloric acid solution, stirring it at 30-60°C for 3-5 h, and then adding a solution of metal ions with a molar concentration of 0.3-1 mol / L, wherein the metal ions can selectively enter the pores or framework of the molecular sieve, stirring it at 40-80°C for 4-6 h, so that the metal ions combine with the atoms in the molecular sieve to form metal species with empty orbitals, thereby introducing Lewis acid centers, and then centrifugally washing to remove excess metal ions, and then vacuum drying it at 80°C for 8 h to obtain a modified molecular sieve with Lewis acid center; The metal ion solution is ferric chloride, tin acetate, copper nitrate or cobalt nitrate; Furthermore, the step three is specifically as follows: The condensed product is heated to 60-90°C and then distilled under reduced pressure until no distillate is produced, and the undistilled product is collected to obtain a phenolamine pharmaceutical intermediate; Furthermore, the mass ratio of the sodium tungstate-catalyst-pyrolytic carbon mixture and deionized water in the step 4 is 1: (5-10); the power of the ultrasonic treatment is 120-180 W, and the time is 30-60 min; the drying temperature is 60-80 ° C, and the time is 6-8 h; the oxygen atmosphere is specifically: a mixed gas of 50% by volume of air and 50% by volume of 99.999% oxygen; the calcination temperature is 600-800 ° C, and the time is 8-10 h; Further, the acid treatment in step 4 is specifically: using an inorganic acid with a molar concentration of 4-6 mol / L to acidify the sodium tungstate solution to pH=2-4 to obtain tungstic acid; the ammoniation treatment is specifically: adding tungstic acid to ammonia water with a mass concentration of 25%-28% under continuous stirring at 50-60 ° C for ammoniation treatment, wherein the mass ratio of tungstic acid to ammonia water is 1:1, and then clarifying for 8-12 hours; the evaporation is specifically: stirring and heating the tungstic acid solution after ammoniation treatment at a constant temperature of 80 ° C, and when the solution evaporates to the appearance of crystal nuclei, continue to evaporate to one-third of the volume of the remaining original solution of the mother liquor, stop evaporation, cool, wash and dry to obtain ammonium tungstate; or, the tungstic acid solution after ammoniation treatment is heated to 85-95 ° C, evaporated and concentrated under continuous stirring until crystal nuclei appear, and then evaporated to a solution concentration of 1.04-1.08 g / mL, stop and wash and dry to obtain ammonium paratungstate, heat the ammonium paratungstate to 220-280 °C and keep it for 10-20 min to obtain ammonium metatungstate; Furthermore, the inorganic acid is nitric acid, hydrochloric acid or sulfuric acid.

[0008] A phenolamine pharmaceutical intermediate based on large-scale pyrolysis of biomass is obtained based on the above-mentioned method for preparing a phenolamine pharmaceutical intermediate based on large-scale pyrolysis of biomass.

[0009] The above technical solution has the following advantages or beneficial effects: The present invention provides a method for preparing phenolamine pharmaceutical intermediates based on large-scale biomass pyrolysis. Through microwave pyrolysis technology, directional and efficient conversion from lignin-rich biomass raw materials to phenolamine pharmaceutical intermediates is achieved, and high-yield catecholamine pharmaceutical intermediates or phenolamine pharmaceutical intermediates can be obtained as needed; at the same time, the method of the present invention innovatively introduces ammonium tungstate substances, which can release key intermediates such as amine active substances and free radicals in situ during the reaction process, thereby effectively regulating the pyrolysis reaction. By controlling the reaction microwave power and heating rate, and combining the use of different catalysts, precise regulation of the pyrolysis process of biomass raw materials is achieved, thereby directional generation of different types of phenolamine pharmaceutical intermediates, providing a new idea for the preparation of phenolamine pharmaceutical intermediates by non-petroleum routes; in addition, the catalyst used also has the characteristic of being recyclable, which not only improves the catalytic efficiency, but also reduces the consumption and waste of the catalyst, reducing production costs and environmental burdens.

[0010] Furthermore, in step 1, the biomass is added to a NaOH solution with a mass concentration of 30%. The addition of NaOH can promote the effective formation of ammonium tungstate-biomass complexes by improving the solubility, and can effectively adjust the pH value of the reaction system, creating favorable conditions for the recycling of sodium tungstate. Specifically, Na in sodium hydroxide +It interacts with tungstate ions to generate sodium tungstate, and its solubility in aqueous solution increases, which facilitates the efficient separation of sodium tungstate and promotes the regeneration of ammonium tungstate substances. In addition, the regeneration process of ammonium tungstate substances is simple to operate, the technology is mature, and the performance of the regenerated product is stable and can be recycled many times. This recycling model not only effectively reduces production costs and reduces resource consumption, but also reduces environmental pressure, achieving a win-win situation of economic and ecological benefits. At the same time, as a type of high-molecular nitrogen-containing ammonium acid substance, ammonium tungstate substances are good nitrogen carriers that can stably carry and store nitrogen elements. In the process of catalytic pyrolysis of biomass raw materials, they not only serve as nitrogen sources, It also exhibits a good sustained-release effect under high temperature conditions, ensuring a stable supply of nitrogen in the reaction system and effectively improving the yield of phenolamine pharmaceutical intermediates; this type of substance can react in situ as the temperature rises, releasing amine active substances and key intermediates such as R-NH2·free radicals on or near the surface of biomass raw materials, participating in and regulating the reaction process, and promoting the directional conversion of biomass raw materials; in addition, in ammonium tungstate substances, tungsten serves as the active center, and the nitrogen vacancy defect caused by the removal of nitrogen makes it have a catalytic effect that can reduce the activation energy of the reaction, accelerate the breaking and recombination of chemical bonds such as ether bonds in biomass, and promote the formation of catecholamines or phenolamine compounds.

[0011] Furthermore, the silica-alumina molecular sieves with Brönsted acid centers can remove methyl groups (-CH3) in biomass raw materials to generate catechol substances, which react with ammonium tungstate substances to generate catecholamine pharmaceutical intermediates; the silica-alumina molecular sieves with Lewis acid centers can remove methoxy groups (-OCH3) in biomass raw materials to generate phenol substances, which react with ammonium tungstate substances to generate phenolamine pharmaceutical intermediates.

[0012] Furthermore, during the biomass pyrolysis process, a demethylation catalyst or a demethoxylation catalyst was introduced. These catalysts were silica-alumina molecular sieves containing Brönsted acid centers and Lewis acid centers, respectively. In this process, the catalytic effects of Brönsted acid and Lewis acid promoted the breaking of bonds in the biomass. Specifically, under the pyrolysis conditions of microwave power of 800-1500 W, heating rate of 80-150 ℃ / min, heating to 350-550 ℃ and keeping temperature for 30 min, it was mainly Brönsted acid that played a role, resulting in C βThe -O bond breaks to generate methylcatecholamines and aliphatic hydrocarbon intermediates. The methyl group of methylcatecholamines is removed under the action of Brönsted acid and reduced by hydrogen radicals released in the reaction process, mainly generating phenolamine compounds with catecholamine as the main component. Under the pyrolysis conditions of microwave power of 2000~4000 W, heating rate of 300~450 ℃ / min, heating to 600~800 ℃ and keeping warm for 5 min, the high heating rate and high temperature are mainly utilized. Due to the introduction of metal into the molecular sieve at high temperature, Lewis acid is stimulated to play a role, resulting in the breaking of the C3-O bond on the benzene ring, directly generating phenolamine compounds with phenolamine as the main component.

[0013] Furthermore, during the biomass pyrolysis process, a coke covering is easily formed on the catalyst surface, affecting its catalytic activity. Through oxygen-enriched calcination, this layer of coke can be prompted to react with oxygen to generate CO or CO2 and escape, effectively removing impurities, restoring and improving the activity and purity of the catalyst, and preventing it from being deactivated due to coke accumulation. This process not only ensures the high catalytic activity of the catalyst, but also enables the treated high-purity catalyst solid to be directly reused in the process of preparing phenolamine pharmaceutical intermediates by biomass pyrolysis, thereby realizing efficient recycling of the catalyst. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] Figure 1 This is a schematic flow chart of a method for preparing phenolamine pharmaceutical intermediates based on large-scale biomass pyrolysis according to the present invention; Figure 2 This is the XRD diagram of the pyrolysis product sodium tungstate in Example 1 of the present invention. DETAILED DESCRIPTION

[0015] The present invention is further described in detail below in conjunction with specific embodiments, which are intended to explain the present invention rather than to limit it. In order to enable those skilled in the art to better understand the scheme of the present invention, the technical scheme in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work should fall within the scope of protection of the present invention. It should be noted that the terms "first", "second", etc. in the specification and claims of the present invention and the above-mentioned drawings are used to distinguish similar objects, and are not necessarily used to describe a specific order or sequence. It should be understood that the data used in this way can be interchanged where appropriate, so that the embodiments of the present invention described herein can be implemented in an order other than those illustrated or described herein. In addition, the terms "including" and "having" and any variations thereof are intended to cover non-exclusive inclusions, for example, a process, method, system, product or device that includes a series of steps or units is not necessarily limited to those steps or units that are clearly listed, but may include other steps or units that are not clearly listed or inherent to these processes, methods, products or devices.

[0016] Embodiment 1: like Figure 1 As shown, the present invention provides a method for preparing phenolamine pharmaceutical intermediates based on large-scale biomass pyrolysis, comprising the following steps: Step 1: add 10 kg of spruce powder to 2 kg of NaOH solution with a mass concentration of 30%, stir at room temperature at a speed of 500 rpm for 30 min, add 15 kg of ammonium paratungstate, ultrasonically treat at an ultrasonic power of 120 W for 30 min, then wash with deionized water for 5 times, and then vacuum dry at 45 ° C for 12 h to obtain an ammonium paratungstate-biomass composite; Step 2: 50 kg of demethylation catalyst and 10 kg of ammonium paratungstate-biomass composite are placed in a microwave pyrolysis reactor, argon with a purity of 99.99% is continuously introduced at 600 mL / min for 1 h, the microwave power is set to 800 W, the temperature is increased to 350 °C at a heating rate of 80 °C / min and kept warm for 30 min for pyrolysis to obtain pyrolysis gas products and pyrolysis solid products, the pyrolysis gas products are condensed at -25 °C to obtain catecholamine bio-oil, and the pyrolysis solid products are cooled to below 100 °C to obtain a sodium tungstate-catalyst-pyrolysis carbon mixture; Preferably, the demethylation catalyst is a modified molecular sieve having a Brönsted acid center, and the specific preparation method is: calcining 100 kg of HZSM-5 molecular sieve at 550 ° C for 2 h to remove impurities, then immersing 50 kg of the HZSM-5 molecular sieve after impurities removal in 20 L of 1 mol / L nitric acid solution, stirring at 40 ° C for 6 h, and then centrifuging and washing to neutrality, and vacuum drying at 80 ° C for 8 h to obtain a modified molecular sieve having a Brönsted acid center, which is a demethylation catalyst; Step 3, heating the catecholamine bio-oil obtained in step 2 to 80° C. and then performing vacuum distillation until no distillate is produced, and the undistilled matter is the catecholamine pharmaceutical intermediate; Step 4: Take 10 kg of the sodium tungstate-catalyst-pyrolytic carbon mixture obtained in step 2 and add it to 50 L of deionized water. After treating it at an ultrasonic power of 120 W for 60 min, centrifuge it and separate the mixture into two parts: sodium tungstate solution and catalyst-pyrolytic carbon solid mixture. Then, dry the separated catalyst-pyrolytic carbon solid mixture at 60 °C for 8 h, and then calcine it in an oxygen-rich atmosphere at 600 °C for 10 h to obtain a demethylation catalyst solid product, which is reused in step 2. Then, add 4 mol / L nitric acid solution to 50 L of sodium tungstate solution until the pH of the solution is 2-4, so that sodium tungstate is converted into tungstic acid. At 50 °C, slowly add tungstic acid to 50 L of ammonia water with a mass concentration of 25%-28% under continuous stirring for ammoniation treatment. After the solution is clarified for 12 h, place the tungstic acid solution after ammoniation treatment in an evaporating dish, heat it to 90 °C, evaporate and concentrate it under continuous stirring, and continue to evaporate to a solution concentration of 1.04-1.08 when tiny crystal nuclei appear. g / mL, stop concentrating and wash and dry to obtain ammonium paratungstate, which is reused in step 1.

[0017] Embodiment 2: like Figure 1 As shown, the present invention provides a method for preparing phenolamine pharmaceutical intermediates based on large-scale biomass pyrolysis, comprising the following steps: Step 1: add 10 kg of spruce powder to 3 kg of NaOH solution with a mass concentration of 30%, stir at room temperature at a speed of 700 rpm for 20 min, add 17 kg of ammonium tungstate, ultrasonically treat at an ultrasonic power of 150 W for 25 min, then wash with deionized water 8 times, and then vacuum dry at 50 ° C for 10 h to obtain an ammonium tungstate-biomass composite; Step 2: 60 kg of demethoxylation catalyst and 10 kg of ammonium tungstate-biomass composite are placed in a microwave pyrolysis reactor, argon with a purity of 99.99% is continuously introduced at 600 mL / min for 1 h, the microwave power is set to 3000 W, the temperature is increased to 700 °C at a heating rate of 350 °C / min and kept warm for 5 min for pyrolysis to obtain pyrolysis gas products and pyrolysis solid products, the pyrolysis gas products are condensed at -25 °C to obtain phenolamine bio-oil, and the pyrolysis solid products are cooled to below 100 °C to obtain a sodium tungstate-catalyst-pyrolysis carbon mixture; Preferably, the demethoxylation catalyst is a modified molecular sieve having a Lewis acid center, and the preparation method is specifically as follows: calcining 100 kg of USY molecular sieve at 550 ° C for 2 h to remove impurities, then immersing 60 kg of the impurity-removed USY molecular sieve in 20 L of 0.5 mol / L dilute hydrochloric acid solution, stirring at 30 ° C for 5 h, placing in a ferric chloride solution with a molar concentration of 0.3 mol / L, stirring at 40 ° C for 6 h, and then centrifugally washing to remove excess metal ions, and vacuum drying at 80 ° C for 8 h to obtain a modified molecular sieve having a Lewis acid center, which is a demethoxylation catalyst; Step 3, heating the phenolamine bio-oil obtained in step 2 to 60° C. and then performing reduced pressure distillation until no distillate is produced, and the undistilled matter is the phenolamine pharmaceutical intermediate; Step 4: Take 10 kg of the sodium tungstate-catalyst-pyrolytic carbon mixture obtained in step 2 and add it to 70 L of deionized water. After treating it at an ultrasonic power of 150 W for 50 min, centrifuge it and separate the mixture into two parts: sodium tungstate solution and catalyst-pyrolytic carbon solid mixture. Then, dry the separated catalyst-pyrolytic carbon solid mixture at 70 °C for 7 h, and then calcine it in an oxygen-rich atmosphere at 700 °C for 9 h to obtain a demethoxylated catalyst solid product, which is reused in step 2. Then, add 5 mol / L hydrochloric acid solution to 50 L of sodium tungstate solution until the pH of the solution is 2-4, so that sodium tungstate is converted into tungstic acid. At 55 °C, slowly add tungstic acid to 50 L of ammonia water with a mass concentration of 25%-28% that is constantly stirred for ammoniation. After the solution is clarified for 10 h, place the ammoniation-treated tungstic acid solution in an evaporating dish and simmer at 80 °C for 3 hours. Stir and heat to evaporate at a constant temperature of ℃. When the solution evaporates to the point where tiny crystal nuclei appear, continue evaporating until the remaining volume of the mother liquor is one-third of the original solution. Stop evaporation, cool, wash and dry to obtain ammonium tungstate, which is then reused in step one.

[0018] Embodiment 3: like Figure 1 As shown, the present invention provides a method for preparing phenolamine pharmaceutical intermediates based on large-scale biomass pyrolysis, comprising the following steps: Step 1: add 10 kg of poplar wood powder to 5 kg of NaOH solution with a mass concentration of 30%, stir at room temperature at a speed of 800 rpm for 10 min, add 20 kg of ammonium metatungstate, ultrasonically treat at an ultrasonic power of 180 W for 20 min, then wash with deionized water 10 times, and then vacuum dry at 55 ° C for 8 h to obtain an ammonium metatungstate-biomass composite; Step 2: 70 kg of demethylation catalyst and 10 kg of ammonium metatungstate-biomass composite are placed in a microwave pyrolysis reactor, argon with a purity of 99.99% is continuously introduced at 600 mL / min for 1.5 h, the microwave power is set to 1500 W, the temperature is increased to 550 °C at a heating rate of 150 °C / min and kept warm for 30 min for pyrolysis to obtain pyrolysis gas products and pyrolysis solid products, the pyrolysis gas products are condensed at -25 °C to obtain catecholamine bio-oil, and the pyrolysis solid products are cooled to below 100 °C to obtain a sodium tungstate-catalyst-pyrolysis carbon mixture; Preferably, the demethylation catalyst is a modified molecular sieve having a Brönsted acid center, and the specific preparation method is: calcining 100 kg of SBA-molecular sieve at 550 ° C for 2 h to remove impurities, then immersing 70 kg of the SBA-molecular sieve after impurities removal in 20 L of 3 mol / L nitric acid solution, stirring at 80 ° C for 4 h, and then centrifuging and washing to neutrality, and vacuum drying at 80 ° C for 8 h to obtain a modified molecular sieve having a Brönsted acid center, which is a demethylation catalyst; Step 3, heating the catecholamine bio-oil obtained in step 2 to 85° C. and then performing vacuum distillation until no distillate is produced, and the undistilled matter is the catecholamine pharmaceutical intermediate; Step 4: Take 10 kg of the sodium tungstate-catalyst-pyrolytic carbon mixture obtained in step 2 and add it to 100 L of deionized water. After treating it at an ultrasonic power of 180 W for 30 min, centrifuge it and divide the mixture into two parts: sodium tungstate solution and catalyst-pyrolytic carbon solid mixture. Then, dry the separated catalyst-pyrolytic carbon solid mixture at 80 °C for 6 h, and then calcine it in an oxygen-rich atmosphere at 800 °C for 8 h to obtain a demethylation catalyst solid product, which is reused in step 2. Then, add 6 mol / L sulfuric acid solution to 50 L of sodium tungstate solution until the pH of the solution is 2-4, so that sodium metatungstate is converted into tungstic acid. At 60 °C, slowly add tungstic acid to 50 L of ammonia water with a mass concentration of 25%-28% under continuous stirring for ammoniation treatment. After the solution is clarified for 8 h, place the tungstic acid solution after ammoniation treatment in an evaporating dish, heat it to 90 °C, evaporate and concentrate it under continuous stirring, and continue to evaporate to a solution concentration of 1.04-1.08 when tiny crystal nuclei appear. g / mL, stop concentrating and wash and dry to obtain ammonium paratungstate; heat the ammonium paratungstate to 220 ℃ and keep it for 20 min to obtain ammonium metatungstate, which is reused in step 1.

[0019] Embodiment 4: like Figure 1 As shown, the present invention provides a method for preparing phenolamine pharmaceutical intermediates based on large-scale biomass pyrolysis, comprising the following steps: Step 1: add 10 kg of poplar wood powder to 2 kg of NaOH solution with a mass concentration of 30%, stir at room temperature at a speed of 500 rpm for 30 min, add 15 kg of ammonium paratungstate, ultrasonically treat at an ultrasonic power of 120 W for 30 min, then wash with deionized water for 5 times, and then vacuum dry at 45 ° C for 12 h to obtain an ammonium paratungstate-biomass composite; Step 2: 50 kg of demethoxylation catalyst and 10 kg of ammonium paratungstate-biomass composite are placed in a microwave pyrolysis reactor, argon with a purity of 99.99% is continuously introduced at 600 mL / min for 1 h, the microwave power is set to 2000 W, the temperature is increased to 600 °C at a heating rate of 300 °C / min and kept warm for 5 min for pyrolysis to obtain pyrolysis gas products and pyrolysis solid products, the pyrolysis gas products are condensed at -25 °C to obtain phenolamine bio-oil, the pyrolysis solid products are cooled to below 100 °C to obtain a sodium tungstate-catalyst-pyrolysis carbon mixture; Preferably, the demethoxylation catalyst is a modified molecular sieve having a Lewis acid center, and the preparation method is specifically as follows: calcining 100 kg of HY molecular sieve at 550°C for 2 h to remove impurities, then immersing 50 kg of the HY molecular sieve after impurities removal in 20 L of 0.5 mol / L dilute hydrochloric acid solution, stirring at 50°C for 4 h, adding a tin acetate solution with a molar concentration of 0.6 mol / L, stirring at 50°C for 5 h, and then centrifugally washing to remove excess metal ions, and vacuum drying at 80°C for 8 h to obtain a modified molecular sieve having a Lewis acid center, which is a demethoxylation catalyst; Step 3, heating the phenolamine bio-oil obtained in step 2 to 65° C. and then performing vacuum distillation until no distillate is produced, and the undistilled matter is the phenolamine pharmaceutical intermediate; Step 4: Take the sodium tungstate-catalyst-pyrolytic carbon mixture obtained in step 2 and add it to 50 L deionized water. After treating it at an ultrasonic power of 120 W for 60 min, centrifuge it and separate the mixture into two parts: sodium tungstate solution and catalyst-pyrolytic carbon solid mixture. Then, dry the separated catalyst-pyrolytic carbon solid mixture at 60 °C for 8 h, and then calcine it in an oxygen-rich atmosphere at 600 °C for 10 h to obtain a demethylation catalyst solid product, which is reused in step 2. Then, add 5 mol / L nitric acid solution to 50 L sodium tungstate solution until the pH of the solution is 2-4, so that sodium tungstate is converted into tungstic acid. At 50 °C, slowly add tungstic acid to 50 L of ammonia water with a mass concentration of 25%-28% that is constantly stirred for ammoniation treatment. After the solution is clarified for 12 h, place the tungstic acid solution after ammoniation treatment in an evaporating dish, heat it to 85 °C, evaporate and concentrate it under continuous stirring, and continue to evaporate to a solution concentration of 1.04-1.08 when tiny crystal nuclei appear. g / mL, stop concentrating and wash and dry to obtain ammonium paratungstate, which is reused in step 1.

[0020] Embodiment 5: like Figure 1 As shown, the present invention provides a method for preparing phenolamine pharmaceutical intermediates based on large-scale biomass pyrolysis, comprising the following steps: Step 1: add 10 kg of bamboo powder to 3 kg of NaOH solution with a mass concentration of 30%, stir at room temperature at a speed of 700 rpm for 20 min, add 17 kg of ammonium tungstate, ultrasonically treat at an ultrasonic power of 150 W for 25 min, then wash with deionized water 8 times, and then vacuum dry at 50 ° C for 10 h to obtain an ammonium tungstate-biomass composite; Step 2: 60 kg of demethylation catalyst and 10 kg of ammonium tungstate-biomass composite are placed in a microwave pyrolysis reactor, argon with a purity of 99.99% is continuously introduced at 600 mL / min for 1 h, the microwave power is set to 1000 W, the temperature is increased to 450 °C at a heating rate of 100 °C / min and kept warm for 30 min for pyrolysis to obtain pyrolysis gas products and pyrolysis solid products, the pyrolysis gas products are condensed at -25 °C to obtain catecholamine bio-oil, and the pyrolysis solid products are cooled to below 100 °C to obtain a sodium tungstate-catalyst-pyrolysis carbon mixture; Preferably, the demethylation catalyst is a modified molecular sieve having a Brönsted acid center, and the specific preparation method is: calcining 100 kg of HZSM-5 molecular sieve at 550 ° C for 2 h to remove impurities, then immersing 60 kg of the HZSM-5 molecular sieve after impurities removal in 20 L of 2 mol / L nitric acid solution, stirring at 60 ° C for 5 h, and then centrifuging and washing to neutrality, and vacuum drying at 80 ° C for 8 h to obtain a modified molecular sieve having a Brönsted acid center, which is a demethylation catalyst; Step 3, heating the catecholamine bio-oil obtained in step 2 to 90° C. and then performing vacuum distillation until no distillate is produced, and the undistilled matter is the catecholamine pharmaceutical intermediate; Step 4: Take 10 kg of the sodium tungstate-catalyst-pyrolytic carbon mixture obtained in step 2 and add it to 70 L of deionized water. After treating it at an ultrasonic power of 150 W for 50 min, centrifuge it and separate the mixture into two parts: sodium tungstate solution and catalyst-pyrolytic carbon solid mixture. Then, dry the separated catalyst-pyrolytic carbon solid mixture at 70 °C for 7 h, and then calcine it in an oxygen-rich atmosphere at 700 °C for 9 h to obtain a demethylation catalyst solid product, which is reused in step 2. Then, add 5 mol / L hydrochloric acid solution to 50 L of sodium tungstate solution until the pH of the solution is 2-4, so that sodium tungstate is converted into tungstic acid. At 55 °C, slowly add tungstic acid to 50 L of ammonia water with a mass concentration of 25%-28% that is constantly stirred for ammoniation. After the solution is clarified for 10 h, place the ammoniation-treated tungstic acid solution in an evaporating dish and simmer at 80 °C for 3 hours. Stir and heat to evaporate at a constant temperature of ℃. When the solution evaporates to the point where tiny crystal nuclei appear, continue evaporating until the remaining volume of the mother liquor is one-third of the original solution. Stop evaporation, cool, wash and dry to obtain ammonium tungstate, which is then reused in step one.

[0021] Embodiment 6: like Figure 1 As shown, the present invention provides a method for preparing phenolamine pharmaceutical intermediates based on large-scale biomass pyrolysis, comprising the following steps: Step 1: add 10 kg of bamboo powder to 5 kg of NaOH solution with a mass concentration of 30%, stir at room temperature at a speed of 800 rpm for 10 min, add 20 kg of ammonium metatungstate, ultrasonically treat at an ultrasonic power of 180 W for 20 min, then wash with deionized water 10 times, and then vacuum dry at 55 ° C for 8 h to obtain an ammonium metatungstate-biomass composite; Step 2: 70 kg of demethoxylation catalyst and 10 kg of ammonium metatungstate-biomass composite are placed in a microwave pyrolysis reactor, argon with a purity of 99.99% is continuously introduced at 600 mL / min for 1.5 h, the microwave power is set to 4000 W, the temperature is increased to 800 °C at a heating rate of 450 °C / min and kept warm for 5 min for pyrolysis to obtain pyrolysis gas products and pyrolysis solid products, the pyrolysis gas products are condensed at -25 °C to obtain phenolamine bio-oil, and the pyrolysis solid products are cooled to below 100 °C to obtain a sodium tungstate-catalyst-pyrolysis carbon mixture; Preferably, the demethoxylation catalyst is a modified molecular sieve having a Lewis acid center, and the preparation method is specifically as follows: calcining 100 kg of SBA-15 molecular sieve at 550 ° C for 2 h to remove impurities, then immersing 70 kg of the SBA-15 molecular sieve after impurities removal in 20 L of 1 mol / L dilute hydrochloric acid solution, stirring at 60 ° C for 3 h, adding a copper nitrate solution with a molar concentration of 1 mol / L, stirring at 80 ° C for 4 h, and then centrifugally washing to remove excess metal ions, and vacuum drying at 80 ° C for 8 h to obtain a modified molecular sieve having a Lewis acid center, which is a demethoxylation catalyst; Step 3, heating the phenolamine bio-oil obtained in step 2 to 60° C. and then performing reduced pressure distillation until no distillate is produced, and the undistilled matter is the phenolamine pharmaceutical intermediate; Step 4: Take 10 kg of the sodium tungstate-catalyst-pyrolytic carbon mixture obtained in step 2 and add it to 100 L of deionized water. After treating it at an ultrasonic power of 180 W for 30 min, centrifuge it and separate the mixture into two parts: sodium tungstate solution and catalyst-pyrolytic carbon solid mixture. Then, dry the separated catalyst-pyrolytic carbon solid mixture at 80 °C for 6 h, and then calcine it in an oxygen-rich atmosphere at 800 °C for 8 h to obtain a demethoxy catalyst solid product, which is reused in step 2. Then, add 6 mol / L sulfuric acid solution to 50 L of sodium tungstate solution until the pH of the solution is 2-4, so that sodium tungstate is converted into tungstic acid. At 60 °C, slowly add tungstic acid to 50 L of ammonia water with a mass concentration of 25%-28% under continuous stirring for ammoniation treatment. After the solution is clarified for 8 h, place the ammoniation-treated tungstic acid solution in an evaporating dish, heat it to 95 °C, evaporate and concentrate it under continuous stirring until crystal nuclei appear, and continue to evaporate to a solution concentration of 1.04-1.08 g / mL, stop and wash and dry to obtain ammonium paratungstate; heat the ammonium paratungstate to 280 °C and keep it for 10 min to obtain ammonium metatungstate, which is reused in step 1.

[0022] Table 1 Yields of phenolamine pharmaceutical intermediates in Examples 1-6

[0023] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or replace some or all of the technical features therein with equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for preparing phenolamine pharmaceutical intermediates based on large-scale biomass pyrolysis, characterized in that: The following steps are involved: S1, adding biomass into sodium hydroxide solution, stirring at room temperature, adding ammonium tungstate substances, performing ultrasonic treatment, washing, and vacuum drying to obtain ammonium tungstate-biomass composites; S2, adding a demethylation catalyst or a demethoxylation catalyst to the ammonium tungstate-biomass composite, introducing argon gas, and then performing a microwave pyrolysis reaction to obtain a pyrolysis gas product and a pyrolysis solid product, condensing the pyrolysis gas product to obtain a condensed product, and cooling the pyrolysis solid product to obtain a sodium tungstate-catalyst-pyrolysis carbon mixture; S3, heating the condensed product obtained in S2 and performing reduced pressure distillation to obtain a phenolamine pharmaceutical intermediate; S4, mixing the sodium tungstate-catalyst-pyrolytic carbon mixture obtained in S2 with deionized water, performing ultrasonic treatment and centrifugation to obtain a sodium tungstate solution and a catalyst-pyrolytic carbon solid mixture, drying the catalyst-pyrolytic carbon solid mixture, and then calcining it in an oxygen atmosphere to obtain the demethylation catalyst or demethoxylation catalyst in S2; The sodium tungstate solution is treated with acid, then subjected to ammoniation treatment, and then evaporated to obtain the ammonium tungstate substance in S1.

2. The method for preparing phenolamine pharmaceutical intermediates based on large-scale biomass pyrolysis according to claim 1, characterized in that: The mass ratio of the biomass, sodium hydroxide solution and ammonium tungstate in the S1 is 1: (0.2-0.5): (1.5-2); the stirring speed is 500-800 rpm, and the time is 10-30 min; the power of ultrasonic treatment is 120-180 W, and the time is 20-30 min; the number of washings is 5-10 times; the temperature of vacuum drying is 45-55 ° C, and the time is 8-12 h; the biomass is coniferous wood, broadleaf wood or grass raw material containing lignin; the ammonium tungstate is ammonium tungstate, ammonium paratungstate or ammonium metatungstate.

3. The method for preparing phenolamine pharmaceutical intermediates based on large-scale biomass pyrolysis according to claim 1, characterized in that: The S2 is specifically: A demethylation catalyst is added to the ammonium tungstate-biomass composite, 600 mL / min of argon is continuously introduced per kilogram of the ammonium tungstate-biomass composite, and then a microwave pyrolysis reaction is performed to obtain a pyrolysis gas product and a pyrolysis solid product, the pyrolysis gas product is condensed to obtain a catecholamine bio-oil, and the pyrolysis solid product is cooled to obtain a sodium tungstate-catalyst-pyrolysis carbon mixture; The demethylation catalyst is a modified molecular sieve with a Brönsted acid center; the time for passing argon is 1-1.5 h; the power of the microwave is 800-1500 W; the pyrolysis reaction is specifically: heating to 350-550 ° C at a heating rate of 80-150 ° C / min and keeping the temperature for 30 min for pyrolysis; the condensation temperature is -25 ° C; and the cooling is specifically cooling to below 100 ° C.

4. The method for preparing a phenolamine pharmaceutical intermediate based on large-scale biomass pyrolysis according to claim 3, characterized in that: The preparation method of the modified molecular sieve with Brönsted acid center is as follows: calcining the silicon-aluminum molecular sieve at 550°C for 2 hours to remove impurities, then immersing it in a 1-3 mol / L nitric acid solution, stirring it at 40-80°C for 4-6 hours, centrifuging it, washing it to neutrality, and vacuum drying it at 80°C for 8 hours to obtain the modified molecular sieve with Brönsted acid center.

5. The method for preparing phenolamine pharmaceutical intermediates based on large-scale biomass pyrolysis according to claim 1, characterized in that: The S2 is specifically: A demethoxy catalyst is added to the ammonium tungstate-biomass composite, argon is continuously introduced at a rate of 600 mL / min per kg of the ammonium tungstate-biomass composite, and then a microwave pyrolysis reaction is performed to obtain a pyrolysis gas product and a pyrolysis solid product, the pyrolysis gas product is condensed to obtain a phenolamine bio-oil, and the pyrolysis solid product is cooled to obtain a sodium tungstate-catalyst-pyrolysis carbon mixture; The demethoxylation catalyst is a modified molecular sieve with a Lewis acid center; the time for introducing argon is 1 to 1.5 h; the power of the microwave is 2000 to 4000 W; the pyrolysis reaction is specifically: heating to 600 to 800 ° C at a heating rate of 300 to 450 ° C / min and keeping the temperature for 5 min for pyrolysis; the condensation temperature is -25 ° C; and the cooling is specifically cooling to below 100 ° C.

6. The method for preparing phenolamine pharmaceutical intermediates based on large-scale biomass pyrolysis according to claim 5, characterized in that: The preparation method of the modified molecular sieve with Lewis acid center is as follows: calcining the silicon-aluminum molecular sieve at 550°C for 2 hours to remove impurities, then immersing it in a 0.5-1 mol / L dilute hydrochloric acid solution, stirring it at 30-60°C for 3-5 hours, adding it into a solution of metal ions with a molar concentration of 0.3-1 mol / L, stirring it at 40-80°C for 4-6 hours, and then centrifugally washing to remove excess metal ions, and vacuum drying it at 80°C for 8 hours to obtain the modified molecular sieve with Lewis acid center; The metal ion solution is ferric chloride, tin acetate, copper nitrate or cobalt nitrate.

7. The method for preparing phenolamine pharmaceutical intermediates based on large-scale biomass pyrolysis according to claim 1, characterized in that: The S3 is specifically: The condensed product is heated to 60-90°C and then distilled under reduced pressure until no distillate is produced, and the undistilled product is collected to obtain a phenolamine pharmaceutical intermediate.

8. The method for preparing phenolamine pharmaceutical intermediates based on large-scale biomass pyrolysis according to claim 1, characterized in that: The mass ratio of the sodium tungstate-catalyst-pyrolytic carbon mixture and deionized water in the S4 is 1: (5-10); the power of the ultrasonic treatment is 120-180 W, and the time is 30-60 min; the drying temperature is 60-80 ° C, and the time is 6-8 h; the oxygen atmosphere is specifically: a mixed gas of 50% by volume of air and 50% by volume of 99.999% oxygen; the calcination temperature is 600-800 ° C, and the time is 8-10 h.

9. The method for preparing phenolamine pharmaceutical intermediates based on large-scale biomass pyrolysis according to claim 1, characterized in that: The acid treatment in S4 is specifically: using an inorganic acid with a molar concentration of 4-6 mol / L to acidify the sodium tungstate solution to pH=2-4 to obtain tungstic acid; The ammoniation treatment is specifically as follows: adding tungstic acid to ammonia water with a mass concentration of 25% to 28% under constant stirring at 50 to 60 °C for ammoniation treatment, wherein the mass ratio of tungstic acid to ammonia water is 1:1, and then clarifying for 8 to 12 hours; The evaporation is specifically performed as follows: the tungstic acid solution after the ammoniation treatment is stirred and heated for evaporation at a constant temperature of 80°C, and when the solution evaporates to the appearance of crystal nuclei, the evaporation is continued until the volume of the remaining original solution of the mother liquor is one-third, and the evaporation is stopped. After cooling, the ammonium tungstate is obtained by washing and drying; or, the tungstic acid solution after the ammoniation treatment is heated to 85-95°C, evaporated and concentrated under constant stirring until crystal nuclei appear, and the evaporation is continued to the solution concentration of 1.04-1.08 g / mL, and the evaporation is stopped and washed and dried to obtain ammonium paratungstate, and the ammonium paratungstate is heated to 220-280°C and maintained for 10-20 min to obtain ammonium metatungstate.

10. A phenolamine pharmaceutical intermediate based on large-scale biomass pyrolysis, obtained by the preparation method of a phenolamine pharmaceutical intermediate based on large-scale biomass pyrolysis according to any one of claims 1 to 9.

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