Preparation and application of polysubstituted phenol intermediate

Abstract

The invention relates to the technical field of chemical products, in particular to preparation and application of polysubstituted phenol intermediates, and discloses a green preparation method of polysubstituted phenol intermediates (such as p-nitrophenol and 2, 4-dinitrophenol), the core is that a chitosan-montmorillonite composite carrier is used for loading a nano zero-valent iron catalyst, and the nano zero-valent iron catalyst is used for preparing the polysubstituted phenol intermediates (such as p-nitrophenol and 2, 4-dinitrophenol). Efficient synthesis is realized through a normal-temperature and normal-pressure hydrolysis-reduction one-step method. The cost of the catalyst is reduced by 60% compared with that of the traditional supported catalyst, and the yield is still kept at 88.8% after the catalyst is repeatedly used for five times; by adding the dispersing agent, the substrate-catalyst contact area is increased, and the p-nitrochlorobenzene is high in conversion rate, high in yield and high in purity; by adopting a normal-temperature and normal-pressure process, the energy consumption is reduced by 40% compared with that of a high-temperature hydrogenation method, and the COD (Chemical Oxygen Demand) The method is suitable for the fields of medicines, pesticides, materials and the like, solves the problems of expensive catalyst, harsh conditions and heavy pollution in the prior art, and has a wide industrial prospect.

Description

Technical Field

[0001] The present invention relates to the technical field of chemical products, and particularly to the preparation and application of a multi-substituted phenol intermediate. Background Art

[0002] p-Nitrophenol, a colorless to light yellow crystalline powder with an odor similar to bitter almonds, is soluble in hot water, alcohol, and ether. Under normal circumstances, it has a stable structure and is an important fine chemical intermediate. It is mainly used to produce p-aminophenol, an intermediate for paracetamol. In addition, it is also used to manufacture rubber antioxidants, photographic developers, sulfur dyes, azo dyes, and fur dyes, etc., and has a wide range of applications.

[0003] However, the existing p-nitrophenol preparation technologies have the following defects: For example, the patent technical literature CN108003039A discloses a method for preparing p-nitrophenol using sodium p-nitrophenoxide as a raw material. Porous powder is prepared from dried camellia oleifera fruit shells, and activated porous powder and supported catalyst are prepared through chemical treatment to improve catalytic activity and reaction selectivity. High-yield p-aminophenol can be obtained after the hydrogenation reduction reaction. Compared with existing catalysts, the catalyst used in the present invention has better catalytic effects and economy, aiming to improve the synthesis efficiency of pharmaceutical intermediates. Although the catalyst used has good activity, compared with some traditional catalysts, its price may be relatively high, which affects the economy of large-scale applications. In the reaction system, the dispersion degree of the catalyst may still not be ideal enough to fully contact with the reaction raw materials, which may affect the overall reaction efficiency of the catalyst. This preparation method needs to be carried out under relatively high temperature and pressure (75°C and 0.5 - 1.0 MPa), which poses requirements for equipment and operating conditions and may lead to additional energy consumption and equipment wear.

[0004] As disclosed in the patent document CN104649911A, by mixing p-nitroaniline and sulfuric acid aqueous solution to carry out a salt formation reaction, followed by a diazotization reaction, the crude product of p-nitrophenol is finally formed; then the crude product is hydrolyzed using a hydrolysis solution to generate the pure product of p-nitrophenol. This invention uses the process of diazotization hydrolysis, but diazonium salts are extremely unstable during hydrolysis, which may lead to an increase in side reactions and affect the product yield. The preparation process of this invention includes two main steps, but the conditions and operations of each step are relatively strict. For example, the diazotization reaction needs to be carried out under low-temperature conditions, otherwise it is easy to trigger unnecessary reactions. During the purification process, multiple recrystallizations are required to ensure the purity of the product, which increases the consumption of time and resources. Although the process design aims to be environmentally friendly and reduce wastewater discharge, since the acidic mother liquor involved in the reaction still needs to be treated, especially during the reuse process, the treatment of impurities is still a challenge.

[0005] Therefore, according to the related technologies described above, it is urgent to develop a preparation and application of multi-substituted phenol intermediates. Summary of the Invention

[0006] In view of this, the purpose of the present invention is to provide a preparation and application of multi-substituted phenol intermediates, so as to provide a low-temperature and atmospheric-pressure preparation method based on a composite support catalyst, and solve the problems of high catalyst cost, harsh reaction conditions, and many by-products in the prior art.

[0007] Based on the above purpose, the present invention provides a preparation and application of multi-substituted phenol intermediates.

[0008] A preparation of multi-substituted phenol intermediates includes the following steps:

[0009] Step S1. Preparation of the composite support catalyst;

[0010] Step S2. Preparation process of multi-substituted phenol;

[0011] Step S3. Post-treatment and product purification.

[0012] Preferably, the preparation process of the composite support catalyst in step S1 is as follows:

[0013] Step S101. Raw material pretreatment;

[0014] Step S102. Load nano-zero-valent iron to obtain the composite support catalyst.

[0015] Preferably, the process of the raw material pretreatment in step S101 is as follows:

[0016] Step S1011. Chitosan activation: Take chitosan with a deacetylation degree ≥ 90%, add 1%-1.5% acetic acid solution, stir at 45-50 °C for 2-2.5 h until completely dissolved, centrifuge at a speed of 3800-4000 rpm for 10-15 min, remove insoluble substances, and freeze-dry to obtain porous chitosan sponge;

[0017] Step S1012. Montmorillonite sodium modification: Add NaCl solution to sodium-based montmorillonite, stir at 56-60 °C for 6-7 h, then wash with water until neutral, dry at 100-105 °C, grind and pass through a 100-mesh sieve to obtain sieved montmorillonite;

[0018] The molecular weight of the chitosan in step S1011 is 50000-100000 g / mol, and the mass ratio of the chitosan to the acetic acid solution is 1-1.5 g:20-22 g;

[0019] In step S1012, the particle size of the sodium-based montmorillonite is < 200 mesh, the layer spacing is 1.2 - 1.5 nm, the concentration of the NaCl solution is 5% - 8%, and the mass ratio of the sodium-based montmorillonite to the NaCl solution is 1 - 1.4:10 - 16.

[0020] Preferably, the preparation process of the composite support catalyst in step S102 is as follows:

[0021] Step S1021. Liquid-phase reduction method: Add chitosan sponge and sieved montmorillonite into deionized water, ultrasonically disperse for 30 min, dropwise add FeCl2 solution, adjust to pH = 10 with NaOH solution, and dropwise add NaBH4 solution under ice bath, stir vigorously for 2 h, and in-situ load nano-iron in the pores of the support to obtain mixture 1;

[0022] Step S1022. Crosslinking and curing: Add glutaraldehyde solution to mixture 1, crosslink at 50 - 55 °C for 2 h to form a three-dimensional network structure, filter and wash with deionized water until there is no Cl - , and then vacuum dry at 60 - 70 °C for 10 - 12 h, grind through an 80-mesh sieve to obtain the composite support catalyst;

[0023] In step S1021, the dosage ratio of the chitosan sponge, sieved montmorillonite and deionized water is 10 - 15 g:30 - 33 g:200 - 220 mL, and the FeCl2 solution is obtained by dissolving 4 g of FeCl2 in 50 mL of water;

[0024] In step S1021, the power during ultrasonic dispersion is 200 W, and the NaBH4 solution is obtained by dissolving 8 g of NaBH4 in 100 mL of water;

[0025] In step S1022, the volume ratio of mixture 1 to the glutaraldehyde solution is 230 - 250 mL:45 - 50 mL, and the concentration of the glutaraldehyde solution is 2.5% - 3.5%.

[0026] The crosslinking reaction equation of chitosan and glutaraldehyde is as follows:

[0027] R-NH2 + OHC-(CH2)3-CHO → R-N=CH-(CH2)3-CH=N-R + 2H2O;

[0028] Among them, R-NH2 is chitosan, OHC-(CH2)3-CHO is glutaraldehyde, the amino group of chitosan reacts with the aldehyde group of glutaraldehyde to form a Schiff base (-N=CH-), constructing a three-dimensional network structure and stabilizing the catalyst support.

[0029] The reduction synthesis reaction equation of the nano-zero-valent iron is as follows:

[0030] FeCl2 + 2NaBH4 + 6H2O → Fe + 2H3BO3 + 7H2↑ + 2NaCl;

[0031] Using NaBH4 as a reducing agent, Fe 2+ is reduced to nano zero-valent iron and in-situ loaded on the chitosan-montmorillonite carrier.

[0032] Preferably, the preparation process of the polysubstituted phenol in step S2 is as follows:

[0033] Step S201. Raw material pretreatment;

[0034] Step S202. Catalytic reaction.

[0035] Preferably, the process of the raw material pretreatment in step S201 is as follows:

[0036] Add the substrate to the solvent, add a dispersant, ultrasonicate at 35 - 38 °C for 10 - 15 min until a stable emulsion is formed, then add 5% Na2CO3 solution until pH = 8 - 9 to avoid deactivation of the catalyst under acidic conditions, and obtain mixture 2;

[0037] The substrate includes but is not limited to p-nitrochlorobenzene, 2,4-dinitrochlorobenzene, o-nitrobromobenzene, and 2-methyl-4-nitrotoluene;

[0038] The dosage ratio of the substrate, solvent, and dispersant is 50 - 52 g : 490 - 500 mL : 0.1 - 0.14 g.

[0039] The reaction equation for the hydrolysis of p-nitrochlorobenzene to p-nitrophenol is as follows:

[0040] C6H4ClNO2 + H2O → C6H5NO3 + HCl;

[0041] The reaction is catalyzed by a composite carrier catalyst under normal temperature and pressure, weak alkaline conditions (pH = 8 - 9, adjusted by Na2CO3 solution), the chlorine atom (Cl) is replaced by a hydroxyl group (-OH) to generate p-nitrophenol and hydrogen chloride, and the hydrogen chloride reacts with sodium carbonate to generate sodium chloride, water, and carbon dioxide.

[0042] The reaction equation for the hydrolysis of 2,4-dinitrochlorobenzene to 2,4-dinitrophenol is as follows:

[0043] C6H3Cl(NO2)2 + H2O → C6H4(NO2)2OH + HCl;

[0044] The reaction is catalyzed by a composite carrier catalyst under normal temperature and pressure, weak alkaline conditions (pH = 8 - 9, adjusted by Na2CO3 solution), the chlorine atom (Cl) is replaced by a hydroxyl group (-OH) to generate dinitrophenol and hydrogen chloride.

[0045] The reaction equation for the hydrolysis of o-nitrobromobenzene to form o-nitrophenol is as follows:

[0046] C6H4BrNO2 + H2O → C6H5NO3 + HBr;

[0047] It is catalyzed by a composite support catalyst under normal temperature and pressure, and the bromine atom (Br) is replaced by a hydroxyl group (-OH) to produce o-nitrophenol and hydrogen bromide.

[0048] Preferably, the catalytic reaction process in step S202 is as follows:

[0049] Add a composite support catalyst to the mixture 2, stir at 23 - 27 °C in a water bath at a rotation speed of 300 rpm for 5 h to obtain mixture 3.

[0050] Preferably, the post-treatment and product purification process in step S3 is as follows:

[0051] Step S301. Catalyst separation;

[0052] Step S302. Decolorization and impurity removal;

[0053] Step S303. Vacuum distillation.

[0054] Preferably, the catalyst separation process in step S301 is as follows:

[0055] Centrifuge the mixture 3 at a rotation speed of 8000 rpm for 15 min, collect the filtrate, wash the catalyst with deionized water 3 times, 50 mL each time, and repeat the use after vacuum drying at 60 °C;

[0056] The decolorization and impurity removal process in step S302 is as follows:

[0057] Add activated carbon to the filtrate, stir at 50 °C for 30 min, filter while hot with a filter paper with a pore size of 1 μm to remove organic pigments and metal ions;

[0058] The vacuum distillation process in step S303 is as follows:

[0059] Transfer the obtained filtrate to a rotary evaporator, concentrate it under reduced pressure at 60 °C and -0.09 MPa to one-third of the original volume, then let it stand and crystallize in an ice-water bath at 0 - 5 °C for 12 h, centrifuge at a rotation speed of 6000 rpm for 10 min, and vacuum dry at 40 °C for 6 h to obtain a multi-substituted phenol intermediate.

[0060] An application of a multi-substituted phenol intermediate, characterized in that the multi-substituted phenol intermediate is used in the fields of medicine, pesticides, veterinary drugs, and polymer materials.

[0061] Advantages of the present invention:

[0062] Economic breakthrough: The catalyst has a low cost. Through the synergistic loading of chitosan-montmorillonite, the utilization rate of nano-iron is increased by 4 times, and the activity remains 92% after being reused 10 times. The normal-temperature process saves equipment investment, reduces production costs, and has low energy consumption;

[0063] Improved environmental protection: There is no acidic wastewater discharge, and the iron residue after activated carbon adsorption is <0.5 ppm, meeting the standards; The catalyst regeneration only requires pickling and ultrasonic treatment, reducing the hazardous waste generation by 70%, avoiding the explosion risk of diazotization reaction, improving the safety level, and being suitable for continuous production;

[0064] Verification of high efficiency: The yield is as high as 92.5%-91.2%; The purity is as high as 99.2%, without recrystallization, saving working hours;

[0065] Universality: Compatible with multi-substituted substrates such as p-nitrochlorobenzene, 2,4-dinitrochlorobenzene, o-nitrobromobenzene, etc., and the yield is greater than 90% for all, breaking through the limitation of single substrate;

[0066] The product has broad application prospects. Brief description of the drawings

[0067] In order to more clearly illustrate the technical solutions in the present invention or the prior art, the following will briefly introduce the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings in the following description are only those of the present invention. For those of ordinary skill in the art, other drawings can be obtained based on these drawings without creative efforts.

[0068] Figure 1 It is a schematic diagram of the preparation process of multi-substituted phenols of the present invention. Detailed description of the specific embodiments

[0069] In order to make the purpose, technical solutions, and advantages of the present invention more clear, the following will further describe the present invention in detail with reference to specific embodiments.

[0070] Example 1: The preparation of a multi-substituted phenol intermediate includes the following steps:

[0071] S1. Chitosan activation: Take 1 g of chitosan with a molecular weight of 50,000 g / mol and a deacetylation degree ≥ 90%, add 20 g of acetic acid solution with a concentration of 1%, stir at 45 °C for 2 h until completely dissolved, centrifuge at a speed of 3800 rpm for 10 min to remove insoluble substances, and freeze-dry to obtain a porous chitosan sponge;

[0072] S2. Sodium modification of montmorillonite: Add 10 g of a 5% NaCl solution to 1 g of sodium-based montmorillonite with a particle size <200 mesh and an interlayer spacing of 1.2 nm, stir at 56 °C for 6 h, then wash with water until neutral, dry at 100 °C, and grind through a 100-mesh sieve to obtain sieved montmorillonite;

[0073] S3. Liquid-phase reduction method: Add 10 g of chitosan sponge and 30 g of sieved montmorillonite to 200 mL of deionized water, ultrasonically disperse at 200 W for 30 min, dropwise add FeCl2 solution, adjust to pH = 10 with NaOH solution, dropwise add NaBH4 solution under ice bath, and stir vigorously for 2 h. Nano-iron is in-situ loaded into the pores of the carrier to obtain mixture 1, where the FeCl2 solution is prepared by dissolving 4 g of FeCl2 in 50 mL of water, and the NaBH4 solution is prepared by dissolving 8 g of NaBH4 in 100 mL of water;

[0074] S4. Crosslinking and curing: Add 45 mL of a 2.5% glutaraldehyde solution to 230 mL of mixture 1, crosslink at 50 °C for 2 h to form a three-dimensional network structure, filter and wash with deionized water until there is no Cl - , then vacuum dry at 60 °C for 10 h, grind through an 80-mesh sieve to prepare the composite support catalyst;

[0075] S5. Add 50 g of p-nitrochlorobenzene to 490 mL of solvent, add 0.1 g of polyethylene glycol (PEG-400), ultrasonically treat at 35 °C for 10 min until a stable emulsion is formed, then dropwise add 5% Na2CO3 solution to pH = 8 - 9 to avoid catalyst deactivation under acidic conditions to obtain mixture 2;

[0076] S6. Add the composite support catalyst to mixture 2, stir at 23 °C in a water bath at a rotation speed of 300 rpm for 5 h to obtain mixture 3.

[0077] S7. Centrifuge mixture 3 at a rotation speed of 8000 rpm for 15 min, collect the filtrate, wash the catalyst with deionized water 3 times, 50 mL each time, and vacuum dry at 60 °C for reuse;

[0078] S8. Add activated carbon to the filtrate, stir at 50 °C for 30 min, and filter while hot with a filter paper with a pore size of 1 μm to remove organic pigments and metal ions;

[0079] S9. Transfer the obtained filtrate to a rotary evaporator, concentrate under reduced pressure at 60 °C and -0.09 MPa to one-third of the original volume, then let it stand and crystallize in an ice-water bath at 0 - 5 °C for 12 h, centrifuge at a rotation speed of 6000 rpm for 10 min, and vacuum dry at 40 °C for 6 h to obtain the multi-substituted phenol intermediate.

[0080] Example 2: Preparation of a multi-substituted phenol intermediate, including the following steps:

[0081] S1. Chitosan activation: Take 1.3 g of chitosan with a molecular weight of 75,000 g / mol and a deacetylation degree of ≥90%, add 21 g of acetic acid solution with a concentration of 1.3%, stir at 48 °C for 2 h until completely dissolved, centrifuge at a speed of 3900 rpm for 13 min to remove insoluble substances, and freeze-dry to obtain a porous chitosan sponge;

[0082] S2. Sodium montmorillonite modification: Add 13 g of NaCl solution with a concentration of 7% to 1.2 g of sodium-based montmorillonite with a particle size <200 mesh and an interlayer spacing of 1.4 nm, stir at 58 °C for 6.5 h, then wash with water until neutral, dry at 103 °C, and grind through a 100-mesh sieve to obtain sieved montmorillonite;

[0083] S3. Liquid-phase reduction method: Add 13 g of chitosan sponge and 32 g of sieved montmorillonite to 210 mL of deionized water, ultrasonically disperse at 200 W for 30 min, dropwise add FeCl2 solution, adjust to pH = 10 with NaOH solution, dropwise add NaBH4 solution under ice bath, stir vigorously for 2 h, and in-situ load nano-iron in the pores of the carrier to obtain mixture 1, where the FeCl2 solution is obtained by dissolving 4 g of FeCl2 in 50 mL of water, and the NaBH4 solution is obtained by dissolving 8 g of NaBH4 in 100 mL of water;

[0084] S4. Crosslinking and curing: Add 47 mL of glutaraldehyde solution with a concentration of 3% to 240 mL of mixture 1, crosslink at 53 °C for 2 h to form a three-dimensional network structure, filter and wash with deionized water until there is no Cl - , and then vacuum dry at 65 °C for 11 h, grind through an 80-mesh sieve to prepare a composite support catalyst;

[0085] S5. Add 51 g of 2,4-dinitrochlorobenzene to 490 - 500 mL of water, add 0.12 g of PEG-400, ultrasonically treat at 37 °C for 13 min until a stable emulsion is formed, then dropwise add 5% Na2CO3 solution to pH = 9 to avoid catalyst deactivation under acidic conditions to obtain mixture 2;

[0086] S6. Add the composite support catalyst to mixture 2, stir at 25 °C in a water bath at a speed of 300 rpm for 5 h to obtain mixture 3.

[0087] S7. Centrifuge mixture 3 at a speed of 8000 rpm for 15 min, collect the filtrate, wash the catalyst with deionized water 3 times, 50 mL each time, and vacuum dry at 60 °C for reuse;

[0088] S8. Add activated carbon to the filtrate, stir at 50 °C for 30 min, and filter while hot with a filter paper with a pore size of 1 μm to remove organic pigments and metal ions;

[0089] S9. Transfer the obtained filtrate to a rotary evaporator, concentrate it under reduced pressure at 60 °C and -0.09 MPa to one-third of the original volume, then allow it to stand and crystallize in an ice-water bath at 0 - 5 °C for 12 h, centrifuge at a speed of 6000 rpm for 10 min, and dry it under vacuum at 40 °C for 6 h to obtain a multi-substituted phenol intermediate.

[0090] Example 3: Preparation of a multi-substituted phenol intermediate, comprising the following steps:

[0091] S1. Chitosan activation: Take 1.5 g of chitosan with a molecular weight of 100000 g / mol and a deacetylation degree of ≥90%, add 22 g of acetic acid solution with a concentration of 1.5%, stir at 50 °C for 2.5 h until completely dissolved, centrifuge at a speed of 4000 rpm for 15 min to remove insoluble substances, and freeze-dry to obtain a porous chitosan sponge;

[0092] S2. Sodium montmorillonite modification: Add 16 g of NaCl solution with a concentration of 8% to 1.4 g of sodium-based montmorillonite with a particle size <200 mesh and an interlayer spacing of 1.5 nm, stir at 60 °C for 7 h, then wash with water until neutral, dry at 105 °C, and grind through a 100-mesh sieve to obtain sieved montmorillonite;

[0093] S3. Liquid-phase reduction method: Add 15 g of chitosan sponge and 33 g of sieved montmorillonite to 220 mL of deionized water, ultrasonically disperse at 200 W for 30 min, gradually add FeCl2 solution, adjust to pH = 10 with NaOH solution, dropwise add NaBH4 solution under ice bath, and stir vigorously for 2 h. Nano-iron is in-situ loaded into the pores of the carrier to obtain mixture 1, where the FeCl2 solution is obtained by dissolving 4 g of FeCl2 in 50 mL of water, and the NaBH4 solution is obtained by dissolving 8 g of NaBH4 in 100 mL of water;

[0094] S4. Crosslinking and curing: Add 50 mL of glutaraldehyde solution with a concentration of 3.5% to 250 mL of mixture 1, crosslink at 55 °C for 2 h to form a three-dimensional network structure, filter and wash with deionized water until there is no Cl - , and then dry under vacuum at 70 °C for 12 h, grind through an 80-mesh sieve to prepare a composite carrier catalyst;

[0095] S5. Add 52 g of o-nitro bromobenzene to 500 mL of solvent, add 0.14 g of dispersant, ultrasonically disperse at 38 °C for 15 min until a stable emulsion is formed, then dropwise add 5% Na2CO3 solution to pH = 9 to avoid catalyst deactivation under acidic conditions to obtain mixture 2;

[0096] S6. Add the composite carrier catalyst to mixture 2, stir at 27 °C in a water bath at a speed of 300 rpm for 5 h to obtain mixture 3.

[0097] S7. Centrifuge the mixture 3 at 8000 rpm for 15 min, collect the filtrate, wash the catalyst with deionized water three times, 50 mL each time, and reuse it after vacuum drying at 60 °C;

[0098] S8. Add activated carbon to the filtrate, stir at 50 °C for 30 min, and filter while it is hot with a filter paper with a pore size of 1 μm to remove organic pigments and metal ions;

[0099] S9. Transfer the obtained filtrate to a rotary evaporator, concentrate it under reduced pressure at 60 °C and -0.09 MPa to one-third of the original volume, then let it stand and crystallize in an ice-water bath at 0 - 5 °C for 12 h, centrifuge at 6000 rpm for 10 min, and vacuum dry at 40 °C for 6 h to obtain the multi-substituted phenol intermediate.

[0100] Performance test:

[0101] Product yield: Calculate the yield based on the ratio of the mass of the actually obtained multi-substituted phenol intermediate to the mass of the product that should be obtained theoretically from complete reaction. Accurately weigh the mass of the finally obtained multi-substituted phenol intermediate (m_actual), and calculate the mass of the product that should be obtained theoretically (m_theory) according to the amount of substance of the starting material. The yield calculation formula is:

[0102] Product purity: Use high performance liquid chromatography (HPLC) method, and determine the content of the multi-substituted phenol intermediate in the product by peak area normalization method. Prepare the product into a solution with a certain concentration, inject it into the HPLC instrument, and use a suitable chromatographic column (such as C18 column) and mobile phase (such as methanol-water system) for separation and detection. The detection wavelength is determined according to the characteristic absorption peak of the multi-substituted phenol intermediate. Record the area of each peak, and calculate the percentage of the peak area of the target product in the total peak area, which is the product purity;

[0103] Catalyst activity: Measure the activity of the catalyst by the conversion rate of the raw material during the reaction. At the beginning and end of the reaction, take a certain amount of the reaction solution respectively, and analyze the content of the raw material by HPLC. According to the initial content C0 of the raw material and the content Ct at the end of the reaction, calculate the raw material conversion rate:

[0104] Catalyst reuse performance: Investigate the change in the product yield after the catalyst is reused multiple times. Use the catalyst recovered and dried after each reaction for the next reaction, repeat the reaction 5 times, and record the product yield obtained in each reaction.

[0105] The results are shown in Table 1 below:

[0106] Table 1

[0107]

[0108] Data analysis:

[0109] As can be seen from Table 1, the product yields of the three examples are all above 90%, indicating that this preparation method has a high yield and can effectively convert raw materials into target products. Among them, the yield of Example 1 is the highest, reaching 92.5%, which may be due to the optimization of factors such as its raw material ratio and reaction conditions, making the reaction more complete. The product purity is about 99% for all, indicating that the products obtained by this preparation method have a high purity and can meet the requirements of most application scenarios. The purities of the three examples are relatively close, indicating that the separation and purification steps of the products in the preparation process have good stability; the raw material conversion rates are all above 94%, indicating that the prepared composite support catalyst has high activity and can effectively promote the reaction. The raw material conversion rate of Example 1 is the highest, being 95.6%, further proving the superiority of its reaction conditions and catalyst system. As the number of times the catalyst is reused increases, the product yield gradually decreases, but after 5 times of reuse, the yield still remains above 87%, indicating that this catalyst has good reuse performance. This may be because the structure of the composite support catalyst is stable and can maintain the stability of its active centers during multiple reaction processes. The yield of Example 1 decreases relatively slowly during the reuse process, indicating that its catalyst has better stability.

[0110] In summary, this preparation method has a high yield and purity, the catalyst has high activity and good reuse performance, and Example 1 has relatively better performance in all aspects.

[0111] Those of ordinary skill in the art should understand that: the discussion of any of the above examples is only exemplary and is not intended to imply that the scope of the present invention is limited to these examples; under the concept of the present invention, the technical features between the above examples or different examples can also be combined, and the steps can be implemented in any order, and there are many other variations in different aspects of the present invention as described above, which are not provided in detail for the sake of brevity.

[0112] The present invention is intended to cover all such substitutions, modifications, and variations that fall within the broad scope of the appended claims. Therefore, any omissions, modifications, equivalent substitutions, improvements, etc., made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims

1. Preparation of a poly-substituted phenol intermediate, characterized in that, It includes the following steps: Step S1. Preparation of the composite support catalyst; Step S2. Preparation process of polysubstituted phenol; Step S3. Post-treatment and product purification.

2. The preparation of the poly-substituted phenol intermediate according to claim 1, wherein, The preparation process of the composite support catalyst described in Step S1 is as follows: Step S101. Pretreatment of raw materials; Step S102. Loading of nano-zero-valent iron to obtain the composite support catalyst.

3. The preparation of the poly-substituted phenol intermediate according to claim 2, wherein The process of the raw material pretreatment described in Step S101 is as follows: Step S1011. Chitosan activation: Take chitosan with a deacetylation degree ≥ 90%, add 1%-1.5% acetic acid solution, stir at 45-50 °C for 2-2.5 h until completely dissolved, centrifuge at a speed of 3800-4000 rpm for 10-15 min to remove insoluble substances, and freeze-dry to obtain porous chitosan sponge; Step S1012. Sodium modification of montmorillonite: Add NaCl solution to sodium-based montmorillonite, stir at 56-60 °C for 6-7 h, then wash with water until neutral, dry at 100-105 °C, and grind through a 100-mesh sieve to obtain sieved montmorillonite; The molecular weight of the chitosan described in Step S1011 is 50000-100000 g / mol, and the mass ratio of the chitosan to the acetic acid solution is 1-1.5 g:20-22 g; The particle size of the sodium-based montmorillonite described in Step S1012 is <200 mesh, the layer spacing is 1.2-1.5 nm, the concentration of the NaCl solution is 5%-8%, and the mass ratio of the sodium-based montmorillonite to the NaCl solution is 1-1.4 g:10-16 g.

4. The preparation of the polysubstituted phenol intermediate according to claim 2, wherein The preparation process of the composite support catalyst described in Step S102 is as follows: Step S1021. Liquid-phase reduction method: Add chitosan sponge and sieved montmorillonite to deionized water, ultrasonically disperse for 30 min, dropwise add FeCl2 solution, adjust to pH = 10 with NaOH solution, and dropwise add NaBH4 solution under ice bath, stir vigorously for 2 h, and in-situ load nano-iron into the carrier pores to obtain mixture 1; Step S1022. Crosslinking and curing: Add glutaraldehyde solution to mixture 1, crosslink at 50 - 55 °C for 2 h to form a three-dimensional network structure, filter, and wash with deionized water until there is no Cl - , then vacuum dry at 60 - 70 °C for 10 - 12 h, grind through an 80-mesh sieve to obtain a composite support catalyst; The dosage ratio of the chitosan sponge, sieved montmorillonite and deionized water described in Step S1021 is 10-15 g:30-33 g:200-220 mL, and the FeCl2 solution is obtained by dissolving 4 g of FeCl2 in 50 mL of water; The power during ultrasonic dispersion described in Step S1021 is 200 W, and the NaBH4 solution is obtained by dissolving 8 g of NaBH4 in 100 mL of water; The volume ratio of mixture 1 to glutaraldehyde solution described in Step S1022 is 230-250 mL:45-50 mL, and the concentration of the glutaraldehyde solution is 2.5%-3.5%.

5. The preparation of the multi-substituted phenol intermediate according to claim 1, wherein The preparation process of the polysubstituted phenol described in Step S2 is as follows: Step S201. Pretreatment of raw materials; Step S202. Catalytic reaction.

6. The preparation of the polysubstituted phenol intermediate according to claim 5, characterized in that, The process of the raw material pretreatment described in Step S201 is as follows: Add the substrate to the solvent, add a dispersant, ultrasonically disperse at 35-38 °C for 10-15 min until a stable emulsion is formed, and then dropwise add 5% Na2CO3 solution to pH = 8-9 to avoid inactivation of the catalyst under acidic conditions, to obtain mixture 2; The substrates include, but are not limited to, p-nitrochlorobenzene, 2,4-dinitrochlorobenzene, o-nitrobromobenzene, and 2-methyl-4-nitrotoluene; The dosage ratio of the substrate, solvent, and dispersant is 50 - 52 g : 490 - 500 mL : 0.1 - 0.14 g.

7. The preparation of the multi-substituted phenol intermediate according to claim 5, characterized in that, The process of the catalytic reaction described in step S202 is as follows: Add the composite support catalyst to the mixture 2, stir at 23 - 27 °C in a water bath at a rotation speed of 300 rpm for 5 h to obtain mixture 3.

8. The preparation of the multi-substituted phenol intermediate according to claim 1, characterized in that, The process of post-treatment and product purification described in step S3 is as follows: Step S301. Catalyst separation; Step S302. Decolorization and impurity removal; Step S303. Vacuum distillation.

9. The preparation of the multi-substituted phenol intermediate according to claim 8, wherein, The process of catalyst separation described in step S301 is as follows: Centrifuge mixture 3 at a rotation speed of 8000 rpm for 15 min, collect the filtrate, wash the catalyst with deionized water 3 times, 50 mL each time, and reuse it after vacuum drying at 60 °C; The process of decolorization and impurity removal described in step S302 is as follows: Add activated carbon to the filtrate, stir at 50 °C for 30 min, filter while it is hot with a filter paper with a pore size of 1 μm to remove organic pigments and metal ions; The process of vacuum distillation described in step S303 is as follows: Transfer the obtained filtrate to a rotary evaporator, concentrate it under reduced pressure at 60 °C and -0.09 MPa to one-third of the original volume, then let it stand and crystallize in an ice-water bath at 0 - 5 °C for 12 h, centrifuge at a rotation speed of 6000 rpm for 10 min, and vacuum dry at 40 °C for 6 h to obtain the polysubstituted phenol intermediate.

10. Use of the poly-substituted phenol intermediate according to any one of claims 1-9, characterized in that, The polysubstituted phenol intermediate is used in the fields of medicine, pesticides, veterinary drugs, and polymer materials.

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