Preparation method of 1, 1-cyclohexyl diacetic acid

Abstract

The invention relates to the technical field of organic synthesis, in particular to a preparation method of 1, 1-cyclohexyl diacetic acid. The preparation method comprises the following steps: taking cyclohexanone and ethyl cyanoacetate as raw materials to react and dehydrate to prepare a product 1, then reacting cyanoacetamide, sodium methoxide and the product 1 at low temperature to obtain a product 2, and then hydrolyzing the product 2 under the catalysis of a magnetic solid double-acid catalyst to obtain the 1, 1-cyclohexyl diacetic acid. The used magnetic solid double-acid catalyst is prepared by loading a metal active layer and a sulfonic acid group on a magnetic mesoporous silicon dioxide carrier step by step, and has Lewis acid and Bronsted acid sites, and the catalyst is separated by an external magnetic field after the reaction. The method is short in reaction time and high in catalytic efficiency, the catalyst can be recycled, the separation problem of traditional homogeneous acid catalysis is avoided, and the method has the advantages of being mild in reaction condition, high in yield, environmentally friendly and the like and is suitable for industrial production of 1, 1-cyclohexyl diacetic acid.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of organic synthesis, and particularly relates to a preparation method of 1,1-cyclohexyl diacetic acid. BACKGROUND

[0002] 1,1-cyclohexyl diacetic acid, as an important intermediate in organic synthesis, has wide application value in the fields of medicine, pesticide, polymer material and the like, especially as a key structural unit of some bioactive molecules. Therefore, it is of great significance to develop an efficient, green and industrialized synthesis method of 1,1-cyclohexyl diacetic acid.

[0003] The traditional synthesis route of 1,1-cyclohexyl diacetic acid usually involves a hydrolysis step of a cyano compound. However, the existing technology has many limitations: firstly, the hydrolysis of cyano often needs to use concentrated sulfuric acid as a catalyst, which is highly corrosive, and the reaction conditions are harsh, resulting in serious equipment corrosion, a large amount of acidic wastewater difficult to handle, serious environmental pollution, and many side reactions, and the yield of the target product is low. Secondly, although some studies have tried to replace concentrated sulfuric acid with high-temperature liquid water or other methods, these methods often have high energy consumption, long reaction time, or problems such as difficult separation and purification of the product, which limits their large-scale industrial application. Thirdly, the existing catalytic system (such as homogeneous acid catalyst) generally has the problem of difficult recycling of the catalyst, which increases the production cost and does not meet the requirements of green chemistry and sustainable development. Especially for the key step of cyano hydrolysis in multi-step synthesis, it is urgent to develop a new type of catalyst with high activity, good selectivity, easy separation and recyclability and a supporting process. SUMMARY

[0004] The present application aims at solving the problems in the prior art and provides a preparation method of 1,1-cyclohexyl diacetic acid.

[0005] In order to achieve the above purpose, the present application provides a preparation method of 1,1-cyclohexyl diacetic acid, which comprises the following steps:

[0006] (1) ethyl cyanoacetate, cyclohexanone, ammonium acetate and acetic acid are added into toluene, and the temperature is raised to 120-140 DEG C, and the reaction is carried out for 3-5 h, after the reaction is completed, the toluene is recovered under reduced pressure, ethyl acetate is added, and the pH is adjusted to neutral with sodium hydroxide solution, the organic layer is separated, the water layer is extracted with ethyl acetate for 2-3 times, the organic phases are combined, dried with anhydrous magnesium sulfate, and the solvent is removed to obtain a colorless liquid as the product 1, and the chemical reaction equation is as follows:

[0007] The structure of the product is confirmed by H NMR;

[0008] (2) methanol, cyanoacetamide and sodium methoxide were added into a reaction bottle, stirred at room temperature for 15-25 min, cooled to -5-0 °C, and the product 1 was added dropwise, the dropwise addition time was 1-2 h, after the dropwise addition was completed, the temperature was increased to 15-25 °C, and the reaction was carried out for 1-2 h, the obtained solid was washed, added into deionized water, heated to dissolve, adjusted to pH 2-3 with concentrated HCl, and a white solid was precipitated, which was filtered, washed, and dried to obtain the product 2, and the chemical reaction equation was as follows: The structure of the product was confirmed by H NMR;

[0009] (3) the product 2, the magnetic solid double acid catalyst and deionized water were added into a high-pressure reaction kettle, the temperature was increased to 140-160 °C, and the reaction was carried out for 2-4 h, the temperature was cooled to room temperature, the magnetic solid double acid catalyst and the product were separated by an external magnetic field, the product was recrystallized in a methanol / water mixed solution to obtain 1,1-cyclohexyl diacetic acid, and the chemical reaction equation was as follows:

[0010] The structure of the product was confirmed by H NMR;

[0011] The preparation steps of the magnetic solid double acid catalyst include:

[0012] S1. ferric chloride solution and ferrous sulfate solution were respectively prepared, the ferric chloride solution and the ferrous sulfate solution were mixed under a nitrogen atmosphere, the temperature was increased to 50-60 °C under stirring, the pH was adjusted to 9-11 with ammonia water, and the reaction was carried out for 1-2 h, after the reaction was completed, the product was precipitated by an external magnetic field, washed, and dried to obtain magnetic Fe3O4 nanoparticles;

[0013] S2. cetyltrimethylammonium bromide was added into deionized water, stirred for 5-10 min, magnetic Fe3O4 nanoparticles were added, ultrasonic dispersion was carried out for 20-40 min, sodium hydroxide solution was added, the temperature was increased to 50-60 °C, stirring was carried out for 20-30 min, tetraethyl orthosilicate and ethanol were finally added, the reaction was carried out for 10-14 h, the temperature was cooled to room temperature, the product was precipitated by an external magnetic field, washed, and dried, and the magnetic mesoporous silica was obtained after calcination at 350-450 °C for 3-5 h;

[0014] S3. The triblock copolymer P123 is added to anhydrous ethanol and stirred for 10-20 min, then aluminum nitrate and zinc nitrate are added, and the pH is adjusted to neutral with triethylamine, and the temperature is raised to 40-50°C and stirred for 1-3 h, then magnetic mesoporous silica is added and stirred for 2-4 h, filtered, washed, and dried, then calcined at 350-450°C for 3-5 h to obtain magnetic silica loaded with metal active layers, which are formed by calcination of aluminum nitrate and zinc nitrate, to introduce Lewis acid sites that form a dual-acid synergistic catalytic system with the sulfonic acid groups grafted in the subsequent step (Bronsted acid sites), Al 3+ and Zn 2+ as Lewis acid centers, which coordinate with the lone pair electrons of the cyano group through empty orbitals, activate the C≡N bond, and reduce the reaction activation energy; at the same time, the addition of triblock copolymer P123 in the preparation process introduces mesoporous structures again in the metal active layer and combines with the high specific surface area of the mesoporous silica support, ensuring uniform distribution of active sites and promoting the hydrolysis of the cyano group in cooperation with the subsequently introduced sulfonic acid groups, achieving efficient synthesis of 1,1-cyclohexyl diacetic acid.

[0015] S4. The magnetic silica loaded with metal active layers and 1,3-propane sulfone are added to anhydrous toluene, the temperature is raised to 100-120°C, and the reaction is carried out for 24-48 h, then the product is settled under an external magnetic field, washed, and dried to obtain a magnetic solid dual-acid catalyst, and the chemical reaction schematic is as follows:

[0016] The introduction of sulfonic acid groups forms a dual-acid site that synergistically activates the cyano group, and the proton (H + ) released by the Bronsted acid site (-SO3H) directly coordinates with the nitrogen atom of the cyano group (-C≡N), forming a positively charged intermediate (-C≡N + H), which causes the π-electron cloud of the carbon-nitrogen triple bond to shift towards nitrogen, making the carbon atom exhibit positive electronegativity (δ + ), making it more susceptible to attack by nucleophiles; at the same time, the Lewis acid site (Al 3+ / Zn 2+ ) coordinates with the nitrogen atom through empty orbitals, further enhancing the activation of the carbon-nitrogen bond, and the activated cyano group undergoes hydrolysis to form a carboxyl group.

[0017] Preferably, in (1), the molar ratio of ethyl cyanoacetate, cyclohexanone, ammonium acetate, and acetic acid is 1:0.7-1.2:0.08-0.12:0.2-0.4, and the weight ratio of ethyl cyanoacetate, toluene, and ethyl acetate is 1:5-9:5-9.

[0018] Preferably, in (1), the concentration of the sodium hydroxide solution is 1 mol / L.

[0019] Preferably, the cyanoacetamide, sodium methoxide and product 1 in (2) are in a molar ratio of 1-1.4:0.15-0.2:1.

[0020] Preferably, the product 1, methanol and deionized water in (2) are in a weight ratio of 1:5-10:10-12.

[0021] Preferably, the concentrated HCl in (2) refers to a hydrochloric acid solution with a mass concentration of 36%.

[0022] Preferably, the product 2, magnetic solid double acid catalyst and deionized water in (3) are in a weight ratio of 1:0.2-0.28:5-7.

[0023] Preferably, the methanol / water mixed solution in (3) refers to a mixture of methanol and water in a weight ratio of 3:2.

[0024] Preferably, the ferric chloride solution and ferrous sulfate solution in S1 are in a weight ratio of 1.2-1.6:0.8-1.

[0025] Preferably, the concentration of the ferric chloride solution and the concentration of the ferrous sulfate solution in S1 are both 0.4 mol / L.

[0026] Preferably, the cetyltrimethylammonium bromide, deionized water, magnetic Fe3O4 nanoparticles, sodium hydroxide solution, tetraethyl orthosilicate and ethanol in S2 are in a weight ratio of 0.08-0.12:80-120:1:80-120:1-1.2:15-25.

[0027] Preferably, the concentration of the sodium hydroxide solution in S2 is 10 mmol / L.

[0028] Preferably, the triblock copolymer P123, magnetic mesoporous silica, aluminum nitrate, zinc nitrate and anhydrous ethanol in S3 are in a weight ratio of 0.04-0.07:1:0.14-0.16:0.1-0.12:8-12.

[0029] Preferably, the magnetic silica loaded with metal active layer, 1,3-propane sultone and anhydrous toluene in S4 are in a weight ratio of 1:1-1.6:8-10.

[0030] Advantages of the present application:

[0031] 1. The preparation method of 1,1-cyclohexyl diacetic acid provided by the present application does not need to undergo long-time low-temperature reaction compared with the traditional synthesis method, greatly shortens the reaction time, provides a preparation method with faster reaction rate, lower cost and less pollution, and is thus suitable for industrialized production.

[0032] 2.The application forms a Lewis acid and Bronsted acid dual acid synergistic catalytic system by constructing a "magnetic core-mesoporous silica-metal active layer-sulfonic acid group" composite structure, and the dual acid sites activate the cyano group through proton coordination and electronic polarization double action, reduce the activation energy of the hydrolysis reaction, significantly improve the catalytic efficiency, and realize the efficient synthesis of 1,1-cyclohexyl diacetic acid, which breaks through the limitations of traditional single acid catalysis, synchronously optimizes the cyano activation and hydrolysis process, shortens the reaction time and improves the product yield.

[0033] 3.The application introduces a magnetic Fe3O4 core to give the catalyst high efficient magnetic responsiveness, which can be quickly separated by an external magnetic field after the reaction is completed, avoiding the catalyst loss and activity attenuation caused by traditional filtration or centrifugation operation, and the separation method is simple in operation and low in energy consumption, and the catalyst can still maintain stable catalytic activity after being used for multiple cycles, thereby reducing the catalyst cost and material loss in industrial production, and improving the process continuity.

[0034] 4.The application forms a regular pore structure of the silica carrier and the metal active layer through a template agent, and the structure has high specific surface area and suitable pore size, and provides a uniform support platform for the metal oxide and the sulfonic acid group, which not only promotes the full contact of the substrate and the active site, but also optimizes the mass transfer efficiency in the reaction system, avoids the pore blockage or active site burial, ensures the efficient performance of the catalytic reaction, and provides a good physical basis for product separation.

[0035] 5.The application avoids using traditional homogeneous strong acid catalysts, adopts an environmentally friendly solid dual acid catalytic system, reduces wastewater discharge and equipment corrosion problems, and through accurate regulation and control of the template agent, metal loading and sulfonation process in the catalyst preparation process, the occurrence rate of side reactions is reduced, the product purity is high, the post-treatment is simple, the green chemical synthesis requirements are met, and the environmentally friendly advantages of industrial application are possessed. BRIEF DESCRIPTION OF DRAWINGS

[0036] Figure 1 H NMR spectrum of product 1 prepared in Example 2 of the application;

[0037] Figure 2 H NMR spectrum of product 2 prepared in Example 2 of the application;

[0038] Figure 3 H NMR spectrum of 1,1-cyclohexyl diacetic acid prepared in Example 2 of the application;

[0039] Figure 4 SEM image of the magnetic solid dual acid catalyst prepared in Preparation Example 2 of the application. DETAILED DESCRIPTION

[0040] In order to make the objectives, technical solutions and advantages of the present application clearer, the present application will be further described in detail below with specific examples.

[0041] Preparation Example 1: the specific preparation process of the magnetic solid dual-acid catalyst, comprising the following steps:

[0042] S1. Prepare a ferric chloride solution and a ferrous sulfate solution with a concentration of 0.4 mol / L respectively, mix 120 ml of the ferric chloride solution and 80 ml of the ferrous sulfate solution under a nitrogen atmosphere, heat to 50℃ under stirring, adjust the pH to 9 with ammonia water, and react for 1 h. After the reaction is completed, the product is settled under an external magnetic field, washed, dried, and then magnetic Fe3O4 nanoparticles are obtained;

[0043] S2. Add 0.4 g of cetyltrimethylammonium bromide to 400 g of deionized water, stir for 5 min, then add 5 g of the magnetic Fe3O4 nanoparticles, ultrasonically disperse for 20 min, add 400 g of a sodium hydroxide solution with a concentration of 10 mmol / L, heat to 50℃, stir for 20 min, finally add 5 g of tetraethyl orthosilicate and 75 g of ethanol, react for 10 h, cool to room temperature, the product is settled under an external magnetic field, washed, dried, and then calcined at 350℃ for 3 h to obtain magnetic mesoporous silica;

[0044] S3. Add 0.2 g of triblock copolymer P123 to 40 g of anhydrous ethanol, stir for 10 min, add 0.7 g of aluminum nitrate and 0.5 g of zinc nitrate, adjust the pH to neutral with triethylamine, heat to 40℃, stir for 1 h, then add 5 g of the magnetic mesoporous silica, stir for 2 h, filter, wash, dry, and then calcine at 350℃ for 3 h to obtain magnetic silica loaded with a metal active layer;

[0045] S4. Add 5 g of the magnetic silica loaded with a metal active layer and 5 g of 1,3-propane sultone to 40 g of anhydrous toluene, heat to 100℃, react for 24 h, cool to room temperature, the product is settled under an external magnetic field, washed, dried, and then a magnetic solid dual-acid catalyst is obtained.

[0046] Preparation Example 2: the specific preparation process of the magnetic solid dual-acid catalyst, comprising the following steps:

[0047] S1. Prepare a ferric chloride solution and a ferrous sulfate solution with a concentration of 0.4 mol / L respectively, mix 140 ml of the ferric chloride solution and 90 ml of the ferrous sulfate solution under a nitrogen atmosphere, heat to 55℃ under stirring, adjust the pH to 10 with ammonia water, and react for 1.5 h. After the reaction is completed, the product is settled under an external magnetic field, washed, dried, and then magnetic Fe3O4 nanoparticles are obtained;

[0048] S2. 0.5 g of cetyltrimethylammonium bromide was added to 500 g of deionized water, stirred for 8 min, 5 g of magnetic Fe3O4 nanoparticles were added, ultrasonic dispersion was carried out for 30 min, then 500 g of a sodium hydroxide solution with a concentration of 10 mmol / L was added, the temperature was raised to 55°C, stirring was carried out for 25 min, finally 5.5 g of tetraethyl orthosilicate and 100 g of ethanol were added, reaction was carried out for 12 h, then the temperature was lowered to room temperature, the product was settled under an external magnetic field, washed, dried, and then calcined at 400°C for 4 h to obtain magnetic mesoporous silica;

[0049] S3. 0.3 g of triblock copolymer P123 was added to 50 g of anhydrous ethanol, stirred for 15 min, 0.75 g of aluminum nitrate and 0.55 g of zinc nitrate were added, the pH was adjusted to neutral with triethylamine, the temperature was raised to 45°C, stirring was carried out for 2 h, then 5 g of magnetic mesoporous silica was added, stirring was carried out for 3 h, then it was filtered, washed, dried, and then calcined at 400°C for 4 h to obtain magnetic silica loaded with metal active layers;

[0050] S4. 5 g of magnetic silica loaded with metal active layers and 6.5 g of 1,3-propane sultone were added to 45 g of anhydrous toluene, the temperature was raised to 110°C, reaction was carried out for 36 h, then the temperature was lowered to room temperature, the product was settled under an external magnetic field, washed, dried to obtain a magnetic solid double acid catalyst.

[0051] Preparation Example 3: The specific preparation process of the magnetic solid double acid catalyst, comprising the following steps:

[0052] S1. Iron trichloride solution and ferrous sulfate solution with a concentration of 0.4 mol / L were prepared respectively, 160 ml of iron trichloride solution and 100 ml of ferrous sulfate solution were mixed under a nitrogen atmosphere, the temperature was raised to 60°C under stirring, the pH was adjusted to 11 with ammonia water, reaction was carried out for 2 h, then the product was settled under an external magnetic field, washed, dried to obtain magnetic Fe3O4 nanoparticles;

[0053] S2. 0.6 g of cetyltrimethylammonium bromide was added to 600 g of deionized water, stirred for 10 min, 5 g of magnetic Fe3O4 nanoparticles were added, ultrasonic dispersion was carried out for 40 min, then 600 g of a sodium hydroxide solution with a concentration of 10 mmol / L was added, the temperature was raised to 60°C, stirring was carried out for 30 min, finally 6 g of tetraethyl orthosilicate and 125 g of ethanol were added, reaction was carried out for 14 h, then the temperature was lowered to room temperature, the product was settled under an external magnetic field, washed, dried, and then calcined at 450°C for 5 h to obtain magnetic mesoporous silica;

[0054] S3. 0.35 g of triblock copolymer P123 was added into 60 g of anhydrous ethanol and stirred for 20 min, 0.8 g of aluminum nitrate and 0.6 g of zinc nitrate were added, the pH was adjusted to neutral with triethylamine, the temperature was raised to 50 °C, and stirred for 3 h, then 5 g of magnetic mesoporous silica was added, stirred for 4 h, filtered, washed, dried, and calcined at 450 °C for 5 h to obtain a magnetic silica loaded with metal active layers;

[0055] S4. 5 g of magnetic silica loaded with metal active layers and 8 g of 1,3-propane sultone were added into 50 g of anhydrous toluene, the temperature was raised to 120 °C, and reacted for 48 h, after cooling to room temperature, the product was settled by an external magnetic field, washed, dried to obtain a magnetic solid double acid catalyst.

[0056] Comparative Preparation Example 1: The difference between Comparative Preparation Example 1 and Preparation Example 2 is that no cetyltrimethylammonium bromide is added in step S2.

[0057] Comparative Preparation Example 2: The difference between Comparative Preparation Example 2 and Preparation Example 2 is that no triblock copolymer P123 is added in step S3.

[0058] Comparative Preparation Example 3: The difference between Comparative Preparation Example 3 and Preparation Example 2 is that no zinc nitrate is added in step S3.

[0059] Comparative Preparation Example 4: The difference between Comparative Preparation Example 4 and Preparation Example 2 is that no aluminum nitrate is added in step S3.

[0060] Comparative Preparation Example 5: The difference between Comparative Preparation Example 5 and Preparation Example 2 is that step S4 is omitted, and the magnetic silica loaded with metal active layers obtained in step S3 is the magnetic solid double acid catalyst.

[0061] Comparative Preparation Example 6: The difference between Comparative Preparation Example 5 and Preparation Example 2 is that step S1 is omitted, and no magnetic Fe3O4 nanoparticles are added in step S2, and finally a non-magnetic solid double acid catalyst is prepared.

[0062] Preparation Examples 1-3 and Comparative Preparation Examples 1-6 were characterized by N2 adsorption-desorption on a Belsorp III-2000PS2 adsorption instrument: 100 mg of catalyst was pretreated in vacuum at 250 °C for 4 h, then N2 adsorption-desorption experiment was performed, the specific surface area of the sample was calculated by Brunauer-Emmett-Teller equation, and the pore size distribution was calculated according to Barrett-Joyner-Halenda (BJH) model, and the specific surface data of the catalysts are shown in Table 1.

[0063] Table 1 Specific surface data of catalysts

[0064]

[0065]

[0066] Example 1: A specific preparation method of 1,1-cyclohexyl diacetic acid, comprising the following steps:

[0067] (1) 113.11 g of ethyl cyanoacetate, 68.70 g of cyclohexanone, 6.17 g of ammonium acetate, and 12.01 g of acetic acid were added to 565.6 g of toluene, heated to 120°C, and reacted for 3 h. After the reaction was completed, the toluene was recovered under reduced pressure, 565.6 g of ethyl acetate was added, and the pH was adjusted to neutral with a 1 mol / L sodium hydroxide solution. The organic layer was separated, the aqueous layer was extracted with ethyl acetate 2-3 times, the organic phases were combined, dried over anhydrous magnesium sulfate, and the solvent was removed by rotary evaporation to obtain a colorless liquid as the product 1 with a yield of 96.4%;

[0068] (2) 350 g of methanol, 30.15 g of cyanoacetamide, and 2.91 g of sodium methoxide were added to a reaction flask, stirred at room temperature for 15 min, cooled to -5°C, and 70 g of product 1 was added dropwise over a period of 1 h. After the addition was completed, the temperature was raised to 15°C, and the reaction was allowed to proceed for 1 h. The resulting solid was filtered, washed, dissolved in 700 g of deionized water, and the pH was adjusted to 2-3 with a 36% concentrated HCl solution. White solids were precipitated, filtered, washed, and dried to obtain product 2 with a yield of 96%;

[0069] (3) 70 g of product 2, 14 g of magnetic solid double acid catalyst prepared according to the preparation method of Example 1, and 350 g of deionized water were added to a high-pressure reaction kettle, heated to 140°C, and reacted for 2 h. The reaction was cooled to room temperature, and the magnetic solid double acid catalyst and the product were separated by an external magnetic field. The product was recrystallized in a methanol / water mixture (3:2 by weight) to obtain 1,1-cyclohexyl diacetic acid with a yield of 95%.

[0070] Example 2: A specific preparation method of 1,1-cyclohexyl diacetic acid, comprising the following steps:

[0071] (1) 113.11 g of ethyl cyanoacetate, 68.70 g of cyclohexanone, 6.17 g of ammonium acetate, and 12.01 g of acetic acid were added to 565.6 g of toluene, heated to 120°C, and reacted for 3 h. After the reaction was completed, the toluene was recovered under reduced pressure, 565.6 g of ethyl acetate was added, and the pH was adjusted to neutral with a 1 mol / L sodium hydroxide solution. The organic layer was separated, the aqueous layer was extracted with ethyl acetate 2-3 times, the organic phases were combined, dried over anhydrous magnesium sulfate, and the solvent was removed by rotary evaporation to obtain a colorless liquid as the product 1 with a yield of 96.4%;

[0072] (2) 640 g of methanol, 41.35 g of cyanoacetamide and 3.98 g of sodium methoxide were added into a reaction bottle, stirred at room temperature for 20 min, cooled to -3 °C, 80 g of product 1 was added dropwise, the dropwise addition was completed in 1.5 h, then the temperature was increased to 20 °C, reacted for 1.5 h, filtered, the obtained solid was washed, added into 880 g of deionized water, heated to dissolve, adjusted to pH 2-3 with 36% concentrated HCl, white solid was precipitated, filtered, washed and dried to obtain product 2, the yield was 95.9%;

[0073] (3) 80 g of product 2, 19.2 g of magnetic solid double acid catalyst prepared according to the preparation method of preparation example 2 and 480 g of deionized water were added into a high-pressure reaction kettle, the temperature was increased to 150 °C, reacted for 3 h, cooled to room temperature, the magnetic solid double acid catalyst and the product were separated by an external magnetic field, the product was recrystallized in a methanol / water mixed solution (prepared by mixing methanol and water at a weight ratio of 3:2) to obtain 1,1-cyclohexyl diacetic acid, the yield was 95.4%.

[0074] Example 3: A specific preparation method of 1,1-cyclohexyl diacetic acid, comprising the following steps:

[0075] (1) 113.11 g of ethyl cyanoacetate, 117.77 g of cyclohexanone, 9.25 g of ammonium acetate and 24.02 g of acetic acid were added into 1018 g of toluene, the temperature was increased to 140 °C, reacted for 5 h, after the reaction was completed, toluene was recovered under reduced pressure, 1018 g of ethyl acetate was added, the pH was adjusted to neutral with a 1 mol / L sodium hydroxide solution, the organic layer was separated, the water layer was extracted with ethyl acetate for 2-3 times, the combined organic phase was dried over anhydrous magnesium sulfate, and the solvent was removed by rotary evaporation to obtain product 1 as a colorless liquid, the yield was 96.1%;

[0076] (2) 900 g of methanol, 53.27 g of cyanoacetamide and 4.98 g of sodium methoxide were added into a reaction bottle, stirred at room temperature for 25 min, cooled to 0 °C, 90 g of product 1 was added dropwise, the dropwise addition was completed in 2 h, then the temperature was increased to 25 °C, reacted for 2 h, filtered, the obtained solid was washed, added into 1080 g of deionized water, heated to dissolve, adjusted to pH 2-3 with 36% concentrated HCl, white solid was precipitated, filtered, washed and dried to obtain product 2, the yield was 95.8%;

[0077] (3) 90 g of product 2, 25.2 g of magnetic solid double acid catalyst prepared according to the preparation method of preparation example 3 and 630 g of deionized water were added into a high-pressure reaction kettle, the temperature was increased to 160 °C, reacted for 4 h, cooled to room temperature, the magnetic solid double acid catalyst and the product were separated by an external magnetic field, the product was recrystallized in a methanol / water mixed solution (prepared by mixing methanol and water at a weight ratio of 3:2) to obtain 1,1-cyclohexyl diacetic acid, the yield was 95.4%.

[0078] Comparative Example 1: The difference between Comparative Example 1 and Example 2 is that the magnetic solid dual acid catalyst prepared according to the preparation method of Comparative Preparation Example 1 is used.

[0079] Comparative Example 2: The difference between Comparative Example 2 and Example 2 is that the magnetic solid dual acid catalyst prepared according to the preparation method of Comparative Preparation Example 2 is used.

[0080] Comparative Example 3: The difference between Comparative Example 3 and Example 2 is that the magnetic solid dual acid catalyst prepared according to the preparation method of Comparative Preparation Example 3 is used.

[0081] Comparative Example 4: The difference between Comparative Example 4 and Example 2 is that the magnetic solid dual acid catalyst prepared according to the preparation method of Comparative Preparation Example 4 is used.

[0082] Comparative Example 5: The difference between Comparative Example 5 and Example 2 is that the magnetic solid dual acid catalyst prepared according to the preparation method of Comparative Preparation Example 5 is used.

[0083] Comparative Example 6: The difference between Comparative Example 6 and Example 2 is that the non-magnetic solid dual acid catalyst prepared according to the preparation method of Comparative Preparation Example 6 is used. Since the catalyst does not contain magnetism, it cannot be separated by an external magnetic field after the reaction is completed, so the specific separation operation in step (3) of Comparative Example 6 is that 80 g of product 2, 19.2 g of the magnetic solid dual acid catalyst prepared according to the preparation method of Comparative Preparation Example 6, and 480 g of deionized water are added to a high-pressure reaction kettle, heated to 150°C, reacted for 3 h, cooled to room temperature, 480 g of methanol is added, stirred for 30 min, the catalyst is removed by filtration, the methanol is removed by distillation under reduced pressure, the crude product is filtered again to obtain the crude product, and the crude product is recrystallized in a methanol / water mixed solution (mixed according to a weight ratio of 3:2) to obtain 1,1-cyclohexyl diacetic acid.

[0084] Comparative Example 7: The difference between Comparative Example 7 and Example 2 is that 1,1-cyclohexyl diacetic acid is prepared by the following synthesis method, which is prepared according to the following chemical reaction equation:

[0085]

[0086] Comparative Example 8: The difference between Comparative Example 8 and Example 2 is that 1,1-cyclohexyl diacetic acid is prepared according to the preparation method disclosed in patent CN105061241A.

[0087] Performance test:

[0088] 1.1,1-cyclohexyldiacetic acid yield: The 1,1-cyclohexyldiacetic acid prepared by example 1-3 and comparative example 1-8 was tested for yield, which is a well-known test method for those skilled in the art, and the specific test process is not described here, and the experimental results are shown in Table 2.

[0089] 2.1,1-cyclohexyldiacetic acid purity: The 1,1-cyclohexyldiacetic acid prepared by example 1-3 and comparative example 1-8 was tested for purity by HPLC high performance liquid chromatography, and the experimental results are shown in Table 2.

[0090] 3. Total reaction time: The time required to obtain the final product 1,1-cyclohexyldiacetic acid by reaction of example 1-3 and comparative example 1-8 was counted, excluding post-processing, feeding and preparation time, and the results are shown in Table 2.

[0091] 4. Recycling experiment: 1,1-cyclohexyldiacetic acid was prepared according to the preparation method of example 1-3 and comparative example 1-6, and the catalyst after each reaction was washed, dried and recorded as one cycle. After ten cycles, the yield of 1,1-cyclohexyldiacetic acid was tested, and the experimental results are shown in Table 2.

[0092] Table 2 Performance test results

[0093]

[0094]

[0095] Performance analysis:

[0096] According to the experimental data in Table 1, the catalyst prepared by preparation example 1-3 exhibits excellent mesoporous structure characteristics, wherein the specific surface area of preparation example 2 is 193.66 m 2 / g, pore volume 0.26 cm 3 / g, pore size 4.3 nm, which is significantly better than the comparative preparation example. This structural feature is derived from the complete "magnetic core-mesoporous silica-metal active layer-sulfonic acid group" four-layer structure construction, which ensures high exposure of active sites and accessibility of substrates, laying the foundation for efficient catalysis.

[0097] From the specific surface area, it can be seen that, in Preparation Example 2, the addition of cetyltrimethylammonium bromide and triblock copolymer P123 as a template agent guides the self-assembly of tetraethyl orthosilicate and metal salt to form a regular mesoporous network, and after calcination, the template agent is removed, so that the mesoporous wall is uniformly distributed, ensuring the maximum specific surface area; in Comparative Preparation Example 1, the absence of cetyltrimethylammonium bromide may cause the amorphous accumulation of silica, forming a large number of closed pore structures, and the specific surface area decreases; in Comparative Preparation Example 2, the absence of P123 may cause the metal salt to agglomerate into block-shaped particles on the mesoporous surface, covering the pore opening, and the specific surface area decreases; in Comparative Preparation Example 3, the single Al loading causes the shrinkage of the crystalline form of alumina during sintering, covering the pore opening, and the specific surface area decreases; in Comparative Preparation Example 4, the single Zn loading causes the grain growth and accumulation of zinc oxide during sintering, reducing the specific surface area; in Comparative Preparation Example 5, the absence of sulfonic acid groups causes the formation of nanogaps on the surface of the metal layer, which may increase the specific surface area, but may reduce the actual active sites and affect the catalytic efficiency; in Comparative Preparation Example 6, the omission of the magnetic core causes the collapse of the mesoporous silica skeleton after calcination due to the lack of support of the magnetic core, and the specific surface area decreases.

[0098] From the pore volume and pore size, the pore volume of Preparation Example 2 is 0.26 cm 3 / g, and the pore size is 4.3 nm, which is formed by the template agent guidance, double metal synergistic loading, and sulfonic acid group grafting to form a regular mesoporous structure; in Comparative Preparation Example 1, the absence of a template agent causes amorphous accumulation of silica, resulting in a decrease in pore volume and a decrease in pore size; in Comparative Preparation Example 2, the absence of a template agent causes metal agglomeration to block the pore, resulting in a decrease in pore volume and a decrease in pore size; in Comparative Preparation Examples 3-4, the single metal loading causes the shrinkage of the crystalline form of alumina or the grain growth of zinc oxide, respectively, resulting in varying degrees of decrease in pore volume and pore size; in Comparative Preparation Example 5, the absence of sulfonic acid group grafting may increase the pore volume, but lacks Bronsted acid sites, which may cause a decrease in catalytic effect; in Comparative Preparation Example 6, the absence of a magnetic core support may cause the mesoporous skeleton to collapse during sintering, resulting in a decrease in pore volume and pore size. The above comparative preparation examples are all caused by the absence of a template agent in the preparation process, single metal loading, the lack of sulfonic acid group grafting or magnetic core support, resulting in a deviation of the pore volume and pore size from the ideal range, affecting the substrate diffusion and active site accessibility, and thus reducing the catalytic performance.

[0099] According to the experimental data in Table 2, it can be seen that the yield of 1,1-cyclohexyl diacetic acid prepared by Examples 1-3 using the catalyst prepared by the present application is 95.0%-95.4%, the purity is >98.7%, and the yield retention rate after ten cycles is >85%, which is significantly better than the comparative examples, and the comprehensive performance of Example 2 is the best, which may be because the high-activity double-acid sites of the catalyst, the stable mesoporous structure, and the magnetic separation characteristics ensure the high efficiency and repeatability of the reaction.

[0100] The catalyst used in Example 2 is a Lewis acid Al 3+ / Zn 2+Synergistic effect with Bronsted acid-SO3H) greatly improves the hydrolysis efficiency, -SO3H releases H + Combined with the nitrogen atom of the cyano group, a protonated intermediate is formed, making the carbon atom strongly positive, reducing the nucleophilic attack energy barrier, Al 3+ / Zn 2+ The empty orbital of / Zn coordinates with the lone pair of electrons of the nitrogen atom of the cyano group, further polarizing the C≡N bond, making the carbon atom more susceptible to nucleophilic attack by H2O; the double acid site controls the small distance through the mesoporous structure, forming a double active center, reducing the activation energy of the hydrolysis reaction, and improving the reaction rate. The same reaction time, the incomplete acid site of Comparative Examples 3-5 leads to reduced catalytic effect, resulting in a decrease in yield; at the same time, the large specific surface area and pore size of the catalyst ensure that the diffusion path of the reactants is shortened and the exposure rate of the active sites is increased. The combination of magnetic separation technology realizes efficient and rapid separation of the catalyst, and the yield still reaches 87.3% after ten cycles; while Comparative Examples 1-2 due to the incomplete mesoporous structure, resulting in a decrease in the loading of the catalytic components, which in turn affects the catalytic efficiency, leading to a decrease in yield, Comparative Example 6 due to the lack of magnetism, needs to be separated by filtration, which inevitably results in loss during filtration and separation, resulting in a significant decrease in yield after repeated use; Comparative Example 7 due to the use of traditional synthesis methods, the reaction time is greatly increased, and the use of concentrated sulfuric acid as a catalyst at high temperature will also exacerbate the occurrence of side reactions, greatly reducing the yield, and concentrated sulfuric acid cannot be separated and recycled, cannot be reused, and will also cause serious pollution to the environment; Comparative Example 8 uses high-temperature liquid water reaction, which consumes more energy and takes longer to react, making it difficult to be used on a large scale in industry.

[0101] The above is only the preferred specific embodiment of the present application, but the protection scope of the present application is not limited thereto, any person skilled in the art can make equivalent replacement or change according to the technical solution and the inventive concept of the present application within the technical range disclosed by the present application, which should be covered within the protection scope of the present application.

Claims

1. A method for preparing 1,1-cyclohexanediacetic acid, characterized in that: The following steps are involved: (1) Ethyl cyanoacetate, cyclohexanone, ammonium acetate, and acetic acid are added to toluene, heated to 120-140° C., and reacted for 3-5 hours. After the reaction, the toluene is recovered under reduced pressure, ethyl acetate is added, and the pH is adjusted to neutral with sodium hydroxide solution. The organic layer is separated, and the aqueous layer is extracted 2-3 times with ethyl acetate. The organic phases are combined, dried over anhydrous magnesium sulfate, and the solvent is removed by vortexing to obtain a colorless liquid as product 1; (2) Methanol, cyanoacetamide, and sodium methoxide were added to a reaction flask, stirred at room temperature for 15-25 minutes, cooled to -5-0°C, and product 1 was added dropwise for 1-2 hours. After the addition was complete, the temperature was raised to 15-25°C, reacted for 1-2 hours, and filtered. The obtained solid was washed and added to deionized water, heated until dissolved, and the pH was adjusted to 2-3 with concentrated HCl to precipitate a white solid, which was filtered, washed, and dried to obtain product 2; (3) adding the product 2, the magnetic solid bis-acid catalyst and deionized water into a high-pressure reactor, heating to 140-160° C., reacting for 2-4 hours, cooling to room temperature, separating the magnetic solid bis-acid catalyst and the product by applying an external magnetic field, and recrystallizing the product in a methanol / water mixed solution to obtain 1,1-cyclohexanediacetic acid; The preparation steps of the magnetic solid diacid catalyst include: S1. Ferric chloride solution and ferrous sulfate solution were separately prepared. Under a nitrogen atmosphere, the ferric chloride solution and ferrous sulfate solution were mixed, heated to 50-60 ° C with stirring, and the pH was adjusted to 9-11 with ammonia water. The reaction was carried out for 1-2 h. After the reaction was completed, the product was precipitated by an external magnetic field, washed, and dried to obtain magnetic Fe3O4 nanoparticles; S2. Hexadecyltrimethylammonium bromide was added to deionized water and stirred for 5-10 minutes. Magnetic Fe3O4 nanoparticles were then added and ultrasonically dispersed for 20-40 minutes. Then, sodium hydroxide solution was added and the temperature was raised to 50-60°C. The mixture was stirred for 20-30 minutes. Finally, ethyl orthosilicate and ethanol were added. The mixture was reacted for 10-14 hours and then cooled to room temperature. The product was precipitated in an external magnetic field, washed, dried, and calcined at 350-450°C for 3-5 hours to obtain magnetic mesoporous silica. S3. The triblock copolymer P123 was added to anhydrous ethanol and stirred for 10-20 minutes. Aluminum nitrate and zinc nitrate were added, and the pH was adjusted to neutral with triethylamine. The temperature was raised to 40-50°C and stirred for 1-3 hours. Magnetic mesoporous silica was then added and stirred for 2-4 hours. The mixture was filtered, washed, dried, and calcined at 350-450°C for 3-5 hours to obtain a magnetic silica loaded with a metal active layer. S4. Add magnetic silica loaded with a metal active layer and 1,3-propane sultone to anhydrous toluene, raise the temperature to 100-120°C, react for 24-48 hours, cool to room temperature, and precipitate the product in an external magnetic field, wash, and dry to obtain a magnetic solid bis-acid catalyst.

2. The method for preparing 1,1-cyclohexanediacetic acid according to claim 1, wherein In the (1), the molar ratio of ethyl cyanoacetate, cyclohexanone, ammonium acetate and acetic acid is 1:0.7-1.2:0.08-0.12:0.2-0.4, the weight ratio of ethyl cyanoacetate, toluene and ethyl acetate is 1:5-9:5-9, and the concentration of the sodium hydroxide solution is 1 mol / L.

3. The method for preparing 1,1-cyclohexanediacetic acid according to claim 1, wherein In said (2), the molar ratio of cyanoacetamide, sodium methoxide and product 1 is 1-1.4:0.15-0.2:1, the weight ratio of product 1, methanol and deionized water is 1:5-10:10-12, and concentrated HCl refers to a hydrochloric acid solution with a mass concentration of 36%.

4. The method for preparing 1,1-cyclohexanediacetic acid according to claim 1, wherein The weight ratio of the product 2, the magnetic solid bis-acid catalyst and the deionized water in (3) is 1:0.2-0.28:5-7, and the methanol / water mixed solution refers to a mixture of methanol and water in a weight ratio of 3:

2.

5. The method for preparing 1,1-cyclohexanediacetic acid according to claim 1, characterized in that: The weight ratio of the ferric chloride solution to the ferrous sulfate solution in S1 is 1.2-1.6:0.8-1, and the concentrations of the ferric chloride solution and the ferrous sulfate solution are both 0.4 mol / L.

6. The method for preparing 1,1-cyclohexanediacetic acid according to claim 1, characterized in that: The weight ratio of hexadecyltrimethylammonium bromide, deionized water, magnetic Fe3O4 nanoparticles, sodium hydroxide solution, ethyl orthosilicate and ethanol in S2 is 0.08-0.12:80-120:1:80-120:1-1.2:15-25, and the concentration of the sodium hydroxide solution is 10 mmol / L.

7. The method for preparing 1,1-cyclohexanediacetic acid according to claim 1, characterized in that: The weight ratio of the triblock copolymer P123, magnetic mesoporous silica, aluminum nitrate, zinc nitrate and anhydrous ethanol in the S3 is 0.04-0.07:1:0.14-0.16:0.1-0.12:8-12.

8. The method for preparing 1,1-cyclohexanediacetic acid according to claim 1, characterized in that: The weight ratio of the magnetic silica supporting the metal active layer, 1,3-propane sultone and anhydrous toluene in S4 is 1:1-1.6:8-10.

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