Application of novel Cu + Zr (OH) 4 physical mixed catalyst in catalytic synthesis of N-benzylidene aniline or derivatives thereof

Abstract

The one-pot method for preparing the imine compound by taking benzyl alcohol or a derivative thereof and nitrobenzene or a derivative thereof as raw materials is a method with economical steps. However, in reported work, the use amount of benzyl alcohol is often three times or even more than three times that of nitrobenzene, which can cause the generation of a large amount of by-product benzaldehyde and violate the atom economy concept. The invention aims to design a bifunctional physical mixed catalyst Cu + Zr (OH) 4 which has the capabilities of catalyzing benzyl alcohol dehydrogenation and nitrobenzene hydrogenation, and N-benzylidene aniline is prepared by catalyzing benzyl alcohol and nitrobenzene in a stoichiometric ratio through a one-pot method in a hydrogen atmosphere. According to the implementation of the method, on one hand, the problem of the material ratio of benzyl alcohol or derivatives thereof to nitrobenzene or derivatives thereof is innovatively solved, the output of byproducts is greatly reduced, and the atom economy concept is completely met; on the other hand, the invention provides a design strategy of a novel physical mixed catalyst, and a new thought is provided for preparing N-benzylidene aniline and derivatives thereof. No matter from the perspective of atomic economy or from the perspective of increasing the added value of the product, the method has extremely important value and profound significance.

Description

Technical Field

[0001] The present invention relates to a design strategy of a physical mixed catalyst and its application, in particular to using Cu+Zr(OH)4 as a catalyst for synthesizing N-benzylidene aniline or its derivatives with benzyl alcohol or its derivatives and nitrobenzene or its derivatives as substrates. Technical Background

[0002] Imine (also known as Schiff base) compounds have certain pharmacological and physiological activities, have always been the subject of attention, and are also key intermediates for a variety of chemical drugs and medical drugs. Due to the presence of unsaturated C=N, they have high reactivity and are very valuable organic reaction intermediates (see "Science", 2022, Vol. 376, No. 6600, 1433-1441.).

[0003] Traditional methods for synthesizing imines mainly involve aldehyde-amine coupling (see "Angewandte Chemie International Edition", 1995, Issue 34, Volume 22, 2443-2465.), self-condensation of benzylamine (see "Journal of the American Chemical Society", 2022, Issue 144, Volume 6, 2580-2589.), direct dehydrogenation of secondary amines (see "Angewandte Chemie International Edition", 2021, Issue 60, Volume 13, 7290-7296.), hydrogen amination of alkynes (see "Journal of the American Chemical Society", 2020, Issue 142, Volume 34, 14455-14460.), and alcoholamine condensation (see "Small", 2023, Issue 19, Volume 18, 2207941.), etc. Among them, alcoholamine condensation is considered an ideal method because the substrate is low cost, easy to obtain, and the only byproduct is water. In addition, the use of more primitive, cheaper, and more easily available nitro compounds to replace amine compounds and another component benzyl alcohol to synthesize imines has great potential.

[0004] In the above reaction system, predecessors have studied homogeneous catalysts with metals such as molybdenum, ruthenium, and iridium as active components and heterogeneous catalysts with metals such as palladium, gold, titanium, and cobalt as active components. However, in their work, the amount of benzyl alcohol used is often three times or even more than that of nitrobenzene, which will lead to the production of a large amount of benzaldehyde by-products, violating the concept of atom-economic synthesis; therefore, we consider designing a heterogeneous catalytic system with benzyl alcohol and nitrobenzene in a stoichiometric ratio as substrates for the synthesis of imines. This catalytic system uses hydrogen as an exogenous hydrogen source, avoiding the production of a large amount of benzaldehyde by-products, which is in line with the concept of atom economy.

[0005] In order to realize the above reaction process, a catalyst having both hydrogenation and dehydrogenation capabilities is required. In our previous work, we found that zirconium hydroxide has both hydrogenation (see "Catalysis Science & Technology" 2024, No. 14, Vol. 4, 1008-1016.) and dehydrogenation (see "Angewandte Chemie International Edition", 2024) bifunctionality, making it a candidate catalyst for catalyzing the one-pot synthesis of imines, and the specific reaction process involves nitrobenzene hydrogenation, benzyl alcohol dehydrogenation, and subsequent coupling reaction between benzaldehyde and aniline. However, when a single zirconium hydroxide is used as a catalyst for the system, the catalytic performance is limited, so we introduce another component copper in the form of physical mixing to enhance the catalytic activity of the overall catalyst. From the perspective of environmental friendliness and sustainable development, the present invention effectively solves the problem of by-product benzaldehyde generation; from the perspective of organic synthesis, a new idea is provided for the synthesis of high value-added fine chemicals. Summary of the invention

[0006] The present invention finds that a catalyst prepared by homemade copper and commercially purchased zirconium hydroxide can catalyze the one-pot coupling of benzyl alcohol and nitrobenzene in a stoichiometric ratio to generate N-benzylidene aniline. Therefore, the present invention not only solves the problem of excessive benzyl alcohol in the traditional synthesis method, effectively reduces the generation of by-product benzaldehyde, but also proposes a low-cost and green and efficient method for preparing imines. The method is simple, low-cost, and highly safe, and is more in line with the concept of green and friendly chemistry. Specifically includes the following contents:

[0007] In a first aspect, the present invention provides a method for preparing a physical mixed catalyst Cu+Zr(OH)4 by a simple physical mixing method using commercially available zirconium hydroxide as a catalyst main body.

[0008] Preferably, the catalyst preparation method comprises the following steps:

[0009] (1) Treatment of zirconium hydroxide catalyst: A certain amount of commercial Zr(OH)4 was weighed and dried at 60°C, and then calcined in a muffle furnace at a heating rate of 3°C / min to 200°C for 4 h.

[0010] (2) Preparation of copper catalyst: Weigh 24.59 g of copper nitrate hydrate into a container, add 1000 mL of deionized water to dissolve it, then add 1 M sodium hydroxide solution until the copper ions are completely precipitated. After continuous stirring for 12 h, separate the solid product, wash with deionized water, dry at 60°C, and finally calcine and reduce it in a hydrogen atmosphere at 200°C for 4 h to obtain a copper catalyst.

[0011] (3) Preparation of physical mixed catalyst: Weigh a specific mass of treated Zr(OH)4 and place it in a reaction container, then weigh a specific mass of metal Cu and place it in the reaction container, thus obtaining a physical mixed catalyst Cu+Zr(OH)4.

[0012] Preferably, the raw materials are benzyl alcohol or its derivatives (I) and nitrobenzene or its derivatives (II), and the structural formula of the product N-benzylidene aniline or its derivatives is shown in the following formula (III), and their structural formulas are shown in the following formulas:

[0013]

[0014] Wherein, R1-R5 are independently selected from any one of hydrogen, halogen, hydroxyl, sulfonic acid, nitro, substituted or unsubstituted straight or branched alkyl, alkoxy, carbonyl, alkenyl, alkynyl, substituted or unsubstituted aryl, acylamino, and cyano, but are not limited to the above substituents.

[0015] Preferably, R1-R5 are independently selected from hydrogen, methyl, chlorine, fluorine, and methoxy.

[0016] Preferably, the benzyl alcohol or its derivatives include: benzyl alcohol, p-methylbenzyl alcohol, p-chlorobenzyl alcohol, p-fluorobenzyl alcohol, and p-methoxybenzyl alcohol.

[0017] Preferably, the nitrobenzene or its derivatives include: nitrobenzene, p-nitrotoluene, p-chloronitrobenzene, p-fluoronitrobenzene, and p-nitroanisole.

[0018] In a second aspect, the present invention provides a method for preparing an imine or a derivative thereof, the method comprising: using benzyl alcohol or a derivative thereof (I) and nitrobenzene or a derivative thereof (II) as raw materials, an organic solvent as a reaction solvent, Cu+Zr(OH)4 as a catalyst, and hydrogen as a reaction atmosphere, and catalytically coupling reaction to synthesize N-benzylidene aniline or a derivative thereof (III) as shown in the following formula, wherein the organic solvent comprises n-octane, n-pentane, n-hexane, petroleum ether, N,N-dimethylformamide, ethanol, toluene, and acetonitrile.

[0019]

[0020] Among them, R1-R5 are independently selected from any one of hydrogen, halogen, hydroxyl, sulfonic acid, nitro, substituted or unsubstituted straight or branched alkyl, alkoxy, carbonyl, alkenyl, alkynyl, substituted or unsubstituted aryl, acylamino, and cyano, but are not limited to the above substituents.

[0021] Preferably, R1-R5 are independently selected from hydrogen, methyl, chlorine, fluorine, and methoxy.

[0022] Preferably, the benzyl alcohol or its derivatives include: benzyl alcohol, p-methylbenzyl alcohol, p-chlorobenzyl alcohol, p-fluorobenzyl alcohol, and p-methoxybenzyl alcohol.

[0023] Preferably, the nitrobenzene or its derivatives include: nitrobenzene, p-nitrotoluene, p-chloronitrobenzene, p-fluoronitrobenzene, and p-nitroanisole.

[0024] Preferably, the usage ratio of Cu to Zr(OH)4 is 0-50:100.

[0025] Preferably, the usage ratio of Cu to Zr(OH)4 is 10:100.

[0026] Preferably, the ratio of the catalyst to benzyl alcohol or its derivatives is 10-15 g:100 mmol.

[0027] Preferably, the ratio of the catalyst to benzyl alcohol or its derivatives is 11 g:100 mmol.

[0028] Preferably, the ratio of the reaction solvent to benzyl alcohol or its derivatives is 1000 mL:100 mmol.

[0029] Preferably, the hydrogen pressure is 0.5 MPa.

[0030] Preferably, the reaction temperature is 100-180°C.

[0031] Preferably, the reaction temperature is 180°C.

[0032] Preferably, the reaction time is 24 hours.

[0033] Preferably, the reaction solvent is n-octane.

[0034] Preferably, the catalyst is Cu+Zr(OH)4.

[0035] Preferably, the method comprises the following steps:

[0036] (1) adding benzyl alcohol or its derivatives, nitrobenzene or its derivatives, and Cu+Zr(OH)4 into a high-pressure sterilization reactor containing a certain amount of reaction solvent n-octane;

[0037] (2) After the atmosphere in the reactor is completely replaced with high-pressure hydrogen, the reaction is carried out at a certain hydrogen pressure and 180° C. for 24 hours;

[0038] (3) Filtration, distillation and recrystallization to obtain N-benzylidene aniline.

[0039] Compared with the prior art, the technical solution of the present invention has the following advantages:

[0040] (1) The present invention designs a novel bifunctional catalytic system that can simultaneously realize hydrogenation and dehydrogenation reactions with one catalyst;

[0041] (2) The present invention uses hydrogen as a hydrogen source and uses benzyl alcohol and nitrobenzene in a stoichiometric ratio as substrates, which greatly reduces the production of byproduct benzaldehyde and conforms to the concept of atomic economy;

[0042] (3) Nitrobenzene or its derivatives used in the present invention are more original, cheaper and easier to obtain than aniline and its derivatives commonly used in traditional industries, thus greatly reducing production costs;

[0043] (4) The method of the present invention can catalyze the coupling of benzyl alcohol or its derivatives and nitrobenzene or its derivatives to generate the corresponding imines, and the yield of the target product is high. BRIEF DESCRIPTION OF THE DRAWINGS

[0044] Figure 1 X-ray diffraction crystal structures of the prepared catalysts (including Cu, Zr(OH)4, Cu+Zr(OH)4);

[0045] Figure 2 SEM images of the prepared physical hybrid catalysts;

[0046] Figure 3 Transmission electron microscope image of the prepared physical hybrid catalyst;

[0047] Figure 4 Mass spectrum of the product N-benzylidene aniline synthesized by the method described in Example 1;

[0048] Figure 5 Mass spectrum of the product N-benzylidene aniline synthesized by the method described in Example 2;

[0049] Figure 6 Mass spectrum of the product N-benzylidene aniline synthesized by the method described in Example 3;

[0050] Figure 7 Mass spectrum of the product N-benzylidene aniline synthesized by the method described in Example 4;

[0051] Figure 8 Mass spectrum of the product (E)-N-(4-methoxybenzylidene)aniline synthesized by the method described in Example 4;

[0052] Fig. 9 Mass spectrum of the product synthesized by the method described in Example 4:

[0053] Fig.10 Mass spectrum of the product (E)-N-(4-chlorobenzylidene)aniline synthesized by the method described in Example 4;

[0054] Fig.11 Mass spectrum of the product N-benzylidene aniline synthesized by the method described in Example 5;

[0055] Fig.12 Mass spectrum of the product 4-methoxy-N-(phenylmethylene)-aniline synthesized by the method described in Example 5;

[0056] Fig.13 Mass spectrum of the product (E)-4-methyl-N-(phenylmethylene)-aniline synthesized by the method described in Example 5;

[0057] Fig.14 Mass spectrum of the product (E)-4-chloro-N-(phenylmethylene)aniline synthesized by the method described in Example 5; DETAILED DESCRIPTION

[0058] The present invention is further described in detail below in conjunction with specific examples, but the protection scope of the present invention is not limited thereto. The raw materials used in the following examples are all commercially available unless otherwise specified.

[0059] Example 1 Synthesis of N-benzylidene aniline with different ratios of Cu and Zr(OH)4

[0060] 1. Add 10.0 g of Zr(OH)4 catalyst with a Cu to Zr(OH)4 ratio of 0:100 into a 2500 mL high pressure sterilization reactor, then add 10.81 g of benzyl alcohol, 12.31 g of nitrobenzene and 1000 mL of n-octane, completely replace the atmosphere in the reactor with hydrogen and increase the pressure to 0.5 MPa, react at 180°C for 24 h, then filter, distill and recrystallize to obtain the product N-benzylidene aniline.

[0061] 2. Add 11 g of Cu+Zr(OH)4 catalyst with a ratio of Cu to Zr(OH)4 of 10:100 into a 2500 mL high pressure sterilization reactor, then add 10.81 g of benzyl alcohol, 12.31 g of nitrobenzene and 1000 mL of n-octane, completely replace the atmosphere in the reactor with hydrogen and increase the pressure to 0.5 MPa, react at 180°C for 24 h, and then filter, distill and recrystallize to obtain the product N-benzylidene aniline.

[0062] 3. Add 12 g of Cu+Zr(OH)4 catalyst with a Cu to Zr(OH)4 ratio of 20:100 into a 2500 mL high pressure sterilization reactor, then add 10.81 g of benzyl alcohol, 12.31 g of nitrobenzene and 1000 mL of n-octane, completely replace the atmosphere in the reactor with hydrogen and increase the pressure to 0.5 MPa, react at 180°C for 24 h, and then filter, distill and recrystallize to obtain the product N-benzylidene aniline.

[0063] 4. Add 13 g of Cu+Zr(OH)4 catalyst with a ratio of Cu to Zr(OH)4 of 30:100 into a 2500 mL high pressure sterilization reactor, then add 10.81 g of benzyl alcohol, 12.31 g of nitrobenzene and 1000 mL of n-octane, completely replace the atmosphere in the reactor with hydrogen and increase the pressure to 0.5 MPa, react at 180°C for 24 h, and then filter, distill and recrystallize to obtain the product N-benzylidene aniline.

[0064] 5. Add 14 mg of Cu+Zr(OH)4 catalyst with a Cu to Zr(OH)4 ratio of 40:100 into a 2500 mL high pressure sterilization reactor, then add 10.81 g of benzyl alcohol, 12.31 g of nitrobenzene and 1000 mL of n-octane, completely replace the atmosphere in the reactor with hydrogen and increase the pressure to 0.5 MPa, react at 180°C for 24 hours, and then filter, distill and recrystallize to obtain the product N-benzylidene aniline.

[0065] 6. Add 15 mg of Cu+Zr(OH)4 catalyst with a Cu to Zr(OH)4 ratio of 50:100 into a 2500 mL high pressure sterilization reactor, then add 10.81 g of benzyl alcohol, 12.31 g of nitrobenzene and 1000 mL of n-octane, completely replace the atmosphere in the reactor with hydrogen and increase the pressure to 0.5 MPa, react at 180°C for 24 hours, and then filter, distill and recrystallize to obtain the product N-benzylidene aniline.

[0066] The yield of N-benzylidene aniline obtained by the preparation method described in 1-6 above was calculated, and the results are shown in Table 1 below:

[0067] Table 1 Process parameters and product yields of the preparation method described in Example 1

[0068]

[0069] The mass spectrum of the main product synthesized by the above reaction is as follows Figure 4 As shown (the mass spectra of all the above products are the same, so only one mass spectrum is provided). The structural formula of the product is shown in Formula 1. The above results show that using n-octane as the reaction solvent and Cu+Zr(OH)4 as the catalyst (the ratio of Cu to Zr(OH)4 is 10:100, and the total catalyst amount is 11g) under the conditions of 24h, 180°C and 0.5MPa hydrogen, it can catalyze the coupling of benzyl alcohol and nitrobenzene to synthesize N-benzylidene aniline with a yield of 95%.

[0070]

[0071] Example 2 Synthesis of N-benzylidene aniline using different reaction solvents

[0072] 1. Add 11 g of Cu+Zr(OH)4 catalyst with a ratio of Cu to Zr(OH)4 of 10:100 into a 2500 mL high pressure sterilization reactor, then add 10.81 g of benzyl alcohol, 12.31 g of nitrobenzene and 1000 mL of n-octane, completely replace the atmosphere in the reactor with hydrogen and increase the pressure to 0.5 MPa, react at 180°C for 24 h, then filter, distill and recrystallize to obtain the product N-benzylidene aniline.

[0073] 2. Add 11 g of Cu+Zr(OH)4 catalyst with a Cu to Zr(OH)4 ratio of 10:100 into a 2500 mL high pressure sterilization reactor, then add 10.81 g of benzyl alcohol, 12.31 g of nitrobenzene and 1000 mL of isopentane, completely replace the atmosphere in the reactor with hydrogen and increase the pressure to 0.5 MPa, react at 180°C for 24 h, and then filter, distill and recrystallize to obtain the product N-benzylidene aniline.

[0074] 3. Add 11 g of Cu+Zr(OH)4 catalyst with a ratio of Cu to Zr(OH)4 of 10:100 into a 2500 mL high pressure sterilization reactor, then add 10.81 g of benzyl alcohol, 12.31 g of nitrobenzene and 1000 mL of n-hexane, completely replace the atmosphere in the reactor with hydrogen and increase the pressure to 0.5 MPa, react at 180°C for 24 h, and then filter, distill and recrystallize to obtain the product N-benzylidene aniline.

[0075] 4. Add 11 g of Cu+Zr(OH)4 catalyst with a Cu to Zr(OH)4 ratio of 10:100 into a 2500 mL high pressure sterilization reactor, then add 10.81 g of benzyl alcohol, 12.31 g of nitrobenzene and 1000 mL of petroleum ether, completely replace the atmosphere in the reactor with hydrogen and increase the pressure to 0.5 MPa, react at 180°C for 24 h, and then filter, distill and recrystallize to obtain the product N-benzylidene aniline.

[0076] 5. Add 11 g of Cu+Zr(OH)4 catalyst with a ratio of Cu to Zr(OH)4 of 10:100 into a 2500 mL high pressure sterilization reactor, then add 10.81 g of benzyl alcohol, 12.31 g of nitrobenzene and 1000 mL of N,N-dimethylformamide, completely replace the atmosphere in the reactor with hydrogen and increase the pressure to 0.5 MPa, react at 180°C for 24 h, then filter, distill and recrystallize to obtain the product N-benzylidene aniline.

[0077] 6. Add 11 g of Cu+Zr(OH)4 catalyst with a ratio of Cu to Zr(OH)4 of 10:100 into a 2500 mL high pressure sterilization reactor, then add 10.81 g of benzyl alcohol, 12.31 g of nitrobenzene and 1000 mL of ethanol, completely replace the atmosphere in the reactor with hydrogen and increase the pressure to 0.5 MPa, react at 180°C for 24 h, and then filter, distill and recrystallize to obtain the product N-benzylidene aniline.

[0078] 7. Add 11 g of Cu+Zr(OH)4 catalyst with a Cu to Zr(OH)4 ratio of 10:100 into a 2500 mL high pressure sterilization reactor, then add 10.81 g of benzyl alcohol, 12.31 g of nitrobenzene and 1000 mL of toluene, completely replace the atmosphere in the reactor with hydrogen and increase the pressure to 0.5 MPa, react at 180°C for 24 h, and then filter, distill and recrystallize to obtain the product N-benzylidene aniline.

[0079] 8. Add 11 g of Cu+Zr(OH)4 catalyst with a ratio of Cu to Zr(OH)4 of 10:100 into a 2500 mL high pressure sterilization reactor, then add 10.81 g of benzyl alcohol, 12.31 g of nitrobenzene and 1000 mL of acetonitrile, completely replace the atmosphere in the reactor with hydrogen and increase the pressure to 0.5 MPa, react at 180°C for 24 h, and then filter, distill and recrystallize to obtain the product N-benzylidene aniline.

[0080] The yield of the N-benzylidene aniline product obtained by the preparation method described in 1-8 above was calculated, and the results are shown in Table 2 below:

[0081] Table 2 Process parameters and product yields of the preparation method described in Example 2

[0082]

[0083]

[0084] The mass spectrum of the main product obtained from the above reaction is as follows Figure 5 As shown (the mass spectra of all the above products are the same, so only one mass spectrum is provided), the structural formula of the product is shown in Formula 1. The above results show that with 1000mL of n-octane as the reaction solvent and Cu+Zr(OH)4 as the catalyst (the ratio of Cu to Zr(OH)4 is 10:100, and the total catalyst amount is 11g), under the conditions of 24h, 180°C and 0.5MPa of hydrogen, benzyl alcohol and nitrobenzene can be coupled to synthesize N-benzylidene aniline with a yield of 95%.

[0085]

[0086] Example 3 Synthesis of N-benzylidene aniline at different reaction temperatures

[0087] 1. Add 11 g of Cu+Zr(OH)4 catalyst with a ratio of Cu to Zr(OH)4 of 10:100 into a 2500 mL high pressure sterilization reactor, then add 10.81 g of benzyl alcohol, 12.31 g of nitrobenzene and 1000 mL of n-octane, completely replace the atmosphere in the reactor with hydrogen and increase the pressure to 0.5 MPa, react at 100 °C for 24 h, then filter, distill and recrystallize to obtain the product N-benzylidene aniline.

[0088] 2. Add 11 g of Cu+Zr(OH)4 catalyst with a ratio of Cu to Zr(OH)4 of 10:100 into a 2500 mL high pressure sterilization reactor, then add 10.81 g of benzyl alcohol, 12.31 g of nitrobenzene and 1000 mL of n-octane, completely replace the atmosphere in the reactor with hydrogen and increase the pressure to 0.5 MPa, react at 110°C for 24 h, and then filter, distill and recrystallize to obtain the product N-benzylidene aniline.

[0089] 3. Add 11 g of Cu+Zr(OH)4 catalyst with a ratio of Cu to Zr(OH)4 of 10:100 into a 2500 mL high pressure sterilization reactor, then add 10.81 g of benzyl alcohol, 12.31 g of nitrobenzene and 1000 mL of n-octane, completely replace the atmosphere in the reactor with hydrogen and increase the pressure to 0.5 MPa, react at 120°C for 24 h, and then filter, distill and recrystallize to obtain the product N-benzylidene aniline.

[0090] 4. Add 11 g of Cu+Zr(OH)4 catalyst with a Cu to Zr(OH)4 ratio of 10:100 into a 2500 mL high pressure sterilization reactor, then add 10.81 g of benzyl alcohol, 12.31 g of nitrobenzene and 1000 mL of n-octane, completely replace the atmosphere in the reactor with hydrogen and increase the pressure to 0.5 MPa, react at 130°C for 24 h, and then filter, distill and recrystallize to obtain the product N-benzylidene aniline.

[0091] 5. Add 11 g of Cu+Zr(OH)4 catalyst with a ratio of Cu to Zr(OH)4 of 10:100 into a 2500 mL high pressure sterilization reactor, then add 10.81 g of benzyl alcohol, 12.31 g of nitrobenzene and 1000 mL of n-octane, completely replace the atmosphere in the reactor with hydrogen and increase the pressure to 0.5 MPa, react at 140°C for 24 h, and then filter, distill and recrystallize to obtain the product N-benzylidene aniline.

[0092] 6. Add 11 g of Cu+Zr(OH)4 catalyst with a Cu to Zr(OH)4 ratio of 10:100 into a 2500 mL high pressure sterilization reactor, then add 10.81 g of benzyl alcohol, 12.31 g of nitrobenzene and 1000 mL of n-octane, completely replace the atmosphere in the reactor with hydrogen and increase the pressure to 0.5 MPa, react at 150°C for 24 h, and then filter, distill and recrystallize to obtain the product N-benzylidene aniline.

[0093] 7. Add 11 g of Cu+Zr(OH)4 catalyst with a ratio of Cu to Zr(OH)4 of 10:100 into a 2500 mL high pressure sterilization reactor, then add 10.81 g of benzyl alcohol, 12.31 g of nitrobenzene and 1000 mL of n-octane, completely replace the atmosphere in the reactor with hydrogen and increase the pressure to 0.5 MPa, react at 160°C for 24 h, and then filter, distill and recrystallize to obtain the product N-benzylidene aniline.

[0094] 8. Add 11 g of Cu+Zr(OH)4 catalyst with a Cu to Zr(OH)4 ratio of 10:100 into a 2500 mL high pressure sterilization reactor, then add 10.81 g of benzyl alcohol, 12.31 g of nitrobenzene and 1000 mL of n-octane, completely replace the atmosphere in the reactor with hydrogen and increase the pressure to 0.5 MPa, react at 170°C for 24 h, and then filter, distill and recrystallize to obtain the product N-benzylidene aniline.

[0095] 9. Add 11 g of Cu+Zr(OH)4 catalyst with a ratio of Cu to Zr(OH)4 of 10:100 into a 2500 mL high pressure sterilization reactor, then add 10.81 g of benzyl alcohol, 12.31 g of nitrobenzene and 1000 mL of n-octane, completely replace the atmosphere in the reactor with hydrogen and increase the pressure to 0.5 MPa, react at 180°C for 24 h, and then filter, distill and recrystallize to obtain the product N-benzylidene aniline.

[0096] The yield of N-benzylidene aniline obtained by the preparation method described in 1-9 above was calculated, and the results are shown in Table 3 below:

[0097] Table 3 Process parameters and product yields of the preparation method described in Example 3

[0098]

[0099] The mass spectrum of the main product obtained from the above reaction is as follows Figure 6 As shown (the mass spectra of all the above products are the same, so only one mass spectrum is provided), the structural formula of the product is shown in Formula 1. The above results show that using n-octane as the reaction solvent and Cu+Zr(OH)4 as the catalyst (the ratio of Cu to Zr(OH)4 is 10:100, and the total catalyst amount is 11g) under the conditions of 24h, 180°C and 0.5MPa hydrogen, it can catalyze the coupling of benzyl alcohol and nitrobenzene to synthesize N-benzylidene aniline with a yield of 95%.

[0100]

[0101] Example 4 Synthesis of the corresponding imine products using different benzyl alcohol derivatives

[0102] 1. Add 11g of Cu+Zr(OH)4 catalyst with a ratio of Cu to Zr(OH)4 of 10:100 to a 2500mL autoclave reactor, then add 10.81g of benzyl alcohol, 12.31g of nitrobenzene and 1000mL of n-octane, completely replace the atmosphere in the reactor with hydrogen and increase the pressure to 0.5MPa, react at 180°C for a certain period of time, filter, distill and recrystallize to obtain the product N-benzylidene aniline. The mass spectrum of the product is shown in the figure below: Figure 7 As shown, the structural formula is shown in Formula 1.

[0103]

[0104] 2. Add 11g of Cu+Zr(OH)4 catalyst with a ratio of Cu to Zr(OH)4 of 10:100 to a 2500mL autoclave reactor, then add 13.82g of p-methoxybenzyl alcohol, 12.31g of nitrobenzene and 1000mL of n-octane, completely replace the atmosphere in the reactor with hydrogen and increase the pressure to 0.5MPa, react at 180°C for a certain period of time, filter, distill and recrystallize to obtain the product (E)-N-(4-methoxybenzylidene)aniline. The mass spectrum of the product is shown in the figure below: Figure 8 As shown, the structural formula is shown in Formula 2.

[0105]

[0106] 3. Add 11g of Cu+Zr(OH)4 catalyst with a ratio of Cu to Zr(OH)4 of 10:100 to a 2500mL autoclave reactor, then add 12.22g of p-methylbenzyl alcohol, 12.31g of nitrobenzene and 1000mL of n-octane, completely replace the atmosphere in the reactor with hydrogen and increase the pressure to 0.5MPa, react at 180°C for a certain period of time, filter, distill and recrystallize to obtain the product benzylidene p-toluidine. The mass spectrum of the product is shown in the figure below: Fig. 9 As shown, the structural formula is as shown in Formula 3

[0107]

[0108] 4. Add 11g of Cu+Zr(OH)4 catalyst with a ratio of Cu to Zr(OH)4 of 10:100 to a 2500mL autoclave reactor, then add 14.26g of p-chlorobenzyl alcohol, 12.31g of nitrobenzene and 1000mL of n-octane, completely replace the atmosphere in the reactor with hydrogen and increase the pressure to 0.5MPa, react at 180°C for a certain period of time, filter, distill and recrystallize to obtain the product (E)-N-(4-chlorobenzylidene)aniline. The mass spectrum of the product is shown in the figure below: Fig.10 As shown, the structural formula is shown in Formula 4.

[0109]

[0110] The yields of the corresponding imine derivative products obtained by the preparation methods described in 1-4 above were calculated, and the results are shown in Table 4 below:

[0111] Table 4 Process parameters and product yields of the preparation method described in Example 4

[0112]

[0113] The above results show that using n-octane as the reaction solvent and Cu+Zr(OH)4 as the catalyst (the ratio of Cu to Zr(OH)4 is 10:100, and the total catalyst amount is 11g) at 180°C and 0.5MPa hydrogen conditions can catalyze the coupling of benzyl alcohol and its derivatives with nitrobenzene to synthesize the corresponding imines and their derivatives in high yield.

[0114] Example 5 Synthesis of corresponding imine products using different nitrobenzene derivatives

[0115] 1. Add 11g of Cu+Zr(OH)4 catalyst with a ratio of Cu to Zr(OH)4 of 10:100 to a 2500mL autoclave reactor, then add 10.81g of benzyl alcohol, 12.31g of nitrobenzene and 1000mL of n-octane, completely replace the atmosphere in the reactor with hydrogen and increase the pressure to 0.5MPa, react at 180°C for a certain period of time, filter, distill and recrystallize to obtain the product N-benzylidene aniline. The mass spectrum of the product is shown in the figure below: Fig.11 As shown, the structural formula is shown in Formula 1.

[0116]

[0117]

[0118] 2. Add 11g of Cu+Zr(OH)4 catalyst with a ratio of Cu to Zr(OH)4 of 10:100 to a 2500mL autoclave reactor, then add 10.81g of benzyl alcohol, 15.31g of p-nitroanisole and 1000mL of n-octane, completely replace the atmosphere in the reactor with hydrogen and increase the pressure to 0.5MPa, react at 180°C for a certain period of time, filter, distill and recrystallize to obtain the product 4-methoxy-N-(phenylmethylene)-aniline. The mass spectrum of the product is as follows: Fig.12 As shown, the structural formula is shown in Formula 5.

[0119]

[0120] 3. Add 11g of Cu+Zr(OH)4 catalyst with a ratio of Cu to Zr(OH)4 of 10:100 to a 2500mL autoclave reactor, then add 10.81g of benzyl alcohol, 13.71g of p-nitrotoluene and 1000mL of n-octane, completely replace the atmosphere in the reactor with hydrogen and increase the pressure to 0.5MPa, react at 180°C for a certain period of time, filter, distill and recrystallize to obtain the product (E)-4-methyl-N-(phenylmethylene)-aniline. The mass spectrum of the product is shown in the figure below: Fig.13 As shown, the structural formula is shown in Formula 6.

[0121]

[0122] 4. Add 11g of Cu+Zr(OH)4 catalyst with a ratio of Cu to Zr(OH)4 of 10:100 to a 2500mL autoclave reactor, then add 10.81g of benzyl alcohol, 15.76g of p-chloronitrobenzene and 1000mL of n-octane, completely replace the atmosphere in the reactor with hydrogen and increase the pressure to 0.5MPa, react at 180°C for a certain period of time, filter, distill and recrystallize to obtain the product (E)-4-chloro-N-(phenylmethylene)aniline. The mass spectrum of the product is shown in the figure below: Fig.14 As shown, the structural formula is shown in Formula 7.

[0123]

[0124] The yields of the corresponding imine derivative products obtained by the preparation methods described in 1-4 above were calculated, and the results are shown in Table 5 below:

[0125] Table 5 Process parameters and product yields of the preparation method described in Example 5

[0126]

[0127]

[0128] The above results show that using n-octane as the reaction solvent and Cu+Zr(OH)4 as the catalyst (the ratio of Cu to Zr(OH)4 is 10:100, and the total catalyst amount is 11g) at 180°C and 0.5MPa hydrogen conditions can catalyze the coupling of benzyl alcohol and nitrobenzene and its derivatives to synthesize the corresponding imines and their derivatives in high yield.

[0129] Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention rather than to limit it. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solution of the present invention can be modified or replaced by equivalents without departing from the purpose and scope of the technical solution of the present invention, which should be included in the scope of the claims of the present invention.

Claims

1. A method for preparing a physically mixed catalyst Cu+Zr(OH) and its application in catalyzing the coupling of benzyl alcohol or its derivatives and nitrobenzene or its derivatives in a stoichiometric ratio to synthesize N-benzylidene aniline or its derivatives.

2. As claimed in claim 1, the preparation method of the physical mixed catalyst Cu+Zr(OH)4 is characterized in that: Taking commercial Zr(OH)4 as the main catalyst, metal Cu was introduced into the catalyst system in the form of physical mixing. The specific operation steps are as follows: Step 1, treatment of Zr(OH)4: weigh a specific mass of commercial Zr(OH)4 and dry and calcine it at a specific temperature. Step 2, preparation of metallic Cu: weigh a certain amount of copper nitrate hydrate and place it in a container, add a certain amount of deionized water to dissolve it, then add an appropriate amount of precipitant, continue stirring for several hours, separate the solid product, wash, dry, calcine and reduce it to obtain metallic Cu. Step 3, weighing a specific mass of treated Zr(OH)4 and metal Cu and placing them in a reaction container to obtain a physical mixed catalyst Cu+Zr(OH)4.

3. The method for preparing a catalyst according to claims 1 and 2, characterized in that: The drying temperature in step 1 is 40-80°C, and the drying time is 2-20h. The precipitant in step 2 is a 1M sodium hydroxide solution, and the stirring time is 2-20h. The reducing atmosphere is hydrogen, the reducing temperature is 180-250°C, the roasting time is 2-20h, and the heating rate is 1-20°C / min. The mass ratio of Cu to Zr(OH)4 in step 3 is 0-50:

100.

4. The use of the method of claim 1 for synthesizing N-benzylidene aniline or its derivatives by coupling benzyl alcohol or its derivatives and nitrobenzene or its derivatives in a catalytic stoichiometric ratio, characterized in that: The structural formula of the N-benzylidene aniline or its derivative is shown in the following formula (III), and the raw materials are benzyl alcohol or its derivative (I) and nitrobenzene or its derivative (II), and their structural formulas are shown in the following formulas respectively: Wherein, R1-R5 are independently selected from any one of hydrogen, halogen, hydroxyl, sulfonic acid, nitro, substituted or unsubstituted straight or branched alkyl, alkoxy, carbonyl, alkenyl, alkynyl, substituted or unsubstituted aryl, acylamino, and cyano, but are not limited to the above substituents.

5. A method for preparing N-benzylidene aniline or a derivative thereof as claimed in claims 1 and 4, comprising: Benzyl alcohol or its derivative (Ⅰ) and nitrobenzene or its derivative (Ⅱ) shown in the following formula are used as raw materials, an organic solvent is used as a reaction solvent, Cu+Zr(OH)4 is used as a catalyst, and hydrogen is used as a reaction atmosphere to synthesize N-benzylidene aniline or its derivative (Ⅲ) shown in the following formula through a catalytic coupling reaction, wherein the organic solvent includes n-octane, isopentane, n-pentane, n-heptane, cyclohexane, n-hexane, petroleum ether, N,N-dimethylformamide, ethanol, methanol, water, toluene, and acetonitrile; Among them, R1-R5 are independently selected from any one of hydrogen, halogen, hydroxyl, sulfonic acid, nitro, substituted or unsubstituted straight or branched alkyl, alkoxy, carbonyl, alkenyl, alkynyl, substituted or unsubstituted aryl, acylamino, and cyano.

6. The synthesis method according to claims 1, 4 and 5, characterized in that: The ratio of Cu to Zr(OH)4 in the catalyst is 0-50:100, the ratio of the catalyst to benzyl alcohol is 10-15 g:100 mmol, the hydrogen pressure is 0.5 MPa, the ratio of the reaction solvent to benzyl alcohol is 1000 mL:100 mmol, the reaction temperature is 100-180°C, and the reaction time is 24 h.

7. The synthesis method according to claim 4-5, characterized in that: The R1-R5 are selected from hydrogen, methyl, chlorine, fluorine and methoxy. The benzyl alcohol or its derivatives and nitrobenzene or its derivatives include benzyl alcohol, p-methylbenzyl alcohol, p-methoxybenzyl alcohol, 4-fluorobenzyl alcohol, 4-chlorobenzyl alcohol, nitrobenzene, p-nitrotoluene, p-nitrobenzene anisole, 4-fluoronitrobenzene and 4-chloronitrobenzene.

8. The synthesis method according to any one of claims 4 to 7, characterized in that: Benzyl alcohol or its derivatives, nitrobenzene or its derivatives, Cu+Zr(OH)4 (wherein the ratio of Cu to Zr(OH)4 is 10:100, and the ratio of catalyst to substrate is 11 g:100 mmol) are added to n-octane (with the ratio of benzyl alcohol being 1000 mL:100 mmol), and the reaction is carried out at a hydrogen pressure of 0.5 MPa and 180°C for 24 hours; N-benzylidene aniline or its derivatives are obtained by filtration, distillation and recrystallization.

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