A method for catalytically preparing 4,4'-di-tert-butyl-2,2'-bipyridine by using a single-atom nickel loaded magnetic covalent organic framework

Abstract

This invention belongs to the field of fine chemical single-atom catalysis technology, specifically relating to a method for preparing 4,4'-di-tert-butyl-2,2'-bipyridine using a single-atom nickel catalyst supported by a magnetic covalent organic framework. (1) 2-chloro-4-tert-butylpyridine, zinc powder, tetrabutylammonium bromide, Mag-COF-Ni catalyst and solvent are mixed and reacted at 75-85℃ for 5-7 h; (2) After the reaction is completed, an external magnetic field is applied, and the mixture is allowed to stand to separate the Mag-COF-Ni catalyst from the reaction liquid, and the liquid mother liquor is collected; (3) Water is added to the liquid mother liquor, and the mixture is stirred at room temperature to crystallize. After solid-liquid separation, washing the filter cake, and drying, 4,4'-di-tert-butyl-2,2'-bipyridine is obtained; wherein, the Mag-COF-Ni catalyst is a single-atom nickel catalyst supported by a magnetic covalent organic framework. This invention utilizes the strong coordination of nitrogen sites in the COF framework to fix single-atom nickel, thereby preventing nickel ion dissolution and chelation in the product from the source. The finished product has a nickel residue of <1ppm and an HPLC purity of ≥99.5%, eliminating the need for costly post-processing steps such as high-vacuum distillation and nickel removal with chelating resin.

Description

Technical Field

[0001] This invention belongs to the field of fine chemical single-atom catalysis technology, specifically relating to a method for preparing 4,4'-di-tert-butyl-2,2'-bipyridine by single-atom nickel catalysis supported on a magnetic covalent organic framework. Background Technology

[0002] 4,4'-Di-tert-butyl-2,2'-bipyridine is a high-performance nitrogen-containing chelating ligand that relies on the coordination of the bispyridine nitrogen atom with a transition metal. It is widely used in homogeneous catalysis, electrochemical electrode materials, organic optoelectronic devices, and drug synthesis catalysis systems, with a global annual market demand of several thousand tons. High-end downstream applications mandate two core indicators for the product: HPLC purity ≥99.5% and nickel heavy metal residue ≤1ppm.

[0003] Current mass production routes in the industry all use nickel-based catalysts to catalyze the Ullmann self-coupling of 2-chloro-4-tert-butylpyridine, which is divided into two major systems: homogeneous nickel chloride / nickel acetate and Raney nickel. Zinc powder is used as a reducing agent and DMF as a solvent. The raw materials are readily available and the reaction conditions are mild, but there are still technical shortcomings that cannot be eradicated: 1. Severe exceedance of heavy metal nickel: Bipyridine contains a strongly coordinated pyridine nitrogen ring, which can react with free Ni 2+ 1. Zero-valent nickel forms stable chelates; homogeneous nickel is completely dissolved in the reaction solution, and water washing and extraction cannot dissociate complexed impurities, resulting in crude product nickel content of 700-900 ppm, far exceeding industry standards; 2. High post-processing costs: only two nickel removal and refining methods are available: ① High-vacuum high-temperature distillation: large equipment investment, high energy consumption, product decomposition due to heat, and a 5%-10% decrease in total yield; ② Heavy metal chelating resin adsorption for nickel removal: high resin procurement and regeneration costs, significantly increasing product prices; 3. Catalyst cannot be efficiently recovered, resulting in significant environmental pressure: homogeneous nickel is completely lost, and the mother liquor forms high-nickel hazardous waste; Raney nickel is a solid particle, resulting in high losses in plate and frame filtration, continuous nickel shedding and contamination of the product, and serious waste of metal resources; 4. Conventional nickel loading improvement schemes are ineffective: activated carbon and silica carriers for loading nano-nickel have no directional nitrogen coordination anchoring points, making nickel particles easy to agglomerate and detach, and the detached nickel still complexes with the product; non-magnetic carriers require filtration and centrifugation, making the production process lengthy.

[0004] In summary, existing technologies lack an industrialized, green synthesis solution that can be magnetically separated, anchored at a single atom to prevent nickel leaching, and requires no additional refining. Summary of the Invention

[0005] To address the problems and shortcomings of existing technologies, this invention aims to provide a method for preparing 4,4'-di-tert-butyl-2,2'-bipyridine using a single-atom nickel catalyst supported on a magnetic covalent organic framework.

[0006] To achieve the above objectives, the present invention adopts the following technical solution: The first aspect of this invention provides a method for preparing 4,4'-di-tert-butyl-2,2'-bipyridine using a single-atom nickel catalyst supported on a magnetic covalent organic framework, comprising the following steps: (1) 2-chloro-4-tert-butylpyridine, zinc powder, tetrabutylammonium bromide, Mag-COF-Ni catalyst and solvent are mixed to obtain a reaction mixture. After the reaction mixture is deoxygenated by inert gas replacement, it is reacted at 75-85°C for 5-7 hours under stirring. (2) After the reaction is complete, apply an external magnetic field and let stand to separate the Mag-COF-Ni catalyst from the reaction liquid and collect the liquid mother liquor; (3) Add water to the liquid mother liquor, stir at room temperature to crystallize, and then separate the solid and liquid, wash the filter cake and dry it to obtain 4,4'-di-tert-butyl-2,2'-bipyridine; The Mag-COF-Ni catalyst is a single-atom nickel catalyst supported on a magnetic covalent organic framework; the nickel loading in the Mag-COF-Ni catalyst is 1.5wt% to 2.5wt%.

[0007] Preferably, in step (1), the ratio of the amount of 2-chloro-4-tert-butylpyridine to Mag-COF-Ni catalyst is (10-15) mmol: (0.15-0.25) g; and the molar ratio of 2-chloro-4-tert-butylpyridine, zinc powder, and tetrabutylammonium bromide is (10-15): (8-12): (0.2-0.5).

[0008] Preferably, in step (1), the solvent is N,N-dimethylformamide; the ratio of 2-chloro-4-tert-butylpyridine to the solvent is (10-15) mmol: (40-60) mL.

[0009] Preferably, in step (1), the Mag-COF-Ni catalyst is prepared by the following method: amino-modified Fe3O4 is dispersed in anhydrous acetonitrile, cyanuric chloride and p-phenylenediamine are added, stirred and mixed, and refluxed at 75-85°C for 10-14 h; after magnetic separation, washing and drying, Fe3O4@COF is obtained; the Fe3O4@COF is dispersed in ethanol, nickel chloride alcohol solution is added, and impregnated at room temperature in the dark for 10-14 h, then sodium borohydride is added, and the reaction is carried out at 0-5°C for 20-40 min. After the reaction is completed, after magnetic separation, washing and drying, the Mag-COF-Ni catalyst is obtained.

[0010] Preferably, the mass ratio of the amino-modified Fe3O4, cyanuric chloride, and p-phenylenediamine is 0.5:(0.2-0.3):(0.15-0.25).

[0011] Preferably, the concentration of the nickel chloride alcohol solution is 0.03 to 0.08 mol / L.

[0012] Preferably, the ratio of Fe3O4@COF to nickel chloride alcohol solution is 0.4g:(5-10)mL, and the mass ratio of Fe3O4@COF to sodium borohydride is (1.5-2.5):1.

[0013] Preferably, in step (3), the amount of water used is 3 times the volume of the solvent; in step (1), the stirring speed is 350-450 r / min.

[0014] Preferably, in step (2), the separated Mag-COF-Ni catalyst is washed twice with N,N-dimethylformamide without activation and can be directly used for the preparation of 4,4'-di-tert-butyl-2,2'-bipyridine; the settling time is 5 to 20 seconds.

[0015] A second aspect of the present invention provides a 4,4'-di-tert-butyl-2,2'-bipyridine prepared by the method described in the first aspect above, wherein the 4,4'-di-tert-butyl-2,2'-bipyridine has a purity ≥99.5% and a nickel residue of 0.42 to 0.6 ppm.

[0016] Compared with the prior art, the beneficial effects of the present invention are as follows: (1) This invention provides a novel low-temperature liquid-phase green process for the synthesis of 4,4'-di-tert-butyl-2,2'-bipyridine via Fe3O4@COF core-shell single-atom nickel catalysis. This invention locks the single-atom nickel active sites at the catalyst molecular structure level, completely eliminating nickel ion ion ion ionization and product chelation; it achieves 10-second-level solid-liquid separation using a superparamagnetic carrier, eliminating the need for two refining processes: high-vacuum distillation and nickel removal using chelating resin. This process is suitable for continuous, low-cost industrial mass production of bipyridine ligands. It solves the technical problems of excessive nickel leaching, high refining costs, difficult catalyst recovery, and large amounts of hazardous waste in existing homogeneous nickel, Raney nickel, and silica-supported nickel processes.

[0017] (2) In the catalyst of this invention, the nitrogen atoms in the COF skeleton are strongly coordinated to lock single-atom nickel, with no free nickel ions. The residual nickel in the finished product is 0.42-0.6 ppm < 1 ppm, and the HPLC purity is stable at ≥ 99.5%. This eliminates the need for two refining processes: distillation and chelation resin, and directly meets the requirements for high-end ligands. At the same time, it eliminates the need for investment in high-vacuum distillation equipment and procurement of chelation resin consumables. The catalyst can be recycled more than 10 times, greatly improving the utilization rate of metallic nickel and significantly reducing the overall cost of raw materials, refining, and labor.

[0018] (3) The external permanent magnet of the present invention completes solid-liquid separation in 10s, eliminating the need for filtration and centrifugation equipment, reducing production time by 40%, and is simple to operate. It can be matched with a continuous reaction device. (4) The present invention has no nickel catalyst leaching loss, does not generate high nickel hazardous waste, and allows for the recycling of metallic nickel resources, making it green and environmentally friendly, with low cost of waste treatment.

[0019] (5) The present invention has a single-atom nickel atom utilization rate of 100%, substrate conversion rate ≥97%, target product selectivity ≥99%, few by-products, activity decay of less than 2% after 10 consecutive cycles, minimal fluctuation of product indicators, good catalytic stability, and high consistency of product batches.

[0020] (6) The tetrabutylammonium bromide of the present invention has a unique phase transfer promoting effect in the magnetic single-atom nickel-DMF-zinc powder reduction system. The lack of this additive will significantly reduce the reaction conversion efficiency and production capacity. Attached Figure Description

[0021] Figure 1 This is a schematic diagram of the synthesis route of the Mag-COF-Ni catalyst of the present invention; Figure 2 The infrared spectrum of the Mag-COF-Ni catalyst of this invention; Figure 3 The magnetometer test curve of the Mag-COF-Ni catalyst VSM vibrating sample of this invention; Figure 4 This is the BET nitrogen adsorption-desorption isotherm of the Mag-COF-Ni catalyst of this invention; Figure 5 The TGA thermogravimetric analysis curve of the Mag-COF-Ni catalyst of this invention is shown. Detailed Implementation

[0022] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.

[0023] Example 1:

[0024] A method for preparing 4,4'-di-tert-butyl-2,2'-bipyridine using a single-atom nickel catalyst supported on a magnetic covalent organic framework, the specific steps of which are as follows: (1) 12 mmol of 2-chloro-4-tert-butylpyridine substrate, 10 mmol of zinc powder, 0.3 mmol of tetrabutylammonium bromide (TBAB), 50 mL of N,N-dimethylformamide (DMF), and 0.2 g of Mag-COF-Ni catalyst were added to the reactor; nitrogen was used to purge the oxygen in the reaction system three times, the stirring speed was controlled at 400 r / min, and the coupling reaction was carried out at 80 °C for 6 h. (2) After the reaction is completed, a permanent magnet is attached to the outer wall of the reactor and allowed to stand for 10 seconds to complete the solid-liquid separation. The upper liquid mother liquor is poured out, and the solid catalyst retained in the reactor is washed twice with DMF and stored for later use. (3) Add 150 mL of deionized water to the poured liquid mother liquor, stir at room temperature for 2 h to crystallize, filter, wash the filter cake with pure water, and dry at 80 °C for 4 h to obtain 4,4'-di-tert-butyl-2,2'-bipyridine.

[0025] The Mag-COF-Ni catalyst was prepared by the following method, and its synthesis route is as follows: Figure 1 As shown: 1.0 g of ferric chloride hexahydrate and 2.5 g of anhydrous sodium acetate were dissolved in 40 mL of ethylene glycol and kept at 190 °C for 9 h using a solvothermal method. After cooling, the mixture was centrifuged, washed successively with ethanol and pure water, and vacuum dried to obtain Fe3O4 nanoparticles. 1.0 g of Fe3O4 nanoparticles were dispersed in an ethanol-water (40 mL ethanol + 10 mL water) mixed solvent, and 0.4 g of... APTES was reacted under nitrogen protection at 60℃ for 4 h with stirring, followed by magnetic separation, washing, and drying to obtain amino-rich Fe3O4-NH2. Fe3O4-NH2 was dispersed in 25 mL of anhydrous acetonitrile, and 0.25 g of cyanuric chloride and 0.2 g of p-phenylenediamine were added. The mixture was stirred at room temperature for 30 min, then heated to 80℃ and refluxed for 12 h. After magnetic separation, the mixture was washed successively with acetonitrile, methanol, and pure water, and dried at 80℃ for 8 h to obtain a nitrogen-rich core-shell support Fe3O4@COF with a pore size of 0.8–1.2 nm. 0.4 g of Fe3O4@COF support was dispersed in ethanol, and 7.5 mL of 0.05 mol / L nickel chloride ethanol solution was added dropwise. The mixture was impregnated at room temperature in the dark for 12 h. 0.2 g of sodium borohydride was added under ice-water bath conditions for reduction for 30 min, followed by magnetic separation, washing, and drying at 40℃ to obtain a Mag-COF-Ni catalyst with a nickel loading of 2.0 wt%.

[0026] Catalyst characterization: Figure 2 The image shows the infrared spectrum of the Mag-COF-Ni catalyst prepared in this embodiment. Figure 2 It can be seen that 1600~1620cm -1 It is a C=N imine bond stretching vibration; 1250–1400 cm⁻¹ -1 Corresponding to CO and CN bonds; 580cm -1 The presence of Fe-O bonds confirms the existence of Fe3O4; the shift in the C=N peak after nickel loading indicates the presence of Ni. 2+ It has electronic interactions with the N ligand of COF.

[0027] Figure 3The image shows the magnetometer test curve of the VSM vibrating sample of the Mag-COF-Ni catalyst prepared in this embodiment. Figure 3 It can be seen that the Mag-COF-Ni catalyst prepared in this embodiment has ferromagnetic behavior, with a saturation magnetization Ms=25-30 emu / g. The decrease in value compared to pure Fe3O4 is due to the organic coating of COF and nickel loading, but it still meets the requirements for rapid magnetic separation and recovery under an external magnetic field.

[0028] Figure 4 This is the BET nitrogen adsorption-desorption isotherm of the Mag-COF-Ni catalyst prepared in this embodiment. Figure 4 It can be seen that the curve belongs to the type IV isotherm and the H3 hysteresis loop, proving that the Mag-COF-Ni catalyst material prepared in this embodiment has a mesoporous structure; the original COF specific surface area is 520 m². 2 / g, reduced to 350m after loading Fe3O4 and Ni. 2 / g, with an average pore size of 3-5nm, which facilitates the diffusion of substrate molecules into the pores to contact the active sites.

[0029] Figure 5 The TGA thermogravimetric analysis curve of the Mag-COF-Ni catalyst prepared in this embodiment is shown. Figure 5 It can be seen that the weight loss is about 7% in the range of room temperature to 100℃, attributed to the volatilization of surface adsorbed water and residual solvent; the weight loss is about 9% in the range of 100 to 300℃, due to the desorption of physical adsorbates and small molecules; a second stage of weight loss occurs in the range of 300 to 450℃, corresponding to the gradual thermal decomposition of the COF organic framework; after 450℃, the mass tends to stabilize, with a final residue of about 78 wt%, consisting of inorganic components such as Fe3O4 and nickel. This indicates that the catalyst does not experience a sharp mass loss at conventional organic reaction temperatures (<200℃), and its thermal stability meets the reaction requirements.

[0030] Catalyst recycling performance test: The Mag-COF-Ni catalyst recovered after magnetic separation and DMF washing in step (2) of Example 1 was directly reused as the catalyst for the next batch of reactions. Except for the catalyst being the one recovered from the previous batch, the substrate amount, zinc powder, TBAB, DMF solvent, and reaction conditions (temperature, time, rotation speed, etc.) in each subsequent batch of reactions were strictly kept consistent with those in Example 1. Ten consecutive reuse experiments were conducted using this method.

[0031] The average results of 10 cycles are as follows: the average substrate conversion rate was 97.3%, the average yield of the target product 4,4'-di-tert-butyl-2,2'-bipyridine was 92.9%, the average HPLC purity of the product was 99.55%, and the average residual nickel content in the product was 0.50 ppm. Compared with the catalytic activity in the first cycle (Example 1), the catalyst activity decreased by less than 2% after 10 consecutive cycles.

[0032] Example 2: The content of Example 2 is basically the same as that of Example 1, except that in step (1), the amount of tetrabutylammonium bromide used is 0.1 mmol.

[0033] Example 3: The content of Example 3 is basically the same as that of Example 1, except that in step (1), the amount of tetrabutylammonium bromide used is 0.2 mmol.

[0034] Example 4: The content of Example 4 is basically the same as that of Example 1, except that in step (1), the amount of tetrabutylammonium bromide used is 0.4 mmol.

[0035] Example 5: The content of Example 5 is basically the same as that of Example 1, except that in step (1), the amount of tetrabutylammonium bromide used is 0.5 mmol.

[0036] Comparative Example 1: Comparative Example 1 is basically the same as Example 1, except that tetrabutylammonium bromide is not added in step (1).

[0037] Performance testing: The purity, nickel residue, substrate conversion rate, and total product yield of the products from Examples 1 to 5 and Comparative Example 1 of this invention were detected and calculated. The specific detection and calculation methods are as follows: 1. HPLC purity determination method for 4,4'-di-tert-butyl-2,2'-bipyridine: Detection instruments and chromatographic conditions: High performance liquid chromatograph (equipped with a UV detector, detection wavelength 265nm); C18 reversed-phase column (4.6mm×250mm, 5μm); mobile phase: methanol:pure water = 85:15 (V / V); flow rate 1.0mL / min; column temperature 30℃; injection volume 10μL; run time 20min.

[0038] Sample preparation: Accurately weigh 0.1000 g of sample, dilute to 100 mL with methanol, sonicate for 5 min to dissolve, and filter through a 0.22 μm organic filter membrane for testing. Calculate the purity according to formula (1) (area normalization method).

[0039]

[0040] In the formula: A: integral area of ​​chromatographic peak.

[0041] 2. Method for detecting residual nickel content in the product (ICP-MS): Accurately weigh 0.5g of sample, add 5mL of analytical grade nitric acid to a microwave digestion vessel, microwave digest completely, cool, and then dilute to 50mL with ultrapure water. Simultaneously perform a reagent blank control. The sample was determined using the external standard method of inductively coupled plasma mass spectrometry. The residual nickel content was calculated according to formula (2):

[0042] In the formula: C 样品 Nickel ion concentration in digestion solution (μg / L); V 定容 : Constant volume (L); m 样品 : Sample mass (g); 1ppm = 1μg / g.

[0043] 3. Substrate conversion rate calculation formula: The remaining 2-chloro-4-tert-butylpyridine substrate in the mother liquor was quantified using HPLC internal standard method, and the substrate conversion rate was calculated according to formula (3):

[0044] In the formula: ninitialsubstrate: the amount of substrate added; nremainingsubstrate: the amount of substrate that was not converted after the reaction.

[0045] 4. Calculation of total product yield: The total yield of the product is calculated according to formula (4):

[0046] In the formula: n is the theoretical maximum product: 1 mol of 2-chloro-4-tert-butylpyridine self-coupling to generate 0.5 mol of the target bipyridine.

[0047] The purity, nickel residue, substrate conversion, and total product yield of Examples 1 to 5 and Comparative Example 1 were calculated, and the results are shown in Table 1.

[0048] Table 1. Purity, nickel residue, conversion rate, and overall yield of Examples 1-5 and Comparative Example 1

[0049] Table 1 shows that without TBAB, solid-liquid mass transfer is poor, and the conversion and yield are significantly reduced. A small amount of TBAB can improve the reaction efficiency. This is because the lack of TBAB phase transfer catalysis results in poor solubility of zinc powder and trace nickel active intermediates in the DMF system, leading to high solid-liquid mass transfer resistance, incomplete substrate conversion, and a significant decrease in product yield. This proves that TBAB is a key auxiliary agent in this system. The conversion and yield are best at 0.2–0.3 mmol. Further increasing the amount added results in a slight increase in impurities and a decrease in purity.

[0050] Example 6: Example 6 is basically the same as Example 1, except that the amount of nickel chloride ethanol solution is changed to control the nickel loading in the Mag-COF-Ni catalyst to 1.0 wt%.

[0051] Example 7: Example 7 is basically the same as Example 1, except that the amount of nickel chloride ethanol solution is changed to control the nickel loading in the Mag-COF-Ni catalyst to 1.5 wt%.

[0052] Example 8: Example 8 is basically the same as Example 1, except that the amount of nickel chloride ethanol solution is changed to control the nickel loading in the Mag-COF-Ni catalyst to 2.5 wt%.

[0053] Example 9: Example 9 is basically the same as Example 1, except that the amount of nickel chloride ethanol solution is changed to control the nickel loading in the Mag-COF-Ni catalyst to 3.0 wt%.

[0054] The purity, nickel residue, substrate conversion rate, and total product yield of Examples 6 to 9 were calculated, and the results are shown in Table 2.

[0055] Table 2 Purity, nickel residue, conversion rate, and overall yield of Examples 6-9 and Example 1

[0056] As shown in Table 2, the purity, conversion and total yield of the product are significantly improved with the increase of nickel loading. The performance is relatively good in the range of 1.5wt% to 2wt%. Above this range, the dissolution of nickel increases and the residue continues to rise.

[0057] Example 10: The content of Example 10 is basically the same as that of Example 1, except that the reaction temperature in step (1) is 70°C.

[0058] Example 11: The content of Example 11 is basically the same as that of Example 1, except that the reaction temperature in step (1) is 75°C.

[0059] Example 12: The content of Example 12 is basically the same as that of Example 1, except that the reaction temperature in step (1) is 85°C.

[0060] Example 13: The content of Example 13 is basically the same as that of Example 1, except that the reaction temperature in step (1) is 90°C.

[0061] The purity, nickel residue, substrate conversion rate, and total product yield of Examples 10 to 13 were calculated, and the results are shown in Table 3.

[0062] Table 3. Purity, nickel residue, conversion rate, and overall yield of Examples 10–13 and Example 1

[0063] As shown in Table 3, when the reaction temperature is low, the reaction rate is slow and the conversion is incomplete. In the range of 75-80℃, the conditions are mild and the nickel residue is low. As the reaction temperature increases, nickel dissolution intensifies. In addition, high temperature destroys the COF anchoring structure, resulting in excessive nickel residue and an increase in by-products.

[0064] Example 14: The content of Example 14 is basically the same as that of Example 1, except that the reaction time in step (1) is 4 hours.

[0065] Example 15: The content of Example 15 is basically the same as that of Example 1, except that the reaction time in step (1) is 5 hours.

[0066] Example 16: The content of Example 16 is basically the same as that of Example 1, except that the reaction time in step (1) is 7 hours.

[0067] Example 17: The content of Example 17 is basically the same as that of Example 1, except that the reaction time in step (1) is 8 hours.

[0068] The purity, nickel residue, substrate conversion and total product yield of Examples 14 to 17 were calculated, and the results are shown in Table 4.

[0069] Table 4. Purity, nickel residue, conversion rate, and overall yield of Examples 14–17 and Example 1

[0070] As shown in Table 4, the conversion rate gradually increases and the yield increases with the extension of reaction time. The reaction effect is better at 5-6 hours. At 7 hours, nickel dissolution increases and the yield decreases slightly. Further extending the reaction time and the high temperature intensifies nickel detachment and the accumulation of by-products.

[0071] Examples 18-21: The contents of Examples 18 to 21 are basically the same as those of Example 1, except that in step (1), the stirring speeds of Examples 18 to 21 are 250, 350, 450, and 550 r / min, respectively.

[0072] The purity, nickel residue, substrate conversion rate, and total product yield of Examples 18 to 21 were calculated, and the results are shown in Table 5.

[0073] Table 5. Purity, nickel residue, conversion rate, and overall yield of Examples 18–21 and Example 1

[0074] Table 5 shows that when the stirring speed is too low (250 r / min), solid-liquid mass transfer is insufficient, zinc powder and catalyst particles are unevenly dispersed, substrate conversion is only 93.5%, and yield decreases significantly. When the stirring speed is increased to 350–450 r / min, mass transfer is good, conversion is ≥97.8%, and yield is ≥93.1%. When the stirring speed is too high (550 r / min), severe shear force may cause mechanical damage to the COF shell, exposure and detachment of nickel anchor points, nickel residue increases to 0.52 ppm, and both purity and yield decrease. The preferred stirring speed is 350–450 r / min.

[0075] Examples 22-24: The contents of Examples 22 to 24 are basically the same as those of Example 1, except that in step (1), the substrate 2-chloro-4-tert-butylpyridine is fixed at 12 mmol, and only the amount of zinc powder is changed. The amount of zinc powder in Examples 22 to 24 is 8, 12, and 14 mmol respectively.

[0076] The purity, nickel residue, substrate conversion rate, and total product yield of Examples 22 to 24 were calculated, and the results are shown in Table 6.

[0077] Table 6. Purity, nickel residue, conversion rate, and overall yield of Examples 22-24 and Example 1

[0078] Table 6 shows that when zinc powder is used as a reducing agent, insufficient dosage (8 mmol, molar ratio 1:0.67) results in insufficient reducing power, a substrate conversion rate of only 92.1%, a large amount of unreacted substrate residue, and a low yield. The optimal overall performance is achieved when the zinc powder dosage is 10 mmol (molar ratio 1:0.83). Excess zinc powder (12–14 mmol) may adsorb trace amounts of nickel reactive species on its surface, which may dissolve during acidic post-treatment, leading to increased nickel residue (0.48–0.55 ppm). Furthermore, excessive zinc slag carries away products, reducing the yield. The preferred molar ratio of 2-chloro-4-tert-butylpyridine to zinc powder is (10–15):(8–12).

[0079] Examples 25-27: The contents of Examples 25 to 27 are basically the same as those of Example 1, except that in step (2), the magnetic separation and standing time of Examples 25 to 27 are 5, 20, and 30 seconds respectively.

[0080] The purity, nickel residue, substrate conversion, and total product yield of Examples 25 to 27 were calculated, and the results are shown in Table 7.

[0081] Table 7. Product purity, nickel residue, substrate conversion, and total product yield for Examples 25–27.

[0082] As shown in Table 7, when the settling time is too short (5s), the Mag-COF-Ni catalyst particles have not completely settled in the magnetic field, and the fine particles are poured out with the mother liquor, resulting in a nickel residue of up to 0.68ppm in the product and a decrease in purity. A settling time of 10s is sufficient to achieve efficient separation of the catalyst from the liquid phase, reducing the nickel residue to 0.42ppm. Further extending the settling time to 20–30s only slightly reduces the nickel residue (0.39–0.40ppm), without significantly improving the separation effect, and instead increases production time. The optimal magnetic separation settling time is 5–20s, balancing separation efficiency and production cycle time.

[0083] Comparative Example 2: A method for preparing 4,4'-di-tert-butyl-2,2'-bipyridine using homogeneous nickel chloride catalysis, comprising the following specific steps: (1) Add 12 mmol of 2-chloro-4-tert-butylpyridine, 10 mmol of zinc powder, 0.3 mmol of TBAB, 50 mL of DMF and 0.6 mmol of anhydrous NiCl2 to the reaction vessel; purge with nitrogen three times to remove oxygen from the reaction system, control the stirring speed at 400 r / min, and keep the reaction at 80 °C for 6 h. (2) After the reaction was completed, there was no magnetic separation. The zinc slag was removed by direct filtration. 160 mL of pure water was added to the mother liquor for crystallization for 2 hours. The solution was then filtered, washed with water, and dried at 80 °C to obtain the crude product. The crude product was tested and found to have the following characteristics: HPLC crude purity 92.1%, nickel residue 812 ppm, substrate conversion rate 97.5%, and crude product yield 95.6%. (3) The crude product is put into a vacuum distillation kettle, the vacuum degree is controlled to be ≤0.5mmHg, the kettle temperature is 220~240℃, and the target fraction is collected; the fraction is cooled and crystallized, filtered and dried to obtain the refined product.

[0084] Post-refining analysis: HPLC purity 98.2%, nickel residue 36 ppm, total yield 87.8% (7.8% loss due to thermal decomposition of distillation products); high-nickel tar hazardous waste remains at the bottom of the vessel, and the nickel catalyst is completely lost and cannot be recovered.

[0085] Comparative Example 3: A method for preparing 4,4'-di-tert-butyl-2,2'-bipyridine using Raney nickel catalysis, the specific steps of which are as follows: (1) Add 12 mmol of 2-chloro-4-tert-butylpyridine, 10 mmol of zinc powder, 0.3 mmol of TBAB, 50 mL of DMF, and 0.2 g of wet Raney nickel to the reaction vessel; purge with nitrogen three times to remove oxygen from the reaction system, control the stirring speed at 400 r / min, and keep the reaction at 80 °C for 6 h. (2) After the reaction was completed, Raney nickel solid was filtered by plate and frame filter (about 15% of the catalyst was lost during filtration, and nickel continued to fall into the mother liquor). The filtrate was added with water to crystallize, filtered and dried to obtain crude product. The crude product was tested and found to have a crude purity of 91.5% by HPLC, a nickel residue of 786 ppm, and a substrate conversion rate of 96.2%.

[0086] (3) Chelating resin deep nickel removal refining step: ①Pretreatment: Fill with CH-90 iminodiacetic acid chelating resin, backwash with pure water, acid wash with 4% hydrochloric acid, alkaline conversion with 5% NaOH, and rinse with pure water until pH is neutral. ②Adsorption: After the crude product is dissolved in methanol, it is passed through a resin adsorption column at a flow rate of 10 BV / h, where nickel ions are chelated and fixed with the resin; ③ Post-processing: Collect the effluent, recover methanol under reduced pressure, add water to crystallize, and dry to obtain the finished product; ④ Resin regeneration: Used resin is eluted with 4% dilute hydrochloric acid to remove nickel, and then regenerated and recycled with alkaline solution, generating nickel-containing elution hazardous waste.

[0087] Post-refining analysis: HPLC purity 98.5%, nickel residue 29 ppm, total yield 88.5%; Raney nickel suffered severe losses after multiple filtrations and could not be stably recycled.

[0088] Example 28: The content of Example 28 is basically the same as that of Example 7, except that in step (1), the reaction temperature is 75°C and the reaction time is 5h.

[0089] Test results show: purity 99.52%, nickel residue 0.58 ppm, conversion rate 97.6%, and yield 92.8%.

[0090] Example 29: The content of Example 29 is basically the same as that of Example 8, except that in step (1), the reaction temperature is 85°C and the reaction time is 7h.

[0091] Test results show: purity 99.58%, nickel residue 0.51 ppm, conversion rate 99.1%, and yield 93.5%.

[0092] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit the scope of protection of the present invention. Those skilled in the art can modify or make equivalent substitutions to the technical solutions of the present invention based on the concept of the present invention, without departing from the essence and scope of the technical solutions of the present invention.

Claims

1. A method for preparing 4,4'-di-tert-butyl-2,2'-bipyridine using a single-atom nickel catalyst supported on a magnetic covalent organic framework, characterized in that, Includes the following steps: (1) 2-chloro-4-tert-butylpyridine, zinc powder, tetrabutylammonium bromide, Mag-COF-Ni catalyst and solvent are mixed to obtain a reaction mixture. After the reaction mixture is deoxygenated by inert gas replacement, it is reacted at 75-85°C for 5-7 hours under stirring. (2) After the reaction is complete, apply an external magnetic field and let stand to separate the Mag-COF-Ni catalyst from the reaction liquid and collect the liquid mother liquor; (3) Add water to the liquid mother liquor, stir at room temperature to crystallize, and then separate the solid and liquid, wash the filter cake and dry it to obtain 4,4'-di-tert-butyl-2,2'-bipyridine; The Mag-COF-Ni catalyst is a single-atom nickel catalyst supported on a magnetic covalent organic framework; the nickel loading in the Mag-COF-Ni catalyst is 1.5wt% to 2.5wt%.

2. The method according to claim 1, characterized in that, In step (1), the ratio of 2-chloro-4-tert-butylpyridine to Mag-COF-Ni catalyst is (10-15) mmol: (0.15-0.25) g; the molar ratio of 2-chloro-4-tert-butylpyridine, zinc powder, and tetrabutylammonium bromide is (10-15): (8-12): (0.2-0.5).

3. The method according to claim 1, characterized in that, In step (1), the solvent is N,N-dimethylformamide; the ratio of 2-chloro-4-tert-butylpyridine to the solvent is (10-15) mmol: (40-60) mL.

4. The method according to claim 1, characterized in that, In step (1), the Mag-COF-Ni catalyst is prepared by the following method: amino-modified Fe3O4 is dispersed in anhydrous acetonitrile, cyanuric chloride and p-phenylenediamine are added, stirred and mixed, and refluxed at 75-85°C for 10-14 h; after magnetic separation, washing and drying, Fe3O4@COF is obtained; the Fe3O4@COF is dispersed in ethanol, nickel chloride alcohol solution is added, and impregnated at room temperature in the dark for 10-14 h, then sodium borohydride is added, and the reaction is carried out at 0-5°C for 20-40 min. After the reaction is completed, after magnetic separation, washing and drying, the Mag-COF-Ni catalyst is obtained.

5. The method according to claim 4, characterized in that, The mass ratio of amino-modified Fe3O4, cyanuric chloride, and p-phenylenediamine is 0.5:(0.2-0.3):(0.15-0.25).

6. The method according to claim 4, characterized in that, The concentration of the nickel chloride alcohol solution is 0.03–0.08 mol / L.

7. The method according to claim 4, characterized in that, The ratio of Fe3O4@COF to nickel chloride alcohol solution is 0.4g:(5-10)mL, and the mass ratio of Fe3O4@COF to sodium borohydride is (1.5-2.5):

1.

8. The method according to claim 1, characterized in that, In step (3), the amount of water used is 3 times the volume of the solvent; in step (1), the stirring speed is 350-450 r / min.

9. The method according to claim 1, characterized in that, In step (2), the separated Mag-COF-Ni catalyst is washed twice with N,N-dimethylformamide. No activation is required, and it can be directly used for the preparation of 4,4'-di-tert-butyl-2,2'-bipyridine. The settling time is 5 to 20 seconds.

10. A 4,4'-di-tert-butyl-2,2'-bipyridine prepared by the method according to any one of claims 1-9, characterized in that, The purity of the 4,4'-di-tert-butyl-2,2'-bipyridine is ≥99.5%, and the nickel residue is 0.42-0.6 ppm.

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