A macromolecular homogeneous hydrogenation catalyst, its preparation method and application

Abstract

This invention relates to the field of homogeneous catalyst technology, and discloses a macromolecular homogeneous hydrogenation catalyst, its preparation method, and its application. This macromolecular homogeneous hydrogenation catalyst utilizes polyethylene segments introduced at specific positions to increase molecular weight while ensuring good catalytic performance, making it easy to separate from the reaction system through a filter membrane for recycling. It also has the advantages of high separation efficiency and low operating pressure required for the filter membrane.

Description

Technical Field

[0001] This invention relates to the field of homogeneous catalyst technology, and in particular to a macromolecular homogeneous hydrogenation catalyst, its preparation method, and its application. Background Technology

[0002] The chiral reduction of the antiepileptic drug licorice mainly includes the following two methods: 1) gas-liquid synthesis reaction using gaseous hydrogen as a raw material; 2) synthesis reaction using a soluble reducing agent in solution. Gas-liquid synthesis has the problems of difficulty in controlling the state of the gas in solution and limited contact area with the solute in the liquid, resulting in a lower synthesis efficiency than that using soluble reducing agents.

[0003] The chiral reduction of licarzepine using a soluble reducing agent requires a noble metal hydrogenation catalyst. However, existing homogeneous noble metal hydrogenation catalysts have a molecular weight of less than 1000 Da and are not easily volatile, making them difficult to separate from organic solutions after the reaction and impossible to recycle. Even when using solvent-resistant nanofiltration membranes for separation, the separation efficiency is low because the molecular weight of the catalyst is close to that of the product. Furthermore, dense nanofiltration membranes have low water production and require high-pressure operation, resulting in high energy consumption. In addition to the inability to recycle the catalyst, the solution containing heavy metals can only be treated as hazardous waste, which is extremely environmentally unfriendly. To solve these problems, many researchers have tried to optimize the process using heterogeneous catalysis, immobilizing the catalyst on a support to form a heterogeneous catalyst, which is then recycled through filtration after the reaction. However, the catalytic performance after immobilization is greatly affected, resulting in a reduced reaction rate. Summary of the Invention

[0004] To address the aforementioned technical problems—namely, the difficulty in recycling noble metal homogeneous hydrogenation catalysts and the poor catalytic performance of heterogeneous catalysts—this invention provides a macromolecular homogeneous hydrogenation catalyst, its preparation method, and its applications. This catalyst possesses good catalytic activity and reaction selectivity, is easily separated from the reaction system using a filter membrane for recycling, and exhibits high separation efficiency with low operating pressure required for the filter membrane.

[0005] The specific technical solution of this invention is as follows: In a first aspect, the present invention provides a macromolecular homogeneous hydrogenation catalyst, the structural formula of which is as follows: .

[0006] Compared to existing homogeneous hydrogenation catalysts, the macromolecular homogeneous hydrogenation catalyst of the present invention has a higher molecular weight. When used in catalytic reactions, the molecular weight difference between the catalyst and the reactants and products is large. After the reaction, it can be separated by a filter membrane. The catalyst is retained by the filter membrane, while the reactants and products pass through the filter membrane. This makes it easy to separate the catalyst from the reaction system after the reaction, so as to achieve recycling. In addition, a filter membrane with a larger pore size (higher flux) can be used, so the separation efficiency is high and the operating pressure required for the filter membrane is low.

[0007] Meanwhile, the macromolecular homogeneous hydrogenation catalyst of the present invention has good solubility in the reaction solvent, enabling homogeneous catalytic reactions and thus exhibiting good catalytic performance. Furthermore, by designing the introduction positions of the two polyethylene segments in the molecular structure of the catalyst of the present invention, steric hindrance to the active sites of the catalyst can be avoided, thereby giving the catalyst high catalytic activity. In addition, the catalyst of the present invention also has high reaction selectivity, with fewer side reactions when used to catalyze the chiral reduction reaction of licarcisine.

[0008] Preferably, the average degree of polymerization of the polyethylene segments in the hydrogenation catalyst is 90-360.

[0009] In this paper, the average degree of polymerization of polyethylene segments is calculated based on their number-average molecular weight.

[0010] When the average degree of polymerization of polyethylene segments is below 90, the retention rate of the hydrogenation catalyst by the ultrafiltration membrane is too low; when the average degree of polymerization of polyethylene segments is above 360, the solubility of the hydrogenation catalyst in the reaction system is too low, resulting in poor catalytic performance. When the average degree of polymerization of polyethylene segments is in the range of 90-360, the macromolecular homogeneous hydrogenation catalyst can be well retained by the ultrafiltration membrane with little impact on the catalyst's catalytic performance, enabling a faster reaction rate in the catalytic hydrogenation reaction.

[0011] Furthermore, in the hydrogenation catalyst, the average degree of polymerization of the polyethylene segments is 90-230.

[0012] When the average degree of polymerization of the polyethylene segment exceeds 230, it creates significant steric hindrance to the active sites in the hydrogenation catalyst, thus adversely affecting its catalytic activity. Therefore, controlling the average degree of polymerization of this segment within the range of 90-230 ensures that the hydrogenation catalyst is easily retained by the ultrafiltration membrane while maximizing its catalytic performance.

[0013] Furthermore, within the aforementioned range of average degree of polymerization of polyethylene segments, a higher average degree of polymerization is more conducive to the retention of the catalyst by ultrafiltration membranes with larger pore sizes. Typically, ultrafiltration membranes with a pore size of 4 nm can retain catalysts with a molecular weight of 10 kDa and above, while ultrafiltration membranes with a pore size of 2-3 nm can retain catalysts with a molecular weight of 5 kDa and above.

[0014] Secondly, the present invention provides a method for preparing the hydrogenation catalyst, comprising the following steps: (1) Compound A undergoes an ester exchange reaction with compound B to produce compound C: ; (2) Compound C undergoes a substitution reaction with compound D to produce compound E: ; (3) Compound E reacts with RuCl3 to form compound F: ; (4) Compound F reacts to form compound G: .

[0015] In the compound structural formulas that appear in the above preparation process, "Ts" and "TOs" are both p-toluenesulfonyl groups, "Ms" is a methanesulfonyl group, and "Me" is a methyl group.

[0016] In the above preparation process, the order of first grafting polyethylene derivative (i.e. compound B) and then synthesizing active sites can improve product yield and purity. The reason is that after grafting polyethylene derivative, the phenolic hydroxyl group can be protected, avoiding side reactions of phenolic hydroxyl group in step (2).

[0017] Preferably, in step (1), the number-average molecular weight of compound B is 2650-10200 Da.

[0018] By using compound B with a number-average molecular weight of 2650-10200 Da, the prepared catalyst can be retained by an ultrafiltration membrane and has good catalytic performance.

[0019] Further, in step (1), the number-average molecular weight of compound B is 2650-6550 Da.

[0020] Using compound B with a number-average molecular weight of 2650-6550 Da can ensure the catalytic performance of the hydrogenation catalyst to a greater extent.

[0021] Preferably, in step (1), the transesterification reaction is carried out under the catalysis of Cs2CO3, the molar ratio of compound A to Cs2CO3 is 1:0.1-10, the temperature of the transesterification reaction is 60-70℃, and the time is 15-24 h.

[0022] Preferably, in step (1), the molar ratio of compound A to compound B is 1:1-5. Preferably, in step (2), the substitution reaction is carried out under the catalysis of diisopropylethylamine, the molar ratio of compound C to diisopropylethylamine is 1:0.1-10, the temperature of the substitution reaction is 130-140℃, and the time is 12-20 h.

[0023] Preferably, in step (2), the molar ratio of compound C to compound D is 1:1-5.

[0024] Preferably, in step (3), the reaction temperature is 115-125℃ and the time is 1-2 h.

[0025] Preferably, in step (3), the molar ratio of compound E to RuCl3 is 1:1-3.

[0026] Preferably, in step (4), the reaction is carried out under the catalysis of triethylamine, the molar ratio of compound F to triethylamine is 1:1-10, the reaction temperature is 60-70℃, and the time is 1-2 h.

[0027] Thirdly, the present invention provides the application of the hydrogenation catalyst in a hydrogenation reaction, wherein the hydrogenation reaction is the reaction of acetophenone with formic acid to prepare phenylethanol.

[0028] Preferably, the hydrogenation reaction is carried out under the catalysis of triethylamine at a temperature of 60-70°C for a time of 60-67 h.

[0029] Preferably, the reaction solvent for the hydrogenation reaction includes one or more of methanol, ethanol, tetrahydrofuran, and N-methylpyrrolidone.

[0030] Preferably, after the hydrogenation reaction is completed, the hydrogenation catalyst is recovered by ultrafiltration membrane separation.

[0031] Compared with the prior art, the present invention has the following advantages: (1) The catalyst of the present invention has increased molecular weight while ensuring good catalytic activity and reaction selectivity, making it easy to separate from the reaction system through the filter membrane, realize recycling, and achieve high separation efficiency and low operating pressure required for the filter membrane.

[0032] (2) In the preparation process of the catalyst, the present invention adopts the method of first grafting polyethylene derivatives and then synthesizing active sites, which can maintain the high catalytic activity of cesium carbonate used in grafting polyethylene derivatives, thereby accelerating the reaction rate and increasing the product yield.

[0033] (3) The catalyst preparation method of the present invention, through the design of the entire reaction route and the control of process details, can reduce side reactions and achieve higher product yield and purity. Detailed Implementation

[0034] The present invention will be further described below with reference to embodiments.

[0035] General Implementation Examples In a first aspect, the present invention provides a macromolecular homogeneous hydrogenation catalyst, the structural formula of which is as follows: .

[0036] In one specific embodiment, the average degree of polymerization of the polyethylene segments in the hydrogenation catalyst is 90-360.

[0037] A method for preparing the above-mentioned hydrogenation catalyst includes the following steps: (1) Compound A undergoes an ester exchange reaction with compound B to produce compound C: ; (2) Compound C undergoes a substitution reaction with compound D to produce compound E: ; (3) Compound E reacts with RuCl3 to form compound F: ; (4) Compound F reacts to form compound G: .

[0038] In one specific implementation, in step (1), the number-average molecular weight of compound B is 2650-10200 Da.

[0039] In one specific implementation, in step (1), the transesterification reaction is carried out under the catalysis of Cs2CO3, the molar ratio of compound A, compound B and Cs2CO3 is 1:1-5:0.1-10, the temperature of the transesterification reaction is 60-70℃, and the time is 15-24 h.

[0040] In one specific implementation, in step (2), the substitution reaction is carried out under the catalysis of (Pr)2EtN, the molar ratio of compound C, compound D and (Pr)2EtN is 1:1-5:0.1-10, the temperature of the substitution reaction is 130-140℃, and the time is 12-20 h.

[0041] In one specific implementation, in step (3), the molar ratio of compound E to RuCl3 is 1:1-3, the reaction temperature is 115-125℃, and the time is 1-2 h.

[0042] In one specific implementation, in step (4), the reaction is carried out under the catalysis of triethylamine, the molar ratio of compound F to triethylamine is 1:1-10, the reaction temperature is 60-70℃, and the time is 1-2 h.

[0043] The above-mentioned hydrogenation catalyst is used in the hydrogenation reaction, in which acetophenone reacts with formic acid to prepare phenylethanol.

[0044] In one specific embodiment, the hydrogenation reaction is carried out under the catalysis of triethylamine at a temperature of 60-70°C for a time of 60-67 h.

[0045] In one specific embodiment, the reaction solvent for the hydrogenation reaction includes one or more of methanol, ethanol, tetrahydrofuran, and N-methylpyrrolidone.

[0046] As one specific implementation, after the hydrogenation reaction is completed, the hydrogenation catalyst is recovered by ultrafiltration membrane separation. Specific Implementation The present invention will now be described through specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Variations and advantages that can be conceived by those skilled in the art without departing from the spirit and scope of the inventive concept are included in the present invention, and the scope of protection of the present invention is defined by the appended claims and any equivalents thereof.

[0048] Unless otherwise defined, all technical and scientific terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure pertains. Unless otherwise specified, the raw materials and equipment used in this invention are conventional in the art and can be obtained through conventional commercial means; unless otherwise specified, the methods used in this invention are conventional methods in the art.

[0049] In this article, the molar amounts of polymers (compounds B, C, and E) are calculated by dividing the mass by the number-average molecular weight.

[0050] Example 1: Preparation of macromolecular homogeneous hydrogenation catalyst E-1 The macromolecular homogeneous hydrogenation catalyst E-1 was prepared through the following steps: (1) The reaction formula is as follows: ; The specific steps are as follows: Take 150 mmol of compound A and compound B (molecular weight M). n = 6550 Da) 150 mmol was added to 200 mL of N,N-dimethylformamide, stirred until fully dissolved, and then 750 mmol of cesium carbonate was added. After mixing, the mixture was heated at 65 °C for 18 h to remove most of the DMF under reduced pressure. The resulting mixture was cooled to 0 °C, and H2O (200 mL) and HCl (2 M, 20 mL) were carefully added. The mixture was extracted with CH2Cl2 (2 × 100 mL). The CH2Cl2 extract was mixed, washed with brine (200 mL), dried over MgSO4, and concentrated to 20 mL. Et2O (400 mL) was added to the concentrated solution, and the mixture was stirred at 0 °C for 0.5 h. The precipitate was separated by filtration and washed with cold isopropanol (i-PrOH) (30 mL) and diethyl ether (Et2O) (100 mL) to give the supported ligand (R)-3 as a grayish-white solid (compound C), with a yield of 96%.

[0051] (2) The reaction formula is as follows: ; The specific steps are as follows: 100 mmol of compound C and 150 mmol of compound D obtained in step (1) were added to 120 mL of toluene and stirred until homogeneous to form a suspension. 100 mmol of diisopropylethylamine ((Pr)2EtN) was added to the suspension and mixed. The mixture was then heated at 135 °C for 14 h. The resulting reaction mixture was concentrated under reduced pressure, and the residue was purified by flash chromatography to obtain a white solid (compound E) with a yield of 55%.

[0052] (3) The reaction formula is as follows: ; The specific steps are as follows: Take 30 mmol of compound E obtained according to step (2), add it to 100 mL of toluene, stir to dissolve completely, and then add 30 mmol of the solution. RuCl3·3H2O was heated at 120 °C for 1 h. The resulting reaction mixture was concentrated under reduced pressure, and then 100 mL of diethyl ether was added. The solid was collected by filtration, washed with diethyl ether, and dried under reduced pressure to give a brown solid (compound F) with a yield of 52%.

[0053] (4) The reaction formula is as follows: ; The specific steps are as follows: Take 10 mmol of compound F obtained in step (3) and 25 mmol of triethylamine, add them to 160 mL of 2-propanol, stir to dissolve completely, heat at 60 °C for 1 h, concentrate the reaction mixture under reduced pressure, and then use CHCls / MeOH = 20 / 1 (i.e., a mixture of chloroform and methanol with a volume ratio of 20:1) as the eluent to purify the residue by flash chromatography, and obtain a brown solid (compound G, catalyst E-1) with a yield of 93% and a purity of 98.0%.

[0054] Example 2: Preparation of macromolecular homogeneous hydrogenation catalyst E-2 The macromolecular homogeneous hydrogenation catalyst E-2 was prepared through the following steps: (1) The reaction formula is as follows: ; The specific steps are as follows: Take 100 mmol of compound A and compound B (molecular weight M). n = 2651 Da) 200 mmol was added to 200 mL of N,N-dimethylformamide, stirred until fully dissolved, and then 300 mmol of cesium carbonate was added. After mixing, the mixture was heated at 60 °C for 15 h to remove most of the DMF under reduced pressure. The resulting mixture was cooled to 0 °C, and H2O (200 mL) and HCl (2 M, 20 mL) were carefully added. The mixture was extracted with CH2Cl2 (2 × 100 mL). The CH2Cl2 extract was mixed, washed with brine (200 mL), dried over MgSO4, and concentrated to 20 mL. Et2O (400 mL) was added to the concentrated solution, and the mixture was stirred at 0 °C for 0.5 h. The precipitate was separated by filtration and washed with cold i-PrOH (30 mL) and Et2O (100 mL) to give the supported ligand (R)-3 as a grayish-white solid (compound C), with a yield of 97%.

[0055] (2) The reaction formula is as follows: ; The specific steps are as follows: Take 90 mmol of compound C and 90 mmol of compound D obtained in step (1), add them to 120 mL of toluene, stir well to prepare a suspension. Add 10 mmol of diisopropylethylamine to the suspension, mix well, and heat at 140 °C for 20 h. Concentrate the resulting reaction mixture under reduced pressure, and purify the residue by flash chromatography to obtain a white solid (compound E) with a yield of 53%.

[0056] (3) The reaction formula is as follows: ; The specific steps are as follows: Take 30 mmol of compound E obtained according to step (2), add it to 100 mL of toluene, stir to dissolve completely, and then add 45 mmol of the solution. RuCl3·3H2O was heated at 115 °C for 2 h. The resulting reaction mixture was concentrated under reduced pressure, and then 100 mL of diethyl ether was added. The solid was collected by filtration, washed with diethyl ether, and dried under reduced pressure to give a brown solid (compound F) with a yield of 56%.

[0057] (4) The reaction formula is as follows: ; The specific steps are as follows: Take 10 mmol of compound F obtained in step (3) and 10 mmol of triethylamine, add them to 160 mL of 2-propanol, stir to dissolve completely, heat at 65 °C for 2 h, concentrate the reaction mixture under reduced pressure, and then use CHCls / MeOH = 20 / 1 as the eluent to purify the residue by flash chromatography to obtain a brown solid (compound G, catalyst E-2), with a yield of 90% and a purity of 97.6%.

[0058] Example 3: Preparation of macromolecular homogeneous hydrogenation catalyst E-3 The macromolecular homogeneous hydrogenation catalyst E-3 was prepared through the following steps: (1) The reaction formula is as follows: ; The specific steps are as follows: Take 130 mmol of compound A and compound B (molecular weight M). n= 3507 Da) 650 mmol was added to 200 mL of N,N-dimethylformamide, stirred until fully dissolved, and then 15 mmol of cesium carbonate was added. After mixing, the mixture was heated at 70 °C for 24 h to remove most of the DMF under reduced pressure. The resulting mixture was cooled to 0 °C, and H2O (200 mL) and HCl (2 M, 20 mL) were carefully added. The mixture was extracted with CH2Cl2 (2 × 100 mL). The CH2Cl2 extract was mixed, washed with brine (200 mL), dried over MgSO4, and concentrated to 20 mL. Et2O (400 mL) was added to the concentrated solution, and the mixture was stirred at 0 °C for 0.5 h. The precipitate was separated by filtration and washed with cold i-PrOH (30 mL) and Et2O (100 mL) to give the supported ligand (R)-3 as a grayish-white solid (compound C), with a yield of 92%.

[0059] (2) The reaction formula is as follows: ; The specific steps are as follows: 100 mmol of compound C and 500 mmol of compound D obtained in step (1) were added to 120 mL of toluene and stirred until homogeneous to form a suspension. 510 mmol of diisopropylethylamine was added to the suspension, and after mixing, the mixture was heated at 130 °C for 12 h. The resulting reaction mixture was concentrated under reduced pressure, and the residue was purified by flash chromatography to obtain a white solid (compound E) with a yield of 63%.

[0060] (3) The reaction formula is as follows: ; The specific steps are as follows: Take 30 mmol of compound E obtained in step (2), add it to 100 mL of toluene, stir to dissolve completely, and then add 90 mmol of the solution. RuCl3·3H2O was heated at 125 °C for 1 h. The resulting reaction mixture was concentrated under reduced pressure, and then 100 mL of diethyl ether was added. The solid was collected by filtration, washed with diethyl ether, and dried under reduced pressure to give a brown solid (compound F) with a yield of 57%.

[0061] (4) The reaction formula is as follows: ; The specific steps are as follows: Take 10 mmol of compound F obtained in step (3) and 100 mmol of triethylamine, add them to 160 mL of 2-propanol, stir to dissolve completely, heat at 70 °C for 1.5 h, concentrate the reaction mixture under reduced pressure, and then use CHCls / MeOH = 20 / 1 as the eluent to purify the residue by flash chromatography to obtain a brown solid (compound G, catalyst E-3), with a yield of 94% and a purity of 97.2%.

[0062] Example 4: Preparation of homogeneous hydrogenation catalyst E-4 The macromolecular homogeneous hydrogenation catalyst E-1 was prepared through the following steps: (1) The reaction formula is as follows: ; The specific steps are as follows: Take 150 mmol of compound A and compound B (molecular weight M). n = 10200 Da) 150 mmol was added to 200 mL of N,N-dimethylformamide, stirred until fully dissolved, and then 750 mmol of cesium carbonate was added. After mixing, the mixture was heated at 65 °C for 18 h to remove most of the DMF under reduced pressure. The resulting mixture was cooled to 0 °C, and H2O (200 mL) and HCl (2 M, 20 mL) were carefully added. The mixture was extracted with CH2Cl2 (2 × 100 mL). The CH2Cl2 extract was mixed, washed with brine (200 mL), dried over MgSO4, and concentrated to 20 mL. Et2O (400 mL) was added to the concentrated solution, and the mixture was stirred at 0 °C for 0.5 h. The precipitate was separated by filtration and washed with cold isopropanol (i-PrOH) (30 mL) and diethyl ether (Et2O) (100 mL) to give the supported ligand (R)-3 as a grayish-white solid (compound C), with a yield of 91%.

[0063] (2) The reaction formula is as follows: ; The specific steps are as follows: 100 mmol of compound C and 150 mmol of compound D obtained in step (1) were added to 120 mL of toluene and stirred until homogeneous to form a suspension. 100 mmol of diisopropylethylamine ((Pr)2EtN) was added to the suspension and mixed. The mixture was then heated at 135 °C for 14 h. The resulting reaction mixture was concentrated under reduced pressure, and the residue was purified by flash chromatography to obtain a white solid (compound E) with a yield of 52%.

[0064] (3) The reaction formula is as follows: ; The specific steps are as follows: Take 30 mmol of compound E obtained according to step (2), add it to 100 mL of toluene, stir to dissolve completely, and then add 30 mmol of the solution. RuCl3·3H2O was heated at 120 °C for 1 h. The resulting reaction mixture was concentrated under reduced pressure, and then 100 mL of diethyl ether was added. The solid was collected by filtration, washed with diethyl ether, and dried under reduced pressure to give a brown solid (compound F) with a yield of 53%.

[0065] (4) The reaction formula is as follows: ; The specific steps are as follows: Take 10 mmol of compound F obtained in step (3) and 25 mmol of triethylamine, add them to 160 mL of 2-propanol, stir to dissolve completely, heat at 60 °C for 1 h, concentrate the reaction mixture under reduced pressure, and then use CHCls / MeOH = 20 / 1 (i.e., a mixture of chloroform and methanol with a volume ratio of 20:1) as the eluent to purify the residue by flash chromatography, and obtain a brown solid (compound G, catalyst E-4) with a yield of 89% and a purity of 97.8%.

[0066] Comparative Example 1: Preparation of Homogeneous Hydrogenation Catalyst E-4 The homogeneous hydrogenation catalyst E-4 was prepared through the following steps: (1) The reaction formula is as follows: ; The specific steps are as follows: 100 mmol of compound H and 150 mmol of compound I were added to 120 mL of toluene and stirred until homogeneous to form a suspension. 100 mmol of diisopropylethylamine was added to the suspension, and the mixture was heated at 135 °C for 14 h. The resulting reaction mixture was concentrated under reduced pressure, and the residue was purified by flash chromatography to obtain a white solid (compound J).

[0067] (2) The reaction formula is as follows: ; The specific steps are as follows: Take 30 mmol of compound J obtained according to step (1), add it to 100 mL of toluene, stir to dissolve completely, and then add 30 mmol of the solution. RuCl3·3H2O was heated at 120℃ for 1 h. The resulting reaction mixture was concentrated under reduced pressure, and then 100 mL of diethyl ether was added. The solid was collected by filtration, washed with diethyl ether, and dried under reduced pressure to give a brown solid (compound K).

[0068] (3) The reaction formula is as follows: ; The specific steps are as follows: Take 10 mmol of compound K and 25 mmol of triethylamine obtained in step (2) and add them to 160 mL of 2-propanol. Stir to dissolve completely and then heat the reaction at 60 °C for 1 h. Concentrate the reaction mixture under reduced pressure and then use CHCls / MeOH = 20 / 1 as the eluent to purify the residue by flash chromatography to obtain a brown solid (compound L, catalyst E-4).

[0069] Comparative Example 2: Preparation of macromolecular homogeneous hydrogenation catalyst E-5 The macromolecular homogeneous hydrogenation catalyst E-5 was prepared through the following steps: (1) The reaction formula is as follows: ; The specific steps are as follows: 200 mmol of compound M and 300 mmol of compound N were added to 120 mL of toluene and stirred until homogeneous to form a suspension. 200 mmol of diisopropylethylamine was added to the suspension, and the mixture was heated at 135 °C for 14 h. The resulting reaction mixture was concentrated under reduced pressure, and the residue was purified by flash chromatography to give a white solid (compound O) in 48% yield.

[0070] (2) The reaction formula is as follows: ; The specific steps are as follows: Take 100 mmol of compound O obtained according to step (1), add it to 100 mL of toluene, stir to dissolve completely, and then add 100 mmol of [the solution]. RuCl3·3H2O was heated at 120 °C for 1 h. The resulting reaction mixture was concentrated under reduced pressure, and then 100 mL of diethyl ether was added. The solid was collected by filtration, washed with diethyl ether, and dried under reduced pressure to give a brown solid (compound P) with a yield of 50%.

[0071] (3) The reaction formula is as follows: ; The specific steps are as follows: Take 40 mmol of compound P obtained in step (2) and 100 mmol of triethylamine, add them to 160 mL of 2-propanol, stir to dissolve completely, heat at 60 °C for 1 h, concentrate the reaction mixture under reduced pressure, and then use CHCls / MeOH = 20 / 1 as the eluent to purify the residue by flash chromatography to obtain a brown solid (compound Q) with a yield of 89%.

[0072] (4) The reaction formula is as follows: ; The specific steps are as follows: Take 20 mmol of compound Q and compound R (molecular weight M). n = 6550 Da) 20 mmol was added to 200 mL of N,N-dimethylformamide, stirred until fully dissolved, and then 100 mmol of cesium carbonate was added. After mixing, the mixture was heated at 65 °C for 18 h to remove most of the DMF under reduced pressure. The resulting mixture was cooled to 0 °C, and H2O (200 mL) and HCl (2 M, 20 mL) were carefully added. The mixture was extracted with CH2Cl2 (2 × 100 mL). The CH2Cl2 extract was mixed, washed with brine (200 mL), dried over MgSO4, and concentrated to 20 mL. Et2O (400 mL) was added to the concentrated solution, and the mixture was stirred at 0 °C for 0.5 h. The precipitate was separated by filtration and washed with cold i-PrOH (30 mL) and Et2O (100 mL) to give the supported ligand (R)-3 as a grayish-white solid (compound S), with a yield of 86% and a purity of 91%.

[0073] Comparing Example 1 and Comparative Example 2, it can be seen that the yield of step (1) in Comparative Example 2 is significantly lower than that of step (2) in Example 1, and the purity of the final product is also lower. This indicates that adopting the order of first grafting polyethylene derivatives and then synthesizing active sites can improve the yield and purity of the reaction.

[0074] Comparative Example 3: Preparation of macromolecular homogeneous hydrogenation catalyst E-6 The macromolecular homogeneous hydrogenation catalyst E-2 was prepared through the following steps: (1) The reaction formula is as follows: ; The specific steps are as follows: Take 100 mmol of compound A and compound B (molecular weight M). n= 1483 Da) 200 mmol was added to 200 mL of N,N-dimethylformamide, stirred until fully dissolved, and then 300 mmol of cesium carbonate was added. After mixing, the mixture was heated at 60 °C for 15 h to remove most of the DMF under reduced pressure. The resulting mixture was cooled to 0 °C, and H2O (200 mL) and HCl (2 M, 20 mL) were carefully added. The mixture was extracted with CH2Cl2 (2 × 100 mL). The CH2Cl2 extract was mixed, washed with brine (200 mL), dried over MgSO4, and concentrated to 20 mL. Et2O (400 mL) was added to the concentrated solution, and the mixture was stirred at 0 °C for 0.5 h. The precipitate was separated by filtration and washed with cold i-PrOH (30 mL) and Et2O (100 mL) to give the supported ligand (R)-3 as a grayish-white solid (compound C), with a yield of 97%.

[0075] (2) The reaction formula is as follows: ; The specific steps are as follows: Take 90 mmol of compound C and 90 mmol of compound D obtained in step (1), add them to 120 mL of toluene, stir well to prepare a suspension. Add 10 mmol of diisopropylethylamine to the suspension, mix well, and heat at 140 °C for 20 h. Concentrate the resulting reaction mixture under reduced pressure, and purify the residue by flash chromatography to obtain a white solid (compound E) with a yield of 54%.

[0076] (3) The reaction formula is as follows: ; The specific steps are as follows: Take 30 mmol of compound E obtained according to step (2), add it to 100 mL of toluene, stir to dissolve completely, and then add 45 mmol of the solution. RuCl3·3H2O was heated at 115 °C for 2 h. The resulting reaction mixture was concentrated under reduced pressure, and then 100 mL of diethyl ether was added. The solid was collected by filtration, washed with diethyl ether, and dried under reduced pressure to give a brown solid (compound F) with a yield of 57%.

[0077] (4) The reaction formula is as follows: ; The specific steps are as follows: Take 10 mmol of compound F obtained in step (3) and 10 mmol of triethylamine, add them to 160 mL of 2-propanol, stir to dissolve completely, heat at 65 °C for 2 h, concentrate the reaction mixture under reduced pressure, and then use CHCls / MeOH = 20 / 1 as the eluent to purify the residue by flash chromatography to obtain a brown solid (compound G, catalyst E-6), with a yield of 93% and a purity of 98.2%.

[0078] Comparative Example 4: Preparation of macromolecular homogeneous hydrogenation catalyst E-7 The macromolecular homogeneous hydrogenation catalyst E-7 was prepared through the following steps: (1) The reaction formula is as follows: ; The specific steps are as follows: Take 130 mmol of compound A and compound B (molecular weight M). n = 16024 Da) 650 mmol was added to 200 mL of N,N-dimethylformamide, stirred until fully dissolved, and then 15 mmol of cesium carbonate was added. After mixing, the mixture was heated at 70 °C for 24 h to remove most of the DMF under reduced pressure. The resulting mixture was cooled to 0 °C, and H2O (200 mL) and HCl (2 M, 20 mL) were carefully added. The mixture was extracted with CH2Cl2 (2 × 100 mL). The CH2Cl2 extract was mixed, washed with brine (200 mL), dried over MgSO4, and concentrated to 20 mL. Et2O (400 mL) was added to the concentrated solution, and the mixture was stirred at 0 °C for 0.5 h. The precipitate was separated by filtration and washed with cold i-PrOH (30 mL) and Et2O (100 mL) to give the supported ligand (R)-3 as a grayish-white solid (compound C), with a yield of 88%.

[0079] (2) The reaction formula is as follows: ; The specific steps are as follows: 100 mmol of compound C and 500 mmol of compound D obtained in step (1) were added to 120 mL of toluene and stirred until homogeneous to form a suspension. 510 mmol of diisopropylethylamine was added to the suspension, and after mixing, the mixture was heated at 130 °C for 12 h. The resulting reaction mixture was concentrated under reduced pressure, and the residue was purified by flash chromatography to obtain a white solid (compound E) with a yield of 59%.

[0080] (3) The reaction formula is as follows: ; The specific steps are as follows: Take 30 mmol of compound E obtained in step (2), add it to 100 mL of toluene, stir to dissolve completely, and then add 90 mmol of the solution. RuCl3·3H2O was heated at 125 °C for 1 h. The resulting reaction mixture was concentrated under reduced pressure, and then 100 mL of diethyl ether was added. The solid was collected by filtration, washed with diethyl ether, and dried under reduced pressure to give a brown solid (compound F) with a yield of 54%.

[0081] (4) The reaction formula is as follows: ; The specific steps are as follows: Take 10 mmol of compound F obtained in step (3) and 100 mmol of triethylamine, add them to 160 mL of 2-propanol, stir to dissolve completely, heat at 70 °C for 1.5 h, concentrate the reaction mixture under reduced pressure, and then use CHCls / MeOH = 20 / 1 as the eluent to purify the residue by flash chromatography to obtain a brown solid (compound G, catalyst E-7), with a yield of 91% and a purity of 97.7%.

[0082] Application Example 1: Catalytic effect of catalyst and separation effect of solvent-resistant ultrafiltration membrane The catalysts prepared in each example and comparative example were used to catalyze the hydrogenation reaction of acetophenone to (S)-(-)-phenylethanol. After the reaction, a solvent-resistant ultrafiltration membrane with a pore size of 3 nm was used for separation. The specific steps are as follows: S1: Dissolve acetophenone in methanol to prepare an acetophenone solution with a concentration of 1 mol / L; dissolve formic acid and triethylamine in methanol to prepare a formic acid / triethylamine mixture, wherein the concentrations of formic acid and triethylamine are 1.5 mol / L and 3 mol / L, respectively; dissolve the catalyst in methanol to prepare a catalyst solution with a concentration of 0.4 mmol / L.

[0083] S2: After mixing 95 mL of acetophenone solution and 95 mL of formic acid / triethylamine mixture, nitrogen gas was introduced into the reaction vessel to purge the air. Then, 10 mL of catalyst solution was added, and the reaction was carried out at 60 °C for 60 h to obtain the reaction mixture.

[0084] S3: The reaction mixture was passed into the solvent-resistant ultrafiltration membrane module at a flow rate of 20 mL / min, and the concentration outlet pressure was set to 0.1 MPa. The solution exiting the membrane end flowed out at a flow rate of 10 mL / min. The solution was colorless, clear, and transparent. A sample was taken when the accumulated volume reached 150 mL. The conversion rate of phenylethanol and the enantiomeric excess percentage were calculated by HPLC analysis, and the catalyst recovery rate was also calculated. The results are shown in Table 1.

[0085] The reaction time in step S2 was extended to 67 h, and steps S1-S3 were repeated. The phenylethanol conversion rate, enantiomeric excess percentage, and catalyst recovery rate were measured and are shown in Table 1. The phenylethanol conversion rate is the total conversion rate of (S)-(-)-phenylethanol and (R)-(+)-phenylethanol. The enantiomeric excess percentage (ee value) was calculated using the following formula: ee = ([R]-[S] / [R]+[S])×100%.

[0086] Table 1

[0087] Application Example 2: Catalytic effect of low molecular weight catalysts and separation effect of solvent-resistant nanofiltration membranes The catalyst E-4 prepared in Comparative Example 1 was used to catalyze the hydrogenation reaction of acetophenone to phenylethanol. After the reaction, a solvent-resistant nanofiltration membrane with a pore size of 1 nm was used for separation. The specific steps are as follows: S1: Perform the hydrogenation reaction according to steps S1 and S2 in Application Example 1 for 67 h.

[0088] S2: The reaction mixture was passed into the solvent-resistant nanofiltration membrane module at a flow rate of 20 mL / min, and the concentration outlet pressure was set to 0.5 MPa. The solution exiting the membrane end flowed out at a flow rate of 5.3 mL / min. The solution was colorless, clear, and transparent. A sample was taken when the accumulated volume reached 150 mL. HPLC analysis showed that the conversion rate of phenylethanol was 100%, and the catalyst recovery rate was 99.4%.

[0089] Analyzing the experimental results in Application Example 1 and Application Example 2, the following conclusions can be drawn: (1) Comparing Example 1 with Comparative Example 1, it can be shown that grafting polyethylene segments into a homogeneous catalyst in accordance with the present invention will not have an excessive impact on the catalytic activity and enantioselectivity of the catalyst, and the catalyst can be separated and recovered from the reaction system by ultrafiltration without the need for nanofiltration, thus greatly improving the separation efficiency and reducing the pressure required for filter membrane operation.

[0090] (2) Comparing Examples 1-3 with Comparative Examples 3-4, it can be shown that when the molecular weight of the polyethylene derivative (compound B) used in the catalyst preparation process is too small, the polyethylene chain segment in the catalyst is too short, which will affect the separation and recovery effect of the ultrafiltration membrane on the catalyst; when the molecular weight of the polyethylene derivative is too large, the polyethylene chain segment in the catalyst is too long, which will cause greater steric hindrance to the active site, resulting in weakened catalytic activity.

[0091] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Any simple modifications, alterations, and equivalent transformations made to the above embodiments based on the technical essence of the present invention shall still fall within the protection scope of the present invention.

Claims

1. A macromolecular homogeneous hydrogenation catalyst characterized in that, The structural formula of the hydrogenation catalyst is as follows: ， Wherein, Ts is p-toluenesulfonyl group, and the average degree of polymerization of the polyethylene segment is 90-230.

2. A method for preparing the hydrogenation catalyst according to claim 1, characterized in that, Includes the following steps: (1) Compound A undergoes an ester exchange reaction with compound B to produce compound C: ； (2) Compound C undergoes a substitution reaction with compound D to produce compound E: ； (3) Compound E reacts with RuCl3 to produce compound F: ； (4) Compound F reacts to form compound G: ； In the compound structural formulas that appear in the above preparation process, "Ts" and "TOs" are both p-toluenesulfonyl groups, "Ms" is a methanesulfonyl group, and "Me" is a methyl group.

3. The preparation method according to claim 2, characterized in that, In step (1), the transesterification reaction is carried out under the catalysis of Cs2CO3, the molar ratio of compound A to Cs2CO3 is 1:0.1-10, the temperature of the transesterification reaction is 60-70℃, and the time is 15-24 h.

4. The preparation method according to claim 2, characterized in that, In step (2), the substitution reaction is carried out under the catalysis of diisopropylethylamine, the molar ratio of compound C to diisopropylethylamine is 1:0.1-10, the temperature of the substitution reaction is 130-140℃, and the time is 12-20 h.

5. The preparation method according to claim 2, characterized in that, In step (3), the reaction temperature is 115-125℃ and the time is 1-2 h.

6. The preparation method according to claim 2, characterized in that, In step (4), the reaction is carried out under the catalysis of triethylamine, the molar ratio of compound F to triethylamine is 1:1-10, the reaction temperature is 60-70℃, and the time is 1-2 h.

7. The application of the hydrogenation catalyst according to claim 1 in the hydrogenation reaction, characterized in that, The hydrogenation reaction is the reaction of acetophenone with formic acid to prepare phenylethanol.

8. The application according to claim 7, characterized in that, The hydrogenation reaction was carried out under the catalysis of triethylamine at a temperature of 60-70°C for 60-67 h.

9. The application according to claim 7, characterized in that, The reaction solvent for the hydrogenation reaction includes one or more of methanol, ethanol, tetrahydrofuran, and N-methylpyrrolidone.

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